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Zeyu Xie, Jia Hu, Mengting Li, Xiao Hu, Jisheng Chen Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jisheng Chen, Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People’s Republic of China, Tel +86 20-87622305, Fax +86 20-61321967, Email cjslym@163.comPurpose: This study provides a reference for healthcare organizations in the selection and rational use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition).Methods: According to the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition) released in 2023, relevant databases such as PubMed, Cochrane, and Embase, drug labels, and clinical guidelines were searched for drug information. We systematically evaluated 7 GLP-1RAs marketed in China for safety, efficacy, economy, pharmacological properties, and other attributes using a percentage scoring method.Results: The final assessment result scores from highest to lowest were semaglutide (71.5 points), dulaglutide (68.9 points), liraglutide (68.7 points), exenatide (62.5 points), lixisenatide (59.9 points), polyethylene glycol loxenatide (55.9 points), and benaglutide (45.1 points).Conclusion: When a healthcare organization introduces GLP-1RAs to their hospital, they can refer to the assessment results and use the top three recommended medications: semaglutide, dulaglutide, and liraglutide.Keywords: glucagon-like peptide-1 receptor agonist, health technology assessment, type 2 diabetes mellitus, drug evaluation

Jia Chen,1– 4,&ast; Xiaoyu Deng,1– 4,&ast; Ting Lin,1– 4 Jiefeng Huang,1– 4 Yisong Yang,1– 4 Ningfang Lian1– 4 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian, People’s Republic of China; 3Institute of Respiratory Disease, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These two authors contributed equally to this workCorrespondence: Ningfang Lian, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian Province, 350005, People’s Republic of China, Tel +86-591-87981698, Email 1533532863@qq.comPurpose: Chronic intermittent hypoxia (CIH) related arterial endothelium injury is a common cause of cardiovascular system injury. However, the mechanism still needs to be clarified. In this study, we aimed to clarify the role and mechanism of ferrostatin-1 (Fer-1) in CIH-related rat arterial endothelial cells (ROAEC) ferroptosis.Methods: ROAEC was divided into control group, CIH group, and CIH+ Fer-1 group. Cell viability was detected by cell counting kit 8 kits (CCK8). The apoptotic rate, reactive oxygen species (ROS) levels, Fe2+ levels, and lipid ROS levels were detected by flow cytometry. Malondialdehyde (MDA) levels and nicotinamide adenine dinucleotide (NAD+)/NADH ratio were detected via Elisa kits. The mRNA and protein levels of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were detected by qRT-PCR and Western blot. Mitochondrial structure and function were observed by transmission electron microscope (TEM) and mitochondrial membrane potential (MMP). Central carbon metabolism was measured to compare metabolites among each group.Results: After the CIH exposure, ROAEC cell viability decreased; The levels of cell apoptosis, ROS, Fe2+, MDA, and lip ROS increased; The levels of NAD+/NADP ratio decreased; The mRNA and protein levels of GPX4 and SLC7A11 decreased (all p< 0.05). Co-cultured with Fer-1 reversed the levels of apoptosis rate, cell viability, ROS, Fe2+, MAD, lipid ROS, NAD+/NADH ratio and the mRNA and protein expression of GPX4 and SLC7A11 (all p< 0.05). The TEM results showed that damaged mitochondrial membrane and the matrix spillover in the CIH group. The results of the JC-1 assay showed decreased MMP in the CIH group. Fer-1 treatment ameliorated the mitochondrial injury. The results of central carbon metabolism found that CIH altered the metabolites in the TCA cycle, which were reversed by Fer-1 treatment.Conclusion: CIH-induced ferroptosis in ROAEC, which were reversed by Fer-1 via reprogramming mitochondrial function.Keywords: obstructive sleep apnea, chronic intermittent hypoxia, arterial endothelium injury, ferroptosis, mitochondrial function

Jinlu Huang,1,&ast; Jiugeng Chen,2,&ast; Le Ma,3,&ast; Xieyi Zhu,4 Lili Wan,1 Xinyan Li,4 Cheng Guo1 1Department of Pharmacy, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai Mental Health Center, Shanghai, People’s Republic of China; 4College of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyan Li; Cheng Guo, Email lixy@sjtu.edu.cn; guopharm@126.comBackground: Ionomics is used to study levels of ionome in different states of organisms and their correlations. Bone cancer pain (BCP) severely reduces quality of life of patients or their lifespan. However, the relationship between BCP and ionome remains unclear.Methods: The BCP rat model was constructed through inoculation of Walker 256 cells into the left tibia. Von Frey test, whole-cell patch-clamp recording and inductively coupled plasma mass spectrometry (ICP-MS) technologies were conducted for measuring tactile hypersensitivity, the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) of neurons of spinal slices, and ionome of spinal cord samples, respectively. Principal component analysis (PCA) was used to explore ionomic patterns of the spinal cord.Results: The BCP rat model was successfully constructed through implantation of Walker 256 cells into the left tibia. The frequency and amplitude of mEPSCs of neurons in the spinal cord slices from the BCP model rats were notably greater than those in the sham control. In terms of ionomics, the spinal cord levels of two macroelements (Ca and S), four microelements (Fe, Mn, Li and Sr) and the toxic element Ti in the BCP group of rats were significantly increased by inoculation of Walker 256 cancer cells, compared to the sham control. In addition, the correlation patterns between the elements were greatly changed between the sham control and BCP groups. PCA showed that inoculation of Walker 256 cells into the tibia altered the overall ionomic profiles of the spinal cord. There was a significant separation trend between the two groups.Conclusion: Taken together, inoculation of Walker 256 cells into the left tibia contributes to BCP, which could be closely correlated by some elements. The findings provided novel information on the relationship between the ionome and BCP.Keywords: bone cancer pain, spinal cord, micronutrient, ionomic profile

Jiaxin Chen,1,2 Li Feng,1,2 Shiyin Li,2 Haiyan Wang,1,2 Xin Huang,1,2 Cunzhou Shen,1,2 Huiyu Feng1,2 1Department of Neurology and Neurointensive Care Unit, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, People’s Republic of ChinaCorrespondence: Huiyu Feng, Department of Neurology and Neurointensive Care Unit, the First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China, Tel +86-020-87755766, Email fenghuiy@mail.sysu.edu.cnBackground: Since there is no clear priority or selection principle in the guidelines for myasthenia crisis, therapeutic plasma exchange (TPE) and intravenous immunoglobulin are often administered randomly. However, it should be more prudent in taking TPE due to its higher cost and risk. Studying its early response factors is crucial for managing myasthenia crisis and can improve medical and economic benefits.Methods: A prospective observational study was conducted, and patients classified as having “impending myasthenia crisis” or experiencing a myasthenia crisis and treated by TPE were included. The primary endpoint was the response after TPE. Univariate logistic regression analysis and repeated measurement were performed to analyze factors related to TPE efficacy.Results: A total of 30 patients who treated with TPE as their fast-acting treatments were enrolled. After TPE, those whose QMGs and/or MGCs decreased by ≥ 5 points or ≥ 30% of the baseline were judged as “response group”, accounting for 66.67% (20/30). Respiratory symptoms had a response rate of 72.00% (18/25), showing the most remarkable improvement. Meanwhile, extraocular symptoms were the least sensitive, with only 8.00% (2/25) showing efficacy. Thymoma (100.00% vs 50.00%, P=0.002) and a high concentration of AChR-Ab (37.37 nmol/L vs 25.4 nmol/L, P=0.039) were common in the early response group. Repeated measures showed significant changes in AChR-Ab and CD19+ B cells before and after TPE (all with P < 0.05). After treatment, the CD19+ B cells tended to decrease in the response group.Discussion: These results indicated that, for AChR-Ab positive generalized MG, TPE can quickly improve respiratory symptoms. Thymoma and a high concentration of AChR-Ab before TPE predict an early better response. Additionally, TPE may work by decreasing AChR-Ab levels and inducing immune regulation. Future prospective and randomized controlled studies are needed.Keywords: plasma exchange, myasthenia gravis, crisis, efficacy, neuroimmunology

Hao Guo,1,&ast; Li-Heng Li,2,&ast; Xiao-Hong Lv,1,&ast; Feng-Zhi Su,1,&ast; Jie Chen,1,&ast; Fei Xiao,1,3 Min Shi,1 Yu-Bo Xie1,3 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, The Guilin Municipal Hospital of Traditional Chinese Medicine, Guangxi, People’s Republic of China; 3Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-Bo Xie, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530000, People’s Republic of China, Tel +86 13977121557, Email xybdoctor@163.comPurpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery.Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥ 6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD.Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04– 1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09– 9.52], P=0.034) were independent risk factors for the development of POD.Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.Keywords: sleep disturbances, postoperative delirium, postoperative sleep quality, postoperative pain, anesthesia

Jiaxin Luo,1,2,&ast; Hanchi Wang,1,2,&ast; Jingxia Chen,1,2 Xuyan Wei,1,2 Jian Feng,1,2 Yidi Zhang,1,2 Yanmin Zhou1,2 1Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yidi Zhang; Yanmin Zhou, Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China, Email zhangyidi@jlu.edu.cn; zhouym@jlu.edu.cnAbstract: Immune cells are pivotal in the dynamic interplay between hypoxia and inflammation. During hypoxic conditions, HIF-1α, a crucial transcription factor, facilitates the adaptation of immune cells to the hypoxic micro-environment. This adaptation includes regulating immune cell metabolism, significantly impacting inflammation development. Strategies for anti-inflammatory and hypoxic relief have been proposed, aiming to disrupt the hypoxia-inflammation nexus. Research extensively focuses on anti-inflammatory agents and materials that target immune cells. These primarily mitigate hypoxic inflammation by encouraging M2-macrophage polarization, restraining neutrophil proliferation and infiltration, and maintaining Treg/TH17 balance. Additionally, oxygen-releasing nano-materials play a significant role. By alleviating hypoxia and clearing reactive oxygen species (ROS), these nano-materials indirectly influence immune cell functions. This paper delves into the response of immune cells under hypoxic conditions and the resultant effects on inflammation. It provides a comprehensive overview of various therapies targeting specific immune cells for anti-inflammatory purposes and explores nano-materials that either carry or generate oxygen to alleviate anoxic micro-environments.Keywords: hypoxia, inflammation, immunometabolism, immunotherapy, nanotherapy

