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Chao Wang,1,* Mei Zhao,2,* Yuanyuan Yue,3 Chao Hu,2 Chunqiu Zhou,2 Zhongyi Zhang,2 Yunliang He,4 Yaqi Luo,4 Tao Shen,2 Sijie Dang,4 Yang Yang,4 Yong Zhang2,4 1Traditional Chinese Medicine Department, Qitai Hospital of the Sixth Division, Xinjiang, 831899, People’s Republic of China; 2College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 3Department of Ultrasound, Chengdu First People’s Hospital, Chengdu, 610095, People’s Republic of China; 4Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Zhang; Yang Yang, Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, People’s Republic of China, Email 18692213920@163.com; 18721326@qq.comBackground: Modified Suanmei-Tang (MST) comprises four plants common to both traditional Chinese medicine and culinary applications, and it can potentially alleviate metabolic-associated fatty liver disease (MAFLD) triggered by a high-fat diet (HFD).Purpose: This research aims to investigate the impact and underlying mechanisms of MST in ameliorating MAFLD caused by an HFD.Methods: UHPLC-Q-Orbitrap-MS/MS was used to determine the constituents of MST and to evaluate its effects on MAFLD mouse models. Transcriptomics, network pharmacology, and bioinformatics analysis (including Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis) were utilized to further clarify the mechanisms by which MST acts on MAFLD. The experimental methods included ELISA, real time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, molecular docking, and metabolomics. Transcriptomics was integrated with metabolomics to find correlations between differentially expressed genes and metabolites, and crucial genes were validated through RT-qPCR.Results: A total of 23 components of MST were identified. The formulation was found to alleviate metabolic disorders, obesity, insulin resistance, inflammation, and oxidative stress in mice with MAFLD. The findings indicate that MST promoted autophagy by suppressing phosphorylation in the PI3K/AKT/mTOR pathway and enhancing lipid management in the livers of MAFLD mice.Conclusion: MST could effectively improve lipid metabolism disorders and liver lipid deposition in MAFLD mice, and its mechanism might be related to regulating the PI3K/AKT/mTOR pathway to improve autophagy. Keywords: modified Suanmei-Tang, MAFLD, transcriptomics, network pharmacology, metabolomics

Min Zhao,1 Changyi Yang,1 Linhong Zhu,1 Xiaoqian Guo,1 Haiyan Ma,2 Yuanhao Luo,3 Qi Wang,4 Juanjuan Chen4 1Department of Periodontology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2School of Stomatology, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3The Second Clinical Medical School, Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China; 4Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of ChinaCorrespondence: Juanjuan Chen; Qi Wang, Email ery_juanjuanchen@lzu.edu.cn; ery_wangqery@lzu.edu.cnIntroduction: Our study investigated the disparities and correlations between oral microbiota and metabolites in pregnant patients with and without periodontitis.Methods: Subgingival plaque samples from all subjects were collected for shotgun metagenomic sequencing and broad-target metabolomics analysis.Results: Forty pathogens, including Porphyromonas gingivalis, Fusobacterium nucleatum, Eubacterium saphenum, Gemella morbillorum, Tannerella forsythia, Streptococcus anginosus group, Selenomonas sputigena etc, were significantly enriched in pregnant patients with periodontitis (PPP). Conversely, symbiotic species such as Morococcus cerebrosus, Streptococcus vestibularis, S. salivarius, S. mitis, and S. pneumoniae were significantly more abundant in healthy controls (HCs). A total of 87 predicted functional modules (PFMs) exhibited significant differences between the two groups; eight PFMs showed high enrichment in PPP with involvement of PPP-enriched species within these pathways. The remaining 79 PFMs encompassing ribonucleotide biosynthesis, carbohydrate, and amino acid metabolism were highly abundant in HCs. For oral microbial metabolome, a total of 105 metabolites related to 150 KEGG pathways displayed significant differences between the two groups. Pathways such as pyruvate metabolism, folate biosynthesis, vascular smooth muscle contraction, and AMPK/mTOR signaling pathway along with their associated metabolites were found to be enriched in PPP, while carbohydrate metabolism predominated among HCs. Spearman’s rank correlation analysis revealed significant positive associations between species enriched in PPP and metabolites enriched in PPP, but significant negative associations between species enriched in PPP and metabolites enriched in HCs.Discussion: Our findings provide potential biomarkers for distinguishing periodontitis during pregnancy while offering valuable insights into mechanisms exploration and clinical intervention.Keywords: Pregnancy-induced periodontitis, oral microbiota composition, predicted functional modules, microbial metabolites profiling, biomarkers identification

Min Zhao,1 Liuxiang Feng,2 Wenhua Li3 1School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China; 2People’s Hospital of Yulong Naxi Autonomous County of Lijiang City, Lijiang, Yunnan, 674112, People’s Republic of China; 3School of Medicine, Xizang Minzu University, Xianyang Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Min Zhao, School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China, Email 1398606492@qq.comObjective: To employee network pharmacology to predict the components and pathways of SanQi-DanShen (SQDS) in treating coronary heart disease, followed by in vitro experiments to validate the molecular mechanism of SQDS in treating coronary heart disease.Methods: We sourced the active ingredients and targets of Panax notoginseng and Danshen from the Traditional Chinese Medicine Systems Pharmacology database. Coronary heart disease related genes were retrieved from the OMIM, Genecards, and Therapeutic Target databases. Using Cytoscape 3.7.2 software, we constructed a network diagram illustrating the components and targets of SQDS. The associated targets were then imported into the STRING database to build a protein-protein interaction network. The Metascape database and WeChat software were utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Lastly, we performed molecular docking between the key components and related targets using AutoDock Vina. To validate the potential mechanism of SQDS in treating coronary heart disease, we established an acute coronary heart disease rat model via tail vein injection of pituitrin.Results: Network pharmacology analysis revealed that 65 active ingredients and 167 targets of SQDS are implicated in the treatment of coronary heart disease. The key targets identified include AKT1, TNF, TP53, IL6, and VEGFA. Notably, the PI3K/AKT signaling pathway emerged as the primary pathway. Furthermore, animal experiments showed that, compared to the model group, SQDS significantly reduced levels of TNF-α, IL-6, Bax, and cardiac troponin I, while increasing Bcl-2 content. It also notably suppressed the expression of p-PI3K and p-AKT, thereby offering protection to myocardial tissue.Conclusion: Through the integrated approach of network pharmacology and molecular docking, we have established that SQDS exerts a multi-component, multi-target, and multi-pathway synergistic therapeutic effect on coronary heart disease. Its mechanism may involve the inhibition of the PI3K/AKT signaling pathway and the reduction of inflammatory factor expression.Keywords: SQDS, cardiac troponin I, PI3K/AKT signaling pathway, coronary heart disease, experiment validation

Ying Pan,1 Mengjie Zhao,1 Tiantian Song,2 Jia Tang,2 Ming Kuang,2 Hongying Liu,2,* Shao Zhong3,* 1Department of General Practice, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, People’s Republic of China; 2Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email drzhong@163.com Hongying Liu, Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, 310000, People’s Republic of China, Tel +86 02164045531, Email hongyingliu@91jkys.comAbstract: Insulin resistance (IR) is the major mechanism in the pathogenesis of type 2 diabetes mellitus (T2DM). Early identification of IR is of great significance for preventing the onset of T2DM and delaying the progression of the disease. Previous studies have shown that triglyceride-glucose (TyG) index can be used as an effective surrogate marker for IR. There is a significant correlation between TyG index and T2DM and its common complications. In addition, the predictive efficacy of TyG index is better than that of other IR surrogate indicators. TyG index may not only become an important marker to identify people at high risk of T2DM and its complications, but is also expected to become a strong predictor of the prognosis of these diseases. However, there are still some challenges in the widespread application of TyG index in clinical practice. In the future, more high-quality studies are needed to clarify the assessment methods of TyG index for the prognosis of T2DM and its complications. Further investigations of the relationship between TyG index and T2DM and its complications will be expected to provide new ideas and methods for the prevention and treatment of T2DM and its complications.Keywords: triglyceride-glucose index, type 2 diabetes mellitus, complication, insulin resistance

Lijuan Liang,1,* Ming Jia,2,3,* Min Zhao,4,* Yiping Deng,5,* Jun Tang,5 Xinghui He,2 Yilin Liu,2 Kexin Yan,2 Xin Yu,6 Hong Yang,7 Chunhong Li,2 Yao Li,2,8 Tao Li4 1Department of Pharmacy, Hejiang County People’s Hospital, Luzhou, Sichuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Nanchong Institute for Food and Drug Control, Nanchong, Sichuan, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Analysis and Testing Center, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Chinese Pharmacy Laboratory, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Science and Technology department, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yao Li; Tao Li, Email lnetyao@163.com; leta49@swmu.edu.cnAbstract: As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.Keywords: manganese dioxide nanoparticles, tumors, inflammation, biomedicine, research progress

Yidan Xu,1,&ast; Lu Zhang,1,&ast; Zhiyang Chen,1 Xiaonan Sun,1 Mengdan Zhao,1 Qirui Wu,2 Jiqing Hao1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiqing Hao, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 81 Meishan Road, Hefei, Anhui, People’s Republic of China, Tel +86-13965029739, Email haojiqing@ahmu.edu.cnPurpose: This study aims to explore the association of inflammatory markers such as the Systemic Immune-Inflammatory Index (SII) and LANR with the comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and lung cancer.Patients and Methods: A cross-sectional analysis was conducted on the clinical data of 309 patients with COPD only and 193 patients with COPD and lung cancer who attended the First Affiliated Hospital of Anhui Medical University. Additionally, we examined autonomous risk factors that contribute to the simultaneous development of COPD and lung cancer through univariate and multivariate logistic regression analyses. This analysis resulted in the development of a nomogram model for visual representation. The effectiveness of the model was assessed using a receiver operating characteristic (ROC) curve, calibration curve, and clinical decision analysis (DCA) curve, with internal validation conducted via repeated sampling methods.Results: Multivariate analysis of clinical characteristics and inflammatory markers showed that smoking history of > 60 pack-years, hemoptysis, emphysema, WBC count > 5.53 (× 10^9/L), SII > 629.285, and LANR < 11.39 were significantly associated with the comorbidity of COPD and lung cancer. These factors were subsequently integrated into the nomogram model. The AUC of the model stood at 0.849 (95% CI: 0.815– 0.882), demonstrating a notable improvement over the COPD-LUCSS scoring system (AUC: 0.716, 95% CI: 0.671– 0.761). The DCA curve indicated a notable clinical advantage provided by the model. Additionally, patients with stage IV tumors exhibited elevated SII levels and reduced LANR levels compared to earlier stages, indicating potential prognostic significance for both markers.Conclusion: Increased levels of the inflammatory markers SII and LANR are associated with the risk of comorbidity of COPD and lung cancer.Keywords: lung cancer, inflammation, systemic immune-inflammation index, nomogram, LANR, chronic obstructive pulmonary disease

