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Mingzhao Wang,1 Ran Liu,1 Joseph Luttrell IV,2 Chaoyang Zhang,2 Juanying Xie1 1School of Computer Science, Shaanxi Normal University, Xian, People’s Republic of China; 2School of Computing Sciences and Computer Engineering, University of Southern Mississippi, Hattiesburg, MS, USACorrespondence: Juanying Xie, School of Computer Science, Shaanxi Normal University, No. 620, West Chang’an Avenue, Chang’an District, Xi’an, 710119, Shaanxi, People’s Republic of China, Tel +86 13088965815, Email xiejuany@snnu.edu.cn Chaoyang Zhang, School of Computing Sciences and Computer Engineering, University of Southern Mississippi, 118 College Drive, Hattiesburg, MS, 39406-0001, USA, Email chaoyang.zhang@usm.eduPurpose: Breast cancer is the most common major public health problems of women in the world. Until now, analyzing mammogram images is still the main method used by doctors to diagnose and detect breast cancers. However, this process usually depends on the experience of radiologists and is always very time consuming.Patients and Methods: We propose to introduce deep learning technology into the process for the facilitation of computer-aided diagnosis (CAD), and address the challenges of class imbalance, enhance the detection of small masses and multiple targets, and reduce false positives and negatives in mammogram analysis. Therefore, we adopted and enhanced RetinaNet to detect masses in mammogram images. Specifically, we introduced a novel modification to the network structure, where the feature map M5 is processed by the ReLU function prior to the original convolution kernel. This strategic adjustment was designed to prevent the loss of resolution for small mass features. Additionally, we introduced transfer learning techniques into training process through leveraging pre-trained weights from other RetinaNet applications, and fine-tuned our improved model using the INbreast dataset.Results: The aforementioned innovations facilitate superior performance of the enhanced RetiaNet model on the public dataset INbreast, as evidenced by a mAP (mean average precision) of 1.0000 and TPR (true positive rate) of 1.00 at 0.00 FPPI (false positive per image) on the INbreast dataset.Conclusion: The experimental results demonstrate that our enhanced RetinaNet model defeats the existing models by having more generalization performance than other published studies, and it can also be applied to other types of patients to assist doctors in making a proper diagnosis. Keywords: computer-aided diagnosis, deep learning, object detection, RetinaNet, transfer learning

Siwei Xia, Xiaoyan Gu, Gaojian Wang, Yizhi Zhong, Fengjie Ma, Qinxue Liu, Junran Xie Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Junran Xie, Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email xiejunran@zju.edu.cnAbstract: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common and serious clinical lung disease characterized by extensive alveolar damage and inflammation leading to impaired gas exchange. Alveolar macrophages (AMs) maintain homeostatic properties and immune defenses in lung tissues. Several studies have reported that AMs are involved in and regulate ALI/ARDS onset and progression via different regulated cell death (RCD) programs, such as pyroptosis, apoptosis, autophagic cell death, and necroptosis. Notably, the effects of RCD in AMs in disease are complex and variable depending on the environment and stimuli. In this review, we provide a comprehensive perspective on how regulated AMs death impacts on ALI/ARDS and assess its potential in new therapeutic development. Additionally, we describe the crosstalk between different RCD types in ALI, and provide new perspectives for the treatment of ALI/ARDS and other severe lung diseases.Keywords: alveolar macrophage, apoptosis, autophagic cell death, necroptosis, pyroptosis, acute lung injury

Manjia Zheng,1 Ziwei Chen,1 Jiling Xie,1 Qiyuan Yang,1 Minhua Mo,1 Jia Liu,2 Liangjiao Chen1 1Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jia Liu, Stomatological Hospital, Southern Medical University, No. 366 jiangnan Road South, Guangzhou, Guangdong, 510280, People’s Republic of China, Email liujia1988@smu.edu.cn Liangjiao Chen, Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, No. 31 huangsha Road, Guangzhou, Guangdong, 510145, People’s Republic of China, Email 2010686017@gzhmu.edu.cnAbstract: Silica nanoparticles (SiNPs) are widely used in biomedical fields, such as drug delivery, disease diagnosis, and molecular imaging. An increasing number of consumer products containing SiNPs are being used without supervision, and the toxicity of SiNPs to the human body is becoming a major problem. SiNPs contact the human body in various ways and cause damage to the structure and function of genetic material, potentially leading to carcinogenesis, teratogenicity and infertility. This review summarizes SiNPs-induced genetic and epigenetic toxicity, especially to germ cells, and explore their potential mechanisms. SiNPs cause genetic material damage mainly by inducing oxidative stress. Furtherly, the molecular mechanisms of epigenetic toxicity are discussed in detail for the first time. SiNPs alter DNA methylation, miRNA expression, histone modification and inhibit chromatin remodeling by regulating epigenetic-related enzymes and transcription factors. This review is beneficial for investigating potential solutions to avoid toxicity and provide guidance for better application of SiNPs in the biomedical field.Keywords: silica nanoparticles, genotoxicity, epigenetic, DNA damage, germ cells

Xinqia Huang,1,* Ziquan Zhao,1,* Weiqiang Zhan,1 Mingzhu Deng,1 Xuyang Wu,1 Zhoutao Chen,1 Jiahao Xie,2 Wei Ye,3 Mingyan Zhao,1,4 Jiaqi Chu3,4 1Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 3Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 4Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaqi Chu; Mingyan Zhao, Affiliated Hospital of Guangdong Medical University, No. 57 Renmin Avenue South Road, Zhanjiang, Guangdong, 524001, People’s Republic of China, Email chujiaqi@gdmu.edu.cn; mingyan.zhao@gdmu.edu.cnPurpose: To investigate the osteogenic potential of human embryonic stem cell-derived exosomes (hESC-Exos) and their effects on the differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs).Methods: hESC-Exos were isolated and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. hUCMSCs were cultured with hESC-Exos to assess osteogenic differentiation through alizarin red staining, quantitative PCR (qPCR), and Western blotting. miRNA profiling of hESC-Exos was performed using miRNA microarray analysis. In vivo bone regeneration was evaluated using an ovariectomized rat model with bone defects treated with exosome-loaded scaffolds.Results: hESC-Exos significantly promoted the osteogenic differentiation of hUCMSCs, as evidenced by increased alizarin red staining and the upregulation of osteogenesis-related genes and proteins (ALP, RUNX2, OCN). miRNA analysis revealed that miR-21-5p is a key regulator that targets YAP1 and activates the Wnt/β-catenin signaling pathway. In vivo, hESC-Exos enhanced bone repair in ovariectomized rats, as demonstrated by increased bone mineral density and improved bone microarchitecture compared to those in controls.Conclusion: hESC-Exos exhibit significant osteogenic potential by promoting the differentiation of hUCMSCs and enhancing bone regeneration in vivo. This study revealed that the miR-21-5p-YAP1/β-catenin axis is a critical pathway, suggesting that the use of hESC-Exos is a promising therapeutic strategy for bone regeneration and repair. Keywords: human embryonic stem cells, exosomes, osteogenic differentiation, bone regeneration, miR-21-5p, YAP1

Runcong Zhang,1,2,* Jing Fan,1,2,* Lu Han,3,4,* Juehui Mao,4,5 Liang Sun,1,2 Yuetian Yu,2,6,7 Weibin Fan,1,2 Jiao Xie,2,8 Bin Lin,1,2,7 Nengming Lin1,2,9 1Department of Pharmacy, Changxing People’s Hospital, Changxing, People’s Republic of China; 2Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou, Changxing, People’s Republic of China; 3School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou, People’s Republic of China; 8Department of Pharmacy, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 9Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Lin, Department of Pharmacy, Changxing People’s Hospital, Changxing, 313100, People’s Republic of China, Tel/Fax +86-572-6267652, Email lb_wzmc@126.com Nengming Lin, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, 310006, People’s Republic of China, Tel/Fax +86-572- 56007905, Email lnm1013@zju.edu.cnPurpose: Nirmatrelvir/ritonavir (N/R) is the first drug to receive emergency authorization for the treatment of COVID-19 infection. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of potential covariates and explore dosing regimen.Patients and Methods: Sparse data of serum concentrations of N/R were obtained from 129 patients with COVID-19 infection receiving oral 300/100 mg N/R twice daily for 5 days. Plasma samples were assayed using ultra-high-performance liquid chromatography–tandem mass spectrometry. The PopPK model was developed using a nonlinear mixed effects approach utilizing the NONMEM 7.4 software. Monte Carlo simulation was conducted to optimize the dosage regimen.Results: A one-compartment model with first-order absorption and first-order elimination provided the best fit for the data. Allometric scaling of parameters on creatinine clearance (CrCl) and body weight were identified as covariates that significantly influenced exposure-efficacy after oral administration of nirmatrelvir. Monte Carlo simulation using the final model generated concentration-time profiles for virtual patients (1,000 per group) with varying renal functions and body weight. Furthermore, we developed a web-based dashboard to visualize the dynamic changes in nirmatrelvir concentration and provide individualized dosage regimens.Conclusion: This study showed that dosing regimen optimization of nirmatrelvir should be based on CrCl and body weight. Moreover, a web-based dashboard has been developed to facilitate individualized pharmacotherapy.Keywords: population pharmacokinetics, nirmatrelvir, COVID-19, simulations, dosing regimen

Liang Chen,1,* Xiaomei Ying,2,* Haohao Wang,1,* Jiaheng Xie,3,* Qikai Tang,4 Wen Liu1 1Department of Hepatobiliary and Pancreatic Surgery, Conversion Therapy Center for Hepatobiliary and Pancreatic Tumors, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 2Department of General Surgery, Suzhou Hospital of Anhui Medical University, Suzhou, Anhui, People’s Republic of China; 3Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 4Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Liu, Department of Hepatobiliary and Pancreatic Surgery, Conversion therapy center for Hepatobiliary and Pancreatic Tumors, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China, Email nickwen2006@163.comBackground: The role of cellular senescence in the tumor microenvironment of pancreatic cancer (PC) remains unclear, particularly regarding its impact on prognosis and immunotherapy outcomes.Methods: We utilized single-cell sequencing datasets (GSE155698 and GSE154778) for pancreatic cancer from the Gene Expression Omnibus (GEO) database and bulk RNA-seq data from the University of California, Santa Cruz (UCSC) and International Cancer Genome Consortium (ICGC) repositories, creating three patient cohorts: The Cancer Genome Atlas (TCGA) cohort, PAAD-AU cohort, and PAAD-CA cohort. Dimensionality reduction cluster analysis processed the single-cell data, while weighted gene co-expression network analysis (WGCNA) and differential expression gene analysis were applied to bulk RNA-seq data. Prognostic models were developed using Cox proportional hazards (COX) and least absolute shrinkage and selection operator (LASSO) regression, with validation through survival analysis, decision curve analysis, and principal component analysis (PCA). Tumor mutation data were analyzed using the “maftools” package, and the immune microenvironment was assessed with TIMER2 data.Results: We developed a senescence-related (SENR) six-gene prognostic signature for PC, which stratifies patients by risk, with high-risk groups showing poorer prognoses. This model also offers predictive insights into tumor mutations and immune microenvironment characteristics. Caveolin-1 (CAV1) emerged as a significant prognostic biomarker, with functional validation showing its role in promoting cancer cell proliferation and migration, highlighting its potential as a therapeutic target.Conclusion: This study provides a novel senescence-related prognostic tool for PC, enhancing patient stratification for prognosis and immunotherapy, and identifies CAV1 as a key gene with clinical significance for targeted interventions.Keywords: pancreatic cancer, cellular senescence, prognosis, biomarker, immunotherapy