Lujie Wei,1,&ast; Pingyang Li,2,&ast; Xiaofeng Liu,1 Yuxia Wang,1 Zhengping Tang,1 Hang Zhao,1 Lu Yu,3 Kaixiu Li,1 Jianping Li,1 Min Du,4 Xinzhu Chen,2 Xin Zheng,2 Yixiong Zheng,5 Yao Luo,2 Jing Chen,5 Xiamin Jiang,6 Xiaobing Chen,7 Huaicong Long1 1Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 2Medical College, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Nanbu County People’s Hospital, Nanbu, Sichuan, People’s Republic of China; 5College of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 6Clinical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaicong Long, Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, People’s Republic of China, Tel +86 18981838105, Fax +86-28-8779 5585, Email longhc69@163.comBackground: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear.Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year.Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People’s Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC).Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P< 0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663– 0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693– 0.891); sensitivity, 86.3%; specificity, 60.0%).Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.Keywords: chronic obstructive pulmonary disease, frailty, acute exacerbations

Shuting Wu, Guichan Liao, Jingchun Mao, Haiming Yan, Juanjuan Chen, Jie Peng Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jie Peng, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Tel +8613802515784, Fax +86 20 87719653, Email Pjie138@163.comPurpose: The purpose of the study was to explore the potential risk factors of mortality in patients with severe pneumonia during the omicron pandemic in South China in 2022.Methods: Clinical data was collected from patients hospitalized with omicron COVID-19. Then, patients were categorized into the non-survival and survival groups. A comprehensive analysis was conducted to analyze the factors associated with negative outcome in individuals suffering from severe omicron COVID-19.Results: In this study, 155 severe COVID-19 patients were included, comprising 55 non-survivors and 100 survivors. Non-survivors, in comparison to survivors, exhibited elevated levels of various biomarkers including neutrophil count, hypersensitive troponin T, urea, creatinine, C-reactive protein, procalcitonin, interleukin-6, plasma D-dimer, and derived neutrophil-to-lymphocyte ratio (dNLR) (P < 0.05). They also displayed reduced lymphocyte count, platelet count, and albumin levels (P < 0.05) and were more prone to developing comorbidities, including shock, acute cardiac and renal injury, acute respiratory distress syndrome, coagulation disorders, and secondary infections. Platelet count (PLT) < 100 × 10^/L, interleukin-6 (IL-6) > 100 pg/mL, and dNLR > 5.0 independently contributed to the risk of death in patients suffering from severe COVID-19.Conclusion: PLT, IL-6, and dNRL independently contributed to the risk of mortality in patients with severe pneumonia during the 2022 omicron pandemic in South China.Keywords: COVID-19, omicron, severe infection, dNLR, risk factors

Zhen Yang,1,&ast; Xingyu Kao,1,&ast; Na Huang,1 Kang Yuan,2 Jingli Chen,2 Mingfeng He2 1The Eighth School of Clinical Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong Province, People’s Republic of China; 2Foshan Hospital of Traditional Chinese Medicine, Foshan, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingli Chen; Mingfeng He, Email fstcmcjl@126.com; he-mingfeng@foxmail.comPurpose: Sepsis-induced lung injury (SLI) is a serious complication of sepsis. PANoptosis, a novel form of inflammatory programmed cell death that is not yet to be fully investigated in SLI. Our research aims to screen and validate the signature genes of PANoptosis in SLI by bioinformatics and in vivo experiment.Methods: SLI-related datasets were downloaded from NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of SLI were identified and intersected with the PANoptosis gene set to obtain DEGs related to PANoptosis (SPAN_DEGs). Then, Protein–Protein Interaction (PPI) network and functional enrichment analysis were conducted based on SPAN_DEGs. SVM-REF, LASSO and RandomForest three algorithms were combined to identify the signature genes. The Nomogram and ROC curves were performed to predict diagnostic value. Immune infiltration analysis, correlation analysis and differential expression analysis were used to explore the immunological characterization, correlation and expression levels of the signature genes. Finally, H&E staining and qRT-PCR were conducted for further verification in vivo experiment.Results: Twenty-four SPAN_DEGs were identified by intersecting 675 DEGs with the 277 PANoptosis genes. Four signature genes (CD14, GSDMD, IL1β, and FAS) were identified by three machine learning algorithms, which were highly expressed in the SLI group, and had high diagnostic value in the diagnostic model. Moreover, immune infiltration analysis showed that most immune cells and immune-related functions were higher in the SLI group than those in the control group and were closely associated with the signature genes. Finally, it was confirmed that the cecum ligation and puncture (CLP) group mice showed significant pathological damage in lung tissues, and the mRNA expression levels of CD14, IL1β, and FAS were significantly higher than the sham group.Conclusion: CD14, FAS, and IL1β may be the signature genes in PANoptosis to drive the progression of SLI and involved in regulating immune processes.Keywords: sepsis, lung injury, PANoptosis, machine learning, immune infiltration analysis

Linlin Liu,1,&ast; Xiufen Wang,2,3,&ast; Li Luo,2,3 Xuhui Liu,2,3 Jingfang Chen1– 4 1Hengyang Medical School, School of Nursing, University of South China, Hengyang, People’s Republic of China; 2Department of the Third Pulmonary Disease, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3National Clinical Research Center for Infectious Diseases, Shenzhen, People’s Republic of China; 4Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuhui Liu; Jingfang Chen, Email liuxuhui666@126.com; 13823139640@163.comBackground: Tuberculosis destroyed lung constitutes a significant worldwide public health challenge, little is known about its associated risk factors and prognosis. Our study aimed to identify the risk factors of tuberculosis destroyed lung among pulmonary tuberculosis and structural lung diseases.Methods: Between January 2019 and December 2021, a case-control study was conducted at the Third People’s Hospital of Shenzhen in China. We collected the clinical data among patients with pulmonary tuberculosis and structural lung diseases. Cases were defined as patients with tuberculosis destroyed lung. Controls were not diagnosed with the tuberculosis destroyed lung. A binary logistic regression was performed.Results: In our study, a total of 341 patients met the inclusion criteria, including 182 cases and 159 controls. We found that age ranges of 46– 60 years (aOR: 4.879; 95% CI: 2.338– 10.180), > 60 years (aOR: 3.384; 95% CI: 1.481– 7.735); history of TB treatment (aOR: 2.729; 95% CI: 1.606– 4.638); malnutrition (aOR: 5.126; 95% CI: 1.359– 19.335); respiratory failure (aOR: 5.080; 95% CI: 1.491– 17.306); and bronchiarctia (aOR: 3.499; 95% CI: 1.330– 9.209) were the independent risk factors for tuberculosis destroyed lung. Conversely, having a normal (aOR: 0.207; 95% CI: 0.116– 0.371) or overweight BMI (aOR: 0.259; 95% CI: 0.090– 0.747) emerged as a protective factor against tuberculosis destroyed lung.Conclusion: This study indicated that tuberculosis destroyed lung is a common condition among patients with pulmonary tuberculosis and structural lung diseases. The independent risk factors for tuberculosis destroyed lung were identified as being within the age groups of 46– 60 and over 60 years, having a previous history of TB treatment, malnutrition, respiratory failure, and bronchiarctia. It is essential to closely monitor patients possessing these risk factors to prevent the progression towards tuberculosis destroyed lung.Keywords: tuberculosis, pulmonary, tuberculosis destroyed lung, structural lung diseases, risk factors

Liang Tan,1,&ast; Feilong Wang,1,&ast; Yi Huang,2 Chuhua Fu,3 Haijun Zhang,4 Jianfei Feng,5 Yincai Xu,6 Xinzhen Ye,7 Rongrui Tang,8 Yinglian Chen,9 Liansheng Mou,10 Ronghao Li,11 Jingyu Chen,1 Jishu Xian1 1Department of Neurosurgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, The Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 3Department of Neurosurgery, Xiangyang No.1 People’s Hospital, University of Medicine, Xiangyang, Hubei, People’s Republic of China; 4Department of Neurosurgery, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 5Department of Encephalopathy, Beibei Traditional Chinese Medical Hospital, Chongqing, People’s Republic of China; 6Department of Neurosurgery, Zheng Coal General Hospital, Zhengzhou, Henan Province, People’s Republic of China; 7Department of Neurosurgery, Songshan General Hospital, Chongqing, People’s Republic of China; 8Department of Neurosurgery, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 9Zhuhai Brainlightning Research Institute, Zhuhai City, Guangdong, People’s Republic of China; 10Department of Neurosurgery, Liangping District People’s Hospital, Chongqing, People’s Republic of China; 11Department of Basic Medicine, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyu Chen; Jishu Xian, Email Cjy1_2001@Hotmail.com; 1370321419@qq.comPurpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs.Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes.Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p> 0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1– 12) vs 4(1– 8), p< 0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p< 0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death.Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients.Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.Keywords: SARS-CoV-2, intensive care unit, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury

Yue Wang,1 Jie Chen,1 Han Dong,2 Rui-Lin Ma,1 Ying Zou,3 Wei Wang,4 Qingmei Zheng,5 Ying Feng,6 Zhangyun Tan,7 Xiaoqin Zeng,8 Yinqing Zhao,7 Yan Deng,1 Yanfang Wang,1 Bei Gu,9 Aijun Sun1,10 1National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, 121000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 5Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266500, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 7Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, Guangxi, 529100, People’s Republic of China; 8Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510000, People’s Republic of China; 9Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, People’s Republic of China; 10Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100010, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnBackground: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare.Methods: This is a multicenter cross-sectional survey. Participants’ basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0– 50 people/yr, 50– 200 people/yr, and > 200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis.Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50– 200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens.Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.Keywords: polycystic ovary syndrome, consultation number, lifelong learning, insulin resistance, obesity, hyperandrogenemia, metformin

Yanxu Zhong,1,2 Huan Lu,3 Xiaodan Lu,4 Zhini He,4 Yuyan Jiang,1 Jie Chen,1 Tippawan Liabsuetrakul2 1Food Safety Monitoring and Evaluation Department, Guangxi Zhuang Autonomous Region Centre for Disease Control and Prevention, Nanning, Guangxi Region, 530000, People’s Republic of China; 2Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; 3Infectious Diseases Department, the Fourth People’s Hospital of Nanning, Nanning, Guangxi Region, 530000, People’s Republic of China; 4Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaCorrespondence: Tippawan Liabsuetrakul, Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand, Tel +66 74 451165, Fax +66 74 281166, Email tippawan.l@psu.ac.thBackground: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth.Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis.Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r &ap;0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ − 0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth.Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.Keywords: aflatoxins, EDI, birthweight, gestational age at birth, AFB1 albumin adducts

