Search

Xiao-Yang Xu,&ast; Ze Wang,&ast; Chen-You Liu,&ast; Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Street, Suzhou, 215006, People’s Republic of China, Email zhuxiaoli90@163.comObjective: To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.Materials: This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.Results: A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5– 32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3−CD19+ (p=0.004), CFB (p=0.027), NLR (p< 0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).Conclusion: The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.Keywords: immune indicator, TACE, immune checkpoint inhibitors, tyrosine kinase inhibitors, tumor microenvironment

Juan Sun, Juxiang Shen, Lei Liu, Juan Du Department of Medical Technology, Jiangsu College of Nursing, Huai’an, Jiangsu Province, People’s Republic of ChinaCorrespondence: Juan Sun, Department of Medical Technology, Jiangsu College of Nursing, Huaian, 223001, People’s Republic of China, Tel +8615162765063, Email 15162765063@163.comBackground: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, causing a serious economic burden worldwide. Traditional Chinese Medicine (TCM) is playing an increasingly important role in the treatment of DN. The purpose of this study was to comprehend the main themes and developments in relevant research throughout the last 11 years.Methods: We looked for publications in the Web of Science Core Collection database (WOS) and the Chinese National Knowledge Infrastructure (CNKI) between 2013 and 2024. CiteSpace 6.3.R1 software was used to analyze the co-authorship of countries/regions, organizations, and co-occurrence of keywords. In addition, burst detection was applied to predict research hotspots and future trends.Results: A total of 530 articles were included. The overall trend of published articles is increasing. China is the country with the highest number of publications and the highest impact. The research institutions are relatively scattered, with Beijing University of Traditional Chinese Medicine having the highest number of publications. The cooperation among institutions is mainly between universities of traditional Chinese medicine and their affiliated hospitals, and the cross-regional cooperation is not common. The research hotspots are the efficacy of TCM on DN and its mechanism of action, the exploration of TCM and formulas related to the treatment of DN, and the identification and typing of DN in TCM. The research frontiers lie in the control of oxidative stress and the effects of TCM on gut microbiota. In addition, the use of network pharmacology to explore the targets of Chinese herbal formulas for the treatment of this disease has also become popular.Conclusion: TCM provides more possibilities for the treatment of DN. Researchers can refer to the research hotspots and trends in this paper for future research direction, on the one hand, they can focus on the study of the clinical efficacy of TCM and its improvement of renal function, on the other hand, they can also start from the pharmacological mechanism of TCM for the treatment of DN. Among them, improving oxidative stress in human body and regulating gut microbiota are the directions that can be studied.Keywords: diabetes nephropathy, traditional Chinese medicine, citespace, bibliometric analysis, visualization

Li Qiao, Zheng Wang, Jian Shen, Xiaohui Xing, Hongxun Yuan Department of Intensive Care Unit, Peking University International Hospital, Beijing, People’s Republic of ChinaCorrespondence: Hongxun Yuan, Department of Intensive Care Unit, Peking University International Hospital, No. 1 of Life Park Road, Life Science Park of Zhong Guancun, Changping District, Beijing, 102206, People’s Republic of China, Tel +86 10 69006109, Email hongxunyuan_yhx@126.comObjective: To investigate the impact of various sedative medications on hemodynamics and plasma levels of epinephrine (E) and norepinephrine (NE) in mechanically ventilated patients postoperatively in the intensive care unit (ICU).Methods: Ninety-seven patients admitted to the ICU undergoing postoperative mechanical ventilation with tracheal intubation and continuous analgesic sedation following general anesthesia were randomly assigned to either the observation group (dexmedetomidine) (n = 49) or the control group (propofol) (n = 48) in this randomized controlled trial. Upon transfer to the ICU, vital signs (heart rate [HR], respiratory rate [RR], mean arterial pressure [MAP]) were recorded prior to the initiation of the sedation treatment (T0), at one-hour post sedation (T1) and two hours following tracheal extubation (T2), plasma levels of epinephrine (E) and norepinephrine (NE) were measured at these time points. The incidence of delirium was recorded in both groups.Results: MAP between the two groups at both T0 and T1 At T2 plasma NE and HR were found to be lower in the observation group compared to the control group (P < 0.001). Among the patients receiving antihypertensive medication in the ICU, NE levels were significantly lower in the observation group compared to the control group (P = 0.019) Among the patients not receiving antihypertensive medication, both NE (P < 0.001) and MAP (P = 0.001) levels were lower in the observation group compared to the control group. The incidence of delirium in the observation group (dexmedetomidine) was not significantly different from that in the control group (propofol).Conclusion: With dexmedetomidine sedation, blood pressure fluctuated less, plasma catecholamine levels were lower, and sympathetic inhibition was stronger in patients before and after extubation. However, it did not significantly reduce the incidence of postoperative delirium.Keywords: delirium, intensive care unit, hemodynamics, plasma norepinephrine, delirium

Muhammad B Qureshi,1 Jose O Garcia,1 Jaxon Quillen,2 Carolyn Mead-Harvey,2 Christina Wentz,3 Cherie B Nau,4 Muriel Schornack,4 Keith Baratz,4 Sanjay V Patel,4 Joanne Shen5 1Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA; 2Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA; 3Illinois College of Optometry, Chicago, IL, USA; 4Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA; 5Department of Ophthalmology, Mayo Clinic, Scottsdale, AZ, USACorrespondence: Joanne Shen, Department of Ophthalmology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, USA, 85259, Tel +1 480-301-8085, Fax +1 480-301-7326, Email shen.joanne@mayo.eduPurpose: To compare baseline characteristics and treatment of chronic ocular graft-versus-host disease (oGVHD) patients in two treatment locations.Patients and Methods: Patients diagnosed with definite chronic oGVHD between September 1, 2014 and September 20, 2021 at two locations were identified. IRB-approved retrospective chart review was conducted for the following data: demographic information, ocular surface disease index (OSDI), corneal fluorescein staining (CFS), and treatment(s) used. Differences by site were assessed using Pearson’s Chi-Square tests and two-sample t-tests; differences by time were assessed using paired t-tests.Results: At baseline, Clinic 1 (C1) patients had a worse mean OSDI score (47.8 vs 36.3, p = 0.011) and CFS in both OD (1.3 vs 0.8, p = 0.005) and OS (1.3 vs 0.6, p < 0.001) compared to Clinic 2 (C2). Comparing baseline to endpoint, C1 patients experienced an improvement in OSDI (− 17.26, p < 0.001), CFS OD (− 0.50, p < 0.001), and CFS OS (− 0.51, p < 0.001) at C1. Change in OSDI, CFS OD, or CFS OS was not statistically significant at C2. Despite similar follow-up length, C1 demonstrated more clinic visits (10.4 vs 3.4, p < 0.001) and more treatment trials (4.9 vs 2.4, p < 0.001) compared to C2. Punctal plugs (85.5% vs 61.2%, p = 0.002), punctal cautery (69.7% vs 28.6%, p < 0.001), topical steroids (72.4% vs 22.4%, p < 0.001), and autologous serum tears (AST) (52.6% vs 8.2%, p < 0.001) were used more frequently at C1 than at C2.Conclusion: oGVHD patients at C1 experienced significant improvement in OSDI and corneal fluorescein staining and compared to patients at C2, had more frequent follow-up and use of punctal plugs, punctal cautery, topical steroids, and AST.Keywords: graft-versus-host disease, GVHD, chronic GVHD, dry eye disease, ocular GVHD, keratoconjunctivitis sicca, KCS

Fan Li,1,&ast; Chuan-Guo Chen,2,&ast; Jiao-Fei Wei,1,3 Jia-Wen Lin,4 Zi-Ang Dou,3,4 Jun Shen,1 Shu-Qin Li1,3,4 1Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of General Surgery, Nanjing Meishan Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Department of Clinical Medicine, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 4Department of clinical medicine, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Shen; Shu-Qin Li, Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, No. 6 Zhenhua East Road, High-tech Square, Lianyungang, Jiangsu Province, 222002, People’s Republic of China, Tel +861896132532 ; +8618961325781, Email shenjun2257@126.com; shuqinlilsh@126.comObjective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR).Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan–Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes.Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06– 6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66– 3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR.Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.Keywords: breast cancer, NACT, neoadjuvant chemotherapy, non-pCR, non-pathologic complete response, reg IV, risk factor

Haoming Luo,1,2,&ast; Miao Guo,3,4,&ast; Mingxing Li,1 Yueshui Zhao,1 Jing Shen,1 Fukuan Du,1 Yu Chen,1 Shuai Deng,1 Yuhong Sun,1 Li Gu,1 Wanping Li,1 Xiaobing Li,1 Meijuan Chen,1 Zhangang Xiao,1,5,6 Shengpeng Wang,3,4 Xu Wu1,7 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2Department of Pharmacy, Three Gorges University Hospital of Traditional Chinese Medicine & Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei, 443003, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 4Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 5Department of Pharmacy, Gulin County Hospital of Traditional Chinese Medicine, Luzhou, Sichuan, 646500, People’s Republic of China; 6School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan, 621000, People’s Republic of China; 7Department of Paediatric Care, Luzhou People’s Hospital, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengpeng Wang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China, Email swang@um.edu.mo Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@swmu.edu.cnIntroduction: Rhodiola species have been utilized as functional foods in Asia and Europe for promoting health. Research has demonstrated that Rhodiola has the potential to alleviate inflammatory bowel disease (IBD) in animal models. However, the specific active components and the underlying mechanism for ameliorating intestinal damage remain unclear. This study aims to explore the relieving effect of Rosavin (Rov), a known active constituent of Rhodiola, in IBD and the regulatory mechanisms.Methods: The therapeutic effect of Rov was evaluated using a murine model of acute colitis induced by dextran sulfate sodium salt (DSS). Inflammatory cytokines and neutrophil activation markers were measured by corresponding kits. Immunohistochemistry, immunofluorescence, TUNEL, and EdU assays were applied to investigate the tight conjunction proteins expression, epithelial marker expression, number of apoptotic cells, and epithelial proliferation, respectively. The protection effect of Rov on gut epithelial injury was assessed using TNF-α-induced intestinal organoids. Additinally, RNA sequencing was applied to observe the genetic alteration profile in these intestinal organoids.Results: Oral administration of Rov significantly attenuated weight loss and restored colon length in mice. Notably, Rov treatment led to decreased levels of pro-inflammatory cytokines and neutrophil activation markers while increasing anti-inflammatory factors. Importantly, Rov restored intestinal despair by increasing the number of Lgr5+ stem cells, Lyz1+ Paneth cells and Muc2+ goblet cells in intestines of colitis mice, displaying reduced epithelial apoptosis and recovered barrier function. In TNF-α-induced intestinal organoids, Rov facilitated epithelial cell differentiation and protected against TNF-α-induced damage. RNA sequencing revealed upregulation in the gene expression associated with epithelial cells (including Lgr5+, Lyz1+ and Muc2+ cells) proliferation and defensin secretion, unveiling the protective mechanisms of Rov on the intestinal epithelial barrier.Discussion: Rov holds potential as a natural prophylactic agent against IBD, with its protective action on the intestinal epithelium being crucial for its therapeutic efficacy. Keywords: rosavin, colitis, inflammatory bowel disease, organoid, intestinal stem cell