Qi-Feng Chen,1,&ast; Xiong-Ying Jiang,1,2,&ast; Yue Hu,1,&ast; Song Chen,1 Jun-Zhe Yi,1 Sui-Xing Zhong,1 Jiong-Liang Wang,1 Ning Lyu,1 Ming Zhao1 1Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510210, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Zhao, Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +862087343272, Email zhaoming@mail.sysu.edu.cnPurpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers.Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at &dollar;30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results.Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of &dollar;10,507.89, while SoHAIC generated 1.66 QALY at a cost of &dollar;32,971.56. When comparing SoHAIC to sorafenib, the ICER was &dollar;18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters.Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.Keywords: HCC, portal vein tumor thrombosis, sorafenib, HAIC, Cost-effectiveness

Jiaying Cai,1,&ast; Xiyue Tan,2,&ast; Qichao Hu,2,&ast; Huafeng Pan,3 Maoyuan Zhao,4 Cui Guo,4 Jinhao Zeng,1,4,5 Xiao Ma,2 Yanling Zhao6 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 5Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 6Department of Pharmacy, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinhao Zeng; Yanling Zhao, Email zengjinhao@cdutcm.edu.cn; zhaoyl2855@126.comAbstract: Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using “gastric cancer”, “stomach cancers”, “flavonoid”, “bioflavonoid”, “ 2-Phenyl-Chromene” as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents.Keywords: flavonoid, gastric cancer, apoptosis, angiogenesis

Xian-Lin Wu,1,2,&ast; Hong-Yan Liu,1,&ast; Qiu-Hong Xiang,1 Zhuan Yin,3 Rong Zhou,1 Ye-Juan Wang,1 Bi-Yu Zhou,1 Fang Wang,1 Min Zhao,1 Mei Chen1 1Department of Obstetrics, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China; 2Department of Nursing, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China; 3Department of Neonatology, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu-Hong Xiang, Department of obstetrics, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, No. 416 of Chengnan Dong Lu, Yuhua District, Changsha, 410007, People’s Republic of China, Tel +18684888525, Email xqhong1313@163.comObjective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction.Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups.Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257– 2.112), fetal distress (OR = 1.371, 95% CI: 1.331– 2.633), and the placement of cervical ripening balloon catheter for > 12h (OR = 1.563, 95% CI: 1.231– 3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455– 0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for > 12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714– 0.811).Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.Keywords: cervical ripening balloon, cervical ripening double balloon, labor induction, oxytocin

Jing Luo,1,2 Yi Luo,2 Maoru Zhao,3 Yulong Liu,2 Jiayin Liu,2 Zhulin Du,2 Hong Gong,2 Lian Wang,2 Jinghui Zhao,2 Xiaqing Wang,2 Zhanjun Gu,3 Wenhui Zhao,1 Tianyao Liu,2 Xiaotang Fan2 1School of Life Sciences, Chongqing University, Chongqing, 401331, People’s Republic of China; 2Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, People’s Republic of ChinaCorrespondence: Xiaotang Fan; Tianyao Liu, Email fanxiaotang2005@163.com; squall277@163.comBackground: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment. Keywords: fullerenols, BTBR, neurogenesis, autism spectrum disorder, hippocampus

Shiyu Zhang,1,2 Caili Chen,1,2 Yi Zhou,1,2 Meirong Pan,1,2 Haimei Li,1,2 Mengjie Zhao,1,2 Min Dong,1,2 Feifei Si,1,2 Lu Liu,1,2 Yufeng Wang,1,2 Qiujin Qian1,2 1Peking University Sixth Hospital/ Institute of Mental Health, Beijing, 100191, People’s Republic of China; 2NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, People’s Republic of ChinaCorrespondence: Qiujin Qian, Peking University Sixth Hospital/ Institute of Mental Health, No. 51 Hua Yuan Bei Road, Haidian District, Beijing, 100191, People’s Republic of China, Email qianqiujin@bjmu.edu.cnPurpose: With the further development of attention-deficit/hyperactivity disorder (ADHD) research, more and more assessment tools related to ADHD have been used. However, there is still no measurement instrument to evaluate the compensatory behavior of ADHD in China. This study aimed to examine the reliability and validity of the Compensatory ADHD Behaviors Scale (CABS) adapted in Chinese and explore ecological characteristics in adults with ADHD using the CABS.Patients and Methods: Data were collected from a sample of 306 adults (Mage = 26.43 years, SD = 5.32; 46.08% male). The original version CABS was translated into Chinese using the forward and backward translation procedures. Participants completed the CABS and questionnaires assessing ADHD symptoms and executive function. We utilized content validity, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and criterion validity to test the validity. Internal consistency and test-retest reliability were employed to test the reliability. Analysis of variance (ANOVA) was employed to compare ADHD subgroups based on gender, ADHD subtype, comorbidities, and medication status, while controlling for demographic variables as covariates.Results: CABS exhibited good construct validity (two factors: present-oriented and future-oriented), content validity (content validity index: 0.98), internal consistency reliability (Cronbach’s alpha coefficient: 0.85 to 0.87) and test-retest reliability (intraclass correlation coefficient: 0.59 to 0.88). The results of CFA showed acceptable fitness for each subscale. CABS demonstrated significant associations with inattention symptoms and plan/organizational abilities. Medicated ADHD individuals scored higher on future-oriented effectiveness subscale of CABS than non-medicated (F = 6.106, p = 0.014).Conclusion: The results indicate that the Chinese CABS exhibited good validity and reliability. It can be considered a valid tool for assessing compensatory behaviors in Chinese adults with ADHD. Further research is needed to explore the connection between medication and compensatory behavior.Keywords: attention-deficit/hyperactivity disorder, adult, compensatory behaviors, reliability, validity, ecological characteristics

Xiaoyi Tang,1,2,&ast; Yijia Liu,1,2,&ast; Mengxin Zhao,3,&ast; Lei He,3 Jiahao Guo,3 Tian Wang,3 Wei Li,3 Jiaqi Zhao1 1Department of Ultrasound, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Ultrasound, the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, People’s Republic of China; 3Department of Nanomedicine, Naval Medical University, Shanghai & School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Jiaqi Zhao, Email liwei@smmu.edu.cn; ultrasoundczzjq@163.comPurpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention.Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery.Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18± 1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA’s potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure’s efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation.Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.Keywords: ultrasonography, nanoscale contrast agent, nanotechnology, musculoskeletal ultrasound, photothermal imaging, microcirculatory perfusion

Yuli Ji,1,2,&ast; Liangyu Mi,1,2,&ast; Miaomiao Zhao,1,2 Xiaoyao He,1,2 Yuting Hu,1,2 Yanan Gao,1,2 Chengliang Yin,3 Ke Xu1,2 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Xu, Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, Shanxi Province, People’s Republic of China, Email xukesxbqeh@hotmail.comAbstract: Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.Keywords: engineered exosomes, autoimmune diseases, genetic engineering, anti-inflammatory applications

Wei Yang,1,&ast; Yahui Peng,1,&ast; Changsong Wang,1,&ast; Hongliu Cai,2 Lina Zhang,3 Jun Xu,2 Yongjie Wang,4 Maonan Wang,4 Mingyan Zhao,1 Kaijiang Yu1 1Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Department of Critical Care Medicine, the First Affiliated Hospital, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Critical Care Medicine, Xiangya Hospital Central South University, Changsha, Hunan Province, People’s Republic of China; 4Department of Critical Care Medicine, Jilin Province People’s Hospital, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaijiang Yu; Mingyan Zhao, Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China, Email drkaijiang@163.com; mingyan1970@126.comIntroduction: The purpose of this study was to compare the viral shedding time in patients infected with the Omicron variant during Paxlovid therapy and conventional therapy and to analyze the effects of Paxlovid on patients infected with COVID-19.Methods: In this study, the demographic and clinical characteristics and laboratory data of 3159 patients infected with the SARS-CoV-2 Omicron variant treated at Jilin Province People’s Hospital were collected and analyzed. A total of 362 patients received Paxlovid therapy, and 2797 patients received conventional therapy. After propensity score matching (PSM), 1086 patients were obtained.Results: The difference in platelet (PLT) count between the two groups was statistically significant but within the normal range (P < 0.05). CT value revealed that the nucleic acid test results became negative more quickly in the Paxlovid therapy group. Analysis of the Paxlovid therapy group showed that IgG and IgM levels were increased after Paxlovid therapy administration.Conclusion: The CT value of the Paxlovid therapy group became negative more quickly. This finding suggests that Paxlovid treatment after early diagnosis of the Omicron variant may achieve good therapeutic efficacy.Keywords: Paxlovid, Omicron variant, a retrospective study, N-CT

Jiahui Ma,1– 4,&ast; Xue Yang,5,&ast; Zhiming Liu,1– 4 Hao Fu,1– 4 Sizhou Fan,1– 4 Kai Wang,1– 4 Yan Li,1– 4 Lvzhen Huang,1– 4 Mingwei Zhao1– 4 1Department of Ophthalmology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Eye Diseases and Optometry Institute, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, People’s Republic of China; 4College of Optometry, Peking University Health Science Center, Beijing, People’s Republic of China; 5Department of Ophthalmology, Peking University International Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Yan Li, Email wang_kai@bjmu.edu.cn; 13801153660@163.comPurpose: To investigate the impact of vergence dysfunction on myopia progression in children with Defocus incorporated multiple segments (DIMS) spectacle lenses.Patients and Methods: We retrospectively enrolled children prescribed DIMS spectacle lenses to slow myopic progression. Baseline vergence dysfunction was determined according to phoria at distance and near. Axial length (AL) measurement and cycloplegic subjective refraction were performed before fitting the lenses and at six-month and one-year follow-ups. The six-month and one-year AL and spherical equivalent (SE) change from baseline were calculated and compared in subgroups stratified with the type of vergence dysfunction.Results: Two hundred and ninety-two myopic children were included. Significant AL elongation and SE progression were observed at six months and one year (P < 0.05 for all comparisons). Multiple regression demonstrated that AL elongation at six months (P < 0.001) and one year (P < 0.001) was negatively correlated with age, and SE progression at six months was associated with age (P = 0.002). The AL elongation at six months in children with convergence excess was significantly greater than in normal myopic subjects (P = 0.011) and subjects with convergence insufficiency (P = 0.008), divergence excess (P = 0.007), divergence insufficiency (P = 0.024) and basic esophoria (P = 0.048) at six months.Conclusion: The present research demonstrated that vergence dysfunction influences myopia progression for myopic children with DIMS, and the children with convergence excess suffer from the greatest myopia progression among different types of vergence dysfunction.Keywords: myopia, vergence dysfunction, defocus spectacles, axial length

