Search

Lin Feng,1 Jiachen Li,1 Zhenbei Qian,2 Chenglong Li,3,4 Darui Gao,3,4 Yongqian Wang,3,4 Wuxiang Xie,3,4 Yutong Cai,5 Zhaohui Tong,2 Lirong Liang1 1Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Heart and Vascular Health Research Center, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, People’s Republic of China; 5Centre for Environmental Health and Sustainability, Department of Health Sciences, University of Leicester, Leicester, UKCorrespondence: Lirong Liang, Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email llrcruie@163.comPurpose: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system.Patients and Methods: Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients’ demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA).Results: Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels.Conclusion: We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance.Keywords: chronic obstructive pulmonary disease, glucocorticoids, prediction model, least absolute shrinkage and selection operator

Zhen Xiao,1,2 Simin Yu,1 Deng Zhang,1 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Chunming Li, Email chunminglincu@163.comBackground: Capsaicin is the main compound found in chili pepper and has complex pharmacologic effects. This study aimed to elucidate the mechanism of the effect of capsaicin on physiological processes by analyzing changes in metabolites and metabolic pathways.Methods: Female C57BL/6 mice were divided into two groups(n = 10/group) and fed with capsaicin-soybean oil solution(group T) or soybean oil(group C) for 6 weeks. Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was undertaken to assess plasma and skin metabolic profile changes and identify differential metabolites through multivariate analysis.Results: According to the OPLS-DA score plots, the plasma and skin metabolic profiles in the group T and group C were significantly separated. In plasma, 38 significant differential metabolites were identified. KEGG pathway enrichment analysis revealed that the most significant plasma metabolic pathways included pyruvate metabolism and ABC transporters. In skin, seven significant differential metabolites were found. Four metabolic pathways with p values < 0.05 were detected, including sphingolipid metabolism, sphingolipid signaling pathway, apoptosis, and necroptosis.Conclusion: These findings will provide metabolomic insights to assess the physiological functions of capsaicin and contribute to a better understanding of the potential effects of a capsaicin-rich diet on health.Keywords: capsaicin, UHPLC-QTOF-MS, metabolomics, plasma, skin

Yuanli Ai,1,&ast; Kun Peng,2,&ast; Chunli Li,1,&ast; Jun Zhang,1 Gang Wang,3,4 Bin Wang,1 Enyi Huang3,4 1Institute of Life Sciences, College of Basic Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Medical and Pharmaceutical College, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education College of Stomatology, College of Stomatology, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Wang; Enyi Huang, Email bwang@cqmu.edu.cn; enyihuang@hospital.cqmu.edu.cnIntroduction: Bone, a pivotal structural organ, is susceptible to disorders with profound health implications. The investigation of gene expression in bone tissue is imperative, particularly within the context of metabolic diseases such as obesity and diabetes that augment the susceptibility to bone fractures. The objective of this study is to identify a set of internal control genes for the analysis of gene expression.Methods: This study employs reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) to assess gene expression in bone tissue. We selected fourteen housekeeping genes and assessed their stability in the cortical bone of mouse models for obesity and diabetes using four well-established algorithms (GeNorm, BestKeeper, NormFinder, and the comparative Delta Ct method).Results and Conclusion: We identified Rpl13a as the mostly stably expressed reference gene in cortical bone tissue from mouse models of obesity and diabetes (db/db), while Gapdh was found to be the most stable reference gene in another diabetes model, KKAy mice. Additionally, Ef1a, Ppia, Rplp0, and Rpl22 were identified as alternative genes suitable for normalizing gene expression in cortical bone from obesity and diabetes mouse models. These findings enhance RT-qPCR accuracy and reliability, offering a strategic guide to select reference gene for studying bone tissue gene expression in metabolic disorders.Keywords: reference genes, Rpl13a, Gapdh, cortical bone, metabolic disorders

Renzhe Tang,1,&ast; Chong Li,2,&ast; Dongmei Di,1 Lin Zhou,2 Yongxiang Qian,1 Chaohua Qiang,3 Chao Ma,1 Rui Zhou,1 Bin Wang,1 Min Wang1 1Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 2Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 3Department of Echocardiography, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wang; Bin Wang, Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, No. 185 of Juqian Street, Changzhou, Jiangsu Province, 213003, People’s Republic of China, Email wangmin80808@163.com; wangbin1987@suda.edu.cnObjective: Obstructive sleep apnea (OSA) is a disorder characterized by disruption in breathing and hypoventilation. In parallel, metabolic syndrome (MetS) mainly co-occur with OSA, however, their association has not been fully elucidated. Therefore, this study aimed to reveal the relationship between OSA and MetS using data from the National Health And Nutrition Examination Survey (NHANES) database and pooled data from Genome-Wide Association Studies (GWAS).Material and Methods: Data from the National Health and Nutrition Examination Survey and pooled data from genome-wide association analysis (GWAS) were used univariate and multivariate logistic regression analyses were carried out to evaluate the correlation between OSA and MetS, and multivariate logistic regression models were utilized for adjusting for potential confounders. Two-sample Mendelian randomization (MR) was used to assess the causal relationship between OSA and MetS. The variance-weighted inverse method was employed as the main method of analysis.Results: A positive relationship of OSA with Mets was evidenced by multivariate logistic regression analysis, and OSA was associated with higher incidence rates of all-cause and cardiovascular mortality. OSA is strongly associated with abdominal obesity, hypertension, hyperglycemia, high triglycerides, and low HDL. Furthermore, except for hypertriglyceridemia, MR analysis indicated that genetically driven OSA was causally associated with a higher risk of MetS.Conclusion: The positive relationship of OSA with Mets was revealed, and higher incidence rates of all-cause mortality and cardiovascular mortality were noted to be correlated with OSA. MR analysis further confirmed the causal relationship of OSA with MetS and cardiovascular disease.Keywords: obstructive sleep apnea, metabolic syndrome, cardiovascular disease, NHANES, Mendelian randomization

Chunhong Li,1,&ast; Zhen Wang,1,&ast; Yifeng Zhang,1 Yuqing Zhu,1 Maochang Xu,1 Hui Lei,1 Dan Zhang1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Green Pharmaceutical Technology Key Laboratory of Luzhou, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Lei; Dan Zhang, Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 1-1 Xianglin Road, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 17360593759 ; +86 18982700067, Email huilei@swmu.edu.cn; zhangdan@swmu.edu.cnPurpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them.Methods: Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier’s inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model.Results: In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of sequential release, co-loading of tretinoin and betulinic acid, and folic acid-mediated active targeting. As expected, the nano-formulation exhibited enhanced cytotoxicity in different cellular models and effectively increased drug accumulation at the tumor site by disrupting the cellular barrier composed of CAFs by tretinoin. Notably, the co-loaded nano-formulations proved to be more potent in inhibiting tumor growth in mice and also showed better anti-metastatic effects in lung metastasis models compared to the formulations with either drug alone. This novel drug delivery system has the potential to be used to develop more effective cancer therapies.Conclusion: Targeting CAFs with celastrol sensitizes tumor cells to chemotherapy, increasing the efficacy of betulinic acid. The combination of drugs targeting tumor cells and CAFs may lead to more effective therapies against various cancers.Keywords: liposomes, targeted delivery, triple-negative breast cancer, anti-tumor, combination therapy, sequential drug delivery

Feng Qiao,1,2 Hong Guo,1,2 Jing Zhang,1,2 Qing Zhang,3 Li Liu,3 Ge Meng,2 Hongmei Wu,2 Yeqing Gu,2 Kun Song,3 Changyi Li,1 Kaijun Niu2,3 1School of Dentistry, Stomatological Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 2Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 3Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Kaijun Niu, Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, People’s Republic of China, Email nkj0809@gmail.com; niukaijun@tmu.edu.cn Changyi Li, School of Dentistry, Stomatological Hospital, Tianjin Medical University, No. 12, Qixiangtai Road, Heping District, Tianjin, 300070, People’s Republic of China, Email lichangyi@tmu.edu.cnBackground: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population.Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1– 2, and ≥ 3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia.Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) (P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) (P for trend < 0.01).Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association.Keywords: tooth loss, dyslipidemia, epidemiological studies, population health, inflammation

Chunxiang Li,1,&ast; Yingbin Lian,1,&ast; Yaoshen Lin,1 Zhihua Li2 1Department of Integrative Medicine Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China; 2Department of Oncology, Zhangzhou Second Hospital, Zhangzhou, Fujian, 363199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihua Li, Department of Oncology, Zhangzhou Second Hospital, No. 35, Ziwei Road, Shima Town, Longhai District, Zhangzhou, Fujian, 363199, People’s Republic of China, Tel +86-13459666448, Email zhihua_leeee@163.comObjective: This study is dedicated to revealing the potential mechanism of Qin Run Hua Jie (QRHJ) decoction in Interstitial pneumonia (IP) treatment.Methods: The TCMSP database predicted the chemical components and targets of QRHJ decoction, and the IP-related genes were from the Genecards database. Cytoscape software was used to establish the interaction network. R package clusterProfiler was utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The molecular docking analysis of target proteins and the corresponding active pharmaceutical ingredients in the core position of the interaction network was conducted. Then, molecular dynamics (MD) simulations of a potential active substance and its key targets were performed. The binding efficiency of EGFR and luteolin, HIF1A and diosgenin was detected by cellular thermal shift assay (CETSA), and protein expression was measured by Western blot. CCK-8 was used to detect cell activity.Results: A total of 153 active ingredients, 127 targets and 362 IP-related genes were obtained. KEGG enrichment analysis identified IP-related signaling pathways including HIF-1 signaling pathway and TNF signaling pathway. The two key components luteolin and diosgenin stably bound to the key targets EGFR and HIF1A. Cell experiments further showed that EGFR and luteolin, HIF1A and diosgenin bound to exert anti-fibrotic effects.Conclusion: As an active ingredient of QRHJ decoction, luteolin and diosgenin may exert therapeutic effect on IP through binding to the key target EGFR and HIF1A. This work initially revealed the key molecular mechanism of QRHJ decoction in IP treatment and offered theoretical evidence.Keywords: Qing Run Hua Jie decoction, interstitial pneumonia, network pharmacology, molecular docking, molecular dynamics