Pengfeng Gong,1,&ast; Jie Shen,1 Yu Yang,2,&ast; Dong Xue,1 Hao Lu,1 Qianfeng Zhuang,1 Xiaogang Wang,1 Zinong Tian,1 Yiming Chen,1 Cheng Chen,1 Yunjie Cao1 1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China; 2Department of Hepato-Pancreato-Biliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunjie Cao, Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China, Tel +86-13775188220, Email caoyunjie1847@163.comObjective: To explore patients’ knowledge, attitude, and practice (KAP) toward varicocele in China and the relationship between treatment selection and KAP.Methods: This cross-sectional study enrolled varicocele patients at the Third Affiliated Hospital of Soochow University (September to October 2023). Structural equation modeling (SEM) was used to explore the relationship between clinical factors and KAP. A score >mean score for each dimension was defined as adequate knowledge, positive attitude, and proactive practice. The patients were grouped according to varicocelectomy vs no surgery. Univariable and multivariable logistic regression analyses were used to identify the factors independently associated with KAP. A structural equation modeling (SEM) analysis was performed to examine how the KAP dimensions influenced each other.Results: Among 502 patients, 44.02%, 35.86%, and 20.12% were ≤ 30, 31– 40, and > 40 years old, respectively. Those who underwent varicocelectomy (n=407) had significantly higher knowledge (20 (15– 22) vs 0 (0– 6), P< 0.001), attitude (26 (24– 26) vs 14 (10– 18), P< 0.001), and practice (20 (17– 24) vs 8 (6– 16), P< 0.001) than those who did not. A higher proportion of patients with varicocelectomy were < 40 years old, more educated, had higher income, and were unmarried compared with those without surgery (all P< 0.001). High school or higher education level and varicocelectomy (irrespective of type) were independently associated with adequate knowledge (all P< 0.001). Knowledge, college/bachelor’s degree education, and varicocelectomy type (irrespective of type) were associated with positive attitudes (all P< 0.05). In the SEM, knowledge directly influenced attitude, knowledge directly influenced practice, and attitude directly influenced practice (all P< 0.001). Having knowledge of the subject may direct varicocele patients to varicocelectomy.Conclusion: Chinese patients who underwent varicocelectomy exhibit appropriate KAP regarding varicocele, while non-surgery patients have poorer KAP. These results suggest that patients who did not undergo surgery should nevertheless be properly informed about their disease.Keywords: knowledge, attitude, practice, varicocele, varicocelectomy, cross-sectional study

Hao-Yu Lu,1,2,&ast; Jia-Jia Wu,1,&ast; Jun Shen,3,4,&ast; Xiang-Xin Xing,1 Xu-Yun Hua,5 Mou-Xiong Zheng,5 Lian-Bo Xiao,3,4 Jian-Guang Xu1,2,6 1Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Orthopedic, Guanghua Hospital of Integrative Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 5Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 6Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Guang Xu, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China, No. 1200 Cailun Road, Shanghai, People’s Republic of China, Tel +86 021-51322091, Fax +86 021-51322042, Email xjg@shutcm.edu.cn Lian-Bo Xiao, Department of Orthopedic, Guanghua Hospital of Integrative Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China, No. 540 Xinhua Road, Shanghai, People’s Republic of China, Tel/Fax +86 021-62805833, Email xiao_lianbo@163.comBackground: The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI).Methods: After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention.Results: EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum.Conclusion: The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.Keywords: knee osteoarthritis, anterior cruciate ligament transection, chronic pain, electroacupuncture, functional connectivity, effective connectivity

Kaiyue Zhang, Chunnan Li, Peitong Wu, Xiaochen Gao, Xueqin Feng, Jiaming Shen, Nanxi Zhang, Xuesheng Hu, Shuo Wang, Hui Zhang, Jingwei Lv, Jiaming Sun Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jiaming Sun; Jingwei Lv, Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Nanguan District, Changchun, 130117, People’s Republic of China, Tel +0431-86763809, Fax + 8676 3968, Email Sun_jiaming2000@163.com; jingwei-lv@hotmail.comPurpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology.Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques.Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes.Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT’s efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management. Keywords: Zhixiao Tang, pneumonia, network pharmacology, integrated metabolomics, 16HBE, Zebrafish

Ming Li,&ast; Xinrui Zhang,&ast; Yujie Zhou, Yuteng Chu, Jie Shen, Yue Cai, Xuanrong Sun Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanrong Sun, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China, Email sunxr@zjut.edu.cnIntroduction: Glioblastoma multiforme (GBM), a highly invasive and prognostically challenging brain cancer, poses a significant hurdle for current treatments due to the existence of the blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions.Methods: We present a biomimetic nanoplatform with angiopep-2-modified macrophage membrane, loaded with indocyanine green (ICG) templated self-assembly of SN38 (AM-NP), facilitating active tumor targeting and effective blood-brain barrier penetration through specific ligand-receptor interaction.Results: Upon accumulation at tumor sites, these nanoparticles achieved high drug concentrations. Subsequent combination of laser irradiation and release of chemotherapy agent SN38 induced a synergistic chemo-photothermal therapy. Compared to bare nanoparticles (NPs) lacking cell membrane encapsulation, AM-NPs significantly suppressed tumor growth, markedly enhanced survival rates, and exhibited excellent biocompatibility with minimal side effects.Conclusion: This NIR-activatable biomimetic camouflaging macrophage membrane-based nanoparticles enhanced drug delivery targeting ability through modifications of macrophage membranes and specific ligands. It simultaneously achieved synergistic chemo-photothermal therapy, enhancing treatment effectiveness. Compared to traditional treatment modalities, it provided a precise, efficient, and synergistic method that might have contributed to advancements in glioblastoma therapy.Keywords: biomimetic macrophage membrane, drug delivery, synergistic treatment, glioma inhibition, near infrared-activatable

Jiping Zhang,&ast; Xianan Sang,&ast; Yichao Yuan, Jiawei Shen, Yuanyuan Fang, Minjing Qin, Hangsheng Zheng, Zhihong Zhu College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 311402, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hangsheng Zheng; Zhihong Zhu, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Email hs-zheng@163.com; zzhjanny@163.comBackground: Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy-&epsiv;-pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound.Methods: The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry.Results: In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype.Conclusion: In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo. Keywords: 4-deoxy-&epsiv;-pyrromycinone, lead compound, drug safety, drug efficacy, anti-tumor drug

Huina Gao,1,* Yijun Song,2,* Kun Liu,1,* Xinyuan Lu,3 Jiacheng Shen,2 Sulan Wei,2 Hongni Jiang,1,2 Nuo Xu2 1Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nuo Xu, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Email xu.nuo@zs-hospital.sh.cn; Hongni Jiang, Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, 668 Jinhu Road, Xiamen, 361015, People’s Republic of China, Email jiang.hongni@zs-hospital.sh.cnPurpose: Cigarette smoking is the most recognized risk factor of chronic obstructive pulmonary disease (COPD) in China. However, there are no studies analyzing the impact of different smoking behaviors on pulmonary function and pulmonary hypertension (PH) among Chinese male patients with COPD.Patients and Methods: Chinese male smokers with COPD performed pulmonary function tests. Clinical characteristics, smoking behavior features, spirometry and echocardiographic results were compared between the two groups stratified by initial smoking age (18 years old) or complicated PH.Results: The early-smoking group had more respiratory symptoms, more severe smoking behavior, worse pulmonary function with lower FEV1%pre (38.5% vs 70.2%) and FEV1/FVC% (47.5% vs 63.8%), and higher systolic pulmonary artery pressure (sPAP: 38.6 vs 33.9 mmHg) than the late-smoking group. Initiating smoking before adulthood was an independently contributing factor of ventilatory dysfunction and Global Initiative for Obstructive Lung Disease (GOLD) stage escalation. It also had a significant interaction with long smoking duration (≥ 30 years), characterized by markedly decreased lung volumes (VC%pre: 64.0% vs 84.5%), impaired diffusing capacity (DLCO%pre: 58.0% vs 76.8%) and severe emphysema (RV/TLC%pre: 145.2% vs 130.2%). COPD patients complicated with PH exhibited worse ventilatory function (FEV1%pre: 43.2% vs 56.2%), impaired diffusion capacity (DLCO%pre: 56.7% vs 77.1%) and decreased lung volume (VC%pre: 67.67% vs 75.38%). Both severe smoking behaviors and impaired pulmonary function had close correlations with sPAP.Conclusion: The early-smoking group exhibited predominantly ventilation dysfunction and had complex interactions with long smoking duration to further affect lung volume and diffusion capacity. Different smoking behaviors influenced variations of pulmonary dysfunction and comorbid PH in patients with COPD.Keywords: chronic obstructive pulmonary disease, pulmonary function, smoking behavior, initial smoking age, pulmonary hypertension

Bo Wang,1,2 Jiquan Shen,2 Changjian Zhou,2 Xinggao Wang,2 Shuanghu Wang,3 Ruixing Hou1 1Department of Orthopaedics, Suzhou Ruihua Orthopedic Hospital Affiliated Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 2Department of Orthopaedics, the Sixth Affiliated Hospital of Wenzhou Medical University, the People’s Hospital of Lishui, Lishui, Zhejiang, 323000, People’s Republic of China; 3Central Laboratory of the Sixth Affiliated Hospital of Wenzhou Medical University, the People’s Hospital of Lishui, Lishui, Zhejiang, 323000, People’s Republic of ChinaCorrespondence: Shuanghu Wang, Central Laboratory of the Sixth Affiliated Hospital of Wenzhou Medical University, the People’s Hospital of Lishui, Lishui, Zhejiang, 323000, People’s Republic of China, Email wangshuanghu@lsu.edu.cn Ruixing Hou, Department of Orthopaedics, Suzhou Ruihua Orthopedic Hospital Affiliated Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China, Email hrx2020@suda.edu.cnBackground: Rheumatoid Arthritis (RA) involves prolonged inflammation of the synovium, damaging joints and causing stiffness and deformity. Celastrol (Cel), derived from the Chinese herbal medicine Tripterygium wilfordii Hook F, offers immunosuppressive effects for RA treatment but is limited by poor solubility and bioavailability.Purpose: In this study, long-circulating Cel-loaded liposomes (Cel-LPs) were used to increase the pharmacokinetics of Cel, thereby improving drug delivery and efficacy for the treatment of RA.Methods: Cel-LPs were prepared and administered orally and intravenously to compare the elimination half-life of drugs and bioavailability of Cel. Cel-LPs were prepared using the lipid thin-layer-hydration-extrusion method. Human rheumatoid arthritis synovial (MH7A) cells were used to investigate the compatibility of Cel-LPs. The pharmacokinetic studies were performed on male Sprague-Dawley (SD) rats.Results: The Cel-LPs had an average size of 72.20 ± 27.99 nm, a PDI of 0.267, a zeta potential of − 31.60 ± 6.81 mV, 78.77 ± 5.69% drug entrapment efficiency and sustained release (5.83 ± 0.42% drug loading). The cytotoxicity test showed that liposomes had excellent biocompatibility and the fluorescence microscope diagram indicated that liposome entrapment increased intracellular accumulation of Rhodamine B by MH7A cells. Furthermore, the results exhibited that Cel-LPs improved the pharmacokinetics of Cel by increasing the elimination half-life (t1/2) to 11.71 hr, mean residence time (MRT(0-∞)) to 7.98 hr and apparent volume of distribution (Vz/F) to 44.63 L/kg in rats, compared to the Cel solution.Conclusion: In this study, liposomes were demonstrated to be effective in optimizing the delivery of Cel, enabling the formulation of Cel-LPs with prolonged blood circulation and sustained release characteristics. This formulation enhanced the intravenous solubility and bioavailability of Cel, developing a foundation for its clinical application in RA and providing insights on poorly soluble drug management.Keywords: celastrol, rheumatoid arthritis, liposomes, oral and intravenous delivery, pharmacokinetic

Shulin Wei,1,2,&ast; Mingxing Li,1,2,&ast; Qin Wang,1,2,&ast; Yueshui Zhao,1,2 Fukuan Du,1,2 Yu Chen,1,2 Shuai Deng,1,2 Jing Shen,1,2 Ke Wu,1,2 Jiayue Yang,1,2 Yuhong Sun,1 Li Gu,1 Xiaobing Li,1 Wanping Li,1 Meijuan Chen,1 Xiao Ling,3 Lei Yu,3 Zhangang Xiao,1,2 Lishu Dong,3 Xu Wu1,2 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, 646100, People’s Republic of China; 3Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lishu Dong, Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China, Email 1275607519@qq.com Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@126.comAbstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.Keywords: mesenchymal stem cells, immunomodulation, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, cell therapy