Yongqiang Xiao,1– 3,&ast; Wanqing Chen,4,&ast; Wei Deng,1,&ast; Guoqing Zhu,1 Jin Xie,1 Laihui Luo,1 Liucong Lin,1 Jiahao Tao,1 Zhigao Hu,1 Renfeng Shan1 1Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Surgery, Ganjiang New Area People’s Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of General Surgery, Ganjiang New Area Hospital of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Gastroenterology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a > 20% decrease in AFP within 4 weeks, and AFP response as a > 75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated.Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p< 0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p< 0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333– 6.585, p=0.008, and HR 6.182, 95% CI 1.780– 21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107– 4.318, p=0.024, and HR 3.078, 95% CI 1.407– 6.730, p=0.005), serving as significant prognostic values.Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Bo Jiang,1 Dong Lu,2 Jiaying Dai,3 Kunfeng Li,4 Qianqian Du,1 Bo Xie,5 Jun Xie,6 Xianhai Zhu,2 Xiang Xie1 1Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences & Medicine, University of Science & Technology of China, Hefei, 230001, People’s Republic of China; 3Department of Interventional Radiology, Anqing Municipal Hospital, Anqing, Anhui, 246000, People’s Republic of China; 4Department of Radiology, Tongling People’s Hospital, Tongling, Anhui, 244300, People’s Republic of China; 5Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 6Department of Radiology, Fuyang People’s Hospital, Fuyang, Anhui, 236600, People’s Republic of ChinaCorrespondence: Xiang Xie, Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email 15956922618@163.comObjective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC).Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems.Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0– 4 points), medium-risk (DTH-B, 5– 6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73± 0.62 months, 12.73± 0.10 months, and 6.93± 0.19 months, respectively (p< 0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems.Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, prognosis prediction model

Yadong Sun,1 Yanjie Shan,1 Jiaqiong Xie,1 Ke Chen,1 Jia Hu2 1Faculty of Social Sciences, Chongqing University, Chongqing, People’s Republic of China; 2Institute for Advanced Studies in Humanities and Social Science, Chongqing University, Chongqing, People’s Republic of ChinaCorrespondence: Ke Chen; Jia Hu, Chongqing University, Shapingba, Chongqing, People’s Republic of China, 400044, Tel +86-13628362626, Email chenke197729@163.com; hujia827@cqu.edu.cnPurpose: With the development of information technology and various social media, recommendation algorithms have increasingly more influence on users’ social media usage. To date, there has been limited research focused on analyzing the impact of recommendation algorithms on social media use and their corresponding role in the development of problematic behaviors. The present study analyzes the impact of recommendation algorithms on college students’ information sharing and internalizing, externalizing problem behaviors to address the aforementioned shortcomings.Methods: An online questionnaire survey was conducted among 34,752 college students in China. A latent profile analysis was conducted to explore the various behavioral patterns of Chinese college students’ information sharing across the three social media platforms identified for this study. The Bolck–Croon–Hagenaars (BCH) method Regression Mixture Modeling was then used to analyze the differences in internalizing and externalizing problem behaviors among the different subgroups of Chinese college students.Results: The level of information sharing by college students across different social media platforms could be divided into “WeChat Moments low-frequency information sharing”, “middle-frequency comprehensive information sharing”, “TikTok high-frequency information sharing”, and “Sina Weibo high-frequency information sharing”. Significant differences were observed regarding internalizing and externalizing problem behaviors among college students in different information-sharing subgroups.Conclusion: This study identified four subgroups with different information-sharing characteristics using latent profile analysis. Among them, college students who are in subgroup of social media information sharing influenced by recommendation algorithms exhibit higher frequency of information sharing and higher level of internalizing and externalizing problematic behaviors. These results expand our understanding of college students’ social media usage and problem behaviors from a technological perspective. In future, the negative impacts of recommendation algorithms on college students can be reduced by improving their awareness of these algorithms and optimizing the algorithms themselves.Keywords: user-generated content, recommendation algorithms, latent profile analysis, internalizing problem behaviors, externalizing problem behaviors

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

Rui Zhou,1,2,&ast; Lijuan Fu,2,&ast; Shu Liu,2,&ast; Sanjie Gao,2 Zhifu Zhao,2 Wencai Jiang,2 Li Liu,2 Weiqiao Ren,2 Dongmei Xiang,2 Xing You,2 Chunyong Tang,2 Yukai Zhou,2 Yanqing Song,2 Juan Xie,2 Li Xie,2 Ru Yu,2 Xianjie Zhang,2 Dan Zhou,2 Jia Han,2 Leqiang Xia,2 Lize Xiong1 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Center for Anesthesiology and Perioperative Medicine, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology, Deyang People’s Hospital, Deyang, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leqiang Xia, Department of Anesthesiology, Deyang People’s Hospital, No. 173, Section 1, North Taishan Road, Deyang, Sichuan, 618000, People’s Republic of China, Tel +8613547098458, Email xialq123184@163.com Lize Xiong, Shanghai Fourth People’s Hospital, No. 1279, Sanmen Road, Shanghai, 200434, People’s Republic of China, Tel +86-21-55603002, Fax +86-21-56660851, Email mzkxlz@126.com; lizexiong@tongji.edu.cnPurpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy.Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected.Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups.Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.Keywords: propofol, ciprofol, remimazolam, endoscopic sedation, dreaming

Chaoping Yang,1,&ast; Jing Xie,2,&ast; Qianjun Chen,2 Qiongyin Yuan,3 Jianping Shang,4 Haibo Wu,5 Youhua Yang,6 Mingfang Wang,7 Xiaolan Shu,8 Jing Yue,9 Danna Tu,10 Ying Lin,1,&ast; Ronghao Zheng,4,&ast; Xiaolin Wu4 1Nursing Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Obstetrical department, Huanggang Maternal and Child Health Hospital, Hubei, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5School of Health and Nursing, Wuchang University of Technology, Wuhan, People’s Republic of China; 6Department of Basic Medical Sciences, School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 7Department of Pediatric Gastroenterology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Pediatric Intensive Care Unit (PICU), Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Emergency Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 10Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu Luo Road, Hongshan District, Wuhan, Hubei Province, 430070, People’s Republic of China, Email hytwo2001@126.com Ying Lin, Nursing department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email 523933025@qq.comPurpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students.Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP.Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ± 26.32, 55.00 ± 12.50, and 71.88 ± 15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score > 80 points was an independent protective factor related to knowledge and practice.Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.Keywords: antibiotic use, antimicrobial resistance, knowledge, attitude, practice, nursing students

Xiaojie Chen,1,2 Jianteng Xie,2 Yifan Zhang,2 Shaogui Zhang,2 Sheng Li,2 Min Lu,2 Danfeng Liu,2 Weiting He,2 Hokhim Yau,2 Runli Jia,2 Yaxi Zhu,2 Wenjian Wang2 1Department of Nephrology, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, People’s Republic of ChinaCorrespondence: Wenjian Wang, Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 106 Zhongshan Er Road, Main Building, Room 1436, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86 (20)83827812-61421, Email wangwenjian@gdph.org.cnObjective: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated.Methods: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin.Results: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521± 22.960 g/L. The median follow-up time was 21.103± 18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males.Conclusion: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.Keywords: hemoglobin, eGFR decline, ESRD, diabetic kidney disease, non-linear, Cox proportional-hazards regression

Yushan Xu, Miaomiao Li, Mengjiao Lin, Dawei Cui, Jue Xie Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaCorrespondence: Jue Xie; Dawei Cui, Tel +86571-87236391 ; +86571-87236390, Email zyyyxj2011@zju.edu.cn; daweicui@zju.edu.cnAbstract: CD4+ T cells play a critical role in the pathogenesis of viral diseases, which are activated by the internal metabolic pathways encountering with viral antigens. Glutaminolysis converts glutamine into tricarboxylic acid (TCA) circulating metabolites by α-ketoglutaric acid, which is essential for the proliferation and differentiation of CD4+ T cells and plays a central role in providing the energy and structural components needed for viral replication after the virus hijacks the host cell. Changes in glutaminolysis in CD4+ T cells are accompanied by changes in the viral status of the host cell due to competition for glutamine between immune cells and host cells. More recently, attempts have been made to treat tumours, autoimmune diseases, and viral diseases by altering the breakdown of glutamine in T cells. In this review, we will discuss the current knowledge of glutaminolysis in the CD4+ T cell subsets from viral diseases, not only increasing our understanding of immunometabolism but also providing a new perspective for therapeutic target in viral diseases.Keywords: CD4+ T cells, viral diseases, glutamine, glutaminolysis, immune response

Linqi Zhou,1 Changyuan Qiao,1 Jialing Huang,2 Jian Lin,2 Haisheng Zhang,2 Jian Xie,2 Yonggui Yuan,3 Changchun Hu2 1School of the Fourth Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Psychosomatics and Psychiatry, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Changchun Hu, Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310002, People’s Republic of China, Tel +86-571-56006902, Email chuntianjs@163.comBackground: Previous studies have demonstrated a strong association between recent stressful life events and non-suicidal self-injury (NSSI) among adolescents. Internalizing symptoms and difficulty in emotion regulation (DER) may mediate this relationship. This study aimed to investigate the relationship between recent stressful life events and NSSI severity in adolescents and the potential moderating role of internalizing symptoms and DER.Methods: A total of 224 adolescent inpatients (78.6% female) participated in the study, with an age range of 12– 18 years old. Data on recent stressful life events, internalizing symptoms, DER, and NSSI behaviors were collected using a clinician-rated questionnaire. A structural equation model was used to test the hypothesized model.Results: The rate of NSSI reporting among adolescents in the past 12 months was 65.18%. Recent stressful life events were found to be directly associated with NSSI severity (β = 0.128, P = 0.023). A chain-mediating effect between recent stressful life events and NSSI was also confirmed (β = 0.034, P = 0.023), with DER and internalizing symptoms playing a chain-mediating role and DER having a significantly indirect association with NSSI through internalizing symptoms.Conclusion: Recent stressful life events appear to play a role in the etiology of NSSI, particularly punishment and interpersonal relationship events that warrant special attention. DER and internalizing symptoms play a chain-mediating role in the relationship between life events and NSSI. Reducing recent stressful life events, screening for internalizing symptoms, and improving emotion regulation may decrease NSSI behavior among adolescents.Keywords: non-suicidal self-injury, adolescents, recent stressful life events, internalizing symptoms, difficulty in emotion regulation, structural equation model

