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Chang Tang,1,2,* Lanting Wang,1,2,* Zihua Chen,1,2,* Jin Yang,1,2 Haiqing Gao,1,2 Chenggong Guan,1,2 Qiaozhi Gu,1,2 Shan He,1,2 Fanping Yang,1,2 Shengan Chen,1,2 Li Ma,1,2 Zhen Zhang,1,2 Ying Zhao,1,2 Lin Tang,1,2 Yu Xu,1,2 Yue Hu,3 Xiaoqun Luo1,2 1Department of Allergy & Immunology, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqun Luo, 12 Wulumuqi Zhong Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86 13918825230, Email luoxiaoqun913@126.comPurpose: Several in vivo experiments have shown that molecular hydrogen is a promising therapeutic agent for interstitial lung diseases (ILD). In this study, hydrogen therapy was investigated to determine whether it is superior to N-Acetylcysteine (NAC) for the treatment of patients with early-stage ILD.Patients and Methods: A prospective, single-center, randomized, controlled clinical trial was conducted in 87 patients with early-stage ILD. Hydrogen or NAC therapy was randomly assigned (1:1 ratio) to the eligible patients. The primary endpoint was the change in the high-resolution computed tomography (HRCT) and composite physiologic index (CPI) scores from baseline to week 48. Pulmonary function was evaluated as a secondary endpoint, and adverse events were recorded for safety analysis.Results: The rate of HRCT image improvement from the baseline in the HW group (63.6%) was higher than that in the NAC group (39.5%). A significant decrease in CPI and improvement in DLCO-sb were observed in the hydrogen group compared with those in the control group. Changes in other pulmonary function parameters, including FVC, FEV1, FEV1/FVC%, and TLC, were not significantly different between the two groups. Adverse events were reported in 7 (15.9%) patients in the HW group and 10 (23.3%) patients in the NAC group, but the difference was not significant (P=0.706).Conclusion: Hydrogen therapy exhibits superior efficacy and acceptable safety compared with NAC therapy in patients with early-stage ILD.Keywords: hydrogen, N-acetylcysteine, interstitial lung disease, therapeutic effects

Yan Liu, Song Yuan, Li-Yi Wang, Si Chen, Yang Li, Wei Ma Department of Infection Control, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Wei Ma, Department of Infection Control, The Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Shijiazhuang, 050000, People’s Republic of China, Tel +86-18603297270, Fax +86 (311) 66007439, Email maweimmw6@126.comObjective: The objective of this study is to examine the qualification rate of hand disinfection in the surgical department wards and analyze the influencing factors.Methods: A surprise assessment was carried out to evaluate the daily adherence to hand hygiene protocols in the surgical department wards. We aimed to investigate the factors that impact the qualification rate of hand disinfection.Results: In this study, the qualification rate of hand disinfection was determined to be 64.38%. Notably, this rate exhibited significant variations based on gender, age, surgical site, and department category. Specifically, the qualification rate of hand disinfection among female participants stood at 82.35%, surpassing the qualification rate observed among male counterparts of 52.83%. Furthermore, doctors in the age group of 41– 50 years demonstrated the highest qualification rate, and the abdominal surgical site exhibited the most noteworthy qualification rate, reaching 79.49%. The outcomes of the multiple logistic regression analysis highlighted the significance of age and gender as influential factors impacting the qualification rate. Specifically, doctors aged 51 years or older exhibited the lowest hand hygiene compliance, whereas female doctors demonstrated a notably higher qualification rate compared to their male counterparts.Conclusion: The disheartening qualification rate of hand disinfection highlights a concerning lack of awareness regarding hand hygiene among surgeons in their professional duties. Consequently, targeted interventions are imperative, focusing on intensified training, educational initiatives, enhanced supervision, and internal performance evaluations for key groups. The findings not only serve as a valuable database but also offer a viable roadmap for similar hospitals to reinforce the management of nosocomial infections.Keywords: hand hygiene, hand disinfection, influencing factors, qualification rate, surgeons

Yijie Wang,1,* Weixiang Weng,2,* Ruiming Liang,3,* Qian Zhou,3 Hangtong Hu,4 Mingde Li,4 Lida Chen,4 Shuling Chen,4 Sui Peng,1,3 Ming Kuang,2,4,5 Han Xiao,6 Wei Wang4 1Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Clinical Trials Unit, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 5Cancer Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 6Department of Medical Ultrasonics, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Han Xiao, Department of Medical Ultrasonics, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China, Tel/Fax +86-20-87755766-8576, Email xiaoh69@mail.sysu.edu.cn Wei Wang, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China, Tel/Fax +86-20-87755766-8576, Email wangw73@mail.sysu.edu.cnPurpose: The T cell-inflamed gene expression profile (GEP) quantifies 18 genes’ expression indicative of a T-cell immune tumor microenvironment, playing a crucial role in the immunotherapy of hepatocellular carcinoma (HCC). Our study aims to develop a radiomics-based machine learning model using contrast-enhanced ultrasound (CEUS) for predicting T cell-inflamed GEP in HCC.Methods: The primary cohort of HCC patients with preoperative CEUS and RNA sequencing data of tumor tissues at the single center was used to construct the model. A total of 5936 radiomics features were extracted from the regions of interest in representative images of each phase, and the least absolute shrinkage and selection operator and logistic regression were used to construct four models including three phase-specific models and an integrated model. The area under the curve (AUC) was calculated to evaluate the performance of the model. The independent cohort of HCC patients with preoperative CEUS and Immunoscore based on immunohistochemistry and digital pathology was used to validate the correlation between model prediction value and T-cell infiltration.Results: There were 268 patients enrolled in the primary cohort and 46 patients enrolled in the independent cohort. Compared with the other three models, the AP model constructed by 36 arterial phase (AP) features showed good performance with a mean AUC of 0.905 in the 5-fold cross-validation and was easier to apply in the clinical setting. The decision curve and calibration curve confirmed the clinical utility of the model. In the independent cohort, patients with high Immunoscores showed significantly higher GEP prediction values than those with low Immunoscores (t=− 2.359, p=0.029).Conclusion: The CEUS-based model is a reliable predictive tool for T cell-inflamed GEP in HCC, and might facilitate individualized immunotherapy decision-making.Keywords: Radiomics, Contrast-enhanced ultrasound, Hepatocellular carcinoma, T cell-inflamed gene expression profile

Chuangjia Huang,1,2,* Yu Zhang,3,* Jianfen Su,1,2,* Xiaoling Guan,1,2 Sheng Chen,1,2 Xiaowei Xu,1,2 Xiaohua Deng,1,2 Lingmin Zhang,1,2 Jionghua Huang1 1Department of Cardiology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China; 2Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jionghua Huang; Lingmin Zhang, Email mdhjh2014@126.com; zhanglm@gzhmu.edu.cnBackground: High-level low-density lipoprotein cholesterol (LDL-C) plays a vital role in the development of atherosclerotic cardiovascular disease. Low-density lipoprotein receptors (LDLRs) are scavengers that bind to LDL-C in the liver. LDLR proteins are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), which mediates the degradation of LDLR and adjusts the level of the plasma LDL-C. The low expression of PCSK9 leads to the up-regulation of liver LDLRs and the reduction of plasma LDL-C. Hepatocytes are attractive targets for small interfering RNA (siRNA) delivery to silence Pcsk9 gene, due to their significant role in LDL-C regulation.Methods: Here, a type of liver-specific ionizable lipid nanoparticles is developed for efficient siRNA delivery. This type of nanoparticles shows high stability, enabling efficient cargo delivery specifically to hepatocytes, and a membrane-active polymer that reversibly masks activity until an acidic environment is reached.Results: Significantly, the siPcsk9 (siRNA targeting to Pcsk9)-loaded nanoparticles (GLP) could silence 90% of the Pcsk9 mRNA in vitro. In vivo study showed that the improved accumulation of GLP in the liver increased LDLR level by 3.35-fold and decreased plasma LDL-C by 35%.Conclusion: GLP has shown a powerful effect on reducing LDL-C, thus providing a potential therapy for atherosclerotic cardiovascular disease. Keywords: ionizable lipid nanoparticles, bad cholesterol, PCSK9, small interfering RNA, liver-specific delivery

Gang Chen,1– 3 Lei Li,2,4 Taipeng Sun,1– 3 Chenguang Jiang,1,2 Wei Xu,1,2 Suzhen Chen,1,2 Changchun Hu,1 Yingying Yue,1,2 Tianyu Wang,1,2 Wenhao Jiang,1,2 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Institute of Psychosomatics, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Medical Psychology, Huai’an NO 3 People’s Hospital, Huaian, People’s Republic of China; 4Department of Sleep Medicine, The Fourth People’s Hospital of Lianyungang, Lianyungang, People’s Republic of ChinaCorrespondence: Wenhao Jiang; Yonggui Yuan, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Gulou District, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86-25-83285124, Email wjiang43@outlook.com; yygylh2000@sina.comBackground: Depression is a heritable brain disorder. Laminin genes were recently identified to affect the brain’s overall thickness through neurogenesis, differentiation, and migration in depression. This study aims to explore the effects of the LAMA2’s single nucleotide polymorphisms (SNP), a subunit gene of laminin, on the detected brain regions of patients with major depressive disorder (MDD).Methods: The study included 89 patients with MDD and 60 healthy controls with T1-weighted structural magnetic resonance imaging and blood samples for genotyping. The interactions between LAMA2 gene SNPs and diagnosis as well as duration of illness (DOI) were explored on brain measures controlled for age, gender, and site.Results: The right transverse temporal gyrus and right parahippocampal gyrus showed reduced thickness in MDD. Almost all seven LAMA2 SNPs showed significant interactions with diagnosis on both gyrus (corrected p < 0.05 or trending). In MDD, rs6569604, rs2229848, rs2229849, rs2229850, and rs2784895 interacted with DOI on the right transverse temporal gyrus (corrected p < 0.05), but not the right parahippocampal gyrus.Conclusion: The thickness of the right transverse temporal gyrus in patients with MDD may be affected by LAMA2 gene and DOI.Keywords: major depressive disorder, right transverse temporal gyrus, LAMA2, interaction

Yinshan Lin,1,2,&ast; Xiaoling Guan,1,2,&ast; Jianfen Su,1,2,&ast; Sheng Chen,2 Xihua Fu,1 Xiaowei Xu,2 Xiaohua Deng,2 Jishuo Chang,2 Aiping Qin,2,&ast; Ao Shen,2,&ast; Lingmin Zhang1,2,&ast; 1Pharmacy Department & Panyu Institute of Infectious Diseases, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, 511400, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingmin Zhang, Guangzhou Panyu Central Hospital, No. 8 Fuyu East Road, Guangzhou, Guangdong, 511400, People’s Republic of China, Email zhanglm@gzhmu.edu.cn Ao Shen; Aiping Qin, Guangzhou Medical University, No. 1 Xinzao Road, Guangzhou, Guangdong, 511426, People’s Republic of China, Email shenao@gzhmu.edu.cn; qinaiping_2008@163.comAbstract: Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery. Keywords: nucleic acids, bioinspired nanoparticles, non-viral vehicles, gene therapy, cell membranes

Zhuoya Jia,1,2 Xiaoyu Pan,1,2 Shuchun Chen2,3 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Key Laboratory of Metabolic Diseases of Hebei Province, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comObjective: To explore the association between levels of remnant cholesterol (RC) and the incidence of non-alcoholic fatty liver disease (NAFLD) in the general population, ultimately leading to the assessment of a novel proposed model combining RC and waist circumference (R-W) as a predictor of NAFLD incidence.Methods: A cross-sectional analysis was conducted of 4913 subjects undergoing physical examinations at Hebei General Hospital, with ultrasound findings being used to classify patients into individuals with and without NAFLD. Median RC values were used to separate subjects into those with low and high levels of RC, after which the predictive performance of RC and the novel R-W model when used to assess NAFLD risk was assessed through multifactorial logistic regression analyses and receiver operating characteristic curves.Results: Subjects exhibiting higher RC levels were found to exhibit an elevated risk of NAFLD incidence with or without adjusting for confounding factors. The binary logistic regression analysis-based R-W model may thus offer utility as a tool to gauge the risk of NAFLD in the general population, as it outperformed RC or WC alone, particularly when assessing women or individuals < 45 years of age. The area under the ROC curve for this combined R-W model was 0.813 (0.802, 0.824), with respective sensitivity and specificity values of 83.86% and 63.91%, all of which were significantly higher than corresponding values for RC and WC (P < 0.001).Conclusion: The present supports a strong association between RC levels and NAFLD in the general populace, and the combined R-W model exhibits greater utility as a tool to predict NAFLD incidence relative to RC or WC in isolation, particularly for individuals who are female or < 45 years old.Keywords: residual cholesterol, waist circumference, non-alcoholic fatty liver disease

