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Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Na Li,1,* Yue-xiang Ren,2,* Heng-ming Ye,1,3 Ying Lin,4 Qiang Liu,5 Jiao Wang,1 Ze-fang Ren,1 Lin Xu1,6,7 1The School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Public Health Service Center of Bao’an District, Shenzhen, People’s Republic of China; 4The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6School of Public Health, the University of Hong Kong, Hong Kong; 7Institute of Applied Health Research, University of Birmingham, Birmingham, UK*These authors contributed equally to this workCorrespondence: Ze-fang Ren; Lin Xu, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel +0086-20-87332577 ; Tel +0086-20- 87335523, Fax +011-86-20-87332577, Email renzef@mail.sysu.edu.cn; xulin27@mail.sysu.edu.cnPurpose: Chlamydia trachomatis (C. trachomatis) is associated with several gynecological tumors; yet its prognostic role in breast cancer remains unclear. Thus, we investigated the prognostic role of anti-C. trachomatis immunoglobulin G (IgG) in breast cancer patients and the modification effects of pro-inflammatory cytokines.Methods: The serum levels of C. trachomatis IgG and four pro-inflammatory cytokines were measured. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), including product terms to assess the modification effects of pro-inflammatory cytokines on the association between C. trachomatis IgG and breast cancer prognosis.Results: From 2008 to 2018, 1121 breast cancer patients were recruited and followed up until December 31, 2021, with a median follow-up time of 63.91 months (interquartile range: 39.16– 90.08 months). Patients positive for C. trachomatis IgG showed HRs of 1.09 (95% CI, 0.67– 1.78) for overall survival (OS) and 1.24 (0.87– 1.78) for progression-free survival (PFS), compared to those who were negative. These associations became statistically significant in women aged 50 years or younger (HR=1.43, 95% CI=0.79– 2.58 for OS; HR=1.79, 95% CI=1.16– 2.77 for PFS). Positive C. trachomatis IgG serology was associated with adverse prognostic effects among patients with higher levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β), but with favorable prognostic effects for those with low levels. These interactions were particularly significant in those aged 50 years or younger.Conclusion: In breast cancer patients younger than 50 years of age or with higher levels of pro-inflammatory cytokines, C. trachomatis infection appeared to have a negative prognostic impact. These findings highlight the significance of C. trachomatis in predicting prognosis and personalized therapy for breast cancer patients.Keywords: Chlamydia trachomatis, breast cancer, prognosis, pro-inflammatory cytokines

Linghong Guo,1,2 Xu Liu,1,2 Qingfeng Liu,1,2 Xiaoqin Xie,1,2 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-028-85423315, Fax +86-028-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comObjective: This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy of tranexamic acid essence combined with iontophoresis in treating melasma.Methods: Thirty participants were recruited and randomly assigned to the experimental (Group A) or control group (Group B). Group A received tranexamic acid essence iontophoresis treatment twice weekly for three months, while Group B received placebo treatment. Melasma Area and Severity Index (MASI) scores and skin luminance (L) values were assessed at baseline and weeks 4, 8, and 12.Results: No significant differences in baseline characteristics were observed between the groups. The mean MASI score reduction rate was significantly higher in Group A (− 0.10± 0.12%) compared to Group B (− 0.02± 0.09%) (p< 0.05). Skin L values significantly increased in Group A from 61.32± 3.53 to 63.32± 1.78, while slightly decreasing in Group B (p=0.037).Conclusion: Tranexamic acid essence combined with iontophoresis significantly improved MASI scores and skin luminance compared to placebo, demonstrating its effectiveness in treating melasma. Further research with larger sample sizes and longer follow-up is warranted to validate long-term effects and recurrence rates.Keywords: tranexamic acid, iontophoresis, melasma, clinical trial

Yue He,1,&ast; Qianhan Liu,1,&ast; Yurong Zheng,1 Shengdan Liu,1 Mingling Yu,1 Changhe Ren,2 Guangxiang Chen1 1Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Pain, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changhe Ren, Department of Pain, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982784626, Email riverrch@163.com Guangxiang Chen, Department of Radiology, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982409881, Email cgx23ly2002@163.comPurpose: Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood.Patients and Methods: Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed.Results: One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively.Conclusion: This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.Keywords: functional MRI, degree centrality, zoster-associated pain, anxiety, depression

Qingyang Liu,1,&ast; Jian Wang,2,&ast; Chunhui Ding,3 Ying Chu,1 Fengying Jiang,1 Yunxia Hu,4 Haifeng Li,2 Qiubo Wang1 1Department of Clinical Laboratory, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 3Department of Pharmacy, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 4Department of Rheumatology and Immunology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiubo Wang, Department of Clinical Laboratory, Wuxi Ninth People’s Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangqiubo2020@suda.edu.cn Haifeng Li, Department of orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, Jiangsu, 214000, People’s Republic of China, Email lihaifeng2008@suda.edu.cnPurpose: Sinomenine (SIN) is commonly used in Traditional Chinese Medicine (TCM) as a respected remedy for rheumatoid arthritis (RA). Nevertheless, the therapeutic mechanism of SIN in RA remains incompletely understood. This study aimed to delve into the molecular mechanism of SIN in the treatment of RA.Methods: The potential targets of SIN were predicted using the TCMSP server, STITCH database, and SwissTarget Prediction. Differentially expressed genes (DEGs) in RA were obtained from the GEO database. Enrichment analyses and molecular docking were conducted to explore the potential mechanism of SIN in the treatment of RA. In vitro and in vivo studies were conducted to validate the intervention effects of SIN on rheumatoid arthritis, as determined through network pharmacology analyses.Results: A total of 39 potential targets associated with the therapeutic effects of SIN in RA were identified. Enrichment analysis revealed that these potential targets are primarily enriched in PI3K-Akt signaling pathway, and the molecular docking suggests that SIN may act on specific proteins in the pathway. Experimental results have shown that exposure to SIN inhibits cytokine secretion, promotes apoptosis, reduces metastasis and invasion, and blocks the activation of the PI3K-Akt signaling pathway in RA fibroblast-like synoviocytes (RA-FLS). Moreover, SIN treatment alleviated arthritis-related symptoms and regulated the differentiation of CD4+ T cells in the spleen of collagen-induced arthritis (CIA) mice.Conclusion: By utilizing network pharmacology, molecular modeling, and in vitro/in vivo validation, this study demonstrates that SIN can alleviate RA by inhibiting the PI3K-Akt signaling pathway. These findings enhance the understanding of the therapeutic mechanisms of SIN in RA, offering a stronger theoretical foundation for its future clinical application. Keywords: sinomenine, rheumatoid arthritis, network pharmacology, PI3K-Akt signaling pathway

Xiao Wei,1,&ast; Yun Zhao,1,&ast; Wenyue Yan,2 Qigang Dai,3 Hui Wu,1 Yang Miao,1 Lei Huang,1 Qing Liu,4 Xuyao Zhang,5 Hongxia Wang,1 Yanan Liu,1 Linlin Zhang1 1Department of Pharmacy, The First People’s Hospital of Yancheng, Yancheng No.1 People’s Hospital, Affiliated Hospital of Medical School, Nanjing University, Yancheng, Jiangsu, 224000, People’s Republic of China; 2Department of Oncology, The First People’s Hospital of Yancheng, Yancheng No.1 People’s Hospital, Affiliated Hospital of Medical School, Nanjing University, Yancheng, Jiangsu, 224000, People’s Republic of China; 3Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, 210009, People’s Republic of China; 4Department of Pharmacy, Yancheng Maternity and Child Health Care Hospital, Yancheng, Jiangsu, 224000, People’s Republic of China; 5Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Zhang; Yanan Liu, Department of Pharmacy, The First People’s Hospital of Yancheng, Yancheng No.1 People’s Hospital, Affiliated Hospital of Medical School, Nanjing University, Yancheng, Jiangsu, 224000, People’s Republic of China, Email 1515605617@qq.com; lynishot@163.comBackground: Anlotinib and apatinib, both vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), are clinically established in the treatment of advanced non-small cell lung cancer (NSCLC) in China, with anlotinib emerging as a standard treatment strategy. This study was conducted to evaluate the efficacy and safety of apatinib and anlotinib, and to compare their differences in treating patients with advanced NSCLC.Patients and Methods: We retrospectively analyzed the data of patients with advanced NSCLC treated with apatinib or anlotinib at a hospital in Eastern China from January 2017 to December 2021. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profile.Results: A total of 145 patients were included in this study. Median PFS (mPFS) was 3.53 months for the apatinib group and 5.3 months for the anlotinib group (HR = 0.59, 95% CI: 0.41– 0.84; P = 0.004), and median OS (mOS) was 7.6 months versus 15.6 months (HR = 0.68, 95% CI: 0.46– 1.00; P = 0.048), which all showed significant differences after adjusting for confounders (P < 0.05). Subgroup analysis revealed that the presence or absence of bone metastases significantly influenced PFS in both treatment groups. The ORR was 3.03% in the anlotinib group versus 10.13% in the apatinib group (P = 0.12), the DCR was 72.73% versus 51.90% (P = 0.21). No unanticipated adverse events (AEs) were observed. The incidence of grade 3– 4 AEs was significantly higher in the apatinib group (31.65% vs 13.64%, P < 0.05).Conclusion: Anlotinib demonstrated greater efficacy and safety compared to apatinib in the treatment of advanced NSCLC, particularly in patients with bone metastases and EGFR(-).Keywords: non-small cell lung cancer, anti-angiogenic drug, VEGFR-TKIs, real-world research, bone metastases

Wenguang Deng, Zhiming Zeng, Qingyan Liu, Jingjing Deng, Liyu Wang, Hui Li, Yuenong Zhang The Anesthesiology Surgery Center of The Third Affiliated Hospital of Sun Yat-sen University-Yuedong Hospital, Guangdong, People’s Republic of ChinaCorrespondence: Yuenong Zhang, Email 36856665@qq.comBackground: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery.Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II–III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups.Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels.Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.Keywords: remimazolam tosilate, propofol, remifentanil, hemodynamic, inflammatory, laparoscopic surgery