Min Zhao,1,&ast; Ming-Zhu Gao,1,&ast; Rong-yan Gu,1,&ast; Lei Luo,1 Song-rui Ding,1 Liang He,2 Yue Jia,3 Hong-ping Zhang,3 Hong-ying Yang,3 Gao-feng Li1 1Medical Administration Department, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, People’s Republic of China; 2Medical Laboratory Department, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, People’s Republic of China; 3Gynecological Department, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-ying Yang; Gao-feng Li, Email yanghy913@126.com; ligaofenghl@126.comBackground: Research on the risk factors for cervical cancer in Yunnan Province’s four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking.Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention.Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis.Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P< 0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P< 0.01) was a causative factor of cervical cancer.Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.Keywords: cervical cancer, risk factors, case-control study, Han, Bai, Dai and Hani ethnic minorities, Yunnan Province

Lingbo Bi,&ast; Chaofan Wang,&ast; Yimei Du,&ast; Changpei Lu, Min Zhao, Yunbu Ding, Weiling Sun, Weixin Fan Department of Dermatology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weixin Fan; Weiling Sun, Department of Dermatology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, 210029, People’s Republic of China, Tel +86-13327805737 ; +86-13813955963, Email swl0560@sina.com; hairmanfwx@163.comPurpose: To investigate whether increased levels of lipids-related metabolites (LRMs) result in androgenic alopecia (AGA).Patients and Methods: A two-sample Mendelian randomization (MR) study was designed, and single nucleotide polymorphisms (SNPs) respectively related to nine LRMs were selected from the genome-wide association study (GWAS) dataset. An MR analysis was performed to assess the causal association between LRMs and AGA.Results: Through the fixed-effect inverse variance weighting (IVW) method, MR analysis indicated that Apolipoprotein B (ApoB), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) had a causal relationship with AGA. No obvious heterogeneity or pleiotropy was observed.Conclusion: The risk of AGA increases significantly when the serum levels of ApoB, LDL, and VLDL increase. This causal relationship is solid and free of interference from confounding factors.Keywords: androgenic alopecia, apolipoprotein B, VLDL, LDL

Huifeng Wu,1 Xiaodong Wu,2 Mengdan Zhao,3 Jingjing Yan,3 Chaoqun Li,3 Zhewei Zhang,1 Sangsang Tang,2 Rong Wang,3 Weidong Fei3 1Department of Urology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 3Department of Pharmacy, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of ChinaCorrespondence: Weidong Fei; Rong Wang, Email feiweidong@zju.edu.cn; 5521085@zju.edu.cnAbstract: During the past decade, “membrane lipid therapy”, which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of “membrane lipid therapy” for tumors. Keywords: cholesterol, tumor, plasma membrane, nanotherapeutics

Min Zhao,1 Fei-xiang Liu,1,&ast; Xiao-lin Wang,2,&ast; Ya-hui Gao,2 Xiang Li3,4 1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 2The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei-xiang Liu, No. 19 Renmin Road, Zhengzhou, 450008, People’s Republic of China, Email spiritofwestlfx@126.comPurpose: The Coronavirus disease 2019 (COVID-19) remains a global public health concern. Many people have been forced to change their lifestyles, which has led to psychological and sleep problem. This study aims to investigate the psychological health problems and factors among patients in the Fangcang Shelter Hospital (FSH) during the COVID-19 pandemic.Patients and Methods: A Cross-Sectional survey was conducted to investigate the sleep, anxiety, depression and stress disorders of 2628 asymptomatic and mild patients treated in FSH of Zhengzhou, Henan Province, from 30 October to 6 December 2022, by scanning a WeChat two-dimensional code. Sociodemographic data and influencing factors in FSH were collected, Insomnia Severity Index (ISI), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Impact of Event Scale-Revised (IES-R) were administered. Descriptive statistics, t-tests or analysis of variance, Spearman or Pearson correlation analysis, and multivariate regression analysis were used to explore the relationships between different variables and their impact on psychological health indicators.Results: The proportions of patients with insomnia, depressive disorder, anxiety, and stress disorders were 33.49%, 35.80%, 31.74%, and 43.57%, respectively. Spearman correlation analysis demonstrated that factors such as gender, higher education level, positive nucleic acid test results, longer illness duration, underlying diseases, and extended electronic device use were associated with elevated psychological distress scores. Notably, within FSH, extended exposure to light, a noisy environment, and sleep schedule management significantly impacted the prevalence of insomnia, depression, anxiety, and stress disorders (p< 0.01). Multivariable binary logistic regression analysis identified higher education level, light exposure, noisy environment, sleep management, and electronic device usage as the primary risk factors for psychological distress.Conclusion: Patients in FSH face psychological distress influenced by sociodemographic factors, environment, and lifestyle, highlighting the need for integrated psychological support in healthcare, particularly in temporary medical facilities during crises.Keywords: anxiety, COVID-19, depressive disorder, insomnia, stress disorders

Qiuyan Guo,1,2,&ast; Tianming Lu,1,3,&ast; Min Zhang,4,&ast; Qixin Wang,1,2 Minghong Zhao,2,5 Tongchun Wang,6 Maobo Du1 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 2Artemisinin Research Center and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 3Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 5Laboratory Medicine, Guizhou Aerospace Hospital, Zunyi, Guizhou, 563000, People’s Republic of China; 6Traditional Chinese Medicine Orthopedics and Traumatology Department, Shandong Wendeng Orthopedic Hospital, Wendeng, Shandong, 264400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maobo Du, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Email mbdu@icmm.ac.cnBackground and Objective: Peptic ulcer is a high incidence gastrointestinal disease in China. Berberine (BBR) is a natural product isolated from the Chinese herb Coptis chinensis Franch that has protective effects in digestive diseases. We aimed to evaluate the ability of BBR to attenuate acute gastric ulcer induced by one-time administration of ethanol in the rat.Methods: Tissue pathological morphology, macroscopic score, ulcer healing rate, and serum levels of the inflammatory cytokines nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), and anti-inflammatory interleukin-10 (IL-10) were used to determine the efficacy of BBR and evaluated to identify the optimal dosage. Subsequently, transcriptome and metabolome sequencing were conducted in Control, Model, and optimal dosage groups to explore the pathogenesis of the disease and the mechanism of action of the drug. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), as well as those of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined by enzyme-linked immunosorbent assay to verify the results of transcriptomics and metabolomics analyses.Results: BBR significantly improved the pathological morphology of gastric ulcers, increased the macroscopic score and healing rate, decreased serum levels of NO, IL-6, and PGE2, and increased serum levels of IL-10, thus effectively alleviating gastric ulcer severity. Transcriptome results showed that the therapeutic effect of BBR was mainly mediated by the arachidonic acid metabolism pathway at the gene level, which is closely associated with inflammation and increased levels of reactive oxygen species (ROS). The differentially accumulated metabolite prostaglandin E1, which is a negative regulator of ROS, was significantly up-regulated after BBR administration. The validation results indicated that BBR pretreatment increased SOD and GSH-Px enzyme activities, while reducing levels of the oxidative products MDA and MPO.Conclusion: This study demonstrated that BBR exerts a protective effect on acute gastric ulcer by promoting tricarboxylic acid cycle-mediated arachidonic acid metabolism. Keywords: Berberine, acute gastric ulcer, transcriptome, untargeted metabolomics

Wenjie Qu,1,2,&ast; Xinyu Wang,1,&ast; Yufei Liu,3 Jinfeng Mao,2 Mengchi Liu,4 Yaqin Zhong,1,2 Bella Gao,5 Miaomiao Zhao,1 Yuexia Gao1,2 1Department of Health Management, School of Public Health, Nantong University, Nantong, People’s Republic of China; 2Institute for Health Development, Nantong University, Nantong, People’s Republic of China; 3Faculty of Health Sciences, University of Macau, Macau, People’s Republic of China; 4National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 5Ulink College of Suzhou Industrial Park, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miaomiao Zhao; Yuexia Gao, Department of Health Management, School of Public Health, Nantong University, 9 Seyuan Road, Jiangsu, 226019, People’s Republic of China, Tel +86150 0450 1812 ; +86139 6296 8819, Email zhaomiaomiao@ntu.edu.cn; yxgao@ntu.edu.cnBackground: Self-medication with antibiotics (SMA) among children is a common practice in low-income and middle-income countries, which has accelerated antibacterial abuse.Objective: This study aimed to estimate the prevalence and associated factors of SMA among children in China, including parents’ knowledge, attitudes, and practices towards antibiotic use.Methods: A cross-sectional study based on a structured questionnaire survey of parents was conducted in Nantong between July and September 2020. A total of 1699 respondents participated. Information on participants’ demographic and family characteristics, knowledge, attitudes, and practices towards antibiotics use was collected. Hierarchical binary logistic regression was used to examine the predictors of SMA among children.Results: Among 1699 participants, 23.31% practiced SMA to their children in the past year. Cough (59.6%) was the most common symptom leading to self-medication and penicillins (85.4%) were the most commonly used drugs. Hierarchical regression indicated that parents with higher level of antibiotic knowledge scores (OR=1.163, 95% CI: 1.067– 1.268) and buying antibiotics without a prescription from pharmacy (OR=1.475, 95% CI: 1.097– 1.983) were more likely to practice SMA to their children both in urban and in rural areas. Storing antibiotics at home resulted in an increased likelihood of self-medication in urban areas but not in rural areas. In addition, there was also a higher probability of non-prescribed antibiotics in children without chronic diseases (OR=1.959, 95% CI:1.072– 3.578).Conclusion: The prevalence of SMA in children is high in China. Higher knowledge scores and practices of buying and storing non-prescribed antibiotics behaviors increased parents’ antibiotic self-medication in their children. Practical and effective education intervention for children’s rational use of antibiotics is urgently strengthened.Keywords: antibiotic, self-medication, children, China, antibiotic knowledge, attitude

Ming Zhou,1,2,&ast; Peng Liu,1,2,&ast; Xiaoqin Yin,1 Caiting Deng,3,4 Yi Xiao,1 Meng Lei,1 Shuo Hu,1 Feifei An,3 Min Zhao1,5,6 1Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Biological, Nanotechnology of National Health Commission, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Science, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 5Department of Nuclear Medicine, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhao; Feifei An, Email mzhao1981@csu.edu.cn; anfeifei@xjtu.edu.cnBackground: Sentinel lymph node (SLN) mapping-guided biopsy is crucial for cancer staging and treatment. Optical/nuclide dual-modality imaging agents for mapping SLN are ideal for preoperative planning and intraoperative biopsy, which are enabled by penetration-depth unlimited nuclide imaging and dynamic real-time optical imaging, respectively. However, commonly reported dual-modality imaging agents are composed of novel but safety-unproven materials, making their quick clinical translation challenging. Herein, we report a novel nanoparticle composed of facile hospital-available drugs and isotope for single-photon emission computed tomography (SPECT)/near-infrared (NIR) fluorescence imaging to detect SLNs.Methods: Indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were synthesized by ICG-induced HSA self-assembly and further 99mTc-labeling via a one-step, facile hospital-available method. After injecting 99mTc-ICG-HSA into the rats’ forepaw pads, the rats’ draining axillary lymph nodes were visualized by preoperative mapping with SPECT/CT and intraoperative biopsy with NIR fluorescence. The axillary lymph nodes of rats were identified by pathology and fluorescent staining after execution. Additionally, its toxicity testing and comparison with 99mTc-sulfur colloid imaging were also explored.Results: The study reported a self-assembled 99mTc-ICG-HSA with a high radiochemical yield (85.6 ± 3.8%). Compared with conventional 99mTc-sulfur colloid, 99mTc-ICG-HSA NPs showed faster SLN identification, higher renal clearance, and lower hepatic retention. Furthermore, NIRF imaging allowed for the accurate visualization of the SLN and guided SLN biopsy intraoperatively. Notably, the 99mTc-ICG-HSA NPs were composed of hospital-available drugs and isotope, which are safe for acute toxicity evaluation by a certified institute.Conclusion: The proposed 99mTc-ICG-HSA NPs are safe and capable of noninvasive SLN identification and biopsy guidance with multi-modal imaging strategies and could be a promising tool for clinically assisted SLN biopsy. Keywords: image-guided surgery, indocyanine green, albumin, fluorescence imaging, near-infrared, single-photon emission computed tomography