Yan Chen, Shengyue Chen, Yuanyuan Han, Qing Xu, Xin Zhao Department of Cardiology, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Xin Zhao, Department of Cardiology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, People’s Republic of China, Tel +86-0411-84671291, Email zx81830@163.comBackground: Apolipoprotein B/apolipoprotein A-1 (apoB/apoA-1) has been shown to be strongly associated with the risk of future cardiovascular disease, but the association between apoB/apoA-1 and the risk of in-hospital death in elderly patients with acute myocardial infarction(AMI) is inconclusive.Aim: To investigate the association between apoB/apoA-1 and the risk of in-hospital death in elderly patients with AMI.Methods: From December 2015 to December 2021, a total of 1495 elderly AMI patients (aged ≥ 60 years) with complete clinical history data were enrolled in the Second Hospital of Dalian Medical University. Outcome was defined as all-cause mortality during hospitalization. Multivariate logistic regression and restricted spline cubic (RCS) models were used to evaluate the association between apoB/apoA-1 and in-hospital mortality risk, respectively. Receiver operating characteristic(ROC) curves were used to evaluate the predictive value of apoB/apoA-1 for in-hospital mortality events. Discordance analysis was performed when apoB/apoA-1 and LDL-C/HDL-C were not in concordance.Results: (1) A total of 128 patients (8.6%) died during hospitalization. Patients in the death group had higher apoB/apoA-1 than those in the non-death group, but lower apoA-1 levels than those in the non-death group, and the difference was statistically significant (P < 0.05); (2) Multivariate logistic regression analysis showed that apoB/apoA-1 was associated with the risk of in-hospital death in elderly AMI patients [Model 3 OR = 3.524 (1.622– 7.659), P = 0.001]; (3) ROC curve analysis showed that apoB/apoA-1 (AUC = 0.572, P = 0.011) had some predictive value for the risk of in-hospital death in elderly AMI patients; (4) RCS models showed a linear dose-response relationship between apoB/apoA-1 and in-hospital death after adjusting for confounders (P for non-linearity = 0.762).Conclusion: ApoB/apoA-1 is associated with the risk of in-hospital death in elderly patients with AMI, and is superior to other blood lipid parameters and blood lipid ratio.Keywords: elderly, apolipoprotein, acute myocardial infarction, in-hospital death, restricted cubic splines

Shuying Rao,1 Chuanzhi Xu,2 Chonghua Wan,1 Zhiwen Huang,3 Xingping Huang,4 Shu Chen1 1Research Center for Quality of Life and Applied Psychology, School of Humanities and Management, Guangdong Medical University, Dongguan, People’s Republic of China; 2Department of Statistics, School of Public Health, Kunming Medical University, Kunming, People’s Republic of China; 3Cardiovascular Department, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China; 4Department of Research and Teaching, Dongguan Eighth’ Hospital, Dongguan, People’s Republic of ChinaCorrespondence: Chonghua Wan, Tel/Fax +86-0769-22896255, Email wanchh@hotmail.comPurpose: Coronary heart disease (CHD) is difficult to cure, so more attention should be paid to improving patients’ health-related quality of life (HRQoL). This paper focuses on identifying factors that affect HRQoL.Patients and Methods: Overall, 189 in-patients with coronary heart disease were investigated at the Affiliated Hospital of Guangdong Medical University between 2015 and 2016. The scale Quality of Life Instruments for Chronic Diseases-Coronary heart disease (QLICD-CHD V2.0) was used to evaluate HRQoL and collect demographic information. Medical records were applied to collect patients’ clinical indicators. A simple correlation analysis, Student’s t-test, and a one-way analysis of variance were first performed to filter factors that might associate with HRQoL, and multiple linear regression was applied to finally identify related factors.Results: Findings from multiple linear regression showed that the total score was related to family economy, treatment, indirect bilirubin, and albumin with regression coefficient B=5.209, − 6.615, 0.378, and 0.548, respectively. The physical functions were related to treatment, albumin, globular proteins, chloride, and red blood cell count with B=− 9.031, 1.000, 0.612, 1.320, and 5.161, respectively. The psychological function was in association with family economy, clinical course, serum phosphorus, and percentage of lymphocyte population with B=7.487, 6.411, − 16.458, and 0.090, respectively. The social function was associated with family economy, blood urea nitrogen, serum creatinine, and platelet distribution width with B=7.391, 1.331, − 0.060, and − 0.929, respectively. The special module was in association with treatment, indirect bilirubin, and serum calcium with B=− 7.791, 0.414, and 23.017, respectively.Conclusion: Clinical indicators including albumin, globular proteins, chloride, red blood cell count, serum phosphorus, percentage of lymphocyte population, blood urea nitrogen, serum creatinine, platelet distribution width, indirect bilirubin, and serum calcium, as well as socio-demographic factors including the family economy, clinical course, and treatment, may affect coronary heart disease patients’ HRQoL.Keywords: quality of life, coronary heart disease, socio-demographic factors, clinical indicators, scale

Mingdong He,1,&ast; Jun Yu,1,&ast; Shaohua Chen,2 Hua Mi1 1Department of Urology, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Urology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Mi; Shaohua Chen, Email mihua2019@163.com; silverchan1994@163.comBackground: The cluster of differentiation 48 (CD48) is a member of the signaling lymphocyte activation molecule family, constitutively expressed on most hematopoietic cells. CD48 was reported to affect immune regulation in certain tumors, thereby influencing tumor development and prognosis, but its impact on the prognosis and immune infiltration in pan-cancer remains unclear.Material and Methods: We systematically analyzed the raw data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), and Tumor Immune Dysfunction and Exclusion (TIDE) databases. Initially, we investigated the differences in CD48 expression between pan-cancer and adjacent normal tissues. Then, the correlation analysis of CD48 with tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), and immune-related genes was evaluated. Moreover, bioinformatics tools: ESTIMATE and gene set enrichment analysis (GSEA) were used for tumor immunology analysis in pan-cancer. We performed validation studies including quantitative real-time PCR (qPCR) and Western blotting.Results: Differential analysis revealed that CD48 was significantly altered in pan-cancer as compared with normal tissues. Meanwhile, the survival analysis demonstrated that CD48 strongly correlated with overall survival (OS), disease-free interval (DFI), progression-free interval (PFI), and disease-specific survival (DSS), indicating its crucial role in the tumor patients’ prognosis. CD48 expression was also associated with TMB and MSI levels in 17 and 14 types of pan-cancers, respectively. Moreover, CD48 was linked to immune infiltrating cells and stromal components in the TME.Conclusion: Concludingly, patients with pan-cancer may benefit from evaluating CD48 as a prognostic and immunotherapy response biomarker.Keywords: CD48, pan-cancer, immunotherapy, tumor microenvironment

Shimin Chen,1– 4 Long Zhang,1– 4 Yukun Chen,1– 4 Xuzhi Zhang,1– 4 Yi Ma1– 4 1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 4Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Xuzhi Zhang; Yi Ma, Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86 13112274921, Email zhxuzh@foxmail.com; anhuimayi2002@163.comAbstract: Hepatocellular carcinoma (HCC) is among the most prevalent and dangerous cancers in the world, which is associated with hepatitis and fibrosis resulting from different etiologies, such as hepatitis B and C virus, alcohol and diabetes. Chronic inflammation is suggested to promote tumorigenesis and progression by producing inflammatory cytokines and free radicals, triggering malignant transformation of cells, promoting tumor cells proliferation and inducing tumor angiogenesis. Immunosuppressive microenvironment established in the liver also plays a vital role in HCC development. The mechanisms include activation of cancer-associated fibroblasts, upregulation of pattern recognition receptors, inhibition of effector T cells, recruitment of regulatory T cells and myeloid-derived suppressor cells, activation of hepatic stellate cells and immunosuppressive M2 macrophages. In this review, we will summarize the most recent studies and discuss the advanced mechanisms of chronic inflammatory microenvironment and immunosuppressive microenvironment promoting HCC development, aiming to explore potential therapeutic targets.Keywords: chronic inflammation, immunosuppression, tumor microenvironment, hepatocellular carcinoma

Qian Cai,1 Sirui Chen,2 Yingqun Zhu,1 Zhe Li1 1Department of Respiratory and Critical Care Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 410015, People’s Republic of China; 2Department of Emergency Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 410015, People’s Republic of ChinaCorrespondence: Sirui Chen, Department of Emergency Medicine, The Third Hospital of Changsha, No. 176, Laodong West Road, Tianxin District, Changsha City, Hunan Province, 410015, People’s Republic of China, Tel +86-0731-85171616, Email realcsr@163.comBackground: Chronic obstructive pulmonary disease (COPD) is a persistent chronic bronchitis disease, and its potential biomarkers have not been fully expounded. This study aims to explore the role of Guanine nucleotide binding protein like-3-like (GNL3L) in COPD induced by cigarette smoking (CS) in vivo.Methods: Two microarray datasets of COPD were selected to screen differentially expressed genes (DEGs). A protein–protein interaction network was constructed to find hub genes. The COPD model was conducted using CS/LPS-induced mouse and cigarette smoke extract induced human bronchial epithelial cells. The pathological changes of lung tissue in mice were observed by hematoxylin–eosin staining and mean linear intercept. Cell viability was measured by CCK8 assay. Oxidative stress-related indicators, inflammatory factors, and ATM/p53 related-proteins were assessed using ELISA and Western blot.Results: In this study, there were 110 common DEGs identified from the two datasets (GSE5058 and GSE38974). The key gene GNL3L was the optimal indicator to distinguish between samples with COPD and healthy controls. Through the in vivo and in vitro experiments, GNL3L knockdown significantly improved the pathological features of CS/LPS-induced COPD mice, promoted cell viability, inhibited inflammation (IL-1β, IL-8, and TNF-α), oxidative stress (MDA, SOD, and CAT), and ATM/p53 related-proteins (ATM, p53, and p21).Conclusion: GNL3L is a novel biomarker of COPD, and knockdown of GNL3L participates in the progression of COPD by inhibiting ATM/p53 pathway.Keywords: COPD, ATM/p53 pathway, hub genes, GNL3L

Shuqi Wang,1,2 Xiaoyu Pan,1,2 Boying Jia,1,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuchunwork88@163.comPurpose: Systemic immune inflammation index (SII), systemic inflammatory response index (SIRI) are new inflammation indicators calculated after integrating multiple indicators in blood routine. This study aims to investigate the correlation between the SII, SIRI and type 2 diabetic retinopathy (T2DR) and the diagnostic significance of these indices in T2DR.Patients and Methods: A retrospective analysis involved 500 patients diagnosed with type 2 diabetes (T2DM), categorized into two groups based on fundus examination results: the non-diabetic retinopathy group (NDR, n=256) and the diabetic retinopathy group (DR, n=244). We calculated SII and SIRI, and analyzed their associations with T2DR.Results: The DR group exhibited significantly higher SII and SIRI values compared to the NDR group (P< 0.001). Mantel-Haenszel’s chi-square trend analysis revealed a notable linear trend (P< 0.001) between SII, SIRI, and DR. SII and SIRI exhibited moderate positive correlations with DR, (r=0.354, P< 0.001; r=0.469, P< 0.001), respectively. Binary logistic regression analysis identified SII and SIRI as independent risk factors for DR. Restrictive cubic spline analysis demonstrated a significant linear relationship between SII and DR (P total trend < 0.001, P nonlinear = 0.0657). Stratification by gender indicated that SII is more sensitive to the onset of DR in men. A significant nonlinear relationship was observed between SIRI and DR (P total trend < 0.001, P nonlinear = 0.0025), with no gender-related differences in SIRI’s association with DR. ROC curve analysis demonstrated that the combined use of SII and SIRI achieved the highest diagnostic accuracy for DR, with an AUC of 0.782, 74.6% sensitivity, and 69.9% specificity.Conclusion: Our findings suggested that SII and SIRI as independent risk factors for DR. The high accuracy of SII combined with SIRI in diagnosing DR underscores their potential as early biological indicators for DR diagnosis.Keywords: systemic immune inflammation index, system inflammatory response index, type 2 diabetic retinopathy, Inflammation