Qiming Gan,1,&ast; Quanzhen Liu,1,2,&ast; Yanjuan Wu,1,&ast; Xiaofeng Zhu,1,2 Jingcun Wang,1 Xiaofen Su,1 Dongxing Zhao,1 Nuofu Zhang,1 Kang Wu1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Disease, Department of Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2Nanshan School, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kang Wu; Nuofu Zhang, Department of Pulmonary and Critical Care Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No. 28 Qiaozhong Mid Road, Guangzhou, Guangdong, 510160, People’s Republic of China, Email d102_wk@126.com; nfzhanggird@163.comPurpose: Obstructive sleep apnea (OSA) had been associated with asthma in observational studies, but the effect of OSA on the onset of asthma in childhood or adulthood remains unclear, and the causal inferences have not been confirmed. This study aims to investigate the potential causal association between OSA with asthma, including different age-of-onset subtypes, providing reliable basis for the clinical treatment of OSA and asthma.Patients and Methods: Causality between OSA and asthma was assessed using a two-sample bi-directional Mendelian randomization (MR) analysis. OSA data were obtained from the FinnGen consortium R9, while asthma and its subtypes (adult-onset asthma, child-onset asthma, and moderate-to-severe asthma) were sourced from the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was chosen as the primary analysis and was complemented by various sensitivity analyses. The MR-PRESSO outlier test was employed to systematically identify and remove outlier variants, mitigating heterogeneity and potential effects of horizontal pleiotropy.Results: The MR analyses provided evidence of genetically predicted OSA having a promoting effect on child-onset asthma (OR,1.49; 95% CI, 1.05– 2.11; P=0.025) and moderate-to-severe asthma (OR,1.03; 95% CI, 1.00– 1.06; P=0.046). However, no causal association between OSA with asthma and adult-onset asthma was observed.Conclusion: Our study revealed a causal association between OSA and child asthma, but not in adults. Moderate-to-severe asthma may have a potential promoting effect on OSA. These findings underscore the importance of age-specific considerations in managing asthma and suggests the need for personalized approaches in clinical practice.Keywords: asthma, obstructive sleep apnea, Mendelian randomization, genetic

Ente Li,1,2,&ast; Qingfeng Zhu,3,&ast; Ziman Lv,1,2,&ast; Songsong Xie,3 Chunju Zhang,4 Wei Li,5 Ligu Mi,1,2 Quan Liu,6 Yuanzhi Wang,1,2 Xiaobo Lu2 1Department of Basic Medicine, School of Medicine, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 2Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 3The First Affiliated Hospital of Shihezi University Medical College, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 4Tumxuk Center for Disease Prevention and Control, Tumxuk City, Xinjiang Uygur Autonomous Region, 843806, People’s Republic of China; 5Department of Basic Medicine, School of Medicine, Tarim University, Alaer City, Xinjiang Uygur Autonomous Region, 843300, People’s Republic of China; 6Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun City, Jilin Province, 30061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanzhi Wang; Xiaobo Lu, Email wangyuanzhi621@126.com; xjykdluxiaobo@126.comAbstract: Visceral leishmaniasis (VL), also known as kala-azar. It is characterized by prolonged intermittent fever, anemia, splenomegaly, hepatomegaly, and skin darkening. VL is primarily endemic in regions, such as Brazil, East Africa, and India. However, Northern Xinjiang, which is located in northwestern China, is considered a low-incidence area for VL, contributing to its status as a neglected infectious disease. In this report, we present a case of VL caused by Leishmania donovani that was diagnosed using metagenomic next-generation sequencing (mNGS). This case underscores the diagnostic value of mNGS, particularly in regions with low incidence of VL. Keywords: Visceral leishmaniasis, Leishmania donovani, metagenomic next-generation sequencing, northwestern China

Qiqi Cheng,1 Xiaolin Zhou,1 Peng Wang,2 Rong Liu,3 Qiang Liu1 1Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 2Department of Clinical Laboratory, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 3Department of Ultrasound, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaCorrespondence: Qiang Liu, Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China, Tel +86 13720181669, Email liuqiang@ctgu.edu.cnAbstract: We report a rare case of mechanical aortic valve infective endocarditis caused by Neisseria sicca. A 44-year-old man, with a history of aortic valve replacement, presented to the hospital with a 10-day history of fever. Investigations revealed that the blood cultures grew Neisseria sicca. Although the transthoracic echocardiogram (TTE) was negative, a transesophageal echocardiogram showed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve. After eight weeks of therapy, according to the antibiotic susceptibility test, the patient’s blood cultures were negative, and repeat TTE showed no vegetation. This report can offer valuable insights for clinical diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics.Keywords: infective endocarditis, Neisseria sicca, aortic valve, bacteremia

Qing Liu,1,2,&ast; Xiao-Jiao Tang,1,2,&ast; Xin-Ke Chen,1,2 Lin Chen1,2 1Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Chen, Children’s Hospital of Chongqing Medical University, 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +8618623041022, Fax +86-23-63651759, Email chenlin1220@126.comObjective: To investigate the effectiveness of flipped classrooms (FC) based on outcomes-based education (OBE) on clinical ophthalmology clerkships.Methods: Ninety-nine undergraduates were non-randomly assigned to the FC based on the OBE (FC-OBE) group or traditional lecture (TL) group in the ophthalmology clerkship. Pre- and post-tests were performed to assess student learning outcomes. Anonymous questionnaires were collected to compare students’ attitudes and classroom engagements between the two groups.Results: More participants agreed FC-OBE was helpful in developing teamwork ability and knowing the work standard. Teaching staff in the FC-OBE classroom received higher evaluations. More participants in the FC-OBE group had higher classroom engagement in skills and emotions than in the TL group. The post-class test scores, mainly case analysis scores were higher in the FC-OBE group than in the TL group.Conclusion: FC-OBE classroom improves student engagement and clinical analysis competence in undergraduate ophthalmology clerkship.Keywords: ophthalmology education, OBE, flipped classroom, clinical clerkship, undergraduate

Xiao-Jiao Tang,1– 4 Jia-Tong He,5 Qing Liu,1– 4 Enmei Liu,2– 4,6 Lin Chen1– 4 1Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2National Clinical Research Center for Child Health and Disorders, Chongqing, People’s Republic of China; 3Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, People’s Republic of China; 5Department of Health Management, Chongqing General Hospital, Chongqing, People’s Republic of China; 6Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Enmei Liu, Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing, Yuzhong District, 400014, People’s Republic of China, Tel +8613368070773, Email emliu186@126.com Lin Chen, Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing, Yuzhong District, 400014, People’s Republic of China, Tel +8618623041022, Email chenlin1220@126.comPurpose: To investigate the patterns of allergens in allergic conjunctivitis (AC) and the association with allergic comorbidity.Methods: This retrospective cross-sectional study enrolled 2972 children with AC. Clinical data, including sex, age, allergic comorbidities (allergic asthma, allergic rhinitis, and atopic dermatitis), and serum allergen-specific immunoglobulin E (sIgE), were collected from the electronic medical record (EMR). The categorical variables were compared with the chi-square test. The characteristics of allergens in children of different ages and comorbidities were analyzed by trend chi-square. The sensitivity level of HDM associated with AC and comorbidities was assessed by odds ratios (ORs) with 95% confidence intervals of logistic regression analysis.Results: A total of 2972 children (2015 boys and 957 girls) with AC were included in the study. The mean age was 3.78 (0.5~12) years. The most common allergen was house dust mite(HDM) (43.41%). With age, the positive rate for inhaled allergens gradually increased, and the positive rate for ingested allergens decreased. With the number of comorbidities increasing, the positive rates of sensitization were 38.33%, 74.51%, 80.72%, and 89.05%, and the incidence of polysensitization was 44.66%, 56.48%, 59.54%, and 74.59%, respectively. With the increase of HDM-sIgE level, the number of comorbidities and the risk increased gradually.Conclusion: HDM is the most common allergen in AC children of different ages. High levels of HDM-sIgE may be a predictor for allergic comorbidities. Children with polysensitization and high levels of HDM sIgE will be an important target population for future intervention in other allergy-related disease prevention.Keywords: allergic conjunctivitis, specific IgE, allergic comorbidity, house dust mite, children

Qingyi Liu,1,2 Qiongdan Zhang,1,2 Zhijian Yao,1,2 Gangqiang Yi,2 Yeonseok Kang,3 Yixing Qiu,1,2 Yupei Yang,1,2 Hanwen Yuan,1,2 Ronggeng Fu,2 Wenbing Sheng,1,2 Lidong Cheng,4 Wei Wang,1,2 Huizhen Wang,1,2 Caiyun Peng1,5 1TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3College of Korean Medicine, Wonkwang University, Jeonbuk, Korea; 4Hunan Yirentang Chinese Herbal Pieces Co., Ltd, Changde, People’s Republic of China; 5Institute of Innovation and Applied Research in Chinese Medicine Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Huizhen Wang; Caiyun Peng, Tel +86-151-1648-1295 ; +86-138-7480-7689, Email whuiz0086@163.com; caiyunpeng@hnucm.edu.cnAbstract: Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018– 2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future. Keywords: EVs, TEVs, DNA walker, detection

Xiaojuan Wu,1,2,&ast; Daoyan Wu,1,2,&ast; Guzhen Cui,1 Khui Hung Lee,3 Tingxiu Yang,1,2 Zhengrong Zhang,1,2 Qi Liu,4 Jinbao Zhang,1 Eng Guan Chua,3 Zhenghong Chen1,2 1Key Laboratory of Microbiology and Parasitology of Education Department of Guizhou & Joint Laboratory of Helicobacter Pylori and Intestinal Microecology of Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, People’s Republic of China; 2Key Laboratory of Endemic and Ethnic Diseases of Ministry of Education, Guizhou Medical University, Guiyang, People’s Republic of China; 3Helicobacter Research Laboratory, the Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia; 4Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghong Chen, Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Guiyang, People’s Republic of China, Tel + 86-13985006815, Email chenzhenghong@gmc.edu.cnBackground: Persistent infections caused by Helicobacter pylori (H. pylori), which are resistant to antibiotic treatment, pose a growing global public health concern. Biofilm formation is known to be associated with persistent infections due to its role in enhancing antimicrobial resistance and the tolerance of many pathogenic bacteria.Objective: This study aims to evaluate the biofilm formation of clinical isolates of H. pylori and its impact on antibiotic eradication.Methods: The thickness, morphology, and structure of biofilms derived from nine H. pylori strains were examined using confocal laser scanning microscopy, scanning electron microscopy, and transmission electron microscopy. Subsequently, the susceptibility of both planktonic and biofilm bacteria was assessed through the determination of minimum inhibitory concentration and minimum biofilm eradication concentration for amoxicillin, clarithromycin, levofloxacin, and tetracycline.Results: The results revealed varying biofilm thicknesses and densities among the strains, characterised by the presence of numerous filaments intertwining and connecting bacterial cells. Additionally, several cases exhibited susceptibility based on MIC measurements but resistance according to MBEC measurements, with MBEC indicating a higher resistance rate. Pearson Correlation analysis demonstrated a positive correlation between biofilm thickness and MBEC results (0 < r < 1), notably significant for amoxicillin (r = 0.801, P = 0.009) and tetracycline (r = 0.696, P = 0.037).Conclusion: Different strains of H. pylori exhibit variations in their capacity to release outer membrane vesicles (OMVs) and form biofilms. Biofilm formation can influence the effectiveness of amoxicillin and tetracycline in eradicating susceptible bacterial strains.Keywords: Helicobacter pylori, antibiotic resistance, biofilm formation, biofilm-specific resistance

