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Jingxia Mao,1,2,&ast; Guibo Yang,1,3,&ast; Qin Su,1,4,&ast; Zhonghong Zeng,1 Jueying Lin,2 Lin Kong,3 Lidun Zhang,4 Lidan Liu,1 Yihua Yang,1 Hongbo Wu1 1Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Obstetrics, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Obstetrics, The Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Obstetrics, The First People’s Hospital of Yulin, Yulin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo Wu; Yihua Yang, Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email 19587200@qq.com; workyyh@163.comObjective: To assess the safety and efficiency of in vitro fertilization/ intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) on maternal and neonatal perinatal outcomes in women (≥ 40y) with singleton pregnancies.Methods: This multi-center retrospective cohort study, carried out from January 2018 to June 2023, enrolled 1762 women (≥ 40y) with singleton pregnancies of at least 28 weeks. Participants were divided into two groups: the IVF/ICSI-ET group (204 cases) and the spontaneous conception (SC) group (1558 cases). After 1:2 propensity score matching (PSM), the two groups were compared for maternal and neonatal outcomes. The SC group (1558 cases) was further divided by age into the < 43 years group (1195 cases) and the ≥ 43 years group (363 cases) for subgroup analysis.Results: Adverse maternal and neonatal outcomes were comparable between the IVF/ICSI-ET group and the SC group, with a higher cesarean section rate (78% vs 67.5%, P =0.013), an increased maternal ICU admissions rate (5.5% vs 1.3%, P =0.008), and a lower birth defects rate (1.1% vs 4.6%, P =0.037) in the IVF/ICSI-ET group. Subgroup analysis showed that women aged ≥ 43 years had higher incidences of gestational diabetes, gestational hypertension, cesarean section, and neonatal asphyxia compared to women aged < 43 years.Conclusion: This study indicated IVF/ICSI-ET is relatively safe for women ≥ 40 years with singleton pregnancies. However, advanced maternal age deteriorated maternal and neonatal outcomes, and IVF/ICSI-ET further heightened the risk of cesarean section and maternal ICU admissions. Therefore, enhanced care and vigilance are crucial for women over 40 undergoing IVF/ICSI-ET.Keywords: in-vitro fertilization, intracytoplasmic sperm injection, advanced maternal age, maternal outcomes, neonatal outcomes

Weilin Lu,1,&ast; Kaiming Li,2,&ast; Haisi Wu,2,&ast; Jinyu Li,2 Yan Ding,2 Xiaolin Li,1 Zhipeng Liu,3 Huae Xu,2 Yinxing Zhu3,4 1The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 3Taizhou Affiliated Hospital of Nanjing University of Chinese Medicine, Taizhou, People’s Republic of China; 4Taizhou People’s Hospital affiliated to Nanjing Medical University, Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huae Xu; Yinxing Zhu, Email xuhuae@njmu.edu.cn; zhuyinxing@njmu.edu.cnBackground: The causal relationship of breast cancer (BC) with cardiovascular disease (CVD) and the underlying mediating pathways remains elusive. Our study endeavors to investigate the causal association between BC and CVD, with a focus on identifying potential metabolic mediators and elucidating their mediation effects in this causality.Methods: In this study, we conducted two-sample Mendelian randomization (MR) to estimate the causal effect of BC (overall BC, ER+ BC, ER- BC) from the Breast Cancer Association Consortium (BCAC) on CVD including coronary heart disease (CHD), hypertensive heart disease (HHD), ischaemic heart disease (IHD), and heart failure (HF) from the FinnGen consortium. Then, we used two-step MR to evaluate 18 metabolic mediators of the association and calculate the mediated proportions.Results: Genetically predicted ER+ BC was causally associated with an increased risk of CVD including CHD (OR = 1.034, 95% CI: 1.004– 1.065, p = 0.026), HHD (OR = 1.061, 95% CI: 1.002– 1.124, p = 0.041), IHD (OR = 1.034, 95% CI: 1.007– 1.062, p=0.013), and HF (OR = 1.055, 95% CI: 1.013– 1.099, p = 0.010), while no causality was observed for overall BC and ER- BC. Furthermore, high-density lipoprotein cholesterol (HDL-C) was identified as a mediator of the association between ER+BC and CVD, including CHD (with 15.2% proportion)) and IHD (with 15.5% proportion), respectively.Conclusion: This study elucidates the potential causal impact of ER+ BC on subsequent risk of CVD, including CHD, HHD, IHD, and HF. We also outline the metabolic mediator HDL-C as a priority target for preventive measures to reduce excessive risk of CVD among patients diagnosed with ER+BC.Keywords: breast cancer, cardiovascular disease, ER status, Mendelian randomization, metabolic mediators, HDL-C

Zehua Yang,&ast; Yamei Zheng,&ast; Lei Zhang, Jie Zhao, Wenya Xu, Haihong Wu, Tian Xie, Yipeng Ding Department of Respiratory and Critical Care Medicine, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, Hainan, 570311, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yipeng Ding; Tian Xie, Department of Respiratory and Critical Care Medicine, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, 19 Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, People’s Republic of China, Tel +86-18976335858, Email yipengding2024@163.com; hpphxietian@163.comBackground and Purpose: Chronic obstructive pulmonary disease (COPD) is a common and progressive disease that is influenced by both genetic and environmental factors, and genetic factors are important determinants of COPD. This study focuses on screening the best predictive models for assessing COPD-associated SNPs and then using the best models to predict potential risk factors for COPD.Methods: Healthy subjects (n=290) and COPD patients (n=233) were included in this study, the Agena MassARRAY platform was applied to genotype the subjects for SNPs. The selected sample loci were first screened by logistic regression analysis, based on which the key SNPs were further screened by LASSO regression, RFE algorithm and Random Forest algorithm, and the ROC curves were plotted to assess the discriminative performance of the models to screen the best prediction model. Finally, the best prediction model was used for the prediction of risk factors for COPD.Results: One-way logistic regression analysis screened 44 candidate SNPs from 146 SNPs, on the basis of which 44 SNPs were screened or feature ranked using LASSO model, RFE-Caret, RFE-Lda, RFE-lr, RFE-nb, RFE-rf, RFE-treebag algorithms and random forest model, respectively, and obtained ROC curve values of 0.809, 0.769, 0.798, 0.743, 0.686, 0.766, 0.743, 0.719, respectively, so we selected the lasso model as the best model, and then constructed a column-line graph model for the 25 SNPs screened in it, and found that rs12479210 might be the potential risk factors for COPD.Conclusion: The LASSO model is the best predictive model for COPD and rs12479210 may be a potential risk locus for COPD.Keywords: COPD, LASSO, machine learning, predictive model, SNP

Xiaoping Xu, Han Wu, Yang Liu Department of Obstetrics and Gynecology, Deyang People’s Hospital, Deyang, Sichuan, People’s Republic of ChinaCorrespondence: Yang Liu, Department of Obstetrics and Gynecology, Deyang People’s Hospital, 173 North Taishan Road Taishan North Road, Deyang, Sichuan, 61800, People’s Republic of China, Email 18783861321@163.comPurpose: To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis in American women.Methods: The study adopted a cross-sectional design, incorporating 3862 women aged over 20 years, selected from the National Health and Nutrition Examination Survey (NHANES) dataset from 2001 to 2006. Six dietary antioxidants were taken into account in calculating CDAI. Endometriosis was determined based on self-report. To evaluate the association between CDAI and the risk of endometriosis, we employed models with multivariable logistic variables. For subgroup assessment in relation to CDAI, a stratified multivariate logistic regression model was utilized.Results: Among all participants, 273 participants (7.1%) were found to exhibit endometriosis. The preliminary analysis showed a reverse association between CDAI and the likelihood of endometriosis (odds ratio [OR] = 0.95; 95% confidence interval [CI]: 0.92~0.98). Upon full adjustment within the multivariable logistic regression, the ORs (95% CI) for endometriosis prevalence per unit increase in CDAI were estimated to be 0.96 (0.93~1). When the CDAI levels were divided into quartiles, it was found that the ORs for endometriosis with CDAI levels in Q2 (− 2.131– 0.023), Q3 (0.023– 2.650), and Q4 (2.650– 42.854) were 0.74 (0.52, 1.05), 0.76 (0.53, 1.1), and 0.53 (0.36, 0.79), respectively, compared to those with CDAI levels in Q1 (− 7.151–− 2.131). We evaluated the association between CDAI and endometriosis using subgroups stratified by age, race/ethnicity, education level, body mass index (BMI), oral contraceptive, and menopausal status, revealing a substantial negative relationship.Conclusion: In this cross-sectional study, increasing CDAI was proportionally associated with a reduced risk of endometriosis among American women, suggesting a diet high in antioxidants may play an important role in reducing the risk of endometriosis. The findings of NHANES data spanning 2001 to 2006 suggest that promoting antioxidant-rich diets could be an important prevention strategy for endometriosis.Keywords: composite dietary antioxidant index, endometriosis, National Health and Nutrition Examination Survey, cross-sectional study

Zhikang Yu,1,2,&ast; Zifang Shang,1,2,&ast; Qingyan Huang,3 Heming Wu,4 Sandip Patil5,6 1Institute of Basic Medical Sciences, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, 514031, People’s Republic of China; 2Guangdong Engineering Technological Research Center of Clinical Molecular Diagnosis and Antibody Drugs, Meizhou Academy of Medical Sciences, Meizhou, 514031, People’s Republic of China; 3Institute of Cardiovascular Disease, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, Guangdong, 514031, People’s Republic of China; 4Meizhou Municipal Engineering and Technology Research Centre for Molecular Diagnostics of Major Genetic Disorders, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, 514031, People’s Republic of China; 5Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, 518038, People’s Republic of China; 6Paediatric Research Institute, Shenzhen Children’s Hospital, Shenzhen, 518038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heming Wu; Sandip Patil, Email wuheming@mzrmyy.com; sandippatil1309@yahoo.comObjective: The polymorphism of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene exerts a marked influence on drug transport, thus playing a pivotal role in personalized drug dosing. This study endeavours to establish a rapid, precise, and straightforward method for detecting SLCO1B1 genetic variants utilizing Duplex Fluorescence Melting Curve Analysis (DFMCA).Methods: Whole blood samples were collected from 54 individuals from Meizhou People’s Hospital (2023.01– 2023.03), with a mean age of 58.90 years (SD = 7.86), including 28 men and 26 women. DNA was extracted from these samples and subjected to PCR amplification targeting two allelic regions. Primers, fluorescent probes, and corresponding allelic target sequences were designed specifically for two common SLCO1B1 polymorphisms (rs2306283 and rs4149056). The functionality of the fluorescent probes in binding to their respective allelic targets was verified using melting curve analysis, enabling the identification of distinct melting temperatures for different genotypes. Subsequently, DFMCA was employed to differentiate genotypes based on the melting temperature shifts of the corresponding fluorescent probes. The sensitivity, accuracy, and consistency of the method were evaluated, with sequencing validation performed on a subset of samples.Results: DFMCA facilitated the concurrent detection and accurate genotyping of both polymorphisms within 2 hours, demonstrating concordance with sequencing results from randomly selected samples. Importantly, stable detection performance was achieved for human genomic DNA at concentrations ≥ 3.125 ng. In a cohort comprising Han Chinese individuals from southern China, the allele frequencies for rs2306283 (A: 28.7%, G: 71.3%) and rs4149056 (T: 88.89%, C: 11.11%) concurred well with previous studies in the Han Chinese population.Conclusion: The SNP typing system utilizing DFMCA technology presents advantages in terms of speed, ease of use, accuracy, and cost-effectiveness, making it a suitable tool.Keywords: SLCO1B1, melting curve analysis, gene polymorphism, drug delivery