Yun Zhao,1,&ast; Lijun Zhao,1,&ast; Zhaohuang Wang,1 Shuhui Cui,1 Chenchen Ren,2 Li Yang,2 Yang Bai,2 Yuanhang Zhu,2 Jingyan Xie,3 Yujuan Li,3 Xiaoqing Wu,3 Jing Feng,3 Shanqing Man,4 Longmei Huang,4 Xiaoqi Li,4 Xiaotian Yu,4 Jianliu Wang1 1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, National Clinical Research Center for Obstetrics and Gynecology, Zhengzhou Key Laboratory of Cervical Disease, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment, Zhengzhou, Henan, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Hangzhou New Horizon Health Technology Co. Ltd, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliu Wang, Department of Obstetrics and Gynecology, Peking University People’s Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8618901086568, Email wangjianliu1203@163.comObjective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value.Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with

Junhui He,1,&ast; Jiaxiu Xie,1,&ast; Guili Zhou,2,&ast; Chunlian Jia,2 Dongbo Han,2 Dongmei Li,1 Jie Wei,1 Yi Li,1 Renshan Huang,1 Chunlian Li,1 Bo Wang,3 Chao Wei,3 Qibiao Su,4 Kedao Lai,1 Guining Wei1 1Department of Pharmacology, Key Laboratory of Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Guangxi Shuangyi Pharmaceutical Co., Ltd, Nanning, Guangxi, 530021, People’s Republic of China; 4College of Health Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guining Wei, Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China, Email weiguining2013@163.com Qibiao Su, College of Health Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Tel +8618376664440, Email suqibiao@163.comPurpose: Neuroinflammation is a significant etiological factor in the development of depression. Traditional Chinese medicine (TCM) has demonstrated notable efficacy in the treatment of inflammation. Our previous study surfaces that the active fraction of Polyrhachis vicina Roger (AFPR) has antidepressant and anti-neuroinflammatory effects, but the specific mechanisms remain to be elucidated. The objective of this study was to examine the impact of AFPR on inflammation in depression via the FTO/miR-221-3p/SOCS1 axis.Methods: Chronic unpredictable stress (CUMS)-induced rats and LPS-induced BV2 cells were employed to simulate depression models in vivo and in vitro. The levels of inflammatory factors were detected using the ELISA assay. The expression of genes and proteins was detected using qRT-PCR and Western blot. Gene interactions were detected using the dual luciferase reporter gene. Protein-RNA interactions were investigated using RNA methylation immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP). Neuroinflammation in the brain was examined through H&E staining, while neuronal apoptosis was assessed using TUNEL staining.Results: The results showed that AFPR ameliorated depression induced inflammation by increasing SOCS1 expression. However, SOCS1 was identified as a target of miR-221-3p. Overexpression of miR-221-3p decreased the expression of SOCS1 and increased the levels of NF-κB, IL-7, and IL-6. In addition, we found that miR-221-3p was regulated by FTO-mediated m6A modification through MeRIP and RIP experiments. Interference with miR-221-3p and overexpression of FTO resulted in increased SOCS1 gene expression and decreased levels of NF-κB, IL-7, and IL-6, which were reversed by AFPR.Conclusion: AFPR inhibits the maturation of pri-miR-221-3p through FTO-mediated m6A modification, reduces the production of miR-221-3p, increases the expression of SOCS1, and reduces the level of inflammation, thereby improving depressive symptoms. Keywords: depression, FTO, SOCS1, inflammation, Polyrhachis vicina Roger

Jieyao Xie, Tingjun Pan, Weiwen Luo, Songsheng Zhang, Yuquan Fang, Zhou Xu Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jieyao Xie, Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email X1275014370@163.comBackground: Vascular diseases such as atherosclerosis usually affect multiple organs. Genetic factors have a certain proportion in the risk factors of atherosclerosis. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with multi-site atherosclerosis.Methods: The study included 410 patients with single-site atherosclerosis and 529 patients with multi-site atherosclerosis. The relationship between CYP2C19 rs4244285 and rs4986893 polymorphisms and single-site atherosclerosis and multi-site atherosclerosis was analyzed.Results: The proportion of CYP2C19 rs4244285 A allele (35.9% vs 29.9%, P=0.007) and rs4986893 G allele (97.7% vs 94.8%, P=0.001) in multi-site atherosclerosis group was significantly higher than that in single-site atherosclerosis group. The distribution of CYP2C19 genotypes was significantly different between the two groups (P=0.002). The results of univariate logistic regression indicated that CYP2C19 &ast;1/&ast;3 genotype (&ast;1/&ast;3 vs &ast;1/&ast;1: odds ratio (OR) 0.456, 95% confidence interval (CI): 0.231– 0.902, P=0.024) may decrease risk of multi-site atherosclerosis, while &ast;2/&ast;2 genotype (&ast;2/&ast;2 vs &ast;1/&ast;1: OR 1.780, 95% CI: 1.100– 2.880, P=0.019) may increase risk of multi-site atherosclerosis. Multivariate logistic regression (adjusted for gender, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 &ast;1/&ast;3 genotype (&ast;1/&ast;3 vs &ast;1/&ast;1: OR 0.459, 95% CI: 0.231– 0.909, P=0.026) may be an independent protective factor for multi-site atherosclerosis, while &ast;2/&ast;2 genotype (&ast;2/&ast;2 vs &ast;1/&ast;1: OR 1.767, 95% CI: 1.091– 2.864, P=0.021) may be an independent risk factor for multi-site atherosclerosis.Conclusion: CYP2C19 &ast;1/&ast;3 genotype may be an independent protective factor for multi-site atherosclerosis, while &ast;2/&ast;2 genotype may be an independent risk factor for multi-site atherosclerosis.Keywords: CYP2C19, genotype, multi-site atherosclerosis, polyvascular disease

Yongqiang Xiao,&ast; Guoqing Zhu,&ast; Jin Xie,&ast; Laihui Luo, Wei Deng, Liucong Lin, Jiahao Tao, Zhigao Hu, Renfeng Shan Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with unresectable hepatocellular carcinoma (u-HCC) treated with hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Patients and Methods: We conducted a retrospective cohort study involving patients diagnosed with u-HCC who underwent HAIC combined with lenvatinib and camrelizumab. Patients were stratified into two cohorts using the median NLR as the cutoff point. We then assessed treatment response, overall survival (OS), progression-free survival (PFS), and adverse events in these patient groups.Results: Between October 2020 and April 2022, a total of 88 patients were enrolled in the study. The overall cohort exhibited a median PFS of 7.9 months, while the median OS was not reached, and a median NLR of 3.46. Notably, the group with NLR< 3.46 demonstrated significantly superior OS (not reached vs 9.6 months, p = 0.017) and PFS (18.3 vs 5.3 months, p = 0.0015) compared to the NLR≥ 3.46 group. Furthermore, multivariate analysis revealed that an alpha-fetoprotein (AFP) ≥ 400 ng/mL [hazard ratio (HR), 2.133; 95% confidence interval (CI), 1.102– 4.126; p = 0.024], Barcelona Clinical Hepatocellular Carcinoma (BCLC) stage C (HR, 2.319; 95% CI, 1.128– 4.764; p = 0.022), and NLR ≥ 3.46 (HR, 2.35; 95% CI, 1.239– 4.494; p = 0.009) were identified as independent risk factors for OS. Additionally, multivariate analysis demonstrated that AFP ≥ 400 ng/mL, BCLC stage C, and NLR ≥ 3.46 were independent negative factors of PFS.Conclusion: NLR can be associated with outcomes in patients with u-HCC treated with HAIC combined with lenvatinib and camrelizumab.Keywords: unresectable hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Zihan Hu,1,&ast; Danjiang Dong,2,&ast; Fei Peng,1,&ast; Xing Zhou,1 Qin Sun,1 Hui Chen,1,3 Wei Chang,1 Qin Gu,2,&ast; Jianfeng Xie,1,&ast; Yi Yang1,&ast; 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; 2Department of Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Xie; Qin Gu, Department of Critical Care Medicine, Zhongda Hospital, School of medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Tel/Fax +00862583262500, Email xie820405@126.com; guqinicu012323@126.comPurpose: Immune dysfunction plays a pivotal role in sepsis pathogenesis. Previous studies have revealed the crucial role of T cells and human leukocyte antigen-DR (HLA-DR) in sepsis. However, the function of natural killer (NK) cells remains unclear. This study aimed to investigate whether NK cells are associated with sepsis prognosis. In addition, we aimed to explore the interrelation and influence between NK and other immunological features in patients with sepsis.Patients and Methods: This retrospective, observational study included patients with sepsis from two hospitals in mainland China. The clinical characteristics and immune results during the early phase were collected. Patients were classified according to the level of immune cells to analyze the relationship between immunological features and 28-day mortality.Results: A total of 984 patients were included in this study. Non-survivors were older and had lower levels of lymphocytes, monocytes, NK cells, HLA-DR, and T cells. Patients were classified into eight groups according to their levels of NK cells, HLA-DR, and T cells. Only patients with decreased NK and T cell counts showed a significant increase in 28-day mortality. An increase in CD8+ T cells was correlated with the alleviation of 28-day mortality only among patients with high NK cell levels.Conclusion: This study provides novel insights into the association between NK cells and 28-day mortality as well as the interrelation between NK cells and other immune cells in sepsis. The relationship between CD8+ T cells and 28-day mortality in sepsis is dependent on NK cell count.Keywords: sepsis, immune dysfunction, natural killer cell, HLA-DR, T cell