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

Pingjiao Chen,1,&ast; Jingyao Liang,2,3,&ast; Changxing Li,1 Qian Li,2,3 Wenyan Liu,2,3 Junhui Zhu,2,3 Weifeng Chen,2,3 Xibao Zhang2,3 1Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, People’s Republic of China; 3Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xibao Zhang, Department of Dermatology Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, People’s Republic of China, Tel +8620-83593476, Email gzpfbfzs@163.comAbstract: Janus kinase (JAK) inhibitors are increasingly being used in dermatology due to their broad potential in managing both local and systemic inflammation. More recently, abrocitinib, an oral JAK 1 inhibitor, has shown promising clinical efficacy in the treatment of various skin disorders beyond moderate to severe atopic dermatitis (AD). We firstly presented three cases, each with diagnosis of pyoderma gangrenosum (PG), livedoid vasculopathy (LV), or hidradenitis suppurativa (HS), and conducted a comprehensive scoping review of the available literature on the use of abrocitinib in the treatment of diverse skin disorders. We summarized a total of 16 skin disorders, including our cases. The results indicated that abrocitinib, whether used as monotherapy or in combination with other treatments, was effective and well-tolerated in these disorders. These findings expanded the range of diseases for which abrocitinib may serve as an alternative therapeutic choice.Keywords: JAK inhibitors, abrocitinib, atopic dermatitis, pyoderma gangrenosum, livedoid vasculopathy, hidradenitis suppurativa

Hao Yang,1– 3,&ast; Guanglin Lei,2,&ast; Zhuoya Deng,1 Fang Sun,1 Yuying Tian,1 Jinxia Cheng,1 Hongyu Yu,1 Cong Li,1 Changqing Bai,4 Shaogeng Zhang,2 Guangwen An,5 Penghui Yang1 1Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Hepatological Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Surgery, Taian City Central Hospital, Taian, People’s Republic of China; 4Department of Respiratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Guangdong, People’s Republic of China; 5Department of Pharmacy, No. 984 Hospital of the PLA, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Penghui Yang; Guangwen An, Email ypenghuiamms@hotmail.com; anchen337722@163.comBackground: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules.Methods: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene. The oncolytic effect of IAV-OX40L was explored on hepatocellular carcinoma (HCC)HCC cells in vitro and in vivo.Results: Hemagglutination titers of the IAV-OX40L virus were stably 27– 28 in specific-pathogen-free chicken embryos. The morphology and size distribution of IAV-OX40L are similar to those of the wild-type influenza. Expression of OX40L protein was confirmed by Western blot and immunofluorescence. MTS assays showed that the cytotoxicity of IAV-OX40L was higher in HCC cells (HepG2 and Huh7) than in normal liver cells (MIHA) in a time- and dose-dependent manner in vitro. We found that intratumoral injection of IAV-OX40L reduced tumor growth and increased the survival rate of mice compared with PR8-treated controls in vivo. In addition, the pathological results showed that IAV-OX40L selectively destroyed tumor tissues without harming liver and lung tissues. CD4+ and CD8+ T cells of the IAV-OX40L group were significantly increased in the splenic lymphocytes of mice. Further validation confirmed that IAV-OX40L enhanced the immune response mainly by activating Th1-dominant immune cells, releasing interferon-γ and interleukin-2.Conclusion: Taken together, our findings demonstrate the novel chimeric influenza OV could provide a potential therapeutic strategy for combating HCC and improve the effectiveness of virotherapy for cancer therapy.Keywords: OVs, OX40L, IAV, HCC

Jiaqi Meng,1 Weichang Yang,2 Ziyong Chen,1 Caixia Pei,1 Xinmin Peng,1 Can Li,1 Fengyuan Li1 1Department of Respiratory and Critical Care Medicine, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Can Li; Fengyuan Li, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email 407329399@qq.com; lifengyuan@126.comPurpose: To investigate the value of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and ApoA1/B ratio in pathogenic diagnosis of chronic obstructive pulmonary disease (COPD) complicated by acute lower respiratory tract infection, assisting comprehensive disease assessment.Patients and Methods: The study enrolled 171 COPD patients with acute lower respiratory tract infections, 35 COPD patients without acute lower respiratory tract infections, and 41 healthy controls. Correlation analysis and binary logistic regression were used to assess the roles of various factors in COPD with acute lower respiratory tract infections. Receiver operating characteristic (ROC) curves were plotted and area under curves (AUC) values were calculated to evaluate the predictive performance.Results: Infections were the cause of alterations in ApoA1, ApoB and ApoA1/B index. In correlation analysis for pathogenic diagnosis of COPD complicated by acute lower respiratory infections, age, ApoA1, ApoA1/B ratio, lymphocyte count (LYMPH), neutrophil count (NEUT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and endotoxin were significantly correlated. For predicting COPD complicated by acute lower respiratory tract bacterial infection, ApoA1 had the highest area under the ROC curve (AUC: 0.889), with sensitivity and specificity of 82.9% and 83.9%, respectively. The combination of NEUT and ApoA1 improved the prediction efficacy (AUC: 0.909; sensitivity/specificity: 85.1%/85.7%).Conclusion: ApoA1, ApoB, and ApoA1/B ratio are good indicators for predicting pathogens in COPD complicated by acute lower respiratory tract infection, especially ApoA1 which has high predictive value.Keywords: ApoA1, ApoB, ApoA1/B, COPD, Acute lower respiratory tract infection, pathogens

Chenxi Li,1,2,&ast; Xueyang Fang,1,&ast; Han Zhang,1,3 Bin Zhang1 1Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Institute of Translational Medicine Department of Otolaryngology Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, 518035, People’s Republic of China; 2Graduate Collaborative Training Base of Shenzhen Second People’s Hospital, Heng Yang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3International Collaborative Laboratory of 2D, Materials for Optoelectronics Science and Technology of Ministry of Education, Institute of Microscale Optoelectronics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Zhang; Xueyang Fang, Email binzhang@email.szu.edu.cn; FANGXueyang0210@163.comAbstract: In recent years, metal-containing two-dimensional (2D) nanomaterials, among various 2D nanomaterials have attracted widespread attention because of their unique physical and chemical properties, especially in the fields of biomedical applications. Firstly, the review provides a brief introduction to two types of metal-containing 2D nanomaterials, based on whether metal species take up the major skeleton of the 2D nanomaterials. After this, the synthetical approaches are summarized, focusing on two strategies similar to other 2D nanomaterials, top-down and bottom-up methods. Then, the performance and evaluation of these 2D nanomaterials when applied to cancer therapy are discussed in detail. The specificity of metal-containing 2D nanomaterials in physics and optics makes them capable of killing cancer cells in a variety of ways, such as photodynamic therapy, photothermal therapy, sonodynamic therapy, chemodynamic therapy and so on. Besides, the integrated platform of diagnosis and treatment and the clinical translatability through metal-containing 2D nanomaterials is also introduced in this review. In the summary and perspective section, advanced rational design, challenges and promising clinical contributions to cancer therapy of these emerging metal-containing 2D nanomaterials are discussed. Keywords: metal-containing two-dimensional nanomaterials, nanotechnology-based therapy, cancer precision treatment, theranostic platform

Xiuping Wang,1 Xiaoliang Ouyang,2 Deng Zhang,1 Yunxia Zhu,1 Liang Wu,1 Zhen Xiao,3 Simin Yu,1 Wei Li,2 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Plastic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 791 86278821, Email chunminglincu@163.comPurpose: Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK.Patients and Methods: Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients.Results: Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as “disease-causing” (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as “deleterious” (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), “probably damaging” (score = 1) by PolyPhen2, and “disease-causing” (p = 0.999) by Mutation Taster.Conclusion: Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.Keywords: porokeratosis, mutation, MVD, FDPS, genetics

Lili Kang,1 Changle Li,1 Duohui Chen,2 Xinxin Bao3 1School of Health Management, Fujian Medical University, Fuzhou, People’s Republic of China; 2College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand; 3School of Foreign Language Studies, Inner Mongolia Medical University, Hohhot, People’s Republic of ChinaCorrespondence: Xinxin Bao, School of Foreign Language Studies, Inner Mongolia Medical University, Hohhot, 010110, People’s Republic of China, Email 20120027@immu.edu.cnObjective: This study was conducted to identify the factors (especially parental involvement, academic self-efficacy, and depression) associated with academic performance among Chinese K-12 students during the COVID-19 pandemic.Methods: This cross-sectional study used data from the 2020 China Family Panel Studies (CFPS). The CFPS was conducted from July to December 2020 during the COVID-19 pandemic. A multistage probability sample proportional to size was used for the survey. The final sample consisted of 1747 K-12 students. This study used the 14-item Chinese Parental Involvement and Support Scale, the Responsibility Scale, and the 8-item Center for Epidemiologic Studies Depression Scale to measure parental involvement, academic self-efficacy, and depression, respectively. An ordered probit regression and structural equation models were employed to analyze the factors associated with academic performance. A multiple imputation technique was applied to compute missing values in selected variables.Results: We found that parental involvement and academic self-efficacy were positively associated with good academic performance. In contrast, depression was negatively associated with good academic performance. Moreover, academic stress, male, rural residency, middle school, family size, high income, online gaming daily, reading, and intelligence quotient were statistically significant predictors on academic performance.Conclusion: The empirical findings suggested that parental involvement and academic self-efficacy were positively and significantly associated with good academic performance. However, depression was negatively and significantly associated with good academic performance. These results showed that policymakers and practitioners can help improve academic success and address educational inequalities among K-12 students by implementing a series of reforms.Keywords: parental involvement, academic self-efficacy, depression, academic performance, K-12, COVID-19 pandemic, China

Fang Yang,1,&ast; Cong Li,2,&ast; Yuling Qiu,1 Xinjie Chen,3 Kelin Zheng,4 Donglin Kang,5 Yin Zhang,2 Baorui Liu,1 Yongzhong Yao,2 Li Xie1 1The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China; 2Department of Breast Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3The Comprehensive Cancer Center, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 4Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Xie, The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China, Email xieli@njglyy.com Yongzhong Yao, Department of Breast Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China, Tel/Fax +86-025-83106666, Email yyz1006@hotmail.comPurpose: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has delayed medical consultations, especially for patients receiving intravenous anti-cancer therapy. We aim to investigate alterations in immune function among breast cancer patients who experience delayed intravenous therapy due to SARS-CoV-2 infection.Patients and Methods: We performed an observational investigation of breast cancer patients in Nanjing Drum Tower Hospital from December 27, 2022, to January 20, 2023. Patients who recovered from SARS-CoV-2 infection were eligible for enrollment. Peripheral blood samples were taken prior to the restart of intravenous anti-cancer therapy to examine hematologic parameters.Results: A total of 131 patients were included in the final analysis. Cough (74.0%), fever (62.6%), and expectoration (46.6%) were identified as the most presenting symptoms of SARS-CoV-2 infection in breast cancer. The average nucleic acid conversion time and delayed treatment time was 13.4 days and 13.9 days, respectively. The patients > 60 years old experienced prolonged nucleic acid conversion time (P = 0.017) and delayed treatment time (P = 0.028) compared to those