Lihua Lin,1,&ast; Juan Lin,2,&ast; Fang Yang,2 Shouzhen Chen,2 Zhaozhen Liu2 1Department of Healthcare, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaozhen Liu, Department of Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13515001752, Email fjsfcliuzz@163.comBackground: To evaluate the association of the baseline triglyceride-glucose (TyG) index in the first trimester of pregnancy with the risk of large for gestational age (LGA) in Southeast Chinese pregnant women.Methods: A prospective birth cohort study recruiting 12,108 pregnant women at their first prenatal visit before 13 gestation weeks was conducted in 2019– 2022. Baseline characteristics were collected from medical records or using questionnaires and blood samples were collected in the first trimester. The TyG index was obtained through the formula: ln[triglyceride (mg/dl)×fasting plasma glucose (mg/dl)/2]. The binary logistic regression model was performed to calculate the odds ratio (OR) and 95% confidence intervals (CI) to reveal the relationship between TyG index and LGA. Receiver-operating characteristic curve analysis was conducted to evaluate the ability of the TyG index to predict the risks of LGA.Results: The overall incidence of LGA in the current study was 11.4% and the incidence of LGA increased with the baseline TyG index increasing. The risk of LGA was 2.05 (1.64, 2.57) for per unit increase in baseline TyG index. The increasing trend was found across the TyG index quartiles and the highest TyG quartiles raised the risk of LGA to 1.86 (95% CI: 1.51, 2.27) compared to the bottom TyG quartiles after full adjustment. The risk of LGA remained positive after stratification analysis. The AUC was 0.584 (95% CI: 0.569~0.600) in the entire subject, and the threshold was 8.34, with a sensitivity of 0.74 and specificity of 0.38.Conclusion: The findings suggested that a higher TyG index in the first trimester was independently associated with higher risk of LGA and high TyG index in the first trimester may play as a early predictor for LGA.Keywords: triglyceride-glucose index, large for gestational age, first trimester

Han-Ze Du,1,&ast; Kang Chen,1,&ast; Li-Yuan Zhang,1,&ast; Yue-Lun Zhang,2 Dan-Ning Wu,1 Xiao-Yuan Guo,1 Lian Duan,1 Lin-Jie Wang,1 Hong-Bo Yang,1 Shi Chen,1 Hui Pan,1 Hui-Juan Zhu1 1Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People’s Republic of China; 2Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Pan; Hui-Juan Zhu, Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Email panhui20111111@163.com; shengxin2004@163.comContext: The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients.Objective: To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement.Methods: Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy.Results: Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (− 0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement.Conclusion: The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.Keywords: craniopharyngioma, dyslipidemias, obesity, human growth hormone, hypothalamic obesity

Shengchen Chen,1 Weihua Wang2 1School of Business Administration, Gyeongsang National University, Jinju, South Korea; 2School of Business Administration, Anhui University of Finance and Economics, Bengbu, People’s Republic of ChinaCorrespondence: Weihua Wang, School of Business Administration, Anhui University of Finance and Economics, Bengbu, People’s Republic of China, Tel +86-552-3171001, Fax +86-552-3175978, Email wwh1999@live.cnPurpose: The objective of this study is to investigate the underlying mechanism connecting internet addiction and academic anxiety, with the aim of assisting higher education professionals and administrators in developing comprehensive solutions to effectively mitigate the systemic risks associated with these issues.Patients and Methods: This study utilizes the smart data collection instrument of Wenjuanxing to gather data from 270 Chinese college students through an online questionnaire survey. Through building and analyzing a structural equation model that consists of four latent variables, such as internet addiction, relational psychological contract, transactional psychological contract, and academic anxiety. The study analyzed the fundamental characteristics of the transformation mechanism of Internet addiction and academic anxiety. It specifically focused on conducting a mediating effects test of the psychological contract variable to validate the significant role of both relational psychological contract and transactional psychological contract in this transformation mechanism.Results: First, the study found that internet addiction (β=0.094; p=0.179) cannot directly impact academic anxiety. It can only influence academic anxiety through the mediating effects of the relational psychological contract (β=0.088; p=0.022) and the transactional psychological contract (β=0.123; p=0.003), with the latter having a more significant impact. Second, the destructive effect of Internet addiction on relational psychological contracts (β=− 0.496; p< 0.001) is greater than that on transactional psychological contracts (β=− 0.476; p< 0.001). Third, compared to the weakening of the relational psychological contract (β=− 0.177; p=0.017), the weakening of the transactional psychological contract (β=− 0.258; p=0.001) has a more significant impact on college students’ academic anxiety.Conclusion: This study shows that the weakening of the corresponding psychological contract is the key link for the development of Internet addiction into academic anxiety. Stabilizing the psychological contracts at the psychological level of college students can help suppress the vicious transformation process from internet addiction to academic anxiety, ensuring students’ mental health and reducing systemic risks in educational work.Keywords: internet addiction, academic anxiety, customer satisfaction, relational psychological contract, transactional psychological contract

Wan Chen,1,&ast; Mingyu Pei,1,&ast; Chunxia Chen,2,&ast; Bo Wang,1,&ast; Lei Shi,1,&ast; Guozheng Qiu,1 Wenlong Duan,1 Shengxin Chen,1 Qiao Wei,1 Xi Zeng,1 Huifeng Pang,1 Yanlin Wei,1 Ruihua Wu,1 Ruikai Zhu,1 Qingwei Ji,3 Liwen Lyu1 1Department of Emergency, the People’s Hospital of Guangxi Zhuang Autonomous Region& Research Center of Cardiovascular Disease, Guang Xi Academy of Medical Sciences, Nanning, People’s Republic of China; 2Department of Pharmacy, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 3Department of Cardiovascular Medicine, The People’s Hospital of Guang Xi Zhuang Autonomous Region& Research Center of Cardiovascular Disease, Guangxi Academy of Medical Sciences Nanning, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liwen Lyu, Department of Emergency, The People’s Hospital of Guangxi Zhuang Autonomous Region, Research Center of Cardiovascular Disease, Guangxi Academy of Medical Sciences, Nanning, 530021, People’s Republic of China, Email iculvliwen@163.com Qingwei Ji, Department of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Research Center of Cardiovascular Disease, Guangxi Academy of Medical Sciences Nanning, Nanning, 530021, People’s Republic of China, Email gxqyyjzk@163.comObjective: The incidence of cardiogenic shock cases treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been on the rise. Acute kidney injury (AKI) is a significant complication of cardiogenic shock and a frequent serious complication in patients requiring ECMO-supported therapy. AKI is strongly associated with unfavorable patient prognosis. However, there is a paucity of data on the influence of AKI on the prognosis of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) who are receiving ECMO support, particularly with regard to long-term outcomes.Methods: This retrospective observational study included 103 patients in the People’s Hospital of Guangxi Zhuang Autonomous Region from January 2017 and June 2022. AKI was defined according to Kidney Disease Improving Global Outcome (KDIGO) criteria. Cox regression and logistic regression were used to identify risk factors.Results: In this study, the incidence of AKI was 63.11%, with AKI stage 1, 2, and 3 accounting for 21.36%, 12.62%, and 29.13%, respectively. Patients with severe AKI had significantly higher in-hospital mortality (43.33% vs 27.40%, P < 0.001), 30-day mortality (60.00% vs 31.51%, P = 0.001), and 1-year mortality (63.67% vs 34.25%, P< 0.001) than those without severe AKI. Furthermore, severe AKI significantly increased the risk of one-year mortality (HR 10.816, CI 3.118– 37.512, P< 0.001). Baseline serum creatinine, baseline platelet, and active cardiopulmonary resuscitation were independent predictors of one-year mortality. In addition, baseline white blood cell count, baseline aspartate aminotransferase, baseline alanine aminotransferase (ALT), baseline serum creatinine, preoperative lactate, and postoperative mean arterial pressure were independent risk factors of severe AKI during hospitalization.Conclusion: In patients with AMI-CS receiving ECMO support, AKI is highly prevalent. Development of severe AKI significantly increased the risk of one-year mortality.Keywords: acute kidney injury, extracorporeal membrane oxygenation, prognosis, risk factors

Sijian Chen,1,2 Honghe Li,1 Deliang Wen1 1Institute for International Health Professions Education and Research, China Medical University, Shenyang, People’s Republic of China; 2School of Nursing, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Deliang Wen, Institute for International Health Professions Education and Research, China Medical University, No. 77 Puhe Road, Shenyang, Liaoning, 110122, People’s Republic of China, Email dlwen@cmu.edu.cnBackground: Sleep problems have become a serious threat to public health worldwide. Daytime sleepiness is an important indicator of many sleep problems, which have a significant impact on academic performance, physical and mental health, and wellbeing among medical students. We aimed to explore the factors associated with daytime sleepiness among medical students.Methods: We conducted a cross-sectional survey of 466 medical students recruited via convenience sampling. Self-rated psychometric scales, including the Social Support Rate Scale, the Epworth Sleepiness Scale, the Chinese version of the UCLA loneliness scale, and the Mobile Phone Addiction Index (MPAI), were utilized to evaluate social support, daytime sleepiness, loneliness, and problematic smartphone use. A sequential mediation model was constructed with daytime sleepiness as the dependent variable, social support as the independent variable, and loneliness and problematic smartphone use as mediating variables. Age, gender, and grade were taken as covariates.Results: Social support among medical students was negatively associated with loneliness, problematic smartphone use, and daytime sleepiness (p < 0.01). A sequential mediation analysis showed that loneliness (the first mediator) and problematic smartphone use (the second mediator) sequentially mediated the path from social support to daytime sleepiness among medical students (β = − 0.008; 95% CI = − 0.016, − 0.002). Moreover, there were also significant mediating roles observed in the relationship between social support and daytime sleepiness via loneliness only (β = − 0.037; 95% CI = − 0.062, − 0.015) and problematic smartphone use only (β = − 0.022; 95% CI = − 0.041, − 0.008).Conclusion: Social support, loneliness, and problematic smartphone use among medical students influenced their daytime sleepiness. Interventions targeting medical student loneliness and problematic smartphone use behaviors might attenuate the effects from low levels of social support and further improve daytime sleepiness.Keywords: social support, daytime sleepiness, loneliness, problematic smartphone use

Shanshan Chen,1,2,&ast; Youjia Duan,2,&ast; Yongchao Zhang,2 Long Cheng,2 Liang Cai,2 Xiaopu Hou,2 Wei Li1,2 1Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Cancer Center, Beijing Tongren Hospital, Capital Medical University, 2 West Ring South Road, Daxing District, Beijing, 100176, People’s Republic of China, Tel +86 15811029005, Email weili8989@ccmu.edu.cnPurpose: Tumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated.Patients and Methods: Peripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis.Results: A total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule.Conclusion: The polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.Keywords: single nucleotide polymorphism, hypoxia, capsule formation, hepatocellular carcinoma

