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Yun Xiang,1,2,* Dini Lin,1,* Qiang Zhou,1 Hongyu Luo,1 Zixin Zhou,1 Shuyi Wu,2 Keyuan Xu,2 Xiaoting Tang,1 Pingping Ma,2 Chunyuan Cai,1 Xinkun Shen1 1Wenzhou Key Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People’s Hospital), Wenzhou, 325016, People’s Republic of China; 2School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China*These authors contributed equally to this work and share first authorshipCorrespondence: Xinkun Shen; Chunyuan Cai, Wenzhou Key Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People’s Hospital), Wenzhou, Zhejiang Province, 325016, People’s Republic of China, 108# Wansong Road, Email shenxinkun123@wmu.edu.cn; caichunyuan123@wmu.edu.cnBackground: Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear.Purpose: This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved.Methods: Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110.Results: In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110’s resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30.Conclusion: TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110’s potential for use in implants for elderly patients.Keywords: osteoporosis, oxidative stress, titania nanotube, protein adsorption, osteogenesis

Xingxing Zhu,1,* Jialu Chen,2,* Shengjie Wu,3 Jiling Zeng,4 Yahong Sun,1 Xiaohong Wu5 1Department of Pulmonary and Critical Care Medicine, Haining People’s Hospital, Haining, People’s Republic of China; 2Department of Gynaecology, Haining Maternal and Child Health Hospital, Haining, People’s Republic of China; 3Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong Wu, Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Shangcheng District, Hangzhou, 310000, People’s Republic of China, Tel +86 13588706901, Email 3192018@zju.edu.cnBackground: The incidence of community-acquired empyema caused by the Streptococcus anginosus group (SAG) has been on the rise in the 2020s. To the best of our knowledge, while empyema caused individually by either strain has been reported, there are no reports on empyema caused by concurrent infection with these two strains. Here, we report for the first time empyema caused by concurrent infection with Streptococcus intermedius and Streptococcus constellatus (both SAG species) in a postoperative patient who had been treated for floor of the mouth carcinoma.Case Presentation: A 61-year-old male patient who had undergone surgical treatment for floor of the mouth carcinoma 2 year earlier suddenly presented with left-sided chest pain. Chest computed tomography (CT) revealed encapsulated pleural effusion on the left side, which was diagnosed as empyema. Metagenomic next-generation sequencing(mNGS) of the pleural fluid sample indicated mixed infection caused by Streptococcus intermedius and Streptococcus constellatus. The patient’s condition improved about 5 weeks after treatment with thoracic fluid drainage and cephalosporin antibiotics.Conclusion: This case highlights the possibility of concurrent infection with two SAG strains in patients with empyema. Currently, it is unclear whether there is a definitive relationship between a surgical history of carcinoma of the floor of the mouth and empyema caused by infection with SAG strains. This case could, perhaps, serve as a reference for future related research on the topic.Keywords: Streptococcus intermedius, Streptococcus constellatus, oral carcinoma, pleural effusion, carcinoma of the floor of the mouth, empyema

Jiying Xiao,1 Lingyue Liu,1 Kamran Ali,2 Suling Wu,1 Junsong Chen1 1Department of Pulmonology, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, 310015, People’s Republic of China; 2Department of Surgery, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, 322000, People’s Republic of ChinaCorrespondence: Junsong Chen, Department of Pulmonology, Hangzhou Children’s Hospital, NO. 195 Wenhui Road, Gongshu Distract, Hangzhou, Zhejiang, 310015, People’s Republic of China, Tel +86-15990067220, Email doctorsong999@126.comObjective: We aimed to observe and analyze the differences in impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in relation to asthma control among preschool children, and to explore the predictive value of IOS combined with FeNO for uncontrolled asthma.Methods: This study enrolled 171 preschool children with asthma and 30 healthy preschool children between June 2022 and June 2023. We categorized the asthmatic children as having controlled asthma (n=85) and uncontrolled asthma (n=86) after a 3-month follow-up. IOS and FeNO were collected on the first visit at baseline. Differences in metrics were compared between controlled asthma, uncontrolled asthma and healthy control groups. The area under the receiver operating characteristic curve (AUROC) was utilized to explore the discriminative ability of IOS and FeNO, alone or in combination, against uncontrolled asthma.Results: Compared to the controlled asthma group, the IOS values of R5, X5, R5-R20, and Fres were significantly higher in the uncontrolled asthma group, except for R20. R5 and R5-R20 had the highest area under the curve (AUC), which could reach 0.74 (95% CI 0.66– 0.82) and 0.72 (95% CI 0.64– 0.80). R20 had the lowest AUC of 0.59. The AUC for FeNO alone was 0.88 (95% CI 0.84– 0.93) with a cutoff value of 17.50 ppb, sensitivity and specificity of 0.73 and 0.89. The AUCs of all IOS metrics combined with FeNO were significantly higher, with the highest AUC of 0.92 (95% CI 0.87– 0.96) for R5-R20+FeNO, and with a sensitivity and specificity of 0.88 and 0.84.Conclusion: There were significant differences in IOS and FeNO in relation to asthma control among preschooler children. FeNO might be the best predictor of asthma control, and adding any of IOS metrics increased moderately the predictive value.Keywords: asthma control, impulse oscillometry, fractional expiratory nitric oxide, preschool children

Yan Jin,1,2,&ast; Ke Zhu,1,&ast; Shiyu Wu,1 Shiyi He,1 Chao Cao1 1Department of Respiratory and Critical Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Municipal Hospital Affiliated to Taizhou University, Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Cao, Email caocdoctor@163.comBackground: Epidemiologic studies have shown that patients with acute exacerbation of COPD (AECOPD) suffer from morbidity and mortality from venous thromboembolism (VTE) and poor diagnosis. Von Willebrand factor (vWF) and plasminogen activator inhibitor type-1 (PAI-1) are frequently investigated in COPD as crucial parameters for coagulation and fibrinolysis. Nevertheless, the role of vWF and PAI-1 in AECOPD needs further exploration.Objective: We sought to evaluate the hypercoagulability in AECOPD and investigate the association of plasma vWF and PAI-1 with occurrence and exacerbation risk of AECOPD patients.Methods: Fifty-seven AECOPD patients and 34 control subjects were enrolled in our study. The concentrations of plasma vWF and PAI-1 antigens were measured by ELISA kit. Independent samples t-test or Wilcoxon rank sum test was applied for group comparison. Spearman correlation analysis, subject work curve (ROC) analysis, and Logistic regression were used to evaluate the role of the plasma vWF and PAI-1 in AECOPD.Results: We observed increased vWF (770.15 ± 325.52 vs 327.62 ± 210.97 ng/mL, P < 0.001) and PAI-1 (0.47 vs 0.17 ng/mL, P < 0.001) levels in AECOPD patients compared with control subjects. Both vWF and PAI-1 are closely related to COPD (vWF: AUC = 0.8741, P < 0.001; PAI-1: AUC = 0.8222, P < 0.001). Moreover, elevated vWF could be an independent risk factor for COPD (OR = 1.01, 95% CI: 1.00– 1.01, P = 0.01). We also discovered higher plasma levels of vWF and PAI-1 in the COPD “E” group in contract to “AB” group (vWF: 966.29 ± 251.18 vs 552.21 ± 253.28, P < 0.0001; PAI-1: 1.02 vs 0.38, P = 0.003). And vWF levels increased with increasing COPD exacerbation risk, moreover, plasma vWF positively related with patients’ CAT scores and SGRQ scores. In addition, plasma vWF and PAI-1 correlated with each other in total participants and AECOPD subgroup analysis.Conclusion: This study demonstrated that AECOPD patients have a prothrombotic state, as demonstrated by vWF and PAI-1 levels in plasma compared with those in control subjects, and the prothrombotic state increases with increasing COPD exacerbation risk.Keywords: chronic obstructive pulmonary disease, exacerbation, vWF, PAI-1, coagulation, fibrinolysis

Yibing Niu,1,2 Ling Zhang,3 Sumin Guo,4 Shucai Wu1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huabei Petroleum Administration Bureau General Hospital, Renqiu, Hebei, People’s Republic of China; 3Department of Respiratory, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Oncology, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shucai Wu, Department of Internal Medicine, Hebei Medical University, 361 Zhongshan East Road, Chang’an District, Shijiazhuang, Hebei, 050017, People’s Republic of China, Tel/Fax +8618232155713, Email shucai_wu@163.comIntroduction: Inflammation and oxidative stress are important factors in the pathogenesis of Chronic obstructive pulmonary disease (COPD). Current treatments for COPD focus on improving symptoms caused by inflammation rather than curing the disease, therefore, emerging research focusing on upstream pathways may help develop effective treatments. Epidemiological investigations have shown that exposure to fine particulate matter (PM2.5) can cause lung inflammation and oxidative stress through nuclear factor NF-E2-associated factor (Nrf2) pathway, leading to COPD. Nrf2 is an important transcription factor regulating anti-inflammatory and antioxidant stress, and its abnormal expression level or changes in transcriptional activity are related to the occurrence and development of COPD. Omaviloxone - RTA-408, a synthetic oleanane triterpene that acts as an Nrf2 activator, RTA-408 may play an important role in COPD.Purpose: In this study, PM2.5 was used to establish HBE cell model in vitro and rat model in vivo to simulate COPD, and the effect of Nrf2 activator RTA-408 on PM2.5-induced COPD model and its mechanism were investigated.Patients and Methods: The HBE cell model in vitro and rat model in vivo were established to simulate COPD, and the effect of RTA-408 on COPD was detected by various experimental methods.Results: The results showed that RTA-408 could activate Nrf2 both in vivo and in vitro. By activating Nrf2/HO-1 pathway, RTA-408 inhibits NF-κB and IFN-γ pathways, alleviates inflammation and oxidative stress of HBE cells in COPD model rats and PM2.5 exposed cells, and plays a therapeutic role in reversing cell damage and delaying disease progression in COPD. In addition, in vitro experiments, silencing Nrf2 eliminated the protective effect of RTA-408 on COPD cell models, which also confirmed the role of RTA-408.Conclusion: We conclude that RTA-408 is well worth considering as a new strategy for the treatment of COPD, and may also have a positive preventive effect.Keywords: chronic obstructive pulmonary disease, inflammation, oxidative stress, Nrf2, RTA-408

Fangqian Du,1,&ast; Yuwei Xie,1,&ast; Shengze Wu,1 Mengling Ji,2 Bingzi Dong,3 Chengzhan Zhu1 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan; 3Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengzhan Zhu, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel +86 0532-82919552, Fax +86 0532-82911885, Email zhuchengz@qduhospital.cn Bingzi Dong, Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel/Fax +86-82911383, Email dongbingzi@hotmail.comAbstract: Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed.Keywords: claudins, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer, targeted therapy