Tessa Fischer,1,2 Jenna Tucker,1,2 Charlie Li,3 Kyungmi Min,3 Dadong Xu,3 Laurence R Upjohn,1 Madhur Kumar1 1Food and Drug Branch, California Department of Public Health, Sacramento, CA, USA; 2California Epidemiologic Investigation Service (Cal EIS) Fellowship Program, California Department of Public Health, Sacramento, CA, USA; 3Food and Drug Laboratory Branch, California Department of Public Health, Richmond, CA, USACorrespondence: Madhur Kumar, Food and Drug Branch, California Department of Public Health, 1500 Capitol Avenue, MS 7602, Sacramento, CA, 95814, USA, Email madhur.kumar@cdph.ca.govPurpose: The Food and Drug Administration (FDA) has warned against tainted products for sexual enhancement containing prescription phosphodiesterase-5 (PDE5) inhibitors marketed as dietary supplements. The California Department of Public Health (CDPH)’s Food and Drug Branch (FDB) initiated a study to assess the presence of such adulterated products, specifically to identify the presence of PDE5 inhibitors in dietary supplements marketed for sexual enhancement, sampled at local retail locations.Methods: A convenience sample of products marketed as sexual enhancement dietary supplements was purchased from retail stores, within a 15-mile radius of downtown Sacramento, California. Samples were submitted to the Food and Drug Laboratory Branch (FDLB) and screened for 19 different PDE5 inhibitors using liquid chromatography-mass spectrometry. Samples were collected and analyzed from 2016 to 2018.Results: One hundred and two different products were purchased from 28 different retail locations. Sixty-seven percent were found to be adulterated with at least one PDE5 inhibitor. Of the positive samples, 40% were found to contain one PDE5 inhibitor and 60% were found to contain two or more. Sildenafil was the most common PDE5 inhibitor identified (74%), followed by tadalafil (59%). Eighteen percent of the tested samples had been associated with previous FDA warnings listed in their Tainted Products Database. Of these warning-associated samples, 72% were found to contain PDE5 inhibitors and 46% of these contained at least one of the same adulterants reported by the FDA.Conclusion: FDA reports and warnings have focused on dietary supplements found online or through screenings of international mail shipments. FDB results add to FDA findings by demonstrating that such adulterated products marketed for sexual enhancement are also sold at retail locations in California. These products have the potential to cause severe adverse health effects and therefore, it is essential to raise awareness of this significant public health concern.Keywords: dietary supplements, sexual enhancement products, adulteration

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

Wei Han,1 Cheng Li,1 Yongheng Wang,1 Binliang Huo,1 Wenhan Li,1 Wen Shi2 1Department of Surgical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 2Department of Gastroenterology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Wen Shi, Department of Gastroenterology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email shiwen02308@aliyun.comBackground: There is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes.Methods: The heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was validated in the GEO database and clinical samples. To explore the association between TENT5C expression and immune cell infiltrations, we performed ESTIMATE and single-sample gene set enrichment analysis (ssGSEA).Results: The low level of heme metabolism score was associated with a poor prognosis in colorectal cancer patients. TENT5C is a prognostic gene and an independent prognostic biomarker for overall survival. Its expression was confirmed in multiple datasets and clinical samples, showing a positive correlation with immune cells and immune score. GSEA results suggested TENT5C’s significant role in regulating immune and inflammatory responses in colorectal cancer.Conclusion: TENT5C can be used as a biomarker in colorectal cancer. Additionally, TENT5C is associated with both prognosis and immune infiltration. These findings lay a strong groundwork for future research to delve into the specific role of TENT5C in the development and advancement of colorectal cancer.Keywords: colon cancer, immune cell infiltrations, prognosis, heme metabolism

Haichuan Guo,1,&ast; Bixuan Song,2,&ast; Ruijuan Zhou,3 Jiahao Yu,1 Pengzhao Chen,1 Bin Yang,1 Naihao Pan,1 Chengsi Li,1 Yanbin Zhu,1,4 Juan Wang1,4 1Department of Orthopedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Division of Medical Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3College of Education, Hebei Normal University, Shijiazhuang, Hebei, 050010, People’s Republic of China; 4Orthopedic Research Institute of Hebei Province, Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang, Hebei, 050051, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Wang; Yanbin Zhu, Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86-311-88602015, Email wangj_heb3y@163.com; zhuyanbin111@126.comBackground: As the worldwide population ages, the population receiving open wedge high tibial osteotomy (OWHTO) is growing, and surgical site infection (SSI) is a rare but fatal surgical complication. This study aimed to identify risk factors independently associated with SSI following OWHTO and develop a predictive nomogram.Methods: Clinical data of patients who received OWHTO and followed up for more than 12 months in our hospital were retrospectively reviewed. Multivariable logistic regression was performed to determine independent risk factors for SSI and to construct predictive nomograms. The study further illustrated the predictive performance of the model by using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).Results: A total of 1294 eligible patients were included in the study. Multivariate analysis revealed tobacco consumption (OR=3.44, p=0.010), osteotomy size ≥ 12 mm (OR=3.3, p=0.015), the use of allogeneic bone or artificial bone graft substitutes (allogeneic bone vs none, OR=4.08, p=0.037; artificial bone vs none, OR=5.16, p=0.047), Kellgren-Lawrence (K-L) grade IV (OR=2.5, p=0.046), systemic immune-inflammation index (SII) > 423.62 (OR=6.2, p< 0.001), high-sensitivity C-reactive protein (HCRP) > 2.6 mg/L (OR=2.42, p=0.044), and a higher level of fasting blood glucose (FBG) (OR=1.32, p=0.022) were the independent predictors of SSI. The cutoff score of the model was 148, with a sensitivity of 76.0% and specificity of 81.0%. The concordance index (C-index) and Brier score of the nomogram were 0.856 and 0.017, and the corrected values after 1000 bootstrapping validations were 0.820 and 0.018, respectively. Furthermore, the ROC curve, calibration curve, and DCA exhibited excellent predictive accuracy and clinical applicability of the model.Conclusion: This study developed a dynamic nomogram based on seven predictors, which allowed surgeons to individualize risk stratification of patients and intervene promptly to reduce SSI rates.Keywords: open wedge high tibial osteotomy, surgical site infection, risk factors, nomogram

Hanwen Cheng,1,&ast; Haoyu Wu,1,&ast; Ni Tan,2,&ast; Zhuojie Liu,1 Ning Wang,1 Ningyi Chen,1 Chunhai Li1,3 1Department of Orthopaedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Cellular and Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Teaching and Research Bureau of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhai Li, Department of Orthopaedics, Sun Yat-sen Memorial Hospital, Sun Yat‐sen University, Guangzhou, Guangdong Province, 510000, People’s Republic of China, Tel +86-18602079796, Fax +86-(20)81332523, Email lichhai@mail.sysu.edu.cnPurpose: Early diagnosis of spinal infections remains challenging, and emerging metagenomic next-generation sequencing (mNGS) technology holds promise in addressing this issue. The aim of this study is to investigate the diagnostic efficacy of mNGS in spinal infections.Patients and Methods: A total of 78 cases with suspected spinal infections were enrolled in this study, all of whom underwent laboratory, histopathological and mNGS examinations upon admission. Lesion samples were obtained by surgical or C-arm-guided puncture. Sensitivity, specificity, positive predictive value and negative predictive value of culture and mNGS were calculated for statistical analysis.Results: With histopathological results as the reference, the included 78 patients were categorized into 50 cases in the spinal infection group and 28 cases in the aseptic group. The sensitivity (84%) and negative predictive value (77.14%) of mNGS were significantly higher than those of culture (32% and 44.26%, respectively), whereas no significant differences were observed in terms of specificity and positive predictive value. In the subgroup analysis for Mycobacterium tuberculosis, the sensitivity of mNGS (90.91%) and T-spot (90.91%) was significantly higher than that of culture (0). Additionally, mNGS demonstrated markedly higher specificity (100%) compared to T-spot (85.07%).Conclusion: This study underscores the substantial advantages of mNGS in terms of diagnostic accuracy and bacterial coverage for spinal infections. The findings provide compelling clinical evidence that supports the enhanced diagnostic efficacy of mNGS.Keywords: culture, diagnosis, sensitivity, specificity, bacteria, clinical evidence

Liang B, Li C, Zhou Z, Xie Y. Drug Des Devel Ther. 2023;17:1037–1045. We, the Editor and Publisher of the journal Drug Design, Development and Therapy have retracted the published article. Following publication of the article, concerns were raised about the duplication of images from Figure 4. Specifically, Images for Figure 4A, Migration, 0 and 200; 400 and 800; and Invasion, 0 and 400 have been duplicated. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Lili Kang,1 Changle Li,1 Huifeng Du2 1School of Health Management, Fujian Medical University, Fuzhou, People’s Republic of China; 2School of Health Management, Inner Mongolia Medical University, Hohhot, People’s Republic of ChinaCorrespondence: Huifeng Du, School of Health Management, Inner Mongolia Medical University, Chilechuan Dairy Development Zone, Hohhot, 010110, People’s Republic of China, Email dhfeng2009_9@163.comPurpose: Medical care delay or avoidance increases morbidity and mortality risk and is costly for the national healthcare system. The objective of this study was to identify factors associated with medical care delay or avoidance among Chinese adults during the COVID-19 pandemic.Materials and Methods: A cross-sectional analysis was conducted using data from the 2020 China Family Panel Study (CFPS). The CFPS was conducted from July to December 2020 during the COVID-19 pandemic. The final sample included 4369 adults. A logistic regression model was employed to identify the factors associated with medical care delay or avoidance.Results: The empirical results indicate that regardless of rural-urban residence, older adults and adults with chronic conditions were less likely to delay or avoid medical care during the pandemic. However, individuals who had completed more than three years of college showed a higher likelihood of delaying or avoiding medical care. In urban areas, larger family sizes, greater general trust in physicians, and higher provider structural quality were associated with a decreased probability of delaying or avoiding medical care during the pandemic. In contrast, employed adults were more likely to delay or avoid medical care. In rural areas, current smokers were more likely to delay or avoid medical care during the pandemic.Conclusion: This study has identified several factors affecting medical care delay or avoidance, some of which are amenable to policy changes. Policymakers can help improve the utilization of health facilities and patient health outcomes by implementing a series of reforms.Keywords: delay or avoidance behavior, medical care, COVID-19 pandemic, China