Yunpeng Feng,1 Shifeng Qiao,1 Jie Chen,1 Xin Wen,2 Yanlei Chen,3 Xiaoyu Song,1 Jiaxin Xu,1 Xiucheng Qiao,1 Jing Yang,2 Shenshen Zhang,1 Yang Feng,1 Yu Gao4 1The Second Ward of Colorectal Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 3The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of ChinaCorrespondence: Yu Gao, School of Basic Medical Sciences, Jinzhou Medical University, No. 40, Section 3 Songpo Road, Jinzhou, Liaoning, 121000, People’s Republic of China, Tel +86 15904161717, Email jzykdxgy@163.comPurpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells.Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases.Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis.Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.Keywords: M2-type macrophages, cancer-associated fibroblasts, colorectal cancer, liver metastasis

Xingping Zhou,1,&ast; Jinjin Luo,1,&ast; Xi Liang,1,2 Peng Li,1 Keke Ren,1 Dongyan Shi,1,2 Jiaojiao Xin,1,2 Jing Jiang,1,2 Jiaxian Chen,1 Lulu He,1 Hui Yang,1 Shiwen Ma,1 Bingqi Li,1 Jun Li1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel/Fax +86-571-87236425, Email lijun2009@zju.edu.cnBackground and Aim: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with high short-term mortality. Effective biomarkers are required for its early diagnosis and prognosis. This study aimed to determine the diagnostic and prognostic value of thrombomodulin (TM) in patients with HBV-ACLF.Methods: The expression of TM during disease progression was evaluated through transcriptomics analysis. The plasma TM concentrations of 393 subjects with HBV-ACLF (n=213), acute-on-chronic hepatic dysfunction (ACHD, n=50), liver cirrhosis (LC, n=50) or chronic hepatitis B (CHB, n=50), and normal controls (NC, n=30) from a prospective multicenter cohort, were measured to verify the diagnostic and prognostic significance of plasma TM for HBV-ACLF patients by enzyme-linked immunosorbent assay (ELISA).Results: TM mRNA was highly expressed in the HBV-ACLF group compared with the ACHD group (AUROC=0.710). High expression of TM predicted poor prognosis for HBV-ACLF patients at 28/90 days (AUROCs=0.823/0.788). Functional analysis showed that TM was significantly associated with complement activation and the inflammatory signaling pathway. External validation confirmed its high diagnostic accuracy for HBV-ACLF patients (AUROC=0.796). Plasma TM concentrations were correlated with organ failure, including coagulation and kidney failure. Plasma TM concentrations showed a potential prognostic value for 28-day mortality rates (AUROC=0.702). Risk stratification specifically identified HBV-ACLF patients with a high risk of death as having a plasma TM concentration of ≥ 8.4 ng/mL.Conclusion: This study reveals that the plasma TM can be a candidate biomarker for early diagnosis and prognosis of HBV-ACLF, and might play a vital role in coagulation and inflammation.Keywords: thrombomodulin, HBV-ACLF, biomarker, organ failure

Meilan Xian,1,2,&ast; Jiaoyuan Xu,1,3,&ast; Yamei Zheng,4 Lei Zhang,4 Jie Zhao,4 Jie Chen,1 Siguang Li,1 Lingsang Lin,1 Yi Zhong,4 Zehua Yang,4 Tian Xie,4 Linhui Huang,4 Yipeng Ding1,4 1Department of General Practice, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, Hainan, 570311, People’s Republic of China; 2Department of General Diseases, Hainan Chengmei Hospital, Haikou, Hainan, 570300, People’s Republic of China; 3Department of General Clinic, Longbo Health Hospital, Lingao County, Hainan, 571800, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yipeng Ding; Linhui Huang, Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, People’s Republic of China, Email ypding@yeah.net; rochelle-11@163.comBackground: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches.Methods: Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments.Results: Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and SRC, ADRB2, MMP2, and NOS3 were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with SRC, ADRB2, MMP2, and NOS3. In vitro experiments demonstrated that peimisine significantly upregulated the expression of ADRB2 and NOS3 and downregulated the expression of SRC and MMP2.Conclusion: These findings indicate that CBM may modulate the expression of SRC, ADRB2, MMP2, and NOS3, thereby exerting a protective effect against COPD.Keywords: chuanbeimu, molecular docking, network pharmacology, experiment verification, chronic obstructive pulmonary disease

Guojun Tong,1,2 Hai Qian,1 Dongli Li,2 Jing Li,2 Jing Chen,2 Xiongfeng Li,3 Zhenhua Tan1 1General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of China; 2Central Laboratory, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of China; 3Orthopedic Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of ChinaCorrespondence: Zhenhua Tan, General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Sanhuan North Road 1558&num;, Huzhou, People’s Republic of China, Email Tanzh99@163.comAim: This study aims to explore the effect of different doses of antibiotics on rats in order to observe alterations in their fecal microbiota, inflammatory changes in the colonic mucosa and four types of inflammatory markers in blood serum.Methods: Our methodology involved separating 84 female Sprague Dawley rats into groups A-G, with each group consisting of 12 rats. We collected the rat feces for analysis, using a distinct medium for bacterial cultivation and counting colonies under a microscope. On the 11th and 15th days of the experiment, half of the rats from each group were euthanized and 5 mL of abdominal aortic blood and colon tissues were collected. Inflammations changes of colon were observed and assessed by pathological Hematoxylin Eosin (HE) staining. Enzyme-linked immune sorbent assay (ELISA) was adopted for detecting C-reactive protein (CRP), IL-6, IL1-β and TNF-α.Results: Our findings revealed that the initial average weight of the rats did not differ between groups (p> 0.05); but significant differences were observed between stool samples, water intake, food intake and weight (p=0.009, < 0.001, 0.016 and 0.04, respectively) within two hours after the experiment. Additionally, there were notable differences among the groups in nine tested microbiota before and after weighting methods (all p< 0.001). There were no difference in nine microbiota at day 1 (all p> 0.05); at day 4 A/B (p=0.044), A/D (p< 0.001), A/E (p=0.029); at day 8, all p< 0.01, at day 11, only A/F exist significant difference (p< 0.001); at day 14 only A/D has difference (p=0.045). Inflammation changes of colon were observed between groups A-G at days 11 and 15. Significant differences between all groups can be observed for CRP, IL-6, IL1-β and TNF-α (p< 0.001).Conclusion: This study suggests that antibiotics administration can disrupt the balance of bacteria in the rat gut ecosystem, resulting in an inflammatory response in their bloodstream and inducing inflammation changes of colon. Keywords: antibiotics, imbalance of intestinal flora, Sprague Dawley rats, inflammatory bowel disease, IBD, colitis model

Baishen Zhang,1 Jing Chen,2 Hui Yu,2 Meichen Li,2 Muyan Cai,3 Likun Chen2 1Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China; 2Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China; 3Department of Pathology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of ChinaCorrespondence: Muyan Cai, Department of Pathology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, 651 Dongfeng E Road, Yuexiu District, Guangzhou, 510060, People’s Republic of China, Email caimy@sysucc.org.cn Likun Chen, Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, 651 Dongfeng E Road, Yuexiu District, Guangzhou, 510060, People’s Republic of China, Email chenlk@sysucc.org.cnBackground: Currently, there is a lack of well-established markers to predict the efficacy of chemoimmunotherapy in small-cell lung cancer (SCLC). Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), advanced lung cancer inflammation index (ALI) and prognostic nutritional index (PNI) are associated with prognosis in several tumors, whereas their predictive role in SCLC remains unclear.Methods: A retrospective study was conducted at Sun Yat-sen University Cancer Center, involving extensive-stage SCLC (ES-SCLC) patients who received first-line chemoimmunotherapy between January 2020 and December 2021. Peripheral blood biomarkers were extracted from medical records and their correlation with prognosis and immune-related adverse events (IRAEs) was analyzed.Results: A total of 114 patients were included. Patients with a low PLR, high ALI and high PNI had prolonged progression-free survival (PFS) compared to those with a high PLR, low ALI and low PNI. Patients with a low NLR, low PLR, high ALI and high PNI had prolonged overall survival (OS) compared to those with a high NLR, high PLR, low ALI and low PNI. Cox regression model showed that PNI was an independent risk factor for both PFS and OS. ROC curve showed that PNI outperforms NLR, PLR and ALI in predicting both PFS and OS. The PNI-based nomogram demonstrated strong predictive capability for both PFS and OS. In addition, there was a significant correlation between PNI and IRAEs.Conclusion: A high baseline PNI might be associated with improved prognosis and the occurrence of IRAEs in ES-SCLC patients treated with first-line chemoimmunotherapy.Keywords: peripheral blood markers, predictive ability, chemoimmunotherapy, small-cell lung cancer, immune-related adverse events

Jinji Chen,1,&ast; Herong Zhu,2,&ast; Shaohua Chen,3 Hua Mi1 1Department of Urology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Urology, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, People’s Republic of China; 3Department of Urology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua MiDepartment of Urology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email mihua2019@163.comShaohua ChenDepartment of Urology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email silverchan1994@163.comBackground: Apolipoprotein E (APOE) is a polymorphic protein that plays a role in lipoprotein transformation and metabolism. It is involved in numerous physiological processes within the body and is closely associated with tumor growth and metastasis. However, the role of APOE in pan-cancer has yet to be evaluated. Therefore, studying the association between APOE and various cancer types is crucial for providing a basis for individualized treatment strategies and clinical prognosis assessment.Methods: We investigated the diagnostic and prognostic significance of APOE across 33 tumor types, as well as its correlation with tumor mutation burden (TMB) and microsatellite instability (MSI). Additionally, we employed the ESTIMATE and CIBERSORT algorithms to analyze the potential impact of APOE on the immune system. Furthermore, gene set enrichment analysis (GSEA) was conducted to explore its underlying physiological function.Results: Based on observations from a pan-cancer dataset, APOE expression was significantly different between cancer and normal tissues, and was simultaneously associated with survival outcomes in terms of cancer type, clinical annotation, TMB, MSI, and TICs abundance. In addition, the results also showed that expression of APOE may respond to a variety of cancer chemotherapy.Conclusion: The findings from this study strongly indicate a close association between APOE and tumor development. Moreover, APOE shows promise as a potential biomarker for predicting prognosis and response to immunotherapy in patients with pan-cancer.Keywords: apolipoprotein E, APOE, pan-cancer, prognosis, immune infiltration

Liqun Yang,1– 3 Zhimei Zhang,3 Yunfeng Zhen,3 Jing Feng,3 Jinhu Chen,3 Guangyao Song1– 3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Hebei Key Laboratory of Metabolic Disease, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Guangyao Song, Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86-0311-8598-8556, Email sguangyao2@163.comPurpose: Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism.Patients and Methods: 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism.Results: In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219– 0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032).Conclusion: The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.Keywords: sirtuin, postprandial hypertriglyceridemia, insulin resistance, genetics