Fengyao Liu,1,2,&ast; Haochen Wang,2,3,&ast; Bingqing Bai,2,4 Han Yin,5 Yuting Liu,2 Yu Wang,2 Quanjun Liu,2 Shuxia Wang,6 Huan Ma,3 Qingshan Geng1,2,5 1School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 5Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 6Department of Nuclear Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Ma, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106 Zhongshan Er Road, Guangzhou, People’s Republic of China, Fax +8620-83827812, Email mahuandoctor@163.com Qingshan Geng, Department of Cardiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), 1080 Cuizhu Road, Luohu District, Shenzhen, Guangdong, Fax +0755-25533018, Email gengqsh@163.netPurpose: Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited.Patients and Methods: We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI.Results: There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (β=1.226, OR = 3.408 (1.200– 9.681), P = 0.021).Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.Keywords: obstructive sleep apnea, mental stress induced myocardial ischemia, angina with no obstructive coronary artery disease, myocardial perfusion imaging

Yidong Cui,1 Qingming Liu,2 Qiqiang Zhang,3 Xuemei Di,3 Hai Zhang3 1Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of China; 2Department of Neurology, Shandong Second Provincial General Hospital, Jinan, 250012, People’s Republic of China; 3Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Hai Zhang, Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No. 2699 West Gaoke Road, Shanghai, 200092, People’s Republic of China, Tel/Fax +8621-20261401, Email zhxdks2005@126.comBackground: Aconitum carmichaelii (Fuzi) has been conventionally used to cure a variety of ailments, such as pain, cold sensations, and numbness of limb muscles (Bi Zheng) in China. Our prior investigations identified Benzoylaconine (BAC) as a bioactive alkaloid derived from Aconitum carmichaelii, with other studies also demonstrating its significant pharmacological potential.Purpose: This study aimed to explore the potential of BAC as a protective agent against skeletal muscle ischemia-reperfusion (I/R) injury and to elucidate the underlying mechanisms.Methods: In vivo models involved subjecting Sprague-Dawley rats to I/R through femoral artery ligation followed by reperfusion, while in vitro models utilized C2C12 cells subjected to hypoxia/reoxygenation (H/R). CCK-8 assay was used to assess cell viability. TUNEL staining and flow cytometric analysis were used to measure cell apoptosis. Biochemical assay was used to assess skeletal muscle injury and oxidative stress. Immunofluorescence and Western blot were performed to determine protein levels.Results: BAC effectively protected muscle tissue from I/R injury, enhancing cell viability (p< 0.01), elevating SOD levels (p< 0.05), and reducing CK (p< 0.01), LDH (p< 0.01), ROS (p< 0.01), MDA (p< 0.01), and apoptosis-related molecules in vivo and in vitro (p< 0.05, p< 0.01). Mechanistically, BAC increased the expression of IF1, phosphorylated AMPK, facilitated the translocation of nuclear Nrf2, and induced the expression of HO-1 (p< 0.01). Notably, AMPK inhibitor Compound C significantly hindered the ability of BAC to ameliorate H/R-induced cell injury (p< 0.05), oxidative stress(p< 0.01), and apoptosis (p< 0.05), as well as promote Nrf2 nuclear translocation (p< 0.01). Moreover, silencing of IF1 with siRNA abolished BAC-induced activation of AMPK/Nrf2 axis (p< 0.01).Conclusion: Our study provides novel evidence supporting the potential of BAC as a myocyte-protective agent against I/R injury, and we establish a previously unknown mechanism involving the activation of the IF1-dependent AMPK/Nrf2 axis in mediating the protective effects of BAC. Keywords: Benzoylaconine, ischemia-reperfusion injury, oxidative stress, AMPK, IF1

Jingyi Lao,1,&ast; Yijie Zeng,1,&ast; Zhangying Wu,1 Gaohong Lin,1 Qiang Wang,1 Mingfeng Yang,1 Si Zhang,1 Danyan Xu,1 Min Zhang,1 Kexin Yao,1 Shuang Liang,1 Qin Liu,1 Jiafu Li,1 Xiaomei Zhong,1 Yuping Ning1– 4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuping Ning; Xiaomei Zhong, The Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Email ningjeny@126.com; lovlaugh@163.comBackground: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear.Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed.Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items.Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.Keywords: late-life depression, microstate, electroencephalogram, resting-state networks

Chuang Qin,1 Xiaofei Ye,1 Hongliang Luo,1 Hu Jin,1 Qiang Liu,1 Jiangfa Li2 1Hepatobiliary Surgery, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou City, Guangxi, People’s Republic of China; 2Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, Guilin City, Guangxi, People’s Republic of ChinaCorrespondence: Jiangfa Li, Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road,Xiufeng District, Guilin City, Guangxi, 541001, People’s Republic of China, Email ljf.126@qq.comPurpose: This study contributes to the evolving understanding of the pivotal involvement of Sirtuins (SIRTs) in various human cancers, with a particular focus on elucidating their expression patterns and clinical relevance within the context of hepatocellular carcinoma (HCC). The investigation involves a comprehensive analysis of mRNA expression and prognostic implications associated with distinct SIRTs in HCC.Patients and Methods: Initial data pertaining to SIRT expression in HCC patients were collated from publicly accessible databases. Subsequently, the expression levels of select members of the SIRT family were validated using clinicopathological specimens from HCC patients. Additionally, HCC tissue microarray was employed to scrutinize the correlation between SIRT7 expression and HCC prognosis.Results: The findings indicated a substantial upregulation of SIRT2, SIRT3, SIRT4, SIRT6, and SIRT7 in HCC tissues. Survival analysis underscored a pronounced association between elevated mRNA levels of SIRT3, SIRT6, and SIRT7 and an adverse prognosis for HCC patients. Particularly, SIRT7 emerged as a potential independent risk factor for poor prognosis in HCC patients. Examination of the HCC tissue microarray revealed heightened expression of SIRT7 in 68 cases (54.8%) of HCC tissues. Multivariate analysis established high SIRT7 expression as an independent risk factor for diminished Disease-Free Survival (DFS) and Overall Survival (OS) in HCC patients.Conclusion: The aberrant expression of SIRT7 presents itself may be as a novel biomarker for predicting the prognosis of HCC patients.Keywords: HCC, microarray, prognosis, SIRT7, survivor

Tingting Wang,1 Yang Wang,2 Qingyue Liu,1 Wenbin Guo,1 Hongliang Zhang,1 Liangliang Dong,3 Jiajun Sun1 1Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 2Department of Laboratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 3Department of Respiratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of ChinaCorrespondence: Jiajun Sun, Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, No. 306 Jiankang Road, Linqing, Shandong, People’s Republic of China, Tel +86-13793092818, Email 13793092818@126.comBackground: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population.Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (> 98), mild malnutrition (92– 98), moderate malnutrition (82– 91), and severe malnutrition (≤ 81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect.Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 > 98), the adjusted HR values for GNRI in Q3 (92– 98), Q2 (82– 91), and Q1 (≤ 81) were 1.81 (95% CI: 1.27– 2.58, p=0.001), 1.23 (95% CI: 0.84– 1.79, p=0.296), 2.27 (95% CI: 1.57– 3.29, p< 0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5.Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.Keywords: geriatric nutritional risk index, 90-day mortality, older adults, chronic obstructive pulmonary disease, MIMIC-IV

Xu Liu,1,&ast; Qingfeng Liu,1,&ast; Linghong Guo,1 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423315, Fax +86-28-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comAbstract: The increasing popularity of tattoo art, including facial cosmetic tattoos, has led to a growing societal acceptance of tattoos. However, complications such as lip inflammation following cosmetic lip tattoos remain a concern. This article presents the case of a 47-year-old Asian woman who experienced recurrent lip swelling, purulent discharge, and scarring after receiving lip tattoos. Despite previous treatment with corticosteroid injections yielding unsatisfactory results, the patient showed significant improvement with topical application of 2% Crisaborole, a phosphodiesterase-4 inhibitor. Crisaborole modulates intracellular cyclic adenosine monophosphate levels, thereby reducing tissue inflammation and swelling associated with chronic cheilitis. Additionally, pulse laser therapy was effective in addressing residual tattoo pigment and scar tissue. This case highlights the therapeutic challenges of managing chronic inflammatory diseases of the lips secondary to cosmetic tattoos and introduces Crisaborole as a promising treatment option, offering insights for managing similar conditions in the future.Keywords: lip tattoo, chronic cheilitis, Crisaborole, phosphodiesterase-4 inhibitor, laser therapy

Qingxiang Liu,1,&ast; Haitao Liu,2,&ast; Zihan Hu,1 Xing Zhou,1 Kai Jin,1 Yingzi Huang,1 Wei Huang,1 Yi Yang1 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Life Science, Fudan University, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Yi Yang, Email whuang@seu.edu.cn; yiyiyang2004@163.comBackground: Sepsis is a life-threatening clinical syndrome caused by dysregulated host response to infection. The mechanism underlying sepsis-induced immune dysfunction remains poorly understood. Natural killer T (NKT) cells are cytotoxic lymphocytes that bridge the innate and adaptive immune systems, the role of NKT cells in sepsis is not entirely understood, and NKT cell cluster differences in sepsis remain unexplored.Methods: Mendelian randomization (MR) analyses were first conducted to investigate the causal relationship between side scatter area (SSC-A) on NKT cells and 28-day mortality of septic patients. A prospective and observational study was conducted to validate the relationship between the percentage of NKT cells and 28-day mortality of sepsis. Then, the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from healthy controls and septic patients were profiled.Results: MR analyses first revealed the protective roles of NKT cells in the 28-day mortality of sepsis. Then, 115 septic patients were enrolled. NKT percentage was significantly higher in survivors (n = 84) compared to non-survivors (n = 31) (%, 5.00 ± 3.46 vs 2.18 ± 1.93, P < 0.0001). Patients with lower levels of NKT cells exhibited a significantly increased risk of 28-day mortality. According to scRNA-seq analysis, NKT cell clusters exhibited multiple distinctive characteristics, including a distinguishing cluster defined as FOS+NKT cells, which showed a significant decrease in sepsis. Pseudo-time analysis showed that FOS+NKT cells were characterized by upregulated expression of crucial functional genes such as GZMA and CCL4. CellChat revealed that interactions between FOS+NKT cells and adaptive immune cells including B cells and T cells were decreased in sepsis compared to healthy controls.Conclusion: Our findings indicate that NKT cells may protect against sepsis, and their percentage can predict 28-day mortality. Additionally, we discovered a unique FOS+NKT subtype crucial in sepsis immune response, offering novel insights into its immunopathogenesis.Keywords: natural killer T cells, sepsis, outcome, Mendelian randomization