Jiawei Zhou,1 Xiaomeng Li,1 Xiang Li,2 Na Wang,3 Xu Cai,4 Lei Zhang,1 Chen Li,1 Wei Wang,1,&ast; Na Yu1,&ast; 1Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Central Hospital Affiliated to Shenyang Medical College, Shenyang, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Tieling County Central Hospital, Tieling, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang; Na Yu, Email wwbycmu@126.com; yunacmu@163.com

Fan Zhang,&ast; Wei Li,&ast; Yingying Zhang, Dong Wang, Jing Li, Chengpeng Li, Liqun He Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liqun He, Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, No. 215, Zhongshan Avenue, Qiaokou District, Wuhan, 430022, People’s Republic of China, Tel/Fax +86-027-85332105, Email heliqundr@163.comPurpose: Acute coronary syndrome (ACS) is a common acute myocardial ischemia syndrome and is one of the death-related causes of cardiovascular diseases. Identifying biomarkers to indicate disease severity and predict the occurrence of major adverse cardiovascular events (MACE) would benefit the clinical prognosis of ACS. This study estimated the expression and significance of lncRNA TPRG1-AS1 in the onset and development of ACS, aiming to explore a novel biomarker for the diagnosis and prognosis of ACS.Patients and Methods: A total of 109 ACS patients and 66 patients who received coronary angiography and excluded ACS were enrolled in this study. TPRG1-AS1 in the serum of study subjects was analyzed by PCR. The significance of TPRG1-AS1 in screening ACS was evaluated by ROC analysis. The association of TPRG1-AS1 with the disease severity of ACS was assessed by Pearson correlation analysis with patients’ clinicopathological features. The potential of TPRG1-AS1 in predicting the occurrence of MACE was assessed by logistic regression analysis.Results: Significant upregulation of TPRG1-AS1 was observed in ACS patients, which served as a risk factor for ACS and distinguish between ACS patients and the normal group. TPRG1-AS1 was positively correlated with Gensini score, cys-C, cTnI, and NT-proBNP levels of ACS patients, which indicate severe development of ACS. Additionally, increasing serum TPRG1-AS1 was associated with the high incidence of MACE during patients’ hospitalization and was identified as a risk factor for MACE in ACS patients.Conclusion: Upregulated TPRG1-AS1 in ACS served as a diagnostic biomarker and predicted the severe development of patients.Keywords: cardiovascular disease, lncRNA, onset, inpatient MACE, severity

Fangzheng Cao,1,&ast; Yiqi Wang,2,&ast; Ruili Wei,3 Chunrong Li,2 Yifan Cheng,2 Yu Zhou,1 Tianyu Jin,1 Houwen Zhang,1 Luting Lin,4 Bin Xu5 1The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Neurology, Center for Rehabilitation Medicine, People’s Hospital of Hangzhou Medical College, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China; 3Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Xu, Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Email xubin2008.love@163.comPurpose: Neuromyelitis optica spectrum disorder (NMOSD) is a rare recurrent autoimmune disease of the central nervous system. However, to date, the peripheral blood profile of the T helper cell subsets in NMOSD remains controversial and poorly understood. This study aimed to compare the levels of helper T cell subsets in the peripheral blood from patients with NMOSD in different phases of the disease and studied their correlation with the clinical severity of the disease.Patients and methods: We used flow cytometry with cellular membrane surface staining to measure the levels of helper T cell subsets in 50 patients with NMOSD during the attack (n = 25) and remission (n = 25) phases and in 21 healthy controls.Results: Patients with NMOSD had higher levels of Th1 and Th17 cells in the attack phase compared to parallel populations in the remission phase and healthy controls. Th1/Th2 and Th17/Treg ratios were positively correlated with the severity of the disease in the attack phase of NMOSD. In contrast, Treg cell levels were negatively correlated with the severity of the disease in the attack phase in patients with NMOSD.Conclusion: The peripheral blood immune profile in NMOSD towards a Th1/Th17 cell-mediated pro-inflammatory immune response, which is associated with disease activity and severity of neuromyelitis optica spectrum disorder.Keywords: neuromyelitis optica spectrum disorder, helper T cell, flow cytometry, lymphocyte subsets

Mei Cong,1,&ast; Houjun Pang,1,2,&ast; Guangxing Xie,1 Feifei Li,3 Chunxiao Li,3 Hao Sun,3 Shaoyou Yang,1 Weidong Zhao3 1School of Pharmacy, Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Pharmacy, Dazhou Women and Children’s Hospital, Dazhou, People’s Republic of China; 3Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Zhao, Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China, Tel +86 0373 3029977, Fax +86 0373 3029977, Email 141051@xxmu.edu.cnPurpose: Molecular targeted therapy is one of the most pivotal strategies in the treatment of non-small cell lung cancer, yet its curative effect is severely compromised by the poor aqueous solubility, low bioavailability and inadequate tumor accumulation of targeted agents. To enhance the efficacy of targeted agents, we demonstrate a novel self-assemble amphiphilic molecule based on erlotinib as an effective nanodrug for anti-cancer treatment.Methods: An amphiphilic molecule composed of hydrophobic erlotinib and hydrophilic biotin block was synthesized and characterized by nuclear magnetic resonance (NMR) as well as high-resolution mass spectrometry (HRMS). Then, nanoassemblies of the amphiphilic molecules are formulated by using nanoprecipitation method. Subsequently, the size, morphology, cell uptake, the anticancer activity and in vivo distribution of the newly constructed erlotinib nanodrug were systematically assessed by some methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), flow cytometry, in vivo imaging system etc.Results: We developed a novel nanoformulation of erlotinib, which possesses a high drug loading of 45%. With the features of well-defined structure and small size, the obtained nanodrug could be effectively accumulated in tumor sites and rapidly internalized by cancer cells. Finally, the erlotinib-based nanoformulation showed considerably better anticancer activity compared to free erlotinib both in vitro and in vivo. Moreover, the nanodrug displayed great tolerability.Conclusion: Combining the advantageous features of both nanotechnology and self-assemble, this novel erlotinib nanomedicine constitutes a promising therapeutic candidate for cancer treatment. This study also underlines the potential use of amphiphilic molecule for improving drug efficacy as well as reducing drug toxicity, which could become a general strategy for the preparation of nanodrugs of active agents.Keywords: erlotinib, amphiphilic molecule, self-assembling, drug self-delivery system, non-small cell lung cancer

Hua-Song Shentu,1 Yi-Hua Chen,1 Zhen-Yu Cheng,1 Bin Fu,1 Yuan-Hao Fu,1 Shu-Feng Zheng,2 Chan Li1 1Department of Neurosurgery, Jinhua People’s Hospital, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua, 321000, People’s Republic of China; 2Department of Endocrinology, Jinhua People’s Hospital, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Shu-Feng Zheng, Department of Endocrinology, Jinhua People’s Hospital, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua, 321000, People’s Republic of China, Email m13819976688@163.comBackground: The inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) may regulate immunity and inflammation. The current study was conducted to determine its role as a biomarker for reflecting the severity and predicting outcomes of intracerebral hemorrhage (ICH).Methods: In this prospective cohort study, 185 patients with supratentorial ICH were enrolled, among whom 62 had blood obtained not only at admission but also on days 1, 3, 5, 7, 10, and 14. In addition, 62 healthy controls underwent blood collection at the start of the study. The serum ITIH4 levels were then quantified. We recorded early neurological deterioration (END) and poor prognosis (modified Rankin Scale [mRS] scores of 3– 6]) six months after ICH.Results: Serum ITIH4 levels decreased prominently in the early phase after ICH, continued to decline until day 5, then gradually increased until day 14, and were significantly lower during 14 days in patients than in controls. Serum ITIH4 levels on admission were independently associated with serum C-reactive protein levels, National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume. Admission serum ITIH4 levels were independently associated with mRS scores, END, and poor prognosis. No substantial differences existed in the areas under the receiver operating characteristic curve of END and poor prognosis prediction between the serum ITIH4 levels, NIHSS scores, and hematoma volume. Prediction models, in which serum ITIH4 levels, NIHSS scores, and hematoma volume were integrated, were relatively reliable and stable using a series of statistical methods. In addition, the prediction model of poor prognosis had a higher discriminatory ability than the NIHSS scores and hematoma volume alone.Conclusion: A dramatic decline in serum ITIH4 levels during the early period following ICH is independently related to the inflammatory response, stroke severity, and poor neurologic outcomes, suggesting that serum ITIH4 may be a useful prognostic biomarker of ICH.Keywords: inter-alpha-trypsin inhibitor heavy chain 4, intracerebral hemorrhage, early neurologic deterioration, prognosis, severity, biomarkers

Jie Dai,1,&ast; Shao Zhang,2,&ast; Yuhan Shi,3 Jinmei Xu,2 Weipeng Liu,1 Jia Yang,1 Li Shi,1 Zhiling Yan,2,4 Chuanyin Li1 1Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China; 2Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China; 3College of Agronomy and Biotechnology, Yunnan Agricultural University, Kunming, 650041, People’s Republic of China; 4Department of Gynaecologic Oncology, The Hospital of Yuanmou, Yuanmou, 651300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiling Yan, Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China, Email yanzhiling2021@126.com Chuanyin Li, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China, Email chuanyinli@imbcams.com.cnBackground: Long noncoding RNAs (LncRNAs) have been revealed to involve in cervical cancer (CC) developing. The current study was designed to explore the association of SNPs (rs217727, rs2366152, rs1859168, rs10505477) located in the lncRNA H19, HOTAIR, HOTTIP and CASC8 genes with the risk of CC in a Chinese Han population.Methods: Four SNPs were selected and genotyped in 1426 participants (274 CIN patients, 448 CC patients, and 704 healthy control individuals) using MassArray. The association of these SNPs with susceptibility to CC was evaluated.Results: Significant differences in allelic distribution of rs217727 were observed in the comparison of CC with control (P = 0.001), indicating the risk of rs217727-A allele in CC (OR = 1.33; 95% CI: 1.12– 1.58). The inheritance model analysis revealed that 2AA+GA genotype represented a certain risk of CC (P = 0.001, OR = 1.35; 95% CI: 1.13– 1.62). The stratified analysis revealed a risk of the rs217727-A allele for cervical squamous cell carcinoma (SCC) (P = 0.002, OR = 1.33; 95% CI: 1.11– 1.60).Conclusion: rs217727 in lncRNA H19 exhibited a significant correlation with CC susceptibility, particularly SCC, and A/A genotype of this SNP might present as a risk in CC.Keywords: cervical cancer, lncRNA, H19, association, SNPs, CC, long noncoding RNAs