Chaoying Jin,1,2,&ast; Ruolin Zhao,3,4,&ast; Weihang Hu,5 Xiaolong Wu,4 Li Zhou,6 Letian Shan,4,6 Huiling Wu1,2 1Department of Plastic and Aesthetic Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China; 3Yichen Biotechnology Co., Ltd, Hangzhou, Zhejiang, 311200, People’s Republic of China; 4Fuyang Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311403, People’s Republic of China; 5Department of Critical Care Medicine, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, People’s Republic of China; 6The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Letian Shan; Huiling Wu, Email letian.shan@zcmu.edu.cn; zywhl@zju.edu.cnBackground: Pressure ulcer is common in the bedridden elderly with high mortality and lack of effective treatment. In this study, human-adipose-derived-stem-cells-hyaluronic acid gel (hADSCs-HA gel) was developed and applied topically to treat pressure ulcers, of which efficacy and paracrine mechanisms were investigated through in vivo and in vitro experiments.Methods: Pressure ulcers were established on the backs of C57BL/6 mice and treated topically with hADSCs-HA gel, hADSCs, hyaluronic acid, and normal saline respectively. The rate of wound closure was observed continuously during the following 14 days and the wound samples were obtained for Western blot, histopathology, immunohistochemistry, and proteomic analysis. Human dermal fibroblasts (HDFs) and human venous endothelial cells (HUVECs) under normal or hypoxic conditions were treated with conditioned medium of human ADSCs (ADSC-CM), then CCK-8, scratch test, tube formation, and Western blot were conducted to evaluate the paracrine effects of hADSCs and to explore the underlying mechanism.Results: The in vivo data demonstrated that hADSCs-HA gel significantly accelerated the healing of pressure ulcers by enhancing collagen expression, angiogenesis, and skin proliferation. The in vitro data revealed that hADSCs strengthened the proliferation and wound healing capabilities of HDFs and HUVECs, meanwhile promoted collagen secretion and tube formation through paracrine mode. ADSC-CM was also proved to exert protective effects on hypoxic HDFs and HUVECs. Besides, the results of proteomic analysis and Western blot elucidated that lipid metabolism and PPARβ/δ pathway mediated the healing effect of hADSCs-HA gel on pressure ulcers.Conclusion: Our research showed that topical application of hADSCs-HA gel played an important role in dermal regeneration and angiogenesis. Therefore, hADSCs-HA gel exhibited the potential as a novel stem-cell-based therapeutic strategy of treating pressure ulcers in clinical practices. Keywords: pressure ulcer, wound healing, human adipose derived stem cell, hydrogel, PPARβ/δ, lipid metabolism, skin regeneration

Liubing Lan,1,2 Dandan Luo,1,2 Jianwen Lian,1 Lingna She,1,3 Bosen Zhang,1,3 Hua Zhong,1 Huaxian Wang,1 Heming Wu1 1Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Obstetrics, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Department of Ultrasound, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Heming Wu, Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email wuheming1986@126.comObjective: Chromosomal microarray analysis (CMA) is a first-line test to assess the genetic etiology of fetal ultrasound abnormalities. The aim of this study was to evaluate the effectiveness of CMA in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities, including structural abnormalities and non-structural abnormalities.Methods: A retrospective study was conducted on 368 fetuses with abnormal ultrasound who received interventional prenatal diagnosis at Meizhou People’s Hospital from October 2022 to December 2023. Samples of villi, amniotic fluid, and umbilical cord blood were collected according to different gestational weeks, and karyotype and CMA analyses were performed. The detection rate of chromosomal abnormalities in different ultrasonic abnormalities was analyzed.Results: There were 368 fetuses with abnormal ultrasound, including 114 (31.0%) with structural abnormalities, 225 (61.1%) with non-structural abnormalities, and 29 (7.9%) with structural combined with non-structural abnormalities. The detection rate of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) of CMA in fetuses with structural abnormalities was 5.26% (6/114), the detection rate of karyotype was 2.63% (3/114), and the additional diagnosis rate of CMA was 2.63%. In the fetuses with ultrasonic non-structural abnormalities, the detection rate of karyotype was 6.22% (14/225), the detection rate of aneuploidy and P/LP CNVs in fetuses with ultrasonic structural abnormalities was 9.33% (21/225), and the additional diagnosis rate of CMA was 3.11%. There was no significant difference in chromosome abnormality detection rate of CMA among structural abnormality, non-structural abnormality, and structural abnormality combined with non-structural abnormality groups (5.3%, 9.3%, and 13.8%, p = 0.241), also among multiple ultrasonic abnormality and single ultrasonic abnormality groups (14.8%, and 7.3%, p = 0.105).Conclusion: CMA can significantly improve the detection rate of genetic abnormalities in prenatal diagnosis of ultrasonic abnormal fetuses compared with karyotype analysis. CMA is a more effective tool than karyotyping alone in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities.Keywords: chromosomal microarray analysis, copy number variation, abnormal ultrasound fetus, prenatal diagnosis

Huaqiong Wu,1,&ast; Guifen Yang,2,&ast; Shaohua Zhang,2 Jinxiang Luo,1 Pei Zhou,1 Yuhua Chen1 1Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 2Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Zhang, Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8618062579072, Email zhangshaohua1258@163.com Jinxiang Luo, Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8602750773333, Email luojinxiang2020@21cn.comObjective: To investigate the correlation between risk factors for coronary stenosis and the degree of coronary artery stenosis based on coronary computed tomography angiography (CCTA).Methods: Two hundred seventy-eight patients with coronary artery disease who received treatment in our hospital between January 2020 and January 2021 were selected as the experimental group, and 100 healthy people who received physical examination in our hospital during the same period were selected as the control group (age and gender matched with the study group). The clinical data and CCTA data of the two groups of patients were collected and compared. Computed tomography fractional flow reserve (FFRCT) values were calculated based on the CCTA data of the patients in the study group, risk factors for coronary artery stenosis were analysed and the correlation between the risk factors and CT flow reserve fraction was explored.Results: The serum total bilirubin (BIL), apolipoprotein A (apoA), low-density lipoprotein cholesterol (LDL-C), uric acid, total cholesterol (TC) and mean platelet volume levels were higher in the experimental group than in the control group (P < 0.05). Unconditional logistic regression analysis showed that LDL-C, uric acid, TC, triglyceride, serum total BIL and apoA were independent risk factors for coronary heart disease (P < 0.05). Serum total BIL (r = 0.27), apoA (r = − 0.30), uric acid (r = − 0.48), TC (r = − 0.35), triglyceride (r = − 0.73) and LDL-C (r = − 0.65) showed a negative correlation with FFRCT values (P < 0.05). A positive correlation was detected between high-density lipoprotein cholesterol and FFRCT values (r = 0.37, P < 0.05).Conclusion: Triglycerides, LDL-C, uric acid, TC, serum total BIL and apoA are risk factors for coronary artery stenosis that should be closely monitored and receive active intervention in clinical practice.Keywords: coronary heart disease, coronary artery stenosis, computed tomography angiography, risk factors, computed tomography fractional flow reserve

Yanan Qi,1,2 Yuanyuan Yan,1,2 Dawei Tang,1,2 Jingjing Han,1,2 Xinyi Zhu,1,2 Mengting Cui,1,2 Hongyan Wu,3 Yu Tao,1,2 Fangtian Fan1,2 1School of Pharmacy, Bengbu Medical University, Bengbu, People’s Republic of China; 2Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu, People’s Republic of China; 3Institute of Biomedical Technology, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224005, People’s Republic of ChinaCorrespondence: Yu Tao; Fangtian Fan, Anhui Engineering Technology Research Center of Biochemical Pharmaceutical Bengbu Medical College, 2600 Donghai Avenue, Bengbu, Anhui, 233003, People’s Republic of China, Tel +86-15852921284 ; +86-16655258065, Email YuTao@bbmc.edu.cn; 2019050@bbmu.edu.cnBackground: Chronic obstructive pulmonary disease (COPD) currently ranks among the top three causes of mortality worldwide, presenting as a prevalent and complex respiratory ailment. Ongoing research has underscored the pivotal role of immune function in the onset and progression of COPD. The immune response in COPD patients exhibits abnormalities, characterized by diminished anti-infection capacity due to immune senescence, heightened activation of neutrophils and macrophages, T cell infiltration, and aberrant B cell activity, collectively contributing to airway inflammation and lung injury in COPD.Objective: This review aimed to explore the pivotal role of the immune system in COPD and its therapeutic potential.Methods: We conducted a review of immunity and COPD published within the past decade in the Web of Science and PubMed databases, sorting through and summarizing relevant literature.Results: This article examines the pivotal roles of the immune system in COPD. Understanding the specific functions and interactions of these immune cells could facilitate the development of novel therapeutic strategies and interventions aimed at controlling inflammation, enhancing immune function, and mitigating the impact of respiratory infections in COPD patients.Keywords: COPD, immune system, inflammation, immune regulation