Qingxiang Liu,1,&ast; Fei Peng,1,&ast; Haitao Liu,2,&ast; Qin Sun,1 Hui Chen,1 Xinyi Xu,1 Zihan Hu,1 Xing Zhou,1 Kai Jin,1 Jianfeng Xie,1 Yingzi Huang,1 Wei Huang,1 Yi Yang1 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Life Science, Fudan University, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Yi Yang, Email whuang@seu.edu.cn; yiyiyang2004@163.comBackground: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood.Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration.Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46± 4.40 vs 11.65± 6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand–receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS.Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.Keywords: ARDS, inflammation, natural killer cells, sepsis

Tianle Chen, Qi Liu, Jie Yang College of Biomedical Engineering, Sichuan University, Chengdu, 610065, People’s Republic of ChinaCorrespondence: Qi Liu, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, People’s Republic of China, Email liuqi@scu.edu.cnIntroduction: Skin disease is one of the most common diseases and can affect people of all ages and races. However, the diagnosis of skin diseases via observation is a highly challenging task for both doctors and patients, and would benefit from the use of an intelligent system. Building a large benchmark with professional dermatologists is resource-intensive, and we believe that few-shot learning (FSL) methods would be helpful in solving the problem of annotated data scarcity. In this paper, we propose CDD-Net (Context Feature Fusion and Dual Attention Dermatology Net), a plug-in module for FSL clinical skin disease classification.Methods: Current FSL methods used in skin disease classification are limited to nonuniversal approaches and few disease classes. Our CDD-Net has a flexible structure, including a context feature–fusion module and dual-attention module to extract discriminating texture feature and emphasize contributive regions and channels. The context feature–fusion module localizes discriminatory texture details of skin lesions by integrating features from different layers, while the dual-attention module highlights discriminative regions via channel-wise and pixel-wise depictions based on weight vectors and restrains the contributions of irrelevant areas. We also present Derm104, a new clinical skin disease data benchmark that has significant coverage of rare diseases and reliable annotation between primary species and subspecies for better validation of our approach.Results: Our experiments validated the versatility of CDD-Net for different FSL methods and achieved an improvement in accuracy of up to 9.14 percentage points compared with the vanilla network, which can be considered state of the art. The ablation study also showed that the dual-attention module and context feature–fusion module worked efficiently in CDD-Net. Keywords: clinical skin image, computer-aided diagnosis, few-shot learning, feature fusion, attention mechanism

Qinghao Liu,&ast; Weiwen Zhao,&ast; Hao Yin Department of Orthopedic, The First Affiliated Hospital of Hunan Normal University Hunan Provincial People’s Hospital, Changsha, China Mainland (PRC)&ast;These authors contributed equally to this workCorrespondence: Hao Yin, Email ehour@hunnu.edu.cnBackground: Spontaneous spinal epidural hematoma (SSEH) presenting in the context of JAK2 V617F-positive myeloproliferative neoplasms is a rare condition, characterized by the compression of the spinal cord leading to various symptoms. The etiology, pathogenesis, and optimal treatment strategies for this condition remain undetermined. The occurrence of spontaneous spinal epidural hematoma (SSEH) in the context of JAK2 V617F-positive myeloproliferative neoplasms (MPNs) represents a rare manifestation. Magnetic Resonance Imaging (MRI) plays a crucial role in the definitive diagnosis of this condition. With a good understanding of the pathogenic characteristics and clinical presentations of this disease, a diagnosis can be reasonably made, even in the absence of MRI, based on physical examinations indicating the affected area. Once diagnosed, immediate surgery is recommended to attempt the restoration of spinal cord function. Postoperatively, the use of hydroxyurea has proven effective in disease control.Case Presentation: We report a case of a 65-year-old male patient who presented with progressive lumbar back pain and bilateral lower limb paralysis lasting for 36 hours. CT imaging revealed an intraspinal lesion at the L1-3 level, and genetic testing confirmed the presence of the JAK2V617F mutation. Following surgery, there was a significant recovery of sensory and motor function in the lower limbs. At one-year follow-up, the patient demonstrated good functional status, and blood tests indicated a platelet count within the normal range.Conclusion: The presented case adds to the existing literature on SSEH by highlighting the association with myeloproliferative neoplasms (MPNs), as evidenced by the JAK2V617F mutation. MPNs constitute a group of hematologic malignancies, and the association with SSEH is a rare occurrence. The exact interplay between MPNs and SSEH warrants further investigation, as the underlying mechanisms linking these conditions remain elusive. The case also underscores the importance of a multidisciplinary approach, involving hematologists and neurosurgeons, in the comprehensive management of such complex cases.Keywords: myeloproliferative neoplasms, spinal epidural hematoma, JAK2V617F

Shuo Tian,1,2,&ast; Haitao Zhong,3,4,&ast; Mengyue Yin,5 Pei Jiang,3 Qiao Liu1 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Clinical Pharmacy, Jining First People’s Hospital, Shandong First Medical University, Jining, Shandong, People’s Republic of China; 3Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, Shandong, People’s Republic of China; 4Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, Shandong, People’s Republic of China; 5The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: This study aims to conduct a comprehensive cost-effectiveness comparison between novel oral anticoagulants (NOACs) and warfarin in Chinese patients with left ventricular thrombosis (LVT). By incorporating the impact of volume-based procurement (VBP) policy for pharmaceuticals in China, this analysis intends to provide crucial insights for informed healthcare decision-making.Patients and Methods: A Markov model was employed to simulate the disease progression of LVT over a 54-week time horizon, using weekly cycles and six mutually exclusive health states. The model incorporated transition probabilities between health states calculated based on clinical trial data and literature sources. Various cost and utility parameters were also included. Additionally, a series of sensitivity analyses were conducted to address parameter variations and associated uncertainties.Results: The study finding suggest that from the perspective of Chinese healthcare, the majority of brand-name drug (BND) NOACs generally lack cost-effectiveness when compared to warfarin. However, when considered the VBP policy, NOACs, particularly rivaroxaban, prove to be more cost-effective than warfarin. Rivaroxaban provided an additional 0.0304 quality-adjusted life years (QALYs) per patient and reduced overall medical costs by 9095.73 CNY, resulting in an incremental cost-effectiveness ratio (ICER) of − 298,786.20 CNY/QALY. Sensitivity analysis indicated a 78.4% probability of any NOACs being more cost-effective compared to warfarin. However, specifically considering NOACs under the VBP policy, the likelihood of them being more cost-effective approached 90%.Conclusion: Taking into account Chinese pharmaceutical procurement policies, the findings highlight the superior efficacy of NOACs, especially rivaroxaban, in enhancing both the quality of life and economic benefits for Chinese LVT patients. NOACs present a more cost-effective treatment option, improving patient quality of life and healthcare cost efficiency compared to warfarin.Keywords: cost-effectiveness, novel oral anticoagulants, left ventricular thrombosis, thrombus resolution

Yuanyuan Ding,&ast; Linjiang Chen,&ast; Jing Xu, Yuhan Feng, Qiong Liu Department of Ophthalmology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong Liu, Department of Ophthalmology, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Baiyun District, Guangzhou, Guangdong Province, 510515, People’s Republic of China, Tel +86-13922442109, Email nanfanglq2023@163.comObjective: Diabetic retinopathy (DR) can cause permanent blindness with unstated pathogenesis. We aim to find novel biomarkers and explore the mechanism of apoptotic protease activating factor 1 (APAF1) in DR.Methods: Differential expression genes (DEGs) were screened based on GSE60436 dataset to find hub genes involved in pyroptosis after comprehensive bioinformatics analysis. DR mice model was constructed by streptozotocin injection. The pathological structure of retina was observed using hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was applied to assess inflammatory factors, vascular endothelial growth factor (VEGF), and oxidative stress. The mRNA and protein expression levels were detected using quantitative real-time polymerase-chain reaction and Western blot. Cell counting kit and flow cytometry were employed to detect proliferation and apoptosis in high glucose-induced ARPE-19 cells.Results: Total 71 pyroptosis-related DEGs were screened. BIRC2, CXCL8, APAF1, PPARG, TP53, and CYCS were identified as hub genes of DR. APAF1 was selected as a potential regulator of DR, which was up-regulated in DR mice. APAF1 silencing alleviated retinopathy and inhibited pyroptosis in DR mice with decreased levels of inflammatory factors, VEGF, and oxidative stress. Moreover, APAF1 silencing promoted proliferation while inhibiting apoptosis and caspase-3/GSDME-dependent pyroptosis with a decrease in TNF-α, IL-1β, IL-18, and lactate dehydrogenase in high glucose-induced ARPE-19 cells. Additionally, caspase-3 activator reversed the promotion effect on proliferation and inhibitory effect on apoptosis and pyroptosis after APAF1 silencing in high glucose-induced ARPE-19 cells.Conclusion: APAF1 is a novel biomarker for DR and APAF1 silencing inhibits the development of DR by suppressing caspase-3/GSDME-dependent pyroptosis.Keywords: diabetic retinopathy, APAF1, caspase-3, GSDME, pyroptosis