Chengyu Li, Ziyou Ding, Yingchao Han State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, 430070, People’s Republic of ChinaCorrespondence: Yingchao Han, Email hanyingchao@whut.comBackground: The integration of diagnostic and therapeutic functions into a biosafe nanoplatform with intelligent response functions at the tumor microenvironment (TME) is a promising strategy for cancer therapy.Methods: Mn-doped nano-hydroxyapatite (nHAPMn) nanoparticles were successfully prepared via a simple coprecipitation method for magnetic resonance imaging (MRI)-guided photothermal therapy. This study is the first to report on the use of Mn to render biodegradable hydroxyapatite suitable for MRI and effective photothermal therapy (PTT) simultaneously by regulating the pH of nHAPMn during the preparation process.Results: Combined with near-infrared (NIR) laser irradiation, a photothermal conversion efficiency of 26% and effective photothermal lethality in vitro were achieved. Moreover, the degradation of nHAPMn led to the release of Mn ions and amplified the MRI signals in an acidic TME, which confirmed that nHAPMn had a good pH-responsive MRI capacity in solid tumors. In animal experiments, tumors in the nHAPMn5+NIR group completely abated after 14 days of treatment, with no significant recurrence during the experiment.Conclusion: Therefore, nHAPMn is promising as a nanotheranostic agent and can be effective in clinical diagnosis and therapy for treating cancer.Graphical Abstract: Keywords: photothermal therapy, magnetic resonance imaging, hydroxyapatite, manganese, pH-amplified

Chunyan Zhang, Zhijian Yang, Wenxiu Xie, Congyong Li, Xuefei Huang Sixth Health Care Department, Second Medical Center of PLA General Hospital, Beijing, 100853, People’s Republic of ChinaCorrespondence: Chunyan Zhang, Sixth Health Care Department, Second Medical Center of PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Tel +86 01066957818, Email zchunyan1668@163.comBackground: The study aimed to investigate the risk factors and interventions for unspecific functional bowel disorders (U-FBDs) in military personnel under maritime environment.Methods: This cross-sectional analytical survey used the Rome III questionnaire for surveying 1018 military personnel involved in overseas humanitarian medical services from June 2013 to January 2016. Individuals diagnosed with U-FBDs were included in the U-FBDs group, while those without FBDs or other diseases were considered the control group. The psychological and sleep conditions of military personnel with U-FBDs were assessed using the SCL-90 scale and the Pittsburgh Sleep Quality Index scale, respectively. Health education and treatment were provided to individuals diagnosed with U-FBDs, and the improvements were evaluated after three months.Results: Among 923 qualified questionnaires, 243 subjects was included in U-FBDs group and 240 in the control group. Smoking, alcohol consumption, and multiple seafaring missions were identified as risk factors for U-FBDs in military personnel on ocean-going missions. The U-FBDs group had significantly worse sleep quality, sleep efficiency, daytime dysfunction score, and total PSQI score compared to the control group (P < 0.05). Additionally, 10 factor scores of SCL-90 and the total score in the U-FBDs group were significantly higher than those in the control group (P < 0.01). Patients with U-FBDs also reported the highest rate of somatic symptoms (P < 0.01).Conclusion: The onset of U-FBDs among military personnel on long-haul maritime may be closely related to mental, psychological, and sleep factors. Health education and treatment may help improve the symptoms of U-FBDs.Keywords: military, maritime environment, non-specific functional enteropathy, functional enteropathy

Wanting Li,1,&ast; Feng Cheng,1,&ast; Jun Zhang,1 Caihong Li,2 Daijing Yu,1 Halimureti Simayijiang,1 Haiyan Liu,2 Sijin Li,2 Jiangwei Yan1 1Shanxi Key Laboratory of Forensic Medicine, Shanxi Medical University, Jinzhong, People’s Republic of China; 2Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiangwei Yan; Sijin Li, Tel +86 03513985386 ; +86 03514639352, Email yanjw@sxmu.edu.cn; lisjnm123@163.comPurpose: Radioactive iodine therapy is administered through oral route, which is accumulated and absorbed in the intestine. However, its effects on the intestine remain unclear. In this study, we investigated the changes in the gut microbiota and metabolites following radioactive iodine therapy.Patients and Methods: A total of 76 stool samples from the same 38 patients were collected at the start of radioactive iodine therapy and three days following the therapy. Stool microbiota and metabolites were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry.Results: Enterobacteriales, Enterobacteriaceae and Escherichia-Shigella were elevated in most patients (27/38) following the therapy. The levels of 2-hydroxyundec-7-enoylcarnitine were significantly lower, whereas those of 5-dehydroavenasterol, butylisopropylamine, and salsoline-1-carboxylate were higher following the therapy. The relative abundance of Escherichia-Shigella was negatively correlated with 2-hydroxyundec-7-enoylcarnitine level (r2 = − 0.661, P = 0.009). Functional pathways were predicted to be involved in amino acid and lipid metabolism following the therapy. Particularly, phenylalanine, linoleic acid, sphingolipid, purine, and alpha-linolenic acid metabolism were the main metabolic pathways.Conclusion: Gut microbiota was disturbed following radioactive iodine therapy, with increased Escherichia-Shigella. Processes associated with energy production seems to be impacted following the therapy, with significantly decreased 2-hydroxyundec-7-enoylcarnitine level. Meanwhile, some metabolites and functional pathways may have a positive effect on intestinal homeostasis, and may be related to the repair and promotion of gut recovery following the therapy. This study provides a basic foundation to explore how radioactive iodine affects gut microbiota and metabolites, and how gut function is regulated in response to radioactive iodine therapy.Keywords: radioactive iodine, gut microbiota, Escherichia-Shigella, metabolism, thyroid carcinoma

Chen Zhang,1 Tianlun Kang,1 Tangliang Qian,1 Mingwei Ma,2 Xiujuan Hou,1,&ast; Chen Li3,&ast; 1Department of Rheumatology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Clinical Medicine, Peking Union Medical College Hospital (PUMC and CAMS), Beijing, People’s Republic of China; 3Department of Rheumatology, Fangshan Hospital Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiujuan Hou, Department of Rheumatology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6, Fangxing Park District 1, Fangzhuang, Fengtai District, Beijing, People’s Republic of China, Email houxiujuan2008@163.com Chen Li, Department of Rheumatology, Fangshan Hospital, Beijing University of Chinese Medicine, No. 4, Chengguan Health Road, Fangshan District, Beijing, People’s Republic of China, Email casio1981@163.comAbstract: Secukinumab, a monoclonal antibody targeting interleukin-17 (IL-17), has exhibited encouraging results in the therapeutic management of palmoplantar pustulosis (PPP). The development of alopecia areata (AA) is closely related to IL-17, and IL-17A inhibitors were considered as a potential treatment modality. Therefore, the development of AA during secukinumab treatment for PPP is a rare adverse event that has been rarely reported worldwide. Here we report a 35-year-old female patient with PPP who developed AA after completing the induction period of secukinumab treatment. Discontinuing secukinumab and initiating treatment with tofacitinib resulted in a significant improvement in both PPP and AA. The emergence of AA in this patient can be attributed to paradoxical skin reactions associated with IL-17 inhibitors. Tofacitinib appears to alleviate biologic-induced AA during PPP syndrome treatment.Keywords: alopecia areata, IL-17, secukinumab, palmoplantar pustulosis

Junquan Zhu, Feifeng Wu,&ast; Cuifang Li,&ast; Jueyi Mao,&ast; Yang Wang,&ast; Xin Zhou,&ast; Haotian Xie,&ast; Chuan Wen Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Wen, Department of Pediatrics, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of China, Tel +86-13755191815, Email chuanwen@csu.edu.cnAbstract: Extracellular vesicles (EVs) are lipid containers that are actively released by cells and contain complex molecular cargoes. These cargoes include abundant material such as genomes and proteins from cells of origin. They are involved in intercellular communication and various pathological processes, showing excellent potential for diagnosing and treating diseases. Given the significant heterogeneity of EVs in complex physiopathological processes, unveiling their composition is essential to understanding their function. Bulk detection methods have been previously used to analyze EVs, but they often mask their heterogeneity, leading to the loss of valuable information. To overcome this limitation, single extracellular vesicle (SEV) analysis techniques have been developed and advanced. These techniques allow for analyzing EVs’ physical information and biometric molecules at the SEV level. This paper reviews recent advances in SEV detection methods and summarizes some clinical applications for SEV detection strategies.Keywords: single extracellular vesicle analysis, heterogeneity, detection methods, disease diagnosis, new therapies

Min Shen,1 Chunjing Li,1 Xiaocen Wei,1 Linlin Zhang,1 Yang Li,1 Hongxue Wu,2 Xiaobin Zhang,1 Zhibin Dong,1 Shuzhong Gao,1 Yuning Ma,1 Yuxia Ma1 1Department of Acupuncture and Massage College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Department of Rehabilitation, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Yuning Ma; Yuxia Ma, Email myning0405@163.com; phdmayuxia@126.comIntroduction: This overview of systematic reviews (SRs) systematically collected, evaluated, and combined the evidence for migraine treatment with transcranial magnetic stimulation (TMS).Methods: We conducted a systematic literature search in various databases, such as PubMed, The Cochrane Library, Web of Science, Embase, the China National Knowledge Infrastructure, Wanfang, VIP, and China Biomedical Literature. Two reviewers independently assessed the methodological quality, risk of bias, reporting quality, and strength of evidence of the included studies using AMSTAR-2, ROBIS, the PRISMA checklist, and the GRADE system.Results: We performed an overview of 7 relevant SRs, of which 4 were of moderate quality and 3 were of low quality according to AMSTAR 2. All SRs had low risk of bias in Phase 1 (Assessing relevance), Domain 1 (Study eligibility criteria), and Domain 4 (Synthesis and findings) as evaluated by ROBIS. In Domain 2 (Identification and selection of studies), 4 SRs (57.1%) had low risk of bias, while in Domain 3 (data collection and study appraisal) and Risk of Bias in the Review Phase 3, 4 SRs (57.1%) had low risk of bias. The PRISMA reporting standards were generally comprehensive, but some limitations were observed in the assessments, pooled results, evidence reliability, registration and protocols, and funding sources. The GRADE levels ranged from moderate to low, with 10 outcomes of moderate quality and 6 outcomes of low quality. The main reason for the low quality of evidence was the small sample size and high heterogeneity of the available studies.Conclusion: TMS may improve migraine severity and frequency, but the evidence is limited due to methodological flaws and heterogeneity. Future studies should standardize use, assess side effects, and compare with other treatments.Keywords: transcranial magnetic stimulation, migraine, evidence, overview, systematic reviews