Mengmeng Wang,1 Huanhuan Wang,1,2 Zhaoyan Feng,1 Shuai Wu,1 Bei Li,1,2 Fang Han,1 Fulong Xiao1 1Division of Sleep Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2School of Nursing, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Fulong Xiao; Fang Han, Division of Sleep Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China, Email xiaofulong1681@163.com; hanfang1@hotmail.comObjective: Depression is a common psychiatric issue among patients with narcolepsy type 1 (NT1). Effective management requires accurate screening and prediction of depression in NT1 patients. This study aims to identify relevant factors for predicting depression in Chinese NT1 patients using machine learning (ML) approaches.Methods: A total of 203 drug-free NT1 patients (aged 5– 61), diagnosed based on the ICSD-3 criteria, were consecutively recruited from the Sleep Medicine Center at Peking University People’s Hospital between September 2019 and April 2023. Depression, daytime sleepiness, and impulsivity were assessed using the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) or the Self-Rating Depression Scale (SDS), the Epworth Sleepiness Scale for adult or children and adolescents (ESS or ESS-CHAD), and the Barratt Impulse Scale (BIS-11). Demographic characteristics and objective sleep parameters were also analyzed. Three ML models-Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM)-were used to predict depression. Model performance was evaluated using receiver operating curve (AUC), accuracy, precision, recall, F1 score, and decision curve analysis (DCA).Results: The LR model identified hallucinations (OR 2.21, 95% CI 1.01– 4.90, p = 0.048) and motor impulsivity (OR 1.10, 95% CI 1.02– 1.18, p = 0.015) as predictors of depression. Among the ML models, SVM showed the best performance with an AUC of 0.653, accuracy of 0.659, sensitivity of 0.727, and F1 score of 0.696, reflecting its effectiveness in integrating sleep-related and psychosocial factors.Conclusion: This study highlights the potential of ML models for predicting depression in NT1 patients. The SVM model shows promise in identifying patients at high risk of depression, offering a foundation for developing a data-driven, personalized decision-making tool. Further research should validate these findings in diverse populations and include additional psychological variables to enhance model accuracy.Keywords: narcolepsy type 1, depression, machine learning, support vector machine

Xi Huang,1,2,&ast; Yu Peng,1,2,&ast; Lingfei Lu,1,&ast; Liwen Gao,1,2 Shanshan Wu,1,2 Jiandong Lu,1 Xinhui Liu1 1Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People’s Republic of China; 2The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhui Liu, Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, People’s Republic of China, Email liuxinhui0317@163.comBackground: Huangqi-Danshen decoction (HDD) is a Chinese medicinal herb pair with good efficacy in treating chronic kidney disease, but its mechanism needs to be clarified.Aim: To uncover the underlying mechanism of HDD antagonizing renal fibrosis through network pharmacology (NP) analysis and experimental validation.Materials and Methods: The chemical components of water extract of HDD were analyzed by combining the ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrum analysis (UHPLC-QE-MS) and HERB database. NP was used to identify core common targets of HDD components and renal fibrosis. Subsequently, male C57BL/6 mice were divided into Sham, unilateral ureteral obstruction (UUO) and UUO+HDD groups. Renal function, histopathology, Western blotting, and immunohistochemistry analyses were used to evaluate the protective effect of HDD on UUO mice. The effects of HDD on signaling pathways were validated in both UUO mice and transforming growth factor-β 1 (TGF-β 1)-induced HK-2 cells.Results: By combining UHPLC-QE-MS analysis and HERB database, 25 components were screened in HDD extract. There were 270 intersection targets of the 25 components and renal fibrosis. Based on their scores in protein-protein interaction analysis and degree values in component-pathway-target triadic network, 6 core common targets of the 25 components and renal fibrosis were identified, namely phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription 3 (Stat3), non-receptor tyrosine kinase Src (Src), epidermal growth factor receptor (EGFR), matrix metalloproteinase 9 (MMP9), and MMP2. HDD ameliorated renal tubular damage and collagen deposition and downregulated fibrosis-related proteins expression in UUO mice. Furthermore, HDD was demonstrated to reduce PI3K, Stat3, Src, EGFR, and MMP2 expressions, and enhance MMP9 expression in the kidney of UUO mice and in TGF-β 1-induced HK-2 cells.Conclusion: HDD can alleviate renal fibrosis which may be related to regulating the expression of essential proteins in the epithelial-mesenchymal transition and extracellular matrix production/degradation signaling pathways. Keywords: renal fibrosis, chronic kidney disease, Huangqi-Danshen decoction, network pharmacology, signaling pathway

Meng Wu,1,&ast; Shuang Wu,1,&ast; Rui Guo2 1Department of Pharmacy, the First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Critical Care Medicine, the First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Guo, Email 18840047020@163.comBackground: Breast cancer is the leading cause of cancer-related deaths among women worldwide. Identifying robust biomarkers for predicting outcomes is essential for improving patient care and reducing fatalities. ZMAT3, a zinc finger protein with potential carcinogenic properties, has been associated with various cancers. However, its role in breast cancer prognosis remains unclear.Methods: We investigated the expression level of ZMAT3 in breast cancer tissues and its association with clinical outcomes through bioinformatics analysis and experimental validation. We examined the correlation between ZMAT3 expression and immune characteristics. ZMAT3 mRNA expression data from The Cancer Genome Atlas (TCGA) were analysed in relation to overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in patients with breast cancer. Immunohistochemistry (IHC) was performed on breast cancer tissues to assess ZMAT3 protein levels, with findings validated using qPCR and cell experiments.Results: ZMAT3 mRNA levels were significantly upregulated in breast cancer samples compared to normal tissues. High ZMAT3 expression was significantly correlated with the poor OS, DSS and PFI. A significant positive correlation was observed between high ZMAT3 mRNA levels and the abundance of tumour-infiltrating lymphocytes (TILs), especially CD8+T cells and regulatory T cells (Tregs). Multivariate Cox regression analysis identified ZMAT3 as an independent prognostic factor for breast cancer. IHC staining confirmed increased ZMAT3 protein expression in breast cancer tissues, which was further validated by qPCR and cell function tests.Conclusion: Our findings suggest that ZMAT3 is a prognostic biomarker linked to immune invasion in breast cancer. Elevated ZMAT3 expression correlates with adverse clinical outcomes, indicating its potential role in disease progression.Keywords: breast cancer, cancer prognosis, immunotherapy, bioinformatics, ZMAT3

Tong Chen,1– 4 Yu Liu,2,3 Shiquan Wu,2 Siyu Long,2 Ling Feng,4,5 Wenqian Lu,6 Wenya Chen,2 Guoai Hong,2 Li Zhou,2 Fang Wang,2 Yuechan Luo,2 Hequn Zou,2,4,6 Weihua Liu7 1Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People’s Republic of China; 2South China Hospital of Shenzhen University, Shenzhen, 518116, People’s Republic of China; 3Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 4Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 6School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 7Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of ChinaCorrespondence: Weihua Liu, Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of China, Email lwh10280465@163.com Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population.Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD.Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyG-WHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P< 0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446– 5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791).Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.Keywords: chronic kidney disease, insulin resistance, obesity, TyG related indicators

Shanshan Wu,1,2,&ast; Shuren Wang,3,&ast; Yonghong Ding,2 Zongwang Zhang1,2 1Department of Anesthesiology, Liaocheng People’s Hospital, Shandong University, Liaocheng, People’s Republic of China; 2Department of Anesthesiology, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 3Department of Anesthesiology, Dongchangfu District Maternal and Child Health Hospital, Liaocheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongwang Zhang, Department of Anesthesiology, Liaocheng People’s Hospital, Shandong University, Liaocheng, People’s Republic of China, Tel +86-13346256809, Email zwzhang68@sina.comObjective: Postoperative pain is a common complication in endoscopic submucosal dissection (ESD) patients. This study aimed to develop and validate predictive models for postoperative pain associated ESD.Methods: We retrospectively constructed a development cohort comprising 2162 patients who underwent ESD at our hospital between January 2015 and April 2022. The dataset was randomly divided into a training set (n = 1541) and a validation set (n = 621) in a 7:3 ratio. The bidirectional stepwise regression with Akaike’s information criterion (AIC) and multivariate logistic regression analysis were used to screen the predictors of post-ESD pain and construct three nomograms. We evaluated the model’s discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, Hosmer–Lemeshow (HL) goodness-of-fit test and decision curve analysis (DCA) in internal validation.Results: The proportion of patients developing postoperative pain in the training and testing data set was 25.6% and 28.5%, respectively. Three nomograms were constructed according to the final logistic regression models. The clinical prediction models for preoperative risks, preoperative and intraoperative risks, and perioperative risks consisted of seven, nine and six independent predictors, respectively, after bidirectional stepwise elimination. The models demonstrated the AUC of 0.794 (95% CI 0.768– 0.820), 0.823 (95% CI 0.799– 0.847) and 0.817 (95% CI 0.792– 0.842) in the training cohort and 0.702 (95% CI 0.655– 0.748), 0.705 (95% CI 0.659– 0.752) and 0.747 (95% CI 0.703– 0.790) in the validation cohort. The calibration plot, HL and DCA demonstrated the model’s favorable clinical applicability.Conclusion: We developed and validated three robust nomogram models, which might identify patients at risk of post-ESD pain and promising for clinical applications.Keywords: endoscopic submucosal dissection, postoperative pain, nomograms

Lili Huang,1,&ast; Yesong Liu,2,&ast; Tingting Geng,1,&ast; Nannan Zhang,2 Liang Sun,1 Shouling Wu,3 Xiang Gao1 1Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, People’s Republic of China; 2Department of Neurology, Kailuan General Hospital, Tangshan, People’s Republic of China; 3Department of Cardiology, Kailuan General Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Gao, Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, 130 Dongan Road, Shanghai, 200032, People’s Republic of China, Email xiang_gao@fudan.edu.cn Shouling Wu, Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, People’s Republic of China, Tel +86 315 3025655, Fax +86 315 3725312, Email drwusl@163.comBackground: Sleep complaints were reported to be associated with stroke, however, the evidence on the association between healthy sleep pattern and stroke risk in Chinese is limited.Objective: The aim of this study was to investigate the association between healthy sleep pattern and stroke in Chinese, and the influence of metabolic diseases on the association.Methods: A total of 11,851 participants from the Kailuan study in China without stroke at baseline were included. We calculated a healthy sleep score according to four sleep factors, and defined the low-risk groups as follows: no insomnia, no excessive daytime sleepiness, no frequent snoring, and sleep 7– 8h/d. Each low-risk sleep factor was assigned a score of 1. Cox proportional hazard models were used to assess the association between healthy sleep score and stroke. Mediation analysis was used to estimate the role of metabolic diseases (obesity, diabetes, and hypertension) in the healthy sleep score-stroke association.Results: During a mean follow-up period of 7.7 years, 504 cases of stroke were identified. A higher healthy sleep score was associated with a lower risk of stroke in a dose-response manner (P-trend=0.03). The adjusted hazard ratio (HR) for participants with a healthy sleep score of 4 versus ≤ 2 was 0.75 (95% confidence interval [CI]: 0.56, 0.96). In addition, obesity, diabetes, and hypertension collectively explained 21.9% (95% CI: 17.2, 26.5) of the association between healthy sleep score and stroke.Conclusion: Adherence to healthy sleep pattern was associated with a lower risk of stroke, and the favorable association was partially mediated by metabolic diseases.Keywords: healthy sleep pattern, metabolic disease, stroke, mediation

Wenwu Zhang,1,2,&ast; Yuhan Xiao,3,&ast; Xin Zhu,1 Yanxia Zhang,1 Qin Xiang,1 Shunhong Wu,1 Xiaoyu Song,1 Junxiu Zhao,3 Ruanfei Yuan,1 Qiguang Li,1 Bin Xiao,1 Linhai Li1 1Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People’s Republic of China; 2Department of Laboratory Medicine, Suzhou Municipal Hospital, Affiliated to Nanjing Medical University, Suzhou, 21500, People’s Republic of China; 3School of Public Health, Dali University, Dali, 671000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linhai Li; Bin Xiao, Email mature303@126.com; xiaobin2518@163.comPurpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored.Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays.Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3.Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.Keywords: meiosis-specific protein, pan-cancer, prognosis biomarker, immune infiltration, cell cycle