Shasha Zhang,1,&ast; Jinchun Li,2,&ast; Li Wan,1 Jing Yu,2 Sumei Chen,2 Zhengjiang Jin3 1Department of Pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 2Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 3Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengjiang Jin, Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China, Email king199735@126.comPurpose: To determine the clinical features, laboratory findings, antibiotic treatment, and outcomes of neonatal listeriosis in a specialized tertiary hospital in Wuhan, China.Patients and Methods: We retrospectively analyzed the medical records of patients diagnosed with neonatal listeriosis at Maternal and Child Health Hospital of Hubei Province from January 2015 to December 2022. Listeriosis was indicated by positive culture for Listeria monocytogenes (LM).Results: A total of 11 cases were included in our study. The incidence rate of neonatal listeriosis was 2.06 per 100,000 live births. Seventy-three percent of the cases were born prematurely, caused early onset sepsis. Respiratory distress (100%) was the most common and earliest symptom, followed by fever (64%) and rashes (27%). The levels of C-reactive protein (CRP) and procalcitonin (PCT) were elevated in 100% of the cases. The median time-to-positivity (TTP) of the culture was 15 hours (range 9– 28hours). Of the 11 neonates, 6 were cured, 2 showed improvement, and 3 died, with a mortality rate of 27%. There were statistically significant differences in Apgar score at 5 minutes (p=0.037) and CRP (p=0.025) between the survival group and fatality group. Ampicillin was sensitive to LM isolates and effective for therapy if initiated early.Conclusion: Neonatal listeriosis is a rare but severe infection with a high mortality rate. Early identification and appropriate use of effective antibiotics are particularly critical for achieving positive outcomes. Apgar score and CRP are relevant indices for prognosis. Ampicillin is the first-line therapy and can be empirically administered to neonates suspected of having listeriosis.Keywords: neonatal listeriosis, Listeria monocytogenes, clinical features, antibiotic treatment, Apgar score, C-reactive protein

Jieying Wang,&ast; Chunchun Yu,&ast; Yuni Xu,&ast; Zhuolin Chen, Wenhua Qiu, Shaowen Chen, Hua Pei, Yeteng Zhong Department of Clinical Laboratory, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yeteng Zhong, Department of Clinical Laboratory, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, People’s Republic of China, Email zhongyeteng@163.comPurpose: Given the high burden of Tuberculosis (TB) in China, the prevalence of multidrug-resistant tuberculosis (MDR-TB) is significant. Whole-genome sequencing (WGS) of Mycobacterium tuberculosis (MTB) enables the identification of lineages, drug-resistant mutations, and transmission patterns, offering valuable insights for TB control, clinical diagnosis, and treatment.Methods: We collected 202 MDR-MTB strains from 3519 suspected pulmonary TB patients treated at The Second Affiliated Hospital of Hainan Medical University between July 2019 and June 2021. Proportional drug-susceptibility testing was performed using 8 common anti-tuberculosis drugs. Subsequently, the genotypic drug resistance and genetic characteristics were analyzed by the WGS.Results: Lineages are identified by TB-profiler revealed 202 MDR-MTB strains, showcasing three predominant lineages, with lineage 2 being the most prevalent. Close genomic relatedness analysis and evidence of MTB transmission led to the formation of 15 clusters comprising 42 isolates, resulting in a clustering rate of 20.8%. Novelty, lineage 2.1 (non-Beijing) accounted for 27.2% of the MDR-MTB strains, which is rare in China and Neighboring countries. Regarding first-line anti-TB drugs, genes associated with rifampicin resistance, primarily the rpoB gene, were detected in 200 strains (99.0%). Genes conferring resistance to isoniazid, ethambutol, and streptomycin were identified in 191 (94.5%), 125 (61.9%), and 100 (49.5%) strains, respectively. Among the second-line drugs, 97 (48.0%) strains exhibited genes encoding resistance to fluoroquinolones. Comparing the results to phenotypic drug susceptibility-based testing, the sensitivity of WGS for detecting resistance to each of the six drugs (rifampicin, isoniazid, ethambutol, ofloxacin, kanamycin, capreomycin) was 90% or higher. With the exception of ethambutol, the specificity of WGS prediction for the remaining drugs exceeded 88%.Conclusion: Our study provides crucial insights into genetic mutation types, genetic diversity, and transmission of MDR-MTB on Hainan Island, serving as a significant reference for MDR-MTB surveillance and clinical decision-making.Keywords: tuberculosis, MDR-TB, whole-genome sequencing, WGS, genetic diversity, Hainan Island, China

Zhimin Shen,1,&ast; Shiping Chen,2,&ast; Yiqiang Duan,1 Juan Yu,3 Dayang Pan,4 Jiaxin Dong,1 Shanglong Wang,1 Qizhe Li,1 Yinlong Xiao,1 Xun Yuan1 1Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang City, People’s Republic of China; 2Department of Orthopedics, The No.1 People’s Hospital of Qingzhen, Qingzhen City, People’s Republic of China; 3The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang City, People’s Republic of China; 4The 4th People’s Hospital of Guiyang, Guiyang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqiang Duan, Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, No. 28, Guiyijie Road, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Email duanyiqiang0114@163.com Juan Yu, The Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Email 416876483@qq.comObjective: To explore the application value of adjustable skin stretchers for repairing skin wound defects.Methods: Twenty patients with skin defects were included in this study. The largest defect was measured to be 45.4 cm × 13.3 cm (length × width) and the smallest one was 4.4 cm × 3.2 cm (length × width). All patients were subjected to adjustable skin stretchers and the short- and long-term clinical efficacy was evaluated.Results: The wounds of all enrolled patients were healed completely except for one patient with a dorsal foot infection (the patient requested to return to the local county hospital for further treatment), with a total satisfaction of 100%. Postoperative 3-month follow-up showed scar formation, a little local hyperpigmentation, normal skin elasticity, and intact organs of involved cases, thus signifying the significant impact of adjacent joint activities.Conclusion: Adjustable skin stretchers can accurately control the tension on wound margins, breaking the limitation of previous stretchers to provide objective quantitative indicators for clinical application. These stretchers are characterized by high use-value and are worth promoting.Keywords: adjustable skin stretchers, wound-related defects, wound repair

Xiayan Xu,1– 3,&ast; Yun Xie,2– 4,&ast; Xia Gu,5– 7,&ast; Yang Zhou,2,3 Yu Kang,2,3,8 Jin Liu,2,3 Wenguang Lai,2– 4 Hongyu Lu,2,3 Shiqun Chen,2,3 Jun-yan Xu,2,3,9 Feng Lin,10 Yong Liu1– 3 1School of Medicine, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4School of Biology and Biological Engineering South China University of Technology, Guangzhou, 510006, People’s Republic of China; 5Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang, 150086, People’s Republic of China; 7Cardiovascular Imaging Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 8Shantou University Medical College, Shantou, 515041, People’s Republic of China; 9Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, People’s Republic of China; 10Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Lin, Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China, Email linfeng3085@163.com Yong Liu, South China University of Technology, No. 382, Waihuan East Road, University City, Panyu District, Guangzhou, Guangdong Province, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email liuyong@gdph.org.cnBackground: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear.Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes.Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56– 1.83]), cardiovascular mortality (2.29 [2.02– 2.59]), and cancer mortality (1.29 [1.01– 1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality.Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.Keywords: systemic immune inflammation index, coronary artery disease, type 2 diabetes, prognosis, mortality

Qiang Wei,1,&ast; Dong Lv,1,2,&ast; Shuna Fu,3,&ast; Dongmei Zhu,1 Minxiao Zheng,1 Si Chen,3 Shihang Zhen4 1Department of Psychology, Jianghan University, WuHan, People’s Republic of China; 2School of Business Administration, Huaqiao University, Quanzhou, People’s Republic of China; 3Department of Applied Psychology & Human Development, University of Toronto, Toronto, Canada; 4College of Economics and Management, Northwest Agriculture and Forestry University, XianYang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Wei, Department of Psychology, Jianghan University, WuHan, HuBei, People’s Republic of China, Tel +86-18671454618, Email weiqiang@jhun.edu.cn Dong Lv, School of Business Administration, Huaqiao University, Quanzhou, FuJian, People’s Republic of China, Tel +86-15798002728, Email lvdong@stu.hqu.edu.cnBackground: Tourism consumption is a topic with heated debates in tourism research, and pricing tourism products is a crucial task for tourism managers. Different types of tourist attractions offer different experiences to tourists, which affect their price perceptions and purchase decisions.Methods: This study combined questionnaires and event-related potentials (ERPs) measures to explore the magnitude of psychological conflict and the degree of emotional arousal that consumers experience when faced with different prices of goods in different scenic types.Results: The questionnaire results showed that attraction type influenced consumers’ price perceptions and that consumers were willing to pay higher prices for products in attractions. The ERP results implied that in the early stage of cognition, attraction type did not affect consumers’ perceptual processing, while price information attracted consumers’ cognitive attention. In the late stage of cognition, attraction type, and price information jointly influenced consumers’ decision-making, and consumers tended to accept high prices of products in entertainment attractions and cultural attractions, but consumers were more sensitive to the price of products in cultural attractions and less tolerant to price increases.Conclusion: The study elucidated how price information influenced consumers’ purchase decisions of tourism products at different stages of the dual-process theory, which can assist tourism managers in devising different pricing strategies and positioning strategies based on the attributes of attractions, to enhance product sales and revenues. This would further the vision of the World Tourism Organization (UNWTO) of “tourism fostering economic development”.Keywords: tourist attractions, price perception, neuromarketing, event-related potentials, P2, LPP

Shi Chen,1 Yi Shi,1 Bingzhu Hu,1 Jie Huang2 1Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan City, Hubei, 430000, People’s Republic of China; 2Department of Respiratory Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, People’s Republic of ChinaCorrespondence: Jie Huang, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, 966 Huaihai Zhong Lu, Xuhui District, Shanghai, Tel +86-13585823471, Email syarhuang@163.comPurpose: To explore the association between red cell distribution width (RDW)-to-platelet ratio (RPR) and in-hospital mortality of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients and establish a prediction model based on RPR and other predictors.Material and Methods: This cohort study included 1922 AECOPD patients aged ≥ 18 years in the Medical Information Mart for Intensive Care (MIMIC)-III and MIMIC-IV as well as 1738 AECOPD patients from eICU Collaborative Research Database (eICU-CRD). Possible confounding factors were screened out by univariate logistic regression, and multivariable logistic regression was applied to evaluate the association between RPR and in-hospital mortality of AECOPD patients. The area under the curve (AUC), calibration curve and decision curve analysis (DCA) curve were plotted to evaluate the predictive value of the model. The median follow-up time was 3.14 (1.87, 6.25) day.Results: At the end of follow-up, there were 1660 patients survived and 262 subjects died. After adjusting for confounders, we found that Log (RPR× 1000) was linked with elevated risk of in-hospital mortality of AECOPD patients [odds ratio (OR)=1.36, 95% confidence interval (CI): 1.01– 1.84]. The prediction model was constructed using predictors including Log (RPR× 1000), age, malignant cancer, atrial fibrillation, ventilation, renal failure, diastolic blood pressure (DBP), temperature, Glasgow Coma Scale (GCS) score, white blood cell (WBC), creatinine, blood urea nitrogen (BUN), hemoglobin, infectious diseases and anion gap. The AUC of the prediction model was 0.785 (95% CI: 0.751– 0.820) in the training set, 0.721 (95% CI: 0.662– 0.780) in the testing set, and 0.795 (95% CI: 0.762– 0.827) in the validation set.Conclusion: RPR was associated with the in-hospital mortality of AECOPD patients. The prediction model for the in-hospital mortality of AECOPD patients based on RPR and other predictors presented good predictive performance, which might help the clinicians to quickly identify AECOPD patients at high risk of in-hospital mortality.Keywords: red cell distribution width-to-platelet ratio, acute exacerbations of chronic obstructive pulmonary disease, red cell distribution width, platelet ratio