Mingtao Liu,1,&ast; Zhangkai J Cheng,1,&ast; Jiaxi Chen,2,&ast; Haiyang Li,1,3 Mingshan Xue,4,5 Xing Fu,1 Yanjun Li,2 Jiaxin Wang,2 Chenwei You,2 Haisheng Hu,1 Haojie Wu,1 Huimin Huang,1 Baoqing Sun1,4 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 511495, People’s Republic of China; 3MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK; 4Guangzhou Laboratory, Guangzhou, 510005, People’s Republic of China; 5Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Huimin Huang, Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China, Tel +86 13824124015 ; +86 13631496651, Email sunbaoqing@vip.163.com; huanghuimin311@126.comBackground: While serum periostin and Krebs von den Lungen-6 (KL-6) have been acknowledged as independent markers in idiopathic pulmonary fibrosis (IPF) diagnosis, the clinical combinatory potential of these biomarkers combined with high-resolution computed tomography (HRCT) has yet to be fully explored.Methods: This retrospective study involved 78 participants, comprising 51 UIP-IPF patients and 27 healthy controls. All subjects underwent clinical and laboratory examinations, particularly the detection of periostin and KL-6 using ELISA with innovative HRCT fibrosis score evaluations at admission and discharge during hospitalization in UIP-IPF patients.Results: In our cohort of patients with IPF, predominantly male, over an average follow-up period of 195.27 days. Serum levels of periostin and KL-6 were significantly elevated in IPF patients compared to healthy controls (&ast;p < 0.05). Post-treatment, KL-6 levels decreased significantly, while periostin levels increased. Notably, periostin exhibited superior prognostic accuracy over KL-6, with a higher AUC of 0.875 than 0.639 in ROC analysis. An increase in periostin levels correlated with disease progression, as evidenced by worsened HRCT fibrotic scores and decreased survival probability. These findings underscore periostin’s potential as a reliable biomarker for assessing IPF severity and therapeutic response.Conclusion: Our findings underscore the preeminence of serum periostin over KL-6 in UIP-IPF diagnosis, particularly when conjoined with HRCT fibrosis score.Keywords: periostin, Krebs von den Lungen-6, idiopathic pulmonary fibrosis, HRCT fibrosis score, diagnostic hematology

Xiaoqin Chen,1 Lifang Lin,2 Qiuping Zhong,1 Heming Wu,2 Zhiyuan Zheng,2 Baisen Zhang,3 Liubing Lan1 1Department of Maternity, Meizhou People’s Hospital, Meizhou City, Guangdong Province, 514031, People’s Republic of China; 2Department of Central Laboratory, Meizhou People’s hospital, Meizhou City, Guangdong Province, 514031, People’s Republic of China; 3Department of Ultrasound, Meizhou People’s hospital, Meizhou City, Guangdong Province, 514031, People’s Republic of ChinaCorrespondence: Liubing Lan, Department of maternity, Meizhou People’s hospital, No. 63, Huang Tang Road, Meijiang District, Meizhou City, Guangdong Province, 514031, People’s Republic of China, Email hipiing1284@sina.comObjective: To explore the influencing factors of fetal birth defects (BD) and construct a nomogram model.Methods: A total of 341 newborns admitted to Meizhou people’s hospital from September 2021 to September 2023 were randomly grouped into a modeling group (239 cases) and a validation group (102 cases). The modeling group fetuses were separated into BD and non-BD groups. Multivariate logistic regression analyzed risk factors for BD; R software constructed a nomogram model; Receiver operating characteristic (ROC) curve evaluated the model’s discrimination for BD.Results: The top 5 types of BD were congenital heart disease, polydactyly/syndactyly, cleft lip/palate, ear malformation, and foot malformation, with incidence rates of 23.81%, 20.63%, 12.70%, 11.11%, and 7.94%, respectively. BD incidence was 26.36% (63/239). Significant differences between BD and non-BD groups were found in maternal age, gestational age, history of adverse pregnancy/childbirth, gestational hypertension, adverse emotions during pregnancy, and folic acid intake duration (P< 0.05). Logistic regression showed maternal age (OR: 4.125), gestational age (OR: 3.066), adverse pregnancy history (OR: 10.628), gestational hypertension (OR: 5.658), adverse emotions (OR: 5.467), and folic acid intake duration (OR: 4.586) were risk factors for BD (P< 0.05). The modeling group’s ROC AUC was 0.938, calibration curve slope close to 1, H-L test =8.342, P=0.692; external validation AUC was 0.961, calibration slope close to 1, H-L test =7.634, P=0.635.Conclusion: Identified risk factors include maternal age, gestational age, adverse pregnancy history, gestational hypertension, adverse emotions, and folic acid intake duration. The nomogram model shows good discrimination and consistency for evaluating neonatal BD risk.Keywords: fetus, birth defects, influencing factors, nomogram

Min He, Huinan Wu, Guanrong Lin, Yongqin Wang, Longling Shi, Chaoling Huang, Qingyun Xu, Zhenxing Li, Shanbo Huang, Yanni Chen, Na Li Department of Endocrinology, Shishi General Hospital, Shishi, Fujian, 362700, People’s Republic of ChinaCorrespondence: Min He, Department of Endocrinology, Shishi General Hospital, No. 2156 Shijin Road, Shishi, Fujian, 362700, People’s Republic of China, Tel +8613506048712, Email heminhem463@163.comObjective: This study proposes a region-wide blood glucose management system to solve the problem of blood glucose management in patients with diabetes.Methods: A professional team of doctors, nurses and dietitians jointly developed a region-wide blood glucose management system. The system operates through a collaborative approach where each team member utilises their specialised role, such as data monitoring, algorithm development or patient support, to contribute to a comprehensive blood glucose management network. This integration ensures accurate glucose tracking, personalised feedback and timely adjustments to treatment plans. The system allows the patient to have a good treatment plan, giving comprehensive medical guidance, and the physician team is responsible for the patient’s health status.Results: The region-wide blood glucose management system increased the overall blood glucose monitoring rate of patients and reduced the hospitalisation time (from 11.27 days to 9.52 days) and hospitalisation costs (from 12,173.8 yuan to 9502.4 yuan). At the same time, the system effectively counted the incidence and occurrence time of hyperglycaemia and hypoglycaemia adverse events, which can provide a reference for clinical prevention of adverse events.Conclusion: A region-wide blood glucose management system can improve medical efficiency, save medical resources and provide a strong guarantee for the health of patients with diabetes. Compared with the traditional diabetes management mode, the region-wide blood glucose management system is more systematic and standardised, meaning it can better meet the needs of patients with diabetes.Keywords: diabetic, glucose management, professional team, guarantee for the health, improve medical efficiency

Xiaoqin Chen,1,2 Liubing Lan,1,2 Heming Wu,1 Mei Zeng,1,2 Zhiyuan Zheng,1 Qiuping Zhong,2 Fengdan Lai,2 Yonghe Hu2 1Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Obstetrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Liubing Lan, Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email 13411221666@163.comObjective: To explore and evaluate the value of chromosomal microarray analysis (CMA) in prenatal diagnosis of fetuses with ultrasound abnormalities.Methods: A retrospective analysis was performed on 370 fetuses with ultrasound abnormalities received invasive prenatal diagnosis at Meizhou People’s Hospital from October 2022 to December 2023. Fetal specimens were analyzed by CMA, and the detection rates of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) in ultrasound structural abnormalities (malformations of fetal anatomy) and non-structural abnormalities (abnormalities of fetal nonanatomical structure) were analyzed.Results: There were 114 (30.8%) cases with isolated ultrasound structural abnormalities, 226 (61.1%) cases with isolated non-structural abnormalities (182 isolated ultrasound soft markers abnormalities, 30 isolated fetal growth restriction (FGR), and 8 isolated abnormalities of amniotic fluid volume), and 30 (8.1%) cases with both structural and non-structural abnormalities. The overall detection rate of aneuploidy and P/LP CNVs in isolated ultrasonic structural abnormalities was 5.3%, among which cardiovascular system abnormalities were the highest. In addition, the largest number of fetuses with non-structural abnormalities was nuchal translucency (NT) thickening (n = 81), followed by ventriculomegaly (n = 29), and nasal bone dysplasia (n = 24). The detection rate of chromosomal abnormalities of fetuses with abnormal ultrasound soft markers was 9.9%, and the detection rate in single abnormal ultrasound soft marker, and multiple ultrasound soft markers abnormalities was 9.7% (16/165) and 11.8% (2/17), respectively. Moreover, the detection rate of chromosomal abnormalities of fetuses with FGR and structural abnormalities combined with non-structural abnormalities was 6.7% (2/30), and 13.3% (4/30), respectively.Conclusion: The incidence of chromosomal abnormalities (aneuploidy and P/LP CNVs) varies among different fetal ultrasound abnormalities.Keywords: chromosomal microarray analysis, copy number variation, abnormal ultrasound fetus, prenatal diagnosis

Ruijing Su,&ast; Yue Yang,&ast; Haiyan Wu, Bo Liu, Xinyuan Tian, Chaoyu Zhou, Yanxin Hu, Tianlong Liu Laboratory of Veterinary Pathology and Nanopathology, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianlong Liu; Yanxin Hu, Email liutianlong@cau.edu.cn; huyx@cau.edu.cnBackground: A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT).Materials and Methods: In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy.Results: MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response.Conclusion: The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors. Keywords: zeolitic imidazolate framework-8, photothermal agent polydopamine, 1-methyl-D-tryptophan, photoluminescence, camptothecin

Li Zhou,1,&ast; Youlin Wu,1,2,&ast; Jiani Wang,1 Haiyun Wu,1 Yongjun Tan,1 Xia Chen,1,3 Xiaosong Song,1,4 Yu Ren,1 Qin Yang1 1Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurology, Chongzhou People’s Hospital, Sichuan, People’s Republic of China; 3Department of Neurology, the Seventh People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 4Department of Neurology, the Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Yang, Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-023-89012008, Fax +86-023-68811487, Email xyqh200@126.comBackground and Purpose: Ischemic stroke is a leading cause of mortality and disability globally, necessitating accurate prediction of intra-hospital mortality (IHM) for improved patient care. This study aimed to develop a practical nomogram for personalized IHM risk prediction in ischemic stroke patients.Methods: A retrospective study of 422 ischemic stroke patients (April 2020 - December 2021) from Chongqing Medical University’s First Affiliated Hospital was conducted, with patients divided into training (n=295) and validation (n=127) groups. Data on demographics, comorbidities, stroke risk factors, and lab results were collected. Stroke severity was assessed using NIHSS, and stroke types were classified by TOAST criteria. Least absolute shrinkage and selection operator (LASSO) regression was employed for predictor selection and nomogram construction, with evaluation through ROC curves, calibration curves, and decision curve analysis.Results: LASSO regression and multivariate logistic regression identified four independent IHM predictors: age, admission NIHSS score, chronic obstructive pulmonary disease (COPD) diagnosis, and white blood cell count (WBC). A highly accurate nomogram based on these variables exhibited excellent predictive performance, with AUCs of 0.958 (training) and 0.962 (validation), sensitivities of 93.2% and 95.7%, and specificities of 93.1% and 90.9%, respectively. Calibration curves and decision curve analysis validated its clinical applicability.Conclusion: Age, admission NIHSS score, COPD history, and WBC were identified as independent IHM predictors in ischemic stroke patients. The developed nomogram demonstrated high predictive accuracy and practical utility for mortality risk estimation. External validation and prospective studies are warranted for further confirmation of its clinical efficacy.Keywords: ischemic stroke, nomogram, predictors, lasso, intra-hospital mortality