Chenkai Yang,1,&ast; Xiangqian Cao,1,&ast; Lei He,2,3,&ast; Cong Wu,2,&ast; Mengxin Zhao,2 Fei Duan,2 Zhiwen Qiu,2 Xiaodong Zhu,2 Yilin Yan,1 Shengzhou Li,1 Wei Li,2 Bing Shen1 1Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, Shanghai, People’s Republic of China; 3School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, 800 Xiangyin Road, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel +86 21 81871644, Fax +86 21 81870801, Email liwei_dds@163.com Bing Shen, Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 85 Wujin Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 18017181979, Email urodrshenbing@shsmu.edu.cnIntroduction: Insufficient tumor permeability and inadequate nanoparticle retention continue to be significant limitations in the efficacy of anti-tumor drug therapy. Numerous studies have focused on enhancing tumor perfusion by improvement of tumor-induced endothelial leakage, often known as the enhanced permeability and retention (EPR) effect. However, these approaches have produced suboptimal therapeutic outcomes and have been associated with significant side effects. Therefore, in this study, we prepared tumor cell membrane-coated gold nanorods (GNR@TM) to enhance drug delivery in tumors through homogeneous targeting of tumor cell membranes and in situ real-time photo-controlled therapy.Methods: Here, we fabricated GNR@TM, and characterized it using various techniques including Ultraviolet-Visible (UV-Vis) spectrophotometer, particle size analysis, potential measurement, and transmission electron microscopy (TEM). The cellular uptake and cytotoxicity of GNR@TM were analyzed by flow cytometry, confocal laser scanning microscopy (CLSM), TEM, CCK8 assay and live/dead staining. Tissue drug distribution was determined by inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence staining. Furthermore, to evaluate the therapeutic effect, mice bearing MB49 tumors were intravenously administered with GNR@TM. Subsequently, near-infrared (NIR) laser therapy was performed, and the mice’s tumor growth and body weight were monitored.Results: The tumor cell membrane coating endowed GNR@TM with extended circulation time in vivo and homotypic targeting to tumor, thereby enhancing the accumulation of GNR@TM within tumors. Upon 780 nm laser, GNR@TM exhibited excellent photothermal conversion capability, leading to increased tumor vascular leakage. This magnification of the EPR effect induced by NIR laser further increased the accumulation of GNR@TM at the tumor site, demonstrating strong antitumor effects in vivo.Conclusion: In this study, we successfully developed a NIR-triggered nanomedicine that increased drug accumulation in tumor through photo-controlled therapy and homotypic targeting of the tumor cell membrane. GNR@TM has been demonstrated effective suppression of tumor growth, excellent biocompatibility, and significant potential for clinical applications. Keywords: intratumor drug accumulation, photo-controlled therapy, homotypic targeting, tumor cell membrane, gold nanorods

Hongwei Wang,1 Fangying Tian,2 Xueyu Wang,3 Ming Zhao,1 Ruiqin Gao,1 Xinyu Cui1 1Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Infection Management Department of the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Infectious Diseases, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Fangying Tian, Department of Hospital Infection Management, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, Shanxi, People’s Republic of China, Tel/Fax +86-0351-3365612, Email tfy8048@163.comBackground: Healthcare-associated infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are now a global public health problem, increasing the burden of disease and public healthcare expenditures in various countries. The aim of this study was to analyse the risk factors for CRKP infections and to develop nomogram models to help clinicians predict CRKP infections at an early stage to facilitate diagnosis and treatment.Methods: The clinical data of patients with Klebsiella pneumoniae (KP) infections in our hospital from January 2018 to January 2023 were collected. 174 patients with CRKP infections and 219 patients with CSKP infections were selected for case-control study. 27 predictors related to CRKP infections were determined. The least absolute shrinkage and selection operator (Lasso) regression was used to screen the characteristic variables, Multivariate logistic regression analysis was performed on the selected variables and a nomogram model was established. The discrimination and calibration of the nomogram model were evaluated by receiver operator curves (ROC) and calibration curves.Results: Six predictive factors of ICU stay, fever time, central venous catheterization time, catheter indwelling time, carbapenem use and tetracycline use screened by lasso regression were included in the logistic regression model, and the nomogram was drawn to visualize the results. The area under ROC curve of training set and validation set was 0.894 (95% CI: 0.857, 0.931) and 0.872 (95% CI: 0.805, 0.939); The results of decision curve analysis also show that the model has good prediction accuracy.Conclusion: This study established a nomogram to predict CRKP infection based on lasso-logistic regression model, which has certain guiding significance for early diagnosis of CRKP infections.Keywords: carbapenem resistance, Klebsiella pneumoniae, risk factors, nomogram model

Menglong Wang,1– 3,&ast; Wei Pan,1– 3,&ast; Cheng Wei,1– 3,&ast; Jianfang Liu,1– 3 Jishou Zhang,1– 3 Junping Yu,1– 3 Mengmeng Zhao,1– 3 Shuwan Xu,1– 3 Jing Ye,1– 3 Zhen Wang,1– 3 Di Ye,1– 3 Yongqi Feng,1– 3 Yao Xu,1– 3 Jun Wan1– 3 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People’s Republic of China; 3Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wan; Yao Xu, Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Tel +86-27-88041911, Fax +86-27-88042293, Email wanjun@whu.edu.cn; whuxuyao@163.comBackground: Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear.Methods: Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis.Results: 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue.Conclusion: 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.Keywords: inflammation resolution, resolvin D1, cardiac hypertrophy, NLRP3 inflammasome, transverse aortic constriction

Kuiliang Li,1 Xiaomei Ren,2 Lei Ren,3 Xuejiao Tan,1 Mengxue Zhao,2 Chang Liu,4 Xi Luo,1 Zhengzhi Feng,2 Qin Dai2 1Department of Medical English, School of Basic Medical Sciences, Army Medical University, Chongqing, People’s Republic of China; 2Department of Medical Psychology, Army Medical University, Chongqing, People’s Republic of China; 3Department of Clinical Psychology, Air Force Medical University, Xi’an, People’s Republic of China; 4BrainPark, Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Clayton, VIC, AustraliaCorrespondence: Zhengzhi Feng, Department of Medical Psychology, Army Medical University, Chongqing, People’s Republic of China, Tel +86 023-68771480, Email fzz@tmmu.edu.cn Qin Dai, Department of Medical Psychology, Army Medical University, Chongqing, 400038, People’s Republic of China, Tel +86 16623460852, Email daiqin101@hotmail.comBackground: Previous studies have explored the relationship between negative life events and depression, but little is known about the bidirectional relationship between negative life events and depression, particularly in specific groups of medical cadets.Purpose: This study aimed to explore the relationship between negative life events and depressive symptoms among medical cadets during their four years of college.Methods: An analysis of 4-wave longitudinal data collected from 2015– 2018 was conducted using a cross-lagged panel network (CLPN) model to explore the complex causal relationship between negative life events and depressive symptoms in medical cadets (N=433).Results: We found differences in negative life events and depressive symptoms among medical cadets across four network models over four years of university. Nodes A-21, A-20, A-23 and A-24, and depressive symptoms D-6 showed greater lagged effect values.Conclusion: Our findings suggest that there is a lagged and mutually causal interaction between negative life events and depressive symptoms in medical cadets over 4 years of college, but that the predictability of negative life events is more important. However, more attention needs to be paid to the predictive role of depressive symptoms, especially those in early life which are often overlooked. Our study provides new insights into the relationship between negative life events and depressive symptoms in university students and helps to refine strategies for prevention and intervention of depression.Keywords: depression, negative life events, CLPN, longitude relationship, vicious circle, network analysis

Zhiqiang He,1 Huan Yang,1 Yufan Gu,1 Yuhan Xie,1 Jianan Wu,1 Chen Wu,1 Jiawei Song,1 Maofang Zhao,2,3 Da Zong,1 Wenlong Du,1 Jiaju Qiao,1 Yipeng Pang,1– 3 Yi Liu1– 3 1Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of ChinaCorrespondence: Yi Liu; Yipeng Pang, Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262084, Email cbpeliuyinew@163.com; pangyipeng.xzmu@foxmail.comPurpose: Herein, an emerging drug delivery system was constructed based on zeolite imidazole backbone (ZIF-8) to improve antibacterial defects of nanosilver (AgNPs), such as easily precipitated and highly cytotoxic.Methods: The homogeneous dispersion of AgNPs on ZIF-8 was confirmed by UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM. The appropriate AgNPs loading ratio on ZIF-8 was screened through the cell and antibacterial experiments based on biosafety and antibacterial performance. The optimal environment for AgNPs@ZIF-8 to exert antibacterial performance was probed in the context of bacterial communities under different acid-base conditions. The potential mechanism of AgNPs@ZIF-8 to inhibit the common clinical strains was investigated by observing the biofilm metabolic activity and the level of reactive oxygen species (ROS) in bacteria.Results: The successful piggybacking of AgNPs by ZIF-8 was confirmed using UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM characterization methods. Based on the bacterial growth curve (0– 24 hours), the antibacterial ability of AgNPs@ZIF-8 was found to be superior to AgNPs. When the mass ratio of ZIF-8 and AgNPs was 1:0.25, the selection of AgNPs@ZIF-8 was based on its superior antimicrobial efficacy and enhanced biocompatibility. Notably, under weakly acidic bacterial microenvironments (pH=6.4), AgNPs@ZIF-8 demonstrated a more satisfactory antibacterial effect. In addition, experiments on biofilms showed that concentrations of AgNPs@ZIF-8 exceeding 1×MIC resulted in more than 50% biofilm removal. The nanomedicine was found to increase ROS levels upon detecting the ROS concentration in bacteria.Conclusion: Novel nanocomposites consisting of low cytotoxicity drug carrier ZIF-8 loaded with AgNPs exhibited enhanced antimicrobial effects compared to AgNPs alone. The pH-responsive nano drug delivery system, AgNPs@ZIF-8, exhibited superior antimicrobial activity in a mildly acidic environment. Moreover, AgNPs@ZIF-8 effectively eradicated pathogenic bacterial biofilms and elevated the intracellular level of ROS.Graphical Abstract: Keywords: MOF, ZIF-8, AgNPs, nanocomplex, ROS, pathogenic biofilm