Guang-Hong Xie,1,&ast; Jun Shen,2,&ast; Fan Li,2 Huan-Huan Yan,2 Ying Qian3 1Department of Operating Room, The First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 2Department of Breast Surgery, The First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 3Department of Operating Room, Wuxi People’s Hospital, Wuxi, Jiangsu, 214063, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Qian Department of Operating Room, Wuxi People’s Hospital, No. 299 Qingyang Road, Liangxi District, Wuxi, 214063, Jiangsu, People’s Republic of China, Tel +8615190209358, Email qianying_q06@126.comObjective: We aimed to analyze the factors related to delay in transfer of patients in the post-anesthesia care unit (PACU) and to develop and validate a prediction model for understanding these factors to guide precise clinical intervention.Methods: We collected data from two cohorts of 1153 and 297 patients who underwent surgery and were treated in the PACU at two time points. We examined their clinical features and anesthesia care data using analytical methods such as logistic regression, Random Forest, and eXtreme Gradient Boosting (Xgboost) to screen out variables and establish a prediction model. We then validated and simplified the model and plotted a nomogram. Using LASSO regression, we reduced the dimensionality of the data. We developed multiple models and plotted receiver operating characteristic (ROC) and calibration curves. We then constructed a simplified model by pooling the identified variables, which included hemoglobin (HB), alanine transaminase (ALT), glucose levels, duration of anesthesia, and the minimum bispectral index value (BIS_min).Results: The model had good prediction performance parameters in the training and validation sets, with an AUC of 0.909 (0.887– 0.932) in the training set and 0.939 (0.919– 0.959) in the validation set. When we compared model 6 with other models, the net reclassification index (NRI) and the integrated discriminant improvement (IDI) index indicated that it did not differ significantly from the other models. We developed a scoring system, and it showed good prediction performance when verified with the training and validation sets as well as external data. Additionally, both the decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated the potential clinical efficacy of the model in guiding patient interventions.Conclusion: Predicting transfer delays in the post-anesthesia care unit using predictive models is feasible; however, this merits further exploration.Keywords: delayed transfer, machine learning, nomogram, post-anesthesia care unit, predictive model

Yutong Zheng,1 Xiaoyi Cai,1 Gui Chen,1 Dexuan Xiang,1 Wei Shi,1 Jianliang Shen,2 Bailin Xiang1 1College of Chemistry and Materials Engineering, Huaihua University, Huaihua, 418000, People’s Republic of China; 2State Key Laboratory of Ophthalmology, Wenzhou Medical University, University of Chinese Academy of Sciences, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Bailin Xiang, College of Chemistry and Materials Engineering, Huaihua University, Huaihua, 418000, People’s Republic of China, Email xsz96@163.com Jianliang Shen, State Key Laboratory of Ophthalmology, Wenzhou Medical University, University of Chinese Academy of Sciences, Wenzhou, 325000, People’s Republic of China, Email shenjl@wiucas.ac.cnPurpose: Recently, Single-atom-loaded carbon-based material is a new environmentally friendly and stable photothermal antibacterial nanomaterial. It is still a great challenge to achieve single-atom loading on carbon materials.Materials and Methods: Herein, We doped single-atom Ag into ZIF-8-derived porous carbon to obtain Ag-doped ZIF-8-derived porous carbon(AgSA-ZDPC). The as-prepared samples were characterized by XRD, XPS, FESEM, EDX, TEM, and HAADF-STEM which confirmed that the single-atom Ag successfully doped into the porous carbon. Further, the photothermal properties and antimicrobial activity of AgSA-ZDPC have been tested.Results: The results showed that the temperature increased by 30 °C after near-infrared light irradiation(1 W/cm2) for 5 min which was better than ZIF-8-derived porous carbon(ZDPC). It also exhibits excellent photothermal stability after the laser was switched on and off 5 times. When the AgSA-ZDPC concentration was greater than 50 μg/mL and the near-infrared irradiation was performed for 5 min, the growth inhibition of S. aureus and E. coli was almost 100%.Conclusion: This work provides a simple method for the preparation of single-atom Ag-doped microporous carbon which has potential antibacterial application.Keywords: Single-atom, Ag, ZIF-8, photothermal, antibacterial

Dongmei Zou,1,&ast; Yanqiong Liu,2,&ast; Youwen Gong,3 Xueqing Zhang,4 Jieqiong Liu,4 Jinhua Shen4 1Department of Cardiovascular Surgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde city), Changde, People’s Republic of China; 2Department of Cardiology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, People’s Republic of China; 3Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, People’s Republic of China; 4Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youwen Gong, Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China, Email 1755144149@qq.com Xueqing Zhang, Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China, Email 382731326@qq.comPurpose: This study investigated the current state of self-efficacy and the association between self-perceived burden (SPB) and health-related quality of life (HRQoL) among Chinese older-adult inpatients.Methods: A cross-sectional study was conducted using convenience sampling to survey Chinese older-adult inpatients. Data regarding demographic characteristics, self-efficacy, SPB, and HRQoL were collected. Pearson’s correlation analysis was used to examine the correlations among the research variables. SPSS® Statistics V26.0, and SPSS® PROCESS Macro Model 4 were used to analyze the available data. The bootstrap method was used to analyze the mediating role of self-efficacy.Results: Survey participants included 514 older-adult inpatients, with a mean age of 72.28± 5.58 years. Self-efficacy (r=0.471, p< 0.01) was positively correlated with HRQoL, whereas self-efficacy (r=− 0.891, p< 0.01) and HRQoL (r=− 0.516, p< 0.01) were negatively correlated with SPB. The mediating effect analysis revealed that self-efficacy either completely or partially mediated the effect of SPB on HRQoL, with the indirect effect accounting for 30.2% of the total.Conclusion: This study provides a mediating model suggesting that SPB exerts both direct and indirect effects on the HRQoL of older-adult inpatients through self-efficacy.Keywords: aging, Chinese, negative emotions, self-efficacy, health-related quality of life, mediating effects

Huaming Xu,1 Chunhui Lin,2,3 Hao Tang,4 Rongrong Li,2,3 Zhaoxin Xia,2,3 Yi Zhu,3 Zhen Liu,2,3 Jilu Shen2,3 1The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, People’s Republic of China; 2The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Public Health Clinical Center, Hefei, People’s Republic of China; 4The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Jilu Shen, Tel +86 151 5515 2963, Email shenjilu@ahmu.edu.cn; 1464675852@qq.comIntroduction: As the last line of defense for clinical treatment, Carbapenem antibiotics are increasingly challenged by multi-drug resistant bacteria containing carbapenemases. The rapid spread of these multidrug-resistant bacteria is the greatest threat to severe global health problems.Methods: To solve the problem of rapid transmission of this multidrug-resistant bacteria, we have developed a rapid detection technology using CRPSPR-Cas12a gene editing based on multiple Recombinase polymerase amplification. This technical method can directly isolate the genes of carbapenemase-containing bacteria from samples, with a relatively short detection time of 30 minutes. The instrument used for the detection is relatively inexpensive. Only a water bath can complete the entire experiment of Recombinase polymerase amplification and trans cleavage. This reaction requires no lid during the entire process while reducing a large amount of aerosol pollution.Results: The detection sensitivity of this method is 1.5 CFU/mL, and the specificity is 100%.Discussion: This multi-scene detection method is suitable for screening populations in wild low-resource environments and large-scale indoor crowds. It can be widely used in hospital infection control and prevention and to provide theoretical insights for clinical diagnosis and treatment.

Runqian Huang,1,&ast; Chunling Zheng,1,2,&ast; Guixiao Xu,1 Xuanwei Chen,1 Jingxian Shen,1 Siyue Mao1 1Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingxian Shen; Siyue Mao, Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Tel/Fax +86-20-87343217, Email shenjx@sysucc.org.cn; maosiy@sysucc.org.cnObjective: To identify imaging features that help distinguish between HCCs and non-HCC malignancies assigned to LI-RADS M (LR-M) and evaluate the diagnostic performance of a LI-RADS with targetoid criteria using thin-rim arterial phase hyperenhancement (APHE).Materials and Methods: This retrospective study included 381 patients (387 observations) at high-risk for HCC who underwent enhanced-MRI before surgery. Three radiologists reviewed images for LI-RADS categorization of hepatic observations. Univariate and multivariate analysis was conducted to determine reliable features to differentiate between HCC and non-HCC malignancies among the LR-M lesions. The thin-rim (< 30%) APHE was defined based on the thickest thickness of rim APHE compared with the tumor radius, and a modified LI-RADS emphasizing thin-rim APHE as a specific feature of LR-M was established. We compared the diagnostic performance of modified LR-M and LI-RADS 5 (LR-5) with the conventional one.Results: Thin-rim APHE and targetoid diffusion-weighted imaging (DWI) were found as independent predictive factors of non-HCC malignancies, while enhancing capsule, thick-rim APHE and peripheral washout were noted as independent variables significantly associated with HCC of LR-M (P< 0.05). The noticeable diagnostic performance of thin-rim APHE in distinguishing non-HCC malignancies from HCCs using the ROC curve. Emphasizing thin-rim APHE on targetoid features, the modified LR-M revealed significantly superior specificity and accuracy (89.4% vs 81.1%, P=0.004; and 87.9% vs 82.2%, P=0.027, respectively) while maintaining high sensitivity (82.2% vs 86.0%; P=0.529) compared with the LR-M. Meanwhile, the modified LR-5 achieved greater sensitivity and accuracy (88.6% vs 79.7%, P=0.004; and 85.8% vs 80.1%, P=0.036, respectively) for diagnosing HCC, without compromising specificity (78.3% vs.81.1%; P=0.608) compared with the LR-5.Conclusion: Thin-rim APHE may be the specific imaging feature for differentiating non-HCC malignancies from HCCs within LR-M. The modified targetoid criteria emphasizing thin-rim APHE can improve the diagnostic performance of LI-RADS for hepatic malignancies.Keywords: hepatic tumors, malignant, targetoid feature, Rim APHE, liver imaging reporting and data system

Hongying Huang, Jinchen Li, Jingyi Shen, Tong Zhao, Rong Xiao, Weiwei Ma School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Weiwei Ma, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83911651, Email weiweima@ccmu.edu.cnBackground and Objective: Cognitive dysfunction is highly prevalent in obese people, and food is a key factor in obesity, and dietary inflammatory index (DII) can reflect whether diet has anti-inflammatory or pro-inflammatory potential. In addition, dietary fatty acid consumption is linked to inflammation, obesity, and cognitive impairment. Erythrocyte membrane fatty acids can reflect dietary fatty acid intake. Our hypothesis was that erythrocyte membrane fatty acids might have a significant impact on the relationship between DII and cognition in obese individuals, and we designed experiments to test the hypothesis.Methods: In three villages in Beijing, we collected 579 respondents from individuals 45 to 75 years old and categorized them by body mass index. The Montreal Cognitive Assessment (MoCA) score and DII score was calculated and gas chromatography was used to measure the proportion of erythrocyte membrane fatty acids. The relationship between the DII score and cognition was examined using multiple linear regression and binary logistic regression. Mediation analysis can help to understand the causal chain between variables, deeply explore the internal relationship and mechanism of action between variables. So a multiple chain mediation model was developed to investigate the mediating factors between the DII score and cognitive association.Results: According to adjusted linear regression, higher DII scores were linked to lower MoCA scores in the obese group. The negative correlation between DII score and cognitive function score remains in binary linear regression. We discovered through mediation analysis that erythrocyte membrane fatty acids mediate the detrimental link between DII and cognitive function in obese individuals.Conclusion: We propose that higher DII scores in obese people are associated with a decline in cognitive function. In addition, this effect might be mediated via the fatty acids in the erythrocyte membrane.Keywords: mild cognitive impairment, dietary inflammatory index, obesity, fatty acids, chain mediation effect

Xian Li,1,&ast; Hong Lai,2,&ast; Peng Wang,3 Shuai Feng,4 Xuexin Feng,4 Chao Kong,3 Dewei Wu,5 Chunlin Yin,5 Jianghua Shen,6 Suying Yan,6 Rui Han,7 Jia Liu,7 Xiaoyi Ren,8 Ying Li,8 Lu Tang,9 Dong Xue,9 Ying Zhao,9 Hao Huang,10 Xiaoying Li,10 Yanhong Zhang,10 Xue Wang,11 Chunxiu Wang,12 Ping Jin,13 Shibao Lu,3 Tianlong Wang,4 Guoguang Zhao,14 Chaodong Wang1 On behalf of the APPLE-MDT Research Team, Xuanwu Hospital, Capital Medical University and National Clinical Research Center for Geriatric Diseases1Department of Neurology & Neurobiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Department of Orthopedic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 5Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 6Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 7Department of Gerontology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 8Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 9Department of Oral Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 10Department of Medical Administration, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 11Department of Medical Library, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 12Center for Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 13Center for Medical Information, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 14Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaodong Wang, Department of Neurology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, No. 45 Changchun Street, Beijing, 100053, People’s Republic of China, Tel/Fax +86-10-8319-8677, Email cdongwang@xwhosp.orgPurpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions.Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥ 1 point between the preoperative and postoperative scale was defined as POCD.Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥ 4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028– 5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057– 0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively.Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.Keywords: cognitive dysfunction, postoperative cognitive complications, orthopedic surgery, comprehensive geriatric assessment, risk factors