Jiao Chen, Danmei Luo, Chengxia Sun, Xiaolan Sun, Changmao Dai, Xiaohong Hu, Liangqing Wu, Haiyan Lei, Fang Ding, Wei Chen, Xueping Li Geriatric Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Xueping Li, Chengdu University of Traditional Chinese Medicine, No. 37, Shier Bridge Road, Chengdu, Sichuan, People’s Republic of China, Tel +86-18380251086, Email 3173907@qq.comPurpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults.Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a “non-re-positive” group and a “re-positive” group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model’s goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively.Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was > 8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was > 80%, the positive estimated value was closer to the actual number of cases.Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.Keywords: malnutrition, COVID-19, re-positive, clinical prediction model

Man Sun,1 Huan Zhang,1 Jiayi Liu,1 Jiayi Chen,1 Yaxin Cui,1 Simiao Wang,1 Xiangyu Zhang,2 Zhaogang Yang1 1School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China; 2Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310020, People’s Republic of ChinaCorrespondence: Xiangyu Zhang; Zhaogang Yang, Tel/Fax +86-431-85155320, Email 3314023@zju.edu.cn; zhaogangyang@jlu.edu.cnAbstract: Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.Keywords: extracellular vesicles, gene therapy, drug delivery system, gene drugs

Yulin Chen,1 Yi Zhang,2 Jianjun Wang,3 Xiong Cai,1 Junzhang Chen,1 Xiaobo Min,1 Yunjie Xu,1 Qi Qin,1 Chidan Wan1 1Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Engineering Research Center of Tumor-Targeted Biochemotherapy, Wuhan, 430030, People’s Republic of China; 3Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of ChinaCorrespondence: Qi Qin; Chidan Wan, Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Email qinqi8441@163.com; wcdwhxhgdwk@163.comBackground: Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment.Methods: Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities.Results: Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in vivo. In vivo, their effectiveness primarily involves enhancing CD8+ T cell infiltration, alleviating T cell immunosuppression, and improving the immune microenvironment to combat tumors. When used in combination with anti-PD-1, their anti-tumor effects are further enhanced. Moreover, some mice treated with Dox-TMPs developed anti-tumor immunity, displaying a self-specific T-cell immune response upon re-challenged with tumor cells. This suggests that Dox-TMPs also have the potential to act as a long-term immune response against tumor recurrence, indicating their capability as a tumor vaccine.Conclusion: Dox-TMPs exhibit a dual role in liver cancer by regulating T cells within the tumor microenvironment, functioning both as an anti-tumor agent and a potential tumor vaccine. Keywords: liver cancer, drug-loaded microparticles, tumor immune microenvironment, tumor vaccine

Wenxuan Li,1,&ast; Zhikai Zheng,2,3,&ast; Jiongliang Wang,2,3,&ast; Tianqing Wu,2,3,&ast; Juncheng Wang,2,3 Yangxun Pan,2,3 Jinbin Chen,2,3 Dandan Hu,2,3 Li Xu,2,3 Yaojun Zhang,2,3 Minshan Chen,2,3 Zhongguo Zhou2,3 1Cancer Center, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncheng Wang; Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343115 ; +86-20-87343117, Email wangjch@sysucc.org.cn; zhouzhg@sysucc.org.cnPurpose: The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC).Patients and Methods: Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed.Results: The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P< 0.05) and 15.6 months (P< 0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P< 0.05) and 45.0 months (P< 0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P< 0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P< 0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P< 0.05) and 21.7 months (P< 0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up.Conclusion: HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.Keywords: hepatic arterial infusion chemotherapy, advanced hepatocellular carcinoma, conversion therapy

Xingqiang Wang,1,2,&ast; Xianna Yang,3,&ast; Shiqi Wang,3,&ast; Xiaofang Tian,1 Jianmei Yin,3 Nian Liu,3 Pengtao Di,1 Jipeng Qi,3 Ya Li,3 Jimin Chen,3,4 Yang Wu,1 Jingjin Wu,1,2 Weiqing Zhao,5 Jiangyun Peng,1,2 Ling Zhang,1,2 Lingli Gu1 1Department of Rheumatology, The No. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 2Yunnan Provincial Clinical Medicine Research Center of Rheumatism in TCM, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 3The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 4Department of Integrative Internal Medicine, The Lijiang Hospital of Traditional Chinese Medicine, Lijiang, Yunnan, 674100, People’s Republic of China; 5Department of Rheumatology and Immunology, The First People’s Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650034, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhang; Lingli Gu, Email zebaiyuan@126.com; guyuxin82@126.comAbstract: Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).Keywords: rheumatoid arthritis, glucocorticoids tapering, clinical trial, traditional Chinese medicine, Yupingfeng Guizhi Decoction, Juanbi Decoction

Chunxia Jiang,1– 4,&ast; Xiumei Ma,1– 4,&ast; Jiao Chen,2– 5,&ast; Yan Zeng,1– 4 Man Guo,2– 4 Xiaozhen Tan,2– 4 Yuping Wang,1,6 Peng Wang,1 Pijun Yan,2– 4 Yi Lei,1– 4 Yang Long,2– 4 Betty Yuen Kwan Law,1 Yong Xu1– 4 1Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology, The Third’s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People’s Republic of China; 6Department of Breast, Thyroid and Vascular Surgery, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Betty Yuen Kwan Law, Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, 999078, People’s Republic of China, Email yklaw@must.edu.mo Yong Xu, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email xywyll@swmu.edu.cnPurpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA).Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P< 0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17– 99% and 0.36, and 24– 99% and 0.24 for the models in normal lactate and high lactate groups, respectively.Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.Keywords: serum lactate, diabetic kidney disease, nomograms, prediction model, risk factors

Kai Zhao,1,2 Yali Gao,1,2 Jianping Zhang,1,2 Shan Wang,1,2 Jiaqi Chen,1,2 Fenglin Guo,1,2,&ast; Sheng Wang1,2,&ast; 1Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, People’s Republic of China; 2Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fenglin Guo; Sheng Wang, Department of Anesthesiology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Tel +86 15395006763 ; +86 19156007726, Email 1030651261@qq.com; iamsheng2020@ustc.edu.cnPurpose: We designed this study to investigate the effect of intravenous use of penehyclidine on postoperative nausea and vomiting (PONV) after gynecological laparoscopic surgery.Patients and Methods: Ninety-two Women Patients (Aged ≥ 18) Scheduled for Elective Gynecologic Laparoscopy Were Enrolled in the Current Study. Patients Were Equally Randomized Assigned Into Penehyclidine group (PHC group: received a bolus of penehyclidine 10 μg/kg during the induction of anesthesia, then followed by a continuous infusion of 10 μg/kg penehyclidine at a fixed rate of 2.0 mL/h in postoperative intravenous analgesia pump over 48h, 0.5 mg upper limit respectively) or Control group (received 0.9% saline in replace of penehyclidine at the same time points). The primary outcome measure was the incidence of postoperative nausea and vomiting in the postanesthesia care unit and ward area. Quality of Recovery-15 (QoR-15) scores and general comfort questionnaire (GCQ) scores were assessed on postoperative day (POD) 1, 2.Results: Patients between two groups had comparable baseline characteristics. Compared with the Control group, the incidence and severity of PONV, postoperative nausea (PON), and postoperative vomiting (POV) were significantly lower in the PHC group at 2h (PONV: P = 0.002, P = 0.004, respectively; PON: P = 0.018, P = 0.038, respectively; POV: P = 0.011, P = 0.072, respectively), 24h (PONV: P = 0.003, P = 0.001, respectively; PON: P = 0.010, P = 0.032, respectively; POV: P = 0.006, P = 0.044, respectively), and 48h (PONV: P = 0.003, P = 0.002, respectively; PON: P = 0.007, P = 0.019, respectively; POV: P = 0.002, P = 0.013, respectively) after surgery. The QoR-15 and GCQ scores of the PHC group were significantly higher than those of the Control group at POD 1, 2 (P < 0.001; P < 0.001, respectively).Conclusion: Our findings suggest that perioperative intravenous application of penehyclidine can effectively prevent postoperative nausea and vomiting in gynecological laparoscopic surgery patients and improve postoperative recovery.Keywords: penehyclidine, gynecologic laparoscopy, postoperative nausea and vomiting, quality of recovery

Shifeng Sheng,1 Jingfeng Chen,1 Yuheng Zhang,1 Weikang Li,1 Feifei Li,1 Rong Gou,2 Lin Tang,2 Suying Ding1 1Health Management Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Lin Tang, Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu Middle Ring Road, Jinshui District, Zhengzhou, 450052, People’s Republic of China, Tel +86 13783623040, Email tanglin@zzu.edu.cn Suying Ding, Health Management Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu Middle Ring Road, Jinshui District, Zhengzhou, 450052, People’s Republic of China, Tel +86 15838023097, Email fccdingsy@zzu.edu.cnObjective: To explore the correlation between serum uric acid (SUA) trajectories and new-onset hypertension, to provide scientific basis for the prevention and treatment of hypertension.Methods: The study cohort was composed of 4372 subjects who met the inclusion criteria in the cohort study of Henan physical examination population. According to the SUA values of the subjects’ physical examination from 2017 to 2019, three different SUA trajectory groups were determined by R LCTM tools, namely low stability group, medium stability group and high stability group. The incidence of hypertension during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product limit method, and the correlation between different SUA trajectories and new-onset hypertension was analyzed by Cox proportional hazards regression model.Results: The incidence rate of hypertension increased with the increase of SUA locus, which was 4.65%, 9.18% and 12.43% respectively, and the difference was statistically significant (P< 0.001). After adjusting multiple confounding factors, such as gender, waist circumference (WC), blood pressure, body mass index (BMI), fasting plasma glucose (FPG) and blood lipid by Cox proportional hazards regression model, the risk of hypertension in SUA medium stability and high stability group was still 1.476 times ( 95% CI: 1.089~2.000) and 1.692 times ( 95% CI: 1.152~2.484) of low-stable SUA group (P< 0.05).Conclusion: The risk of hypertension increases with the increase of SUA level in the long-term normal range. It is necessary to carry out the intervention for hypertension with long-term normal high value to avoid the progress of hypertension disease, to achieve the purpose of early prevention of hypertension.Keywords: uric acid, hypertension, trajectories, correlation, health physical examination