ChuoChuo Yu,1,&ast; ZhiQun Liu,2,&ast; Mingyang Zhao,3 Yanhui Liu,2 Yuxin Zhang,1 Ai Lin,2 Xiaohan Sang,1 Huan Wan2 1Department of Nursing, Hunan Normal University School of Medicine, Changsha, 410013, People’s Republic of China; 2Department of Nursing, The First Hospital Affiliated with Hunan Normal University (Hunan Provincial People`s Hospital), Changsha, 410005, People’s Republic of China; 3Operating Room, Guangzhou Dongsheng Hospital, Guangzhou, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Wan, Department of Nursing, The First Hospital Affiliated with Hunan Normal University (Hunan Provincial People`s Hospital), No. 61 Jiefang West Road, Changsha City, Hunan Province, 410005, People’s Republic of China, Tel +86 137 8725 7287, Fax +86 731 8227 8012, Email huanwan3013@163.comObjective: To explore the influence of negative psychology and burnout in clinical nurses, and to analyse the mediating role between self-efficacy and emotional intelligence in emotion management.Methods: From January 2022 to December 2022, 12,704 clinical nurses from 32 general hospitals in Hunan Province were selected as research participants by convenience sampling. Negative psychology, emotion management, self-efficacy, emotional intelligence and burnout in clinical nurses were measured, and structural equation models were constructed to explore their impact on burnout in clinical nurses.Results: Clinical nurses’ negative psychology had a positive effect on burnout (β=0.60, 95% CI: 0.63– 0.66), emotional intelligence (β=˗0.08, 95% CI: ˗0.10, ˗0.06) and the self-efficacy of emotion management (β=− 0.60, 95% CI: ˗0.05, ˗0.03) on burnout. Moreover, emotional intelligence and emotion management self-efficacy played a mediating role between negative psychology and burnout in nurses.Conclusion: Clinical nurses’ negative psychology had a positive impact on burnout, and emotional intelligence and the self-efficacy of emotion management could alleviate the influence of negative psychology on burnout among nurses. Nurses’ emotional intelligence and emotion management self-efficacy can be improved through practical training to help them cope with emotionally loaded situations and reduce stress responses.Keywords: clinical nurse, job burnout, negative psychology, emotional management self-efficacy, emotional intelligence

Xiangze Wang,1 Minghui Zhao,1 Chensheng Zhang,1 Haobo Chen,1 Xingyu Liu,2 Yang An,1 Lu Zhang,1 Xiangqian Guo1 1Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, 475004, People’s Republic of China; 2School of Computer and Information Engineering, Henan University, Kaifeng, 475004, People’s Republic of ChinaCorrespondence: Lu Zhang; Xiangqian Guo, Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, 475004, People’s Republic of China, Tel/Fax +86-371-23880585, Email zhanglu9128@126.com; xqguo@henu.edu.cnAbstract: Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy, accounting for approximately 90% of all primary liver cancers, with high mortality and a poor prognosis. A large number of predictive models have been applied that integrate multiple clinical factors and biomarkers to predict the prognosis of HCC. Nomograms, as easy-to-use prognostic predictive models, are widely used to predict the probability of clinical outcomes. We searched PubMed with the keywords “hepatocellular carcinoma” and “nomogram”, and 974 relative literatures were retrieved. According to the construction methodology and the real validity of the nomograms, in this study, 97 nomograms for HCC were selected in 77 publications. These 97 nomograms were established based on more than 100,000 patients, covering seven main prognostic outcomes. The research data of 56 articles are from hospital-based HCC patients, and 13 articles provided external validation results of the nomogram. In addition to AFP, tumor size, tumor number, stage, vascular invasion, age, and other common prognostic risk factors are included in the HCC-related nomogram, more and more biomarkers, including gene mRNA expression, gene polymorphisms, and gene signature, etc. were also included in the nomograms. The establishment, assessment and validation of these nomograms are also discussed in depth. This study would help clinicians construct and select appropriate nomograms to guide precise judgment and appropriate treatments.Keywords: hepatocellular carcinoma, nomograms, prognosis, biomarker, precision medicine

Xiaochong Li,1,&ast; Bowen Hu,1,&ast; Jiachen Zheng,2,3 Zhiyong Pan,1 Yuxiang Cai,4 Mingjuan Zhao,1 Xiaoqing Jin,2 Zhi-Qiang Li1 1Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 3The Second Clinical School, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 4Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqing Jin; Zhi-Qiang Li, Email redjin@whu.edu.cn; lizhiqiang@whu.edu.cnIntroduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ.Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1β, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKβ, IκBα, and P65 with their phosphorylation in jejunum were measured.Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos–IKKβ and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group.Conclusion: LGG inhibits the activation of the TLR4–NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.Keywords: Lactobacillus rhamnosus GG, temozolomide, intestinal mucosal injury, TLR4, NFκB

Mengnan Zhao,&ast; Na Li,&ast; Hong Zhou Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhou, Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +86 151 3011 9625, Email zhoubs2013@163.comAbstract: SGLT1 and SGLT2 are the two main members of the sodium-glucose cotransporters (SGLTs), which are mainly responsible for glucose reabsorption in the body. In recent years, many large clinical trials have shown that SGLT2 inhibitors have cardiovascular protection for diabetic and non-diabetic patients independent of lowering blood glucose. However, SGLT2 was barely detected in the hearts of humans and animals, while SGLT1 was highly expressed in myocardium. As SGLT2 inhibitors also have a moderate inhibitory effect on SGLT1, the cardiovascular protection of SGLT2 inhibitors may be due to SGLT1 inhibition. SGLT1 expression is associated with pathological processes such as cardiac oxidative stress, inflammation, fibrosis, and cell apoptosis, as well as mitochondrial dysfunction. The purpose of this review is to summarize the protective effects of SGLT1 inhibition on hearts in various cell types, including cardiomyocytes, endothelial cells, and fibroblasts in preclinical studies, and to highlight the underlying molecular mechanisms of protection against cardiovascular diseases. Selective SGLT1 inhibitors could be considered a class of drugs for cardiac-specific therapy in the future.Keywords: sodium glucose cotransporter 1, SGLT1 inhibitor, heart failure, cardioprotection, molecular mechanism

Min Zhao, Chang Tian, Xin Di, Shan Cong, Yingshu Cao, Xijia Zhou, Ke Wang Department of Respiratory and Critical Care Medicine, the Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Ke Wang, The Second Hospital of Jilin University, No. 218 Ziqiang Road, Nanguan District, Changchun, 130041, People’s Republic of China, Email wke@jlu.edu.cnIntroduction: The pathogenesis of sarcoidosis, which involves several systems, is unclear, and its pathological type is non-caseating epithelioid granulomas. tRNA-derived small RNA (tsRNA) is a novel class of short non-coding RNAs with potential regulatory functions. However, whether tsRNA contributes to sarcoidosis pathogenesis remains unclear.Methods: Deep sequencing technology was used to identify alterations in tsRNA relative abundance profiles between patients with sarcoidosis and healthy controls and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate. The clinical parameters were analysis to evaluate the clinical feature correlations initially. Target prediction and bioinformatics analysis of validated tsRNA were conducted to explore the mechanisms of tsRNAs in sarcoidosis pathogenesis.Results: A total of 360 tsRNAs were identified for exact matches. Among them, the relative abundance of three tRNAs (tiRNA-Glu-TTC-001, tiRNA-Lys-CTT-003, and tRF-Ser-TGA-007) was markedly regulated in sarcoidosis. The levels of various tsRNAs were significantly correlated with age, the number of affected systems, and calcium levels in the blood. Additionally, target prediction and bioinformatics analyses revealed that these tsRNAs may play roles in chemokine, cAMP, cGMP-PKG, retrograde endorphin, and FoxO signalling pathways. The related genes, APP, PRKACB, ARRB2, and NR5A1 finding may participate in the occurrence and development of sarcoidosis through immune inflammation.Conclusion: This study provides novel insights to explore tsRNA as a novel and efficacious pathogenic target of sarcoidosis.Keywords: sarcoidosis, tRNA-derived small RNA, tsRNA, noncoding RNAs, bioinformatics analysis

Mengyang Zhao,1 Liu Yao,2 Rao Ma,3 Muhammad Sarmad,4 Orangzab,5 Arslan Ayub,6 Zhou Jun7 1School of Economics and Management, Harbin Engineering University, Harbin, Heilongjing, 150001, People’s Republic of China; 2Faculty of Management Engineering, Huaiyin Institute of Technology, Huai’an, Jiangsu, People’s Republic of China; 3Business School, University of International Business and Economics, Beijing, 100029, People’s Republic of China; 4Riphah School of Leadership, Riphah International University, Islamabad, Pakistan; 5Department of Management Sciences, COMSATS University Islamabad, Vehari, Pakistan; 6Department of Management Studies, the University of Faisalabad, Faisalabad, Pakistan; 7Faculty of Transportation Engineering, Huaiyin Institute of Technology, Huai’an, 223003, People’s Republic of ChinaCorrespondence: Mengyang Zhao, Email zhaomy_92@163.comAim: The study is based on the self-determination theory and aims to investigate the mediating role of green intrinsic motivation and the moderating role of green shared vision in the association between frontline managers’ green mindfulness and green creative behavior to leverage their capacity to think creatively and act sustainably.Methods: The study employs a time-lagged, multi-source research methodology to collect data from frontline managers of service businesses in the tourism and hospitality industry. Data are analyzed using SmartPLS Structural Equation Model to evaluate the structural and measurement models. The authors evaluated the measurement model by employing the criteria of internal consistency: reliability and Cronbach’s alpha, validity: convergent and discriminant validity; and the structural model using the path coefficient, coefficient of determination, predictive relevance, and goodness-of-fit metrics.Results: Our findings indicate that green mindfulness significantly improves frontline managers’ green creative behavior. Additionally, green intrinsic motivation mediates the connection between green mindfulness and green creative behavior. In addition, the direct effect of green mindfulness on green intrinsic motivation as well as the indirect effect of green mindfulness on green creative behavior through green intrinsic motivation, are both significantly moderated by green shared vision.Discussion: To the best of the authors’ knowledge, this is one of the few efforts that outstretch the boundary conditions of green mindfulness and green creative behavior through the mediating role of green intrinsic motivation and the moderating role of green shared vision.Keywords: green mindfulness, green creative behavior, green intrinsic motivation, green shared vision, self-determination theory