Hai-Tao Zhang,1 Kuo Wang,2 Ze-Shi Li,1 Chuang-Shi Wang,3 Xi-Kun Han,4,5 Wei Chen,6 Fu-Dong Fan,7 Jun Pan,7 Qing Zhou,7 Hai-Long Cao,7 Hao-Dong Pan,8 Xiateke Hafu,9 Chen Li,10 Guo-Liang Fan,10 Tuo Pan,1 Dong-Jin Wang,1,2,6,7 Wei Wang9 1Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, Jiangsu, 210008, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, 210008, People’s Republic of China; 3Medical Research and Biometrics Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 102300, People’s Republic of China; 4Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA; 5Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, MA, USA; 6Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210008, People’s Republic of China; 7Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, People’s Republic of China; 8Department of Clinical Medicine, Norman Bethune Health Science Center of Jilin university, Changchun, Jilin, 130021, People’s Republic of China; 9The Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, People’s Republic of China; 10Department of Cardiac Surgery, Dong Fang Hospital Affiliated to Tongji University, Shanghai, 200120, People’s Republic of ChinaCorrespondence: Dong-Jin Wang, Chief of department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Number 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email dongjin_wang@126.com Wei Wang, The Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, People’s Republic of China, Email wangwei3342@163.comBackground: Early postoperative bacterial pneumonia and sepsis (ePOPS), which occurs within the first 48 hours after cardiovascular surgery, is a serious life-threatening complication. Diagnosis of ePOPS is extremely challenging, and the existing diagnostic tools are insufficient. The purpose of this study was to construct a novel diagnostic prediction model for ePOPS.Methods: Least Absolute Shrinkage and Selection Operator (LASSO) with logistic regression was used to construct a model to diagnose ePOPS based on patients’ comorbidities, medical history, and laboratory findings. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model discrimination.Results: A total of 1203 patients were recruited and randomly split into a training and validation set in a 7:3 ratio. By early morning on the 3rd postoperative day (POD3), 103 patients had experienced 133 episodes of bacterial pneumonia or sepsis (15 patients had both). LASSO logistic regression model showed that duration of mechanical ventilation (P=0.015), NYHA class ≥ III (P=0.001), diabetes (P< 0.001), exudation on chest radiograph (P=0.011) and IL-6 on POD3 (P< 0.001) were independent risk factors. Based on these factors, we created a nomogram named DICS-I with an AUC of 0.787 in the training set and 0.739 in the validation set.Conclusion: The DICS-I model may be used to predict the risk of ePOPS after cardiovascular surgery, and is also especially suitable for predicting the risk of IRAO. The DICS-I model could help clinicians to adjust antibiotics on the POD3.Keywords: early postoperative pneumonia and sepsis, IL-6, LASSO, nomogram

Lei Pang,1– 4,&ast; Xiaomei Xue,1– 4,&ast; Yuwei He,1– 4 Can Wang,1– 4 Lin Han,1– 4 Maichao Li,1– 4 Han Qi,1– 4 Changgui Li,1– 4 Jie Lu1– 4 1Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 3Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 4Institute of Metabolic Diseases, Qingdao University, Qingdao, 266003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lu; Changgui Li, Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Tel +86 17853297395, Fax +86 532-82912019, Email 13127006046@163.com; changguili@vip.163.comPurpose: Higher baseline serum urate or higher initial urate-lowering medication dose increased risk of gout flares during urate-lowering therapy (ULT) initiation. The decrease in serum urate may play a crucial role in this process. Therefore, we aim to explore the relationship between decrease in serum urate and the risk of gout flares during ULT initiation.Patients and Methods: A 12-week prospective cohort study of Chinese male gout patients was conducted at Shandong Provincial Clinical Research Center for Immune Diseases and Gout in China. Patients were grouped by baseline serum urate (7– 7.9 mg/dL, 8– 8.9 mg/dL and ≥ 9 mg/dL). All patients received febuxostat 20 mg daily during weeks 0– 4, then escalated to 40mg during weeks 4– 12 if serum urate > 6mg/dL. The main outcomes were the number of gout flares and the decrease in serum urate. Poisson regression was performed.Results: A total of 282 participants were enrolled, of whom 260 completed (84, 87 and 89 in each group) from March 2021 to December 2021. A 44.2% of all participants experienced at least one gout flare. In the multivariate Poisson regression 1, Δ serum urate 0– 12 weeks (IRR 1.184, 95% CI, 1.062– 1.320; P=0.002), the number of gout flares before treatment 1 year (1.017, 1.010– 1.024; P< 0.001) and tophus (1.580, 1.023– 2.440; P=0.039) were independently associated with the number of gout flares. While in the multivariate Poisson regression 2, baseline serum urate (1.256, 1.050– 1.503; P=0.013) and the number of gout flares before treatment 1 year (1.014, 1.007– 1.022; P< 0.001) were independently associated with the number of gout flares, Δ serum urate 0– 12 weeks (1.055, 0.923– 1.207; P=0.433) was no longer a risk factor.Conclusion: ULT-induced gout flares depend on the degree of decrease in serum urate, which is affected by baseline serum urate. Higher baseline serum urate and greater decrease in serum urate lead to higher risk of gout flares.Keywords: baseline serum urate, decrease in serum urate, gout flares, febuxostat

Changlan Li,1,&ast; Zhezhe Cui,2 Du Wei,3,4,&ast; Quan Zhang,5,&ast; Junli Yang,3 Wenju Wang,1 Xiaobo Luo,1 Yue Chang3,4 1School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi Province, People’s Republic of China; 3School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 4Center of Medicine Economics and Management Research, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 5Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Chang, School of Medicine and Health Management, Guizhou Medical University, Guizhou Medical University, University Town, GUI ‘an New District, Guiyang, Guizhou Province, People’s Republic of China, Tel/Fax +86-0851-88308118, Email 4567401@qq.com Zhezhe Cui, Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, 18 Jinzhou Road, Nanning, Guangxi Province, People’s Republic of China, Tel/Fax +86-0771-2518785, Email czz6997@163.comPurpose: To explore the prescription patterns and usage trends of antibiotics within primary care institutions located in underdeveloped regions of China from 2017 to 2022.Methods: A retrospective analysis of antibiotic prescriptions was conducted from 25 primary care institutions in Guizhou Province during the period of 2017– 2022. Antibiotic prescriptions were categorized into appropriate and inappropriate use. Appropriate use is further categorized into preferred medication, and antibiotics can be used or substituted. Inappropriate use is further categorized into unnecessary use, incorrect spectrum of antibiotics and combined use of antibiotics. Factors associated with inappropriate use were investigated using generalized estimation equations. Holt-Winters and SARIMA models were employed to predict the number of inappropriate antibiotic prescriptions as the alternative model.Results: A total of 941,924 prescriptions were included, revealing a decreasing trend in both the number and inappropriate rates of antibiotic prescriptions from 2017 to 2022. Diseases of the respiratory system (70.66%) was the most frequent target of antibiotic use, with acute upper respiratory infections of multiple and unspecified sites representing 52.04% of these cases. The most commonly used antibiotics were penicillins (64.44%). Among all prescriptions, inappropriate antibiotic prescriptions reached 66.19%. Physicians aged over 35, holding the title of associate chief physician and possessing more than 11 years of experience were more likely to prescribe antibiotics inappropriately. The phenomenon of inappropriate antibiotic use was commoner among children aged five or younger. By comparing model parameters, it was determined that the SARIMA model outperforms the Holt-Winters model in predicting the number of inappropriate antibiotic prescriptions among primary care institutions.Conclusion: The number and inappropriate rates of antibiotic prescriptions in southwest China exhibited a downward trend from 2017 to 2022, but inappropriate prescription remains a serious problem in primary care institutions. Therefore, future efforts should focus on strengthening physician education, training, and clinical practice. Additionally, physicians’ awareness of common misconceptions about inappropriate antibiotic use must be improved, and the prescribing behavior of physicians who fulfill patients’ expectations by prescribing antibiotics needs to be modified.Keywords: antibiotics, primary care institution, trends, prescription patterns, inappropriate medication

Liang Yan,1,2 Chongli Yu,1 Zhenkai Zhao,1 Yuan Zhang,1 Rui Wang,1 Chengxin Li1 1Department of Dermatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Dermatology, General Hospital of Central Theater Command of PLA, Wuhan, Hubei, 430070, People’s Republic of ChinaCorrespondence: Chengxin Li; Rui Wang, Department of Dermatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Tel +86-01066939315 ; Tel +86-01066939314, Email chengxinderm@163.com; wr0699@163.comPurpose: The underlying pathophysiology linking psoriasis vulgaris (PV) and metabolic syndrome (MetS) is not fully understood. The present study aimed to investigate the serum level of interleukin (IL)-9 and tissue levels of IL-9 and its receptor in PV patients with MetS and analyze the correlation of IL-9 levels with psoriasis disease severity and MetS.Methods: This study enrolled 75 PV patients with MetS, 57 PV patients without MetS, 20 healthy blood donors, and 7 healthy skin donors. Clinical, socio-demographic, and anthropometric data were obtained from all individuals. Fasting blood glucose, insulin, lipid profile levels, and serum levels of IL-9 and IL-17A were measured. The expression of IL-9 and its receptor in skin specimens in PV patients and healthy controls was determined using immunohistochemistry. Normal human epidermal keratinocytes were stimulated with five pro-inflammatory cytokines (tumor necrosis factor-α, oncostatin M, IL-22, IL-17A, and IL-1α) to establish a psoriatic keratinocyte model and subsequently treated with IL-9. Their mRNA levels of antimicrobial peptides and chemokines were measured using quantitative real-time polymerase chain reaction.Results: Serum level of IL-9 and tissue levels of IL-9 and its receptor were upregulated in PV patients with MetS. IL-9 level was positively correlated to IL-17A level; however, no significant correlation of IL-9 level with psoriasis area severity index was observed. IL-9 level had a positive correlation with the presence of MetS and its components. Correspondingly, IL-9 level positively correlated with waist circumference, body mass index, homeostasis model assessment-insulin resistance, blood pressure, and triglyceride level and negatively correlated with high-density lipoprotein cholesterol level. Additionally, IL-9 stimulated the expression of antimicrobial peptides and chemokines in a psoriatic keratinocyte model.Conclusion: Our findings confirmed that higher IL-9 level is associated with PV complicated by MetS, suggesting that IL-9 may be a link between PV and MetS.Keywords: interleukin-9, interleukin-17A, psoriasis vulgaris, metabolic syndrome