Yu-Kai Li,1,&ast; Song Wu,2,&ast; Yu-Shan Wu,3,&ast; Wei-Hu Zhang,4,&ast; Yan Wang,5,&ast; Yue-Hua Li,1,&ast; Qiang Kang,1,&ast; Song-Quan Huang,1,&ast; Kai Zheng,1 Gai-Ming Jiang,1 Qing-Bo Wang,1 Yu-Bo Liang,1 Jin Li,1 Yawhan Lakang,1 Chen Yang,1 Jing Li,1 Jia-Ping Wang,4 Xiang Kui,5 Yang Ke1,6,7 1Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 2Preventive Medicine Division, School of Life Science, Anhui University of Chinese Medicine, Hefei, AH, 230012, People’s Republic of China; 3The Second Clinical Medical College, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 4Department of Radiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 6Department of Surgical Education and Research, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 7Yunnan Yunke Bio-Technology Institution, Kunming, YN, 650201, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Kui, Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8613708729335, Email kuixiang@foxmail.com Yang Ke, Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8615808875159, Email keyang1218@126.comBackground: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy.Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models.Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534– 2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290– 1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149– 2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380– 2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005– 2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236– 2.263), higher BCLC stage (HR 1.516, 95% CI 1.300– 1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198– 2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060– 1.997).Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients. Keywords: blood supply, computed tomography, hepatectomy, hepatocellular carcinoma, recurrence, survival

Lina Du,1 Dezhi Yang,2 Lan Wu,1 Li Mei,1 Sarula Wu,1 Yasula Ba,1 Yongchang Bao,1 Rigugaqiqige Su,1 Lin Song1 1College of Mongolian Medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Innovative Mongolian Medical Engineering Research Center, Inner Mongolia International Mongolian Hospital, Hohhot, Inner Mongolia, People’s Republic of ChinaCorrespondence: Lin Song, Inner Mongolia Medical University, Tel +15849163188, Email songlinwpsword@163.comObjective: To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia.Methods: DL-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot.Results: The weights of the insomnia-model rats were significantly raised (p ≤ 0.05), the total exercise distance in the OFT increased (p ≤ 0.05), the rest time shortened, and the number of standing times increased (p ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of insomnia rats reduced after drug treatment. MMS-4D may treat insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses.Conclusion: This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse. Keywords: Mongolian medicine sugemule-4 decoction, insomnia, metabolomics, gut microbiota, network pharmacology, molecular mechanism

Naijing Li,1,&ast; Weiying Zhang,2,&ast; Siyuan Wu,3,&ast; Muhammad Shafiq,4 Peihan Xie,3 Lixiang Zhang,5 Shichao Jiang,3 Yue Bi1 1Department of Orthopedic Oncology, Yantai Shan Hospital, Yantai, People’s Republic of China; 2Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Innovation Center of Nanomedicines, Kawasaki Institute of Industrial Promotion, Kawasaki, Japan; 5Department of Health Management, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Bi; Shichao Jiang, Email dr_yuebi@126.com; mailjsc@163.comPurpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management.Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats.Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.).Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.Keywords: electrospinning, nanofiber membrane, wound healing, mesoporous silicon, strontium

Na Li,1 Liufu Cui,1 Gary Tse,2,3 Panagiotis Korantzopoulos,4 Konstantinos P Letsas,5 George Bazoukis,6,7 Shuohua Chen,8 Nan Zhang,2 Xuemei Yang,9 Peipei Liu,10 Lili Wu,11 Gan-Xin Yan,12,13 Gregory Yoke Hong Lip,14,15 Shouling Wu,8 Tong Liu2 1Department of Rheumatology and Immunology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 4First Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece; 5Arrhythmia Unit, Laboratory of Cardiac Pacing and Electrophysiology, Onassis Cardiac Surgery Center, Athens, Greece; 6Department of Cardiology, Larnaca General Hospital, Larnaca, Cyprus; 7European University Cyprus, Medical School, Nicosia, Cyprus; 8Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 9School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 10School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 11Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 12Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA, USA; 13Department of Cardiology, Fuwai Huazhong Hospital, Zhengzhou, Henan Province, People’s Republic of China; 14Liverpool Centre for Cardiovascular Sciences, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK; 15Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Tong Liu, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China, Email liutong@tmu.edu.cn; liutongdoc@126.com Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China, Email drwusl@163.comObjective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP.Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP> 3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB.Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22– 1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27– 2.77), and right bundle branch block (HR:1.47, 95% CI:1.02– 2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP.Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP. Keywords: hyperuricemia, inflammation, cardiac conduction block, combined exposure, risk factors, mediation

Hui-E Zheng, Yun Wang, Shuhui Wu, Ming-Fang Zhu Department of Dermatology, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Ming-Fang Zhu, Department of Dermatology, The Second Affiliated Hospital of Hunan University of Chinese Medicine, 233 Cai E North Road, Kaifu District, Changsha, People’s Republic of China, Tel +86-13907317358, Fax +86-731-84917727, Email 1220824642@qq.comAbstract: Porokeratosis (PK), characterized by keratotic lesions with an atrophic center and a prominent peripheral ridge, with a typical histological hallmark, namely, the cornoid lamella, has two forms: disseminated and localized. While PK often converts into squamous cell carcinoma (SCC), conversion from disseminated superficial porokeratosis (DSP) alone is rarely reported except for one case in which DSP and LP coexisted and converted to SCC. Here, we report the case of a patient with SCC converted from DSP alone, presenting with coin-sized macules on the bottom right of his waist that developed into an ulcer at the center. The patient underwent radiation therapy, which effectively treated the SCC but did not resolve the PK. This article highlights regular follow-up and undergo comprehensive diagnosis, both of which are beneficial to enable early detection and management of DSP that has converted to into SCC; in addition, standardized medical treatment may help improve the treatment therapeutic effect of in similar diseases.Keywords: disseminated superficial porokeratosis, porokeratosis, squamous cell carcinoma

Kaiyu Wang,1,&ast; Yan Gao,1,&ast; Shan Wu,1,&ast; Jin Zhang,1 Manfang Zhu,2 Xiayu Chen,1 Xizi Fu,1 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.com Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.comBackground: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments.Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (&epsiv;-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates.Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models.Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.Keywords: mRNA gene therapy, dual-mRNA delivery, tumor cell lysates, Bim and IL-23A mRNAs, immune response

Nan Wang,1 Qiqi Hou,2 Shouling Wu,3 Quanle Han,4 Kangbo Li5 1Catheterization Unit, Tangshan Gongren Hospital, Tangshan, People’s Republic of China; 2Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Cardiology, Kailuan General Hospital, Tangshan, People’s Republic of China; 4Department of Cardiology, Tangshan Gongren Hospital, Tangshan, People’s Republic of China; 5School of Clinical Medicine, North China University of Science and Technology, Tangshan, People’s Republic of ChinaCorrespondence: Quanle Han, Email quanle.han@outlook.comBackground: Aspirin (ASA), the mainstay antiplatelet treatment in patients with cardiovascular disease (CVD), has been received by a considerable number of AF patients. This study sought to examine the association between ASA monotherapy and the risk of major adverse cardiac and cerebrovascular events (MACCE) in patients with atrial fibrillation (AF).Methods: A total of 850 patients with AF were identified from a community-based Kailuan study. All patients were assigned to two groups according to their medicine history: an aspirin therapy group (ASA group) (n = 174), and a non-aspirin therapy group (non-ASA group) (n = 676). The clinical endpoints are MACCE, including myocardial infarction (MI), ischemic stroke (IS), and hemorrhagic stroke (HS). Incidence curves for MACCE were plotted using the Kaplan–Meier method, and the Log rank test was used to assess the differences in incidence rates. The hazard ratios (HR) and 95% confidence intervals (CI) for MACCE were analyzed using Cox proportional-hazards analysis regression models.Results: During the 7.2-year follow-up, 30 MACCE occurred in the ASA group, and 101 in the non-ASA group, with a cumulative incidence of 19.88% vs 17.27%, P = 0.511; 3 cases of MI occurred in the ASA group, and 18 cases in the non-ASA group, with a cumulative incidence of 1.78% vs 2.90%, P = 0.305. Twenty-seven cases of IS occurred in the ASA group, and 84 cases in the non-ASA group, with a cumulative incidence of 1.78% vs 2.90%, P = 0.305. Eight cases of HS occurred in the ASA group, and 13 cases in the non-ASA group, with a cumulative incidence of 5.01% vs 2.34%, P = 0.045. Multivariate regression analysis showed that ASA therapy was not associated with MACCE (HR: 1.130, 95% CI: 0.747– 1.710, P = 0.562). In addition, ASA therapy was not associated with IS (HR: 1.309, 95% CI: 0.843– 2.034, P = 0.231). However, ASA therapy was significantly associated with HS (HR: 2.563, 95% CI: 1.024– 6.418, P = 0.044).Conclusion: ASA monotherapy is not associated with a lower risk of ischemic events, while significantly associated with a higher risk of bleeding events. Patients with AF are unlikely to benefit from aspirin monotherapy.Keywords: atrial fibrillation, aspirin monotherapy, major adverse cardiac and cerebrovascular events, myocardial infarction, ischemic stroke, hemorrhagic stroke

Yujie Xie,1 Fanglin Shao,1 Yuxiu Ji,1 Dechao Feng,1,2 Ling Wang,3 Zonghai Huang,3 Shengjian Wu,1 Fuhua Sun,1 Hong Jiang,4 Akira Miyamoto,5 Haiming Wang,6 Chi Zhang1 1Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3School of Information and Communication Engineering, University of Electronic Science and Technology, Chengdu, Sichuan, People’s Republic of China; 4Rehabilitation Medicine Department, Xichong County People’s hospital, Nanchong, Sichuan, People’s Republic of China; 5Faculty of Rehabilitation, Nishikyushu University, Kansaitama, Japan; 6Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Haiming Wang, Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China, Tel +868950771, Fax +86 830 8950771, Email wanghaiming866@163.com Chi Zhang, Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email chizhang_swmu@126.comPurpose: To provide a comprehensive analysis of associated genes with osteoarthritis (OA). Here, we reported a network analysis of OA progression by using a Steiner minimal tree algorithm.Methods: We collected the OA-related genes through screening the publications in MEDLINE. We performed functional analysis to analyze the associated biochemical pathways of the OA-related genes. Pathway crosstalk analysis was constructed to explore interactions of the enriched pathways. Steiner minimal tree algorithm was used to analyze molecular pathway networks. The average clustering coefficient was compared with the corresponding values of the Osteoarthritis-specific network. The new finding RNA was compared with former single-cell RNA-seq analysis results.Results: A gene set with 177 members reported to be significantly associated with Osteoarthritis was collected from 187 studies. Functional enrichment analysis revealed a specific related-OA gene including skeletal system development, cytokine-mediated signaling pathway, inflammatory response, cartilage development, and extracellular matrix organization. We performed a pathway crosstalk analysis among the 72 significantly enriched pathways. A total of 151 of the 177 genes in the Osteoarthritis gene set were included in the human interactome network. There were 31 genes in the former single-cell RNA-seq analysis results. The CLU, ENO1, SRRM1, UBC, HMGB1, NR3C1, NOTCH2NL, and CBX5 have significantly increased expression in seven molecularly defined populations of OA cartilage.Conclusion: The Steiner tree-based approach finds new biological molecules associated with OA genes.Keywords: network analysis, Steiner minimal tree, osteoarthritis, bioinformatics, osteoarthritis genes