Mingjun Zhao,1,&ast; Bin Qin,2,&ast; Yage Mao,3 Yang Zhang,4 Ruisheng Zhao,5 Aiqin Wang,1 Hailing Wang,1 Jianting Zhao,6 Changhong Wang7 1Department of Pharmacy, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, People’s Republic of China; 2Department of Neurology, Liuzhou General Hospital, Liuzhou, People’s Republic of China; 3Department of Pharmacy, Maternal and Child Health Care hospital of Xinxiang City, Xinxiang, People’s Republic of China; 4Department of Respiratory, The People’s Hospital of Jiaozuo City, Jiaozuo, People’s Republic of China; 5Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China; 6Department of Neurology, Central Hospital of Xinxiang City, Xinxiang, People’s Republic of China; 7Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changhong Wang, Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), 207&num; QianJin Road, Xinxiang, Henan, 453000, People’s Republic of China, Tel +86-373-3388798, Fax +86-373-3374082, Email wangchdr@163.comPurpose: The aim of this study was to assess the efficacy and safety of paliperidone palmitate (PP) treatment compared with risperidone long-acting injectable (LAI) treatments for patients with schizophrenia.Patients and Methods: Data mining was conducted in April 2022 across PubMed, Web of Science, Embase, the Cochrane Library, ClinicalTrials.gov, and PsycINFO. All published randomized controlled trials (RCTs) that assessed the effect of PP treatment for patients with schizophrenia when compared with the risperidone-LAIAs group were included. Relevant data were extracted and synthesized narratively. Results were expressed as standardized mean differences (SMDs) or risk ratios (RRs), with 95% confidence intervals (CIs).Results: Four RCTs with 2451 patients met all the inclusion and exclusion criteria. Efficacy analyses showed no significant statistical differences in Positive and Negative Syndrome Scale (PANSS) total score changes at the endpoint (SMD = 0.10, P = 0.19), or in response rates (RR = 0.93; P = 0.40). Regarding the safety outcomes, PP treatment showed significantly increased risks of discontinuation rates for any reason (35.7% vs 30.4%; RR = 1.19; 95% CI, 1.03 to 1.39; P = 0.02) and nonsignificantly increased risks of total treatment emergent adverse events (TEAEs) (66.6% vs.64.8%; RR = 1.01; 95% CI, 0.94 to 1.09; P = 0.78) compared with the risperidone-LAIAs-treated group. Furthermore, PP may significantly increase total discontinuation rates compared with risperidone-LAIAs.Conclusion: Our meta-analysis did not find a more beneficial effect of PP compared to risperidone-LAIAs treatments for schizophrenia. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of randomized controlled trials and patients.Keywords: paliperidone palmitate, risperidone, long-acting injectable, schizophrenia, meta-analysis

Mei Zhao,1,2 Lijuan Fu,1,2 Panling Xu,1,2 Ting Wang,1,2 Ping Li1,2 1Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Ping Li, Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, No. 120 Wanshui Road, Hefei, 230032, Anhui, People’s Republic of China, Email liping1964@ahmu.edu.cnPurpose: Kanglaite injection (KLTi), made of Coix seed oil, has been shown to be effective in the treatment of numerous cancers. However, the anticancer mechanism requires further exploration. This study aimed to investigate the underlying anticancer mechanisms of KLTi in triple-negative breast cancer (TNBC) cells.Methods: Public databases were searched for active compounds in KLTi, their potential targets and TNBC-related targets. KLTi’s core targets and signaling pathways were determined through compound-target network, protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was carried out to predict the binding activity between active ingredients and key targets. In vitro experiments were conducted to further validate the predictions of network pharmacology.Results: Fourteen active components of KLTi were screened from the database. Fifty-three candidate therapeutic targets were selected, and bioinformatics analysis was performed to identify the top two active compounds and three core targets. GO and KEGG enrichment analyses indicated that KLTi exerts therapeutic effects on TNBC through the cell cycle pathway. Molecular docking results showed that the main compounds of KLTi exhibited good binding activity to key target proteins. Results from in vitro experiments showed that KLTi inhibited proliferation and migration of TNBC cell lines 231 and 468, induced apoptosis, blocked cells in the G2/M phase, downregulated the mRNA expression of seven G2/M phase-related genes cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), and checkpoint kinase 1 (CHEK1), cell division cycle 25A (CDC25A), cell division cycle 25B (CDC25B), maternal embryonic leucine zipper kinase (MELK), and aurora kinase A (AURKA), as well as downregulated CDK1 protein expression and up-regulated protein expression of Phospho-CDK1.Conclusion: By utilizing network pharmacology, molecular docking, and in vitro experiments, KLTi was confirmed to have anti-TNBC effects by arresting cell cycle and inhibiting CDK1 dephosphorylation.Keywords: Kanglaite injection, triple-negative breast cancer, network pharmacology, cell cycle, CDK1

Chaofan Wang, Yimei Du, Lingbo Bi, Xuewen Lin, Min Zhao, Weixin Fan Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Weixin Fan, Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu Province, People’s Republic of China, Tel +86 13327805737, Email hairmanfwx@163.comIntroduction: Androgenetic alopecia (AGA) has negative impacts on both men and women in terms of appearance and mental stress. Spironolactone is a synthetic aldosterone receptor antagonist known to stimulate hair growth and has been widely used by dermatologists to treat AGA.Objective: To conduct a systematic review evaluating the efficacy and safety of topical and oral spironolactone in AGA treatment.Methods: We searched PubMed, Embase, the Cochrane Library, and the Web of Science until October 23rd, 2022, for human studies evaluating the efficacy of spironolactone for the treatment of AGA, regardless of doses and routes.Results: We retrieved 784 papers and ultimately 7 articles matched our inclusion criteria and comprised 618 AGA patients (65 men, 553 women), 414 of them received spironolactone treatment. Oral spironolactone doses ranged from 25mg to 200mg daily, with the vast majority between 80mg and 110 mg. Dosage forms for topical spironolactone use include gels of 1% and solutions of 5% twice daily. Both oral and topical spironolactone have been shown efficacy for alopecia recovery, but topical use has significantly fewer side effects and is suitable for any gender. It showed better efficacy in combination with other therapies such as oral or topical minoxidil compared with monotherapy.Conclusion: Spironolactone is an effective and safe treatment of androgenic alopecia which can enhance the efficacy when combined with other conventional treatments such as minoxidil. Topical spironolactone is safer than oral administration and is suitable for both male and female patients, and is expected to become a common drug for those who do not have a good response to minoxidil. Furthermore, more high-quality clinical randomized controlled studies should be performed.Keywords: androgenetic alopecia, spironolactone, dosage, combine therapy, efficacy, adverse effects

Junpeng Wang,1,2 Xiaofan Zhang,3 Mengjun Li,4 Ruoying Li,4 Ming Zhao1 1Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Urology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 3Medical Research Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Ming Zhao, Tel/Fax + 86 020 62782501, Email zhaoming02@hotmail.comBackground: Antibody-mediated rejection (AMR) is emerging as the main cause of graft loss after kidney transplantation. Our previous study revealed the gut microbiota alternation associated with AMR in kidney transplant recipients, which was predicted to affect the metabolism-related pathways.Methods: To further investigate the shifts in intestinal metabolic profile among kidney transplantation recipients with AMR, fecal samples from kidney transplant recipients and patients with end-stage renal disease (ESRD) were subjected to untargeted LC-MS-based metabolomics.Results: A total of 86 individuals were enrolled in this study, including 30 kidney transplantation recipients with AMR, 35 kidney transplant recipients with stable renal function (KT-SRF), and 21 participants with ESRD. Fecal metabolome in patients with ESRD and kidney transplantation recipients with KT-SRF were parallelly detected as controls. Our results demonstrated that intestinal metabolic profile of patients with AMR differed significantly from those with ESRD. A total of 172 and 25 differential metabolites were identified in the KT-AMR group, when compared with the ESRD group and the KT-SRF group, respectively, and 14 were common to the pairwise comparisons, some of which had good discriminative ability for AMR. KEGG pathway enrichment analysis demonstrated that the different metabolites between the KT-AMR and ESRD groups or between KT-AMR and KT-SRF groups were significantly enriched in 33 or 36 signaling pathways, respectively.Conclusion: From the metabolic point of view, our findings may provide key clues for developing effective diagnostic biomarkers and therapeutic targets for AMR after kidney transplantation.Keywords: antibody-mediated rejection, kidney transplantation, intestinal metabolic profile, LC-MS, end-stage renal disease

Xiaoxu Li,1,&ast; Shifang Zhuang,2,&ast; Lin He,2 Shanmei Wang,3 Ming Zhao,1 Xiaodong Lyu4 1Department of Neurosurgery, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China; 2Genskey Medical Technology Co., Ltd, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Lyu, Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, Zhengzhou, 450000, People’s Republic of China, Tel/Fax +8613523417973, Email zlyyxiaodonglyu1268@zzu.edu.cnAbstract: Nocardia brain abscess is relatively rare and generally occurs in immunodeficient patients. Here, we present the first case of brain abscess due to Nocardia brevicatena in an immunocompetent patient, with unknown origin. In this case, a 49-year-old man was admitted to our hospital with limb twitching and complained of a history of intermittent headache. He was diagnosed with brain abscess through brain imaging and cured after craniotomy for abscess excision and targeted antibiotic treatment. Surgical specimens were sent for further detection. The causative organism was identified by weak acid-fast staining, culture and metagenomic next-generation sequencing (mNGS). We hope this case could provide a reference for incoming patients as well as their clinical management.Keywords: brain abscess, Nocardia brevicatena, non-immunocompromised, mNGS, surgical treatment

Meng Zhang,1,&ast; Wenyi Lu,2,&ast; Danni Xie,1 Jiaxi Wang,1 Xia Xiao,2 Yedi Pu,2 Juanxia Meng,2 Hairong Lyu,2 Mingfeng Zhao2 1First Center Clinic College of Tianjin Medical University, Tianjin, 300192, People’s Republic of China; 2Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingfeng Zhao; Hairong Lyu, Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China, Email mingfengzhao@sina.com; 18802235939@163.comBackground: Metagenomic next-generation sequencing (mNGS) is a fast, sensitive and accurate diagnostic method for pathogens detection. However, reports on the application of mNGS in mucormycosis remain scarce.Methods: From January 2019 to December 2021, we recruited 13 patients with hematological malignancies who were suspected of mucormycosis and completed mNGS in D20. Then we retrospectively analyze the clinical data, diagnosis, therapeutic process, and outcomes. In order to evaluate the diagnostic value of mNGS in hematological malignancies patients with suspected mucormycosis.Results: All patients had high risk factors of Invasive Fungal Disease, including hematopoietic stem cell transplantation, immunosuppression, glucocorticoids, etc. The clinical presentations were pulmonary (n=9), rhino-orbito-cerebral (n=4). But the manifestations were nonspecific. All enrolled patients completed mNGS. And most (8/13, 61.54%) of the samples were from blood. Fungi can be detected in all specimens, including Rhizopus (n=7), Rhizomucor (n=4) and Mucor (n=2). In addition, 7/13 (53.85%) specimens were detected bacteria at the same time and virus were detected in 5/13 (38.46%). Histopathological examination was completed in 5 patients, 3 of which were completely consistent with the results of mNGS. After treatment, 6 patients were cured, while the other 7 patients died.Conclusion: mNGS may be a complementary method for early diagnosis, especially for patients who are not suitable for histopathology examination or unable to obtain culture specimen. mNGS can also help detect bacteria and viruses simultaneously, allowing for appropriate and timely antibiotic administration and thus improving patient outcomes.Keywords: metagenomic next-generation sequencing, mucormycosis, retrospectively, hematological malignancies, invasive fungal disease