Yan Hu,1,&ast; Jiawei Shen,2,&ast; Youzhong An,2 Yanwen Jiang,1 Huiying Zhao2 1Department of Respiratory and Critical Care Medicine, Peking University International Hospital, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiying Zhao, Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China, Email zhaohuiying@pkuph.edu.cnObjective: We aim to identify the clinical phenotypes of immunocompromised patients with pneumonia-related ARDS, to investigate the lung microbiota signatures and the outcomes of different phenotypes, and finally, to develop a machine learning classifier for a specified phenotype.Methods: This prospective study included immunocompromised patients with pneumonia-related ARDS. We identified phenotypes using hierarchical clustering to analyze clinical variables and serum cytokine levels. We then compared outcomes and lung microbiota signatures between phenotypes. Based on lung microbiota markers, we developed a random forest classifier for a specified phenotype with worse outcomes.Results: This study included 92 patients, who were divided into three phenotypes, namely “type α” (N = 33), “type β” (N = 12), and “type γ” (N = 47). Compared to type α or type β, patients with type γ had no obvious inflammatory presentation and had significantly lower IL-6 levels and more severe oxygenation failure. Type γ was also related to higher 30-day mortality and lower ventilator free days. The microbiota signatures of type γ were characterized by lower alpha diversity and distinct compositions than those of other patients. We developed a lung microbiota-derived random forest model to differentiate patients with type γ from other phenotypes.Conclusion: Immunocompromised patients with pneumonia-related ARDS can be clustered into three clinical phenotypes, namely type α, type β, and type γ. Phenotypes were distinguished from each other with different outcomes and lung microbiota signatures. Type γ, which was characterized by insufficient inflammation response and worse outcomes, can be detected with a random forest model based on lung microbiota markers.Keywords: immunocompromised host, respiratory failure, microbiota

Jiangling Wang,1,2,&ast; Lijuan Yang,3,&ast; Wei Liu,1 Chaogang Wei,1 Junkang Shen1 1Department of Radiology, The Second Affiliated Hospital of Soochow University, Soochow, Jiangsu, People’s Republic of China; 2Department of Physical Diagnosis, Huadong Sanatorium, Wuxi, Jiangsu, People’s Republic of China; 3Department of Geriatric, Huadong Sanatorium, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junkang Shen; Chaogang Wei, Department of radiology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Soochow, 215004, People’s Republic of China, Email shenjunkang@suda.edu.cn; weichaogang1122@163.comObjective: Previous research on the correlation between thyroid function and carotid plaque has revealed conflicting results, possibly attributable to the sensitivity of thyroid hormone indices. In this study, we aimed to analyze the association between thyroid hormone sensitivity indices and the risk of carotid plaque development in a Chinese health check-up population.Methods: A total of 19,388 health check-up subjects were included in this study (mean age: 50.78± 10.17 years). Central sensitivity to thyroid hormone was evaluated using the thyroid feedback quantile-based index (TFQI), the Chinese-referenced parametric TFQI (PTFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI), while peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Multivariable logistic regression analyses were performed to detect the association between thyroid hormone sensitivity indices and carotid plaque risk, and subgroup analysis was also conducted to explore this association stratified by sex, age, obesity, and the status of smoking, drinking, diabetes, hypertension and dyslipidemia.Results: Among the 19,388 participants, 3753 (19.4%) had carotid plaque. In multivariable adjustment models, the risk of carotid plaque was positively associated with TSHI (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.18~1.28), TT4RI (OR: 1.28; 95% CI: 1.23~1.33), TFQI (OR: 1.06; 95% CI: 1.02~1.10), and PTFQI (OR: 1.11; 95% CI: 1.07~1.16), respectively. Conversely, the risk of carotid plaque was negatively correlated with FT3/FT4 (OR: 0.94; 95% CI: 0.90~0.98). In stratified analyses, all thyroid hormone sensitivity indices significantly increased the risk of carotid plaque especially in females, subjects< 65 years, non-obese individuals, and those without current smoking, drinking, diabetes, hypertension and dyslipidemia.Conclusion: In Chinese health check-up populations, a considerable connection between reduced sensitivity to thyroid hormones and carotid plaque has been observed, especially in females, those younger than 65 years, non-obese individuals, and those without any current smoking, drinking, diabetes, hypertension, or dyslipidemia.Keywords: carotid plaque, thyroid hormone sensitivity, euthyroid, resistance to thyroid hormone, Chinese population

Zhan Shi,1,&ast; Sihui Zhu,2,&ast; Yuncheng Jin,1 Liang Qi,1 Mingzhen Zhou,1 Ziyan Zhou,1 Juan Zhang,1 Baorui Liu,1 Jie Shen1 1Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China; 2The Comprehensive Cancer Centre of Nanjing International Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Shen; Baorui Liu, Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China, Fax +86-025-83106666, Email shenjie2008nju@163.com; baoruiliu@nju.edu.cnBackground: Stereotactic body radiotherapy (SBRT) has emerged as an alternative approach for patients with hepatocellular carcinoma (HCC), and we aim to find potential prognostic biomarkers for HCC patients who received SBRT.Methods: In this study, we retrospectively analyzed HCC patients who underwent SBRT in our institution from January 2018 to December 2022. The inflammatory parameters, along with baseline patients’ characteristics were collected to elucidate the potential relationship with survival benefits and liver toxicities.Results: Overall, 35 patients were enrolled in our study. For the efficacy population (25 patients who underwent SBRT for primary liver lesions), the objective response rate (ORR) and disease control rate (DCR) were 60% and 100%, respectively. The median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI) 5.6– 14.1 months], and the median overall survival (OS) was 18.5 months (95% CI 14.2– 22.8 months). We further confirmed that higher baseline lymphocyte-C-reactive protein ratio (LCR) (≥ 2361.11) was positively related to both longer PFS (12.0 vs 4.3 months, P = 0.002) and OS (21.9 vs 11.4 months, P = 0.022). Moreover, patients with diabetes and higher alpha-fetoprotein (AFP) (≥ 400 ng/mL) were also found to be associated with worse OS. The most common hepatotoxicity was elevated gamma-glutamyl transferase (GGT) (84.0%).Conclusion: In conclusion, for patients with inoperable HCC, SBRT resulted in satisfactory local control, survival benefits, and acceptable liver toxicity. Pre-radiotherapy LCR might be an independent and readily available predictor for survival, which facilitates us to find the most appropriate treatment options.Keywords: hepatocellular carcinoma, stereotactic body radiotherapy, lymphocyte-C-reactive protein ratio, survival, liver toxicity

Yuye Chen,1 Yue Liu,2 Hong Lv,1 Qian Li,1 Jingjia Shen,1 Weiyun Chen,2 Jia Shi,1 Chenghui Zhou3 1Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, 100037, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of ChinaCorrespondence: Chenghui Zhou, Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-137-1889-4919, Email chenghuizhou@vip.163.com Jia Shi, Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, No. 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email shijia@fuwai.comBackground: The potential myocardial protective effect of nicorandil (NICD) in patients undergoing percutaneous coronary intervention has been established. However, its efficacy in the context of cardiac surgery remains controversial. The present study aimed to evaluate the myocardial protective effect of perioperative NICD use in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).Methods: We retrospectively gathered data from patients undergoing cardiac bypass surgery between 12/2018 and 04/2021 in Fuwai Hospital. Subsequently, the patients were divided into two groups, NICD group and non-nicorandil (non-NICD) group. A 1, 3 propensity score matching (PSM) was conducted. The primary outcome was the incidence of myocardial injury. The secondary outcomes included the mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of chest drainage, the drainage volume, the total cost, the incidence of acute kidney injury (AKI), and the incidence of acute liver injury (ALI). Subsequently, we divided the entire population into two distinct subgroups based on their administration of NICD, and performed a comprehensive subgroup analysis.Results: A total of 2406 patients were ultimately included in the study. After PSM, 250 patients in NICD group and 750 patients in non-NICD group were included in the analysis. Perioperative NICD reduced the incidence of myocardial injury (47.2% versus 38.8%, P=0.025). Our subgroup analysis revealed that preoperative NICD administration not only provided myocardial protection benefits (45.7% vs 35.8%, OR 0.66, 95% CI [0.45– 0.97], P=0.041), but also demonstrated statistically significant reduction in ALI, the ICU and hospital LOS, and the duration of chest drainage (all P< 0.05).Conclusion: The perioperative NICD administration may confer myocardial protection in patients undergoing cardiac surgery with CPB. Furthermore, the preoperative utilization of NICD has the potential to mitigate the incidence of postoperative ALI, a reduction in the ICU and hospital LOS, and the duration of chest drainage.Keywords: nicorandil, cardiopulmonary bypass, perioperative myocardial injury, acute kidney injury, acute liver injury

Jiaming Shen,1,2,&ast; Xia Wang,2,&ast; Guangde Yang,2,&ast; Li Li,2 Juanjuan Fu,2 Wei Xu,3 Qingqiao Zhang,3 Xiucheng Pan2 1Department of Gastroenterology, People’s Hospital of Jingjiang, Taizhou, People’s Republic of China; 2Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Interventional Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiucheng Pan, Tel +8618052268129, Email xzpxc68@126.comPurpose: Recently, the triple therapy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) has become a new treatment option for advanced or unresectable hepatocellular carcinoma (HCC) patients. We aimed to explore the liver injury and its effect on overall survival (OS) in patients treated with this combination therapy.Patients and Methods: Patients with HBV-related HCC who were treated with TACE-TKIs-ICIs from January 2020 to December 2021 were enrolled. Liver injury and survival time were the main endpoints of the study. Logistic regression analysis was used to analyze the factors associated with liver injury. Cox regression and Kaplan–Meier analysis were used to determine prognostic factors for OS.Results: As of March 2022, 52 of the 119 enrolled patients developed any grade hepatotoxicity: 15 cases with grade 1, 19 cases with grade 2, 16 cases with grade 3 and 2 cases with grade 4. Our analysis indicated that lack of antiviral prevention was a risk factor for liver injury (OR = 0.149; 95% CI: 0.050– 0.442; P = 0.001). The findings suggested that liver injury events (HR = 1.912; 95% CI: 1.031– 3.546; P = 0.040) was associated with patient death. The median OS of patients without liver injury, grade 1– 2 and grade 3– 4 liver injury were undefined, 13.7 months and 11.1 months, respectively (log-rank P = 0.034).Conclusion: Liver injury adverse events are common in HBV-related HCC patients treated with TACE-TKIs-ICIs. Patients who developed liver injury had a poor prognosis. For HBV-related HCC patients, effective prophylactic antiviral therapy and regular liver function testing are required before and during this triple therapy. Keywords: HBV-related HCC, TACE, TKI, ICI, liver injury, survival time

Liang Zhang,1,&ast; Jun Wang,1,&ast; Yang Li,2 Leina Hou,3 Jianguo Xia,4,&ast; Jialin Shen1,&ast; 1Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Anesthesiology, Shaanxi Provincial Cancer Hospital, Xi’an, Shaanxi, People’s Republic of China; 4Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianguo Xia, Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NO. 160 Pujian Road, Shanghai, People’s Republic of China, Tel +86-13671807078, Fax +86-21-34506514, Email xiajianguo@renji.com Jialin Shen, Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NO. 160 Pujian Road, Shanghai, People’s Republic of China, Tel +86-13501794493, Fax +86-21-34506368, Email jialinshen123@163.comPurpose: To investigate the feasibility and efficacy of implanting an iodine-125 (125I) seed strand inside a portal vein stent (PVS) in the treatment of patients with hepatocellular carcinoma (HCC) and main portal vein tumor thrombus (mPVTT).Patients and Methods: Twenty-three patients who diagnosed with HCC and mPVTT and underwent endovascular implantation 125I seed strands and portal vein stenting were included in this study. Patients were divided into two groups. For patients in group A (n = 12), the 125I seed strand was placed outside the PVS, and for those in group B (n = 11), the strand was placed inside the PVS. Technical success, pain intensity during the procedure (numeric rating scale), procedure-related complications, changes in liver function, stent patency, and survival rates were recorded and analyzed.Results: The procedures were successful in all patients, and no serious procedure-related complications occurred in either group. Pain intensity during the procedure was significantly lower in group B than in group A (2.64 ± 1.50 vs 4.08 ± 1.78, p = 0.048), and there were no significant differences between pre- and post-procedure liver function in either group. The median duration of stent patency was 9 months (95% CI 2.21– 15.79 months) in group A and 12 months (95% CI 3.63– 18.37 months) in group B (p = 0.670). Median survival was 12 months (95% CI 10.30– 13.70 months) in group A and 13 months (95% CI 10.03– 15.97 months) in group B (p = 0.822). The cumulative stent patency and survival rates at 3, 6, and 12 months were 75%, 50%, and 41.7%, and 83.3%, 75%, and 50% in group A and 72.7%, 62.3%, and 31.2%, and 90.9%, 80.8%, and 50.5%, respectively.Conclusion: Implantation of 125I seed strand inside the PVS is effective and feasible for treating patients with HCC and mPVTT.Keywords: portal vein tumor thrombus, 125I seed, portal vein stent, endovascular brachytherapy, hepatocellular carcinoma