Shan Chen,1 Jie Zhang,1 Chengjia Qian,2 Xiaowei Qi,3 Yong Mao,1 Tingxun Lu1 1Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214122, People’s Republic of China; 2Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214122, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214122, People’s Republic of ChinaCorrespondence: Tingxun Lu, Department of Oncology, Affiliated Hospital of Jiangnan University, 1000, Hefeng Road, Wuxi, 214122, Jiangsu, People’s Republic of China, Email lutingxun@163.comPurpose: We aim to investigate the clinical significance of dynamic changes in the lymphocyte-to-monocyte ratio (LMR) and neutrophil-lymphocyte ratio (NLR) in peripheral blood at different time points combined with CEA in the prediction of postoperative-recurrence-in-patients with colorectal cancer (CRC).Patients and Methods: This study collected 357 patients with stage I–III CRC between 2016 and April 2018. The dynamic changes from preoperative to postoperative LMR (p-LMR-p) and NLR (p-NLR-p) were analyzed using COX regression for multivariate analysis. Logistic regression was used to investigate whether the dynamic changes from post-treatment to pre-end of follow-up LMR (p-LMR-f) and NLR (p-NLR-f) were independent risk factors for CRC recurrence and to construct a predictive model. Internal validation using bootstrapping was performed to validate the discrimination ability of the model. The models’ discriminative effect, calibration degree, and clinical utility were assessed.Results: In both the total cohort and the adjuvant therapy group, the dynamic changes of p-LMR-p (High-High vs Low-Low: p=0.006; HR:2.210, 95% CI: 1.256– 3.890) were found to be independent prognostic factors for recurrence-free survival (RFS) in CRC patients. Additionally, logistic regression analysis revealed that N stage, CEA, LMR of pre-end of follow-up (f-LMR), and p-LMR-f were independent risk factors for CRC recurrence. In the total cohort, the p-LMR-f had an area under the curve (AUC) of 0.704, with a sensitivity of 64% and a specificity of 75.3%. By combining p-LMR-f with CEA, a predictive model was constructed, which showed an AUC of 0.913 (0.986– 0.913) in the total cohort and an AUC of 0.924 (0.902– 0.924) in the adjuvant therapy group during internal validation using bootstrapping.Conclusion: Dynamic changes in LMR can be used to predict the prognosis of CRC and serve as a biomarker for predicting CRC recurrence. Combined with CEA, it can improve the predictive performance for detecting CRC recurrence.Keywords: colorectal cancer, postoperative recurrence, predictive model, inflammatory markers

Jiangli Ban,1,2 Xiaoyu Pan,2,3 Liqun Yang,2 Zhuoya Jia,2,3 Ruoxi Zhen,2,3 Xueqing Zhang,2,4 Shuchun Chen2,3 1Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: This study aimed to examine the correlation between fibrinogen/albumin (FAR) and diabetic peripheral neuropathy (DPN).Patients and Methods: A total of 342 patients were included and categorized into either the DPN group or the Non-DPN (NDPN) group based on their DPN status. The FAR index was determined by calculating the ratio of fibrinogen (FIB) to serum albumin (ALB), multiplied by 100. The participants were then divided into a High-FAR group and a Low-FAR group using the median FAR value as the threshold. Neurophysiological data were collected from the participants, which included motor conduction velocity (MCV) and sensory conduction velocity (SCV).Results: The DPN group displayed higher FAR levels [(DPN vs NDPN:6.72 (5.89,7.74) vs 5.94± 1.14], in addition to slower SCV and MCV data compared to the NDPN group. The high FAR group had a higher prevalence of DPN (78.9% vs 55.6%) (P< 0.05). There was a negative correlation between FAR and NCV, including bilateral median nerve SCV, left ulnar nerve SCV, bilateral median nerve MCV, bilateral common peroneal nerve MCV, bilateral tibial nerve MCV, and left ulnar nerve MCV. FAR was revealed to be an independent risk factor for the development of DPN in patients and demonstrated a greater predictive value for DPN development in Type 2 diabetes mellitus (T2DM) compared with FIB, HbA1c.Conclusion: The results suggest that monitoring FAR levels in patients with T2DM could identify those at higher risk for developing DPN, making the FAR index a valuable predictor of DPN development. Furthermore, since FAR has an inverse relationship with NCV, it stands to reason that high FAR levels may indicate nerve damage and slower conduction velocities. Thus, managing FAR could prove beneficial in both preventing and delaying the onset of DPN in T2DM patients.Keywords: type 2 diabetes mellitus, diabetic peripheral neuropathy, fibrinogen/albumin

Yifan Wang,1,2,&ast; Fen Yao,2,&ast; Shenglong Chen,3 Xin Ouyang,4 Jinhua Lan,5 Zheng Wu,2 Yirong Wang,2 Jingchun Chen,2 Xipei Wang,6,7 Chunbo Chen1 1Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 3Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 4Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 5Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, 510010, People’s Republic of China; 6Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunbo Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China, Email gghccm@163.com Xipei Wang, Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Email xipei_wang@163.comPurpose: To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin.Methods: This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations.Results: The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (Vc), inter-compartmental clearance (Q) and volumes of the peripheral compartments (Vp) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m2) to attain target trough concentration (Cmin, PTA 52.8%). When eGFR > 30 mL/min/1.73 m2, increasing dose and the administration times of loading doses were the preferred options to achieve target Cmin based on the renal function and types of infection.Conclusion: The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.Keywords: teicoplanin, pharmacokinetics, Monte Carlo simulation, intensive care unit, renal function

Shu Niu,1,&ast; Qingjuan Ren,1,&ast; Shuchun Chen,2 Xiaoyu Pan,2,3 Lin Yue,4 Xing Chen,2 Zelin Li,2 Ruoxi Zhen3 1Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu Niu, Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of China, Email niushucccc@163.comPurpose: Among chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) is one of the commonest. Although empagliflozin has several therapeutic uses in treating cardiovascular and renal disorders, its impacts and mechanisms on NAFLD are poorly understood. This research aimed to examine the metabolic regulatory mechanism through which empagliflozin protects against NAFLD.Methods: Equal grouping of twenty-seven male C57BL/6J mice into those fed a normal diet (NCD), those fed a high-fat diet (HFD), and those fed an HFD with empagliflozin (Empa) was approached. HE, oil red O staining, and Masson staining were utilized for evaluating the pathological damage to the liver and the mice’s liver and body weights. Lipids, blood glucose, and inflammation index were compared across the three groups. Liquid chromatography/mass spectrometry (LC-MS) has been employed for identifying liver metabolomics.Results: The findings suggested that empagliflozin mitigated the inflammatory and oxidative stress response associated with the buildup of lipids caused by HFD. Differentially expressed metabolites (DEMs) were identified by metabonomics analysis as present in both the HFD/NCD and Empa/HFD groups. These DEMs were primarily found in lipids and organic acids like lysophosphatidylcholine (lysoPC), lecithin (PC), triglyceride (TG), palmitic acid, and L-isoleucine. Among the enriched pathways that were shown to be important were those involved in the metabolism of histidine, arachidonic acid, the control of lipolysis in adipocytes, and insulin resistance. There was a strong correlation between inflammation and oxidative stress in most of the metabolites. The inflammation and oxidative stress unbalance were ameliorated by empagliflozin.Conclusion: NAFLD mice model showed considerable improvement in metabolic abnormalities and liver protection after treatment with empagliflozin. The process may include the overexpression of L-isoleucine and the downregulation of lysoPC, PC, TG, and palmitic acid to reduce liver harm caused by lipotoxicity.Keywords: NAFLD, empagliflozin, metabolomics, differentially expressed metabolites, obesity

Zu-Fei Wu,1,&ast; Wen-Tao Su,2,3,&ast; Shi Chen,4 Bai-Da Xu,2 Gang-Jun Zong,2,3 Cun-Ming Fang,1 Zheng Huang,1 Xue-Jun Hu,1 Gang-Yong Wu,2,3 Xiao-Lin Ma1 1Department of Cardiology, Xuancheng People’s Hospital, Xuanchen, Anhui, 242000, People’s Republic of China; 2Department of Cardiology, the 904th Hospital of the PLA Joint Logistics Support Force, Wuxi, Jiangsu, 214044, People’s Republic of China; 3Department of Cardiology, Wuxi Clinical College of Anhui Medical University, Wuxi, Jiangsu, 214044, People’s Republic of China; 4Department of Cardiology, Wuxi No.5 People’s Hospital, Wuxi, Jiangsu, 214044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang-Yong Wu, Department of Cardiology, the 904th Hospital of the PLA Joint Logistics Support Force, Wuxi, Jiangsu, 214044, People’s Republic of China, Email wuwangyi520@sina.comObjective: To investigate the correlation between serum parathyroid hormone (PTH) levels and in-hospital major adverse cardiovascular events (MACE) in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI), and establish a risk prediction model based on parameters such as PTH for in-hospital MACE.Methods: This observational retrospective study consecutively enrolled 340 patients who underwent primary PCI for STEMI between January 2016 and December 2020, divided into a MACE group (n=92) and a control group (n=248). The least absolute shrinkage and selection operator (LASSO) and logistic regression analyses were used to determine the risk factors for MACE after primary PCI. The rms package in R-studio statistical software was used to construct a nomogram, to detect the line chart C-index, and to draw a calibration curve. The decision curve analysis (DCA) method was used to evaluate the clinical application value and net benefit.Results: Correlation analysis revealed that PTH level positively correlated with the occurrence of in-hospital MACE. Receiver operating characteristic curve analyses revealed that PTH had a good predictive value for in-hospital MACE. Multivariate logistic regression analysis indicated that Killip class II–IV, and FBG were independently associated with in-hospital MACE after primary PCI. A nomogram model was constructed using the above parameters. The model C-index was 0.894 and the calibration curve indicated that the model was well calibrated. The DCA curve suggested that the nomogram model was better than TIMI score model in terms of net clinical benefit.Conclusion: Serum PTH levels in patients with STEMI are associated with in-hospital MACE after primary PCI, and the nomogram risk prediction model based on PTH demonstrated good predictive ability with obvious clinical practical value.Keywords: parathyroid hormone, acute ST-segment elevation myocardial infarction, percutaneous coronary intervention, nomograms

Shi Chen,1,&ast; Jiaqi Qiang,1,2,&ast; Bin Zhao,3 Ran Tian,4 Tao Yuan,1 Ming Li,1 Mei Li,1 Zhaoqi Gu,5 Liping Yang,6 Huijuan Zhu,1 Hui Pan,1,7 Yan Tang,3 Yuxiu Li1 1Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Eight-Year Program of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 4Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 6Department of Pharmacy, Handan First Hospital, Handan, Hebei Province, People’s Republic of China; 7State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxiu Li, Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of China, Email liyuxiu@medmail.com.cn Yan Tang, Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of China, Email tangyan@pumch.cnAbstract: The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. For patients with cardiovascular disease taking clopidogrel for vascular protection, this adverse event hypoglycemia increases the risk of cardiovascular events. However, discontinuing clopidogrel leaves patients without appropriate antiplatelet therapy. Treating IAS with glucocorticoids is also risky for these patients’ primary cardiovascular diseases. Early recognition and appropriate treatment of clopidogrel-induced IAS (CIAS) would be beneficial for patients. This research aimed to discover the clinical features and investigate optimal therapeutic management of CIAS. We systematically searched for cases of CIAS in PubMed and Embase and performed data mining in Food and Drug Administration Adverse Event Reporting System (FAERS). In the CIAS series, clinical features were summarized and compared to 287 IAS cases, including demographic information, HLA alleles, onset, and symptoms. The therapeutic effect of glucocorticoids was compared between the receiving group and the not-receiving group. The possibilities of common antiplatelet drugs to induce hypoglycemia/IAS were investigated with chemical structure and FAERS reports. A CIAS series of 51 patients was established. CIAS had an onset age of 74.8± 8.6 years old, 92.2% male, and a balanced proportion of East Asians and non-East Asians. Confusion occurred more frequently in CIAS than in IAS from various causes, while the other symptoms and hypoglycemia types were similar. The recovery time was approximately the same whether using glucocorticoids/immunotherapy in CIAS or not. Among common antiplatelet drugs, ticagrelor and rivaroxaban were unlikely to induce hypoglycemia/IAS. Clopidogrel is a distinctive cause of IAS featuring an elderly male presenting confusion as the symptom of hypoglycemia. Glucocorticoids/immunotherapy might not be necessary for the long-term recovery of CIAS. To balance the risks of hypoglycemia and cardiovascular events, substituting clopidogrel with ticagrelor and rivaroxaban might be considered.Keywords: autoimmune hypoglycemia, antiplatelet therapy, glucocorticoids, cardiovascular diseases, ticagrelor