Miao Zhao, Tengteng Liu, Sufang Qi, Wenjie Li, Xin Liu, Xinming Li, Guanglei Xun Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Guanglei Xun, Department of Psychiatry, Shandong Mental Health Center, Shandong University, No. 49 Wenhua Eastern Road, Jinan, People’s Republic of China, Tel +86 15069053599, Email xungl@163.com; xungl2019@163.comPurpose: Previous studies suggest that homocysteine (Hcy) may be involved in the pathogenesis of bipolar disorder (BD) and major depressive disorder (MDD) by influencing glutamatergic transmission, inflammation, and other mechanisms. There are no established biomarkers to distinguish BD from MDD. This study aims to compare Hcy levels between BD and MDD.Patients and Methods: We collected medical records of patients aged 14– 75 admitted to the hospital from January 1 to July 1, 2022 with a discharge diagnosis of MDD or BD, including all examinations of patients at admission (acute phase) and discharge (non-acute phase). We measured Hcy levels in healthy controls (HC).Results: The analysis included 104 patients with MDD, 103 patients with BD, and 80 HC. Hcy levels were higher in the MDD and BD group than in the HC group and higher in the BD group than in the MDD group, both in the acute and non-acute phases (all P < 0.05). There was no significant difference in Hcy levels between the psychotropic medication users and non-users in the BD or MDD group (all P > 0.05). Multivariate logistic regression analysis only for the MDD and BD group indicated that the likelihood of BD diagnosis was significantly associated with Hcy levels (in the acute phase: OR = 1.052, P = 0.016; in the non-acute phase: OR = 1.101, P < 0.001) after controlling for gender, age, and metabolic indicators.Conclusion: Our study suggests that Hcy levels were elevated in MDD and BD patients and were higher in BD patients than in MDD patients, which provides evidence for a possible relationship between one-carbon metabolism and the pathogenesis of BD. Besides, Hcy may be one of the potential biomarkers to distinguish BD from MDD.Keywords: affective disorder, biomarker, pathophysiology, differential diagnosis

Xinwei Li,1,&ast; Yongfei Fan,2,&ast; Mingyue Tang,1 Huiyuan Li,1 Yue Zhang,1 Jiaqi Mi,1 Yanyan Wang,1 Menglin Zhao,1 Zishu Wang,1 Fang Su1 1Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China; 2Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Su; Zishu Wang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China, Tel +86 13605523272; +86 13955254185, Email sufang@bbmc.edu.cn; wzshahbb@163.comBackground: Research has revealed that Plexin domain containing 1 (PLXDC1) is correlated with the prognosis of a variety of tumors, but its role in the tumor microenvironment (TME) of gastric cancer has not been reported.Methods: In this study, we analyzed PLXDC1 expression in gastric cancer using the Oncomine and the Cancer Genome Atlas (TCGA) databases and immunohistochemical staining experiments, and performed prognostic assessment with data from the TCGA and Kaplan–Meier Plotter databases. The immunomodulatory role of PLXDC1 in the gastric cancer TME was analyzed by signaling pathway enrichment, immune cell correlation analysis, immunomodulator risk model construction and immunohistochemical staining experiments of immune cells.Results: The results indicated that PLXDC1 was overexpressed in gastric cancer and that its overexpression was associated with poor prognosis. Multivariate Cox analysis revealed that PLXDC1 could be an independent biomarker of the risk of gastric cancer. Signaling pathway enrichment revealed that high PLXDC1 expression was involved in signaling pathways related to immune activation and stromal activation, and Tumor Immune Dysfunction and Exclusion (TIDE) assessment indicated that high PLXDC1 expression was associated with a significantly higher risk of immune evasion than low PLXDC1 expression. A Cox risk model based on PLXDC1-associated immunomodulators also presented poor prognosis, and immune evasion was significantly higher in the high-risk group than in the low-risk group. In addition, immunohistochemical staining of CD8/CD3/CD4+ T cells in the high and low PLXDC1 expression groups also observed immune cell distribution characteristics of immune evasion.Conclusion: This study analyzed PLXDC1 from multiple biological perspectives and revealed that PLXDC1 can be a biomarker for poor prognosis and immune evasion in gastric cancer.Graphical Abstract: Keywords: PLXDC1, biomarker, tumor microenvironment, immune evasion, prognosis, immunotherapy

Jin Gao,1,2 Tingting Liu,1 Xingyu Xiong,1 Mei Zhao,1 Kun Du,1,2 Jiwei Li2,3 1Department of Neonates; 2Yunnan Province Clinical Research Center for Children’s Health and Disease, Kunming, People’s Republic of China; 3Department of Pathology, Kunming Children’s Hospital, The Affiliated Children’s Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Kun Du; Jiwei Li, Email Dukun@etyy.cn; 360623155@qq.comAbstract: Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi, which is transmitted by larval trombiculid mites. Due to nonspecific clinical presentation, scrub typhus is grossly underdiagnosed in pregnant women, fetuses and neonates. Here, we present a congenital infection case and hope to provide more insight into this disease.Keywords: neonatal scrub typhus, vertical transmission, congenital infection, Orientia tsutsugamushi, meningitis

Tingting Xu,1,&ast; Wei Sun,2,&ast; Hongqing Zhao,3,&ast; Xinmin Wang,4 Qi Yuan,1 Xijie Zhang,1 Shan Mao,5 Xiuwei Zhang,6 Mingming Zhao,7 Zebo Sheng,8 Mingshun Zhang,9 Mao Huang,1 Ningfei Ji1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Wuxi Second People’s Hospital, Wuxi, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shuyang Hospital of Traditional Chinese Medicine, Suqian, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Nanjing First Hospital, Nanjing, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Nanjing Jiangning Hospital, Nanjing, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Nanjing Gaochun People’s Hospital, Nanjing, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Changshu First People’s Hospital, Suzhou, People’s Republic of China; 9Department of Immunology, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao Huang; Ningfei Ji, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel/Fax +86-13813886116 ; +86-18951080699, Email hm6114@163.com; jiningfei@163.comPurpose: Hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is considered as severe exacerbations. Readmission for severe exacerbations is a crucial event for COPD patients. However, factors associated with readmission for severe exacerbations are incomplete. The study aimed to investigate different characteristics between the severe and non-severe exacerbation groups.Patients and Methods: Patients hospitalized for severe AECOPD were included in multi-centers, and their exacerbations in next 12 months after discharge were recorded. According to exacerbations, patients were separated into the severe-exacerbation group and the non-severe exacerbation group. Propensity-score matching (PSM) and multivariable analyses were performed to compare the baseline characteristics of two groups. The Hosmer-Lemeshow test and receiver operating characteristic curve were applied to evaluate how well the model could identify clusters.Results: The cohort included 550 patients with severe AECOPD across 27 study centers in China, and 465 patients were finally analyzed. A total of 41.5% of patients underwent readmission for AECOPD within 1 year. There were no significant differences in baseline characteristics between groups after PSM. Severe exacerbations in the 12 months were related to some factors, eg, the duration of COPD (13 vs 8 years, P< 0.001), the COPD Assessment Test (CAT) score (20 vs 17, P< 0.001), the blood eosinophil percentage (1.5 vs 2.0, P< 0.05), and their inhaler therapies. Patients readmitted with AECOPD had a longer time of diagnosis (≥ 9 years), more symptoms (CAT ≥ 10), and lower blood eosinophils (Eos < 2%). A clinical model was derived to help identify patients at risk of readmission with severe exacerbations.Conclusion: These analyses confirmed the relevance of COPD at admission with future severe exacerbations. A lower blood eosinophils percentage appears to be related to readmission when combined with clinical history. Further studies are needed to evaluate whether this study can predict the risk of exacerbations.Keywords: chronic obstructive pulmonary disease, acute exacerbation, eosinophils, prognosis

Wenhao Liao,1,&ast; Yuchen Li,1,2,&ast; Jing Wang,3,&ast; Maoyuan Zhao,1 Nianzhi Chen,1 Qiao Zheng,1 Lina Wan,1 Yu Mou,1 Jianyuan Tang,1,4 Zhilei Wang1,4 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Obstetrics and Gynecology, Bishan Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China; 4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianyuan Tang; Zhilei Wang, Email tangjy@cdutcm.edu.cn; wangzl1993@outlook.comAbstract: Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.Keywords: cancer, cancer stem cells, nanoformulations, natural products, targeted therapy

Yi Zhang,1,&ast; Chunhua Xi,1,&ast; Jianying Yue,1 Mengmeng Zhao,2 Guyan Wang1 1Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Operation Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, 1 Dongjiaominxiang Road, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-10-58268101, Email guyanwang2006@163.comPurpose: Mivacurium, the shortest-acting benzylisoquinoline nondepolarizing neuromuscular blocker used in clinical practice, is suitable for short-term ambulatory operations under general anesthesia. We investigated the neuromuscular blockade effect of different maintenance doses of mivacurium during ambulatory vitreoretinal surgery under general anesthesia and tried to determine the appropriate maintenance dose.Patients and Methods: Ninety-nine patients undergoing general anesthesia for elective ambulatory vitreoretinal surgery were randomly divided into three groups using the random number table method. Patients received three maintenance doses of mivacurium during surgery as follows: 3 μg/(kg·min) in group M1 (n = 33), 6 μg/(kg·min) in group M2 (n = 33), and 9 μg/(kg·min) in group M3 (n = 33). The primary outcome was the time from mivacurium withdrawal to a train-of-four stimulation ratio (TOFr) ≥ 0.9, and the secondary outcomes were the time from mivacurium withdrawal to TOFr ≥ 0.7, extubation time, incidence of TOFr < 0.9 after surgery and neuromuscular block effect.Results: The time from mivacurium withdrawal to TOFr ≥ 0.9 and to TOFr ≥ 0.7 was significantly longer in group M3 than in groups M1 and M2 (25.6± 7.2 min vs 16.4± 5.9 min and 18.6± 5.3 min, P < 0.001; 22.1± 6.3 min vs 13.6 ± 5.8 min and 15.5 ± 4.8 min; P < 0.001, respectively). There was a significant difference in the extubation time, the incidence of TOFr < 0.9 during extubation and upon leaving the operating room between group M3 and group M1 (all P < 0.05), but there was no such significant difference between group M2 and group M1 (all P > 0.05). The intraoperative depth of neuromuscular blockade in the three groups was significantly different, with 69.7% shallow block in group M1, 75.8% moderate block in group M2 and 63.6% deep block in group M3 (P < 0.001). One patient in group M1 experienced slight body movement during the operation.Conclusion: An intraoperative continuous infusion of 6 μg/(kg·min) mivacurium can not only achieve good postoperative recovery but also provide a satisfactory neuromuscular blockade effect during surgery, and this maintenance dose is suitable for neuromuscular blockade during ambulatory vitreoretinal surgery.Keywords: mivacurium, vitreoretinal surgery, neuromuscular blocking agents, neuromuscular monitoring, postoperative period

Zheng S, Zhang M, Bai H, et al. Int J Nanomedicine. 2019;14:9513–9524. The authors have advised due to an error at the time of figure assembly, the image of Spleen at 1 day in Figure 8B on page 9522 is incorrect. The correct Figure 8 is shown below. Figure 8 In vivo toxicity test of Mn-MoS2 QDs: (A(a–l)) Mouse serum biochemistry analysis and blood routine analysis before (0d, control) and after injection of Mn-MoS2 QDs for 1, 7, 21d. (B) Histological images of the heart, lungs, liver, spleen and kidneys of mice 1, 7 and 21 days post-intravenous injection of Mn-MoS2 QDs and in control mice. The organs were sectioned and stained with hematoxylin and eosin (H&E) and observed under a light microscope, scale bar = 100 μm. The authors apologize for this error and advise it does not affect the results of the paper.