Jianjun Huang,1 Fangping Shao,2 Bin Chen,1 Guanrong Zheng,1 Jia Shen,1 Shenzhong Qiu1 1Department of Neurosurgery, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of China; 2Emergency Department, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of ChinaCorrespondence: Shenzhong Qiu, Department of Neurosurgery, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of China, Email chengiftboy@163.comBackground: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability and is up-regulated during axonal regeneration. Here, serum SPARCL1 was determined for estimating severity and prognosticating early neurological deterioration (END) and functional outcomes of acute intracerebral hemorrhage (ICH).Methods: In this prospective observational cohort study of 156 patients with supratentorial ICH, blood samples of 53 were acquired not only at admission but also ad days 1, 3, 5, 7 and 10. Another group of 53 healthy controls were recruited. The modified Rankin Scale (mRS) scores of 3– 6 at poststroke six months were regarded as poor prognosis.Results: As opposed to controls, serum SPARCL1 levels were markedly elevated during the early ten days after ICH, with the highest levels at days 1 and 3. Admission serum SPARCL1 levels were independently correlated with National Institutes of Health Stroke Scale scores and hematoma volume, were significantly increased in the order of six-month mRS scores from 0 to 6 and were independently correlated with six-month mRS scores. Serum SPARCL1 levels were linearly related to risks of poor six-month prognosis and END under restricted cubic spline, had significant efficiency under receiver operating characteristic (ROC) curve and were independently associated with END and poor prognosis. Subgroup analysis confirmed that no interactions existed for associations of serum SPARCL1 levels with other variables, such as age, gender and some specific vascular risk factors. END and poor prognosis prediction models integrating serum SPARCL1 were displayed using the two nomograms. The poor prognosis prediction model, but END prediction model not, performed well under calibration curve, decision curve and ROC curve.Conclusion: A substantial elevation of serum SPARCL1 levels during the early period after ICH is independently related to illness severity and poor neurological outcomes, thus signifying that serum SPARCL1 may appear as a prognostic biomarker of ICH.Keywords: Secreted protein acidic and rich in cysteine-like 1, intracerebral hemorrhage, early neurologic deterioration, prognosis, severity, biomarkers

Jun Shen,1,2,&ast; Junqing Liang,1,2,&ast; Manzeremu Rejiepu,1,2,&ast; Ping Yuan,3 Jie Xiang,1,2 Yankai Guo,1,2 Jiasuoer Xiaokereti,1,2 Ling Zhang,1,2 Baopeng Tang1,2 1Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhang, Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Tel/Fax +86 18690280833, Email ydzhangling@126.com Baopeng Tang, Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan Road, Urumqi, Xinjiang, 830000, People’s Republic of China, Tel/Fax +86 13477301883, Email tangbaopeng1111@163.comObjective: This study aimed to identify a newly identified target involved in atrial fibrillation (AF) linked to chronic obstructive sleep apnea (COSA) through an integrative analysis of transcriptome and proteome.Methods: Fifteen beagle canines were randomly assigned to three groups: control (CON), obstructive sleep apnea (OSA), and OSA with superior left ganglionated plexi ablation (OSA+GP). A COSA model was established by intermittently obstructing the endotracheal cannula during exhalation for 12 weeks. Left parasternal thoracotomy through the fourth intercostal space allowed for superior left ganglionated plexi (SLGP) ablation. In vivo open-chest electrophysiological programmed stimulation was performed to assess AF inducibility. Histological, transcriptomic, and proteomic analyses were conducted on atrial samples.Results: After 12 weeks, the OSA group exhibited increased AF inducibility and longer AF durations compared to the CON group. Integrated transcriptomic and proteomic analyses identified 2422 differentially expressed genes (DEGs) and 1194 differentially expressed proteins (DEPs) between OSA and CON groups, as well as between OSA+GP and OSA groups (1850 DEGs and 1418 DEPs). The analysis revealed that differentially regulated DEGs were primarily enriched in mitochondrial biological processes in the CON-vs.-OSA and OSA-vs.-GP comparisons. Notably, the key regulatory molecule GSTZ1 was activated in OSA and inhibited by GP ablation.Conclusion: These findings suggest that GSTZ1 may play a pivotal role in mitochondrial damage, triggering AF substrate formation, and increasing susceptibility to AF in the context of COSA.Keywords: atrial fibrillation, obstructive sleep apnea, transcriptome, proteomic, ganglionated plexi ablation

Ze-Xin Hu,&ast; Xiao-Yang Xu,&ast; Ze Wang,&ast; Jin-Tao Huang, Wan-Ci Li, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu; Bin-Yan Zhong, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, 215006, People’s Republic of China, Tel/Fax +86 512 67972173, Email zhuxiaoli90@163.com; byzhongir@sina.comBackground: The CRAFITY (C-reactive protein and alpha-fetoprotein in immunotherapy) score has demonstrated prognostic significance in hepatocellular carcinoma (HCC) patients undergoing immunotherapy. The study aimed to validate accuracy of CRAFITY score on predicting prognosis for patients with HCC treated with transarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapy.Methods: Eighty-five HCC patients who underwent TACE in combination with molecular targeted therapy (MTT) and PD-(L)1 Inhibitors were consecutively enrolled from November 2019 to November 2022. Patients were divided into CRAFITY 0 score (n=32), CRAFITY 1 score (n=31), and CRAFITY 2 score (n=22), respectively. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes included tumor response rate and treatment-related adverse events (TRAEs). Factors affecting survival were identified via Cox regression analysis.Results: The median overall survival (OS) for HCC patients with CRAFITY scores of 0, 1, and 2 was 33.4 months (95% confidence interval [CI]: 27.1– 39.7), 34.5 months (95% CI: 23.1– 45.9), and 24.2 months (95% CI: 13.9– 39.3), respectively, there were statistical differences among the three groups (p< 0.05). The progression-free survival (PFS) was 14.1 months (95% CI: 10.0– 18.2), 14.1 months (95% CI: 9.0– 19.2), and 9.3 months (95% CI: 7.2– 11.4) for patients with CRAFITY scores of 1, 2, and 3, respectively, with a significant difference between the three groups (p< 0.05). In patients with CRAFITY scores of 1, 2, and 3, the disease control rates (DCR) were 94%, 84%, and 73%, respectively (p < 0.05), while the overall response rates (ORR) were 78.1%, 67.7%, and 59.1%, respectively (p = 0.318). A higher CRAFITY score showed a correlation with an increased frequency of fatigue and grade 3 fever (p< 0.05). Moreover, CRAFITY 2 score was an independent risk factor for both OS (HR = 2.610(1.281– 4.564), p = 0.014) and PFS (HR = 2.419(1.281– 4.564), p = 0.006).Conclusion: The CRAFITY score may provide an efficient predictive capacity for prognosis in HCC patients undergoing TACE combined with PD-(L)1 inhibitors and molecular targeted therapy.Keywords: hepatocellular carcinoma, transarterial chemoembolization, C‑reactive protein and alpha‑fetoprotein in immunotherapy score, PD-(L)1 inhibitors, tyrosine kinase inhibitors, combination therapy

Rongrong Li,1,2 Xuhang Shen,3 Zhengyuan Li,4 Jilong Shen,2 Hao Tang,5 Huaming Xu,6 Jilu Shen,1,7 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Department of Clinical Laboratory, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China; 7Anhui Public Health Clinical Center, Hefei, People’s Republic of ChinaCorrespondence: Yuanhong Xu, Tel +86 13505694447, Email xyhong1964@163.comBackground: In recent years, carbapenem-resistant Pseudomonas aeruginosa (CRPA) has spread around the world, leading to a high mortality and close attention of medical community. In this study, we aim to find a new strategy of treatment for CRPA infections.Methods: Eight strains of CRPA were collected, and PCR detected the multi-locus sequence typing (MLST). The antimicrobial susceptibility test was conducted using the VITEK@2 compact system. The minimum inhibitory concentration (MIC) for AS101 and mefloquine was determined using the broth dilution method. Antibacterial activity was tested in vitro and in vivo through the chessboard assay, time killing assay, and a mouse model. The mechanism of AS101 combined with mefloquine against CRPA was assessed through the biofilm formation inhibition assay, electron microscopy, and detection of reactive oxygen species (ROS).Results: The results demonstrated that all tested CRPA strains exhibited multidrug resistance. Moreover, our investigation revealed a substantial synergistic antibacterial effect of AS101-mefloquine in vitro. The assay for inhibiting biofilm formation indicated that AS101-mefloquine effectively suppressed the biofilm formation of CRPA-5 and CRPA-6. Furthermore, AS101-mefloquine were observed to disrupt the bacterial cell wall and enhance the permeability of the cell membrane. This effect was achieved by stimulating the production of ROS, which in turn hindered the growth of CRPA-3. To evaluate the therapeutic potential, a murine model of CRPA-3 peritoneal infection was established. Notably, AS101-mefloquine administration resulted in a significant reduction in bacterial load within the liver, kidney, and spleen of mice after 72 hours of treatment.Conclusion: The present study showed that the combination of AS101 and mefloquine yielded a notable synergistic bacteriostatic effect both in vitro and in vivo, suggesting a potential clinical application of this combination in the treatment of CRPA.Keywords: AS101, mefloquine, carbapenem resistance, Pseudomonas aeruginosa, synergy, biofilm

Huang J, Shao F, Chen B, Zheng G, Shen J, Qiu S. Neuropsychiatr Dis Treat. 2023;19:2709–2728. The authors have advised that the funding statement on page 2727 is incorrect. The text “(No. 202107071918000249496)” should read “(No. 20201203B59)”. The authors apologize for this error.

Wenwen Sun,1,&ast; Jun Shen,1,&ast; Ru Sun,1 Dan Zhou,1 Haihong Li2 1Department of Breast Surgery, the First People’s Hospital of Lianyungang, the Affiliated Hospital of XuZhou Medical University, LianYunGang, Jiangsu, 222002, People’s Republic of China; 2Department of Nursing, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, LianYunGang, Jiangsu, 222002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haihong Li, Department of Nursing, the First People’s Hospital of Lianyungang, the affiliated hospital of XuZhou medical university, No. 6 Zhenhua East Road, High-Tech Square, LianYunGang, Jiangsu Province, 222002, People’s Republic of China, Tel +86 18961322059, Email haihonglired@126.comObjective: In this study, we aim to establish and evaluate a predictive model for post-treatment anxiety state based on basic patient attributes and pre-treatment SAS scores, with the expectation that this model will guide clinical precision intervention.Methods: Data were collected from 606 patients with breast cancer who underwent surgery at our hospital between January 1, 2015 and December 30, 2018 and 144 newly diagnosed patients with breast cancer who were admitted between June 1, 2019 and December 30, 2019, for a total of 750 patients with breast cancer. The relationship between SAS_A scores and prognosis was verified by analyzing patient baseline characteristics, follow-up data, pre-treatment self-rating anxiety scale (SAS) scores, and SAS_A scores in follow-up period after the end of treatment. A risk prediction model was developed in view of the SAS_A scores, which was then screened, validated, and simplified by scoring, with a nomogram plotted.Results: The SAS_A score can be utilized to differentiate prognosis. In K-M analysis, the high SAS_A score group had a significantly poorer progression-free survival rate than the low score group, p-value < 0.0001. Through model feature selection and clinical analysis, all variables were finally incorporated to establish a predictive model with a ROC AUC of 0.721 (0.637– 0.805) for the validation set and external data, and an AUC of 0.810 (0.719– 0.902) for external data, demonstrating good predictive performance. Calibration curves and probability distribution maps were constructed. DCA and CIC analyses demonstrated that model intervention could boost clinical benefits more effectively than intervention for all patients.Conclusion: Using a predictive model to guide clinical management for anxiety in breast cancer patients is feasible, but additional research is required.Keywords: breast cancer, negative emotions, nomogram, predictive model