Deng Zhang,1 Simin Yu,1 Xiaoliang Ou Yang,1 Xiuping Wang,1 Yunxia Zhu,1 Zhen Xiao,2 Yanping Tan,3 Liang Wu,1 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of China; 3Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email chunminglincu@163.comBackground: Acne vulgaris (AV) is a common inflammatory disorder involving the pilosebaceous unit. The study aimed to explore the plasma lipidome signatures and identify specific lipid biomarkers in moderate-to-severe acne patients.Patients and Methods: Untargeted plasma lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was employed on 30 moderate-to-severe acne patients aged between 16– 25 years and 30 healthy controls. Multivariate data analyses were used to identify the distinguishing lipid metabolites.Results: All 1449 species of 37 lipid subclasses were identified from the MS data. There were apparent differences in plasma lipid profiles between acne groups and control groups. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 26 significantly different lipid metabolites were identified. These metabolites consisted mainly of glycerophospholipids (GPs), sphingolipids (SPs), and glycerolipids (GLs). Combining with AUC≥ 0.800 as the elected criteria, we obtained five differential lipids with good diagnostic performance for acne severity, including 2 sphingomyelins (SM), 1 phosphatidylglycerol (PG), 1 trihexosylceramide (Hex3Cer), and 1 Phosphatidylcholine (PC). Among them, PG (44:0) had the highest AUC values.Conclusion: Our study revealed the plasma lipidome signature of patients with moderate-to-severe acne. The results will provide a novel light into the perturbed lipid metabolism leading to the development of acne.Keywords: moderate-to-severe acne, lipidomics, sphingolipids, glycerophospholipids

Chen Li,1,&ast; Jun Hao,2,&ast; Chuangshi Wang,2 Jie Yang,1 Yitian Zheng,1 Kuo Zhang,3 Wen Hui,4 Xiangbin Meng,1 Jun Gao,1 Wei Li,2 Yi-Da Tang1,5 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, People’s Republic of China; 2Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Yi-Da Tang, Email liwei@mrbc-nccd.com; tangyida@bjmu.edu.cnObjective: The incidence rate of thyroid diseases increased worldwide. This study aims to overview the changing landscape of drug clinical trials on thyroid disease during 2009– 2022.Methods: The detailed information of thyroid disease drug trials registered on the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Studies was searched and collected. The thyroid drug clinical trials were analyzed by the characteristics, time trends, indications, and geographical distribution.Results: Sixty-five thyroid disease drug clinical trials were launched from 2009 to 2022 in China, which included 21 trials in nontumorous thyroid disease and 44 trials in thyroid carcinoma. The number of registered trials of thyroid diseases including thyroid carcinoma and nontumorous thyroid disease increased steadily from 2009 to 2020. Bioequivalence studies accounted for the largest proportion (32[49.2%]), while phase I and Phase II studies both only accounted for 18.5% (12/65). A significant difference was observed in the trials phase, and randomization between thyroid carcinoma and nontumorous thyroid disease. In terms of clinical indications and drug mechanisms, the number of trials in multi-target tyrosine kinase inhibitors for thyroid carcinoma (n=35) ranked first, followed by thyroid hormone for hypothyroidism (n=7), thyrotropin for thyroid carcinoma (n=6). Sixty-five trials were led by 36 principal investigator (PI) units, and more than 30% of PI-leading units were located in Shanghai (n=7) and Beijing (n=4).Conclusion: During the past 13 years, the development of thyroid diseases drugs trials has achieved certain progress in thyroid carcinoma, especially the molecular targeted therapy, yet the development of drug trials on nontumorous thyroid disease was very slow.Keywords: thyroid disease, thyroid carcinoma, nontumorous thyroid disease, China, drug clinical trial

JiaYi Ye,1,&ast; YanYan Wei,1,&ast; JiaHui Zeng,1 YuQing Gao,1 XiaoChen Tang,1 LiHua Xu,1 YeGang Hu,1 XiaoHua Liu,1 HaiChun Liu,2 Tao Chen,3,4 ChunBo Li,1 LingYun Zeng,5,&ast; JiJun Wang,1,6,7 TianHong Zhang1 1Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Engineering Research Center of Intelligent Psychological Evaluation and Intervention, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, 200030, People’s Republic of China; 2Department of Automation, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 3Big Data Research Lab, University of Waterloo, Ontario, Canada; 4Labor and Worklife Program, Harvard University, Cambridge, MA, USA; 5Department of Psychiatric Rehabilitation, Shenzhen Kangning Hospital, ShenZhen, GuangDong, People’s Republic of China; 6Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, Shanghai, People’s Republic of China; 7Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: TianHong Zhang; JiJun Wang, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Engineering Research Center of Intelligent Psychological Evaluation and Intervention, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, 200030, People’s Republic of China, Email zhang_tianhong@126.com; jijunwang27@163.comIntroduction: Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment.Methods: A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score.Results: Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = − 0.212, p = 0.010) and in the subgroup with higher positive scores (r = − 0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines.Discussion: TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.Keywords: ultra high risk, prodromal psychosis, inflammation, TNF-α, VEGF

Jie Wang,1,2 Zhen Wei,1,2 Nan Yao,1,2 Caifeng Li,1,2 Long Sun1,2 1Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Long Sun, Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 531-88382678, Email sunlong@sdu.edu.cnPurpose: In recent years, mental health problems have become the most serious social problems worldwide. Past studies have proposed that some links exist between sunlight and mental health; however, relevant studies examining low-dose sunlight exposure populations are lacking. We conducted a study among a group of operating room nurses (ORNs) who work long hours in operating rooms and have limited sunlight exposure. We aim to add to and refine previous researches on the association between mental health and sunlight exposure in community population.Patients and Methods: A total of 787 ORNs were interviewed and analyzed. Mental health, sunlight exposure duration, sociodemographic and work-related variables, and chronic diseases were evaluated. The Kessler 10 scale (K10) was used to assess participants’ mental health status, and their sunlight exposure duration was assessed using their self-reports. Multiple linear regression analysis was adopted to examine the association between sunlight exposure and mental health.Results: The average K10 score of ORNs was 25.41. ORNs exhibit poorer mental health than other populations. Poor mental health was negatively associated with greater sunlight exposure hours per day (β=− 0.378) and sleep regularity (β=− 3.341). Poor mental health was positively associated with chronic disease (β=3.514).Conclusion: This study indicated that the positive association between sunlight exposure and mental health existed. Appropriate enhancement of sunlight exposure will be beneficial to mental health. Hospitals, related organizations and individuals should pay greater attention to ORNs’ mental health and sunlight exposure conditions. More policy recommendations as well as building structure recommendations should be proposed.Keywords: sunlight exposure, mental health, operating room nurses, China

Han Li,1,&ast; Lu Guo,2,&ast; Ke Su,1,&ast; Changlun Li,3 Yi Jiang,1 Pan Wang,4 Jiali Chen,1 Zhenying Wu,1 Ke Xu,5 Tao Gu,1 Hao Zeng,1 Kun He,6 Hao Chi,1 Wenxi Zhao,7 Lei Han,3 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 4Clinical Skills Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 6Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598, Email Lanpaoxiansheng@126.com Lei Han, Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China, Email hanleixxf@126.comBackground: TACE and TACE with or without targeted immunotherapy are crucial comprehensive therapies for middle and advanced HCC. However, a reasonable and concise score is needed to evaluate TACE and TACE combined with systemic therapy in HCC treatment.Methods: The HCC patients were grouped into two groups: training group (n = 778) (treated with TACE) and verification group (n = 333). The predictive value of baseline variables on overall survival was analyzed using COX model, and easy-to-use ALR (AST and Lym-R) scores. The best cut-off value of AST and Lym-R were determined using X-Tile software based on total survival time (OS) and further verified via a restricted three-spline method. Meanwhile, the score was further verified using two independent valid sets: TACE combined with targeted therapy and TACE with targeted combined immunotherapy.Results: In multivariate analysis, baseline serum AST> 57.1 (p < 0.001) and Lym-R≤ 21.7 (p < 0.001) were identified as independent prognostic factors. The OS of patients in the TACE pooled cohort with 0, 1, and 2 scores were 28.1 (95% CI 24– 33.8) months, 15 (95% CI 12.4– 18.6) months, and 7.4 (95% CI 5.7– 9.1) months, respectively. The time-varying ROC curve based on ALR showed that the AUC values for predicting 1, -2-and 3-year OS were 0.698, 0.718, and 0.636, respectively. These results are confirmed in two independent valid sets of TACE combined with targeted therapy and TACE with targeted combined immunotherapy. And we established a nomogram after COX regression to predict the 1 -, 2- and 3-year survival time.Conclusion: Our study confirmed that ALR score can predict the prognosis of HCC treated with TACE or TACE combined with systemic therapy.Keywords: TACE, immunotherapy, targeted therapy, nomogram

Deng Zhang,1 Zhen Xiao,2 Xiaoliang Ouyang,1 Xiuping Wang,1 Yunxia Zhu,1 Simin Yu,1 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 791 86278821, Email chunminglincu@163.comPurpose: Hailey–Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited blistering dermatosis. Pathogenic variants in ATP2C1 have been associated with HHD since 2000. This study aimed to identify the mutations in the ATP2C1 gene in two Chinese pedigrees and two sporadic cases with HHD.Patients and Methods: Two Chinese pedigrees and two sporadic cases were included in this study. Whole-exome sequencing and Sanger sequencing were performed to detect the mutation of the ATP2C1 gene. Predictions of protein structure and function were performed using bioinformatics tools, including Mutation Taster, Polyphen-2, SIFT, and Swiss-Model.Results: In this study, we detected three heterozygous mutations, including novel compound mutations of (c.1840– 4delA and c.1840_1844delGTTGC), splice site mutation of c.1570+3A>C, and a previously known nonsense mutation c.1402C>T in the ATP2C1 gene. Combined with our previous study, ten patients with c.1402C>T mutation in the ATP2C1 gene have been identified, and all these patients originated from Jiangxi Province.Conclusion: c.1402C>T mutation in the ATP2C1 gene was considered a regional highly prevalent mutation in the Chinese population with HHD. The results added new variants to the database of ATP2C1 mutations associated with HHD.Keywords: Hailey–Hailey disease, novel mutation, ATP2C1, Chinese pedigree, Sanger sequencing