Fei Zhang,&ast; Qintao Ge,&ast; Jialin Meng, Jia Chen, Chaozhao Liang, Meng Zhang Department of Urology, The First Affiliated Hospital of Anhui Medical University; Institute of Urology, Anhui Medical University; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaozhao Liang; Meng Zhang, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Shushan District, Hefei City, Anhui Province, 230022, People’s Republic of China, Tel/Fax +86 55162922034, Email liang_chaozhao@ahmu.edu.cn; zhangmeng1930@126.comBackground: The specific involvement of the CD8+ T effector memory RA (TEMRA) subset in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has largely not been explored in the literature.Methods: Targeted single-cell RNA sequencing (scRNA-seq) profiles were generated from peripheral blood mononuclear cells (PBMCs) obtained from two CP/CPPS patients and two healthy controls (HCs) in our recent study. Pseudotime series algorithms were used to reveal the differentiation trajectory, CellChat analysis was used to explore the communication between individual cells, and the SCENIC program was used to identify potential transcription factors (TFs). Based on the cosine similarity, clusters of differentially expressed genes (DEGs) were considered to be further enriched in different pathways. To confirm the functional role of the critical clusters, flow cytometry was employed.Results: The results revealed the molecular landscape of these clusters, with TEMRA cells exhibiting pronounced cytokine-mediated signaling pathway enrichment. Pseudotime trajectory analysis further mapped the evolution from naïve T cells to that of TEMRA cells, elucidating the developmental pathways involved in the immune context. A significant finding from CellChat analysis was the differential expression of ligands and receptors, with CD8+ TEMRA cells showing enhanced signaling, particularly in the CP/CPPS context, compared to HCs. Flow cytometry confirmed these results, revealing a heightened proinflammatory cytokine profile in patients with chronic prostatitis-like symptoms (CP-LS), suggesting that TEMRA cells play a significant role in disease pathogenesis. TF profiling across the T-cell clusters identified key regulators of cellular identity, identifying novel therapeutic targets. Elevated TNF signaling activity in CD8+ TEMRA cells underscored the involvement of these cells in disease mechanisms.Conclusion: This study elucidates the pivotal role of the CD8+ TEMRA cell subset in CP/CPPS, which is characterized by increased TNF signaling and proinflammatory factor expression, highlighting potential biomarkers and opening new avenues for therapeutic intervention.Keywords: chronic prostatitis/chronic pelvic pain syndrome, targeted single-cell RNA sequencing, CD8+ TEMRA, periblood memory T-cell

Jin Chen,1,2,&ast; Zhi-Yong Li,2,&ast; Fei Xu,2,&ast; Chao-Qun Wang,1 Wen-Wen Li,1 Jin Lu,1 Chao-Yu Miao2 1Department of Endocrinology and Metabolism, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, People’s Republic of China; 2Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao-Yu Miao, Department of Pharmacology, Second Military Medical University/Naval Medical University, 325 Guo He Road, Shanghai, 200433, People’s Republic of China, Email cymiao@smmu.edu.cn Jin Lu, Department of Endocrinology and Metabolism, Changhai Hospital, Second Military Medical University/Naval Medical University, 168 Chang Hai Road, Shanghai, 200433, People’s Republic of China, Email lujin-sh@139.comObjective: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Metrnl is a secreted protein that plays an important role in kidney disease. The aim of this study was to investigate DKD-related factors and the correlation between serum Metrnl levels and the severity of DKD.Methods: Ninety-six type 2 diabetes mellitus (T2DM) patients and 45 DKD patients were included in the study. A range of parameters were measured simultaneously, including waist-to-hip ratio (WHR), body mass index (BMI), urinary albumin/creatinine ratio (UACR), monocyte–lymphocyte ratio (MLR), albumin/globulin (A/G), liver and kidney function, blood lipid profile, islet function, and others. Subsequently, the related factors and predictive significance of DKD were identified. The correlation between the relevant factors of DKD and serum Metrnl levels with DKD was evaluated.Results: The duration of the disease (OR: 1.12, 95% CI: 1.01– 1.24, P=0.031), hypertension (OR: 4.86, 95% CI: 1.16– 20.49, P=0.031), fasting blood glucose (OR: 1.23, 95% CI: 1.03– 1.48, P=0.025), WHR (OR: 2.53, 95% CI: 1.03– 6.22, P=0.044), and MLR (OR: 1.91, 95% CI: 1.18– 3.08, P=0.008) are independent risk factors for DKD (P < 0.05). Conversely, A/G (OR: 0.13, 95% CI: 0.02– 0.76, P=0.024) and Metrnl (OR: 0.99, 95% CI: 0.98– 1.00, P=0.001) have been identified as protective factors against DKD. Furthermore, the level of Metrnl was negatively correlated with the severity of DKD (rs=− 0.447, P< 0.001). The area under receiver operating characteristic (ROC) curves for the diagnostic accuracy of Metrnl for DKD is 0.765 (95% CI: 0.686– 0.844).Conclusion: The duration of the disease, hypertension, fasting blood glucose, WHR, and MLR are major risk factors for DKD. Metrnl and A/G are protective factors for DKD. Serum Metrnl concentrations are inversely correlated with DKD severity.Keywords: diabetic kidney disease, urinary albumin/creatinine ratio, Metrnl, albumin/globulin

Qing Wang,1 Ke Liu,1 Tian Zhang,1 Ting Wang,2 Huan Li,1 Chang Wang,1 Jinhu Chen,1 Luping Ren1 1Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Clinical laboratory, Nanjing Medical College, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Luping Ren, Email renluping1122@163.comBackground: The study estimated the association between NAFLD and SUA/Cr in Chinese non-obese patients with type 2 diabetes mellitus (T2DM) and also investigated mediating effect of TG.Methods: All patients were divided into NAFLD group (n = 420) and non-NAFLD group (n = 347). The differences of biochemical indicators between the two groups were compared. The link between SUA/Cr and other parameters was checked through Spearman correlation analysis. Differences in the incidence rate of NAFLD between SUA/Cr and TG 3 tertile subgroups were tested by chi-squared. To explore the independent influence of SUA/Cr and TG on NAFLD, logistic regression was performed. The predictive value of SUA/Cr and SUA/Cr combined with BMI for NAFLD was analyzed using ROC curves. In addition, to confirm whether TG has a mediating effect on the link of SUA/Cr and NAFLD, we conducted a mediating analysis.Results: NAFLD group had higher SUA/Cr values than individuals without NAFLD (P < 0.01). SUA/Cr was linked with TC and TG (r = 0.081, 0.215 respectively). NAFLD prevalence increased progressively from quartile 1 to quartile 3 of SUA/Cr (44% vs 57% vs 62%). Prevalence of NAFLD increased from quartile 1 to quartile 3 of TG (35.8% vs 58.7% vs 69.9%). Analysis of the logistic regression revealed that SUA/Cr and TG were statistically linked with NAFLD. The ROC curve pointed out that the area under the curve (AUC), sensitivity and specificity of SUA/Cr were 0.59, 0.629 and 0.522, respectively. The AUC, sensitivity and specificity for SUA/Cr combined with BMI were 0.719, 0.644 and 0.677, separately. The mediation analysis showed a statistically direct effect of SUA/Cr on NAFLD (β=0.148, 95% CI: 0.0393, 0.2585). The function of SUA/Cr on NAFLD partially mediated by TG (β=0.1571, 95% CI: 0.0704, 0.2869).Conclusion: SUA/Cr was significantly associated with NAFLD in non-obese T2DM patients, and TG partially mediated this association. SUA/Cr can be applied to predict for NAFLD.Keywords: nonalcoholic fatty liver disease, type 2 diabetes mellitus, serum uric acid to creatinine ratio

Jiakang Chen,1,&ast; Kasim Allel,2– 4,&ast; Chuyue Zhuo,1,&ast; Wenwei Luo,5 Nanhao He,1 Xu Yang,1 Yingyi Guo,1 Jiong Wang,1 Likang Yao,1 Jiahui Li,1 Yexin Lin,1 Ruiyang Tu,6 Laith Yakob,2,3 Chao Zhuo1 1State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Disease Control, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; 3Antimicrobial Resistance Centre, London School of Hygiene & Tropical Medicine, London, UK; 4Institute for Global Health, University College London, London, UK; 5Department of Clinical Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Science and Technology Studies, University College London, London, UK&ast;These authors contributed equally to this workCorrespondence: Chao Zhuo, State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, People’s Republic of China, Email chaosheep@gzhmu.edu.cnIntroduction: Although Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) significantly contribute to bloodstream infections, their economic repercussions remain largely unquantified.Data Source and Methods: We performed a retrospective analysis of inpatients diagnosed with Escherichia coli or Klebsiella pneumoniae bacteremia in a tertiary hospital from January 2020 to December 2022 in Guangzhou, China. We employed the chi-square test to examine ESBL risk factors and utilized propensity score matching (PSM) to negate baseline confounding factors, assessing economic burden through disability-adjusted life years (DALYs), hospital costs and productivity losses. We employed mediation analysis to eliminate confounding factors and better identify ESBL sources of burden related.Results: We found 166 ESBL-EC/KP BSI patients (52.2% of the total examined 318 patients). Post-PSM analysis revealed that ESBL-producing EC/KP will reduce the effectiveness of empirical medication by 19.8%, extend the total length of hospitalization by an average of 3 days, and increase the patient’s financial burden by US&dollar;2047. No significant disparity was found in overall mortality and mean DALYs between the groups. Mediation analysis showed that the link between ESBL and hospital costs is predominantly, if not entirely, influenced by the appropriateness of empirical antibiotic treatment and length of hospital stay.Conclusion: Patients with BSI due to ESBL-producing ESBL-EK incur higher costs compared to those with non-ESBL-EK BSI. This cost disparity is rooted in varying rates of effective empirical antimicrobial therapy and differences in hospital stay durations. A nuanced approach, incorporating a thorough understanding of regional epidemiological trends and judicious antibiotic use, is crucial for mitigating the financial impact on patients.Keywords: Escherichia coli, Klebsiella pneumoniae, bacteremia, ESBL, risk factors, medical costs

Qian-Qian Liao,1,&ast; Yan-Ju Mo,2,&ast; Ke-Wei Zhu,3,4,&ast; Feng Gao,2 Bin Huang,2 Peng Chen,4 Feng-Tian Jing,5 Xuan Jiang,6 Hong-Zhen Xu,1 Yan-Feng Tang,7 Li-Wei Chu,8 Hai-Ling Huang,1 Wen-Li Wang,8 Fang-Ning Wei,9 Dan-Dan Huang,9 Bin-Jing Zhao,9 Jia Chen,9 Hao Zhang1 1Department of Pharmacy, People’s Hospital of Guilin, Guilin, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, People’s Hospital of Guilin, Guilin, People’s Republic of China; 3GuangZhou BaiYunShan Pharmaceutical Holdings CO.,LTD. BaiYunShan Pharmaceutical General Factory, Guangzhou, People’s Republic of China; 4Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 5Department of Respiratory Medicine, Xing An County People’ Hospital, Guilin, People’s Republic of China; 6Department of Hospital Infection Management, People’s Hospital of Guilin, Guilin, People’s Republic of China; 7Department of Geriatrics, People’s Hospital of Guilin, Guilin, People’s Republic of China; 8Department of Laboratory Medicine, People’s Hospital of Guilin, Guilin, People’s Republic of China; 9School of Clinical Pharmacy, Guilin Medical University, Guilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke-Wei Zhu, GuangZhou BaiYunShan Pharmaceutical Holdings CO.,LTD. BaiYunShan Pharmaceutical General Factory, No. 88 Yunxiang Road Tonghe Street, Baiyun District, Guangzhou, Guangdong Province, 510515, People’s Republic of China, Tel +86-020-87062636, Fax +86-020-87095309, Email zhukew2018@outlook.comPurpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed.Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799– 0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability.Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.Keywords: healthy volunteers, in-hospital mortality, length of stay, nomogram, pneumonia, pulmonary heart disease