Qiang Liu,1,&ast; FeiFei Su,1,&ast; Aruhan Mu,1 Xiang Wu1,2 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Yunnan Key Laboratory of Service Computing, Yunnan University of Finance and Economics, Kunming, 650221, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aruhan Mu, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science &Technology, Wuhan, 430030, People’s Republic of China, Tel +86 15872374100, Email aruhan@hust.edu.cnPurpose: How individuals engage with social media can significantly impact their psychological well-being. This study examines the impact of social media interactions on mental health, grounded in the frameworks of the Elaboration Likelihood Model and Schema Activation Theory. It aims to uncover behavioral differences in information sharing between the general population and individuals with depression, while also elucidating the psychological mechanisms underlying these disparities.Methods: A pre-experiment (N=30) and three experiments (Experiment 1a N=200, Experiment 1b N=180, Experiment 2 N=128) were executed online. These experiments investigated the joint effects of information quality, content valence, self-referential processing, and depression level on the intention to share information. The research design incorporated within-subject and between-subject methods, utilizing SPSS and SPSS Process to conduct independent sample t-tests, two-factor ANOVA analyses, mediation analyses, and moderated mediation analyses to test our hypotheses.Results: Information quality and content valence significantly influence sharing intention. In scenarios involving low-quality information, individuals with depression are more inclined to share negative emotional content compared to the general population, and this tendency intensifies with the severity of depression. Moreover, self-referential processing acts as a mediator between emotional content and intention to share, yet this mediation effect weakens as the severity of depression rises.Conclusion: Our study highlights the importance of promoting viewpoint diversity and breaking the echo chamber effect in social media to improve the mental health of individuals with depression. To achieve this goal, tailoring emotional content on social media could be a practical starting point for practice.Keywords: depression, information-sharing behavior, cognitive schema, self-referential processing, information quality, content valence, social media

Lan-Fang Li,1 Ran Qi,1 Tian-Tian Wei,1 Lei Feng,1 Xin Zhang,1 Qiao Liu2 1Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, People’s Republic of China; 2Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: The IPSOS study provided evidence supporting the efficacy and tolerability of first-line atezolizumab compared to single-agent chemotherapy for non-small-cell lung cancer (NSCLC) patients ineligible for treatment with a platinum-containing regimen. This study aimed to assess the cost-effectiveness of atezolizumab specifically in this population, considering the perspective of the Chinese healthcare system.Patients and Methods: In this analysis, a three-state Markov model was utilized. The survival data were derived from the IPSOS clinical trial. Direct medical costs and utility values were collected from national authoritative database and published literature. The primary outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). To ensure the robustness of our model, both one-way and probabilistic sensitivity analyses were conducted.Results: Atezolizumab monotherapy led to an increase in costs of &dollar;4139.23 compared to single-agent chemotherapy. Additionally, it resulted in a gain of 0.14 QALYs, leading to an ICER of &dollar;29,365.79 per QALY, which was below the willingness-to-pay threshold of &dollar;36,066 per QALY used in the model. One-way sensitivity analyses revealed cost of atezolizumab and utility of progressive disease (PD) as major influencing factors for ICER. Furthermore, probabilistic sensitivity analyses confirmed our base-case results.Conclusion: From the perspective of the Chinese healthcare system, atezolizumab emerges as a cost-effective choice for the first-line treatment of NSCLC patients ineligible for platinum-based chemotherapy.Keywords: atezolizumab, cost-effectiveness, NSCLC, IPSOS

Bennan Zhao,1,&ast; Qingxiao Liu,2,&ast; Qing Du,3 Jun Kang,1 Rong Tang,4 Yalan Tu,5 Dafeng Liu1 1The First Ward of Internal Medicine, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 2Department of Neurology, Hospital of Chengdu University of TCM, Chengdu, People’s Republic of China; 3The Second Ward of ICU, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 4Department of Integrated Chinese and Western Medicine, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 5Scientific Research and Teaching Department, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dafeng Liu, The First Ward of Internal Medicine, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China, Tel +86 1 309 449 4836, Email ldf312@126.com Yalan Tu, Scientific Research and Teaching Department, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China, Tel +86 1 501 326 6454, Email tyl950330@163.comPurpose: To date, there are few reports about mpox case series in China, and scarce information is available about the in-vivo kinetics of T-cell responses in the early stage of mpox infection. This study aims to investigate the clinical difference among mpox patients with and without human immunodeficiency virus (HIV) infection.Patients and Methods: A total of 56 patients diagnosed with mpox by Chengdu Center for Disease Control and Prevention (CDC) and hospitalized in Public Health Clinical Center of Chengdu were retrospectively included and divided into an HIV-infected group (n=23) and a non-HIV-infected group (n=33). Clinical characteristics and serum chemistry findings of mpox patients were collected in order to analyze the differences between the HIV-infected group and the non-HIV-infected group.Results: Multiple laboratory abnormalities, including elevated C-reactive protein (69.1%), hypocalcemia (50.9%), elevated CD3+CD8+T counts (47.0%) and inverted ratio of CD3+CD4+T to CD3+CD8+T (64.7%) were common in mpox cases. There were statistically significant differences (all P < 0.05) in age, serum calcium levels, CD3+CD4+T counts, the ratio of CD3+CD4+T to CD3+CD8+T, proportion with > 10 rashes, incidence of proctitis anus and time from rash growth to rash scab shedding between HIV-infected group and non-HIV-infected group. In the early stage of mpox infection, the median of CD3+CD8+T counts in the non-HIV-infected group was significantly higher than that in healthy donors (P< 0.001), and the median of CD3+CD4+T/CD3+CD8+T ratio was significantly lower (P< 0.001). The median of CD3+CD4+T counts in mpox patients co-infected with HIV significantly decreased compared to the pre-infection level (p =0.033).Conclusion: Our study indicates that mpox co-infected with HIV patients have longer lasting rash lesions and a higher incidence of proctitis anus. T-cell responses may be different between HIV-infected and non-HIV-infected individuals in the early stage of mpox infection.Keywords: mpox, HIV, clinical characteristics, complication, T-cell response

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Xue-Jun Dou,1,&ast; Run-Yang Ma,1,&ast; De-Wang Ren,1 Qiang Liu,2 Peng Yan3 1Department of Thoracic Surgery, Aerospace Center Hospital, Beijing, 100049, People’s Republic of China; 2Department of Thoracic Surgery, Peking University International Hospital, Beijing, 102206, People’s Republic of China; 3Department of Respiratory Medicine, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Liu, Department of Thoracic Surgery, Peking University International Hospital, Beijing, 102206, People’s Republic of China, Tel +86 15901472799, Email liuqiang8548@163.com Peng Yan, Department of Respiratory Medicine, China Aerospace Science & Industry Corporation 731 hospital, Beijing, 100071, People’s Republic of China, Email yanpeng301@163.comObjective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC).Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored.Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3– 35.9%) and a disease control rate of 85.1% (95% CI: 74.3– 92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37– 9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73– 22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity.Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.Keywords: previously immunotherapy treated NSCLC, anlotinib, PD-1 blockades, effectiveness, safety

Kaifang Yao,1,&ast; Zhihan Chen,1,&ast; Yanwei Li,1 Baomin Dou,1 Zhifang Xu,1– 3 Yajing Ma,1 Simin Du,1 Jiangshan Wang,1 Jiangjiang Fu,1 Qi Liu,1 Zezhi Fan,1 Yangyang Liu,1– 3 Xiaowei Lin,1– 3 Yuan Xu,1– 3 Yuxin Fang,1– 3 Shenjun Wang,1– 3 Yi Guo1,3,4 1Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 2School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 3National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin City, People’s Republic of China; 4School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Guo; Shenjun Wang, School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China, Tel +86 22-5959-6290, Email guoyi_168@163.com; shenjunwang@163.comPurpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia.Patients and Methods: We injected complete Freund’s adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1−/− mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1.Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1−/− ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated.Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.Keywords: acupuncture, TRPA1, ST36, inflammation, immune, analgesia

Chang Chen,1 Qian Mei,2 Qi Liu,3 Meichen Lu,4 Lu Hou,1 Xiaohong Liu,3 Xuezheng Gao,3 Limin Chen,3 Zhenhe Zhou,1– 4 Hongliang Zhou5 1Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, People’s Republic of China; 2School of Humanities and Management Science, Wannan Medical College, Wuhu City, People’s Republic of China; 3Grade 2021 Class 3, First Clinical Medical College of Jinzhou Medical University, Jinzhou City, People’s Republic of China; 4Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi City, People’s Republic of China; 5Department of Psychology, The Affiliated Hospital of Jiangnan University, Wuxi City, People’s Republic of ChinaCorrespondence: Zhenhe Zhou, Wuxi Mental Health Center, No. 156, Qianrong Road, Binhu District, Wuxi City, Jiangsu Province, People’s Republic of China, Tel +86-1-335-811-8986, Fax +86-510-83219366, Email zhouzh@njmu.edu.cn Hongliang Zhou, The Affiliated Hospital of Jiangnan University, No. 200, Huihe Road, Binhu District, Wuxi City, Jiangsu Province, People’s Republic of China, Tel +86-1-536-525-1126, Fax +86-510-85808820, Email Hongliangzh2022@hotmail.comPurpose: Schizophrenia patients show impaired conditional reasoning. This study was to investigate event-related potential (ERP) characteristics of the conditional reasoning in schizophrenia.Patients and methods: Participants included 24 schizophrenia patients and 30 normal controls (NCs), and the measurements of ERPs were conducted during the Wason selection task.Results: Results showed that NCs consistently outperformed schizophrenia patients in terms of accuracy. Among the different rule types of the task, the precautionary type experiment yielded the highest accuracy rates. In contrast, both the descriptive and abstract type experiments resulted in lower accuracy. The RTs of the abstract type experiment were the shortest among the four experiments. In the abstract type of the Wason selection task, the NCs exhibited higher amplitudes for both the N1 and P2 components compared to the schizophrenia patients. At the parietal lobe, the N2 amplitudes were higher for the social contract type of the task compared to the precautionary version. At the frontal lobe, the N2 amplitudes were highest for the abstract type of the task. In the abstract type, the N2 amplitude at the parietal lobe was higher than that at the central lobe. The NCs displayed lower amplitudes for both the P3 and slow wave compared to the schizophrenia patients. Differences were observed between the NC and schizophrenia groups in terms of the latencies for N1, P2, N2, P3 and slow wave components across different experiment types and regions of interest.Conclusion: In conclusion, the observed ERP patterns provide valuable insights into the neural mechanisms underlying the Wason selection task, highlighting the differences between NCs and patients with schizophrenia.Keywords: event-related potential, wason selection task, schizophrenia, conditional reasoning, neural mechanism