Junsong Chen,1 Jiying Xiao,1 Lingyue Liu,1 Kamran Ali,2 Suling Wu1 1Department of Pulmonology, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, 310015, People’s Republic of China; 2Department of Oncology, the Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, People’s Republic of ChinaCorrespondence: Suling Wu, Department of Pulmonology, Hangzhou Children’s Hospital, No. 195 Wenhui Road, Gongshu Distract, Hangzhou, 310015, Zhejiang, People’s Republic of China, Tel +86-18758853716, Email 565969515@qq.comObjective: Prediction of asthma in preschool children is challenging and lacks objective indicators. The aim is to observe and analyze the variances between impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in preschool children with wheezing, establish a joint prediction model, and explore the diagnostic value of combining IOS with FeNO in diagnosing asthma among preschool children.Patients and methods: This study enrolled children aged 3– 6 years with wheezing between June 2021 and June 2022. They were categorized as asthmatic (n=104) or non-asthmatic (n=109) after a 1-year follow-up. Clinical data, along with IOS and FeNO measurements from both groups, underwent univariate regression and multiple regression analyses to identify predictive factors and develop the most accurate model. The prediction model was built using the stepwise (stepAIC) method. The receiver operating characteristic curve (ROC), calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were employed to validate and assess the model.Results: During univariate analysis, a history of allergic rhinitis, a history of eczema or atopic dermatitis, and measures including FeNO, R5, X5, R20, Fres, and R5-R20 were found to be associated with asthma diagnosis. Subsequent multivariate analysis revealed elevated FeNO, R5, and X5 as independent risk factors. The stepAIC method selected five factors (history of allergic rhinitis, history of eczema or atopic dermatitis, FeNO, R5, X5) and established a prediction model. The combined model achieved an AUROC of 0.94, with a sensitivity of 0.89 and specificity of 0.88, surpassing that of individual factors. Calibration plots and the HL test confirmed satisfactory accuracy.Conclusion: This study has developed a prediction model based on five factors, potentially aiding clinicians in early identification of asthma risk among preschool children.Keywords: asthma, impulse oscillometry, fractional expiratory nitric oxide, prediction model, preschool children

Min Fang,1,2 Wei Yin,3 Chunyan Qiu,4 Tao Song,2 Baihua Lin,2 Ying Wang,2 Hanchu Xiong,2 Shixiu Wu1 1Department of Radiation Oncology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of ChinaCorrespondence: Wei Yin, Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China, Email hzyinwei@live.cn Shixiu Wu, Department of Radiation Oncology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang, People’s Republic of China, Email wushixiu@yeah.netObjective: Immune cells play a key role in tumor microenvironment. The purpose of this study was to investigate the infiltration and clinical indication of immune cells including their combined prognostic value in microenvironment of triple negative breast cancer.Methods: We investigated 100 patients with triple negative breast cancer by Opal/Tyramide Signal Amplification multispectral immunofluorescence between 2003 and 2017 at Zhejiang Provincial people’s Hospital. Intratumoral and stromal immune cells of triple negative breast cancer were classified and quantitatively analyzed. Survival outcomes were compared using the Kaplan–Meier method and further analyzed with multivariate analysis.Results: Infiltration level of stromal B lymphocytes, stromal and intratumoral CD8+ T cells, stromal CD4+ T cells, stromal PD-L1 and intratumoral tumor associated macrophages 2 cells were shown as independent factors affecting disease-free survival and overall survival in univariate analysis. Stromal B lymphocytes, T stage, N stage and pathological type were independent predictive factors for both DFS and OS in multivariate analysis. We firstly found that patients with B lymphocytes-enriched subtypes have a better prognosis than those with T lymphocytes-enriched subtypes and tumor-associated macrophage-enriched subtypes.Conclusion: The present study identified a bunch of immune targets and subtypes, which could be exploited in future combined immunotherapy/chemotherapy strategies for triple negative breast cancer patients.Keywords: triple negative breast cancer, B lymphocytes, T lymphocytes, tumor associated macrophages, multispectral immunofluorescence, prognosis

Yu Huang,1,&ast; Shuyang Wu,1,&ast; Jingjing Li,1,2 Chenglin He,1 Yanfen Cheng,3 Nan Li,1 Yitao Wang,1,4 Yihan Wu,1 Jinming Zhang1 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China; 3Chengdu University, Chengdu, People’s Republic of China; 4Macau Center for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinming Zhang; Yihan Wu, State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email cdutcmzjm@126.com; yihanwuone@126.comBackground: Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent, when combined with the photosensitizer Chlorin e6 (Ce6), has shown to provide enhanced anti-tumor benefits. However, the development of stimuli-responsive nanovehicles for the co-delivery of TPL and Ce6 could further enhance the efficacy of this combination therapy.Methods: In this study, we synthesized a pH/ROS dual-responsive mPEG-TK-PBAE copolymer, which contains a pH-sensitive PBAE moiety and a ROS-sensitive thioketal (TK) linkage. Through a self-assembly process, TPL and Ce6 were successfully co-loaded into mPEG-TK-PBAE nanoparticles, hereafter referred to as TPL/Ce6 NPs. We evaluated the pH- and ROS-sensitive drug release and particle size changes. Furthermore, we investigated both the in vitro suppression of cellular proliferation and induction of apoptosis in HepG2 cells, as well as the in vivo anti-tumor efficacy of TPL/Ce6 NPs in H22 xenograft nude mice.Results: The mPEG-TK-PBAE copolymer was synthesized through a one-pot Michael-addition reaction and successfully co-encapsulated both TPL and Ce6 by self-assembly. Upon exposure to acid pH values and high ROS levels, the payloads in TPL/Ce6 NPs were rapidly released. Notably, the abundant ROS generated by the released Ce6 under laser irradiation further accelerated the degradation of the nanosystem, thereby amplifying the tumor microenvironment-responsive drug release and enhancing anticancer efficacy. Consequently, TPL/Ce6 NPs significantly increased PDT-induced oxidative stress and augmented TPL-induced apoptosis in HepG2 cells, leading to synergistic anticancer effects in vitro. Moreover, administering TPL/Ce6 NPs (containing 0.3 mg/kg of TPL and 4 mg/kg of Ce6) seven times, accompanied by 650 nm laser irradiation, efficiently inhibited tumor growth in H22 tumor-bearing mice, while exhibiting lower systemic toxicity.Conclusion: Overall, we have developed a tumor microenvironment-responsive nanosystem for the co-delivery of TPL and Ce6, demonstrating amplified synergistic effects of chemo-photodynamic therapy (chemo-PDT) for hepatocellular carcinoma (HCC) treatment.Keywords: triptolide, PDT, ROS, Ce6, pH responsive, hepatic carcinoma

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

Tao Xue,1,&ast; Hongbin Yu,2,&ast; Wenming Feng,2 Yao Wang,2 Shiyong Wu,3 Lili Wang,4 Peiqin Zhu,5 Jianming Guan,6,7 Quan Sun8 1Clinical Research Center, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 3Department of Radiology, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 4Department of Nursing, Physical Examination Center of Aishan, Huzhou, People’s Republic of China; 5Department of Internal Medicine, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, People’s Republic of China; 6Department of Ultrasound, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 7Department of Ultrasound, Mingzhou Hospital, Huzhou, People’s Republic of China; 8Laboratory of Blood Transfusion Research, Huzhou Center Blood Station, Huzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quan Sun, Laboratory of Blood Transfusion Research, Huzhou Center Blood Station, Fenghuang Road 577&num;, Huzhou, 313000, People’s Republic of China, Email sunquanhz@163.com Jianming Guan, Department of Ultrasound, First People’s Hospital Affiliated to Huzhou University, Guangchanghou Road 158&num;, Huzhou, 313000, People’s Republic of China, Email guan9300@126.comBackground: The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI.Methods: The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups.Results: The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40– 0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03– 2.16; P=0.032) and AFP (> 1000; HR, 1.61; 95% CI: 1.08– 1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009).Conclusion: Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.Keywords: hepatocellular carcinoma, macrovascular invasion, cinobufacini, hepatic arterial infusion, efficacy

Shuman Wu,1,&ast; Huiting Liu,2,&ast; Yimeng Li,2,&ast; Yanrong Teng1 1School of Education, South China Normal University, Guangzhou, Guangdong province, People’s Republic of China; 2School of Economic, Jinan University, Guangzhou, Guangdong province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiting Liu, School of Economic, Jinan University, Guangzhou, Guangdong province, 510632, People’s Republic of China, Email carrie620@qq.comPurpose: Mainland universities have become one of the important choices for students from Hong Kong, Macao and Taiwan, but the maladaptation caused by environmental migration will have a negative impact on the mental health of them. Therefore, it is urgent to explore the psychological mechanism of sociocultural adaptation of Hong Kong, Macao and Taiwan students.Methods: In order to explore the influence of self-esteem on the sociocultural adaptation of college students of Hong Kong, Macao and Taiwan studying in mainland universities, as well as the mechanism of social support and school belonging, a survey was conducted among 1108 college students from Hong Kong, Macao and Taiwan studying in mainland universities, with the help of Rosenberg Self-Esteem Scale, Sociocultural Adaptation Scale, Perceptive Social Support Scale and The Psychological Sense of School belonging Scale.Results: The results show that (1) Different grades of college students of Hong Kong, Macao and Taiwan have differences in school belonging and sociocultural adaptation (P< 0.05); (2) Self-esteem, social support, school belonging and sociocultural adaptation were positively correlated (P < 0.01); (3) The mediation model test showed that self-esteem could directly and positively predict sociocultural adaptation with a direct effect size of 0.245; Social support and school belonging played a mediating role between self-esteem and sociocultural adaptation, and the mediating effect sizes were 0.094 and 0.085, respectively. The chain mediating effect of social support and school belonging was also significant, and the mediating effect size was 0.108.Conclusion: Self-esteem can not only directly affect college students’ sociocultural adaptation, but also indirectly affect college students’ sociocultural adaptation through the chain mediating effect of social support and school belonging. This study further reveals the mechanism of self-esteem on sociocultural adaptation and provides psychological basis for universities to improve the sociocultural adaptation level of different groups of students.Keywords: self-esteem, sociocultural adaptation, social support, school belonging, college students of Hong Kong, Macao and Taiwan

Sijin Wu,1 Zhongli Chen,1 Yuan Gao,1 Songren Shu,2 Feng Chen,1 Ying Wu,1 Yan Dai,1 Shu Zhang,1 Keping Chen1 1Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Keping Chen, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email chenkeping@263.netBackground: The diagnosis of cardiac syncope remains a challenge. This study sought to develop and validate a diagnostic model for the early identification of individuals likely to have a cardiac cause.Methods: 877 syncope patients with a determined cause were retrospectively enrolled at a tertiary heart center. They were randomly divided into the training set and validation set at a 7:3 ratio. We analyzed the demographic information, medical history, laboratory tests, electrocardiogram, and echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. Then a multivariable logistic regression analysis was performed to identify independent predictors and construct a diagnostic model. The receiver operating characteristic curves, area under the curve (AUC), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy and clinical value of this nomogram.Results: Five independent predictors for cardiac syncope were selected: BMI (OR 1.088; 95% CI 1.022– 1.158; P =0.008), chest symptoms preceding syncope (OR 5.251; 95% CI 3.326– 8.288; P < 0.001), logarithmic NT-proBNP (OR 1.463; 95% CI 1.240– 1.727; P < 0.001), left ventricular ejection fraction (OR 0.940; 95% CI 0.908– 0.973; P < 0.001), and abnormal electrocardiogram (OR 6.171; 95% CI 3.966– 9.600; P < 0.001). Subsequently, a nomogram based on a multivariate logistic regression model was developed and validated, yielding AUC of 0.873 (95% CI 0.845– 0.902) and 0.856 (95% CI 0.809– 0.903), respectively. The calibration curves showcased the nomogram’s reasonable calibration, and the decision curve analysis demonstrated good clinical utility.Conclusion: A diagnostic tool providing individualized probability predictions for cardiac syncope was developed and validated, which may potentially serve as an effective tool to facilitate early identification of such patients.Keywords: cardiac syncope, syncope, diagnosis, nomogram, prediction model