Hangting Li,1,&ast; Xiaolian Wu,1,&ast; Jiaoni Shen,2 Shuhui Lou2 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, People’s Republic of China; 2School of Nursing, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuhui Lou, School of Nursing, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Email loushh@zcmu.edu.cnBackground: Drug treatment is critical for patients with aplastic anemia, and medication adherence directly impacts the therapeutic effect. Poor medication adherence is common among patients with chronic diseases. However, knowledge of the perceptions and experiences of patients with aplastic anemia regarding taking prescribed medicines is limited.Objective: To gain insights into the perceptions and experiences of patients with aplastic anemia regarding taking prescribed medicines.Methods: A descriptive qualitative design was used. Fifteen patients with aplastic anemia were recruited from the hematology department. Individual semi-structured interviews were conducted. The data were analyzed using the thematic analysis method and conceptualized using the Health Belief Model.Results: Five themes emerged: the perceived threat of aplastic anemia, perceived benefits and barriers of taking prescribed medicines, cues to action, self-efficacy, and modifying factors. While patients’ knowledge was limited, they acknowledged the threat of aplastic anemia and the necessity of drug treatments, but they also encountered some barriers in practice. The desire for health and healthcare providers’ opinions were the main clues to medication adherence. The expectation of the future and the sense of self-competency made participants adopt good behavior.Discussions: This study provided new perspectives on the medication adherence of patients with aplastic anemia, which may be valuable in clinical work and research. Further interventions should be developed for intentional and unintentional non-compliance. Future research can start with developing professional assessment tools addressing the influence of cognition and emotion on compliance.Keywords: aplastic anemia, China, health belief model, medication adherence, perception, qualitative research

Weiqiang Fei,1 Jun Shen,2 Hui Cai3 1College of Nursing, Hangzhou Vocational & Technical College, Hangzhou, Zhejiang Province, People’s Republic of China; 2Nursing Department, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Nursing Department, Jiangsu Province Hospital Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Weiqiang Fei, College of Nursing, Hangzhou Vocational & Technical College, 68 Xueyuan Street, Xiasha Higher Education Park, Qiantang District, Hangzhou, Zhejiang Province, 310018, People’s Republic of China, Tel/Fax +86-571-56700120, Email weiqiangfei@126.comPurpose: The purpose of the study is to analyze FAERS data to identify drugs associated with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), determine demographics, drug classes involved, most likely resulted in death, and highlight emerging trends in SJS/TEN reactions.Patients and Methods: We reviewed the publicly available FAERS database from 2004– 2021. Using search terms “Stevens-Johnson syndrome” or “Toxic epidermal necrolysis”, we identified the reports of SJS/TEN or SJS/TEN followed by death that might associated with specific drugs. Then the amounts and trends were counted analyzed.Results: During the study period of 2004– 2021, the Food and Drug Administration (FDA) received a total of 14,363,139 reports of adverse reactions, among which 24,976 were linked to SJS or TEN. After excluding the cases with incomplete or insufficient information on age, gender, or country of origin, the median median age of patients was 53.82 (IQR = 57.52), the females accounted for 56.59% (12,827 cases) and 8,507 (38.34%) originated in the United States. The top 50 drugs were associated with 15,149 cases (60.65%). The subsequent fatal outcome occurring in 4878 out of 24,976 cases (19.53%). Top 3 drug classes associated with SJS/TEN in FAERS were antiepileptics, non-steroidal anti-inflammatory drugs (NSAIDs) and others. Top drug classes associated with SJS/TEN deaths were antineoplastic agents and cephalosporins. Linear regression showed that the annual percentage of monoclonal antibody-related SJS/TEN reactions increased at an average rate of 0.25% (95% confidence interval: 0.18, 0.32) from 0.00% in 2004 to 4.79% in 2021, faster than any other drug class except antigout drug (allopurinol).Conclusion: By using the publicly available FAERS data, we have identified some important themes and trends in drug-related SJS/TEN reactions. Monoclonal antibodies and proton pump inhibitors are drugs with emerging trends causing SJS/TEN. Additionally, cephalosporin antibiotics have a higher mortality rate following SJS/TEN.Keywords: Stevens-Johnson syndrome, SJS, toxic epidermal necrolysis, TEN, adverse drug reactions, fatal outcome, trends

Chunhui Lin,1,2,&ast; Hao Tang,3,&ast; Xinyi Hu,1,2 Ge Li,1,2 Tong Jiang,1,2 Wensu Yang,1,2 Zhaoxin Xia,1,2 Yi Zhu,1,2 Huaming Xu,4 Jing Zhou,1,2 Jilu Shen1,2 1Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Clinical Laboratory, Anhui Public Health Clinical Center Hefei, Hefei, People’s Republic of China; 3Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Clinical Laboratory, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jilu Shen, Tel +86 151 5515 2963, Email shenjilu@ahmu.edu.cnIntroduction: It is time-consuming to identify fungal pathogens from positive blood cultures using the standard culture-based method. And delayed diagnosis of bloodstream infection leads to significantly increased mortality.Methods: We developed a PCR-reverse dot blot hybridization combined with microfluidic chip techniques to rapidly identify 13 fungal pathogens within 3– 4 h using the sample of blood cultured over a period of time.Results: We performed clinical validation using 43 blood culture-positive samples with a sensitivity of 96.7%, a specificity of 100%, and a concordance rate of 97.7%. Samples with different culture durations were evaluated using our approach, showing a detection rate of 85.2% at 16 h and 96.3% at 24 h; the platform could reach a detection limit of 103cfu/mL for the Candida spp. and 103 copies/mL for Aspergillus spp.Discussion: The detection rate of the platform is much higher than the positive rates of concurrent blood cultures. This method bears substantial clinical application potential as it incorporates the microfluidic platform with low reagent consumption, automation, and low cost (about 10 dollars).Keywords: fungemia, bloodstream infection, microfluidics, Candida auris, PCR-reverse dot blot hybridization

JianBo Wu,1,&ast; ZhuJun Tao,1,&ast; NingZhou Gao,1 Jie Shen,1 Zhi-Long Chen,1 HaiFeng Zhou,1 SongBai Zheng2 1Department of Pharmacy, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Geriatrics, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: HaiFeng Zhou, Department of Pharmacy, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 13918194105, Email zhouhaifeng23@126.comObjective: To evaluate the psychometric properties of the 14-item health literacy scale (HL-14) in patients living with type 2 diabetes mellitus (T2DM) in clinical setting.Methods: Cross-sectional study using item response theory and structural equation modeling (SEM) for testing the item difficulty and three dimensional-HL configurations was adopted in this study. Chinese patients living with T2DM admitted to endocrinology department of Huadong hospital were evaluated by the HL-14 including communication, functional and critical health literacy from August to December 2021.Results: The multidimensional random coefficients multinomial logistic model indicated the difficulty settings of the scale are appropriate for the study populations, and differential item functioning was not observed for sex in the study. SEM demonstrated that the three-dimensional configuration of the scale is good in the study population (x2/df=2.698, Comparative Fit Index = 0.965, Root Mean Square Error of Approximation = 0.076, standard residual mean root = 0.042).Conclusion: The HL-14 scale is a reliable and valid measurement, which can perform equitably across sex in evaluating the health literacy in Chinese patients living with T2DM. Moreover, the scale may help fill the gaps of multidimensional health literacy assessment and rapid screening of health literacy ability for clinical practice.Keywords: health literacy, type 2 diabetes, psychometric properties, multidimensional item response theory, structural equation model

Chunhui Shu,1,&ast; Jiaqiang Zhou,2,&ast; Hongqiong Yu,1 Weijing Fu,1 Jiayi Shen,1 Linchun Liang,3 Lisi Zheng,4 Lin Mao,5 Xuyan Fu,4 Tao Lv,4,6 Yunbo Chen4 1Department of Laboratory Medicine, Ningbo Mingzhou Hospital, Ningbo, People’s Republic of China; 2Department of Neurosurgery, Ningbo Mingzhou Hospital, Ningbo, People’s Republic of China; 3Department of Oncology, Ningbo Mingzhou Hospital, Ningbo, People’s Republic of China; 4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 5Department of Rehabilitation Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 6Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Lv; Yunbo Chen, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Tel/Fax +86 571-87236756, Email xifan_lvtao@163.com; chenyunbo@aliyun.comBackground: Clostridioides difficile is an important pathogen causing approximately 20– 30% of the cases-with antibiotic-associated diarrhea and 90% of those with Pseudomembranous enteritis. However, limited surveillance of C. difficile infections (CDI) in China is done at present, especially in terms of multi-hospital epidemiological reports.Methods: Between June 2020 and November 2020, we conducted a prospective study addressing antimicrobial susceptibility profiles and genomic epidemiology of C. difficile strains isolated from inpatients with diarrhea in seven tertiary hospitals in the same city.Results: In total, 177 strains of toxin-producing C. difficile were isolated, and the dominant toxin gene profiles were tcdA+tcdB+ (84.2%, 149/177) and tcdA-tcdB+ (15.8%, 28/177). Furthermore, 130 isolates were successfully analyzed for antimicrobial susceptibility phenotype in which the rates of resistance to clindamycin, erythromycin, levofloxacin, and moxifloxacin were higher than to other antibiotics. All strains were susceptible to metronidazole and vancomycin. Fluoroquinolone-associated mutations (such as gyrA) were the most frequently found ones in the analyzed genomes. Moreover, 24 different sequence types (STs) were identified in the 130 isolates, and the most prevalent types were ST3 (26.2%, 34/130) followed by ST54 (16.9%, 22/130) and ST2 (10%, 13/130). The so-called highly virulent strain ribotyping 027 (B1/NAP1/ST1) was not identified. In addition, we also compared single nucleotide polymorphisms (SNPs) among the isolates and carried out genomic epidemiological studies on the isolates. We found that ST3 and ST54 could cause transmission in both intra- and inter-hospital settings.Conclusion: Although it is the so-called hypervirulent epidemic strain, ribotyping 027 (ST1), was not detected. ST3 and ST54 can be transmitted through different hospitals. Therefore, it is necessary to conduct further molecular epidemiological monitoring of C. difficile and screening of patients admitted to key departments.Keywords: Clostridioides difficile infection, genomic analysis, toxin gene, antibiotic resistance, transmission

Jun-Peng Zhang,1,&ast; Jun Shen,2,3,&ast; Yun-Ting Xiang,1,&ast; Xiang-Xin Xing,4 Bing-Xin Kang,5 Chi Zhao,2 Jia-Jia Wu,4 Mou-Xiong Zheng,4,6 Xu-Yun Hua,4,6 Lian-Bo Xiao,2,3 Jian-Guang Xu1,4,7 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Orthopedic, Guanghua Hospital of Integrative Chinese and Western Medicine, Shanghai, People’s Republic of China; 3Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 5The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 6Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 7Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China&ast;These authors contributed equally to this workCorrespondence: Jian-Guang Xu, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, People’s Republic of China, Email xjg@shutcm.edu.cn Lian-Bo Xiao, Department of Orthopedic, Guanghua Hospital of Integrative Chinese and Western Medicine, 540 Xinhua Road, Changning District, Shanghai, People’s Republic of China, Email xiao_lianbo@163.comIntroduction: Osteoarthritis is a chronic, ongoing disease that affects patients, and pain is considered a key factor affecting patients, but the brain changes during the development of osteoarthritis pain are currently unclear. In this study, we used electroacupuncture (EA) to intervene the rat model of knee osteoarthritis and analyzed the changes in topological properties of brain networks using graph theory.Methods: Sixteen SD rat models of right-knee osteoarthritis with anterior cruciate ligament transection (ACLT) were randomly divided into electroacupuncture intervention group and control group. The electroacupuncture group was intervened on Zusanli (ST36) and Futu (ST32) for 20 min each time, five times a week for 3 weeks, while the control group was applied sham stimulation. Both groups were measured for pain threshold. The small-world properties and node properties of the brain network between the two groups after the intervention were statistically analyzed by graph theory methods.Results: The differences are mainly in the changes in node attributes between the two groups, such as degree centrality, betweenness centrality, and so on in different brain regions (P< 0.05). Both groups showed no small-world characteristics in the brain networks of the two groups. The mechanical thresholds and thermal pain thresholds were significantly higher in the EA group than in the control group (P< 0.05).Conclusion: The study demonstrated that electroacupuncture intervention enhanced the activity of nodes related to pain circuit and relieved pain in osteoarthritis, which provides a complementary basis for explaining the effect of electroacupuncture intervention on pain through graphical analysis of changes in brain network topological properties and helps to develop an imaging model for pain affected by electroacupuncture.Keywords: osteoarthritis, electroacupuncture, pain, spatio-temporal analysis, neural plasticity