Pengwen Ouyang,1 Zhijie Zhou,2 Chanyuan Pan,3 Peijuan Tang,1 Sheng Long,1 Xiangjian Liao,1 Qiong Liu,1 Liangyi Xie1 1Department of Clinical Laboratory, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, People’s Republic of China; 3Department of Respiratory Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, People’s Republic of ChinaCorrespondence: Liangyi Xie, Email lyxie78@hunnu.edu.cnPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is closely related to respiratory tract infection. The aim of this study was to investigate the clinical features and prognostic factors of CRKP-induced pneumonia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Methods: A single-centre, retrospective case-control study on COPD patients hospitalized for acute exacerbation and CRKP-induced pneumonia was conducted from January 1, 2016, to December 31, 2022. The mortality rate of acute exacerbation due to CRKP-induced pneumonia was investigated. The patients were divided into the CRKP-induced pneumonic acute exacerbation (CRKPpAE) group and the non-CRKP-induced pneumonic acute exacerbation (non-CRKPpAE) group, and the clinical characteristics and prognostic factors were compared using univariate analysis and multivariate analysis.Results: A total of 65 AECOPD patients were included, composed of 26 patients with CRKPpAE and 39 patients with non-CRKPpAE. The mortality rate of CRKPpAE was 57.69%, while non-CRKPpAE was 7.69%. Compared with non-CRKPpAE, a history of acute exacerbation in the last year (OR=8.860, 95% CI: 1.360– 57.722, p=0.023), ICU admission (OR=11.736, 95% CI: 2.112– 65.207, p=0.005), higher NLR levels (OR=1.187, 95% CI: 1.037– 1.359, p=0.013) and higher D-dimer levels (OR=1.385, 95% CI: 1.006– 1.905, p=0.046) were independently related with CRKPpAE. CRKP isolates were all MDR strains (26/26, 100%), and MDR strains were also observed in non-CRKP isolates (5/39, 12.82%).Conclusion: Compared with non-CRKPpAE, CRKPpAE affects the COPD patient’s condition more seriously and significantly increases the risk of death.Keywords: chronic obstructive pulmonary disease, acute exacerbation, carbapenem-resistant K. pneumoniae, pneumonia

Yu Gong,1,&ast; Qianxia Liu,2,&ast; Qiang Hu3 1Department of Internal Medicine, Division of Nephrology, Telemedicine Center, Shanghai Municipal Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Medical Affairs Management, Division of Medical Record Management, Shanghai Municipal Eighth People’s Hospital, Shanghai, People’s Republic of China; 3Department of Surgery, Shanghai Municipal Eighth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Gong, Department of Internal medicine, Division of Nephrology, Telemedicine Center, Shanghai Municipal Eighth People’s Hospital, 8 Caobao Road, Shanghai, 200235, People’s Republic of China, Email gyfd66@sina.com Qiang Hu, Department of Surgery, Shanghai Municipal Eighth People’s Hospital, 8 Caobao Road, Shanghai, 200235, People’s Republic of China, Email huqiang20230828@163.comBackground: Despite great achievements in clinical medicine, the in-hospital mortality of older patients remains high. How to reduce the in-hospital mortality of older inpatients is of great clinical value in clinical practice. This study is to analyze the leading causes of in-hospital death of older inpatients of different ages in Shanghai.Methods: An observational study was conducted in Shanghai. A total of 3894 older inpatients (≥ 60 years old) were investigated. According to the age stratification standard of World Health Organization, they were divided into young older patients group (aged 60 to 74), old older patients group (aged 75 to 89) and very old patients group (aged ≥ 90). Diseases of in-hospital death of older inpatients in different age groups were classified according to the 10th edition of the International Classification of Diseases. Constituent ratio of causes of in-hospital death in each group was analyzed.Results: The constituent ratio of pulmonary infection had the highest rate of in-hospital death in older patients. The constituent ratio of lung malignant tumors had the highest rate of in-hospital death in young older patients. The constituent ratio of pulmonary infection had the highest rate of in-hospital death in old older patients. The constituent ratio of pulmonary infection had the highest rate of in-hospital death in very old patients.Conclusion: The leading cause of in-hospital death of young older patients group was lung malignant tumor. The leading cause of in-hospital death of old older patients group and very older patients group was pulmonary infection. Great importance should be attached to the prevention of lung tumor and lung infection in the elderly. Results of this study will provide a basis for health administrative departments to formulate corresponding health-care policies for older patients.Keywords: causes of in-hospital death, older patients, age stratified analysis, lung malignant tumor, pulmonary infection

Qiongdan Zhang,1,2,&ast; Huizhen Wang,1,2,&ast; Qingyi Liu,1,2 Ni Zeng,1,2 Gang Fu,1,2 Yixing Qiu,1,2 Yupei Yang,1,2 Hanwen Yuan,1,2 Wei Wang,1,2 Bin Li1,2 1TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang; Bin Li, Tel +86-136-5743-8606 ; +86-158-7410-0917, Email wangwei402@hotmail.com; libin@hnucm.edu.cnAbstract: Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials’ signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures. Keywords: tumor, exosomes, nanomaterials, DNA signal amplification

Yunzhi Xiang,&ast; Guanghui Wang,&ast; Baoliang Liu, Haotian Zheng, Qiang Liu, Guoyuan Ma, Jiajun Du Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiajun Du, Shandong Provincial Hospital, No. 324 Jingwu Road, Huaiyin District, Jinan, 250000, People’s Republic of China, Email dujiajun@sdu.edu.cnBackground: In recent years, the immunotherapy of lung adenocarcinoma has developed rapidly, but the good therapeutic effect only exists in some patients, and most of the current predictors cannot predict it very well. Tumor-infiltrating macrophages have been reported to play a crucial role in lung adenocarcinoma (LUAD). Thus, we want to build novel molecular markers based on macrophages.Methods: By non-negative matrix factorization (NMF) algorithm and Cox regression analysis, we constructed macrophage-related subtypes of LUAD patients and built a novel gene signature consisting of 12 differentially expressed genes between two subtypes. The gene signature was further validated in Gene-Expression Omnibus (GEO) datasets. Its predictive effect on prognosis and immunotherapy outcome was further evaluated with rounded analyses. We finally explore the role of TRIM28 in LUAD with a series of in vitro experiments.Results: Our research indicated that a higher LMS score was significantly correlated with tumor staging, pathological grade, tumor node metastasis stage, and survival. LMS was identified as an independent risk factor for OS in LUAD patients and verified in GEO datasets. Clinical response to immunotherapy was better in patients with low LMS score compared to those with high LMS score. TRIM28, a key gene in the gene signature, was shown to promote the proliferation, invasion and migration of LUAD cell.Conclusion: Our study highlights the significant role of gene signature in predicting the prognosis and immunotherapy efficacy of LUAD patients, and identifies TRIM28 as a potential biomarker for the treatment of LUAD.Keywords: lung adenocarcinoma, macrophage, TRIM28, prognosis, immunotherapy

Li Chen,1,2,&ast; Qiang Liu,2,&ast; Chunlei Tan,3,&ast; Tiangen Wu,4,&ast; Meng Wu,5 Xiaosheng Tan,5 Jinwen Liu,1 Jing Wang2 1Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 4Department of Hepatobiliary&Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email wangjing@cicams.ac.cn Jinwen Liu, Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Email Liujinwen@tjh.tjmu.edu.cnObjective: The current study is conducted to investigate the potential prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in breast cancer patients with liver metastasis after surgery.Methods: This is a retrospective study of 178 breast cancer patients who developed liver metastasis after surgery. These patients were treated and followed up from 2000 to 2018 at our hospital. The aMAP risk score was estimated in accordance with the following formula: . The optimal cutoff value of the aMAP was evaluated via X-tile. Kaplan-Meier, Log-rank and Cox proportional hazards regression models were applied to determine the clinical influence of the aMAP score on the survival outcomes. The nomogram models were established by multivariate analyses. The calibration curves and decision curve analysis were applied to evaluate the estimated performance of the nomogram models.Results: A total of 178 breast cancer patients were divided into low aMAP score group (< 47.6) and high aMAP score group (≥ 47.6) via X-tile plots. The aMAP score was a potential prognostic factor in multivariate analysis. The median disease free survival (p=0.0013) and overall survival (p=0.0003) in low aMAP score group were longer than in high aMAP score group. The nomograms were constructed to predict the DFS with a C-index of 0.722 (95% CI, 0.673– 0.771), and the OS with a C-index of 0.708 (95% CI, 0.661– 0.755). The aMAP-based nomograms had good predictive performance.Conclusion: The aMAP score is a potential prognostic factor in breast cancer with liver metastasis after surgery. The aMAP score-based nomograms were conducive to discriminate patients at high risks of liver metastasis and develop adjuvant treatment and prevention strategies.Keywords: breast cancer, aMAP score, liver metastasis, albumin, prognosis

Panpan Zi,1,&ast; Ming Fang,2,&ast; Hongfu Yang,1 Jiahao Zheng,3 Ning Ma,1 Qilong Liu1 1Department of Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute for Infection Disease Control, Shandong Center for Disease Control and Prevention, Jinan, People’s Republic of China; 3Institute of Animal Quarantine, Chinese Academy of Inspection and Quarantine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Panpan Zi, Department of Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, No. 1 Longhu Zhonghuan Road, Jinshui District, Zhengzhou, Henan, People’s Republic of China, Tel +86-0371-66271356, Email zipanda123456@163.comPurpose: The continuous rise in carbapenemase-producing Enterobacteriaceae infections is a major public health concern. However, there is limited information available on New Delhi metallo-β-lactamase-1 (NDM-1) producing Citrobacter koseri. In this study, we isolated a blaNDM-1-carrying C. koseri from a stool sample of an inpatient. Our aim was to investigate the phenotypic and genomic features of this clinically derived carbapenem-resistant C. koseri isolate and to characterize the transmission pattern of the IncFII/IncN plasmid that carries the blaNDM-1 gene.Methods and Results: S1-PFGE, Southern blot and conjugation assay confirmed the presence of blaNDM-1 gene in a conjugative plasmid. C. koseri L2395 and transconjugant L2395-EC600 strains showed similar resistance spectrum. Whole-genome analysis revealed that pL2395_NDM is an IncFII/IncN plasmid with a length of 67,839 bp. Moreover, blaNDM-1 gene was found encoded in the ISKpn19-blaNDM-1-ble-tnpF-dsbD-cutA-ISKpn19 cassette array. Phylogenetic analysis revealed that strain L2395 was close to an IMP-4-bearing C. koseri from Australia.Conclusion: Ongoing surveillance will be essential to control and prevent the spread of carbapenem-resistant Citrobacter spp. in the future.Keywords: Citrobacter koseri, carbapenem-resistant, NDM-1, whole-genome sequencing