Xiaoye Yuan, Caixia Lv, Sisi Wu, Huiying Wang, Xiaoyu Liu Department of Geriatric Cardiovascular, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Xiaoye Yuan, Department of Geriatric Cardiovascular, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, 050000, People’s Republic of China, Tel +86-15511308370, Email yxymoon2000@163.comPurpose: To investigate the predictive value of hemoglobin (Hb) to red blood cell distribution width (RDW) (Hb/RDW) ratio in combination with serum sodium for major adverse cardiovascular events (MACE) in elderly acute heart failure patients with preserved ejection fraction at 30 days after discharge.Methods: 130 elderly acute heart failure patients with preserved ejection fraction were enrolled and followed up at 30 days after discharge. They were classified into the MACE group (n=11) and none-MACE group (n=119). On the day of admission, clinical baseline characteristics were measured and results from laboratory tests were gathered. The correlation and predictive value of Hb/RDW and serum sodium with the occurrence of MACE at 30 days after discharge in acute heart failure patients with preserved ejection fraction in the elderly were analyzed.Results: Spearman correlation analysis showed that the occurrence of MACE was negatively correlated with Hb/RDW, serum sodium (r=− 0.209, r=0.291, p< 0.05) and Hb/RDW (OR=0.484, 95% CI:0.254, 0.922), serum sodium (OR=0.779, 95% CI:0.646,0.939) were independent risk factors (p< 0.05) analyzed by multifactorial logistic. Receiver operating characteristic curves (ROC) analysis showed that the area under the curve (AUC) for the prediction of MACE by Hb/RDW was 0.73, with an optimal threshold of 9.28, sensitivity 81.80%, specificity 70.60%, positive predictive value (PPV) 20.50%, negative predictive value (NPV) 97.70%; the AUC of serum sodium for predicting the occurrence of MACE was 0.76, with an optimal threshold of 140.35 mmol/L, sensitivity 90.90%, specificity 57.10%, PPV 16.40%, NPV 98.60%; and the AUC of Hb/RDW combined serum sodium to predict the occurrence of MACE was 0.83, with sensitivity 90.90%, specificity 78.20%, PPV 27.80% and NPV 98.90%.Conclusion: Hb/RDW and serum sodium had negative correlation with MACE and were independent risk factors of 30-day MACE; Hb/RDW combined with serum sodium can predict 30-day MACE occurrence in elderly acute heart failure patients with preserved ejection fraction.Keywords: hemoglobin to red cell blood distribution width ratio, serum sodium, acute heart failure, MACE, predictive value, elderly

Xiajun Guo,&ast; Sijia Wu,&ast; Wanglin Dong, Yiqiu Zhang, Yue Su, Chaoran Chen Institute of Nursing and Health, School of Nursing and Health, Henan University, Kaifeng, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoran Chen, Email kfccr@126.comBackground & Aim: Non-suicidal self-injury (NSSI) in adolescents is a serious public health issue influenced by the interaction of multiple factors. The purpose of this study was to investigate the multiple mediating roles of alexithymia and self-esteem in the association between bullying victimization and NSSI in a sample of Chinese adolescents.Methods: A survey of 1299 adolescents from two public middle schools in Henan Province, China, was undertaken. Data were collected using the Chinese version of the Delaware bullying victimization scale-student (DBVS-S), the Toronto Alexithymia-20 Scale (TAS-20-C), the Rosenberg self-esteem scale (RSES), and the adolescent self-injury questionnaire. Besides, we performed a structural equation modeling (SEM) with latent variables using AMOS 26.0 to examine the relationship between variables and the mediating effects.Results: The SEM analysis found that not only can bullying victimization directly impact NSSI, but that alexithymia and self-esteem have a chain mediating effect in the association between bullying victimization and NSSI. This mediating effect contributed 22.47% to the total effect.Conclusion: These findings validate bullying victimization, alexithymia, and low self-esteem are important variables that affect NSSI among Chinese adolescents. Educators need to implement some prevention and intervention strategies to ameliorate the campus atmosphere and adolescents’ mental health aimed at avoiding NSSI behavior in adolescence.Keywords: bullying victimization, non-suicidal self-injury, alexithymia, self-esteem, adolescents

Shuo Wu,1,2 Jiahong Lao,1 Feitong Jian1 1E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, People’s Republic of ChinaCorrespondence: Shuo Wu, E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China, Tel +86-20-85252239, Email wush68@sysu.edu.cnPurpose: This study aimed to determine indices to diagnose and predict eosinophilic chronic rhinosinusitis (ECRS) during the initial clinic visit.Patients and Methods: We retrospectively analyzed 116 patients with chronic rhinosinusitis who underwent endoscopic sinus surgery and were classified according to the postoperative pathological diagnosis. General data and various clinical indicators were analyzed, and indicators with statistically significant differences between groups were further incorporated into a multivariate logistic regression to establish a comprehensive prediction model. The receiver operating characteristic (ROC) curve was used to compare the two significant valuable single factors from previous studies, the difference in CT scores between the ethmoid sinus and the sum difference of the maxillary sinus (EM difference) and the absolute value of peripheral blood eosinophil (bEOS), with a comprehensive prediction model.Results: There were significant differences in history of allergic asthma (p < 0.001), visual analog scale (VAS) score (p=0.005), sino-nasal outcome test-22(SNOT-22) scale score (p=0.004), Lund-Mackay scale score (p=0.017), EM difference (p=0.002), percentage of bEOS (%)(p=0.001), and absolute value of bEOS (× 109/L) (p=0.000) between the two groups (p< 0.05). The history of allergic disease, VAS and bEOS were screened out and included in the comprehensive prediction model. The area under the curve (AUC) of the comprehensive prediction model (0.804)> the AUC of the absolute value of the bEOS (0.764)>the AUC of the EM difference (0.655). The AUC of the EM difference and the comprehensive prediction model were statistically different (P=0.025). There was no statistical difference between the absolute value of bEOS and the AUC of the comprehensive prediction model.Conclusion: The comprehensive prediction model covering the three aspects of allergic asthma history, VAS score, and bEOS count had the highest AUC compared to the other predictors and had good predictive power for the diagnosis of ECRS.Keywords: eosinophilic chronic rhinosinusitis, non-eosinophilic chronic rhinosinusitis, prediction model, the difference of the CT scores between the ethmoid sinus and maxillary sinus, European position paper on rhinosinusitis and nasal polyps 2020

Hongqi Meng,1 Ying Zhao,1 Hang Cai,2 Di You,3 Ying Wang,4 Siyu Wu,1 Yixin Wang,5 Wenlai Guo,1 Wenrui Qu1,6 1Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 3Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130031, People’s Republic of China; 4Institute of Neural Tissue Engineering, Mudanjiang College of Medicine, Mudanjiang, 157011, People’s Republic of China; 5Department of Plastic Surgery, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 6Joint International Research Laboratory of Ageing Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Wenlai Guo, Email guowl19@jlu.edu.cnPurpose: Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats.Methods: Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition.Results: Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance.Conclusion: Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing. Keywords: MRSA, infection, diabetic wounds, hydrogels, CS-AuNPs, antimicrobial

Xiaotian Ji,1 Shuhui Wu,1 Dan Zhao,1 Qi Bai,1 Yun Wang,1 Ke Gong,2 Huie Zheng,1 Mingfang Zhu1 1Department of Dermatology, the Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2Department of Traditional Chinese Medicine, Cangzhou Central Hospital, Cangzhou, People’s Republic of ChinaCorrespondence: Mingfang Zhu, Department of Dermatology, the Second Affiliated Hospital of Hunan University of Chinese Medicine, 233 Cai E North Road, Kaifu District, Changsha, People’s Republic of China, Tel +86-13907317358, Fax +86-731-84917727, Email 320492@hnucm.edu.cnBackground: The association between acne and gut microbiota has garnered considerable attention; nevertheless, given the substantial diversity within gut microbiota, the precise cause-and-effect relationship linking specific microbial species to acne remains elusive. To address this gap in knowledge, our study utilized Mendelian randomization analysis to elucidate a potential causal link between gut microbiota composition and acne development while also investigating underlying mechanisms involving microbial factors associated with metabolic disorders.Materials and Methods: The independent single nucleotide polymorphisms (SNPs) closely associated with 196 gut microbiota samples (N=18340) were selected as variable tools. The relationship between gut microbiota and acne (N=212438) was analyzed using the Twosample package in R4.3.1, employing various methods including inverse variance weighting (IVW), weighted median, MR-Egger, Simple-mode, and Weighted-mode. To ensure the stability of the estimates, a series of sensitivity analyses were conducted, such as Cochran’s Q-test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Additionally, the impact of each instrumental variable was calculated.Results: In the Mendelian randomization analysis, we identified twelve microbial taxa potentially associated with acne: family.Bacteroidaceae, family.Clostridiaceae1, genus.Allisonella, genus.Bacteroides, genus.Butyricimonas, genus.Clostridiumsensustricto1, and genus.Coprococcus3. These seven bacterial groups were found to be potential risk factors for acne. Conversely, family.Lactobacillaceae and genus.Ruminococcustorquesgroup along with genus.CandidatusSoleaferrea, genus.Fusicatenibacter, family.Lactobacillaceae, and genus.Lactobacillus exhibited a protective effect against acne. Furthermore, our investigation revealed that some of these microbial taxa have been implicated in metabolic diseases through previous studies. Importantly though, no causal relationship was observed in the reverse Mendelian randomization analysis.Keywords: acne, gut microbiota, Mendelian randomization, metabolic disease

Qiu Zeng, Xiaoyi Liu, Lina Li, Qin Zhang, Chengping Luo, Shu Yang, Shuqiang Wu, An Yang, Jie Li Department of Rehabilitation Medicine, The Sixth People’s Hospital of Yibin, Yibin, Sichuan, People’s Republic of ChinaCorrespondence: An Yang; Jie Li, Email yangan19661063@163.com; lijieyibin@163.comBackground: Osteoarthritis (OA) is a common disease in geriatric rehabilitation medicine caused by the progressive destruction of articular cartilage. Traditional Chinese exercise (TCE) is an important component of traditional sports in China and aims to stretch the musculoskeletal tract and relieve joint pain. Bibliometrics can help researchers find suitable partners and understand the research hotspots and trends in a certain field. However, there is still a lack of bibliometric analysis in the field of TCE and OA.Methods: All the literature was obtained from the Web of Science Core Collection database. The last search was performed on July 28, 2023. The bibliometric indicators, such as publications, citations, and H-index, were recorded. Bibliometrix and CiteSpace were used for visualization analysis. In addition, randomized controlled trials were included to summarize the exercise prescription of TCE for OA.Results: A total of 170 articles were included. The field of OA with TCE had great development potential and was in the rising period. The countries, institutions, and authors with the most publications were the United States, Tufts Medical Center, and Harvey WF, respectively. The most popular journal was Osteoarthritis and Cartilage. The recent burst keywords in this field were mainly “hip”, “pilot”, and “risk”. Tai Chi was the most studied TCE with the most detailed content of exercise prescription, followed by Baduanjin and Wuqinxi.Conclusion: Our study provides a basis for researchers in this field to choose appropriate partner and academic journals. Moreover, pain, muscle strength, and quality of life management of elderly OA patients are research hotspots in this field. The intervention of hip OA risk through TCE is expected to become a research direction for emerging teams. The TCE prescription we summarized can better provide researchers with more treatment details.Keywords: osteoarthritis, traditional Chinese exercise, traditional Chinese medicine, rehabilitation, bibliometrics