Chao Cao,1– 4 Obulkasim Memet,1– 3 Fuli Liu,1,2 Hanbing Hu,1– 3 Lin Zhang,1,2 Heng Jin,4 Yiqun Cao,4 Jian Zhou,3,5,6 Jie Shen1– 3 1Center of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, Shanghai, People’s Republic of China; 3Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 4Emergency Department, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 6Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Jie Shen, Center of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, Shanghai, 201508, People’s Republic of China, Tel +86 2134189990, Email jshen_@fudan.edu.cnPurpose: Chemically induced acute lung injury (CALI) has become a serious health concern in our industrialized world, and abnormal functional alterations of immune cells crucially contribute to severe clinical symptoms. However, the cell heterogeneity and functional phenotypes of respiratory immune characteristics related to CALI remain unclear.Methods: We performed scRNA sequencing on bronchoalveolar lavage fluid (BALF) samples obtained from phosgene-induced CALI rat models and healthy controls. Transcriptional data and TotalSeq technology were used to confirm cell surface markers identifying immune cells in BALF. The landscape of immune cells could elucidate the metabolic remodeling mechanism involved in the progression of acute respiratory distress syndrome and cytokine storms. We used pseudotime inference to build macrophage trajectories and the corresponding model gene expression changes, and identified and characterized alveolar cells and immune subsets that may contribute to CALI pathophysiology based on gene expression profiles at single-cell resolution.Results: The immune environment of cells, including dendritic cells and specific macrophage subclusters, exhibited increased function during the early stage of pulmonary tissue damage. Nine different subpopulations were identified that perform multiple functional roles, including immune responses, pulmonary tissue repair, cellular metabolic cycle, and cholesterol metabolism. Additionally, we found that individual macrophage subpopulations dominate the cell-cell communication landscape. Moreover, pseudo-time trajectory analysis suggested that proliferating macrophage clusters exerted multiple functional roles.Conclusion: Our findings demonstrate that the bronchoalveolar immune microenvironment is a fundamental aspect of the immune response dynamics involved in the pathogenesis and recovery of CALI.Graphical Abstract: Keywords: single cell RNAseq, phosgene-inhalation, chemically induced acute lung injury, immune microenvironment, heterogeneity, phenotypes

Wensu Yang,1,2 Zhaoxin Xia,1,2 Yi Zhu,1,2 Hao Tang,1,2 Huaming Xu,1,2 Xinyi Hu,1,2 Chunhui Lin,1,2 Tong Jiang,1,2 Pei He,1,2 Jilu Shen1,2 1The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China; 2Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of ChinaCorrespondence: Jilu Shen, Tel +86-15155152963, Email shenjilu@ahmu.edu.cnBackground: Fecal microbiota transplantation (FMT) has emerged as a new therapy targeting gastrointestinal microbiota for the treatment of a growing number of diseases in recent years. Previous studies have suggested that FMT may be a potential therapy for type 2 diabetes (T2D), but the underlying mechanism remains unclear. Therefore, in the present study, we aimed to investigate the role of FMT in T2D and its underlying mechanisms.Methods: To induce T2D, mice were fed a high-fat diet and injected with low-dose streptozotocin (STZ) for four weeks. The mice were then randomly divided into four groups: control group (n = 7), T2D group (n = 7), metformin (MET)-treated group (n = 7), and FMT group (n = 7). The MET group was orally administered 0.2 g/kg MET, the FMT group was orally administered 0.3 mL of bacterial solution, and the other two groups were orally administered the same volume of saline for four weeks. Serum and fecal samples were collected for non-targeted metabolomics, biochemical indicators, and 16S rRNA sequencing, respectively.Results: Our results demonstrated that FMT had a curative effect on T2D by ameliorating hyperlipidemia and hyperglycemia. Using 16S rRNA sequencing and serum untargeted metabolomic analysis, we found that FMT could restore the disorders of gastrointestinal microbiota in T2D mice. Moreover, corticosterone, progesterone, L-urobilin, and other molecules were identified as biomarkers after FMT treatment. Our bioinformatics analysis suggested that steroid hormone biosynthesis, arginine, proline metabolism, and unsaturated fatty acid biosynthesis could be potential regulatory mechanisms of FMT.Conclusion: In summary, our study provides comprehensive evidence for the role of FMT in the treatment of T2D. FMT has the potential to become a promising strategy for the treatment of metabolic disorders, T2D, and diabetes-related complications.Keywords: type 2 diabetes, fecal microbiota transplantation, gastrointestinal microbiota, untargeted metabolomics, 16S rRNA, corticosterone

Zeyi Liang,&ast; Jiahao Shen,&ast; Jing Liu, Xu Sun, Yayuan Yang, Yanan Lv, Juanshan Zheng, Xiaoqing Mou, Hongsheng Li, Xuezhi Ding, Feng Yang Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, Gansu, 730050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Yang; Xuezhi Ding, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, No. 335 Jiangouyan, Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China, Tel +86-931-2115262, Fax +86-931-2114180, Email yangfeng@caas.cn; dingxuezhi@caas.cnPurpose: This study aimed to investigate the prevalence and genetic characterization of Serratia marcescens isolates from clinical bovine mastitis in Ningxia Hui Autonomous Region of China.Methods: S. marcescens was identified by the polymerase-chain reaction of 16S rRNA gene and sequencing. Antimicrobial susceptibility was tested by the disk diffusion method. Genes of resistance and virulence were determined by the PCR.Results: Overall, S. marcescens were confirmed from 32 of 2897 (1.1%) mastitis milk samples. These isolates showed high resistance to cefazolin (30/32, 93.8%) and chloramphenicol (28/32, 87.5%). A 12.5% (4/32) of the isolates displayed multidrug resistance (MDR). The most prevalent resistant genes found in S. marcescens were TEM (32/32, 100%) and CTX-M (24/32, 75.0%; CTX-M-15, 14/32, 43.8%; CTX-M-14, 8/32, 25.0%; CTX-M-65, 2/32, 6.3%) for extended-spectrum beta-lactamase, cmlA (28/32, 87.5%) and floR (16/32, 50.0%) for chloramphenicol resistance, SIM-1 (2/32, 6.3%) for carbapenemases, and sdeB (28/32, 87.5%), sdeY (26/32, 81.3%), sdeR (26/32, 81.3%) and sdeD (20/32, 62.5%) for efflux pumps. Moreover, all isolates carried virulence genes flhD, entB, and kpn, and most of them contained mrkD (30/32, 93.8%), ycfM (26/32, 81.3%), bsmB (26/32, 81.3%), pigP (26/32, 81.3%), kfu (24/32, 75.0%) and shlB (24/32, 75.0%).Conclusion: To our knowledge, this is the first report of genetic determinants for antimicrobial resistance and virulence in S. marcescens isolated from bovine mastitis cases in China. These findings are useful for developing strategies for prevention and treatment of bovine mastitis caused by S. marcescens in China.Keywords: Serratia marcescens, bovine mastitis, antimicrobial resistance, virulence

Guanxiang Huang,1– 3,&ast; Hangjing Gao,1– 3,&ast; Yanlin Chen,1,2 Wenyu Lin,1– 3 Jun Shen,4 Shuxia Xu,5 Dabin Liu,6 Zhihui Wu,7 Xite Lin,1– 3 Tingting Jiang,1– 3 Binhua Dong,1– 3 Pengming Sun1– 3 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China; 2Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children’s Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 4Fujian Provincial Cervical Disease Diagnosis and Treatment Health Center, Fujian Maternity and Child Health Hospital, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 5Department of Pathology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 6Department of Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 7Department of Clinical Laboratory, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengming Sun; Binhua Dong, Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-591-87558732 ; +86-13599071900, Fax +86-591-87551247, Email fmsun1975@fjmu.edu.cn; sunfemy@hotmail.com; dongbinhua86@fjmu.edu.cn; dbh18-jy@126.comPurpose: The platelet-to-lymphocyte ratio (PLR) is considered correlated with cancer prognosis including cervical cancer, in addition to high-risk papillomavirus (HR-HPV) infection, of which the predictive value in prognosis of high-grade squamous intraepithelial lesions (HSILs) remains unknown. Here, the prognostic predictive value of PLR in HSIL after loop electrosurgical excision procedure (LEEP) was evaluated.Patients and Methods: This study included 335 nonpregnant participants with histopathologically confirmed HSIL and 3- and 5-year follow-ups from the Fujian Cervical Lesions Screening Cohorts (FCLSCs) between September 2016 and September 2018. PLR and other variables were evaluated to identify the factors related to the recurrence/residual cervical intraepithelial neoplasia (CIN)-free survival (RFS), namely, the time from LEEP at baseline to first detection of recurrence/residual CIN or end of follow-up, by logistic and Cox regression.Results: In the Kaplan‒Meier analysis, HR-HPV infection (p=0.049/0.012), higher PLR (p=0.031/0.038), and gland invasion (p=0.047) had a higher risk for recurrence/residual CIN at the 3-/5-year follow-up. The univariate logistic and Cox regression analyses showed significant differences and a higher cumulative risk in patients with HR-HPV infection (OR=3.917, p=0.026; HR=3.996, p=0.020) and higher PLR (OR=2.295, p=0.041; HR=2.161, p=0.030) at the 5-year follow-up. The findings by multivariate Cox regression analysis were similar, indicating a poor prognosis for patients with HR-HPV infection (HR=3.901, p=0.023) and higher PLR (HR=2.082, p=0.038) at the 5-year follow-up. The calibration plot showed a better model fit for RFS at the 3-year follow-up.Conclusion: Preoperative PLR level and HR-HPV infection could be available markers for predicting recurrence/residual disease of HSIL after LEEP. Clinically, combining PLR with HR-HPV tests may provide novel evaluation method and reference for management in post-treatment patients with cervical precancerous lesions.Keywords: systemic inflammatory response, cervical intraepithelial neoplasia, human papillomavirus, HPV, conization, prognosis

Jiacheng Sun,1,2,&ast; Guoping Cai,1,2,&ast; Jinlong Shen,1,2 Pu Cheng,1,2 Jiapeng Zhang,1,2 Dengteng Jiang,1,2 Xianquan Xu,1,2 Fangying Lu,1,2 Lihua Chen,1,2 Haixiao Chen1,2 1Department of Orthopaedics, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, People’s Republic of China; 2Bone Development and Metabolism Research Center of Taizhou Hospital, Linhai, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixiao Chen; Lihua Chen, Department of Orthopaedics, Taizhou Hospital Affiliated to Wenzhou Medical University, N.150 Ximen Road of Linhai City, Taizhou, Zhejiang Province, People’s Republic of China, Tel +86 15268400288, +86 13757624851, Email sun846231221@163.com; lhchen2008@126.comBackground: Osteoporosis is a metabolic bone disease. Osteoclasts are significantly involved in the pathogenesis of osteoporosis. AS-605240 (AS) is a small molecule PI3K-γ inhibitor and is less toxic compared to pan-PI3K inhibitors. AS also exerts multiple biological effects including anti-inflammatory, anti-tumor, and myocardial remodeling promotion. However, the involvement of AS in the differentiation and functions of osteoclasts and the effect of AS in treating patients with osteoporosis is still unclear.Purpose: This study aimed to investigate if AS inhibits the differentiation of osteoclasts and resorption of the bones induced by M-CSF and RANKL. Next, we evaluated the therapeutic effects of AS on bone loss in ovariectomy (OVX)-induced osteoporosis mice models.Methods: We stimulated bone marrow-derived macrophages with an osteoclast differentiation medium containing different AS concentrations for 6 days or 5μM AS at different times. Next, we performed tartrate-resistant acid phosphatase (TRAP) staining, bone resorption assay, F-actin ring fluorescence, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting (WB). Next, MC3T3-E1s (pre-osteoblast cells) were differentiated to osteoblast by stimulating the cells with varying AS concentrations. Next, we performed alkaline phosphatase (ALP) staining, RT-qPCR, and WB on these cells. We established an OVX-induced osteoporosis mice model and treated the mice with 20mg/kg of AS. Finally, we extracted the femurs and performed micro-CT scanning, H&E, and TRAP staining.Results: AS inhibits the formation of osteoclasts and resorption of bone triggered by RANKL by inhibiting the PI3K/Akt signaling pathway. Furthermore, AS enhances the differentiation of osteoblasts and inhibits bone loss due to OVX in vivo.Conclusion: AS inhibits osteoclast production and enhances osteoblast differentiation in mice, thus providing a new therapeutic approach for treating patients with osteoporosis.Keywords: AS-605240, PI3Kγ, osteoclast, PI3K/Akt, osteoporosis