Yuanyuan Xie,1,&ast; Shifang Li,1,&ast; Dinan Wu,2 Yining Wang,2 Jiepeng Chen,3 Lili Duan,3 Shuzhuang Li,4 Yuyuan Li2 1The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 3Sungen Bioscience Co., Ltd, Guangdong, People’s Republic of China; 4College of Basic Medical Science, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuyuan Li; Shuzhuang Li, Tel +86 411 86118983, Email liyuyuan831221@163.com; shuzhuangli@126.comAbstract: Vitamin K (VK) comprises a group of substances with chlorophyll quinone bioactivity and exists in nature in the form of VK1 and VK2. As its initial recognition originated from the ability to promote blood coagulation, it is known as the coagulation vitamin. However, based on extensive research, VK has shown potential for the prevention and treatment of various diseases. Studies demonstrating the beneficial effects of VK on immunity, antioxidant capacity, intestinal microbiota regulation, epithelial development, and bone protection have drawn growing interest in recent years. This review article focuses on the mechanism of action of VK and its potential preventive and therapeutic effects on infections (eg, asthma, COVID-19), inflammation (eg, in type 2 diabetes mellitus, Alzheimer’s disease, Parkinson’s disease, cancer, aging, atherosclerosis) and autoimmune disorders (eg, inflammatory bowel disease, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis). In addition, VK-dependent proteins (VKDPs) are another crucial mechanism by which VK exerts anti-inflammatory and immunomodulatory effects. This review explores the potential role of VK in preventing aging, combating neurological abnormalities, and treating diseases such as cancer and diabetes. Although current research appoints VK as a therapeutic tool for practical clinical applications in infections, inflammation, and autoimmune diseases, future research is necessary to elucidate the mechanism of action in more detail and overcome current limitations.Keywords: vitamin K, VK-dependent proteins, infection, inflammation, auto-immune disease

Beijie Qi,1,&ast; Yuqi Li,2,&ast; Zhen Peng,2 Zhiwen Luo,3 Xingyu Zhang,2 Jiwu Chen,2 Guoqi Li,2 Yaying Sun2 1Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China; 2Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaying Sun; Guoqi Li, Tel +86 17621642602 ; +86 13816307547, Email yaying.sun@shgh.cn; etherlords@163.comBackground: Acute skeletal muscle injury is common in sports. The injured muscle cannot fully recover due to fibrosis resulting from myofibroblasts. Understanding the origin of fibroblasts is, therefore, important for the development of anti-fibrotic therapies. Accumulating evidence shows that a mechanism called macrophage-myofibroblast transition (MMT) can lead to tissue or organ fibrosis, yet it is still unclear whether MMT exists in skeletal muscle and the exact mechanisms.Methods: Single-cell transcriptome of mice skeletal muscle after acute injury was analyzed with a specific attention on the process of MMT. Cell–cell interaction network, pseudotime trajectory analysis, Gene Ontology (GO), and Kyoto Genome Encyclopedia (KEGG) were conducted. A series of experiments in vivo and in vitro were launched for verification.Results: Single cell transcriptomic analysis indicated that, following acute injury, there were much interactions between macrophages and myofibroblasts. A detailed analysis on macrophages indicated that, CD68+α-SMA+ cells, which represented the status of MMT, mainly appeared at five days post-injury. KEGG/GO analysis underlined the involvement of complement system, within which C3ar1, C1qa, C1qb, and C1qc were up-regulated. Trajectory analysis also confirmed a potential shift from macrophages to myofibroblasts. These findings were verified by histological study in mice skeletal muscle, that there were much MMT cells at five days, declined gradually, and vanished 14 days after trauma, when there was remarkable fibrosis formation within the injured muscle. Moreover, C3a stimulation could directly induce MMT in BMDMs.Conclusion: Fibrosis following acute injury is disastrous to skeletal muscle, but the origin of myofibroblasts remains unclear. We proved that, following acute injury, macrophage-myofibroblast transition happened in skeletal muscle, which may contribute to fibrosis formation. This phenomenon mainly occurred at five days post-injury. The complement system can activate MMT. More evidence is needed to directly support the pro-fibrotic role of MMT in skeletal muscle fibrosis after acute injury.Keywords: skeletal muscle, fibrosis, macrophage-myofibroblast transition, single-cell transcriptomic analysis, complement system

Yiyang Li,1,&ast; Jiali Chen,1,&ast; Xingping Quan,1 Ying Chen,2 Yan Han,1 Jinfen Chen,1 Li Yang,1 Youhua Xu,3 Xu Shen,4 Ruibing Wang,1,5 Yonghua Zhao1,5 1Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macau SAR, People’s Republic of China; 2School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, People’s Republic of China; 4Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghua Zhao, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China, Tel +853-88224877, Fax +853-28841358, Email yonghuazhao@um.edu.moBackground: Ischemic stroke (IS) causes tragic death and disability worldwide. However, effective therapeutic interventions are finite. After IS, blood–brain barrier (BBB) integrity is disrupted, resulting in deteriorating neurological function. As a novel therapeutic, extracellular vesicles (EVs) have shown ideal restorative effects on BBB integrity post-stroke; however, the definite mechanisms remain ambiguous. In the present study, we investigated the curative effects and the mechanisms of EVs derived from bone marrow mesenchymal stem cells and brain endothelial cells (BMSC-EVs and BEC-EVs) on BBB integrity after acute IS.Methods: EVs were isolated from BMSCs and BECs, and we investigated the therapeutic effect in vitro oxygen-glucose deprivation (OGD) insulted BECs model and in vivo rat middle cerebral artery occlusion (MCAo) model. The cell monolayer leakage, tight junction expression, and metalloproteinase (MMP) activity were evaluated, and rat brain infarct volume and neurological function were also analyzed.Results: The administration of two kinds of EVs not only enhanced ZO-1 and Occludin expressions but also reduced the permeability and the activity of MMP-2/9 in OGD-insulted BECs. The amelioration of the cerebral infarction, BBB leakage, neurological function deficits, and the increasing ZO-1 and Occludin levels, as well as MMP activity inhibition was observed in MCAo rats. Additionally, the increased levels of Caveolin-1, CD147, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor A (VEGFA) in isolated brain microvessels were downregulated after EVs treatment. In vitro, the employment of Caveolin-1 and CD147 siRNA partly suppressed the expressions of VEGFR2, VEGFA and MMP-2/9 activity and reduced the leakage of OGD insulted BECs and enhanced ZO-1 and Occludin expressions.Conclusion: Our study firstly demonstrates that BEC and BMSC-EVs administrations maintain BBB integrity via the suppression of Caveolin-1/CD147/VEGFR2/MMP pathway after IS, and the efficacy of BMSC-EVs is superior to that of BEC-EVs. Keywords: extracellular vesicles, ischemic stroke, Caveolin-1, CD147, matrix metalloproteinase, VEGFR2, blood-brain barrier

Jun Li,1,2 Hongrui Zhu,2 Yu Wang,3 Jiaqi Chen,2 Keqiang He,2 Sheng Wang2 1Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of ChinaCorrespondence: Sheng Wang, Department of Anesthesiology, The First Affiliated Hospital of USTC, No. 17, Lujiang Road, Luyang District, Hefei, Anhui, People’s Republic of China, Email iamsheng2020@ustc.edu.cnBackground: Emergence agitation (EA) is one of the most common complications in clinical general anesthesia during recovery in adults. Remifentanil and propofol can reduce the incidence of EA, but with no randomized controlled trial to evaluate their effectiveness for treating EA. This study aims to compare the effectiveness of remifentanil and propofol for treating EA following general anesthesia.Patients and methods: Among 152 randomized patients with a mean of 49.5 years, and 99 (65.1%) of them being male, 149 were divided into two groups for subsequent analysis. The remifentanil group (Group R, n = 74) received a 0.5μg kg– 1 remifentanil infusion followed by a 0.05μg kg– 1 min– 1 infusion until 15 minutes, after the onset of agitation. The propofol group (Group P, n = 75) received a 1mg kg– 1 propofol infusion once agitation occurred. Emergence agitation was assessed using the Riker Sedation Agitation Score, with a score of ≥ 5 defining emergence agitation. During the post–anesthesia care unit (PACU), the recurrence of emergence agitation, time to extubation, and discharge from PACU were evaluated.Results: The incidence of reoccurring emergence agitation was lower in Group R (29.7%) compared with Group P (49.3%), with an odds ratio of 0.44 (95% CI 0.22– 0.85; P=0.014). The time to extubation was shorter in Group R (mean 12min, range 8– 15 min) compared with Group P (mean 17min, range 13– 21 min) (P< 0.001), as was the time discharge from the PACU (mean 30.5 min, range 25– 40 min) vs Group P (mean 37.5 min, range 31– 50 min) (P=0.001).Conclusion: Treatment of emergence agitation in adults with remifentanil infusion is more effective than propofol, with a shorter time to extubation and discharge from PACU.Keywords: anesthesia, emergence agitation, remifentanil, propofol

Jingchao Jia,1,2,&ast; Jing Yang,3,&ast; Leimin Qian,2 Biao Zhou,2 Xiaodong Tang,2 Shuanghai Liu,2 Li Wu,4 Jifeng Chen,5 Yuting Kuang1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People’s Republic of China; 3Jiangnan University Medical Center, Wuxi, People’s Republic of China; 4Department of Pharmaceutics, People’s Hospital of Shanggao, Yichun, People’s Republic of China; 5The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuting Kuang, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Email yuting_kuang@163.com Jifeng Chen, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China, Email chenjifeng-1987@163.comIntroduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range.Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2’-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy.Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth.Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA.Keywords: NIR-controlled siRNA release, nanopolyplex, UCNPs, anti-tumor therapy