Min Li,1,2,&ast; Binlong Zhang,3,&ast; Jiangbo Xie,4 Ran Meng,1,2 Xunming Ji2,5 1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China; 3Department of Acupuncture, Moxibustion, and Neurology, Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Department of Neurology, Weifang Traditional Chinese Hospital, Weifang, Shandong, People’s Republic of China; 5Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ran Meng, Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-13693080599, Email ranmeng2011@126.com Xunming Ji, Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-13911077166, Email jixm@ccmu.edu.cnBackground: Although numerous prognostic markers for cerebral venous thrombosis (CVT) have been reported, inconsistencies exist in their predictive values, leading to contradictory forecasts. This study was designed to develop a comprehensive clinical outcome prediction score for Chinese patients with CVT, integrating key prognostic markers to furnish an overall prognosis.Methods: Participants were selected from the CCC cohort, a multicenter study encompassing 26 tertiary hospitals across mainland China. Between January 2021 and May 2022, 170 patients with CVT were prospectively recruited. Potential prognostic markers were extracted from the CCC database and subsequently analyzed.Results: Age, diastolic blood pressure (DBP), neutrophil-to-lymphocyte ratio (NLR), and neuron-specific enolase (NSE) emerged as significant prognostic markers for CVT after a multivariate logistic analysis. Specific cut-off values were identified: Age > 27.5 years, DBP > 79.5 mmHg, NLR > 6.6, and NSE > 16.5 ng/mL. The points assigned were: one each for age and NSE level, two for DBP, and three for NLR, based on the adjusted odds ratio. A positive correlation was found between the baseline CVT outcome score and the mRS at six months’ follow-up. A CVT outcome score of 3.5 served as an effective cut-off value for predicting CVT clinical outcomes. Further analysis revealed that patients with CVT outcome scores > 3 exhibited significantly higher mRS scores than those with scores ≤ 3.Conclusion: This study led to the development of the CVT outcome score, consisting of age, DBP, NLR, and NSE level, specifically for Chinese patients with CVT. The baseline CVT outcome score positively correlated with the mRS score at the six-month follow-up. A CVT outcome score of > 3 serves as a reliable indicator to identify patients at a higher risk of unfavorable clinical outcomes. These patients may benefit from additional care and early interventions to avert potential deterioration.Keywords: clinical outcome, prognosis, cerebral venous thrombosis, prediction score, validation

Junlong Ma,1,2,&ast; Jie Huang,1,&ast; Chan Zou,1 Qian Wu,1 Jinlian Xie,1 Xingfei Zhang,1 Xiaoyan Yang,1 Shuang Yang,1 Ziteng Wu,3 Yan Jiang,3 Sen Yu,3 Xuqing Zhang,4 Guoping Yang,1,5 Mingyuan Li1 1The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 3Nanjing Delova Biotech Co., Ltd., Nanjing, Jiangsu, 210042, People’s Republic of China; 4King-eagle Med Co., Ltd., Changsha, Hunan, 410013, People’s Republic of China; 5Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingyuan Li, Email lmyuan3@126.comBackground: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects.Methods: The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg MobicⓇ (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated.Results: A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15– 60 mg (Cmax and AUC0-t were 5.82– 17.66 μg/mL and 58.08– 251.17 μg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference.Conclusion: QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain.Trial Registration: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).Keywords: meloxicam, phase I trial, pharmacokinetic, safety, novel formulation

Lei Ji,1 Tingting Jiang,1 Xin Zhao,2 Damin Cai,1 Kouzhen Hua,1 Peng Du,1 Yuanyuan Chen,3 Jianping Xie4 1School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of International Registration, Ustar Biotechnologies (Hangzhou) Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, Ministry of Education, Chongqing Municipal Key Laboratory of Karst Environment, School of Life Sciences, Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Lei Ji, School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, No. 481 Binwen Road, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel +86 571 8769 2681, Fax +86 571 8769 2673, Email jilei@hmc.edu.cnPurpose: Fatty acid metabolism plays an important role in the survival and pathogenesis of Mycobacterium tuberculosis. During dormancy, lipids are considered to be the main source of energy. A previous study found that Rv0494 is a starvation-inducible, lipid-responsive transcriptional regulator. However, the role of Rv0494 in bacterial persister survival has not been studied.Methods: We constructed a Rv0494 deletion mutant strain of Mycobacterium tuberculosis H37Rv and evaluated the susceptibility of the mutant strain to antibiotics using a persistence test.Results: We found that mutations in Rv0494 lead to survival defects of persisters, which reflected in increased sensitivity to isoniazid.Conclusion: We conclude that Rv0494 is important for persister survival and may serve as a good target for developing new antibiotics that kill persister bacteria for improved treatment of persistent bacterial infections.Keywords: drug target, drug tolerance, lipids, persisters

Zehui Qin,1 Minhua Li,1,2 Juanjuan Cheng,1,2 Ziwei Huang,1,2 Gaoxiang Ai,1,2 Chang Qu,3 Youliang Xie,1 Yucui Li,1 Huijun Liao,4 Jianhui Xie,5– 7 Ziren Su1,2 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China; 3College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, 510006, People’s Republic of China; 4Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of ChinaCorrespondence: Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China, Email suziren@gzucm.edu.cn Huijun Liao, Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated hospital of Shenzhen University), Shenzhen, People’s Republic of China, Email liaohuijun1016@163.comPropose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application.Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators.Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR.Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.Graphical Abstract: Keywords: berberine, sodium taurocholate, intermolecular interactions, self-assembled, nanoparticles, hyperuricemia

Shaolei Ma,&ast; Haofei Wang,&ast; Kongbo Zhu, Hui Chen, Jianfeng Xie, Yingzi Huang Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, Nanjing, 210009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingzi Huang, Jiangsu 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, Tel +86-025-83262553, Email yz_huang@126.comPurpose: This study aimed to determine the clinical profile connected to the nucleic acid conversion time of COVID-19 patients harboring the SARS-CoV-2 Omicron variant at the hospitals at the Fangcang shelter.Methods: We reported 39,584 COVID-19 patients who were hospitalized in Shanghai, China, between April 5 and May 5, 2022, and who had contracted the Omicron strain of SARS-CoV-2. Demographic data, medical and vaccination history, clinical symptoms, and NCT were reported for the patient.Results: The median age of the patients with COVID-19 included in this study was 45 (interquartile range [IQR]: 33– 54), and 64.2% of them were male. The two most prevalent comorbidities among the patients were hypertension and diabetes. Additionally, we discovered that the percentage of unimmunized patients was negligible (13.2%). We found that male sex, age under 60, and other comorbidities including hypertension and diabetes are significant risk factors for extending NCT when we analyzed the risk variables for NCT. We discovered that vaccination with two or more doses can significantly reduce NCT. The analysis of the young (18– 59 years) and older (60 years) populations produced the same outcomes.Conclusion: Our findings confirm that a full COVID-19 vaccine series or booster doses are highly recommended to significantly reduce NCT. In order to reduce NCT, it is also advised that elderly people who have no clear contraindications take vaccination shots.Keywords: COVID-19, nucleic acid conversion time, Fangcang shelter hospitals, vaccination

Jingjun Xie,1 Jinxia Li,2 Qi Sun1 1Department of Acupuncture, The First People’s Hospital of Huzhou, Zhejiang, 313000, People’s Republic of China; 2Department of Acupuncture, Huzhou Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang Chinese Medical University, Zhejiang, 313000, People’s Republic of ChinaCorrespondence: Jinxia Li, Email lijinxia310@163.comObjective: The purpose of this study was to evaluate the clinical efficacy of extracorporeal shock wave combined with warm acupuncture for external humeral epicondylitis.Methods: Eighty-two patients with external humeral epicondylitis were randomly divided into an observation group and a control group. Patients in the control group were treated with extracorporeal shock waves while those in observation group with warm acupuncture on the basis of the control group. Patients in both groups were evaluated by Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) before and after treatment. The inflammatory factors such as IL-6, IL-10, TNF-ɑ and clinical outcomes were contrasted before and after treatment.Results: There were statistically significant differences in VAS score, MEPS score and DASH score between the two groups before and after treatment (P< 0.05), and the improvement of each score in the observation group was more obvious than that in the control group. After treatment, the inflammatory factors of the two groups were lower than those before treatment, and the difference was statistically significant (P< 0.05). The decrease of inflammatory factors in the observation group was more obvious than that in the control group. The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P< 0.05).Conclusion: Extracorporeal shock wave combined with warm acupuncture could effectively improve the pain symptoms and dysfunction of external humeral epicondylitis and reduce the expression of inflammatory factors, and its effect may be better than that of extracorporeal shock wave treatment alone.Clinical Trial Registration: ChiCTR2200066075.Keywords: extracorporeal shock wave, warm acupuncture, external humeral epicondylitis, a randomized clinical trial

Ying Wu,1 Jing Wen,1 Xiaohui Wang,1 Qingyao Wang,1 Wen Wang,2 Xiangjia Wang,1 Jiang Xie,1 Li Cong1 1School of Medicine, Hunan Normal University, Changsha, 410013, People’s Republic of China; 2Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, 41008, People’s Republic of ChinaCorrespondence: Li Cong, School of Medicine, Hunan Normal University, Changsha, People’s Republic of China, Tel +86-0731-88912446, Fax +86-0731-88912478, Email congli@hunnu.edu.cnBackground: The Chinese population is aging, and chronic non-communicable diseases (NCDs) prevalence is correspondingly increasing, along with associated disability and healthcare costs. Although self-management has been associated with social support and is a recognized priority, its mediating variables have not been studied in detail, particularly among old people with chronic diseases.Purpose: To examine the mediating role of e-health literacy and general self-efficacy in the relationship between social support and self-management of chronic NCDs in Chinese community home-based aging institution residents.Patients and Methods: A random sample of 289 community home-based aging institution elders (≥ 60 years) with chronic NCDs in China was recruited. Questionnaire data were recorded on self-reported socio-demographics, self-management, social support, e-health literacy, and general self-efficacy. Pearson’s correlation analysis identified the relationship between these factors and self-management. Serial multiple mediation model was used to test the hypothesized relationships.Results: The self-management mean (±SD) score was 29.39 ± 9.60, and the level of self-management was medium. Social support (r = 0.283; P

Jiaheng Xie,&ast; Wei Yan,&ast; Zhechen Zhu,&ast; Ming Wang, Jingping Shi Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingping Shi; Ming Wang, Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +8613082555422, Email drshi_njmu@163.com; wangming@jsph.org.cnAbstract: Breast reconstruction can be divided into prepectoral breast reconstruction (PPBR) and subpectoral breast reconstruction (SPBR) according to the implant plane. The original prepectoral breast reconstruction was abandoned for a long time due to the frequent and severe complications. Now, advances in materials technology and improved methods of mastectomy have made safe prepectoral breast reconstruction possible. Moreover, a number of studies have gradually demonstrated the advantages of prepectoral breast reconstruction. As prepectoral breast reconstruction becomes more and more attractive, it is time to review the current advances in prepectoral breast reconstruction.Keywords: breast reconstruction, breast cancer, complications, patient report outcome, prepectoral, subpectoral