Ruoxi Zhen,1,2 Jiangli Ban,2,3 Zhuoya Jia,1,2 Yanhui Liu,2,3 Zelin Li,1,2 Shuchun Chen1,2,4 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Graduate School, Hebei North University, Zhangjiakou, People’s Republic of China; 4Hebei Key Laboratory of Metabolic Diseases, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +86 31185988406, Fax +86 31185988406, Email chenshuc2014@163.comPurpose: The objective of this research was to examine the relationship between non-HDL cholesterol/HDL cholesterol ratio (NHHR) and vitamin D in type 2 diabetes mellitus (T2DM).Patients and Methods: This study enrolled 617 T2DM participants. Participants were separated into two groups: no vitamin D deficiency and vitamin D deficiency. Participants were split into two categories: individuals who had a high NHHR and those with a low NHHR, with the median NHHR serving as the cut-off. Eventually, the study participants were classified into two groups by gender, which were further classified into vitamin D deficient and non-vitamin D deficient groups.Results: NHHR values were substantially greater in vitamin D deficient group than in the non-deficient group in both male and female T2DM patients (P< 0.05). The high NHHR group displayed substantially lower vitamin D levels than the low NHHR group [16.21 (12.55,21.35) vs 19.05 (14.59,24.07), P< 0.001]. NHHR was discovered to be negatively and independently associated with vitamin D levels, and there was no sex difference.Conclusion: For the first time, our research revealed a negative relationship between NHHR and vitamin D in patients with T2DM.Keywords: vitamin D, diabetes, type 2 diabetes, lipid ratio, non-HDL-C /HDL-C

Shan Chen,1 Houming Liu,1 Tianpin Li,1 Wenjie Lai,1 Lei Liu,1 Youchun Xu,2 Jiuxin Qu1 1Department of Clinical Laboratory, Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Diseases, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, 518112, People’s Republic of China; 2Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084, People’s Republic of ChinaCorrespondence: Jiuxin Qu, Department of Clinical Laboratory, Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Diseases, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China, Email Qujiuxin@163.com Youchun Xu, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, People’s Republic of China, Email CYX040198@163.comBackground: The currently used conventional susceptibility testing for drug-resistant Mycobacterium tuberculosis (M.TB) is limited due to being time-consuming and having low efficiency. Herein, we propose the use of a microfluidic-based method to rapidly detect drug-resistant gene mutations using Kompetitive Allele-Specific PCR (KASP).Methods: A total of 300 clinical samples were collected, and DNA extraction was performed using the “isoChip®” Mycobacterium detection kit. Phenotypic susceptibility testing and Sanger sequencing were performed to sequence the PCR products. Allele-specific primers targeting 37 gene mutation sites were designed, and a microfluidic chip (KASP) was constructed using 112 reaction chambers to simultaneously detect multiple mutations. Chip validation was performed using clinical samples.Results: Phenotypic susceptibility of clinical isolates revealed 38 rifampicin (RIF)-resistant, 64 isoniazid (INH)-resistant, 48 streptomycin (SM)-resistant and 23 ethambutol (EMB)-resistant strains, as well as 33 multi-drug-resistant TB (MDR-TB) strains and 20 strains fully resistant to all four drugs. Optimization of the chip-based detection system for drug resistance detection showed satisfactory specificity and maximum fluorescence at a DNA concentration of 1× 101 copies/μL. Further analysis revealed that 76.32% of the RIF-resistant strains harbored rpoB gene mutations (sensitivity, 76.32%; specificity 100%), 60.93% of the INH-resistant strains had katG gene mutations (sensitivity, 60.93%; specificity, 100%), 66.66% of the SM-resistant strains carried drug resistance gene mutations (sensitivity, 66.66%; specificity, 99.2%), and 69.56% of the EMB-resistant strains had embB gene mutations (sensitivity, 69.56%; specificity, 100%). Further, the overall agreement between the microfluidic chip and Sanger sequencing was satisfactory, with a turnaround time of the microfluidic chip was approximately 2 hours, much shorter than the conventional DST method.Conclusion: The proposed microfluidic-based KASP assay provides a cost-effective and convenient method for detecting mutations associated with drug resistance in M. tuberculosis. It represents a promising alternative to the traditional DST method, with satisfactory sensitivity and specificity and a much shorter turnaround time.Graphical Abstract: Keywords: Mycobacterium tuberculosis, multidrug-resistance, drug resistance, resistance-conferring gene mutations, polymerase chain reaction, microfluidic analytical techniques, Sanger sequencing

Shuanghong Chen,1,2 Todd Jackson,3 Ying He1 1Xinqiao Hospital and the Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Faculty of Psychology, Southwest University, Chongqing, People’s Republic of China; 3Department of Psychology, University of Macau, Taipa, Macau, People’s Republic of ChinaCorrespondence: Ying He, Xinqiao Hospital and the Second Affiliated Hospital, Army Medical University, Chongqing, 400715, People’s Republic of China, Email hy1996jw@163.comPurpose: Expectations and modification gained through critical learning influence pain perception. We tested how pain tolerability was influenced by the effects of orally delivered false feedback and participant status immediately prior to performing tasks.Patients and Methods: A total of 125 healthy college students (69 females and 56 males) were randomly assigned to 3 groups (positive, negative, and control) to participate in two formal cold pressor tests (CPTs). Participants completed the same series of task-related questionnaires (perceived importance, intended effort, current affect, and self-efficacy) before each CPT. False performance feedback was delivered after completion of the baseline level CPT. After completion of each CPT, both pain intensity and pain tolerability (duration in ice water) were recorded.Results: The results of linear mixed models revealed significant condition × time interactions on pain tolerability and task self-efficacy after controlling for individual variance as a random effect. Participants who received negative feedback exhibited increased pain tolerability without decreasing their self-efficacy, whereas participants who received positive feedback showed increased self-efficacy with no change in pain tolerability. A longer pain tolerance duration was also predicted by a more intentional investment of effort and a lower intensity of experienced pain as well as the effect of false feedback.Conclusion: The research highlights the effect of powerful situational influences on laboratory-induced pain tolerance.Keywords: cold pressor test, pain, false feedback, effort, self-efficacy, social norms

Xinyi Hong,1,&ast; Shanhu Qiu,2,&ast; Xia Wu,3 Sizhen Chen,4 Xiaoxiang Chen,5 Bei Zhang,6 Aiqin He,3 Yun Xu,7 Jianqing Wang,8 Yingchun Gao,9 Xizhong Xu,10 Li Sun,11 Yang Zhang,12 Libing Xiang,13 Jundong Zhou,14 Qun Guan,15 Yanling Zhu,16 Haiyan Liu,17 Hao Xu,18 Ying Zhou,19 Bingwei Chen,4 Yang Shen1 1Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 2Department of General Practice, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Gynecological Oncology, Tumor Hospital Affiliated to Nantong University, Nantong, Jiangsu, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, People’s Republic of China; 5Department of Gynecological Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 6Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 7Department of Obstetrics and Gynecology, The First People’s Hospital of Changzhou, Changzhou, People’s Republic of China; 8Department of Obstetrics and Gynecology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, People’s Republic of China; 9Department of Obstetrics and Gynecology, Huai’an First People’s Hospital, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an, People’s Republic of China; 10Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 11Department of Gynecological Oncology, Qingdao Central Hospital, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, People’s Republic of China; 12Gynecology Department, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 13Ovarian Cancer Program, Department of Gynecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 14Radio-oncology Department, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 15Gynecology Department, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China; 16Gynecology Department, Xuzhou Cancer Hospital, Xuzhou, People’s Republic of China; 17Department of Obstetrics and Gynecology, Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 18Gynecology Department, Huangshi Love & Health Hospital Affiliated to Hubei Polytechnic University, Huangshi, People’s Republic of China; 19The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Shen, Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86 15366166769, Fax +86 +25 83272111, Email shenyang@seu.edu.cn Bingwei Chen, Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, 210009, People’s Republic of China, Email drchenbw@126.comPurpose: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting.Patients and Methods: Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1– 14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).Results: A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (> 700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%).Conclusion: In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.Keywords: molecular-targeting therapy, angiogenesis inhibitors, real-world study

Yunxia Huang,1,&ast; Yi Guo,2,&ast; Qin Xiao,3,&ast; Shuyu Liang,2 Qiang Yu,4 Lang Qian,1 Jin Zhou,1 Jian Le,1 Yuchen Pei,5 Lei Wang,4 Cai Chang,1 Sheng Chen,4 Shichong Zhou1 1Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 3Department of Electronic Engineering, Fudan University and Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Shanghai, People’s Republic of China; 4Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 5Precision Cancer Medical Center Affiliated to Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shichong Zhou, Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 21-64175590, Email sczhou@hotmail.com Sheng Chen, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 21-64175590, Email 0456177@fudan.edu.cnPurpose: The emergence of genomic targeted therapy has improved the prospects of treatment for breast cancer (BC). However, genetic testing relies on invasive and sophisticated procedures.Patients and Methods: Here, we performed ultrasound (US) and target sequencing to unravel the possible association between US radiomics features and somatic mutations in TNBC (n=83) and non-TNBC (n=83) patients. Least absolute shrinkage and selection operator (Lasso) were utilized to perform radiomic feature selection. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was utilized to identify the signaling pathways associated with radiomic features.Results: Thirteen differently represented radiomic features were identified in TNBC and non-TNBC, including tumor shape, textual, and intensity features. The US radiomic–gene pairs were differently exhibited between TNBC and non-TNBC. Further investigation with KEGG verified radiomic–pathway (ie, JAK-STAT, MAPK, Ras, Wnt, microRNAs in cancer, PI3K-Akt) associations in TNBC and non-TNBC.Conclusion: The pivotal network provided the connections of US radiogenomic signature and target sequencing for non-invasive genetic assessment of precise BC treatment.Keywords: triple-negative breast cancer, radiomics, somatic mutation, signaling pathway

Xiaoyu Zhu,1 Ran Li,1 Yu Zhu,1 Jia Zhou,1 Junchao Huang,1 Yanfang Zhou,1 Jinghui Tong,1 Ping Zhang,1 Xingguang Luo,2 Song Chen,1 Yanli Li,1 Baopeng Tian,1 Shu-Ping Tan,1 Zhiren Wang,1 Xiaole Han,1 Li Tian,3 Chiang-Shan R Li,2 Yun-Long Tan1 1Psychosomatic Department, Beijing HuiLongGuan Hospital, Beijing, People’s Republic of China; 2Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; 3Institute of Biomedicine and Translational Medicine, Department of Physiology, Faculty of Medicine, University of Tartu, Tartu, EstoniaCorrespondence: Yun-Long Tan, Psychosomatic Department, Beijing HuiLongGuan Hospital, Beijing, People’s Republic of China, Tel +86-10-83024319, Fax +86-10-62710156, Email yltan21@126.comObjective: Accumulating evidence suggested that immune system activation might be involved in the pathophysiology of schizophrenia. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) can measure inflammation. This study aimed to investigate the inflammatory state in patients with schizophrenia by using these indicators.Methods: In this study, the complete blood count data for 187 continuing hospitalized patients with schizophrenia and 187 age- and sex-matched healthy participants was collected annually from 2017 to 2019. Platelet (PLT), lymphocyte (LYM), monocyte (MON) and neutrophil (NEU) counts were aggregated and NLR, MLR, PLR, and SII were calculated. Using a generalized linear mixed model, we assessed the impact of age, sex, diagnosis, and sampling year on the above indicators and evaluated the interaction between the factors.Results: According to the estimation results of the generalized linear mixed model, the NLR increased by 0.319 (p = 0.004), the MLR increased by 0.037 (p < 0.001), and the SII increased by 57.858 (p = 0.018) in patients with schizophrenia. Data after two years of continuous antipsychotic treatment showed that the NLR and MLR were higher in patients with schizophrenia than those in healthy controls, while the PLT and LYM counts were decreased in patients with schizophrenia. The schizophrenia diagnosis was correlated to the MON and LYM count, NLR, MLR, and SII (p < 0.05).Conclusion: The differences in these markers were stable and cannot be eliminated by a full course of treatment. This study provides impetus for the inflammatory hypothesis of schizophrenia.Keywords: schizophrenia, systemic immune-inflammation index, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, platelet/lymphocyte ratio