Zhanlin Liao,1,&ast; Liangzhi Huang,1,&ast; Jun Chen,2 Ting Chen,1 Dezhi Kong,1 Qifeng Wei,1 Qiao Chen,1 Bin Deng,1 Yanyan Li,1 Shuai Zhong,1 Zugui Huang1 1Department of Endocrine, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People’s Republic of China; 2Department of Ophthalmology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zugui Huang, Department of Endocrine, Affiliated Nanping First Hospital of Fujian Medical University, No. 317 Zhongshan Road, Nanping, Fujian, 353006, People’s Republic of China, Email 15159969783@163.comBackground: Type 2 diabetes (T2DM) combined nonalcoholic fatty liver disease (NAFLD) are characterized by metabolic disruptions. Liraglutide has been proved to be effective in T2DM. If LRG could regulate NAFLD combined T2DM has not been reported.Methods: Intraperitoneal injection of 1% streptozotocin (STZ) plus high-sugar and high-fat diet was used to induce NAFLD combined T2DM animal model. Palmitic acid (200 μmol/L) and glucose (25 mmol/L) incubation were used to induce cell model. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and Western blotting, respectively.Results: Liraglutide significantly improved the liver injury of NAFLD combined T2DM rats, but Com-C reversed the effect of liraglutide. The decreased AMPK/mTOR signaling pathway in the NAFLD combined T2DM animals was greatly activated by liraglutide. Com-C reversed the protection effects of liraglutide on palmitic acid+glucose induced cell damage.Conclusion: Liraglutide could greatly alleviate the damage caused by NAFLD+T2DM and palmitic acid+glucose. The protection effects of liraglutide were greatly inhibited by suppressing AMPK/mTOR signaling pathway. This research might provide a novel therapeutic strategy for the prevention and treatment of NAFLD combined T2DM disease.Keywords: type 2 diabetes, nonalcoholic fatty liver disease, liraglutide, AMPK/mTOR, autophagy

Enyi Zhu,1,2,&ast; Ming Zhong,3,&ast; Tiantian Liang,4,&ast; Yu Liu,3,&ast; Keping Wu,1,2 Zhijuan Zhang,1,2 Shuping Zhao,1,2 Hui Guan,5 Jiasi Chen,6 Li-Zhen Zhang,7 Yimin Zhang1,2 1The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, 510000, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 517108, People’s Republic of China; 4Nephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 6Department of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510030, People’s Republic of China; 7Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yimin Zhang, The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People’s Republic of China, Email zhangyim@mail.sysu.edu.cn Li-Zhen Zhang, Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China, Email zhanglzh3@mail2.sysu.edu.cnObjective: Diabetic nephropathy (DN) represents the principal cause of end-stage renal diseases worldwide, lacking effective therapies. Fatty acid (FA) serves as the primary energy source in the kidney and its dysregulation is frequently observed in DN. Nevertheless, the roles of FA metabolism in the occurrence and progression of DN have not been fully elucidated.Methods: Three DN datasets (GSE96804/GSE30528/GSE104948) were obtained and combined. Differentially expressed FA metabolism-related genes were identified and subjected to DN classification using “ConsensusClusterPlus”. DN subtypes-associated modules were discovered by “WGCNA”, and module genes underwent functional enrichment analysis. The immune landscapes and potential drugs were analyzed using “CIBERSORT” and “CMAP”, respectively. Candidate diagnostic biomarkers of DN were screened using machine learning algorithms. A prediction model was constructed, and the performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The online tool “Nephroseq v5” was conducted to reveal the clinical significance of the candidate diagnostic biomarkers in patients with DN. A DN mouse model was established to verify the biomarkers’ expression.Results: According to 39 dysregulated FA metabolism-related genes, DN samples were divided into two molecular subtypes. Patients in Cluster B exhibited worse outcomes with a different immune landscape compared with those in Cluster A. Ten potential small-molecular drugs were predicted to treat DN in Cluster B. The diagnostic model based on PRKAR2B/ANXA1 was created with ideal predictive values in early and advanced stages of DN. The correlation analysis revealed significant association between PRKAR2B/ANXA1 and clinical characteristics. The DN mouse model validated the expression patterns of PRKAR2B/ANXA1.Conclusion: Our study provides new insights into the role of FA metabolism in the classification, immunological pathogenesis, early diagnosis, and precise therapy of DN.Keywords: diabetic nephropathy, fatty acid metabolism, molecular subtypes, immune landscape, pharmacotherapy, diagnostic model

Jiaxu Lu,1,2,&ast; Jiaxian Chen,2,&ast; Junhong Ye,2 Zhen Shi,2 Xiang Gao,1 Peicong Chen,2 Yanzhou Chang,2 Hao Lin,2 Peng Li1 1Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 2Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Lin, Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China, Email linhao@gdmu.edu.cn Peng Li, Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China, Email 13763086273@163.comIntroduction: Osteosarcoma is a prevalent and highly malignant primary bone tumor. However, current clinical therapeutic drugs for osteosarcoma are not suitable for long-term use due to significant side effects. Therefore, there is an urgent need to develop new drugs with fewer side effects. Dipsacus asperoides C. Y. Cheng et T. M. Ai, a traditional Chinese medicine, is commonly used for its anti-inflammatory, anti-pain, bone fracture healing, and anti-tumor effects. In this study, we investigated the effects of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) on osteosarcoma cells in vitro and in vivo.Methods: DAELNs were isolated and purified from Dipsacus asperoides and their physical and chemical properties were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The cellular uptake of DAELNs in osteosarcoma cells was analyzed by PKH26 staining. The proliferation, invasion, migration, and apoptosis of osteosarcoma cells were assessed using CCK8 assay, EdU assay, colony-formation assay, transwell assay, wound healing assay, and mitochondrial membrane potential measurement, respectively. The regulatory mechanism of DAELNs inhibiting the progression of osteosarcoma via activating P38/JNK signaling pathway was investigated using Western blotting and immunohistochemistry. Moreover, the therapeutic effects of DAELNs were evaluated using in vivo small animal imaging assay, HE staining, and immunohistochemistry.Results: Our results showed that DAELNs inhibited the proliferation, invasion, migration, and fostered the apoptosis of osteosarcoma cells in vitro and suppressed the tumor growth of osteosarcoma cells in a xenograft nude mouse model. Furthermore, the bio-distribution of DiD-labeled DAELNs showed preferential targeting of osteosarcoma tumors and excellent biosafety in histological analysis of the liver and kidney. Mechanistically, DAELNs activated the P38/JNK signaling pathway-induced apoptosis.Conclusion: Taken together, DAELNs are novel, natural, and osteosarcoma-targeted agents that can serve as safe and effective therapeutic approaches for the treatment of osteosarcoma.Keywords: osteosarcoma, Dipsacus asperoides-derived exosomes-like nanoparticles, P38/JNK signaling pathway

Jia Chen,1– 3 Xiaoyu Deng,1– 3 Hansheng Xie,1– 3 Caiyun Wang,1– 3 Jiefeng Huang,1– 3 Ningfang Lian1– 3 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Provincial Sleep-Disordered Breathing Clinic Center, Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Ningfang Lian, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian Province, 350005, People’s Republic of China, Tel +86-591-87981698, Email 1533532863@qq.comPurpose: Circular RNA (circRNA) plays an important role in various biological processes. However, their functions in cigarette smoke extract (CSE) induced human normal lung epithelial cells (BEAS-2B) injury remain vague. The study aimed to explore circRNA expression profiles and reveal their potential roles in CSE-treated BEAS-2B cells.Methods: 5% CSE exposure for 24 hours were used to build the BEAS-2B cells ferroptosis model. Differentially expressed circRNAs (DECs) were identified by next-generation RNA sequencing. Six randomly selected DECs were validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis were conducted to clarify the potential functions of the DECs. Furthermore, the role of hsa_circ_0025843 in CSE-related BEAS-2B cells ferroptosis was confirmed.Results: 5% CSE exposure induced BEAS-2B cells ferroptosis. Fifty-one up-regulated cirRNAs and 80 down-regulated circRNAs were revealed in CSE-treated BEAS-2B cells. Hsa_circ_0003461, hsa_circ_0007548, hsa_circ_0025843, hsa_circ_0068896, hsa_circ_0005832, and hsa_circ_0053378 were selected randomly to validate the reliability of next-generation RNA sequencing by qRT-PCR. After KEGG pathway analysis, DECs were found to participate in the process of EGFR tyrosine kinase inhibitor resistance and glycerophospholipid metabolism. The knockdown of hsa_circ_0025843 significantly alleviated CSE-induced BEAS-2B cells ferroptosis.Conclusion: The study indicated the circRNA expression profiles in CSE-treated BEAS-2B cells. Hsa_circ_0025843 alleviated CSE induced BEAS-2B cells ferroptosis, which might be a potential therapeutic target of CSE related lung injury.Keywords: cigarette smoke extract, Circular RNA, next-generation RNA sequencing, lung injury, ferroptosis

Chunhui Jiang,1– 3 Jiani Chen,1– 3 Tong Sun,2,3 Jiaqin Xu,2,3 Hongguo Zhu,2,3 Jiaxi Chen1– 3 1School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Department of Laboratory Medicine, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, People’s Republic of ChinaCorrespondence: Jiaxi Chen, Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen Street, Linhai, Zhejiang Province, 317000, People’s Republic of China, Tel +86-13606652901, Email chenjx@enzemed.comPurpose: The pathogenesis of T cell subsets in sepsis during the body’s resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis.Patients and Methods: Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC.Results: Twenty-two CD4+ T-cell subpopulations and 10 CD8+ T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6− Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6− Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis.Conclusion: We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells’ function and regulatory mechanisms during sepsis pathogenesis.Keywords: scRNA-seq, pySCENIC, GRN, reference mapping

Ying Zhu,1 Liyuan Jiang,2 Tiantian Ye,3 Yan Liu,4 Li Sun,2 Lijuan Xiao,5 Jiayu Chen,6 Ting Wang,7 Yinghua Ren,8 Hongjun Xu,8 Huihui Zhao,8 Xiaozhen Mao,8 Tiantian Shen9 1School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, 310005, People’s Republic of China; 3The 1st Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 5Department of Rehabilitation, Chun’an County Hospital of Traditional Chinese Medicine, Chun’an, 311799, People’s Republic of China; 6Department of Rehabilitation, Huzhou Central Hospital, Huzhou, 313099, People’s Republic of China; 7The 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 8Department of Acupuncture and Tuina, Community Health Service Center of Zhuantang Street, Hangzhou, 310024, People’s Republic of China; 9Department of Acupuncture and Rehabilitation, Shengzhou Municipal Hospital of Traditional Chinese Medicine, Hangzhou, 312499, People’s Republic of ChinaCorrespondence: Liyuan Jiang, Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, No. 453, Stadium Road, Xihu District, Hangzhou, 310005, People’s Republic of China, Tel +86-13018976755, Email Jiangliyuan520j@163.comPurpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women.Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann–Whitney U-test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis).Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery (P = 0.002), number of pregnancies (P = 0.035), parity (P = 0.012), number of births (P = 0.02), fetal birth weight (P = 0.014), and waist-to-hip ratio in the supine position (P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group.Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life.Keywords: risk factors, patient-reported outcome measures, diastasis recti abdominis, postpartum period