Songsheng Zhang,1,2 Weiwen Luo,1,2 Tingjun Pan,1,2 Jieyao Xie,1,2 Zhou Xu,1,2 Yuquan Fang1,2 1Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Songsheng Zhang, Intensive Care Unit, Meizhou People’s Hospital, No. 63 Huangtang Road, Meizhou, Guangdong Province, People’s Republic of China, Email Zsongsheng@163.comBackground: Hypertension is the main risk factor for hemorrhagic stroke. Aldehyde dehydrogenase 2 (ALDH2) may inhibit the occurrence of hypertension by anti-oxidative stress and vascular dilation. The purpose was to investigate the relationship of ALDH2 polymorphisms with hemorrhagic stroke in Hakka Chinese.Methods: A total of 329 patients with hemorrhagic stroke and 515 controls were enrolled, and medical records (smoking and drinking history, hypertension, and diabetes) were collected. The genotypes of ALDH2 rs671 of the two groups were detected and analyzed.Results: The proportion of the ALDH2 rs671 G/G, G/A, and A/A genotype in patients with hemorrhagic stroke was 55.9%, 37.4%, and 6.7%, respectively, while those were 65.0%, 30.7%, and 4.3% in controls, respectively. There was statistically significant difference in ALDH2 rs671 genotypes distribution (P=0.021) and alleles distribution (P=0.005) between patients and controls. Among hemorrhagic stroke patients, no statistically significant differences were observed between patients with ALDH2 different genotypes. Logistic regression analysis showed that there was significantly high risk of hemorrhagic stroke in men (male vs female: adjusted OR 1.711, 95% CI 1.154– 2.538, P=0.008), the presence of hypertension (with vs without hypertension: adjusted OR 16.095, 95% CI 10.958– 23.641, P< 0.001), and the presence of ALDH2 rs671 G/A genotype (G/A vs G/G: adjusted OR 1.679, 95% CI 1.151– 2.450, P=0.007) or A/A genotype (A/A vs G/G: adjusted OR 2.516, 95% CI 1.132– 5.591, P=0.024).Conclusion: ALDH2 rs671 polymorphism likely a risk factor for hemorrhagic stroke.Keywords: ALDH2, polymorphism, hemorrhagic stroke, Hakka

Zike Sheng,1 Junjie Li,2 Chihua Chen,3 Jing Xie,4 Yumin Xu,5 Huijuan Zhou,1 Qing Xie1 1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Infection Control/Department of Nursing, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Huijuan Zhou, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Building 36, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Tel +86-21-64370045-680419, Fax +86-21-64454930, Email hjzhou419@163.comIntroduction: Human melioidosis is an emerging infectious disease in tropical areas of China, and chronic melioidosis can be a rare cause of fever of unknown origin (FUO). Timely diagnosis may improve the prognosis of melioidosis.Case Presentation: We report a case of melioidosis with splenic abscesses caused by Burkholderia pseudomallei in a 57-year-old man, who presented with FUO. Positron emission tomography/computed tomography (PET/CT) revealed multiple hypermetabolic lesions in the spleen. The spleen biopsy was conducted and metagenomics next-generation sequencing (mNGS) of the spleen specimen identified the presence of B. pseudomallei, confirming the diagnosis of melioidosis. Antimicrobial treatment was initiated with intravenous meropenem, followed by oral faropenem. During the follow-up, the patient was in good condition except having a low-grade fever occasionally. A splenectomy was performed, and subsequent culture and mNGS of the spleen pus were both positive for B. pseudomallei. Histopathological characteristics of chronic splenic melioidosis were noted.Conclusion: Melioidosis is a serious endemic disease, and it is critical to raise awareness about this disease.Keywords: melioidosis, Burkholderia pseudomallei, metagenomics next-generation sequencing, splenectomy

Jie Xie,&ast; Xu Xiao,&ast; Zhenjia Dong, Qiangdong Wang Department of Urology, the Fifth People’s Hospital of Huai’an, Huai’an City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiangdong Wang, Email fhhywm@163.comBackground: The systemic inflammation score (SIS) based on the albumin (Alb) level and lymphocyte-to-monocyte ratio (LMR), has been associated with survival in some cancers. However, its prognostic role in prostate cancer (PCa) remains unclear.Methods: The associations between the SIS and the clinicopathological features of PCa were evaluated. The correlations between the SIS and overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and the Log rank test. Univariate and multivariate Cox analyses were conducted to determine the prognostic factors for PCa. Hazard ratios and 95% confidence intervals were calculated.Results: A total of 253 patients with PCa were included in this study. The Kaplan-Meier analysis and Log rank test suggested that patients with a higher Alb level, higher LMR, or a lower SIS had better 5-year OS and PFS compared with patients with a lower Alb level or lower LMR or higher SIS. Univariate and multivariate Cox analyses showed that drinking, prostate-specific antigen level > 100 ng/mL, and neutrophil-to-lymphocyte ratio > 2.09 were significant prognostic factors for OS and PFS in patients with PCa. Nomograms for 5-year OS and PFS were established with concordance index values of 0.888 and 0.824, respectively. The calibration curve was consistent between the actual observations and the prediction nomogram for OS and PFS probability at 5 years.Conclusion: A high SIS is associated with unfavorable survival in patients with PCa. The SIS serves as a novel independent prognostic factor for OS in patients with PCa.Keywords: systemic inflammation score, prostate cancer, progression-free survival, overall survival

Junhui He,1,&ast; Dongbo Han,2,&ast; Chunlian Jia,2,&ast; Jiaxiu Xie,1 Fucui Zhu,2 Jie Wei,1 Dongmei Li,1 Dongmei Wei,1 Yi Li,1 Li Tang,3 Guining Wei,1,4 Jing Yan,4 Yuanming Tong,1 Lifang Yang,4,&ast; Xuecai Tan4,&ast; 1Department of Pharmacology, Key Laboratory of Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Department of Pharmacology, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, 530022, People’s Republic of China; 4Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning, 530008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuecai Tan; Lifang Yang, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning, 530008, People’s Republic of China, Tel +86 0771-5877473, Email gxunxctan@126.com; yanglf1990@163.comPurpose: To investigate the mechanisms of antidepressant action of active fraction of Polyrhachis vicina Rogers (AFPR) through network pharmacology, molecular docking and experimental validation.Methods: GC-MS was used to predict chemical compounds, corresponding databases were used to predict chemical compound targets and depression targets, Cytoscape software was used to construct and analyze the protein interaction network map, DAVID database was used to analyze gene ontology (GO) and KEGG signaling pathway, and AGFR software was used to perform molecular docking. Subsequently, the underlying action mechanisms of AFPR on depression predicted by network pharmacology analyses were experimentally validated in a CORT-induced depression model in vitro and in vivo.Results: A total of 52 potential targets of AFPR on antidepressant were obtained. GO is mainly related to chemical synaptic transmission, signal transduction and others. KEGG signaling pathways are mainly related to cAMP signaling pathway and C-type lectin receptor signaling pathway. The experiment results showed that AFPR significantly increased the expression of PRKACA, CREB and BDNF in mouse brain tissue and PC12 cells. Furthermore, after interfered of cAMP in PC12 cells, the decreased expression of PRKACA, CREB and BDNF was reversed by AFPR.Conclusion: AFPR may exert antidepressant effects through multiple components, targets and pathways. Furthermore, it could improve neuroplasticity via the cAMP signaling pathway to improve depression-like symptoms.Graphical Abstract: Keywords: PC12 cells, BDNF, corticosterone, CAMP signaling pathway, GC-MS

Jinxia Li,1 Jingjun Xie,2 Xiaoqing Guo,1 Ruiyang Fu,1 Yaling Wang,1 Xinjun Guan1 1Huzhou Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, 313000, People’s Republic of China; 2The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of ChinaCorrespondence: Jingjun Xie, Email jingjun.1101@163.comAim: The aim of this research is to analyze the effects of mind-regulation acupuncture on serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels, fatigue, quality of sleep, depression, and quality of life in survivors of breast cancer with cancer-related fatigue.Methods: Total 136 breast cancer survivors with cancer-related fatigue were randomly allocated to the mind-regulation acupuncture group and the control group in a 1:1 ratio, with 68 cases in each group. Finally, 57 cases each in both groups completed the study. The serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels were measured in pre-treatment and post-treatment. The 20-item Multidimensional Fatigue Symptom Inventory, Pittsburgh Sleep Quality Index, Hamilton Depression Scale, and Karnofsky Performance Status were used to evaluate patients’ fatigue, quality of sleep, symptoms of depression, and quality of life, respectively.Results: In post-treatment, the serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels significantly reduced, 20-item Multidimensional Fatigue Symptom Inventory, Pittsburgh Sleep Quality Index, and Hamilton Depression scores were remarkably decreased, whereas the Karnofsky Performance Status scores were significantly increased in mind-regulation acupuncture group and control group comparing to those pre-treatment, while those in mind-regulation acupuncture group changed more significantly. The 20-item Multidimensional Fatigue Symptom Inventory, Pittsburgh Sleep Quality Index, and Hamilton Depression scores were remarkably lower, and remarkably higher Karnofsky Performance Status scores in the mind-regulation acupuncture group were seen than those in the control group.Conclusion: Mind-regulation acupuncture could reduce serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels of breast cancer survivors with cancer-related fatigue. In addition, it alleviates cancer-related fatigue, sleep disturbance, and depression in these survivors and improves their quality of life. Therefore, mind-regulation acupuncture may have potential as an alternative and complementary therapy for breast cancer survivors with cancer-related fatigue.Keywords: mind-regulation acupuncture, traditional Chinese medicine, cancer-related fatigue, breast cancer, metabolites

Yihan Wang,1,2 Yizhen Wei,1,2 Yichun Wu,1,2 Yue Zong,1,2 Yingying Song,2 Shengyan Pu,2 Wenwen Wu,2 Yun Zhou,1 Jun Xie,2 Haitao Yin1 1Department of Radiotherapy Central Hospital, Affiliated Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, 221009, People’s Republic of China; 2Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, People’s Republic of ChinaCorrespondence: Haitao Yin; Jun Xie, Email yinhaitao@njmu.edu.cn; xiejun@jsnu.edu.cnPurpose: Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel.Methods: We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel.Results: The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a “sustainable reactive oxygen species (ROS) generator” can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT.Conclusion: Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a “promising future” for the old drug in clinically comprehensive applications.Keywords: NRA@DH Gel, glioma, inhibition of the PPP, ROS, radiosensitization, synergistic therapy