Jun Shen,1,&ast; Huanhuan Yan,1,&ast; Congying Yang,2 Haiyue Lin,2 Fan Li,1 Jun Zhou1 1Department of Breast Surgery, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 2Department of Pathology, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhou, Department of Breast surgery, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, No. 6 Zhenhua East Road, High-Tech Square, Lianyungang, Jiangsu Province, 222002, People’s Republic of China, Tel +86 18961326373, Email zhoujunzj91@126.comObjective: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients.Methods: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression.Results: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714– 0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786– 0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581– 0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use.Conclusion: We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.Keywords: breast cancer, nomograms, prediction model, prognosis, UBE2C

Rongrong Li,1,2 Huaming Xu,3 Hao Tang,4 Jilu Shen,1,5 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, People’s Republic of China; 3The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China; 4Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Anhui Public Health Clinical Center, Hefei, People’s Republic of ChinaCorrespondence: Yuanhong Xu, Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China, Tel +86 13505694447, Email xyhong1964@163.comBackground: Bloodstream infection (BSI) is a common type of infection frequently diagnosed in clinics. The emergence and spread of ESBLs-producing Escherichia coli (E. coli) has emerged as one of the biggest challenges in global community health.Methods: The production of ESBLs was determined by the composite disk diffusion method. The expression of the various resistance and virulence genes were detected by PCR and sequencing. Multi-locus sequence typing (MLST) and phylogenetic groups were used for the classification. The transfer of resistant plasmids was determined by conjugation assay. The statistical differences were analyzed using Statistical Product and Service Solutions (SPSS) version 23.0.Results: A total of 60 strains of ESBLs-producing E. coli were collected. The resistance genes that were identified included blaCTX-M, blaTEM, blaSHV, blaOXA-1 and mcr-1. The most common one was the blaCTX-M including blaCTX-M-27 (n = 16), blaCTX-M-14 (n = 15), blaCTX-M-15 (n = 11), blaCTX-M-55 (n = 14) and blaCTX-M-65 (n = 5). A total of 31 STs were detected, and the most abundant among which was ST131 (n = 16, 26.7%). Most of the E. coli (n = 46, 76.7%) belonged to the groups B2 and D. And some virulence genes were related to the classification of the E. coli. Among them, the detection rates of hek/hra, kpsMII and papGII-III in groups B2 and D were higher than those in groups A and B1. The detection rates of cnf1, iucC and papGII-III in ST131 were higher than those in non-ST131. And the distributions of hek/hra, iroN, iucC, kpsMII and papGII-III were related to the blaCTX-M subtypes. Finally, most bacterial (n = 32, 53.3%) resistance genes could be transferred between the bacteria by plasmids, especially IncFIB.Conclusion: ESBLs-producing E. coli in BSI exhibited had high resistance rates and carried a variety of virulence factors (VFs). This is necessary to strengthen the monitoring of ESBLs-producing isolates in the medical environment.Keywords: Escherichia coli, sepsis, beta-lactamases, blaCTX-M

Jian Lin,1,&ast; Tianpeng Shi,2,&ast; Yi Wang,1 Zhiqi He,1 Zhixiang Mu,1 Xiaojun Cai,1 Hui Deng,1 Jianliang Shen,3– 5 Fen Liu6 1School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Stomatology, PLA Strategic Support Force Medical Center, Beijing, People’s Republic of China; 3State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, People’s Republic of China; 5Department of Regenerative Medicine, Vision, and Brain Health, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Wenzhou, People’s Republic of China; 6Department of Histology and Embryology, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Deng; Fen Liu, Email dh0726@gmail.com; liufen6459@163.comBackground: Much attention has been paid to sustained drug release and anti-infection in wound management. Hydrogels, which are biocompatible materials, are promising tools for controlled drug release and infective protection during wound healing. However, hydrogels also demonstrate limitations in the highly efficient treatment of wounds because of the diffusion rate. In this work, we explored pH-sensitive hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties.Methods: We constructed a hybrid gelatin methacrylate (GelMA) system with sustainable antibacterial properties combining hyaluronic acid (HA)-coated mesoporous silica nanoparticles (MSN), which loaded host-guest complexes of chlorhexidine (CHX) with β-cyclodextrins (β-CD) (CHX⊂CD-MSN@HA@GelMA). The release mechanism of CHX was explored using UV-vis spectra after intermittent diffusion of CHX. The hybrid hydrogels were characterized, and the drug content in terms of the release profile, bacterial inhibition, and in vivo experiments were investigated.Results: Except for dual protection from both hydrogels, MSN in the HA improved the drug loading efficiency to promote the local drug concentration. It showed that complicated CHX-loaded MSN releases CHX more gradually and over a longer duration than CHX-loaded MSNs. This demonstrated a 12-day CHX release time and antibacterial activity, primarily attributable to the capacity of β-CD to form an inclusion complex with CHX. Meanwhile, in vivo experiments revealed that the hydrogels safely promote skin wound healing and enhance therapeutic efficacy.Conclusion: We constructed pH-sensitive CHX⊂CD-MSN@HA@GelMA hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties. The combination of β-CD and MSN would be better suited to release a reduced rate of active molecules over time (slow delivery), making them great candidates for wound dressing anti-infection materials.Keywords: mesoporous silica, cyclodextrin, pH-responsive, antibacterial property, wound healing

Li Chang,1,2 Chaoyin Zhang,1 Jingjing Lu,1 Jiahui Shen,1 Krishna Hamal,1 Donghua Liu1,2 1Department of Dermatology and Venereology, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Guangxi Key Laboratory of AIDS Prevention and Treatment, Nanning, People’s Republic of ChinaCorrespondence: Donghua Liu, Department of Dermatology and Venereology, the First Affiliated Hospital of Guangxi Medical University, No. 6, Shuang Yong Road, Nanning, Guangxi Province, 530021, People’s Republic of China, Tel +86 771-5356752, Email ldhgxmu@163.comPurpose: To examine the clinical and pathological features, laboratory markers, therapeutic options and risk factors indicating poor prognosis of hydroa vacciniforme-like lymphoproliferative disorder (HVLPD).Patients and Methods: Seven patients with HVLPD had their clinical and pathological data collected. Immunohistochemical staining, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization experiments, T-cell receptor (TCR) gene rearrangement, RT-PCR tests and the Elisa assay were carried out.Results: The main clinical manifestations were papulovesicular lesions and ulcers on the face, neck, or trunk. Five cases had systemic symptoms. Three of the deceased patients had significant facial edema, deep body necrosis, and ulceration. The pathological results demonstrated that lymphocytes infiltrated blood vessels and sweat glands in addition to the dermis and subcutaneous tissues. All patients tested positive for CD3 and EBER. Six cases tested positive for TCRβF1, but none tested positive for TCRδ. TCRγ monoclonal rearrangement, strongly positive expression of TIA-1 and a Ki67 proliferation index of 40% occurred in 3 fatal cases. When compared to the survival group, the plasma EBV DNA in the deceased group was considerably higher (P< 0.05). IFN-γ and TNF-α cytokine levels in patients were higher than in the control group, particularly in the deceased group (P< 0.05). The skin lesions on all patients recovered quickly underwent conservative care. Nonetheless, 3 patients passed away as the disease progressed in its latter stages.Conclusion: In our cases, the main infiltrating cells were T cells and the dominant lymphocyte subclass was αβT cells. A significant increase in lgE level, plasma EBV DNA, IFN-γ, and TNF-α cytokine levels, decreased hemoglobin level, strongly positive expression of TIA-1, high Ki67 proliferation index, and positive TCR gene rearrangement are all indicators of a poor prognosis.Keywords: hydroa vacciniforme-like lymphoproliferative disorder, hydroa vacciniforme, Epstein-Barr virus, Epstein-Barr virus-encoded RNA, risk factors

Wangxing Lu,1,&ast; Wenjie Liu,1,&ast; Anna Hu,1 Jian Shen,1 Hanxi Yi,2 Zeneng Cheng1 1Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410000, People’s Republic of China; 2School of Basic Medical Science, Central South University, Changsha, 410000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanxi Yi; Wenjie Liu, Email hanxiyi2022@csu.edu.cn; wenjie.liu@csu.edu.cnIntroduction: Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Methods: ICG and DOX were co-incorporated in polyethylene glycol modified liposomes, which were further coated with PDA by a facile two-step method to construct PDA-liposome nanoparticles (PDA@Lipo/DOX/ICG). The safety of nanocarriers was investigated on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, and combinatorial treatment effect of the nanoparticles were assessed on human breast cancer cells MDA-MB-231. In vivo biodistribution, thermal imaging, biosafety assessment, and combination therapy effects were estimated based on MDA-MB-231 subcutaneous tumor model.Results: Compared with DOX·HCl and Lipo/DOX/ICG, PDA@Lipo/DOX/ICG showed higher toxicity on MDA-MB-231 cells. After endocytosis by target cells, PDA@Lipo/DOX/ICG produced a large amount of ROS for PDT by 808 nm laser irradiation, and the cell inhibition rate of combination therapy reached up to 80.4%. After the tail vein injection (DOX equivalent of 2.5 mg/kg) in mice bearing MDA-MB-231 tumors, PDA@Lipo/DOX/ICG significantly accumulated at the tumor site at 24 h post injection. After 808 nm laser irradiation (1.0 W/cm2, 2 min) at this timepoint, PDA@Lipo/DOX/ICG efficiently suppressed the proliferation of MDA-MB-231 cell and even thoroughly ablated tumors. Negligible cardiotoxicity and no treatment-induced side effects were observed.Conclusion: PDA@Lipo/DOX/ICG is a multifunctional nanoplatform based on PDA-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Keywords: reactive oxygen species, photodynamic therapy, photothermal therapy, polydopamine, liposome

Jie Shen,1,2,&ast; Xiao Long,3,&ast; Qi Jiang,1 Hao Xu,2 Qinming Wei,1 Qingmiao Shi,2 Yi Liu,2 Shanshan Xu,1 Xiaolu Ma,1 Lanjuan Li2 1Department of Medical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Orthopedics, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lanjuan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel +86-571-87236458, Fax +86-571-87236459, Email ljli@zju.edu.cnPurpose: In China, vancomycin-resistant enterococci (VRE) was not a common occurrence, and research on the genetic context and transmission mechanism of vanA-plasmid was scarce. The aim of this study was to molecularly characterise a vancomycin-resistant Enterococcus faecium isolate from a bloodstream infection and determine the genetic environment and delivery pattern of the plasmid carrying vancomycin-resistant gene.Materials and Methods: In May 2022, a vancomycin-resistant strain of Enterococci was identified during routine screening for VRE bacteria at the First Affiliated Hospital, Zhejiang University School of Medicine. Utilizing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), the isolate was accurately identified. Antimicrobial susceptibility and whole-genome sequencing (WGS) were employed to perform phenotypic and genomic analysis, respectively. Further bioinformatics analyses was carried out to characterize the vanA-bearing plasmid.Results: The antimicrobial susceptibility test showed that SJ2 strain was resistant to multiple antimicrobials, including ampicillin, benzylpenicillin, ciprofloxacin, erythromycin, levofloxacin, streptomycin, and vancomycin. Whole-genome analysis revealed that SJ2 strain carries several antimicrobial resistance genes and virulence determinants. MLST analysis found that SJ2 strain belongs to an unknown ST type. Plasmid analysis confirmed that the vanA gene was located on a variant of ~50 kb rep2 plasmid.Conclusion: Our study found that vanA-bearing rep2 plasmid is a potential source of dissemination and outbreak, and continuous surveillance is necessary to control its spread in Hangzhou, China.Keywords: vancomycin-resistant Enterococcus faecium, vanA, whole genome sequencing, rep2