Zhijian Wu,1– 3 Xiaotian Jin,1 Ilyas Tudahun,1 Shangjie Wu,2,3 Mingxian Chen,1 Jianjun Tang1 1Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Hunan Centre for Evidence-Based Medicine, Changsha, 410011, People’s Republic of ChinaCorrespondence: Jianjun Tang; Mingxian Chen, Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, Hunan, 410011, People’s Republic of China, Fax + 86 731 85533525, Email tom200210@csu.edu.cn; xymingxianchen@csu.edu.cnBackground and Aims: Whether IMH can directly cause persistent myocardial necrosis after reperfusion therapy in STEMI patients is still unclear. We conducted a prospective study to compare the cardiovascular parameters in patients with STEMI with and without IMH to explore the potential correlations between IMH and poor outcomes.Methods and Results: We prospectively enrolled 65 consecutive patients with newly diagnosed STEMI admitted to the CCU of the Second Xiangya Hospital of Central South University between April 2019 and November 2021, all of whom underwent primary PCI. Of these, 38 (58.5%) and 27 (41.5%) patients were in the IMH-absent and IMH-present groups, respectively. At a mean time of 5– 7 days after reperfusion therapy, the volume of MI measured using LGE sequence was larger in STEMI patients with IMH than in patients without IMH (34.2 ± 12.7 cm3 vs 21.1 ± 13.1 cm3, P< 0.001). HsTNT levels were significantly higher in the IMH-present group than in the IMH-absent [2500.0 (1681.5– 4307.0) pg/mL vs 1710.0 (203.0– 3363.5) pg/mL, P=0.021] group during hospitalization. The LVEF measured using CMR in the IMH-present group was lower than that in the IMH-absent group (30.7 ± 9.8% vs 42.3 ± 11.0%, P < 0.001). The rate of MACE at 12 months in IMH-present group was significantly higher than in the IMH-absent group (9/27 VS 2/38, P = 0.012).Conclusion: IMH can lead to further expansion of MI volumes in patients with STEMI, resulting in lower LVEF and higher MACE rate in the post-discharge follow-up.Keywords: myocardial infarction, cardiac magnetic resonance, intramyocardial hemorrhage, infarction volume, outcome

Tong Chen,1– 3 Shiquan Wu,1 Ling Feng,4 SiYu Long,1 Yu Liu,1,2 WenQian Lu,5 Wenya Chen,1 Guoai Hong,1 Li Zhou,1 Fang Wang,1 Yuechan Luo,1 Hequn Zou1,3,5 1Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, People’s Republic of China; 3Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Department of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of ChinaCorrespondence: Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: The annual prevalence of metabolic syndrome (MetS) is increasing. Therefore, early screening and recognition of MetS are critical. This study aimed to evaluate the association between high-density lipoprotein (HDL) subclasses and MetS and to examine whether they could serve as early indicators in a Chinese community-based population with normal high-density lipoprotein cholesterol (HDL-C) levels.Methods: We used microfluidic chip technology to measure HDL subclasses in 463 people with normal HDL levels in 2018. We assessed how HDL subclasses correlated with and predicted insulin resistance (IR) and metabolic syndrome (MetS), evaluated by homeostatic model insulin resistance index (HOMA-IR) and the 2009 International Diabetes Federation (IDF), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) criteria, respectively. We used correlation tests and ROC curves for the analysis.Results: The results indicate that there was a negative association between HDL2b% and the risk of IR and MetS in both sexes. Subjects in the highest quartile of HDL2b% had a significantly lower prevalence of IR and MetS than those in the lowest quartile (P< 0.01). Correlation analysis between HDL2b% and metabolic risk factors showed that HDL2b% had a stronger association with these factors than HDL-C did in both sexes. ROC curve analysis also showed that HDL2b% had significant diagnostic value for IR and MetS compared to other lipid indicators.Conclusion: This study showed that MetS alters the distribution of HDL subclasses even when HDL-C levels are within the normal range. HDL-2b% has better diagnostic value for IR and MetS than HDL-C alone and may be a useful marker for early screening.Keywords: HDL subclass, insulin resistance, metabolic syndrome, normal HDL-C population

Changyu Yao,&ast; Jian Kong,&ast; Fei Xu, Shaohong Wang, Shilun Wu, Wenbing Sun, Jun Gao Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbing Sun; Jun Gao, Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86-010-51718382, Fax +86-010-51718372, Email sunwenbing@bjcyh.com; gaojun8430@163.comPurpose: Systemic inflammatory response syndrome (SIRS) is a common complication of radiofrequency ablation (RFA) for hepatic hemangiomas. RFA can cause hemolytic reactions during hepatic hemangioma ablation. However, the mechanisms underlying RFA-induced SIRS remain unclear.Methods: We established an orthotopic liver hemangioma model and performed radiofrequency ablation. The levels of interleukin (IL)-1β and IL-18 and the production of ROS were measured. The wet-to-dry lung ratio, inflammation score, and in vivo endothelial cell permeability were examined. GSDMD−/− mice were used to investigate the effect of heme-inducing SIRS. RNA sequencing (RNA-seq) was performed to identify the main pathways underlying heme-induced SIRS. Western blotting and immunoprecipitation were used to determine the changes and interactions of associated proteins.Results: The levels of heme, IL-1β, and IL-18 were significantly increased after RFA. The wet-to-dry lung ratio increased in hepatic hemangiomas after RFA, indicating that SIRS occurred. Heme induced increased levels of IL-1β and IL-18, cell death, wet-to-dry lung radio, and inflammation score in vitro and in vivo, indicating that heme induced SIRS and pyroptosis. Furthermore, GSDMD participates in heme-induced SIRS in mice, and GSDMD deletion in mice reverses the effect of heme. Heme regulates NLRP3 activation through the NOX4/ROS/TXNIP-TRX pathway, and an N-acetyl-L-cysteine (NAC) or NOX4 inhibitor (GLX351322) reverses heme-induced SIRS.Conclusion: Our findings suggest that heme induces endothelial cell pyroptosis and SIRS in mice and decreasing heme levels and ROS scavengers may prevent SIRS in hepatic hemangioma after RFA. Keywords: hemangioma, radiofrequency ablation, systemic inflammatory response syndrome, pyroptosis, endothelial cells

Yan Fang,1,2,&ast; Chuang Xiao,1,&ast; Lueli Wang,1,&ast; Youlan Wang,3 Jun Zeng,1 Yaping Liang,1 Rong Huang,1 Yunke Shi,2 Sha Wu,1 Xiaohua Du,2 Shibo Sun,2 Min Li,2 Yuanyuan Zheng,2 Hongxiang Wu,1 Qiuzhe Guo,4 Weimin Yang1 1School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, People’s Republic of China; 2The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Kunming Institute of Medical Sciences, Kunming, People’s Republic of China; 4Fuwai Yunnan Cardiovascular Hospital, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuzhe Guo; Weimin Yang, Email drguoqz@163.com; ywmbessie@yeah.netBackground: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation.Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR.Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2.Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.Keywords: isoforskolin, sepsis, acute lung injury, pulmonary inflammation, glucocorticoids, regulator of G-protein signaling 2

Xiaojuan Qian,1,2,&ast; Weiwei Bao,1,2,&ast; Shenghai Wu,2 Jiawei Zhou,3 Yunxing Yang,2 Xianjun Wang,2 Daojun Yu,2 Qiong Chen2 1Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3State Key Laboratory of Diagnosis and Treatment for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong Chen, Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China, Email chenqiong2002@126.comPurpose: This study aims to investigate the clinical and molecular characteristics of carbapenemase-producing E. coli strains (CPECO).Patients and Methods: We collected 38 non-repetitive CPECO strains, identified them using MALDI-TOF, and assessed their antimicrobial susceptibility via the VITEK-Compact II system. We gathered demographic and clinical patient data. Phenotypic assays were employed to detect carbapenemase types. Polymerase chain reaction (PCR) was utilized to identify the carbapenemase genes. Seven housekeeping genes were amplified and sequenced to determine the multilocus sequence typings (MLSTs).Results: These CPECO strains, primarily isolated from aseptic site and stool screening specimens, exhibited significant resistance to most clinical antibiotics, except for tigecycline and amikacin. Most patients had underlying medical conditions and underwent invasive procedures. There were significant differences among patients concerning the presence of malignancies, digestive system disorders, endoscopic retrograde cholangiopancreatography (ERCP) surgeries and abdominal drainage tubes. However, no significant differences were observed among patients regarding conditions, including hypertension, diabetes, respiratory diseases, urinary diseases and cardiovascular diseases, as well as invasive procedures such as deep venous catheterization, endotracheal intubation and gastrointestinal catheterization. Metallo-β-lactamase was primarily responsible for carbapenem resistance, including blaNDM-5(24/38), blaNDM-1(5/38), blaNDM-9(1/38) and blaIMP-4(1/38). Additionally, 7 CPECO strains carried blaKPC-2. The distribution of CPECO sequence types (STs) was diverse, with seven strains being ST131, six strains being ST410, three strains each of ST1196 and ST10, although most STs were represented by only one strain.Conclusion: CPECO infections in patients with biliary system diseases may result from intestinal CPECO translocation, with ERCP surgery potentially facilitating this. Meanwhile, malignant tumor was found to be a significant factor affecting CPECO infections in patients with hematological diseases. blaNDM-5, blaNDM-1 and blaNDM-9 were primarily responsible for carbapenem resistance in CPECO strains. The emergence of carbapenem-resistant ST131 and ST410 strains should be alert to prevent the spread of carbapenem-resistant genes within high-risk epidemic clones.Keywords: carbapenemase-producing E. coli, underlying diseases, endoscopic retrograde cholangiopancreatography, ERCP, NDM

Ye Wang,1,&ast; Fenxiang Li,1,&ast; Jian Liu,2 Jing Liu,3 Pei Qin,4 Jiayi Zhang,5 Yingtao Zhang,5 Shuning Wu6 1Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, People’s Republic of China; 2Department of General Surgery, Maternal and Child Health Hospital, Qingyuan, Guangdong, People’s Republic of China; 3Intensive Care Unit 1, The First Affiliated Hospital, Jinan University, Guangdong, Guangzhou, People’s Republic of China; 4Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, People’s Republic of China; 5Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 6Department of Thyroid and Breast Surgery, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingtao Zhang, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 510000, People’s Republic of China, Tel +86 15918805867, Email zhangyt9@mail2.sysu.edu.cn Shuning Wu, Thyroid and Breast Surgical Department, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518067, People’s Republic of China, Tel +86 13480209989, Email jessica540wu@outlook.comPurpose: This study aims to identify common COVID-19 symptoms and asymptomatic infection rates during the epidemic in China. We also introduce the concepts of “Time-point asymptomatic rate” and “Period asymptomatic rate”.Object and Methods: A questionnaire survey was conducted online from December 2022 to January 5, 2023, collecting demographic characteristics, laboratory results, clinical symptoms, lifestyle and vaccination history. Statistical methods were used to analyze symptom characteristics, associated factors, and patterns during an 8-day observation period. Numerical variables were described by median M (Q1-Q3) or mean and standard deviation (). Categorical variables are described by frequency (N), ratio (%) or rate (%). The influencing factors were studied by Wilcoxon or Kruskal-Willis H rank sum test or logistic regression analysis, and the trend of symptom incidence by Spearman rank correlation. P value being ≤ 0.05 was statistically significant.Results: Out of 536 participants, 493 (91.98%) were infected, with 3 asymptomatic cases and 490 symptomatic cases within 8 days. The time-point asymptomatic rate increased from 0.61% on day 1 to 15.42% on day 8. Fever, cough, and fatigue were the main symptoms, with additional symptoms such as vomiting, diarrhea, and hyposmia reported. Symptom durations varied, with cough and expectoration lasting longer and vomiting and diarrhea lasting shorter. Several symptoms showed a downward trend over time.Conclusion: Our online survey highlighted that most COVID-19 patients experienced symptoms, and the time-point asymptomatic rate showed a dynamic change among the infected population. Onset patterns and demographic factors influence symptom occurrence and duration. These findings have implications for clinical practitioners and decision-makers in public health measures and strategies.Keywords: Novel coronavirus infection, onset patterns, clinical features, associated factors, time-point asymptomatic, period asymptomatic rate