Kai Guo,1,&ast; Yong Wang,1,&ast; Zi-Xuan Feng,1 Xiao-Ying Lin,1 Zhang-Rui Wu,1 Xin-Cao Zhong,1 Ze-Ming Zhuang,1 Tao Zhang,1 Jian Chen,2 Wei-Qiang Tan1 1Department of Plastic Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Ultrasonography, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Chen, Department of Ultrasonography, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang Province, People’s Republic of China, Email chenjianzuj4h@zju.edu.cn Wei-Qiang Tan, Department of Plastic Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China, Email tanweixxxx@zju.edu.cnAbstract: The various tissue damages are a severe problem to human health. The limited human tissue regenerate ability requires suitable biomaterials to help damage tissue repair and regeneration. Therefore, many researchers devoted themselves to exploring biomaterials suitable for tissue repair and regeneration. Polydopamine (PDA) as a natural and multifunctional material which is inspired by mussel has been widely applied in different biomaterials. The excellent properties of PDA, such as strong adhesion, photothermal and high drug-loaded capacity, seem to be born for tissue repair and regeneration. Furthermore, PDA combined with different materials can exert unexpected effects. Thus, to inspire researchers, this review summarizes the recent and representative development of PDA biomaterials in tissue repair and regeneration. This article focuses on why apply PDA in these biomaterials and what PDA can do in different tissue injuries. Keywords: polydopamine, biomaterial, tissue damage, tissue regeneration

Sachula,&ast; Zhenjie Yang,&ast; Tianyuan Yu, Jinping Chen, Runlong Zhang, Yingqi Zhang, Jiayue Liu, Hanyu Zhang, Jiawei Sun School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianyuan Yu, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Tel +8618210220868, Email yutianyuan@sina.comPurpose: This study aimed to investigate changes in metabolomic expression in the spinal dorsal horn (SDH) and thalamus during a Tuina session, aiming to elucidate the mechanism of immediate analgesia.Methods: The rats were randomly divided into three groups: the Sham group, the Model group, and the Tuina group. A minor chronic constriction injury (minor CCI) model was established in both the Model group and the Tuina group. The therapeutic effect of Tuina was determined using the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. Differential metabolites of the SDH and thalamus were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatic analysis was performed using CV, PCA, Venn, and KEGG.Results: The therapeutic effect of MWT and TWL after instant Tuina intervention was significant. The therapeutic effect of Tuina instant was significantly better compared to the Model group. In the Veen analysis, it was found that Tuina instantly regulates 10 differential metabolites in the SDH and 5 differential metabolites in the thalamus. In the KEGG enrichment analysis, we found that differential metabolites were enriched in 43 pathways in the thalamus and 70 pathways in the SDH.Conclusion: Tuina therapy may have analgesic effects by metabolizing neurotransmitters such as 2-Picolinic Acid, 5-Hydroxy-Tryptophan Glutathione Betaine-aldehyde-chloride Leucine Lysine Methionine Sarcosine Succinic Acid Histidine Acetylcholine and 5-Hydroxyindoleacetic Acid through the cAMP pathway. It also affects pathways of neurodegeneration-multiple diseases, butanoate metabolism, tyrosine metabolism. Keywords: neuropathic pain, tuina, neurotransmitters, thalamus, spinal dorsal horn, LC-MS

Guancheng Ye,1,&ast; Ruiheng Miao,2,&ast; Jiaqi Chen,3 Jian Huang,4 Min Jiang2 1Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of TCM, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of China; 4Department of Acupuncture, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Huang, Department of Acupuncture, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, Fangxingyuan District 1, Beijing, 100078, People’s Republic of China, Fax +86 10 67689713, Email xiamenhuangjian@sina.com Min Jiang, Department of TCM, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Beijing, 100038, People’s Republic of China, Fax +86 10 63926060, Email jiangmin545@bjsjth.cnObjective: Fibromyalgia (FM) is a prevalent chronic disorder characterized by widespread skeletal muscle pain. In recent years, complementary and alternative medicine (CAM) has increasingly been recognized for its potential in treating FM symptoms. This study aims to assess the efficacy of CAM therapies in mitigating the symptoms of FM.Methods: This systematic review was registered with INPLASY. A thorough search of both English and Chinese databases was undertaken from their inception until April 15, 2023. The search criteria focused on prospective controlled trials examining CAM therapies in FM patients. The statistical analysis employed mean values and standard deviations. Additionally, an evaluation of the literature’s quality and potential biases was conducted.Results: The search yielded 41 articles, encompassing 2877 FM patients and involving 20 different interventions. All studies were randomized controlled trials (RCTs). The results of the network meta-analysis (NMA) indicated that a combination of Acupuncture and Massage therapy, as well as Navel Needling therapy, effectively alleviated pain symptoms in FM patients. Furthermore, Abdominal Acupuncture and Electroacupuncture were found to be beneficial in improving patients’ mood and sleep quality.Conclusion: Acupuncture + Massage and Umbilical Acupuncture emerged as the most efficacious therapies in relieving pain symptoms in FM patients. Abdominal Acupuncture and Electroacupuncture demonstrated their effectiveness in enhancing mood and sleep quality. Overall, CAM therapies exhibited a high safety profile for patients with fibromyalgia.Keywords: complementary and alternative medicine, CAM, fibromyalgia, FM, effectiveness, network meta-analysis, NMA

Xinyue Hu,1– 3 Beibei Wang,1– 3 Jing Chen,1– 3 Dong Han,1– 3 Jing Wu1– 3 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, People’s Republic of ChinaCorrespondence: Jing Wu, Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +86-27-85351618, Email drjingwu@hust.edu.cnPurpose: Many studies have focused on the association between Autism spectrum disorder (ASD) and epidural labor analgesia (ELA), which is the most effective way to manage labor pain. The purpose of this meta-analysis was to summarize the current state of the association between ELA and ASD.Methods: A search of the literature yielded 201 relevant studies, of which 7 cohort studies met our inclusion criteria. Two independent reviewers screened the inclusion results, extracted data, and assessed the risk of bias and quality of evidence.Results: Compared to parturient who did not receive ELA, parturient who received ELA had a slightly increased risk of ASD (adjusted hazard ratio [aHR], 1.12; 95% confidence interval [CI], 1.06– 1.17; I2, 69%; P < 0.001; seven studies). After excluding one literature (aHR, 1.09; 95% CI, 1.06– 1.12; I2, 4%; P < 0.001; six studies). The sensitivity analyses had consistent outcomes with the main analyses involving siblings (aHR 1.11; 95% CI 1.03– 1.19), cesarean section and instrumental deliveries (aHR 1.07; 95% CI 1.03– 1.10), non-overlapping populations (aHR 1.09; 95% CI 1.05– 1.12), full-term birth populations (aHR 1.10; 95% CI 1.06– 1.14), and studies assessed to have moderate risk of bias (aHR 1.09; 95% CI 1.02– 1.16).Conclusion: This meta-analysis revealed a modest positive association between ELA and ASD, acknowledging a slight potential risk. However, it is important to note that this risk cannot be completely dismissed due to the possibility of bias and this association is based on low-quality evidence. Future studies are required to assess and mitigate different confounding biases and investigate the time-dose-response relationship.Keywords: Autism spectrum disorder, epidural analgesia, epidural labor analgesia, ELA, neuraxial labor analgesia, pregnancy, meta-analysis

Wenpeng Yu,1– 4,&ast; Jingli Ding,5,&ast; Jianfeng Chen,1– 3,&ast; Ying Jiang,4 Jinping Zhao,1– 3 Jichun Liu,4,6 Jianliang Zhou,1– 3 Jinping Liu1– 3 1Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, 430071, People’s Republic of China; 3Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, 430071, People’s Republic of China; 4Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 5Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 6Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliang Zhou; Jinping Liu, Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, People’s Republic of China, Tel +86 13767117511 ; +86 27-67812888, Email zjl20210802@whu.edu.cn; liujinping@znhospital.cnIntroduction: Excessive generation of reactive oxygen species (ROS) following myocardial ischemia-reperfusion (I/R) can result in additional death of myocardial cells. The rapid clearance of ROS after reperfusion injury and intervention during subsequent cardiac repair stages are crucial for the ultimate recovery of cardiac function.Methods: Magnesium-doped mesoporous bioactive glasses were prepared and loaded with the antioxidant drug gallic acid into MgNPs by sol-gel method. The antioxidant effects of MgNPs/GA were tested for their pro-angiogenic and anti-inflammatory effects based on the release characteristics of GA and Mg2+ from MgNPs/GA. Later, we confirmed in our in vivo tests through immunofluorescence staining of tissue sections at various time points that MgNPs/GA exhibited initial antioxidant effects and had both pro-angiogenic and anti-inflammatory effects during the cardiac repair phase. Finally, we evaluated the cardiac function in mice treated with MgNPs/GA.Results: We provide evidence that GA released by MgNPs/GA can effectively eliminate ROS in the early stage, decreasing myocardial cell apoptosis. During the subsequent cardiac repair phase, the gradual release of Mg2+ from MgNPs/GA stimulated angiogenesis and promoted M2 macrophage polarization, thereby reducing the release of inflammatory factors.Conclusion: MgNPs/GA acting on multiple cell types is an integrated solution for comprehensive attenuation of myocardial ischaemia-reperfusion injury and cardiac function protection.Keywords: myocardial ischemia/reperfusion injury, mesoporous bioactive glass, gallic acid, magnesium ion, macrophage polarization

Lin Liu, Jin Chen Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jin Chen, Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 15023188592, Email chenjin19771010@163.comAbstract: Throughout history, alcohol consumption has been an integral part of human culture. Alcohol consumption, alcoholism in particular, influences the onset and progression of liver diseases, neurological disorders, and multiple types of cancer. However, the role of alcohol consumption in influencing skin diseases has often been overlooked. In this review, we present the progress of research investigating the effects and potential mechanisms of action of alcohol consumption on acne, rosacea, psoriasis, atopic dermatitis, melanoma, and non-melanoma skin cancer.Keywords: ethanol, acne, rosacea, psoriasis, atopic dermatitis, skin tumor