Jialin Gu,1,2,&ast; Hailan Wu,1,3,&ast; Wanjing Diao,1,&ast; Yi Ji,1 Jianyue Li,1 Jiege Huo1 1Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, People’s Republic of China; 2Department of Traditional Chinese medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China; 3Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210016, People’s Republic of China&ast;These authors contribute equally to this workCorrespondence: Jiege Huo; Jianyue Li, Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, People’s Republic of China, Email huojiege@jsatcm.com; tnt2vb@126.comObjective: To examine potential factors affecting sleep duration and explore its association with the risk of mortality among adults in the United States.Methods: The study population consisted of adults aged 26 to 79 years who participated in the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2016. Sleep duration was classified into three categories: short (< 7 hours), optimal (7– 8 hours), and long (≥ 9 hours). The associations between sleep duration and both all-cause mortality and cause-specific mortality (including heart disease, tumors, cerebrovascular disease, and others) were examined in the overall population and subgroups using weighted Cox regression models. Dose-response associations between sleep duration and risk of all-cause mortality were explored using restricted cubic spline (RCS) analyses. Additionally, a multinomial logistic regression analysis was conducted to investigate potential factors that influence sleep duration in adults.Results: The study included a total of 24,141 subjects, with a population-weighted mean age of 48.93 years. Over 30% of the subjects exhibited unhealthy sleep habits. Fully adjusted models revealed that both short sleep duration (HR=1.169, 95% CI 1.027– 1.331) and long sleep duration (HR=1.286, 95% CI 1.08– 1.531), were associated with an increased risk of all-cause mortality. The RCS curves showed a U-shaped relationship between sleep duration and risk of all-cause mortality. Subgroup analyses showed a significant association between poor sleep patterns and all-cause mortality among adults aged 26– 64 years, males, and non-Hispanic whites. Furthermore, multinomial logistic regression identified several predictors associated with short and long sleep durations.Conclusion: Both short and long sleep duration are associated with an increased risk of all-cause mortality, with a U-shaped dose-response relationship. It is imperative to implement appropriate primary prevention strategies aimed at monitoring and providing health education to populations at risk of developing unhealthy sleep patterns.Keywords: sleep duration, mortality, adults, association, NHANES

Liang Hu,1 Han Wu,1 Jiamin Wang,2 Yang Hu1 1Department of Urology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 2Department of Intervention, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of ChinaCorrespondence: Yang Hu, Department of Urology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China, Email yanghu2024@126.comAbstract: Minimally invasive percutaneous nephrolithotomy (mini-PCNL) maintains a stone clearance rate similar to standard PCNL while reducing blood loss. Bleeding is a complex and serious complication that can arise after PCNL surgery. Pseudoaneurysm (PA) is an uncommon type of delayed bleeding problem, which affects less than 1% of patients after PCNL. The most effective treatment for severe post-PCNL hemorrhage is super-selective renal angiographic embolization (SRAE), but it can fail in some patients and require additional surgical intervention. This report details the case of a male patient, 55 years old, who experienced severe bleeding four times and had three SRAE procedures and one laparoscopic procedure after PCNL. The presence of a renal artery pseudoaneurysm was not initially identified during the first two attempts of angiography due to arterial spasm and a small, undeveloped lesion. This case report is intended to enhance awareness of tiny pseudoaneurysms, emphasizing the importance of avoiding oversight to improve the success rate of embolization.Keywords: super-selective renal angiographic embolization, percutaneous nephrolithotomy, haemorrhage, case

Tong Zhang,1– 3,&ast; Han Wu,1,2,&ast; Chenling Qiu,1,2 Mingxin Wang,1,2 Haiting Wang,1,2 Shunhua Zhu,1,4 Yinhai Xu,2 Qingli Huang,1,4 Shibao Li1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 3Chuzhou Center for Disease Control and Prevention, Chuzhou City, Anhui, 239000, People’s Republic of China; 4Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingli Huang; Shibao Li, Email qlhuang@xzhmu.edu.cn; sdjnshlb@xzhmu.edu.cnIntroduction: Insulin and C-peptide played crucial roles as clinical indicators for diabetes and certain liver diseases. However, there has been limited research on the simultaneous detection of insulin and C-peptide in trace serum. It is necessary to develop a novel method with high sensitivity and specificity for detecting insulin and C-peptide simultaneously.Methods: A core-shell-satellites hierarchical structured nanocomposite was fabricated as SERS biosensor using a simple wet-chemical method, employing 4-MBA and DTNB for recognition and antibodies for specific capture. Gold nanorods (Au NRs) were modified with Raman reporter molecules and silver nanoparticles (Ag NPs), creating SERS tags with high sensitivity for detecting insulin and C-peptide. Antibody-modified commercial carboxylated magnetic bead@antibody served as the capture probes. Target materials were captured by probes and combined with SERS tags, forming a “sandwich” composite structure for subsequent detection.Results: Under optimized conditions, the nanocomposite fabricated could be used to detect simultaneously for insulin and C-peptide with the detection limit of 4.29 × 10− 5 pM and 1.76 × 10− 10 nM in serum. The insulin concentration (4.29 × 10− 5– 4.29 pM) showed a strong linear correlation with the SERS intensity at 1075 cm− 1, with high recoveries (96.4– 105.3%) and low RSD (0.8%– 10.0%) in detecting human serum samples. Meanwhile, the C-peptide concentration (1.76 × 10− 10– 1.76 × 10− 3 nM) also showed a specific linear correlation with the SERS intensity at 1333 cm− 1, with recoveries 85.4%– 105.0% and RSD 1.7%– 10.8%.Conclusion: This breakthrough provided a novel, sensitive, convenient and stable approach for clinical diagnosis of diabetes and certain liver diseases. Overall, our findings presented a significant contribution to the field of biomedical research, opening up new possibilities for improved diagnosis and monitoring of diabetes and liver diseases.Keywords: surface-enhanced Raman scattering, SERS, nanocomposites, insulin, C-peptide

Yupeng Han,1,2,&ast; Liangcheng Qiu,1,2,&ast; Haixing Wu,1,2,&ast; Zhiwei Song,3 Peng Ke,1,2 Xiaodan Wu1,2 1Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, Fujian, People’s Republic of China; 3Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Wu, Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China, Email wxiaodan@sina.comAbstract: Sepsis is a severe systemic inflammatory response commonly occurring in infectious diseases, caused by infection with virulent pathogens. In the pathogenesis of sepsis, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves a crucial role as a fundamental immunoregulatory mechanism. This signaling pathway activates STING upon recognizing intracellular DNA damage and pathogen-derived DNA, subsequently inducing the production of numerous inflammatory mediators, including interferon and inflammatory cytokines, which in turn trigger an inflammatory response. The aim of this paper is to explore the activation mechanism of the cGAS-STING signaling pathway in sepsis and its impact on inflammatory regulation. By delving into the mechanism of action of the cGAS-STING signaling pathway in sepsis, we aim to identify new therapeutic strategies for the treatment and prevention of sepsis.Keywords: sepsis, cGAS, STING, inflammation

Xianmin Zhu,1 Shuang Dong,1 Jing Tang,1 Rong Xie,1 Huijing Wu,1 Jun Guan,2 Sheng Hu1 1Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Wuhan NO.1 Hospital, Wuhan, People’s Republic of ChinaCorrespondence: Sheng Hu, Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116 South Road, Wuhan, 430079, People’s Republic of China, Email ehusmn@163.comAbstract: In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death − 1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient’s enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.Keywords: hepatocellular carcinoma, complete response, immune checkpoint inhibitor, tislelizumab, chemotherapy failure, metastasis

Youren Dai,1,&ast; Huiyun Wu,1,&ast; Jiahui Cao,1,&ast; Yang Li,2 Wenjun Cheng,1 Chengyan Luo1 1Department of Gynecology, First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Pathology, First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengyan Luo, Department of Gynecology, First Affiliated Hospital with Nanjing Medical University, 368 North Jiangdong Road, Nanjing, 210036, People’s Republic of China, Email betteryuan66@njmu.edu.cnPurpose: To investigate prognostic factors affecting cancer-specific survival (CSS) and to analyze the survival outcomes of patients with undifferentiated and dedifferentiated endometrial carcinoma (UDEC) who underwent various postoperative adjuvant therapies.Methods: The independent risk factors affecting CSS were studied using univariate and multivariate Cox regression analysis, and CSS in the presence of various postoperative treatments was evaluated using Kaplan-Meier method based on the cohort with pathologically confirmed UDEC from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, the study included 18 cases with UDEC in our center and explored their molecular characteristics and prognosis.Results: Between 2000 and 2019, a total of 443 patients were included from the SEER database. The median CSS duration was 14 months, with corresponding 3- and 5-year CSS rates of 45.9% and 44.0%, respectively. Factors such as pTNM stage, surgical resection of primary lesion, and chemoradiation independently influenced CSS. Postoperative chemotherapy alone improved CSS in patients with initial tumor spread beyond the uterus (pT3 and pT4), or lymph node (LN) invasion, or distant metastases. Additionally, postoperative radiotherapy enhanced CSS in patients who had undergone postoperative chemotherapy, those with primary tumors progressing to stage pT3, and those with LN involvement but without distant metastases. Of the 18 patients diagnosed at our center, with a median follow-up of 15.5 months, one experienced relapse and two succumbed to UDEC, who exhibited aberrant p53 expression in immunohistochemical staining.Conclusion: Postoperative chemotherapy and radiotherapy are beneficial for UDEC patients with tumors extending beyond the uterus or involving lymph nodes.Keywords: undifferentiated and dedifferentiated endometrial carcinoma, cancer-specific survival, prognostic factors, postoperative adjuvant therapy

Zhi Hui Gu, Jia Yi Wang, Chen Xin Yang, Hui Wu Department of Social Medicine, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Hui Wu, Department of Social Medicine, School of Health Management, China Medical University, Shenyang North New District, No. 77 Puhe Road, Shenyang, Liaoning, 110122, People’s Republic of China, Email hwu@cmu.edu.cnBackground: Gynecological cancer generally refers to malignant tumors in gynecology, commonly including cervical cancer, endometrial cancer, and ovarian cancer. Patients with gynecological cancer often suffer from sleep disorders after clinical treatment. Except for serious sleep disorders, female characteristics, family roles, and feudal beliefs make their self-stigma at a medium to high level, leading to huge pressure. This study aims to identify potential categories of sleep disorders, and analyze the relationship between self-stigma, perceived stress, and sleep disorders.Methods: A cross-sectional study was conducted in 2021– 2022. Two hundred and two patients’ data were collected from ShengJing Hospital Affiliated to China Medical University in Liaoning, Shenyang by using paper questionnaires for face-to-face surveys. The survey tools included the Pittsburgh Sleep Quality Index (PSQI), the Perceived Stress Scale (PSS), and the Social Impact Scale (SIS). Potential profile analysis (LPA), multiple logistic regression analysis, and structural equation modeling (SEM) were performed by Mplus 8.3, SPSS 26.0, and Amos 24.0 statistical tools, respectively.Results: Three latent patterns of sleep disorders were found: “Good Sleep group (42.5%)”, “Sleep Deficiency group (32.4%)”, and “Sleep Disturbance group (25.1%)”. Patients with high perceived stress were more likely to report a moderate (OR=1.142, 95% CI: 1.061– 1.230) or high (OR=1.455, 95% CI: 1.291– 1.640) level of sleep disorders. Self-stigma did not have a direct effect on sleep disorders (0.055, P> 0.05), but it could have indirect effect on sleep disorders through perceived stress (0.172, P< 0.01).Conclusion: The perceptions of sleep disorders among gynecological cancer patients varies and exhibits individual differences. Gynecological cancer patients who feels alienated or discriminated may cause high pressure. This internal pressure can exacerbate sleep disorders.Keywords: sleep disorders, self-stigma, perceived stress, latent profile analysis, mediating effect, gynecological cancer