Jiaxun Ying,1 Hanbo Tao,1 Qingyuan He,1 Zhiruo Zhang,1 Wenfei Hu,1 Shuting Chen,2 Ye Guan1 1Savaid Stomatology School, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2School of Basic Medicine and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ye Guan, Savaid Stomatology School, Lin’an Campus, Hangzhou Medical College, No. 8, Yikang Street, Lin’an District, Hangzhou, 310000, People’s Republic of China, Tel +86 18868105499, Email 21818734@zju.edu.cn Shuting Chen, School of Basic Medicine and Forensic Medicine, Lin’an Campus, Hangzhou Medical College, No. 8, Yikang Street, Lin’an District, Hangzhou, 310000, People’s Republic of China, Tel +86 88892867, Email shutinren@163.comAbstract: Children’s dental fear (CDF) has become one of the main reasons affecting the quality of dental treatment. In order to reduce the incidence of CDF in China before and after children’s dental visits, this review applies literature analysis and empirical summary methods to analyze and summarize academic discussions on this topic, including occurrence mechanism, prevention guidance, and the conclusion that the occurrence and prevention of CDF is closely related with children’s internal characteristics and external influences. In the end, we propose a breakthrough of combining the CFSS-DS scale and three-grade prevention theory together in the future to provide new ideas and hypotheses for the prevention of CDF.Keywords: dental anxiety, character, environment, family, hospital, three-grade prevention

Haowei Li,1,&ast; Hao Chen,2,3,&ast; Zifeng Ye,4 Xuehang Li,1 Lei Yang,1,5 Shengshu Wang,1 Shanshan Yang,6 Shaohua Liu,1 Shimin Chen,1 Rongrong Li,1 Junhan Yang,1,3 Huaihao Li,1 Yinghui Bao,1 Yueting Shi,1,3 Jianhua Wang,1 Yao He,1,7 Miao Liu3 1Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Healthcare Office of Medical Service Department, Hainan Hospital, Chinese PLA General Hospital, Sanya, Hainan, People’s Republic of China; 3Department of Statistics and Epidemiology, Graduate School of PLA General Hospital, Beijing, People’s Republic of China; 4Department of Medical Psychology of Hainan Hospital, Chinese PLA General Hospital, Sanya, Hainan, People’s Republic of China; 5Healthcare Office of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 6Department of Disease Prevention and Control, First Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 7State Key Laboratory of Kidney Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao He, Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National clinical research center for geriatrics diseases, State Key Laboratory of Kidney Diseases, Second Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86-10-66876411, Email yhe301@x263.net Miao Liu, Department of statistics and epidemiology, Graduate School of PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86-10-66937715, Email liumiaolmbxb@163.comBackground: As the focal point of epidemic prevention and control, the mental health of COVID-19 patients cannot be ignored. Online Mindfulness-Based Stress Reduction (MBSR) allows for the provision of conveniently accessible, effective and low-cost interventions on a large scale. We aim to evaluate the effectiveness of an online MBSR intervention in alleviating anxiety and depression among asymptomatic/mild patients limited by COVID-19-related restrictions.Methods: Fifty-eight patients treated in Sanya Fangcang hospital were randomly allocated to either to the experimental group (n = 29) following daily, for 5 days, an online-based mindfulness intervention or to the control group (n = 29). Patients from both groups underwent online questionnaires including assessment of anxiety and depression status at pre- and post-tests using Self-rating Anxiety Scale and Self-Rating Depression Scale.Results: After the online-based MBSR program, the anxiety and depression scores of the patients in the MBSR group decreased significantly in comparison to the scores of those in the control group (respectively η2 = 0.175, η2 = 0.215, p < 0.001). And the proportion of severe anxiety and depression patients in the MBSR group decreased to 0% which lower than the control group, and the proportion of light anxiety and depression patients was significantly more than that in the control group after the MBSR intervention.Conclusion: The online-based MBSR intervention appears to be an effective way of alleviating anxiety and depression symptoms among COVID-19 patients with associated quarantine in Fangcang hospital. Given the seriousness of mental health threat that could be posed by this ongoing pandemic, our study provides a new idea and method for cost-effective and time-efficient interventions in the future of epidemic prevention and control.Keywords: COVID-19 patients, online mindfulness, psychological intervention, anxiety, depression

Sijian Chen,1,2 Honghe Li,1 Lihong Pang,3 Deliang Wen1 1Institute for International Health Professions Education and Research, China Medical University, Shenyang, People’s Republic of China; 2School of Nursing, China Medical University, Shenyang, People’s Republic of China; 3School of Nursing, Qiqihar Medical University, Qiqihar, People’s Republic of ChinaCorrespondence: Deliang Wen, Institute for International Health Professions Education and Research, China Medical University, No. 77 Puhe Road, Shenyang, Liaoning, 110122, People’s Republic of China, Email dlwen@cmu.edu.cnObjective: This study aimed to examine the mediating role of fear of missing out (FoMO) and the moderating role of resilience in the association between social media use and negative emotions among medical college students in China during the COVID-19 pandemic.Participants and Methods: A cross-sectional study design was conducted, medical college students from Qiqihar Medical University, China participated in the study. A total of 470 medical college students were recruited voluntarily to complete questionnaires on social media use, FoMO, resilience, and negative emotions.Results: Social media use was positively associated with FoMO and negative emotions among medical students (p < 0.01). The total effect of social media use on negative emotions was significant (β = 1.101, SE = 0.079, p < 0.001). Social media use had no significant direct effect on negative emotions (β = 0.168, SE = 0.096, p > 0.05), but it had an indirect effect on negative emotions via mediation of FoMO (β = 0.933, SE = 0.106, 95% CI: 0.731 to 1.149). Moreover, resilience had a significant moderating effect on the relationship between FoMO and negative emotions (β = − 0.021, SE = 0.005, 95% CI: − 0.032 to − 0.012). FoMO had a significant positive predictive effect on negative emotions at both levels of resilience (low resilience individuals: β = 1.079, SE = 0.076, p < 0.001; high resilience individuals: β = 0.212, SE = 0.094, p < 0.05).Conclusion: Social media use and FoMO may be risk factors for increased negative emotions, and resilience should be considered in prevention and intervention strategies designed to mitigate negative emotions among medical college students.Keywords: social media use, negative emotions, fear of missing out, resilience, COVID-19

Shuangshuang Chen,1– 3,&ast; Xinqiang Wang,4,&ast; Danhui Li,5,&ast; Jiawen Zhao,4 Jingjing Zhang,3 Yongzhong Zhang,6 Xiujun Zhang,4 Xiaohong Kan2– 4 1Department of Tuberculosis Prevent and Control, Center for Disease Control and Prevention of Hefei, Hefei, Anhui, 230051, People’s Republic of China; 2Department of Scientific Research and Education, Anhui Chest Hospital, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Scientific Research and Education, Anhui Provincial Tuberculosis Institute, Hefei, Anhui, 230022, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 5Department of Hospital Infection and Management, Anhui Chest Hospital, Hefei, Anhui, 230022, People’s Republic of China; 6Department of Tuberculosis Prevent and Control, Anhui Provincial Tuberculosis Institute, Hefei, Anhui, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Kan, Department of Scientific Research and Education, Anhui Chest Hospital (Anhui Provincial Tuberculosis Institute), Hefei, Anhui, 230022, People’s Republic of China, Email ahfidelis@126.com Xiujun Zhang, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China, Email zhangxiujun@ahmu.edu.cnIntroduction: Evidence has shown that air pollutant exposure plays a vital role in the progression of tuberculosis (TB). The aim of this research was to assess the short-term effects of ozone (O3) exposure and TB outpatient visits in 16 prefecture-level cities of Anhui, China, 2015– 2020.Methods: Distributed lag nonlinear model (DLNM), Poisson generalized linear regression model and random effects model were applied in this study. The effects of different age and gender on TB were investigated by stratified analysis, and then we performed sensitivity analyses to verify the stability of the results.Results: A total of 186,623 active TB cases were registered from January 1, 2015 to December 31,2020 in Anhui. The average concentration of ozone is 92.77 ± 42.95 μg/m3. The maximum lag-specific and cumulative relative risk (RR) of TB outpatient visits was 1.0240 (95% CI: 1.0170– 1.0310, lag 28 days) for each 10 μg/m³ increase in O3 in the single-pollutant model. Estimation for 16 prefecture-level cities indicated that the strong association between O3 and the risk of TB outpatient visits was in tongling (RR = 1.0555, 95% CI: 1.0089– 1.1042), Suzhou (RR = 1.0475, 95% CI: 1.0268– 1.0687), wuhu (RR = 1.0358, 95% CI: 1.0023– 1.0704). Stratified analysis showed that the health effects of ozone exposure remained significant in male and older adults, and there was no significant association between exposure to ozone in children and adolescents and the risk of tuberculosis.Discussion: We found that ozone exposure increases the risk of TB infection in outpatient patients, with males and the elderly being more susceptible, and it is necessary for government departments to develop targeted publicity and prevention measures in response to the local air quality conditions.Keywords: air pollution, ozone, tuberculosis, distributed lag nonlinear model, Poisson generalized linear regression model

Meng Zhou,&ast; Fang Lu,&ast; Ling Jiang, Chen Chen, Si Chen, Luhan Geng, Rui Sun, Qing Li, Suyan Duan, Bo Zhang, Huijuan Mao, Changying Xing, Yanggang Yuan Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan; Changying Xing, Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, Tel/Fax +86-25-6830-6462, Email ygyuan@njmu.edu.cn; cyxing62@126.comAim: Diabetic kidney disease (DKD) continues to be devastating complication of diabetes mellitus. Immune response and inflammatory reaction play essential roles in the progression of DKD. But the specific mechanism of immune cells, and their act on renal innate cells remains unclear. This article focused on immune cells and their communication with renal innate cells to provide bioinformatic evidence for further understanding the immune mechanism in DKD.Methods: Data were analyzed to evaluate the differentially expressed genes (DEGs) and their pathways in DKD patients and mice. Gene set enrichment analysis (GSEA) was used to explore the immune inflammation-related pathways. CIBERSORT was applied to evaluate the distribution of inflammatory cells in different states. Cell-type DEGs and their enrichment pathways were further explored in podocytes, proximal tubule cells and injured tubule cells. Cellchat was used to reveal the cellular communication between immune cells and renal innate cells in DKD.Results: GO and KEGG analysis showed that DEGs were mainly enriched in immune inflammation-related pathways. Monocytes, M2 macrophages and T cells were significantly increased in DKD samples, especially in renal tubule. ScRNA datasets showed that the immune cells number in DKD were significantly increased. Cell-type DEGs were involved in kidney growth and development. In DKD, the interaction numbers and strength between immune cells and innate cells were significantly increased. VISTANT, SPP1 and IGF signal flow were increased in DKD. SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1-Igf1r receptor ligand pairs were enhanced in DKD, which mediated the communication between immune-inflammatory cells and innate cells.Conclusion: Our study explored the pathogenesis of renal injury promoted by immunoinflammatory in DKD. VISTANT, SPP1, and IGF signaling pathways and SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1- Igf1r receptor ligand pairs might occupy essential place in the occurrence and progress of DKD.Keywords: diabetic kidney disease, immune cells, renal innate cells, bioinformatics

Xue Zhao,&ast; Junde Zhu, Shan Chen,&ast; Ruojing Liu, Tingting Long Department of Human Anatomy, School of Basic Medicine, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junde Zhu, Department of Human Anatomy, School of Basic Medicine, Guizhou Medical University, Guian New Area, Guiyang, 550025, People’s Republic of China, Tel +86-851-88416251, Email jdzhu73@126.comPurpose: To investigate the effect of neural stem cell-derived exosomes (NSC-Exos) on neural function after rat cerebral ischemia-reperfusion injury by regulating microglia-mediated inflammatory response.Methods: SD rats were randomly divided into Sham group, IRI group, PBS group and NSC-Exos group. Each group was divided into 1d, 3d, 7d and 14d subgroups. In the Sham group, only cervical vessels were isolated without blockage. MCAO model was constructed in the other three groups by blocking middle cerebral artery with thread embolism. PBS group and NSC-Exos group were, respectively, injected into the lateral ventricle of PBS and Exos. Neurobehavioral deficit scores were performed for each subgroup at relative time points, then brains were taken for TTC staining, parietal cortex histopathology and microglia-mediated inflammatory response-related factors were detected.Results: Compared with Sham group, neurological defect score and infarction volume in both the IRI and PBS groups were significantly increased. The exploration target quadrant time and escape latency time of maze test were increased. The number of CD86+/Iba1+ double-positive cells increased, while CD206+/Iba1+ double-positive cells decreased. The expressions of IL-6 and CD86 in parietal cortex were increased, while the expressions of Arg1 and CD206 were decreased. Compared with the IRI group and PBS group, neurological defect score and infarction volume in NSC-Exos group were decreased. The exploration target quadrant time and escape latency time of water maze test were decreased. The number of CD206+/Iba1+ double-positive cells increased, while CD86+/Iba1+ double-positive cells decreased. The expressions of Arg1 and CD206 in parietal cortex were increased, while the expressions of IL-6 and CD86 were decreased.Conclusion: NSC-Exos can promote the polarization of microglia, that is, inhibit the polarization of M1 and promote polarization of M2, reduce microglia-mediated neuroinflammation, suggesting that NSC-Exos may be a strategy for the treatment of microglia-mediated neuroinflammation after ischemic brain injury.Graphical Abstract: Keywords: cerebral ischemia, neural stem cell, exosome, microglia, neuroinflammation