Yanhong Xu,1 Ting Liu,1 Yunxia Jiang,1 Xianzhi Zhao,2 Fei Meng,1 Guangyi Xu,1 Mengjiao Zhao1 1School of Nursing, Qingdao University, Qingdao, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Ting Liu, School of Nursing, Qingdao University, 1 Ningde Road, Qingdao, Shandong, 266073, People’s Republic of China, Tel +86 15066237573, Email liuting201516@163.comPurpose: Patients with inflammatory bowel disease (IBD) suffer from physical symptoms and psychosocial issues. This generates risks of psychosocial maladjustment that is closely linked with self-care ability and health-related quality of life. The study aimed to explore psychosocial adaptation of IBD patients in China and the influencing factors from individual and family levels.Patients and Methods: Using a cross-sectional design, 191 Chinese patients with IBD were recruited from October 2020 to September 2021. General information questionnaire, general family functioning scale, resilience scale for IBD, and psychosocial adaptation questionnaire for IBD were used for investigation. Multivariate linear regression was used to identify predictive factors of psychosocial adaptation.Results: IBD patients reported a moderate level of psychosocial adaptation. Regression analysis showed that personal resilience especially the three dimensions (i.e., positive illness perception, disease management, and support from fellow IBD patients), general family functioning, and disease conditions (i.e., extra-intestinal manifestations and current disease status) were the main contributing factors of psychosocial adaptation, explaining 49.3% of the total variance.Conclusion: The findings suggest that healthcare providers could focus on improving patients’ illness perception about IBD and strengthening their disease management abilities, together with optimizing patients’ family functioning to enhance their psychosocial adaptation level.Keywords: inflammatory bowel disease, psychosocial adaptation, family functioning, resilience

Mingjun Zhao,1,&ast; Bin Qin,2,&ast; Yage Mao,3 Hailing Wang,1 Aiqin Wang,1 Chuansheng Wang4 1Department of Pharmacy, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, Henan, People’s Republic of China; 2Department of Neurology, Liuzhou General Hospital, Liuzhou, Guangxi, People’s Republic of China; 3Department of Pharmacy, Maternal and Child Health Care Hospital of Xinxiang City, Xinxiang, Henan, People’s Republic of China; 4Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuansheng Wang, Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), 207# QianJin Road, Xinxiang, Henan, 453000, People’s Republic of China, Tel +86-373-3388772, Fax +86-373-3374082, Email chuansonwang@126.comPurpose: The purpose of this meta-analysis was to compare the efficacy and safety profile of low-dose brexpiprazole (< 2 mg/d) compared to placebo and standard-dose brexpiprazole (2– 4 mg/d).Patients and Methods: We identified relevant studies pertaining to the specific purpose of our meta-analysis by searching PubMed, Web of Science, Embase, Cochrane library, and PsycINFO using the search terms “schizophrenia” or “schizophrenic” AND “brexpiprazole” or “REXULTI”. We systematically reviewed all randomized controlled trials (RCTs) comparing low-dose brexpiprazole with placebo. Primary efficacy outcomes were the PANSS total score change and response rate. Primary safety outcomes were total treatment discontinuation rate, and total serious adverse events (SAEs). Risk ratios (RR) and standardized mean differences (SMDs) were pooled implementing a random effect model.Results: Four RCTs (2178 patients) were included for effect assessment of low-dose brexpiprazole treatment on the patients with acute schizophrenia. Low-dose brexpiprazole was not superior to placebo (SMD = − 0.11, 95% CI = − 0.23, 0.02, P = 0.10, I2 = 0%), and significantly inferior to standard-dose brexpiprazole (SMD = 0.15, 95% CI = 0.03, 0.26, P = 0.01, I2 = 0%) for PANSS total score change. Low-dose brexpiprazole did not result in significant difference for response rate when compared to placebo and standard-dose brexpiprazole (RR = 1.16, 95% CI = 0.95, 1.41, P = 0.14, I2 = 25%; RR = 0.92, 95% CI = 0.76, 1.12, P = 0.40, I2 = 38%, respectively). For ratio of total discontinuation, low-dose brexpiprazole did not exhibit significant difference when compared to placebo (RR = 0.95, 95% CI = 0.81, 1.11, P = 0.53, I2 = 0%) and standard-dose brexpiprazole group (RR = 1.11, 95% CI = 0.95, 1.29, P = 0.19, I2 = 0%). Total SAEs in low-dose brexpiprazole group did not differ significantly from placebo and standard-dose brexpiprazole group (RR = 0.96, 95% CI = 0.52, 1.80, P = 0.90, I2 = 0%; RR = 1.29, 95% CI = 0.65, 2.57, P = 0.47, I2 = 26%, respectively).Conclusion: The results indicated that low-dose brexpiprazole may be not superior for improving the efficacy and safety for acute schizophrenia compared to placebo and standard-dose brexpiprazole, and may cause additional risk of increasing body weight. Therefore, using low-dose brexpiprazole in acute schizophrenia patients may be not recommended.Keywords: brexpiprazole, placebo, acute schizophrenia, RCTs, meta-analysis

Meng Zhang,1,2,&ast; Zhao Wang,2,&ast; Jiaxi Wang,1 Hairong Lv,2 Xia Xiao,2 Wenyi Lu,2 Xin Jin,2 Juanxia Meng,2 Yedi Pu,2 MingFeng Zhao2 1First Central Clinical College, Tianjin Medical University, Tianjin, 300192, People’s Republic of China; 2Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: MingFeng Zhao, Department of Hematology, Tianjin First Central Hospital, No. 24, Fukang Road, Nankai District, Tianjin, 300192, People’s Republic of China, Tel +16622082788, Email mingfengzhao@sina.comBackground: It was crucial to use empirical antibiotics in febrile neutropenia (FN) patients. However, most patients still died from infection due to poor efficacy. Metagenomic next-generation sequencing (mNGS) is a rapid microbiological diagnostic method. The value of mNGS in patients with FN remains to be studied, especially after empiric antibiotic treatment.Methods: We retrospectively analyzed the differences between mNGS and the traditional methods in 192 patients with hematological malignancies who have received empiric antibiotic treatment. Samples were collected when patient had chills or half an hour before peak body temperature. And we compared the differences between FN and non-FN patients, mainly including types of pathogens and the diagnostic value of different pathogens.Results: Despite receiving empirical treatment, the pathogen detection rate of mNGS was significantly higher than the traditional method (80.21% vs 25.00%, P< 0.001). And it has obvious advantages in detecting mixed pathogens infection (80.21% vs 4.17%, P< 0.001). Then, we found that mNGS saw more pathogens in the FN than in the non-FN group, especially fungus. 21/33 (63.63%) of FN patients was diagnosed with fungal infections. The fungal detection rate in FN was significantly higher than non-FN group (32.35% vs 12.22%, P=0.001). Besides, the sensitivity of mNGS was higher than the traditional methods in both FN and non-FN group (P< 0.001), but no significant difference in specificity (P> 0.05). In the FN group, empiric antibiotic treatment of 46/102 (45.10%) patients did not treat all the pathogens detected by mNGS. After adjusting the antimicrobial regimen according to the results of mNGS, the effective rate at 72 hours and 7 days was 22/46 (47.83%) and 24/102 (52.17%), respectively.Conclusion: mNGS had a significant impact on the diagnosis of infection and the second-line antimicrobial therapy in FN. mNGS plays a more important role in FN patients, especially in the diagnosis of fungal infections.Purpose: Firstly, we compared the difference between mNGS and the traditional methods in the diagnosis of infection. Secondly, we assessed the value of mNGS in FN patients by comparing it with non-FN patients, including types of pathogens and the diagnostic value of different pathogens. In order to show that mNGS plays a more important role in FN.Keywords: metagenomic next-generation sequencing, febrile neutropenia, infection, fever, empiric antibiotic treatment

Miaomiao Zhao,1,2 Longbing Ren,3 Zhitong Zhou,3 Tao Wang,3 Jue Li2 1School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 2Department of Epidemiology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Institute of Clinical Epidemiology and Evidence-Based Medicine, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jue Li, Department of Epidemiology, Tongji Hospital Affiliated to Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200442, People’s Republic of China, Tel +86-21-65986735, Fax +86-21-65980448, Email jueli@tongji.edu.cnPurpose: The effects of statins on renal outcomes have already been studied in patients with chronic kidney disease (CKD); however, data on the general population are limited. We evaluated the association between statin use and risk of CKD in community-dwelling older people in Shanghai, China.Patients and Methods: This registry-based cohort study was conducted in four communities in four districts in Shanghai. Participants with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 in 2016 were eligible for the study, and new-onset CKD in 2017, 2018, and 2019 was recorded. Poisson generalized linear models were conducted to examine the relationships among statin therapy, dyslipidemia, and CKD; linear mixed-effects models were conducted to examine the relationships between statin therapy and changes in eGFR. All analyses were performed with both conventional adjustment and propensity score-matching methods.Results: Of the study cohort of 2455 participants (41.1% men; average age, 68.06 years), 624 (25.4%) were treated with stains. Two propensity score-matched cohorts of 604 participants each were analyzed (statin users and nonusers). Statin use was significantly associated with a decreased risk of new-onset CKD with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.73 (0.59 to 0.91) (p< 0.01) in the unmatched cohort and 0.75 (0.59 to 0.97) (p=0.02) in the matched cohort. There were significant differences in the eGFR decline between statin users and nonusers from baseline to 3 years in the unmatched and matched cohorts (both p< 0.05). In addition, both statin users and nonusers with dyslipidemia experienced more new-onset CKD (both p< 0.05).Conclusion: Statin use was significantly associated with a decreased risk of new-onset CKD and a slower decline in eGFR in community-dwelling older people. Meanwhile, dyslipidemia was a risk factor for CKD progression among both statin users and nonusers.Keywords: chronic kidney disease, statins, dyslipidemia, community-dwelling older people