Ning Xu,1,&ast; Guanzheng Cui,1,&ast; Shengyin Zhao,1 Yu Li,1 Qian Liu,2 Xuchang Liu,1 Chuanliang Zhao,3 Rongjie Feng,1 Mingjie Kuang,1 Shijie Han1 1Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250014, People’s Republic of China; 2Department of Pain, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 3Department of Orthopedic Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijie Han; Mingjie Kuang, Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250014, People’s Republic of China, Email hanshijie@sdfmu.edu.cn; doctorkmj@tmu.edu.cnIntroduction: Osteoporosis is a common bone disease in which the bone loses density and strength and is prone to fracture. Bone marrow mesenchymal stem cells (BMSCs) are important in bone-related diseases. Exosomes, as mediators of cell communication, have potential in cell processes. Previous studies have focused on muscle factors’ regulation of bone remodeling, but research on exosomes is lacking.Methods: In order to confirm the therapeutic effect of mechanically stimulated myocytes (C2C12) derived exosomes (Exosome-MS) on the Glucocorticoid-induced osteoporosis(GIOP) compared with unmechanically stimulated myocytes (C2C12) derived exosomes (Exosomes), we established a dexamethasone-induced osteoporosis model in vivo and in vitro. Cell viability and proliferation were assessed using CCK8 and EDU assays. Osteogenic potential was evaluated through Western blotting, real-time PCR, alkaline phosphatase activity assay, and alizarin red staining. Differential expression of miRNAs was determined by high-throughput sequencing. The regulatory mechanism of miR-92a-3p on cell proliferation and osteogenic differentiation via the PTEN/AKT pathway was investigated using real-time PCR, luciferase reporter gene assay, Western blotting, and immunofluorescence. The therapeutic effects of exosomes were evaluated in vivo using microCT, HE staining, Masson staining, and immunohistochemistry.Results: In this study, we found that exosomes derived from mechanical stress had a positive impact on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Importantly, we demonstrated that miR-92a-3p mimics could reverse dexamethasone-induced osteoporosis in vitro and in vivo, indicating that mechanical stress-induced mouse myoblast-derived exosomes could promote osteogenesis and prevent the occurrence and progression of osteoporosis in mice through miR-92a-3p/PTEN/AKT signaling pathway.Conclusion: Exosomes derived from mechanical stress-induced myoblasts can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through miR-92a-3p/PTEN/AKT signaling pathway, and can have a therapeutic effect on glucocorticoid-induced osteoporosis in mice in vivo. Keywords: Human bone marrow mesenchymal stem cells, Mechanical stimulation, Exosome, miR-92a-3p, AKT signaling

Puxin Yang,&ast; Xiao Liang,&ast; Xingzhu Xu, Qingtao Liu, Zhiyuan Guo, Hongru Yuan, Hui Wang, Wenyuan Ding Department of Spine Surgery, HeBei Medical University Third Hospital, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenyuan Ding; Hui Wang, Department of Spine Surgery, HeBei Medical University Third Hospital, Shijiazhuang, The People’s Republic of China, Tel +86 311 88602317, Fax +86 311 87023626, Email dingwymanuscript@163.com; wanghuiwenxian@163.comIntroduction: To explore the incidence and predictive factors of new onset postoperative sacroiliac joint pain (PSJP) after posterior lumbar fusion surgery for degenerative lumbar disease.Methods: Three hundred and sixty-seven patient medical records from January 2020 to December 2021 were retrieved. The patients were divided into two groups: PSJP group and N-PSJP (non-postoperative sacroiliac joint pain group). To investigate potential risk factors for PSJP, HU value (Hounsfield unit value) was assessed on CT scans. ImageJ software was used to assess the fat and muscle of the lumbar multifidus muscle (LMM) in the axial MRI image, the red area was marked as fat and the rest were muscles to calculate the ratio of fatty infiltration. Patient characteristics, surgical variables and radiographic parameters were analyzed statistically.Results: Twenty of 367 patients were diagnosed with PJSP at postoperative follow-up. Patients with PSJP presented with significantly higher HU value. For surgical variables, PSJP patients received more operations including distal fusion level at sacrum than the N-PSJP group. For radiographic parameters, most of the patients in the PSJP group had more severe fatty atrophic muscle in the LMM compared to the N-PSJP group. There was no statistically significant difference between the two groups in preoperative and postoperative lumbar lordosis (LL), angle of lumbar lordosis of fixed lumbar vertebrae (FV-LL), pelvic incidence (PI), sacrum slope (SS). The bivariate logistic regression model revealed preoperative fat infiltration rate of the LMM, and higher HU value were independently associated with PSJP.Conclusion: PSJP for degenerative lumbar disease was 5.4%, the predictive factors included preoperative severe infiltration of LMM, distal fusion level at sacrum and higher HU value.Keywords: sacroiliac joint pain, lumbar instrumented fusion surgery, bone mineral density, paraspinal muscles

Qiong Liu,1,2 Yafei Chen,1 Bo Wang,1 Yinying Chen,3 Bing Li,4 Shuang Guan,1 Kehe Du,5 Xiaoyang Liu,5 Yanan Yu,1 Jun Liu,1 Zhong Wang1 1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Postdoctoral Research Station, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 5iPhase Pharma Services, Beijing, People’s Republic of ChinaCorrespondence: Zhong Wang, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email zhonw@vip.sina.comAim: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach.Methods: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers.Results: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups.Conclusion: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.Keywords: diabetic peripheral neuropathy, Traditional Chinese Medicine, Liu-Wei-Luo-Bi granules, untargeted metabolomics, arginine biosynthesis

Qiping Liu,1,&ast; Huiling Gong,1,&ast; Qiqi Chen,1 Chunyan Yuan,2 Bin Hu1 1Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Hu; Chunyan Yuan, Email Niuniuhu1213@qq.com; masterychy@126.comObjective: To study the clinical application value of contrast-enhanced ultrasound (CEUS) in diagnosing renal space-occupying lesions.Methods: Sixty-seven patients with renal space-occupying lesions detected by routine ultrasound examination received the contrast-enhanced ultrasound examination. When observing the perfusion mode of the mass, we analyzed the perfusion characteristics of contrast-enhanced ultrasound and compared them with the surgical pathological results.Results: Sixty-seven lesions, which were identified in 67 patients with renal space-occupying lesions, included 55 renal malignant tumors and 12 benign ones. The sensitivity of qualitative diagnosis by CEUS imaging was 96.4%, the specificity was 66.7%, and the accuracy was 91.0%.Conclusion: The real-time blood supply of renal space-occupying lesions helps judge their nature according to the enhancement mode. It has high clinical application value in diagnosing benign and malignant lesions.Keywords: ultrasound examination, renal lesions, contrast-enhanced ultrasound

Qianfei Liu,1,&ast; Liping Tan,2 Jianbo He,2 Ruiling Ning,2 Aiping Zeng,2,&ast; Yilin Chen1,&ast; 1Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hu Bei, People’s Republic of China; 2Department of Respiratory Oncology, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aiping Zeng, No. 71 Hedi Road, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email zengaipingone@163.com Yilin Chen, No. 158 Wuyang Avenue, Enshi City, Hu Bei, 445000, People’s Republic of China, Email chenyl891128@163.comPurpose: This study examined the association between plasma D-dimer levels and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated with osimertinib.Methods: In this multicenter study, 88 patients with advanced non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations and receiving osimertinib were enrolled. The target independent and dependent variables were the D-dimer levels before osimertinib treatment and OS time, respectively. The t-test or chi-square test was utilized to analyze the variances among various groups. The predictive significance of D-dimer for overall survival (OS) was assessed using Kaplan-Meier survival analysis and the Cox proportional hazard regression model.Results: The selected patients had an average age of 58.01± 10.72 years, with females comprising 54.55%. Based on their D-dimer levels, the patients were categorized into three groups: low-level (< 0.6 mg/L), middle-level (0.6 ~ 2 mg/L), and high-level (≥ 2 mg/L). After accounting for possible confounding variables, the Cox proportional hazard model showed that increased D-dimer levels were linked to a greater likelihood of death (HR 2.28, 95% CI = 1.09 ~ 4.76, p = 0.029). Importantly, there was a significant trend indicating that as D-dimer levels rose, the risk of mortality also increased (p for trend, HR 1.15, 95% CI = 1.03 ~ 1.28, p = 0.012). Consistently comparable outcomes were noted in the majority of subcategories. Patients with low-middle and high D dimer levels had a median OS of 28.6 and 17 months, respectively (p =0.014).Conclusion: In conclusion, elevated levels of D-dimer in the bloodstream were found to have a significant negative correlation with the overall survival (OS) of patients with EGFR-positive non-small cell lung cancer (NSCLC) who underwent treatment with osimertinib.Keywords: D-dimer, EGFR, NSCLC, osimertinib, prognosis

Qingsong Liu,1,2,&ast; Lunyu Li,2,&ast; Dan Zheng,1 Songlin Jin,2 Xiaotian Guan,2 Zeting Fu,2 Zhigang Xiong,1 Haili Ding3 1Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2School of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China; 3Insititute of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haili Ding, No. 2, Gymnasium Road, Chengdu, Sichuan, People’s Republic of China, Tel +86 13688467479, Email dingdingtang111@163.comPurpose: This study examined the underlying mechanisms of SJD’s anti-inflammatory and analgesic effects on acute GA flares.Methods: This study used pharmacology network and molecular docking methods. The active ingredients of ShuiJingDan (SJD) were obtained from the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP), and the relevant targets of GA were obtained from the Online Mendelian Inheritance in Man (OMIM) database and Therapeutic Target Database (TTD). The core drug group–target–disease Venn diagram was formed by crossing the active ingredients of SJD and the relevant targets. Gene Ontology (GO) analysis was conducted for functional annotation, DAVID was used for Kyoto Encyclopedia of Genes, and Genomes pathway enrichment analysis, and R was used to find the core targets. The accuracy of SJD network pharmacology analysis in GA treatment was verified by molecular docking simulations. Finally, a rat GA model was used to further verify the anti-inflammatory mechanism of SJD in the treatment of GA.Results: SJD mainly acted on target genes including IL1B, PTGS2, CXCL8, EGF, and JUN, as well as signal pathways including NF-κB, Toll-like receptor (TLR), IL-17, and MAPK. The rat experiments showed that SJD could significantly relieve ankle swelling, reduce the local skin temperature, and increased the paw withdrawal threshold. SJD could also reduce synovial inflammation, reduced the concentrations of interleukin-1β (IL-1β), IL-8, and COX-2 in the synovial fluid, and suppressed the expression of IL1B, CXCL8, and PTGS2 mRNA in the synovial tissue.Conclusion: SJD has a good anti-inflammatory effect to treat GA attacks, by acting on target genes such as IL-1β, PTGS2, and CXCL8.Keywords: ShuiJingDan, gouty arthritis, network pharmacology, molecular docking, IL-1β, COX-2