Hongmei Yang,1,&ast; Zhongqi Liu,1,&ast; Fan Liu,1,2,&ast; Haixuan Wu,1 Xiaoyan Huang,1 Rong Huang,1 Phei Er Saw,3,4 Minghui Cao1,2 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Department of Anesthesiology, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516600, People’s Republic of China; 3Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Phei Er Saw; Minghui Cao, Email caipeie@mail.sysu.edu.cn; caomh@mail.sysu.edu.cnBackground: Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia.Methods: To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA.Results: Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine (p < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group (p < 0.0001).Conclusion: Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.Keywords: lipid nanoparticle, Tet1, peripheral nerve-targeted, pain management, chronic neuropathic pain

Tingting Liu,1,&ast; Haojie Wu,1,&ast; Lin Sun,2 Jianshe Wei1 1Institute for Brain Sciences Research, School of Life Sciences, Henan University, Institute of Neurourology and Urodynamics, Huaihe Hospital of Henan University, Kaifeng, 475004, People’s Republic of China; 2College of Chemistry and Molecular Sciences, Henan University, Kaifeng, 475004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Sun; Jianshe Wei, Email sunlin@vip.henu.edu.cn; jswei@henu.edu.cnBackground: The coronavirus disease 2019 (COVID-19) can lead to neurological symptoms such as headaches, confusion, seizures, hearing loss, and loss of smell. The link between COVID-19 and Parkinson’s disease (PD) is being investigated, but more research is needed for a definitive connection.Methods: Datasets GSE22491 and GSE164805 were selected to screen differentially expressed gene (DEG), and immune infiltration and gene set enrichment analysis (GSEA) of the DEG were performed. WGCNA analyzed the DEG and selected the intersection genes. Potential biological functions and signaling pathways were determined, and diagnostic genes were further screened using gene expression and receiver operating characteristic (ROC) curves. Screening and molecular docking of ibuprofen as a therapeutic target. The effectiveness of ibuprofen was verified by constructing a PD model in vitro, and constructing “COVID19-PD” signaling pathway, and exploring the role of angiotensin-converting enzyme 2 (ACE2) in PD.Results: A total of 13 DEG were screened from the GSE36980 and GSE5281 datasets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that the DEG were mainly associated with the hypoxia-inducible factor (HIF-1), epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, etc. After analysis, it is found that ibuprofen alleviates PD symptoms by inhibiting the expression of nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Based on signal pathway construction, the importance of ACE2 in COVID-19-induced PD has been identified. ACE2 is found to have widespread distribution in the brain. In the 1-methyl-4-phenyl-1,2,3,6-te-trahydropyridine (MPTP)-induced ACE2-null PD mice model, more severe motor and non-motor symptoms, increased NF-κB p65 and α-synuclein (α-syn) expression with significant aggregation, decreased tyrosine hydroxylase (TH), severe neuronal loss, and neurodegenerative disorders.Conclusion: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the risk of PD through an inflammatory environment and downregulation of ACE2, providing evidence for the molecular mechanism and targeted therapy associated with COVID-19 and PD.Keywords: Parkinson’s disease, COVID-19, ibuprofen, nuclear factor kappa-B, angiotensin-converting enzyme 2

Ruifang Shi,1,&ast; Fan Yang,1,&ast; Hongli Wu,2 Yonggang Liu1 1Department of Pathology, Tianjin Institute of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China; 2Department of Clinical Lab, Tianjin Institute of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonggang Liu, Department of Pathology, Tianjin Institute of Hepatology, Tianjin Second People’s Hospital, No. 7, Sudi South Road, Nankai District, Tianjin, 300192, People’s Republic of China, Tel +86 22 27426025, Email liuyonggang_2023@163.comObjective: To analyse clinical manifestations of unexplained abnormal liver function and perform hepatobiliary histopathology procedures on patients to evaluate the value of liver biopsy in diagnosing the aetiology of unexplained abnormal liver function.Methods: A convenience sampling method was used to retrospectively collect the data of patients who were diagnosed with unexplained abnormal liver function and who received liver biopsy in the Pathology Department of Tianjin Second People’s Hospital, China, between March 2022 and July 2023 to analyse liver pathology and clinical manifestations.Results: A total of 1302 patients were included in this study, which mainly included 11 diseases: autoimmune liver disease (74 cases, 5.68%), drug-induced liver injury (DILI) (204 cases, 15.67%), cancer (237 cases, 18.20%), non-alcoholic fatty liver disease (104 cases, 7.99%), non-alcoholic steatohepatitis (74 cases, 5.68%), viral hepatitis (490 cases, 37.63%), other types of hepatitis (30 cases, 2.30%), cholestatic liver disease (17 cases, 1.31%), alcoholic liver disease (15 cases, 1.15%), hepatic cyst (5 cases, 0.38%) and Gilbert syndrome (4 cases, 0.31%). The success rate of liver biopsy sampling was 100%, and (1.52 ± 0.130) tissue strips were sampled. The average operating time was 11.52 minutes. The percutaneous liver biopsy did not significantly increase short-term liver function index values (serum γ-glutamyl transpeptidase, total bilirubin, alanine transaminase, aspartate aminotransferase, alkaline phosphatase). Ninety-two patients had a small amount of liver subcapsular fluid, but there was no progress after medical treatment.Conclusion: Ultrasound-guided percutaneous liver biopsy has value in the diagnosis of unexplained abnormal liver function. Viral hepatitis, cancer and DILI are the most common causes of unexplained abnormal liver function. Liver biopsy does not aggravate the organic and functional impairment of the liver.Keywords: unexplained abnormal liver function, clinical manifestations, liver biopsy, pathology

Hao Wu, Yan Na Shen, Zhongxiao Wu, Feng Mao, You Gang Ren, Li Zhang Department of Dermatology, Ningbo No 6 Hospital, Ningbo, 315040, People’s Republic of ChinaCorrespondence: Li Zhang, Email lishay1022@hotmail.comAbstract: Although the use of biologics has led to great improvement in psoriasis patients, the treatment of psoriasis during pregnancy still faces many challenges. We herein report on a 29-year-old pregnant woman treated with ustekinumab for generalized pustular psoriasis. Upon becoming pregnant, the woman underwent continued treatment with ustekinumab in the first trimester. We also considered the need for neonatal vaccination. The patient discontinued ustekinumab therapy in the second trimester, and during the period of drug discontinuation we noted a slight rash recurrence. The patient was treated with ultraviolet B phototherapy and topical corticosteroids, and the rash was localized to the abdomen. However, in the 27th week of pregnancy, the patient was infected with COVID-19, which made the condition worse. The rash erupted rapidly and spread throughout her body, and she experienced a high fever with her blood count showing augmented numbers of white blood cells. The patients self-administered 0.3 g of acetaminophen three times per day, and after four days her core body temperature was 38.0°C; the rash, however, did not diminish. We diagnosed an outbreak of generalized pustular psoriasis and treated the patient with ustekinumab. The rash resolved quickly, and a healthy newborn was delivered by caesarean section at 39 weeks.Keywords: Ustekinumab, interleukin-12/-23, generalized pustular psoriasis, pregnancy, COVID-19

Zhihua Zhang,1 Yuhong Wang,2 Yankun Zhang,3 Shujun Geng,2 Haifeng Wu,4 Yanxin Shao,5 Guannan Kang6 1Department of Science & Education, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 2Department of Tuberculosis, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 3Department of Ophthalmology, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 4Clinical Laboratory, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 5Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 6Department of Tuberculosis, Hebei Chest Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yanxin Shao, Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, No. 372, Sheng Li North Street, Shijiazhuang, Hebei, 050041, People’s Republic of China, Email shaoyanxin163@163.comBackground: Tuberculosis (TB) is one of the most infectious diseases caused by Mycobacterium tuberculosis (M. tb), and the diagnosis of active tuberculosis (TB) and latent TB infection (LTBI) remains challenging.Methods: Gene expression files were downloaded from the GEO database to identify the differentially expressed genes (DEGs). The ssGSEA algorithm was applied to assess the immunological characteristics of patients with LTBI and TB. Weighted gene co-expression network analysis, protein-protein interaction network, and the cytoHubba plug-in of Cytoscape were used to identify the real hub genes. Finally, a diagnostic model was constructed using real hub genes and validated using a validation set.Results: Macrophages and natural killer cells were identified as important immune cells strongly associated with TB. In total, 726 mRNAs were identified as DEGs. MX1, STAT1, IFIH1, DDX58, and IRF7 were identified as real hub immune-related genes. The diagnostic model generated by the five real hub genes could distinguish active TB from healthy controls or patients with LTBI.Conclusion: Our study may provide implications for the diagnosis and drug development of M. tb infections.Keywords: tuberculosis, latent tuberculosis infection, mycobacterium tuberculosis, immune, diagnostic model

Hongmei Yu,1 Cheng Luo,1 Ru Linghu,2 Juan Yang,3 Haiqiao Wu3 1Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Internal Medicine, Hospital of Chongqing University, Chongqing, People’s Republic of China; 3Department of Respiratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of ChinaCorrespondence: Hongmei Yu, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +8618996009679, Email yhm920@126.comBackground: Diabetes mellitus predisposes individuals to respiratory infections. The airway epithelial barrier provides defense against inhaled antigens and pathogens. Ezrin, is a component of the membrane-cytoskeleton that maintains the cellular morphology, intercellular adhesion, and barrier function of epithelial cells. This study aimed to explore the role of ezrin in airway epithelial barrier damage and correlate its expression and activation with diabetes mellitus.Methods: This study was performed in a murine model of diabetes mellitus and with human bronchial epithelial BEAS-2B cells using real-time PCR, Western blotting, immunohistochemical and immunofluorescence staining. Ezrin was knocked down in BEAS-2B cells using siRNA. Ezrin phosphorylation levels were measured to determine activation status. The integrity of the airway epithelial barrier was assessed in vivo by characterizing morphological structure, and in vitro in BEAS-2B cells by measuring tight junction protein expression, transepithelial electrical resistance (TER) and permeability.Results: We demonstrated that ezrin expression levels were lower in the lung tissue and airway epithelium of diabetic mice than those in control mice. The morphological structure of the airway epithelium was altered in diabetic mice. High glucose levels downregulated the expression and distribution of ezrin and connexin 43, reduced the expression of tight junction proteins, and altered the epithelial barrier characteristics of BEAS-2B cells. Ezrin knockdown had effects similar to those of high glucose levels. Moreover, a specific inhibitor of ezrin Thr567 phosphorylation (NSC305787) inhibited epithelial barrier formation.Conclusion: These results demonstrate that ezrin expression and activation are associated with airway epithelial damage in diabetes mellitus. These findings provide new insights into the molecular pathogenesis of pulmonary infections in diabetes mellitus and may lead to novel therapeutic interventions for airway epithelial barrier damage.Keywords: morphological structure, bronchial epithelial cells, high glucose, tight junction, gap junction