Yubo Li,1,2,&ast; Chengming Li,1,2,&ast; Tao Luo,3,&ast; Tian Yue,4 Wenjing Xiao,5 Ling Yang,1,2 Zaiyuan Zhang,6 Fei Han,3,&ast; Pan Long,3 Yonghe Hu6 1School of Clinical Medicine, Chengdu University of TCM, Chengdu, People’s Republic of China; 2Basic Medical Laboratory, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 3Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 4School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, People’s Republic of China; 5Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 6College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan Long, Department of Ophthalmology, The General Hospital of Western Theater Command, Rongdu Avenue &num;270, Chengdu, People’s Republic of China, Tel +86-181-9125-6132, Email longpan1005@qq.com Yonghe Hu, College of Medicine, Southwest Jiaotong University, No. 111, North First section of the Second Ring Road, Chengdu, People’s Republic of China, Tel +86-138-8059-6789, Email huyonghezyy@163.comAbstract: With the increasing of altitude activities from low-altitude people, the study of high altitude cerebral edema (HACE) has been revived. HACE is a severe acute mountain sickness associated with exposure to hypobaric hypoxia at high altitude, often characterized by disturbance of consciousness and ataxia. As for the pathogenesis of HACE, previous studies suggested that it might be related to the disorder of cerebral blood flow, the destruction of blood-brain barrier and the injury of brain parenchyma cells caused by inflammatory factors. In recent years, studies have confirmed that the imbalance of REDOX homeostasis is also involved in the pathogenesis of HACE, which mainly leads to abnormal activation of microglia and destruction of tight junction of vascular endothelial cells through the excessive production of mitochondrial-related reactive oxygen species. Therefore, this review summarizes the role of REDOX homeostasis and the potential of the treatment of REDOX homeostasis in HACE, which is of great significance to expand the understanding of the pathogenesis of HACE. Moreover, it will also be helpful to further study the possible therapy of HACE related to the key link of REDOX homeostasis.Keywords: high altitude cerebral edema, hypobaric hypoxia, REDOX homeostasis, mitochondria dysfunction, microglia

Haotian Wu,1,&ast; Chunxia Li,2,&ast; Song Liu,1 Shuangquan Yao,1 Zhaohui Song,1 Dong Ren,1 Pengcheng Wang1 1Department of Orthopaedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Department of Imaging Medicine, General Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia, 010017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haotian Wu, Department of Orthopaedic Surgery, The 3rd Hospital, Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86-311-88603682, Fax +86-311-87023626, Email surgeon_wu@126.comPurpose: Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and red blood cell distribution width (RDW) are novel biomarkers to indicate the inflammatory/immune response, and demonstrated to be effective in diagnosis, severity evaluation, and prognosis in a variety of chronic or acute conditions. This study aims to examine whether NLR, PLR and EDW are independently associated with mortality in necrotizing fasciitis (NF).Methods: This study retrospectively enrolled patients diagnosed with NF and based on vitality status during hospitalization or within 30 days after discharge, survival and non-survival groups were defined. For distinctly comparing NLR, PLR, RDW and others, we enrolled the matched healthy controls of the same age and sex as the survivors of NF in a 1:1 ratio, which constituted the healthy control group. Comparisons were made between three groups. Variables tested with a P value < 0.10 were further entered into the multivariate logistic regression model to identify their independent association with mortality.Results: A total of 281 subjects were included, including 127 healthy controls, 127 survivors, and 27 nonsurvivors with NF, respectively, indicating a mortality rate of 17.5%. ROC analysis showed that the optimal cutoff value for NLR, PLR and RDW was 11.1, 196.0 and 15.5%, respectively, and was tested as significant only for the first two (P < 0.001, = 0.004). Multivariate logistic analysis showed that NLR ≥ 11.1 (OR, 2.51) and PLR ≥ 196.0 (OR, 2.09) were independently associated with an increased risk of mortality in NF patients, together with age ((OR, 1.28, for each 10-year increment), comorbid diabetes mellitus (OR, 2.69) and liver disease (OR, 1.86), and elevated creatinine level (OR, 1.21 for each 10 umol/L elevation).Conclusion: Elevated NLR and PLR are significant and independent predictors of mortality and can be considered for use when evaluating patients at risk of mortality.Keywords: necrotizing fasciitis, prognosis, NLR, PLR, RDW

Cuiling Li, Peng Zhou, Yuanqin Liu, Lei Zhang Department of Neurosurgery, Shandong Medicine and Health Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of ChinaCorrespondence: Lei Zhang, Department of Neurosurgery, Shandong Medicine and Health Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Road, Lixia District, Jinan, People’s Republic of China, Email zhanglei134@163.comAbstract: Post-neurosurgical infection is a common complication of neurosurgery, and serious infection can threaten the life of patients. In recent years, the increase in multidrug-resistant bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE), has proved fatal to patients. Although there are a few cases of CRE meningitis and few clinical trials have been carried out, it has attracted increasing attention with the increasing probability of its occurrence, especially considering that there are few successful cases. An increasing number of studies are also looking for the risk factors and clinical symptoms of CRE intracranial infection. In terms of treatment, some new antibiotics are gradually being used in the clinic, but due to the complicated drug-resistant mechanism of CRE and the obstruction of the blood‒brain barrier (BBB), the therapeutic effect is still very poor. In addition, obstructive hydrocephalus and brain abscess caused by CRE meningitis are still important causes of patient death and are also difficult to treat.Keywords: CRE, ventriculitis and meningitis, polymyxin, ceftazidime-avibactam, cefiderocol

Zhongyu Li,1 Xiangmin Yuan,2 Xin Liu,2 Yuping Yang,2 Li Huang,2 Qiuhong Tan,2 Cuilin Li2 1Department of Blood Transfusion, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, 412007, People’s Republic of China; 2Department of Pharmacy, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, 412007, People’s Republic of ChinaCorrespondence: Cuilin Li, Email licuilincindy@163.comBackground: Solute carrier family 22 member 3 (SLC22A3) gene had been reported to be associated with the efficacy of metformin in type 2 diabetes mellitus (T2DM). However, few studies reported the relationship between SLC22A3 polymorphism and T2DM. The aim of this study was to investigate the association of SLC22A3 polymorphism and susceptibility to T2DM in Chinese population.Methods: We identified SLC22A3 rs555754, rs3123636, rs3088442 genotypes of 450 T2DM patients and 220 healthy controls from the Chinese population. The association between SNPs of SLC22A3 and susceptibility of T2DM was evaluated.Results: The clinical characteristics were significantly different between T2DM patients and healthy controls. The polymorphisms of SLC22A3 rs555754 and rs3123636 were obviously associated with the susceptibility of T2DM which was adjusted for age, sex and BMI, while rs3088442 did not. And there was haplotype association of SLC22A3 rs3088442-rs3123636 with T2DM susceptibility.Conclusion: SLC22A3 rs555754 and rs3123636 polymorphisms were associated with the susceptibility to T2DM in Chinese Han population. Large sample size studies would be required to verify this association.Keywords: type 2 diabetes mellitus, SLC22A3 gene, polymorphism, T2DM

Chao Li,1 Xiang Li,1 Yuming Li,1 Xiaoru Niu2 1Business School, Shandong University, Weihai, People’s Republic of China; 2School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai, People’s Republic of ChinaCorrespondence: Chao Li; Xiaoru Niu, Shandong University, No. 180 Wenhuaxi Road, Weihai, 264209, People’s Republic of China, Tel +86 631 5694065, Email chao_li@sdu.edu.cn; niuxiaoru@sdu.edu.cnPurpose: Existing studies on the association between BMI and depression report conflicting results with some demonstrating a positive relationship, while others a negative link or insignificant correlation. Very limited research on the nonlinear relationship between BMI and depression has yet to clarify the reliability and robustness of the potential nonlinearity and whether a more complex association exists. This paper aims to systematically investigate the nonlinear relationship between the two factors applying rigorous statistical methods, as well as explore the heterogeneity of their association.Materials and Methods: A large-scale nationally representative dataset, Chinese General Social Survey, is used to empirically analyze the nonlinear relationship between BMI and perceived depression. Various statistical tests are employed to check the robustness of the nonlinearity.Results: Results indicate that there is a U-shaped relationship between BMI and perceived depression, with the turning point (25.718) very close to while slightly larger than the upper limit of the range of healthy weight (18.500 ≤ BMI < 25.000) defined by World Health Organization. Both very high and low BMIs are associated with increased risk for depressive disorders. Furthermore, perceived depression is higher at almost all BMI levels among individuals who are older, female, lower educated, unmarried, in rural areas, belonging to ethnic minorities, non-Communist Party of China members, as well as those with lower income and uncovered by social security. In addition, these subgroups have smaller inflection points and their self-rated depression is more sensitive to BMI.Conclusion: This paper confirms a significant U-shaped trend in the association between BMI and depression. Therefore, it is important to account for the variations in this relationship across different BMI categories when using BMI to predict depression risk. Besides, this study clarifies the management goals for achieving an appropriate BMI from a mental health perspective and identifies vulnerable subgroups at higher risk of depression.Keywords: body mass index, self-rated depression, mental health, biopsychosocial model, Chinese population

Xiyuan Li,1,2 Xiaomeng Wang,1 Liangshan Wang,1 Chenglong Li,1 Xing Hao,1 Zhongtao Du,1 Haixiu Xie,1 Feng Yang,1 Hong Wang,1 Xiaotong Hou1 1Center for Cardiac Intensive Care, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China; 2Department of Intensive Care Unit, Aviation General Hospital of China Medical University, Beijing, 100012, People’s Republic of ChinaCorrespondence: Xiaotong Hou; Hong Wang, Center for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 10 64456631 ; +86 15010516438, Email xt.hou@ccmu.edu.cn; 914286855@qq.comObjective: There was no consensus on the impact of nosocomial infection on In-hospital mortality rate in patients receiving ECMO. This study aimed to investigate the impact of nosocomial infection (NI) on In-hospital mortality rate in adult patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) after cardiac surgery.Materials and Methods: This retrospective study included 503 adult patients who underwent VA-ECMO after cardiac surgery. The impact of time-dependent NIs on In-hospital mortality rate within 28 days of ECMO initiation was investigated using a Cox regression model. The cumulative incidence function for death was compared between patients with NIs and those without NIs using a competing risk model.Results: Within 28 days after ECMO initiation, 206 (41.0%) patients developed NIs, and 220 (43.7%) patients died. The prevalence rates of NIs were 27.8% and 20.3% during and after ECMO therapy, respectively. The incidence rates of NIs during and after ECMO therapy were 49‰ and 25‰, respectively. Time-dependent NI was an independent risk factor for predicting death (hazard ratio = 1.05, 95% confidence interval = 1.00– 1.11). The cumulative incidence of death in patients with NI was significantly higher than that in patients without NI at each time point within 28 days of ECMO initiation. (Z = 5.816, P = 0.0159).Conclusion: NI was a common complication in adult patients who received VA-ECMO after cardiac surgery, and time-dependent NI was an independent risk factor for predicting mortality in these patients. Using a competing risk model, we confirmed that NIs increased the risk of In-hospital mortality rate in these patients.Keywords: venoarterial extracorporeal membrane oxygenation, nosocomial infection, in-hospital mortality rate, Cox regression, competing risk model