Shaoping Wu,1 Junnan Chen,1 Enmin Huang,2– 4 Yongfa Zhang1 1Department of Anesthesiology, the Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Gastroenterological Surgery and Hernia Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Enmin Huang; Yongfa Zhang, Email huangenm5@mail.sysu.edu.cn; 10yfzhang1@stu.edu.cnIntroduction: The relationship between the expression of opioid-associated receptors and cancer outcomes is complex and varies among studies.Methods: This study focused on six opioid-related receptors (OPRM1, OPRD1, OPRK1, OPRL1, OGFR, and TLR4) and their impact on cancer patient survival. Bioinformatics analysis was conducted on 33 cancer types from The Cancer Genome Atlas database to examine their expression, clinical correlations, mechanisms in the tumor microenvironment, and potential for immunotherapy. Due to significantly lower expression of OPRM1, OPRD1, and OPRK1 compared to OGFR and TLR4, the analysis concentrated on the latter two genes.Results: OGFR was highly expressed in 16 tumor types, while TLR4 showed low expression in 13. Validation from external samples, the Gene Expression Omnibus, and the Human Protein Atlas supported these findings. The diagnostic value of these two genes was demonstrated using the Genotype-Tissue Expression database. Univariate Cox regression models and Kaplan-Meier curves confirmed OGFR’s impact on prognosis in a cancer type-specific manner, while high TLR4 expression was associated with a favorable prognosis. Analysis of the tumor microenvironment using a deconvolution algorithm linked OGFR to CD8+ T cells and TLR4 to macrophages. Single-cell datasets further validated this correlation. In 25 immune checkpoint blockade treatment cohorts, TLR4 expression showed promise as an immunotherapy efficacy predictor in non-small cell lung cancer, urothelial carcinoma, and melanoma.Conclusion: In a pan-cancer analysis of 33 tissues, OGFR was consistently highly expressed, while TLR4 had low expression. Both genes have diagnostic and prognostic significance and are linked to immune cells in the tumor microenvironment. TLR4 has potential as an immunotherapeutic response marker.Keywords: opioid-related receptors, pan-cancer analysis, immune checkpoint blockade therapy, TLR4, OGFR, prognosis, macrophage, CD8+ T cell

Dongyi Yu,1,2,&ast; Libo Wang,2,&ast; Xin Zhou,2,&ast; Lili Liu,2 Shuang Wu,2 Qing Tang,3 Xiaofeng Zhang1 1Department of Ophthalmology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of Ophthalmology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, People’s Republic of China; 3Department of Neurology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng Zhang, Email zhangxiaofeng@suda.edu.cnPurpose: To identify potential demographic and lifestyle factors associated with progression of myopia with orthokeratology (ortho-k) treatment via follow-up of axial length (AL).Methods: In this retrospective observational study, demographics, ocular parameters, near-work distance, outdoor activities, and sleep quality were analyzed in 134 children with myopia aged 8~15 years using ortho-k and a follow-up for one year.Results: Compared with the slow progression group, the participants in the fast progression group were younger in age (10.55 ± 1.70 years vs 9.90 ± 1.18 years, P = 0.009), demonstrated higher spherical equivalent (SE) value (− 2.52 ± 0.63 diopters (D) vs − 3.05 ± 0.89 D, P < 0.001), shorter near-work distance (P = 0.010), and poorer sleep quality (Pittsburgh sleep quality index [PSQI], 4.79 ± 1.29 vs 3.81 ± 1.38, P < 0.001) in the one-year follow-up. Furthermore, multivariate linear regression analyses showed that baseline age (B =− 0.020, P = 0.020), SE (B = 0.0517, P < 0.001), and total PSQI (B=0.026, P = 0.001) were associated with axial elongation. Advanced logistic regression analyses demonstrated that shorter average near-work distance (P = 0.034), higher SE value (P = 0.023), and poorer sleep quality (P = 0.003) were associated with fast axial elongation.Conclusion: Sleep quality is one of the key factors associated with axial elongation in children with myopia after using ortho-k for one year. Further studies are required to confirm this observation and expand its practical applications.Keywords: orthokeratology, myopia, axial length, sleep quality, retrospective study

Man Li,1,2,&ast; Xintao Li,3,&ast; Hongwei Gao,4 Peng Li,1 Li Zhang,1 Xiaoling Zhang,1 Peipei Liu,5 Xuemei Yang,2 Lili Wu,6 Jiangwei Zeng,2 Shouling Wu,7 Lixia Sun1 1Department of Emergency, The Affiliated Hospital of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Graduate School, North China University of Science and Technology, Tangshan, People’s Republic of China; 3Department of Cardiology, The First Hospital of Soochow University, Jiangsu, People’s Republic of China; 4Department of Emergency, Caofeidian District hospital of Tangshan City, Tangshan, People’s Republic of China; 5School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 6Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 7Department of Cardiology, Kailuan Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixia Sun, Department of Emergency, The Affiliated Hospital of North China University of Science and Technology, Tangshan, 063000, People’s Republic of China, Email 13323151999@189.cn Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, 063000, People’s Republic of China, Email drwusl@163.comPurpose: Inflammation plays a critical role in the development of cardiac conduction block (CCB), which is associated with an increased risk of morbidity and mortality. The monocyte-lymphocyte ratio (MLR) acts as a novel inflammatory marker; however, its association with CCB has not yet been studied. This study aimed to investigate the association between MLR and CCB risk.Patients and Methods: In total, 82,472 CCB-free participants were identified from the Kailuan study. MLR was calculated using the monocyte count/lymphocyte count. The participants were stratified based on quartiles of MLR levels. Incident CCB and its subtypes were ascertained from electrocardiograms at biennial follow-up visits. The Cox proportional hazards model and restricted cubic spline analysis were used to investigate the association between MLR with CCB and its subtypes.Results: During a median follow-up of 10.4 years, 3222 incident CCB cases were observed. A U-shaped association was observed between MLR and CCB risk (Pnonlinearity < 0.05). After multivariate adjustment, individuals in the highest MLR quartile had a hazard ratio (HR) of 1.212 (95% CI: 1.097-1.340; Q4 vs Q2), while those in the lowest MLR quartile had an HR of 1.106 (95% CI: 1.000-1.224; Q1 vs Q2). Sensitivity and subgroup analyses yielded consistent results. The U-shaped association persisted for atrioventricular block (AVB) in subtype analyses.Conclusion: MLR was significantly associated with an increased risk of new-onset CCB. Assessing MLR may have clinical relevance for predicting CCB risk, providing valuable insights for preventive strategies and patient management.Pre-Registered Clinical Trial Number: The pre-registered clinical trial number is ChiCTR-TNC-11001489. Keywords: cardiac arrhythmia, cardiac conduction block, inflammation, monocyte-lymphocyte ratio, risk factors

Xuejiao Liao,1,&ast; Yuan Guan,1,2,&ast; Zixun Lin,1 Qingrong Tang,3 Zhenghua Ma,1 Shuting Wu,1 Xiaobin Wang,1 Jingke Dong,1 Liping Zhang,1 Jiayu Deng,1 Zhonghui Liao,1,4 Sumei Yang,1,4 Cheng Wang,1,4 Shuo Song,1 Hongyang Yi,1 Song Wu,5 Tetsuya Asakawa,6 Hongzhou Lu1 1Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Epidemiology, School of Public Health Fudan University, Shanghai, People’s Republic of China; 3The First Hospital of Changsha, Infectious Diseases Department, Changsha, People’s Republic of China; 4School of Public Health, Bengbu Medical College, Bengbu, People’s Republic of China; 5Department of Central Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen, People’s Republic of China; 6Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhou Lu, Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Hospital Affiliated with the School of Medicine, Southern University of Science and Technology, No. 29 Bulan Road, Long Gang District, Shenzhen, Guangdong, 518112, People’s Republic of China, Email luhongzhou@fudan.edu.cn Tetsuya Asakawa, Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, No. 29 Buji Bulan Road, Shenzhen, Guangdong, 518112, People’s Republic of China, Email asakawat1971@gmail.comPurpose: The purpose was to review relevant clinical data and formulate recommendations supporting the use of saline as a simple rinse for an early reassuring intervention to reduce the occurrence of re-positive COVID-19 patients.Methods: We conducted a single-centre retrospective cohort study, which enrolled patients with confirmed re-testing positive COVID-19 during 7– 60 days after discharge from Third People’s Hospital of Shenzhen. By one-to-two propensity score matching for age and sex, the control group of those not re-testing positive during the same period served as matched control.Results: A total of 223 patients were included in our study, 94 in re-positive group and 129 in non-re-positive group. The result shows that the rates of nasal douche treatment in the non-re-positive group were considerably higher than that of the re-positive group. And the Ct value of nasal douche group increased faster than that of non-nasal douche group after the Ct value reaching ≥ 35. Further analysis revealed that the higher the Ct value at the time of readmission, the shorter the time of average Ct values to reach ≥ 35.Conclusion: These findings suggest that nasal douche is beneficial to shorten the time of virus nucleic acid turning negative, thereby reducing the incidence of re-positive. The prevention and control of epidemics focuses on re-positive patients with Ct values < 35.Keywords: COVID-19, nasal douche, re-positive, RT-PCR

Matthew M Mirsky,1 Carley Mitchell,1 Augustine Hong,1 Shufen Cao,2 Pingfu Fu,2 Seunghee Margevicius,2 Sulin Wu,1 Afshin Dowlati,1 Ariel Nelson,1 J Eva Selfridge,1 Nikhil Ramaiya,1 Christopher Hoimes,1 Asrar Alahmadi,1,&ast; Debora S Bruno1,&ast; 1University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 2Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA&ast;These authors contributed equally to this workCorrespondence: Debora S Bruno, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA, Tel +1 216 844-3951, Email Debora.Bruno@uhhospitals.orgPurpose: Disparities in cancer care delivery remain a pressing health-care crisis within the United States (US). The use of immune checkpoint inhibitors (ICIs) and their management may be a disparity generator that impacts survival. This retrospective study assessed disparities in a cohort of patients with a variety of solid tumors treated with ICIs within a single health-care organization focusing on the impact of race, socioeconomic status (SES) and site of care delivery on survival and the development of severe immune-related adverse events (irAEs).Patients and Methods: Manual chart review was performed on all patients with solid tumors treated with ICIs within a health-care organization from 2012 to 2018. Care delivery was dichotomized as DOP (disease-oriented provider at academic center) and COP (community oncology provider). Primary and secondary outcomes were overall survival (OS) and rates of grade 3– 4 irAEs, respectively. Relationships with covariates of interest, including race, socioeconomic status and type of care delivery, were assessed among both outcomes.Results: A total of 1070 eligible patients were identified. Of those, 11.4% were of Black race, 59.7% had either non-small cell lung cancer (NSCLC) or melanoma and 82.8% had stage IV disease. Patients of Black race and lower SES were more likely to be treated by DOPs (p< 0.0001). A superior OS was associated with care delivered by DOPs when compared to COPs (HR 0.68; 95% CI 0.56– 0.84; p=0.0002), which was durable after accounting for race, SES, histopathologic diagnosis and disease stage. Melanoma patients experienced higher rates of severe irAEs (HR 2.37; 95% CI 1.42– 3.97; p=0.001). Race, SES and site of care delivery were not related to rates of severe irAEs.Conclusion: In a large health-care organization, patients treated with checkpoint inhibitors by DOPs benefited from a significant OS advantage that was durable after controlling for racial and socioeconomic factors, providing evidence that disease-oriented care has the potential to mitigate racial and socioeconomic disparities.Keywords: disparities, healthcare delivery, immunotherapy outcomes