Song Chen,1 Feng Shi,2 Zhiqiang Wu,3 Liguang Wang,4 Hongjie Cai,3 Ping Ma,5 Yuanmin Zhou,5 Qicong Mai,2 Fan Wang,3 Shuangyan Tang,3 Wenquan Zhuang,3 Jiaming Lai,6 Xiaoming Chen,2 Huanwei Chen,4 Wenbo Guo3 1Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China; 5Department of Oncology, the Twelfth People’s Hospital of Guangzhou, Guangzhou, People’s Republic of China; 6Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Huanwei Chen, Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China, Email chwei_fsyyy@163.com Wenbo Guo, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China, Email guowenbo@mail.sysu.edu.cnPurpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load.Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9– 14.8) and 5.0 months (95% CI, 4.2– 5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients.Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.Keywords: hepatocellular carcinoma, transhepatic arterial embolization, hepatic arterial infusion chemotherapy, lenvatinib, tislelizumab

Shaopeng Chen,1,2,&ast; Mindan Wu,3,&ast; Zhilin Xiong,1,&ast; Jiewen Huang,1 Yingying Lv,1 Yuyan Li,4 Minjuan Zeng,5 Tianwen Lai1 1Institute of Respiratory Diseases, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China; 2Blood Donation Service Department, Zhanjiang Blood Center, Zhanjiang, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Shantou Central Hospital, Shantou, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Dongguan Hospital of Southern Medical University, Dongguan, People’s Republic of China; 5Laboratory Animal Center, Guangdong Medical University, Zhanjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianwen Lai; Minjuan Zeng, Email laitianwen2011@163.com; mjzeng@gdmu.edu.cnPurpose: Particulate matter (PM2.5) is a common risk factor for airway inflammation. Alveolar macrophages play a critical role in airway inflammation. Sirtuin 6 (SIRT6) is a class Ill histone deacetylase that exerts an anti-inflammatory effect in airway diseases. However, the role of SIRT6 on PM2.5-induced airway inflammation in macrophages remains unclear. We aimed to determine whether SIRT6 protects against PM2.5-induced airway inflammation in macrophages.Methods: The effect of SIRT6 on PM2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6fl/fl-LysMCre) in vivo.Results: PM2.5 increased SIRT6 expression in THP1 cells, but SIRT6 gene silencing decreased PM2.5 induced inflammatory cytokines in THP1 cells. Moreover, the expression of SIRT6 and inflammatory cytokines was also decreased in BMDMs with myeloid-specific deletion of SIRT6 after stimulation of PM2.5. In vivo, Sirt6fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM2.5 exposure.Conclusion: Our results revealed that SIRT6 promotes the PM2.5-induced airway inflammation in macrophages and indicated that inhibition of SIRT6 in macrophages may represent therapeutic strategy for airway disorders induced by airborne particulate pollution.Keywords: particulate matter, SIRT6, macrophage, lung inflammation

Jing Feng,1– 3 Xiaohua Xie,4 Zhenjie Teng,4,5 Wenjie Fei,1,2 Yunfeng Zhen,2 Jingzhen Liu,2 Liqun Yang,2 Shuchun Chen1– 3 1Department of Endocrinology, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 3Hebei Key Laboratory of Metabolic Disease, Shijiazhuang, Hebei Province, People’s Republic of China; 4Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 5Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comObjective: To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM.Results: Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001).Conclusion: Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.Keywords: diabetic kidney disease, type 2 diabetes mellitus, retinal venules, retinal arterioles, diameter

Xiaoyu Pan,1,2 Zhuoya Jia,1,2 Ruoxi Zhen,1,2 Lin Yue,3 Shu Niu,1,4 Jiangli Ban,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: Studies have shown that atherosclerotic plaques are associated with changes in the microbial composition of the intestinal flora and obesity, and that the small intestine plays an irreplaceable role in regulating intestinal flora homeostasis, but the role of the small intestine in the development of obesity-related atherosclerosis remains understudied. Therefore, this study explores the role of the small intestine in obesity-induced atherosclerosis and its molecular mechanisms.Methods: In the GSE59054 data, small intestine tissue samples from 3 normal and 3 obese mice were analyzed using bioinformatics methods. Screening for differentially expressed genes (DEGs) using the GEO2R tool. The DEGs were next processed for bioinformatics analysis. We constructed an obese mouse model and measured aortic arch pulse wave velocity (PWV). Aortic and small intestine tissues were stained with hematoxylin-eosin (HE) to observe pathological changes. Finally, immunohistochemistry was performed to verify the expression of small intestinal proteins.Results: We identified a total of 122 DEGs. Pathway analysis revealed that BMP4, CDH5, IL1A, NQO1, GSTM1, GSTA3, CAV1 and MGST2 were mainly enriched in the Fluid shear stress and atherosclerosis pathway. In addition, BMP4, NQO1 and GSTM1 are closely related to atherosclerosis. Ultrasound and pathological findings suggest the presence of obesity atherosclerosis. Immunohistochemistry verified high expression of BMP4 and low expression of NQO1 and GSTM1 in obese small intestine tissues.Conclusion: The altered expression of BMP4, NQO1 and GSTM1 in small intestine tissues during obesity may be related to atherosclerosis, and Fluid shear stress and atherosclerosis pathway may be the molecular mechanism of their role.Keywords: obesity, differentially expressed genes, atherosclerosis, small intestine, bioinformatics analysis

Liping Mai,1,&ast; Guodong He,1,&ast; Jing Chen,1 Jiening Zhu,1 Shaoxian Chen,1 Hui Yang,1 Mengzhen Zhang,1 Xinghua Hou,1 Miaola Ke,2 Xiaohong Li1,3 1Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 2Department of Blood Transfusion, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Li, Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Email lixiaohong@gdph.org.cn Miaola Ke, Department of Blood Transfusion, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email keml@sysucc.org.cnBackground: Profilin-1 (PFN1) regulates the dynamic balance of actin and plays an important role in cell functions as a hub protein in signaling molecule interaction networks. Dysregulation of PFN1 is related to pathologic kidney diseases. Diabetic nephropathy (DN) was recently reported as an inflammatory disorder, however, the molecular mechanisms of PFN1 in DN remain unclear. Therefore, the present study was conducted to explore the molecular and bioinformatic characteristics of PFN1 in DN.Methods: Bioinformatics analyses were performed on the chip of database in DN kidney tissues. A cellular model of DN was established in human renal tubular epithelial cells (HK-2) induced by high glucose. The PFN1 gene was overexpressed or knocked-down to investigate its function in DN. Flow cytometry was used to detect cell proliferation and apoptosis. PFN1 and proteins in the related signaling pathways were evaluated by Western blotting.Results: The expression of PFN1 was significantly increased in DN kidney tissues (P < 0.001) and was correlated with a high apoptosis-associated score (Pearson’s correlation = 0.664) and cellular senescence-associated score (Pearson’s correlation = 0.703). PFN1 protein was mainly located in cytoplasm. Overexpression of PFN1 promoted apoptosis and blocked the proliferation of HK-2 cells treated with high levels of glucose. Knockdown of PFN1 led to the opposite effects. Additionally, we found that PFN1 was correlated with the inactivation of the Hedgehog signaling pathway in HK-2 cells treated with high levels of glucose.Conclusion: PFN1 might play an integral role in the regulation of cell proliferation and apoptosis during DN development by activating the Hedgehog signaling pathway. This study provided molecular and bioinformatic characterizations of PFN1, and contributed to the understanding of the molecular mechanisms leading to DN.Keywords: PFN1, diabetic nephropathy, bioinformatic characterization, Hedgehog signaling pathway, apoptosis

Xiaoyi Chen,1,2 Jingyu Zhao,3 Yanxue You,1,2 Zelin Li,2 Shuchun Chen2 1Graduate School, Hebei North University, Zhangjiakou, 075000, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 3Graduate School, North China University of Science and Technology, Tangshan, 063210, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email chenshuchunwork88@163.comPurpose: Type 2 diabetic retinopathy is a long-term chronic inflammatory disease. The aim of this study was to investigate the relationship between fibrinogen to albumin ratio (FAR) and retinopathy in type 2 diabetic patients.Methods: This was a retrospective study that included 500 patients with type 2 diabetes mellitus (T2DM), and were divided into non-diabetic retinopathy group (NDR, n=297) and diabetic retinopathy group (DR, n=203) according to fundus examination findings, and the DR group was further divided into non-proliferative retinopathy group (NPDR, n=182) and proliferative retinopathy group (PDR, n=21). Baseline data of patients were collected, and the fibrinogen to albumin ratio (FAR) and neutrophil to lymphocyte ratio (NLR) were calculated to analyze the correlation between FAR and NLR and type 2 diabetic retinopathy.Results: The FAR and NLR were significantly higher in the DR group compared with the NDR group (both P < 0.001). Spearman correlation analysis showed that FAR was positively correlated with NLR and DR (P < 0.05). As the FAR quartile increased, the prevalence of DR increased (14.8%, 16.7%, 25.1%, and 43.30%, respectively; P < 0.05). Multifactorial logistic regression analysis showed that FAR, diabetic course, systolic blood pressure (SBP) and diabetic peripheral neuropathy (DPN) were risk factors for the development of DR in patients with T2DM. The area under the ROC curve for FAR to predict DR progression was 0.708, with an optimal critical value of 7.04, and the area under the ROC curve for diabetes duration and SBP to predict DR was 0.705 and 0.588, respectively.Conclusion: Our findings show for the first time that FAR is an independent risk factor for assessing DR in patients with type 2 diabetes.Keywords: fibrinogen to albumin ratio, type 2 diabetes mellitus, diabetic retinopathy, inflammation, influencing factors

Peng Chen,1 Zhongxin Li,2 Yulong Liang,1 Ming Wei,2 Haibo Jiang,2 Shihao Chen,2 Zengren Zhao2 1Department of General Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Zengren Zhao, Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, No. 89 Donggang Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email zhaozengren@hebmu.edu.cnPurpose: Colon cancer is the main malignant tumor of the digestive tract. Hypoxia is highly related to the occurrence, progression and tumor immune microenvironment (TIME) of cancer. The aim of this study was to identify a hypoxia-associated signature with high accuracy for predicting the prognosis and TIME of colon cancer.Methods: Download colon cancer data from the GEO and TCGA databases. A novel hypoxia risk model was identified to predict the prognosis of colon cancer patients. Subsequently, GSEA, TIME and mutation analysis were performed in the hypoxia high and low risk score groups. Finally, the signature gene ANKZF1 was selected for functional verification at the cellular level.Results: A novel hypoxia risk model was identified. The risk score was significantly associated with poorer overall survival in colon cancer, and could be used as an independent prognostic factor for colon cancer. GSEA analysis found that the processes related to stimulate tumor proliferation and anti-apoptosis were significantly enriched in the hypoxia high risk score group. The expression of immunosuppressive cells and most immune checkpoints in the high risk score group was significantly higher than that in the low risk score group. In vitro cell experiments showed that knockdown the expression of ANKZF1 could inhibit the proliferation, migration and invasion of colon cancer cells.Conclusion: Hypoxia plays an important role in evaluating the TIME and predicting the prognosis of colon cancer.Keywords: colon cancer, hypoxia, prognosis, risk score, tumor immune microenvironment