Kongbo Zhu,1 Shaolei Ma,2 Hui Chen,3 Jianfeng Xie,3 Dan Huang,1 Cuiping Fu,4 Genshan Ma,1 Yingzi Huang3 1Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Emergency and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 4Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Yingzi Huang, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Email yz_huang@126.comBackground: The pathogenicity of Omicron is different from that of the previous strains. The value of hematological indicators in patients at high risk of Omicron infection remains unclear. We need rapid, inexpensive and widely available biomarkers to guide the early detection of people at risk of pneumonia and to provide early intervention. We aimed to assess the value of hematological indicators as risk factors for pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.Patients and Methods: The study enrolled 144 symptomatic COVID-19 patients with Omicron infection. We collected available clinical details, including laboratory tests and CT examinations. Univariate and multivariate logistic analyses and receiver operating characteristic (ROC) curve analyses were used to assess the value of laboratory markers in predicting the development of pneumonia.Results: Among the 144 patients, 50 (34.7%) had pneumonia. The ROC analysis revealed that the areas under the ROC curve (AUC) for leukocytes, lymphocytes, neutrophils, and fibrinogen were 0.603 (95% confidence interval (CI): 0.501– 0.704, P=0.043), 0.615 (95% CI: 0.517– 0.712, P=0.024), 0.632 (95% CI: 0.534– 0.730, P=0.009) and 0.635 (95% CI: 0.539– 0.730, P=0.008), respectively. The AUC for neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), fibrinogen to lymphocyte ratio (FLR), and fibrinogen to D-dimer ratio (FDR) were 0.670 (95% CI: 0.580– 0.760, P=0.001), 0.632 (95% CI: 0.535– 0.728, P=0.009), 0.669 (95% CI: 0.575– 0.763, P=0.001) and 0.615 (95% CI: 0.510– 0.721, P=0.023), respectively. Univariate analysis showed that elevated levels of NLR (odds ratio (OR): 1.219, 95% CI: 1.046– 1.421, P=0.011), FLR (OR: 1.170, 95% CI: 1.014– 1.349, P=0.031) and FDR (OR: 1.131, 95% CI: 1.039– 1.231, P=0.005) were significantly correlated with the presence of pneumonia. Multivariate analysis indicated elevated NLR (OR: 1.248, 95% CI: 1.068– 1.459, P=0.005) and FDR (OR: 1.160, 95% CI: 1.054– 1.276, P=0.002) levels were associated with the existence of pneumonia. The AUC for the combination of NLR and FDR was 0.701 (95% CI: 0.606– 0.796, P< 0.001, sensitivity 56.0%, specificity 83.0%).Conclusion: NLR and FDR can predict the presence of pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.Keywords: COVID-19, Omicron, pneumonia, neutrophil to lymphocyte ratio, fibrinogen, D-dimer

Laihui Luo,1,&ast; Yongzhu He,1,&ast; Guoqing Zhu,1,&ast; Yongqiang Xiao,1 Shengjiang Song,1 Xian Ge,2 Tao Wang,3 Jin Xie,1 Wei Deng,1 Zhigao Hu,1 Renfeng Shan1 1Department of General Surgery, The First Affiliated Hospital of Nanchang, Nanchang, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanchang, Nanchang, People’s Republic of China; 3Department of Day Surgery Ward, The First Affiliated Hospital of Nanchang, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renfeng Shan, Department of General Surgery, The First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, People’s Republic of China, Tel +86 0791-88692522, Email srf1978@126.comPurpose: Conversion therapy gives some patients with initially unresectable hepatocellular carcinoma (HCC) access to surgery. The purpose of this study was to evaluate the safety and efficacy of hepatectomy after conversion therapy and how it differed from those who undergoing direct hepatectomy.Patients and Methods: From January 2018 to April 2022, 745 patients underwent hepatectomy for HCC were enrolled. Among them, 41 patients of unresectable HCC underwent hepatectomy after conversion therapy. A demographically and clinically comparable cohort was created from the remaining patients in a 1:1 ratio using propensity score matching.Results: The median duration of conversion therapy was 108 (42– 298) days, 8 patients achieved complete response (CR) and 33 achieved partial response (PR). Conversion therapy resulted in some degree of myelosuppression, but liver function index remained good. Compared with the direct hepatectomy group, the conversion group had more blood loss (600 mL vs 400 mL, p=0.015), longer operative time (270 min vs 240 min, p=0.02), higher blood transfusion rates, and longer hospital stay (8 days vs 11 days, p< 0.001). Patients in the conversion group had significantly more complications of any grade (82.9% vs 51.2%, p=0.002) and grade 3/4 (26.8% vs 4.9%, p=0.013), and 6 patients developed post-hepatectomy liver failure (PHLF). There were no deaths in either group. All patients achieved R0 resection, 6 (6/41, 14.6%) achieved pathological complete response (pCR), 14 achieved major pathologic responses (MPR). During a median follow-up of 12.8 months, 14 patients in the conversion group experienced recurrence or metastasis, no deaths.Conclusion: Hepatectomy after conversion therapy was more difficult than direct hepatectomy, but accurate preoperative assessment could ensure the safety of the surgery. The damage of liver function after conversion therapy was more severe than expected, PHLF should be prevented and treated. Hepatectomy was effective and necessary, postoperative pathological examination could provide guidance for adjuvant therapy.Keywords: hepatocellular carcinoma, conversion therapy, hepatectomy, post-hepatectomy liver failure, pathological complete response

Minhua Li,1,&ast; Zehui Qin,1,&ast; Qiuxia Yu,2 Ziwei Huang,3 Juanjuan Cheng,1 Linjiang Zhong,1 Yuhong Liu,1 Jianhui Xie,4– 6 Yucui Li,1 Jiannan Chen,1 Ruoting Zhan,1 Ziren Su1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 3The First Affiliated Hospital of Chinese Medicine Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 4The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 5State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruoting Zhan; Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, People’s Republic of China, Email zhanrt@gzucm.edu.cn; suziren@gzucm.edu.cnBackground: Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC.Methods: The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed.Results: Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage.Conclusion: BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.Graphical Abstract: Keywords: erythrocytes, Phellodendri Chinensis Cortex, transformation, berberine, anti-inflammation

Jianwan Xie,1,&ast; Yanchu Li,1,&ast; Man Wang,2,&ast; Wenping He,3 Xinxin Zhao1 1Department of Geriatric Medicine, Xuzhou No.1 People’s Hospital, Xuzhou, 221002, People’s Republic of China; 2Medical Oncology, Xuzhou No.1 People’s Hospital, Xuzhou, 221002, People’s Republic of China; 3Department of Pharmacy, Xuzhou No.1 People’s Hospital, Xuzhou, 221002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinxin Zhao, Department of Geriatric Medicine, Xuzhou No.1 People’s Hospital, 269 University Road, Xuzhou, 221002, People’s Republic of China, Tel/Fax +86-0516-962011, Email zhaoxx1985@163.com Wenping He, Department of Pharmacy, Xuzhou No.1 People’s Hospital, 269 University Road, Xuzhou, 221002, People’s Republic of China, Email hei33822lai@163.comPurpose: Previous studies have shown that microRNA is involved in regulating a variety of human inflammatory diseases. The purpose of this study was to investigate the expression of miR-10a-3p in the blood of patients with severe pneumonia and evaluate its value in the diagnosis and prognosis of severe pneumonia.Patients and Methods: Seventy patients with severe pneumonia and 75 healthy individuals were included in this study. Venous blood of all subjects was obtained for RT-qPCR analysis to obtain the relative expression level of miR-10a-5p. The diagnostic accuracy of miR-10a-5p for severe pneumonia was assessed by ROC curve. After standardized treatment, the prognosis of patients with severe pneumonia was analyzed by a 28-day follow-up method. Kaplan–Meier curve and multivariate Cox regression analysis were used to determine the basic factors influencing the prognosis of patients.Results: Compared with healthy control, serum miR-10a-3p expression in patients with severe pneumonia was distinctly upregulated (P < 0.001). Besides, ROC analysis showed that miR-10a-3p had high diagnostic accuracy for severe pneumonia, with an AUC of 0.881, sensitivity and specificity of 75.7% and 84.0%, respectively. Kaplan-Meier curve exhibited that high miR-10a-3p expression group had a higher probability of death than those with low miR-10a-3p expression. Multivariate Cox regression analysis demonstrated that miR-10a-3p and CRP were independent risk factors affecting the prognosis of patients.Conclusion: The expression of miR-10a-3p was increased in patients with severe pneumonia, and abnormally expressed miR-10a-3p has the potential to be used as a diagnostic and prognostic marker for severe pneumonia, which provides a new biological direction for the early detection and risk assessment of severe pneumonia.Keywords: severe pneumonia, miR-10a-3p, diagnosis, prognosis

Dexiong Li,1,&ast; Jing Xie,1,&ast; Yubei Qiu,1,2 Sihui Zhang,1,3 Jiang Chen1,&ast; 1School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Fujian College and University, Fujian Medical University, Fuzhou, People’s Republic of China; 3Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiang Chen, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China, Tel +86 591 83735488, Fax +86 591 83700838, Email jiangchen@fjmu.edu.cnBackground: Existing implant materials cannot meet the essential multifunctional requirements of repairing infected bone defects, such as antibacterial and osteogenesis abilities. A promising strategy to develop a versatile biomimicry composite of the natural bone structure may be accomplished by combining a multifunctional nanoparticle with an organic scaffold.Methods: In this study, a quaternary ammonium silane-modified mesoporous silica containing nano silver (Ag@QHMS) was successfully synthesized and further combined with silk fibroin (SF) to fabricate the multifunctional nano-reinforced scaffold (SF-Ag@QHMS) using the freeze-drying method. Furthermore, the antibacterial and osteogenic effects of this composite were evaluated in vitro and in vivo.Results: SF-Ag@QHMS inherited a three-dimensional porous structure (porosity rate: 91.90 ± 0.62%) and better mechanical characteristics (2.11 ± 0.06 kPa) than that of the SF scaffold (porosity rate: 91.62 ± 1.65%; mechanic strength: 2.02 ± 0.01 kPa). Simultaneously, the introduction of versatile nanoparticles has provided the composite with additional antibacterial ability against Porphyromonas gingivalis, which can be maintained for 15 days. Furthermore, the expression of osteogenic-associated factors was up-regulated due to the silver ions eluting from the composite scaffold. The in vivo micro-CT and histological results indicated that the new bone formation was not only localized around the border of the defect but also arose more in the center with the support of the composite.Conclusion: The multifunctional silver-loaded mesoporous silica enhanced the mechanical strength of the composite while also ensuring greater and sustained antibacterial and osteogenic properties, allowing the SF-Ag@QHMS composite to be used to repair infected bone defects.Keywords: silk fibroin, quaternary ammonium silane, multifunctional, nano-reinforce, composite scaffold