Han Wu,1,&ast; Hui Wang,2,&ast; Lixia Sun,3,&ast; Mengchen Liu,1 Haoran Wang,1 Xianchang Sun,4 Wenjuan Zhang1 1Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, People’s Republic of China; 2Gynecological Minimally Invasive Surgery Center, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 3Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 4Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjuan Zhang, Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, 366 Taishan Street, Taian, 271000, People’s Republic of China, Email wenjuanzhang1119@163.com Xianchang Sun, Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan, 250117, People’s Republic of China, Email hotsss@163.comPurpose: To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS).Patients and methods: A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups.Results: The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype.Conclusion: Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.Keywords: angiopoietin-like protein 8, insulin resistance, metabolic disorder, obesity, polycystic ovary syndrome, single nucleotide polymorphism

Hao Wu, Qing-Jie Ji, Yu-Yang Xu, Jian-Wei Zhu Department of Dermatology, Quzhou TCM Hospital at the Junction of Four Provinces Affiliated to Zhejiang Chinese Medical University, Quzhou, People’s Republic of ChinaCorrespondence: Jian-Wei Zhu, Email zjwmed@163.comAbstract: Pityriasis rosea (PR) is a common inflammatory, erythematous and scaly skin condition that usually affects individuals aged from 20 to 40 years old. The disease often exhibits a self-limiting course up to 6– 8 weeks. We report a 25-year-old female patient with a six-month history of red scaly rashes on the trunk and proximal limbs, accompanied by severe pruritus that has been remained ineffective conventional treatments. She was diagnosed as persistent pityriasis rosea. As abrocitinib has been proved to be effective for many inflammatory diseases, therefore in this case, we tried abrocitinib for the patient, and a good result had been achieved.Keywords: pityriasis rosea, abrocitinib, JAK-STAT pathway

Jiayan Li,1,&ast; Jie Ding,1,&ast; Haoyang Wu,1 Chenyan Lu,1 Jian Wu,2 Qianqian Luo1 1Department of Hypoxic Biomedicine, Institute of Special Environmental Medicine and Coinnovation Center of Neuroregeneration, Nantong University, Nantong, 226019, People’s Republic of China; 2Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wu, Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, People’s Republic of China, Tel +86-21-54601295, Email jianwu12@fudan.edu.cn Qianqian Luo, Department of Hypoxic Biomedicine, Institute of Special Environmental Medicine and Coinnovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, People’s Republic of China, Tel +86-513-85503378, Email qianqianluo@ntu.edu.cnBackground: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite.Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin–eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue.Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated.Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice.Keywords: frostbite, Tat-CIRP, inflammation, angiogenesis

Yang Yang,1,2 Zongze Yao,1 Jiazhen Zhang,1 Wei Shao,3 Bo Li,2 Huihui Wu,2 Wenjian Tang,3 Jing Zhang2 1School of Medicine, Anhui University of Science and Technology, Huainan, People’s Republic of China; 2Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, People’s Republic of China; 3School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Wenjian Tang; Jing Zhang, Tel +86-551-63672601, Email ahmupharm@126.com; hfzj2552@163.comBackground: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of staph infection that is difficult to treat because of resistance to some antibiotics. A recent study indicated that diarylurea ZJ-2 is a novel antibacterial agent against multi-drug resistant Enterococcus faecium. In this work, we refined the bactericidal mechanism of ZJ-2 as a peptidoglycan (PG) hydrolase by affecting AtlA-mediated PG homeostasis.Methods: A wild-type strain (WT) and a mutant strain (ΔatlA) were used to investigate the effects of ZJ-2 on the cell wall, PG, and autolysin regulatory system by antimicrobial susceptibility testing, hemolytic toxin assay, microanalysis, autolysis assay, qRT-PCR, ELISA and mouse model of pneumonia.Results: The results revealed that ZJ-2 down-regulated the expression of genes related to peptidoglycan hydrolase (PGH) (sprX, walR, atlA, and lytM), and reduced the levels of PG, muramyl dipeptide (MDP), cytokines, and hemolytic toxin, while ΔatlA interfered with the genes regulation and PG homeostasis. In the mouse MRSA pneumonia model, the same trend was observed in the nucleotide oligomerization domain protein 2 (NOD2) and relative proinflammatory factors.Conclusion: ZJ-2 may act as a novel inhibitor of PG hydrolyse, disrupting autolysin-mediated PG homeostasis, and reducing inflammation by down-regulating the MDP-NOD2 pathway. Keywords: MRSA, peptidoglycan hydrolase, homeostasis, autolysis, NOD2

Qianyu Bai,1,&ast; Yichi Zhang,1,&ast; Runqiu Cai,1 Haiyan Wu,1 Huiqun Fu,2 Xuemei Zhou,2 Jie Chai,3 Xuepeng Teng,3 Tianlong Liu1 1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People’s Republic of China; 2 101 Institute of the Ministry of Civil Affairs, Beijing, People’s Republic of China; 3Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemei Zhou, 101 Institute of the Ministry of Civil Affairs, South Fourth Ring West Road No.188, Beijing, 100070, Email zxmcaur@126.com; Tianlong Liu, College of Veterinary Medicine, China Agriculture University, Yuanmingyuan West Road No. 2, Beijing, 100193, Email liutianlong@cau.edu.cnBackground: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed.Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs.Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 μg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs.Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.Keywords: nanoparticles, otitis media, zinc oxide, mesoporous titanium dioxide, antimicrobial peptide, antimicrobial, hydroxyl radical

Aineng Peng,1 Jianbo Chai,2 Haiyuan Wu,1 Bing Bai,3 Huihui Yang,1 Weizhi He,1 Yonghou Zhao2 1Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China; 2Heilongjiang Mental Hospital, Harbin, 150036, People’s Republic of China; 3Tongde Hospital of Zhejiang Province, Hangzhou, 311100, People’s Republic of ChinaCorrespondence: Yonghou Zhao, Heilongjiang Mental Hospital, 153 Hengdao Street, Harbin, Heilongjiang, 150036, People’s Republic of China, Tel +86 13904638645, Email zyszbx2020@126.comAbstract: Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects. The second generation of antipsychotics acts by dual blockade of 5-hydroxytryptamine and dopamine receptors. From the third generation of antipsychotics onwards, the therapeutic targets for antipsychotic schizophrenia expanded beyond D2 receptor blockade to explore D2 receptor partial agonism and the antipsychotic effects of new targets such as D3, 5-HT1A, 5-HT7, and mGlu2/3 receptors. The main advantages of the second and third generation antipsychotics over first-generation antipsychotics are the reduction of side effects and the improvement of negative symptoms, and even though third-generation antipsychotics do not directly block D2 receptors, the modulation of the dopamine transmitter system is still an important part of their antipsychotic process. According to recent research, several receptors, including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine receptors and norepinephrine, play a role in the development of schizophrenia. Therefore, the focus of developing new antipsychotic drugs has shifted towards agonism or inhibition of these receptors. Specifically, the development of NMDARs stimulants, GABA receptor agonists, mGlu receptor modulators, cholinergic receptor modulators, 5-HT2C receptor agonists and alpha-2 receptor modulators has become the main direction. Animal experiments have confirmed the antipsychotic effects of these drugs, but their pharmacokinetics and clinical applicability still require further exploration. Research on alternative targets for antipsychotic drugs, beyond the dopamine D2 receptor, has expanded the potential treatment options for schizophrenia and gives an important way to address the challenge of refractory schizophrenia. This article aims to provide a comprehensive overview of the research on therapeutic targets and medications for schizophrenia, offering valuable insights for both treatment and further research in this field.Keywords: schizophrenia, target, neurotransmitter, antipsychotic drugs

Chaoping Yang,1,&ast; Jing Xie,2,&ast; Qianjun Chen,2 Qiongyin Yuan,3 Jianping Shang,4 Haibo Wu,5 Youhua Yang,6 Mingfang Wang,7 Xiaolan Shu,8 Jing Yue,9 Danna Tu,10 Ying Lin,1,&ast; Ronghao Zheng,4,&ast; Xiaolin Wu4 1Nursing Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Obstetrical department, Huanggang Maternal and Child Health Hospital, Hubei, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5School of Health and Nursing, Wuchang University of Technology, Wuhan, People’s Republic of China; 6Department of Basic Medical Sciences, School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 7Department of Pediatric Gastroenterology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Pediatric Intensive Care Unit (PICU), Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Emergency Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 10Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu Luo Road, Hongshan District, Wuhan, Hubei Province, 430070, People’s Republic of China, Email hytwo2001@126.com Ying Lin, Nursing department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email 523933025@qq.comPurpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students.Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP.Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ± 26.32, 55.00 ± 12.50, and 71.88 ± 15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score > 80 points was an independent protective factor related to knowledge and practice.Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.Keywords: antibiotic use, antimicrobial resistance, knowledge, attitude, practice, nursing students

Wenying Yi,1,2 Haibo Wu,1,2 Weibin Fu,1,2 Huimei Feng,1,2 Jie Huang,1,2 Haijing Li,1,2 Zhen Song,1,2 Yuwei Chen,1,2 Yingjun Zheng,1,2 Shenglin She1,2 1Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shenglin She, Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou MedicalUniversity, No. 36 Mingxin Road, Liwan District, Guangzhou, People’s Republic of China, Tel +86-13825154669, Fax +86-20-82068107, Email shenglinshe@gzhmu.edu.cnBackground: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China.Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m2 was considered obese, and BMI < 25 kg/m2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University.Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients.Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia.Keywords: schizophrenia, NAFLD, non-obese, obese, risk factors, China