Dongchu Zhou,1 Xinrui Dong,1 Zhen Zhou,2 Qiao Liu1 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, AustraliaCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410000, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: The market price of adebrelimab, the first Chinese-developed anti-PD-L1 antibody used as a first-line treatment for extensive stage-small-cell lung cancer (ES-SCLC), has garnered significant public attention. This study sought to investigate the affordable price of adebrelimab for Chinese patients with untreated ES-SCLC through a cost-effectiveness analysis.Patients and Methods: We conducted a cost-effectiveness analysis using a Markov model, incorporating a what-if scenario of adding adebrelimab to first-line etoposide/platinum (EP) chemotherapy is cost-effective for ES-SCLC patients from the perspective of the Chinese healthcare system. The model included three mutually exclusive health states, with transition probabilities derived from the CAPSTONE-1 trial. Health state utilities and costs were acquired from a myriad of authoritative sources. We compared the incremental cost-effectiveness ratios (ICERs) for adebrelimab plus EP chemotherapy (AEP) versus EP with a willingness-to-pay threshold of &dollar;37,654 per quality-adjusted life-years (QALYs) to estimate the affordable price ceiling of the upcoming adebrelimab.Results: For the entire ES-SCLC population, the estimated price ceiling of adebrelimab/mg was &dollar;0.542 (95% CI, &dollar;0.542-&dollar;0.552). Subgroup analyses found that the highest price ceiling of adebrelimab/mg was observed in ES-SCLC patients with lactate dehydrogenase concentration ≤ upper normal limit [&dollar;0.824 (95% CI, &dollar;0.815-&dollar;0.830)]; and the lowest was found in ES-SCLC patients with liver metastasis [&dollar;0.252 (95% CI, &dollar;0.250- &dollar;0.256)]. Sensitivity analysis revealed a heightened probability of cost-effectiveness for the first-line AEP as the price of adebrelimab decreased, encompassing both the entire ES-SCLC population and its subgroups.Conclusion: The affordable price range for adebrelimab/mg Chinese patients with untreated ES-SCLC was estimated to be between &dollar;0.252 and &dollar;0.824, with variations observed across different subgroups. In the context of universal healthcare coverage, our study provides valuable evidence to inform the implementation of a value-based pricing strategy for cancer treatment.Keywords: cost-effectiveness, extensive stage-small-cell lung cancer (ES-SCLC), adebrelimab, drug pricing, China

Linlan Yang,1,&ast; Kaijiong Zhang,2,&ast; Dongming Zheng,1 Yuxin Bai,1 Daifan Yue,1 Lichun Wu,2 Han Ling,2 Sujiao Ni,2 Haimin Zou,2 Bo Ye,2 Chang Liu,2 Yao Deng,2 Qiancheng Liu,3 Yan Li,1 Dongsheng Wang1,2 1College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Clinical Laboratory of Mianyang People’s Hospital, Mianyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Wang, Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email wangdongshengnc@163.com Yan Li, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email Liliana@cdutcm.edu.cnAbstract: In addition to hemostasis and coagulation, years of studies have proved that platelets are involved in the whole process of tumor progression, including tumor invasion, intravasation, extravasation, and so on. It means that this property of platelets can be used in anti-tumor therapy. However, traditional platelet-based antitumor drugs often cause autologous platelet damage due to lack of targeting, resulting in serious side effects. Therefore, the researchers designed a variety of anti-tumor drug delivery systems based on platelets by targeting platelets or platelet membrane coating. The drug delivery systems have special response modes, which is crucial in the design of nanoparticles. These modes enhance the targeting and improve the anti-tumor effect. Here, we present a review of recent discoveries in the field of the crosstalk between platelets and tumors and the progress of platelet-based anti-tumor nanoparticles.Keywords: platelet, tumor, targeted platelet, platelet membranes, stimuli-responsive drug delivery system, nanoparticle

Yinghui Zhang,1 Yanhua Jin,1 Huan Wang,1 Long He,2 Yanning Zhang,1 Qi Liu,1 Yu Xin,1 Xueyu Li3 1Department of Nephrology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, People’s Republic of China; 2Organ Transplant Center, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, People’s Republic of China; 3Nursing Department, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Xueyu Li, Nursing Department, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning Province, 110016, People’s Republic of China, Tel/Fax +18909882688, Email lxy_dr@163.com Yanning Zhang, Department of Nephrology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning Province, 110016, People’s Republic of China, Tel/Fax +18604105316, Email 18604105316@163.comPurpose: Chronic kidney disease (CKD) will become an end-stage renal disease (ESRD) at stage 5. Peritoneal dialysis (PD) is required for renal replacement therapy. This study aims to identify monocytes-related genes in peritoneal cells from long-term PD (LPD) patients and short-term PD (SPD) patients.Methods: Bulk RNA-seq data (GSE125498 dataset) and ScRNA-seq data (GSE130888) were downloaded to identify differentially expressed genes, monocytes-related genes, and monocytes marker genes in LPD patients. Immune infiltration was analyzed in the GSE125498 dataset. Core genes associated with monocytes changes were screened out, followed by functional analysis and expression validation using RT-PCR.Results: Monocytes are the most abundant immune cell in PD. The number of monocytes was remarkably decreased in LPD compared with SPD. A total of 16 up-regulated core genes negatively correlated with the abundance of monocytes were obtained in LPD. The expression of 16 core genes was lower in monocyte clusters than that in other cell clusters. In addition, LCK, CD3G, CD3E, CD3D, and LAT were involved in the signaling pathways of Th1 and Th2 cell differentiation, T cell receptor signaling pathway, and Th17 cell differentiation. CD2 was involved in hematopoietic cell lineage signaling pathway.Conclusion: Identification of monocytes related-genes and related signaling pathways could be helpful in understanding the molecular mechanism of monocytes changes during PD.Keywords: long-term peritoneal dialysis, short-term peritoneal dialysis, monocytes, peritoneal cells, single-cell sequencing, signaling pathway

Suyang Zheng,1,&ast; Dong Li,1,2,&ast; Qingbai Liu,1,3 Cheng Tang,1 Wenhao Hu,1,4 Shengshan Ma,1,5 Yan Xu,1,6,7 Yong Ma,8 Yang Guo,8 Bo Wei,1 Chuanlin Du,9 Liming Wang1,6,7 1Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Trauma Center, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 3Department of Orthopedics, Lianshui People’s Hospital of Kangda College Affiliated to Nanjing Medical University, Huai’an, Jiangsu Province, People’s Republic of China; 4Department of Orthopedics, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu Province, People’s Republic of China; 5Department of Sports Medicine, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu Province, People’s Republic of China; 6Key Laboratory of Additive Manufacturing Technology, Institute of Digital Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 7Cartilage Regeneration Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 8Laboratory of New Techniques of Restoration and Reconstruction of Orthopedics and Traumatology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, People’s Republic of China; 9Department of Orthopedics, Ganyu District People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Wang; Chuanlin Du, Tel +86-25-5227-1000 ; +86-518-8621-2626, Fax +86-25-5226-9924 ; +86-518-8622-5984, Email wlmnjsy@outlook.com; chuanlindu@foxmail.comPurpose: This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved osteochondral regeneration outcomes.Methods: In this study, we modified the surface of nano-hydroxyapatite (n-HAp) through alkylation reactions to prepare n-HApMA. Characterization techniques, including X-ray diffraction, infrared spectroscopy scanning, thermogravimetric analysis, particle size analysis, and electron microscopy, were employed to analyze n-HApMA. Bioinks were prepared using n-HApMA, high porosity GelMA hydrogel, and adipose tissue derived stromal cells (ADSCs). The rheological properties of the bioinks during photocuring were investigated using a rheometer. Based on these bioinks, a biphasic scaffold was constructed. The viability of cells within the scaffold was observed using live-dead cell staining, while the internal morphology was examined using scanning electron microscopy. The stiffness of the scaffold was evaluated through compression testing. Scaffolds were implanted into the osteochondral defects of New Zealand rabbit knees, and microCT was utilized to observe the subchondral bone repair. Hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, and Safranin O/Fast Green staining were performed to assess the regeneration of subchondral bone and cartilage. Furthermore, immunohistochemical staining was employed to detect the expression of osteogenic and chondrogenic-related molecules.Results: Scaffold characterization revealed that surface modification enables the uniform distribution of n-HApMA within the GelMA matrix. The incorporation of 5% n-HApMA notably enhanced the elastic modulus and stiffness of the 6% high-porosity GelMA in comparison to n-HAp. Moreover, in-vivo study showed that the homogeneous dispersion of n-HApMA on the GelMA matrix facilitated the osteogenic differentiation of adipose-derived stem cells (ADSCs) and promoted osteochondral tissue regeneration.Conclusion: These findings suggest potential applications of the n-HApMA/GelMA composite in the field of tissue engineering and regenerative medicine.Graphical Abstract: Keywords: subchondral bone, surface modification, bio-ink, scaffold, hydrogel

Dunmin She,1,2,&ast; Wei Xu,3,&ast; Jing Liu,4,&ast; Zikai Zhang,5 Ping Fang,3 Ran Li,3 Dehong Kong,3 Miao Xuan,3 Qi Liu,3 Mo Yuan Pan,6 Yan Wang,1,2 Ying Xue3 1Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Department of Endocrinology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 5Department of Oncology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 6The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Xue, Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, No. 389, Xincun Road, Shanghai, People’s Republic of China, Tel +86-21-66111061, Email doxy0622@163.com Yan Wang, Clinical Medical College, Yangzhou University, No. 98, Nantong West Road, Yangzhou, Jiangsu Province, People’s Republic of China, Email yzyan1972@126.comPurpose: Metabolic syndrome (MetS) is a rising global concern with an increasing prevalence. This study aimed to evaluate the relationship between serum uric acid to creatinine ratio (SUA/Cr) and MetS in adults with overweight/obesity in China.Patients and Methods: We conducted a cross-sectional study comprising 4699 participants with overweight/obesity who underwent physical examinations. Their serum levels of various components, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), fasting plasma glucose (FPG), creatinine (Cr), and uric acid (UA) were measured. Renal function-normalized SUA was calculated using SUA/Cr. Logistic regression analysis was employed to investigate the association between SUA/Cr and MetS in adults with overweight/obesity.Results: SUA/Cr levels were lower in non-MetS participants (OR: 2.159, 95% CI: 1.82 to 2.56; p < 0.001), and tended to rise with the increasing number of MetS components. Additionally, elevated SUA/Cr levels were associated with a higher risk of hypertension, hyperglycemia, and dyslipidemia.Conclusion: SUA/Cr levels were significantly associated with MetS and its components in Chinese adults with overweight/obesity.Keywords: metabolic syndrome, serum uric acid to creatinine ratio, overweight/obesity