Zhan Gao,1,2 Yun Ti,1 Bin Lu,1 Fang-qiang Song,1,3 Lei Zhang,1 Bo-ang Hu,1 Jia-ying Xie,1 Wei Zhang,1 Lu Han,1,4 Ming Zhong1 1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Qilu College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, People’s Republic of China; 4Department of General Practice, Qilu Hospital, Qilu College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Lu Han; Ming Zhong, Email luhan_sdu@163.com; zhongming2sdu@163.comBackground: Previous studies have reported that six transmembrane protein of prostate 2 (STAMP2) attenuates metabolic inflammation and insulin resistance in diabetes mellitus. However, the role of STAMP2 in the diabetic heart is still unclear.Methods: A diabetic rat cardiomyopathy model was established via intraperitoneal STZ injection. STAMP2 was overexpressed in the treatment group using adeno-associated virus. Rat heart diastolic function was measured using echocardiography and a left ventricular catheter, and cardiac interstitial fibrosis was detected by immunohistochemistry and histological staining. Insulin sensitivity and NF-κB expression were shown by Western blotting. NMRAL1 distribution was illustrated by immunofluorescence.Results: STAMP2 expression in the diabetic rat heart was reduced, and exogenous overexpression of STAMP2 improved glucose tolerance and insulin sensitivity and alleviated diastolic dysfunction and myocardial fibrosis. Furthermore, we found that NF-κB signaling is activated in the diabetic heart and that exogenous overexpression of STAMP2 promotes NMRAL1 translocation from the cytoplasm to the nucleus and inhibits p65 phosphorylation.Conclusion: STAMP2 attenuates cardiac dysfunction and insulin resistance in diabetic cardiomyopathy, likely by promoting NMRAL1 retranslocation and NF-κB signaling inhibition.Keywords: STAMP2, diabetic cardiomyopathy, NADPH, NMRAL1, NF-κB

Jiangbo Xie,1,2 Tingting Zhang,3 Peichun Li,3 Dong Wang,2 Tao Liu,2 Shunliang Xu1 1Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Neurology, Weifang Traditional Chinese Hospital, Weifang, People’s Republic of China; 3Department of Rehabilitation Medicine, Weifang Traditional Chinese Hospital, Weifang, People’s Republic of ChinaCorrespondence: Shunliang Xu, Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Road, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 15153169998, Email xushandaeryuan@163.comBackground: Dihydromyricetin (DHM) exerts protective effects in various brain diseases. The aim of this research was to investigate the biological role of DHM in cerebral ischemia reperfusion (I/R) injury.Methods: We generated a rat model of cerebral I/R injury by performing middle cerebral artery occlusion/reperfusion (MCAO/R). The neurological score and brain water content of the experimental rats was then evaluated. The infarct volume and extent of apoptosis in brain tissues was then assessed by 2,3,5-triphenyltetrazolium (TTC) and TdT-mediated dUTP nick end labeling (TUNEL) staining. Hippocampal neuronal cells (HT22) were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) and cell counting kit-8 (CCK-8) assays and flow cytometry were performed to detect cell viability and apoptosis. The levels of lipid reactive oxygen species (ROS) and iron were detected and the expression levels of key proteins were assessed by Western blotting.Results: DHM obviously reduced neurological deficits, brain water content, infarct volume and cell apoptosis in the brain tissues of MCAO/R rats. DHM repressed ferroptosis and inhibited the sphingosine kinase 1 (SPHK1)/mammalian target of rapamycin (mTOR) pathway in MCAO/R rats. In addition, DHM promoted cell viability and repressed apoptosis in OGD/R-treated HT22 cells. DHM also suppressed the levels of lipid ROS and intracellular iron in OGD/R-treated HT22 cells. The expression levels of glutathione peroxidase 4 (GPX4) was enhanced while the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4) and phosphatidylethanolamine binding protein 1 (PEBP1) were reduced in OGD/R-treated HT22 cells in the presence of DHM. Moreover, the influence conferred by DHM was abrogated by the overexpression of SPHK1 or treatment with MHY1485 (an activator of mTOR).Conclusion: This research demonstrated that DHM repressed ferroptosis by inhibiting the SPHK1/mTOR signaling pathway, thereby alleviating cerebral I/R injury. Our findings suggest that DHM may be a candidate drug for cerebral I/R injury treatment.Graphical Abstract: Keywords: dihydromyricetin, ferroptosis, SPHK1, mTOR, cerebral ischemia reperfusion injury

Qianting Yang, Jiao Xie, Yan Cai, Na Wang, Yan Wang, Li Zhang, Youjia Li, Jingjie Yu, Ya Li, Haitao Wang, Kanghuai Zhang Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Kanghuai Zhang, Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, 710004, People’s Republic of China, Tel +86-29-87679282, Email zhangkanghuai12@163.comPurpose: To determine whether combinations of antifungal drugs are effective and safe for patients in intensive-care units.Methods: This study compared the efficacy and safety of caspofungin (CAS), voriconazole (VOR), amphotericin B liposome (L-AmB), CAS+VOR, and CAS+L-AmB as empirical, preemptive, and targeted therapies for invasive fungal infection (IFI).Results: Comparing the CAS, VOR, and CAS+VOR groups revealed that there were no differences in response rates between all therapy types, IFI-associated death within 90 days was less common in the CAS+VOR group (1.8%) than the VOR group (14.3%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For empirical or preemptive therapy, the CAS group had a better response rate (80.0%) than the CAS+VOR group (47.1%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For targeted therapy, no differences were found for efficacy and safety. There were no differences among the CAS, L-AmB, and CAS+L-AmB groups in efficacy and safety.Conclusion: Patients who received CAS monotherapy as an empirical or preemptive therapy could achieve good outcomes. Patients who received CAS+VOR or CAS+L-AmB achieved almost the same outcomes when compared with those who received CAS, VOR, and L-AmB monotherapy as targeted therapies, but those who received CAS+VOR had a lower IFI mortality rate than did those who received VOR monotherapy.Keywords: caspofungin, voriconazole, amphotericin B liposome, combination therapy, invasive fungal infection, intensive-care units

Qingxiang Liu,1 Ming Xue,1 Qianwen Song,1 Jianfeng Xie,1 Yi Yang,1 Songqiao Liu1,2 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; 2Department of Critical Care Medicine, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Nanjing, People’s Republic of ChinaCorrespondence: Yi Yang; Songqiao Liu, Email yiyiyang2004@163.com; liusongqiao@ymail.comBackground: PD-1 is an important immune checkpoint expressed on T lymphocytes and is associated with T-cell function in sepsis. However, the role of PD-1 in naive and memory T-cell responses in sepsis is not well understood. We aimed to determine the expression of PD-1 induced on naive and memory T lymphocytes in patients with sepsis and its association with clinical outcome.Methods: A prospective observational study was conducted at a general intensive care unit (ICU). Whole blood samples were collected from patients within 48 h after sepsis diagnosis. PD-1 expression on naive and memory T cells was measured by flow cytometry. The levels of IFN-γ, IL-2 and TNF-α released by memory T cells were also determined. All patients were followed up to 28 days, and 28-day mortality was recorded.Results: PD-1 expression showed no difference in naive CD4+ T cells (P=0.617) or naive CD8+ T cells (P=0.079) between survivors (n = 21) and nonsurvivors (n = 9). Increased PD-1 expression on memory CD4+ T cells was found in nonsurvivors (P=0.030) and memory CD8+ T cells (P=0.006) in comparison with survivors. According to the cutoff value of the percentage of PD-1 on memory CD8+ T cells in predicting 28-day mortality of patients with sepsis, patients were divided into two groups. The 28-day mortality rates between the two groups were significantly different (P=0.009). A Kaplan Meier curve was constructed to derive a hazard ratio of 9.33 (95% CI: 2.52– 34.60) for the percentage of PD-1 on memory CD8+ T cells regarding 28-day mortality. In addition, the IFN-γ secretion of memory CD4+ T cells (P=0.046) and IL-2 secretion of memory CD8+ T cells (P=0.014) were significantly greater in survivors than nonsurvivors.Conclusion: Flow cytometric assessment of PD-1 expression on memory CD8+ T cells identifies patients with poor outcomes during sepsis.Keywords: PD-1, memory T cells, sepsis, outcome

Ling Lu,1 Yan Ma,2 Jie Deng,1 Jiaqiong Xie,1 Chaolin Huang1 1Department of Gynaecology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Obstetrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of ChinaCorrespondence: Chaolin Huang; Jiaqiong Xie, Department of Gynaecology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China, Email huang.chaolin@qq.com; 475105126@qq.comObjective: This study aimed to investigate ATG7 levels in pregnant women with and without gestational diabetes mellitus (GDM) and explore the potential associations between ATG7 levels and GDM.Methods: This was a cross-sectional study conducted in a large tertiary hospital in Chengdu, China. The ATG7 levels in pregnant women at between 24 and 28 weeks of gestation with (n=84) and without GDM (n=649) were measured by using an ELISA kit. Glucose, HbA1c, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemistry analyser. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin secretion (HOMA-β) were calculated according to published formulas. The associations of ATG7 levels with laboratory parameters, GDM, and insulin resistance were evaluated using correlation analysis or a regression model.Results: The ATG7 levels were significantly lower in pregnant women with GDM than in those without GDM. The correlation analyses found that ATG7 levels correlated positively with HOMA-β but correlated negatively with HOMA-IR, oral glucose tolerance test (OGTT) glucose levels, TGs, and LDL-C. There were no significant correlations between ATG7 levels and HbA1c, HDL-C, or TC. After adjusting for potential confounders, lower ATG7 levels were shown to be associated with a higher risk of GDM. Furthermore, multiple linear regression analyses showed that ATG7 levels were negatively associated with insulin resistance.Conclusion: ATG7 levels are significantly lower in pregnant women with GDM than in those without GDM, and lower ATG7 levels are associated with a higher risk of GDM. ATG7 levels were negatively associated with insulin resistance. Autophagy deficiency, which is caused by lower ATG7 levels, may be the underlying mechanism that mediates insulin resistance in the development of GDM.Keywords: ATG7, autophagy, cross-sectional study, gestational diabetes mellitus, insulin resistance

Zhiying Shen,1,2 Zhuqing Zhong,2,3 Jianfei Xie,2,3 Qiuxiang Zhang,2,3 Shougen Li4 1Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Clinical Nursing Safety Management Research Center of Central South University, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Nursing, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Emergency Department, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Qiuxiang Zhang; Shougen Li, Email nursing_qiuxiangz@163.com; xiaosa20130103@126.comBackground: The COVID-19 pandemic caused by the novel SARS-CoV-2 virus represents an ongoing public health challenge that necessitates a heightened need to understand people’s risk perceptions as well as their information-seeking behavior.Objective: The aim of this study is to explore the impact of different information-seeking behaviors on people’s risk perceptions during the COVID-19 pandemic.Methods: We employed convenience sampling in order to administer questionnaires to 3048 residents in Hunan Province, China. After screening the questionnaires for inclusion in the study, multiple linear regressions were then used to analyze the impact of the characteristics of respondents’ information-seeking behavior on their risk perceptions.Results: From the 3048 distributed 2611 were included. New media (80.20%) was the most frequently used source of information seeking, and traditional media were participants’ most trusted source of COVID-19 information. Statistics of COVID-19 were the type of information most frequently queried by respondents, and approximately 30.0% of them reported that most or all of the COVID-19 information they sought was negative. Approximately one in five respondents reported that they sought COVID-19 information more than 10 times per day. The results of our multivariate linear regression analysis showed that “seeking information from new media ”, “level of trust in new media and local propaganda”, “information content being about protective behaviors and personal related information”, “proportion of negative information”, and “frequency of information seeking” were positively associated, and “seeking information from traditional media” and “level of trust in traditional media” were negatively associated with people’s risk perception of COVID-19.Conclusion: We find that specific types of channels of information acquisition and public trust in these information channels, their informational content, and proportion of negative information, as well as a frequency of information seeking all had an impact on risk perception during COVID-19.Keywords: information seeking behavior, risk perception, COVID-19