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

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

Fenge Li,1,2,&ast; Yupeng Wang,1,&ast; Jin Yan,1,&ast; Huancheng Wu,3 Xueming Du,1 Weihong Feng,1 Xiaoqing Zhang,4 Yongming Xue,4 Huaqing Wang,5,6 Wenxin Liu7 1Department of Oncology, Tianjin Beichen Hospital Tianjin People’s Republic of China; 2Core Laboratory, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 4Department of Basic Research, Suzhou Lanma Biotechnology Co, Suzhou, People’s Republic of China; 5Department of Oncology, Tianjin Union Medical Center, Tianjin, People’s Republic of China; 6Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 7Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxin Liu, Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, People’s Republic of China, Tel +8618622221101, Email wenxin1973@163.com Huaqing Wang, Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Jieyuan Road No. 190, Nankai District, Tianjin, People’s Republic of China, Tel +8618622221223, Email huaqingw@163.comIntroduction: Tumor-infiltrating lymphocytes (TILs) therapy is one of the most promising adoptive T cell therapies, which has shown great clinical efficacy against several solid malignancies. Nevertheless, clinical response to TILs mono-therapy in Asian patients with recurrent cervical cancer has not been well reported.Case Presentation: Here, we report two patients who were diagnosed with metastatic cervical cancer and tumor progression following multiple conventional treatments. In particular, one of the patients has a history of severe myelosuppression after chemotherapy. The patients received lymphodepletion therapy, which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m2) for 5 days, approximately 24 hr before receiving intravenous autologous TILs infusion. These two patients then received high doses of IL-2 for 10 days with the purpose of maintaining T cell survival and proliferation. Patient 1 experienced clinical partial response (PR) at 6 weeks post TILs infusion and a 33% tumor shrinkage at 12 weeks follow-up, and patient 2 was evaluated as stable disease (SD) at 6 weeks post treatment. Mild and manageable adverse events were observed and soon subsided after the TILs treatment. A time-course study examining the peripheral blood cell count and cytokine secretion demonstrated the persistence of infused TILs and long-term immune response.Conclusion: These results suggest that TILs mono-therapy can be a promising treatment strategy for Asian patients with late-stage metastatic cervical cancer even with severe myelosuppression. TILs infusion can induce persistence and a long-term systematic immune response that reversed peripheral CD4+T and CD8+T percentages implying that TILs infusion increased cytotic T cell responses, which is consistent with clinical responses in these patients. Trial registration number: NCT05366478.Keywords: tumor-infiltrating lymphocytes, clinical response, immune response, metastatic cervical cancer, treatment

Huifang Nie,1 Jinwen Ge,1,2 Kailin Yang,1 Zhuli Peng,1 Haihui Wu,1 Tong Yang,1 Zhigang Mei1 1Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Hunan Academy of Chinese Medicine, Changsha, Hunan, 410006, People’s Republic of ChinaCorrespondence: Zhigang Mei; Jinwen Ge, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China, Email meizhigang@hnucm.edu.cn; 001267@hnucm.edu.cnBackground: Ischemic stroke (IS) is a leading cause of mortality worldwide. Naotaifang III is a new Chinese herbal formula to treat IS. Previous studies have shown that Astragali Radix, Puerariae Lobatae Radix, Chuanxiong Rhizoma, and Rhei Radix Et Rhizoma in Naotaifang III were able to regulate the imbalance of intestinal microbiota during cerebral ischemia injury.Methods: Rats were randomly divided into sham operation group, normal control group, middle cerebral artery occlusion (MCAO) group, intestinal microbiota imbalance MCAO group, Naotaifang III group, and normal bacteria transplantation group, with 15 rats in each group. Then, neurological function scores and cerebral infarction volume were detected; haematoxylin and eosin staining and Golgi silver staining were used to observe morphological changes in brain tissue. Meanwhile, the lipopolysaccharide (LPS) and cerebral cortex interleukin (IL)-1β were detected by enzyme-linked immunosorbent assay (ELISA); the expressions of Toll-like receptor (TLR)-4 and nuclear factor kappa-B (NF-κB) proteins were detected by immunofluorescence and Western blot. The cecal flora was detected by 16S rDNA. The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1β, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis. In summary, Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis.Results: The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1β, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis.Conclusion: Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis. Keywords: Naotaifang III, ischemic stroke, intestinal microbiota, LPS/TLR4 signaling pathway, microbiota–gut–brain axis

Zupeng Xiao, Hanyi Wu, Xin Chen, Xiaoli Chen, Rentao Yu, Aijun Chen Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Aijun Chen; Rentao Yu, Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 13062377863; +86-18123303562, Email chenaijun@hospital.cqmu.edu.cn; rentaoyu@hotmail.comPurpose: Herpes zoster ophthalmicus (HZO) causes trouble in patients’ daily life and work. In severe cases, it may even lead to a decrease or loss of vision. To understand the demographic information and ocular symptoms of hospitalized patients with HZO, and to find potential factors related to improvement time of skin rash and duration of ocular symptoms at discharge, we design this study.Patients and Methods: This is a retrospective study. All patients diagnosed with HZO who were hospitalized in the Department of Dermatology of a hospital in Chongqing, China from January 1, 2015 to December 30, 2021 were included in this study. A total of 189 patients were included in this study. Clinical manifestations of the disease during hospitalization, improvement time of ocular skin lesions, and whether ocular skin lesions disappeared completely at discharge were recorded.Results: The most common ocular symptom was eyelid swelling (92.6%), followed by eye pain (48.7%). The most common ocular sign was conjunctivitis (78.3%), followed by keratitis (15.9%). There were 149 cases without residual ocular symptoms and 40 cases with residual ocular symptoms. There was no statistically significant difference in demographic characteristics between the two groups (P> 0.05). Age ≥ 70 years (B=0.381, − 0.061~0.022, P=0.005), use of glucocorticoids (B=0.260, 0.024~0.496, P=0.031), and use of topical antiviral drugs (B=0.380, 0.054~0.705, P=0.023) were factors affecting the time interval from admission to improvement of skin rash. Tearing (HR, OR=4.827, 1.956~11.909, P< 0.001) and blood urea nitrogen (OR=0.787, 0.620– 1.000, P=0.050) were factors influencing residual ocular symptoms.Conclusion: This study could help clinicians gain a deeper understanding of the clinical manifestations and partial influencing factors of HZO patients, which may contribute to future clinical work.Keywords: herpes zoster ophthalmicus, clinical manifestations, disease outcome, risk factors

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

Xing Li, Zhuyuan Zhang, Wen Cai, Xuexin Zhou, Yan Zhang, Cailiang Wu, Xianming Xu, Hao Wu Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of ChinaCorrespondence: Hao Wu; Xianming Xu, Email zhuwy2007@126.com; xuxm11@163.comBackground: The relationship of iron deficiency and thyroid hormone has been researched a lot among pregnant or other healthy population. However, invisible iron deficiency, namely shortage of serum ferritin (sFer) level, has been barely investigated among Chinese pregnant women. This study aimed to explore the effects of sFer status on thyroid function and pregnancy outcomes in a population-based upper first-class hospital.Methods: A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in this retrospective cohort study. The participants were divided into four groups by quartiles of serum ferritin levels (Q1– 4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across sFer quartiles. Categorical measures were compared by Fisher exact test or chi-square test.Results: As the sFer concentration rises, incidence of premature birth (15.8%vs 12.3% vs 9.20% vs 6.20% p = 0.016) as well as threatened miscarriage (14.8% vs 7.2% vs 8.70% vs 6.70% p = 0.021) presented a downward trend. Compared with the other sFer group, subjects of the low sFer group were older, more often to be found to have lower serum γT3 and FT4 levels in early pregnancy but not in middle pregnancy.Conclusion: sFer concentration in the first trimester can affect thyroid function. The correction of invisible iron deficiency with inadequate sFer status prior to pregnancy or during early pregnancy is imperative, not only to prevent anemia, but also for maintaining optimum thyroid function and normal fetal development. For clinicians, sFer status of pregnant women should be attached great importance apart from attention to iron level.Keywords: serum ferritin, thyroid hormone, subclinical hypothyroidism, thyroid-stimulating hormone, pregnant women

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

Zhijun Zhang,1,2 Tiehong Yang,2 Jingwei Wang,2 Zhe Yu,2 Youbei Qiao,2 Chaoli Wang,2 Zhenggang Yue,1 Hong Wu2 1School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, People’s Republic of China; 2Department of Medicine Chemistry and Pharmaceutical Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Hong Wu, Department of Medicine Chemistry and Pharmaceutical Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of China, Tel/Fax +86 29 84776823, Email wuhong@fmmu.edu.cn Zhenggang Yue, School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, People’s Republic of China, Tel +86 18092086211, Email liuxingjian1981@163.comPurpose: The remarkable peroxidase-like activity of single-atom nanozymes (SAzymes) allows them to catalyze the conversion of H2O2 to •OH, rendering them highly promising for antibacterial applications. However, their practical in vivo application is hindered by the near-neutral pH and insufficient H2O2 levels present in physiological systems. This study was aimed at developing a SAzyme-based nanoreactor and investigating its in vivo antibacterial activity.Methods: We developed a hollow mesoporous molybdenum single-atom nanozyme (HMMo-SAzyme) using a controlled chemical etching approach and pyrolysis strategy. The HMMo-SAzyme not only exhibited excellent catalytic activity but also served as an effective nanocarrier. By loading glucose oxidase (GOx) with HMMo-SAzyme and encapsulating it with hyaluronic acid (HA), a nanoreactor (HMMo/GOx@HA) was constructed as glucose-triggered cascade catalyst for combating bacterial infection in vivo.Results: Hyaluronidase (HAase) at the site of infection degraded HA, allowing GOx to convert glucose into gluconic acid and H2O2. An acid environment significantly enhanced the catalytic activity of HMMo-SAzyme to promote the further catalytic conversion of H2O2 to •OH for bacterial elimination. In vitro and in vivo experiments demonstrated that the nanoreactor had excellent antibacterial activity and negligible biological toxicity.Conclusion: This study represents a significant advancement in developing a cascade catalytic system with high efficiency based on hollow mesoporous SAzyme, promising the advancement of biological applications of SAzyme. Keywords: nanozyme, nanocarrier, glucose oxidase, reactive oxygen species, bacterial infection