Shuhui Wu,1 Xi Zhang,2 Yun Wang,1 Huie Zheng,1 Mingfang Zhu1 1Department of Dermatology, Key Laboratory of Vascular Biology and Translational Medicine, Education Department of Hunan Province, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Department of Physical Education and Health Promotion, Hunan University of Technology and Business, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Mingfang Zhu, Department of Dermatology, Key Laboratory of Vascular Biology and Translational Medicine, Education Department of Hunan Province, The Second Affiliated Hospital of Hunan University of Chinese Medicine, 233 Caie North Road, Kaifu District, Changsha, Hunan, People’s Republic of China, Tel/Fax +86 731 8491 7727, Email 320492@hnucm.edu.cnAbstract: Acne vulgaris is one of the most widespread skin conditions and the main reason for visiting a dermatologist. Inflammatory response and abnormal infiltrations of immune cells are the main pathogenesis of acne. The increased lipid is the prerequisite for the acne, and the perturbation of lipid composition and content is consistent with the severity of acne. Furthermore, the increased lipid production not only contributes to the occurrence and development of acne, but also sensitizes the function of immune cells. The lipid metabolic dysfunction aggravates the severity of local tissue and provides pro-inflammatory-cytokine cues, which indicates the crucial roles of lipid metabolism on immune cells. Recent advances have demonstrated the lipid metabolism reprogramming of various immune cells in acne lesion. The abnormal lipid accumulation, lipolysis, and fatty acid oxidation lead to the activation and differentiation of immune cells, which promotes the pro-inflammatory cytokines production. Thus, this review discusses the emerging role of lipid metabolism reprogramming of immune cells in the progress of acne and aims to constitute food for others’ projects involved in acne research.Keywords: acne vulgaris, inflammatory response, lipid, reprogramming

Siyao Wu,1,&ast; Ting Guo,2,&ast; Hui Zhang,1 Zhiyi He,1 Jianquan Zhang,3 Wen Zeng1 1Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Department of Dermatology and Venereology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Zeng, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86 18589883694, Email zengwen@stu.gxmu.edu.cnAbstract: Adult-onset acquired immunodeficiency caused by anti-IFN-γ autoantibodies is associated with severe opportunistic infection. Due to lack of specific symptoms and different manifestations, this form of infection can be easily misdiagnosed or overlooked. Herein, we present a case of Nocardia farcinica and Talaromyces marneffei co-infection in a patient with anti-IFN-γ autoantibodies (AIGAs). The patient, a 54-year-old man, presented with a 1-month history of fever, coughing and expectoration, dizziness, headache and gait imbalance. Laboratory workup revealed increased inflammatory markers, negative anti-HIV antibody and a high positive titer of AIGAs. Chest computed tomography (CT) showed multiple patches of high-density shadows in both lungs, and brain enhanced magnetic resonance imaging (MRI) showed an irregular lesion. The patient underwent a craniotomy for resection of the lesion. Pulmonary T. marneffei infection was diagnosed through sputum and bronchoalveolar lavage fluid culture, and brain nocardiosis was confirmed via purulent fluid culture of brain tissue. With regular antibiotic therapy, his symptoms improved and there was no recurrence during 18-month follow-up. This may be the first detailed case report detailing infection with these two distinct pathogens in disparate anatomical locations.Keywords: nocardia, Talaromyces marneffei, adult-onset acquired immunodeficiency, anti-IFN-γ autoantibodies, brain abscess

Du Wei,1,&ast; Yue Chang,1,2,&ast; Qi Chen,3,&ast; Qin Wang,4 Hanni Zhou,1,2 Shengyan Wu,1,2 Xiaomin Xian,5 Zhezhe Cui6 1School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Center of Medicine Economics and Management Research, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Pharmacy Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 4Department of Health Education, Tongren Centre for Disease Control and Prevention, Tongren, Guizhou, People’s Republic of China; 5School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 6Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi Key Discipline platform of Tuberculosis Control, Guangxi Centre for Disease Control and Prevention, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhezhe Cui, Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi key discipline platform of tuberculosis control, Guangxi Centre for Disease Control and Prevention, Nanning, Guangxi, People’s Republic of China, Tel/Fax +86-0771-2518785, Email czz6997@163.com Yue Chang, School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China, Tel/Fax +86-0851-88308118, Email changyue@gmc.edu.cnPurpose: To establish a concise and easy-to-understand reference manual for outpatient primary care providers, promoting correct diagnosis of digestive system diseases and rational antimicrobial use.Methods: The establishment of the manual encompassed two processes: the development of a draft manual and the validation of the manual. The development process was based on a literature review and expert discussion. The manual comprises portions for disease diagnosis and rationality of antimicrobial use. The validation process employed a two-round Delphi technique, collecting consensus through paper-based or mail-based communications. The response of the Delphi group was assessed by the level of authority and commitment of the panelists and the degree of agreement among them. Furthermore, the manual was preliminarily applied among primary care physicians.Results: A total of 29 panelists completed the Delphi working process. They were authoritative in their professional fields with authority coefficients of 0.813 and 0.818 for the two portions of the manual, respectively. The level of commitment of the panelists was measured by response rates, which were 100.00% and 96.67% for Round 1 and 2. After two rounds, a consensus was achieved with the consensus rates for the two portions of the manual being greater than 65% and 70%, respectively. Kendall W-tests had P-values < 0.001 in both rounds. This reference manual provides 200 diagnostic indicators for 29 common digestive diseases and recommendations for the rational use of antimicrobial agents for 13 categories of digestive diseases. The primary care physicians who used the reference manual reported high satisfaction and frequent usage.Conclusion: Based on a collective consensus of professionals, a reference manual has been established, to provide a concise and easy-to-understand guide specifically for physicians and pharmacists in outpatient primary care. It could facilitate rapid learning to improve the accuracy of diagnosis and treatment for digestive disorders.Keywords: primary health care, digestive system, diagnosis, antimicrobial agents, rational drug use, Delphi technique

Tianyou Chen,1,&ast; Chong Liu,1 Zide Zhang,2 Tuo Liang,2 Jichong Zhu,1 Chenxing Zhou,1 Shaofeng Wu,1 Yuanlin Yao,1,&ast; Chengqian Huang,1 Bin Zhang,1 Sitan Feng,1 Zequn Wang,1 Shengsheng Huang,1 Xuhua Sun,1 Liyi Chen,1 Xinli Zhan1 1Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Spine Ward, Liuzhou People’s Hospital, Liuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Zhan, Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email zhanxinli@stu.gxmu.edu.cnObjective: The objective of this study was to utilize machine learning techniques to analyze perioperative factors and identify blood glucose levels that can predict the occurrence of surgical site infection following posterior lumbar spinal surgery.Methods: A total of 4019 patients receiving lumbar internal fixation surgery from an institute were enrolled between June 2012 and February 2021. First, the filtered data were randomized into the test and verification groups. Second, in the test group, specific variables were screened using logistic regression analysis, Lasso regression analysis, support vector machine, and random forest. Specific variables obtained using the four methods were intersected, and a dynamic model was constructed. ROC and calibration curves were constructed to assess model performance. Finally, internal model performance was verified in the verification group using ROC and calibration curves.Results: The data from 4019 patients were collected. In total, 1327 eligible cases were selected. By combining logistic regression analysis with three machine learning algorithms, this study identified four predictors associated with SSI, namely Modic changes, sebum thickness, hemoglobin, and glucose. Using this information, a prediction model was developed and visually represented. Then, we constructed ROC and calibration curves using the test group; the area under the ROC curve was 0.988. Further, calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index of our model was 0.986 (95% CI 0.981– 0.994). Finally, we used the validation group to validate the model internally; the AUC was 0.987. Calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index was 0.982 (95% CI 0.974– 0.999).Conclusion: Logistic regression analysis and machine learning were employed to select four risk factors: Modic changes, sebum thickness, hemoglobin, and glucose. Then, a dynamic prediction model was constructed to help clinicians simplify the monitoring and prevention of SSI.Keywords: surgical site infection, lumbar spine surgery, machine learning, blood glucose, dynamic prediction model

Sinan Wu,1– 4,&ast; Ke Huang,1– 4,&ast; Chenli Chang,1– 5 Xu Chu,1– 4,6 Kun Zhang,7 Baicun Li,1– 4 Ting Yang1– 4 1National Center for Respiratory Medicine, Beijing, People’s Republic of China; 2National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 3Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, People’s Republic of China; 7Biotree-Shanghai, Focus Dream Park, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Yang; Baicun Li, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No. 2, East Yinghua Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 10-84206273, Email zryyyangting@163.com; lbc19890303@126.comPurpose: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with high morbidity and mortality rates. This study used proteomic profiling of serum to identify the differentially expressed proteins in COPD patients compared with healthy controls, to expand the knowledge of COPD pathogenesis and to ascertain potential new targets for diagnosis and treatment of COPD.Methods: Serum samples were collected from 56 participants (COPD group n = 28; Healthy Control group n = 28). A data-independent acquisition quantitative proteomics approach was used to identify differentially expressed proteins (DEPs) between the two groups. Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment, and protein–protein interaction analyses of DEPs were conducted to identify their relevant biological processes, cellular components, and related pathways. We used a parallel reaction monitoring (PRM)-based targeted quantitative proteomics approach to validate those findings.Results: Of 8484 peptides identified by searching the UniProtKB/Swiss-Prot knowledgebase, 867 proteins were quantifiable, of which 20 were upregulated and 35 were downregulated in the COPD group. GO functional annotation indicated that the subcellular localization of most DEPs was extracellular. The top three molecular functions of the DEPs were signaling receptor binding, antigen binding, and immunoglobulin receptor binding. The most relevant biological process was immune response. The transforming growth factor-β signaling pathway, Staphylococcus aureus infection, and hematopoietic cell lineage were the top three pathways identified in the KEGG pathway functional enrichment. Our PRM analyses confirmed the identification of 11 DEPs identified in our data-independent acquisition analyses, 8 DEPs were upregulated and 3 DEPs were downregulated.Conclusion: This study using data-independent acquisition analyses with PRM confirmation of findings identified 11 DEPs in the serum of patients with COPD. These DEPs are potential diagnostic or prognostic biomarkers or may be future targets for the treatment of COPD.Keywords: chronic obstructive pulmonary disease, proteomics, differentially expressed proteins, data-independent acquisition, parallel reaction monitoring