Shuang Yang,1,2,* Xin Yin,3,* Yanan Zhang,4 Hanwei Zhao,4 Zixuan Zheng,2 Junqing Li,2 Xiaoying Hu,1 Juan Xie,2 Zhijun Jie,2 Na Wang,3 Jindong Shi2 1Department of General Medicine, Jiangchuan Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 4Department of General Medicine, Zhuanqiao Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jindong Shi, Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China, Tel +86 18918168579, Email shijindong@5thhospital.com Na Wang, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 13564748559, Email na.wang@fudan.edu.cnPurpose: To evaluate the screening efficacy of a self-designed questionnaire for chronic obstructive pulmonary disease (COPD) and the potential gender disparity in its efficacy.Patients and Methods: A screening questionnaire, the COPD Screening Questionnaire-Minhang (COPD-MH), was designed with reference to the self-scored COPD population screener (COPD-PS) and the COPD screening questionnaire (COPD-SQ), incorporating characteristics of the local population in Shanghai, China. The revised questionnaire included only five questions. Each question scored 0– 4, with a highest total score of 20. The COPD-PS and COPD-SQ comprised 5 and 7 questions, respectively. Their scoring criteria were not consecutive integers and, thus, not easily counted. The COPD-MH focused on symptoms, and each item was set the same answers for convenience. Screening for COPD was conducted among residents over 40 years old in a community in Shanghai using the three aforementioned questionnaires. Each participant also received spirometry tests. A receiver operator characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to assess the validity of each questionnaire.Results: A total of 1197 community residents in Minhang District completed the screening. A total of 1023 participants were finally included in analysis with a detected prevalence of 12.4% for COPD. The best cut-off values for the COPD-PS, COPD-SQ, and COPD-MH were 4, 16, and 7 points, respectively. The AUCs for these three questionnaires were > 0.5, but the sensitivity of the COPD-MH was higher than those of the COPD-PS and COPD-SQ. The sensitivity of COPD-MH was 80.77% for males and 77.5% for females. The COPD-MH had higher diagnostic efficiency and higher sensitivity with gender-specific cut-off values.Conclusion: The COPD-MH is comparable to and less time-consuming than the existing screening methods for COPD. Gender-related factors affect the optimal cut-off values of the COPD screening questionnaire, and rectifying this can improve the practical screening efficacy.Keywords: chronic obstructive pulmonary disease, screening questionnaire, gender, spirometry, ROC curve

Wang N, Feng Y, Xie J, Han H, Dong Q, Wang W. Cancer Manag Res. 2020;12:13285-13300. At the author’s request, we, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 5 and 7 with images from other unrelated articles. Specifically, The image for Figure 5G, HL-60, ZNF667-AS1 si+miR-206 inh, has been duplicated with the image for Figure 5d, H460, miR-520a control, from Xie Y, Xue C, Guo S, Yang L. MicroRNA-520a Suppresses Pathogenesis and Progression of Non-Small-Cell Lung Cancer through Targeting the RRM2/Wnt Axis. Analytical Cellular Pathology. 2021;2021: Article ID 9652420. https://doi.org/10.1155/2021/9652420. The image for Figure 7H, HL-60, miR-206 inh+NC, has been duplicated with the image for Figure 4H, HSC-1, TIMP3 si, from Yin S, Lin X. MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis. Int J Gen Med. 2021;14:27-39. https://doi.org/10.2147/IJGM.S275016. In addition, Figure 5G, HL-60, ZNF667-AS1 si+miR-206 inh and Figure 7H, HL-60, miR-206 inh+NC, have been duplicated. When approached for an explanation, the authors were cooperative and provided some data for their study. However, the author’s explanation and the provided data did not sufficiently explain how the duplication of these images occurred and was unable to alleviate the journal’s concerns regarding the validity of the findings. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Dan Mu,1,&ast; Xin Wang,1,&ast; Huiting Wang,1 Xuan Sun,2 Qing Dai,2 Pin Lv,1 Renyuan Liu,1 Yu Qi,2 Jun Xie,2 Biao Xu,2,3 Bing Zhang1,4 1Department of Radiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 2Department of Cardiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, 210023, People’s Republic of China; 4Institute of Brain Science, Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Xu; Bing Zhang, Email xubiao62@nju.edu.cn; zhangbing_nanjing@nju.edu.cnBackground: Photodynamic therapy (PDT) has achieved continued success in the treatment of tumors, but its progress in the treatment of atherosclerosis has been limited, mainly due to the low tissue-penetration ability of the excitation light for photosensitizers.Methods: In this study, we designed a chemiexcited system producing singlet oxygen in an attempt to apply PDT for the treatment of atherosclerosis without the irradiation of external light. The system designed was polymeric nanoparticles (NPs) equipped with chemical fuel and photosensitizers, cross-linked with an Fe3+–catechol complex for stabilization and magnetic resonance imaging (MRI).Results: The system (FeCNPs for short) accumulated effectively in plaques, providing persistent and enhanced T1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T1-weighted MRI. Expression of CD68, MCP1, and TNFα was significantly reduced after treatment. However, low doses of FeCNPs exhibited better therapeutic efficacy than high doses. Furthermore, low-dose FeCNPs exhibited effective macrophage elimination in aortic arches and abdominal aortae, but inefficiency in the thoracic aorta, aortic hiatus, and aorta–iliac bifurcation.Conclusion: This study provides the first example of a combination of MRI and chemiexcited PDT for atherosclerosis, evidencing the effectiveness of PDT and providing significant pointers for developing nanotherapy on atherosclerosis.Keywords: photodynamic therapy, atherosclerosis, chemi-excited, macrophages, MRI

Lin Wang,1 Qingqing Liu,2 Dongsheng Sun,1 Jianhong Xie,1 Dibo Lao,1 Li Zhang1 1Heart Center, Department of Geriatrics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shulan (Hangzhou) Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Li Zhang, Heart Center, Department of Geriatrics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014, Zhejiang, People’s Republic of China, Tel/Fax +86 571-85893957, Email blueapplezl@163.comBackground: Hypertension commonly co-exists with depression and is associated with adverse health outcomes. This meta-analysis aimed to examine whether combination treatment can improve the outcomes of patients with comorbid hypertension and depression.Methods: We searched for relevant randomized controlled trials (RCTs) published through July 2021 using PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang Data. RCTs on patients with an antihypertensive outcome and data on mean blood pressure differences were extracted for both intervention and control groups. Continuous and dichotomous measures of outcomes were pooled using weighted mean differences (WMD) and risk ratios (RR) with 95% confidence intervals (CI) by random or fixed effects. Subgroup and meta-regression analyses were performed to identify any existing heterogeneous sources.Results: A total of 27 RCTs with 2606 participants were included. Combination treatment significantly improved systolic blood pressure (SBP) by 11.27 mmHg (WMD = − 11.27, 95% CI: − 14.12 to − 8.43), I2 = 95.4%), diastolic blood pressure (DBP) by 8.21 mmHg (WMD = − 8.21, 95% CI: − 10.73 to − 5.69), I2 = 96.9%), and antihypertensive efficiency by 42% (RR = 1.42, 95% CI: 1.32 to 1.52, I2 = 0.0%) compared with in the control group. Combination treatment improved SBP and DBP levels in patients aged < 65 years compared with those in patients aged ≥ 65 years (p = 0.020 and 0.007, respectively).Conclusion: Pooled evidence suggests that combination treatment significantly improves both blood pressure levels and antihypertensive efficiency in hypertensive patients with depression. Elderly patients with comorbid hypertension and depression may require a more collaborative approach to improve their outcome.Registration: PROSPERO registration number CRD42020213430. Registered on November 08, 2020.Keywords: hypertension, depression, combination treatment, meta-analysis, RCTs

Jianhao Xie,1,2,&ast; XueYu Yuan,1,&ast; Weiqing Mao,1,&ast; Haidong Cai,1 Kejia Gao,3 Zhongwei Lv,1 Hui Wang,4 Chao Ma1 1Department of Nuclear Medicine, Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of China; 2Department of Orthopaedic, Beijing Jishuitan Hospital, Beijing, People’s Republic of China; 3Department of Nuclear Medicine, Shanghai No. 4 People’s Hospital, Shanghai, People’s Republic of China; 4Department of Nuclear Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongwei Lv; Chao Ma, Tel/Fax +86-21-66302075, Email shtjnmd@163.com; mc_7419@hotmail.comObjective: To investigate the effects of 99Tc-methylene diphosphonate (99Tc-MDP) on osteoporosis (OS) in postmenopausal patients with differentiated thyroid cancer (DTC) under thyroid stimulating hormone (TSH) suppression.Patients and Methods: Patients (n = 142) were divided into two groups: (1) 99Tc-MDP (n = 70) and (2) alendronate (n = 72) treatments (NCT 02304757). Bone mineral density (BMD) in the lumbar spine and hip was evaluated by DXA, along with bone turnover markers, safety, and quality of life (QOL) using SF-36 at three time points: before treatment and at 6 and/or 12 months after treatment.Results: The percentage change of BMD in total lumbar spine or hip showed no significant difference throughout the study (P > 0.025). 99Tc-MDP and alendronate treatment alone significantly increased BMD in the lumbar spine, but alendronate treatment also significantly increased BMD in total hip at 6 and 12 months, as compared with the baseline. There were no significant differences in the results of the SF-36 scores between the two treatment groups at any time during the whole study period. 99Tc-MDP significantly increased bone formation markers of osteocalcin at 6 and 12 months (P all < 0.05), PINP at 12 months (P = 0.001), and bone resorption markers of β-CTX at 6 and 12 months (p < 0.05) as compared with the alendronate treated group. No adverse event was observed in the 99Tc-MDP treatment group compared with alendronate (P = 0.014).Conclusion: 99Tc-MDP was as efficacious as alendronate in the improvement of lumbar BMD for DTC patients with OS under TSH stimulation. 99Tc-MDP was shown to be safe and improved patients’ QOL.Keywords: osteoporosis, 99Tc-MDP, thyroid stimulating hormone suppression, differentiated thyroid cancer