Baixing Wei, Han Wu Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Han Wu, Department of Orthopedics, China-Japan Union Hospital of Jilin University, No. 126 Xi’antai Avenue, Changchun, Jilin, People’s Republic of China, Tel +86 43189876902, Email wu_han@jlu.edu.cnPurpose: To study the distribution of lumbar Modic changes (MC) in low back pain patients, and to explore the relationship between Modic changes and age, gender, segment and lumbar degeneration diseases (disc degeneration, spinal stenosis, lumbar spondylolisthesis).Patients and Methods: Modic changes were counted and analysed in 500 randomly selected patients who visited the outpatient clinic for lumbar spine MRI for low back pain from 2019 to 2022. The relationship between Modic changes and bulging disc, protrusion, extrusion, sequestration, Schmorl’s node, spinal stenosis, and lumbar spondylolisthesis was studied. Data correlations were compared using the chi-square test, P< 0.05 was considered a statistically significant difference.Results: Modic changes were present in 184 segments. 58 were type I, 119 were type II, and 7 were type III. The number of Modic changes segments in L1-2, L2-3, L3-4, L4-5, and L5-S1 was 10, 22, 22, 58, and 72, respectively. Modic changes by gender occurred in 44 males and 82 females, and by age grouping were 0 cases in 10– 19 years, 3 cases in 20– 29 years, 6 cases in 30– 39 years, 41 cases in 40– 49 years, 64 cases in 50– 59 years, 38 cases in 60– 69 years, 15 cases in 70– 79 years, and 5 cases in 80– 89 years, respectively. Modic changes occurred in 56 with bulging disc, 45 with Protrusion, 57 with Extrusion and Sequestration, 32 with Schmorl’s node, 32 with spondylolisthesis, and 56 with stenosis. Modic changes correlated with all of the above factors except bulging disc, and all differences were statistically significant (P< 0.05).Conclusion: The most common type of Modic changes is type II; Modic changes have correlation with age, gender, segment, lumbar disc herniation, lumbar spondylolisthesis, and lumbar spinal stenosis, and are a very important factor in low back pain.Keywords: low back pain, Modic changes, disc degeneration, spinal stenosis, lumbar spondylolisthesis

Jiao Sun,1,&ast; Lichao Fan,2,&ast; Yanping Zhao,3,&ast; Haoyu Wu,2 Ran Li,2 Yao Tian,2 Moxin Cheng,2 Xin Ma,1 Yingying Ma,1 Xinru Yang,1 Adong Shen,4 Yanhong Yu,1 Yu Chen2 1Tuberculosis Laboratory, Shenyang Tenth People’s Hospital/Shenyang Chest Hospital, Shenyang, People’s Republic of China; 2Department of Tuberculosis, Shenyang Tenth People’s Hospital/Shenyang Chest Hospital, Shenyang, People’s Republic of China; 3School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 4National Clinical Research Center for Respiratory Disease, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanhong Yu; Yu Chen, Email 438735174@qq.com; yuchensyxk@163.comObjective: Drug-resistant tuberculosis (DR-TB) in children seriously threatens TB control. Information on the epidemiology and characteristics of DR-TB in children in China is limited. We studied data in Shenyang Tenth People’s Hospital to understand the DR-TB epidemiology in children in Shenyang.Design or Methods: We retrospectively analyzed drug resistance testing data of pediatric TB patients between 2017 and 2021, and included 2976 clinically-diagnosed pediatric TB patients. We described the epidemiology of DR-TB and analyzed the trends of DR-TB incidence. The Kappa value was calculated to assess the agreement between MGIT 960 DST and Xpert MTB/RIF for detecting rifampicin resistance. Multivariate logistic regression was used to identify the risk factors for DR-TB in pediatric patients.Results: Of the 2976 TB patients, 1076 were confirmed by MGIT 960 culture and/or Xpert MTB/RIF. Among the 806 patients identified by MGIT 960 culture, 232 cases (28.78%) were DR-TB. Resistance to the six drugs was in the following order: streptomycin (21.09%), isoniazid (9.35%), rifampin (15.01%), levofloxacin (6.20%), ethambutol (4.22%), and amikacin (3.23%). Alarmingly, 12.90% were MDR-TB (104/806), including 28 (3.47%) pre-XDR-TB. Of the 1076 pediatric TB patients, 295 (27.4%) developed DR-TB to any one drug (including 69 rifampicin-resistant cases identified by Xpert MTB/RIF only). No difference was found in the incidence of pediatric DR-TB between 2017 and 2021. Among 376 patients who were positive for both methods, using the MGIT 960 DST results as the gold standard, Xpert MTB/RIF’s sensitivity for detecting rifampicin resistance was 91.38% and its specificity was 94.65%.Conclusion: Between 2017 and 2021, the DR-TB incidence in children remained unchanged in Shenyang. RR-TB, MDR-TB, and even Pre-XDR-TB require attention in children with drug-resistant TB. Xpert MTB/RIF helped to detect more rifampicin-resistant pediatric patients; thus Xpert MTB/RIF should be widely used as an important complementary tool to detect rifampicin-resistant TB in children.Keywords: tuberculosis, drug-resistant, children, rifampicin, Xpert MTB/RIF, drug susceptibility testing

Hao Wu,1,2,&ast; Qianyu Chen,2,3,&ast; Yanxin Liu,4 Yingdan Tang,5 Yang Zhao,5 Xueying Zhang,6 Xun Chen,2 Xiaoyan Ying,1 Boqun Xu1 1Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Obstetrics and Gynecology, the Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Obstetrics and Gynecology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 4Department of Obstetrics and Gynecology, Pukou Branch of Jiangsu People’s Hospital, Nanjing, Jiangsu, People’s Republic of China; 5Department of Statistics, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boqun Xu, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, Jiangsu, 210000, People’s Republic of China, Tel +86-13805164016, Email boqun_xu@njmu.edu.cnObjective: The purpose is to establish a model to predict endometrial carcinoma and assess its value in the preliminary diagnosis of endometrial carcinoma.Methods: The data of 381 patients undergoing hysteroscopy were incorporated into the model, including 282 cases in the training cohort and 99 cases in the validation cohort. Significant morphological indexes were selected using the chi-square test and subjected to the binary logistic regression analysis. Besides, the scoring interval was set, and the nomogram of the prediction model was established. Model calibration curves were drawn using the data from the validation cohort. The study was approved by the Ethics Committee of the Affiliated Sir Run Run Hospital of Nanjing Medical University, and written informed consent was obtained from the patients.Results: The sensitivity, specificity, positive predictive value, and negative predictive value of the model were 96.7%, 92.3%, 77.3%, and 99.0%, respectively. Analysis of the receiver operating characteristic curve in the training cohort showed an area under the curve of 0.984 (95% CI: 0.974– 0.995). The receiver operating characteristic curve in the validation cohort revealed an area under the curve of 0.976 (95% CI: 0.950– 1.000). The calibration curve indicated that the probability in the actual setting was consistent with that predicted by the nomogram in the training cohort.Conclusion: Our model has high sensitivity and specificity in predicting endometrial carcinoma, and helps clinicians to make accurate diagnosis.Keywords: hysteroscopy, endometrial carcinoma, morphology, prediction model

Yanqi Song,1 Yeqing Gu,2 Honglei Guo,3 Honghao Yang,4– 6 Xuena Wang,4– 6 Hongmei Wu,4– 6 Aidi Wang,1 Haijin Wang,1 Quan Zhang,1 Qing Zhang,7 Li Liu,7 Ge Meng,6 Baoshan Liu,1 Kaijun Niu4– 6 1Department of Traditional Chinese Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of China; 3School of Graduate, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4School of Public Health, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 6Nutritional Epidemiology Institute, Tianjin Medical University, Tianjin, People’s Republic of China; 7Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Kaijun Niu, Nutritional Epidemiology Institute, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, People’s Republic of China, Tel +86-22-83336613, Email nkj0809@gmail.com; niukaijun@tmu.edu.cn Baoshan Liu, Department of Traditional Chinese Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Tel +86-22-60362808, Email lbs-cd@163.comPurpose: The prevalence of benign prostatic hyperplasia (BPH) in the general Chinese adult male population has risen sharply over the past few decades. Increasing evidence suggests that inflammation plays an important role in the pathogenesis of BPH. To better understand the role of inflammation in the pathogenesis of BPH, we can use the neutrophil-to-lymphocyte ratio (NLR) because it is a simple and effective marker of inflammation and immunity. This study aims to prospectively investigate the association between NLR levels and the prevalence of BPH in a general Chinese adult male population.Patients and Methods: This study included a total of 15,783 male participants free from BPH at baseline. NLR was measured according to the complete blood count. BPH was defined as total prostate volume (TPV) ≥ 30 mL, and TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels.Results: During a median follow-up of 2.7 years, 5078 BPH cases were documented. After adjusting for age, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, and inflammation markers, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.08 (95% CIs 0.99, 1.17), 1.10 (95% CIs1.02, 1.19), and 1.12 (95% CIs1.03, 1.21), respectively, for participants with NLR in the first, second, third, and fourth quartiles (P for trend < 0.01).Conclusion: Higher NLR levels were associated with a higher risk of BPH in Chinese adult male population. Our findings support the notion that NLR levels may be an important target for BPH prevention and intervention.Keywords: neutrophil to lymphocyte ratio, inflammation, benign prostatic hyperplasia, prospective cohort study

MinChao Feng,1,&ast; Fang Luo,1,&ast; HuiMin Wu,1 Yushan Chen,1 Jinjin Zuo,1 Xueying Weng,1 Guozhong Chen,2 Jian Zhong3 1The First Clinical Medical College, Guangxi University of Traditional Chinese Medicine, Nannig, People’s Republic of China; 2Department of Gastroenterology, the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China; 3Department of Nephrology, the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhong, Department of Nephrology, the First Affiliated Hospital of Guangxi University of traditional Chinese Medicine, No. 89-9, Dong Ge Lu, Xixiangtang District, Nanning, 530023, People’s Republic of China, Tel +86-18677920877, Email 18922005825@163.comPurpose: YiShen HuoXue decoction (YSHXD) is a formulation that has been used clinically for the treatment of renal fibrosis (RF) for many years. We aimed to clarify therapeutic effects of YSHXD against RF and potential pharmacological mechanisms.Materials and Methods: We used network pharmacology analysis and machine-learning to screen the core components and core targets of YSHXD against RF, followed by molecular docking and molecular dynamics simulations to confirm the reliability of the results. Finally, we validated the network pharmacology analysis experimentally in HK-2 cells and a rat model of RF established by unilateral ureteral ligation (UUO).Results: Quercetin, kaempferol, luteolin, beta-sitosterol, wogonin, stigmasterol, isorhamnetin, baicalein, and dihydrotanshinlactone progesterone were identified as the main active components of YSHXD in the treatment of unilateral ureteral ligation-induced RF, with IL-6, IL1β, TNF, AR, and PTGS2 as core target proteins. Molecular docking and molecular dynamics simulations further confirmed the relationship between compounds and target proteins. The potential molecular mechanism of YSHXD predicted by network pharmacology analysis was confirmed in HK-2 cells and UUO rats. YSHXD downregulated NLRP3, ASC, NF-κBp65, Caspase-1, GSDMD, PTGS2, IL-1β, IL-6, IL-18, TNF-α, α-SMA and upregulated HGF, effectively alleviating the RF process.Conclusion: YSHXD exerts important anti-inflammatory and anti-cellular inflammatory necrosis effects by inhibiting the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway, indicating that YSHXD represents a new strategy and complementary approach to RF therapy.Graphical Abstract: Keywords: pyroptosis, YiShen HuoXue decoction, renal fibrosis, molecular docking simulation, machine-learning