Hao Chen

To analyze the global trends, drivers, and health inequalities of non-alcoholic fatty liver disease (NAFLD) burden to identify key predictors of NAFLD-related mortality. Using data from the Global Burden of Disease (GBD) Study 2021, we extracted global measures of NAFLD from 1990 to 2021, and the trends were analyzed using joinpoint regression. Decomposition analysis was used to quantify the contributions of population growth, aging, and epidemiological changes. The health inequality was assessed using the concentration index. Using XGBoost-SHAP machine learning, the mortality predictors were identified, and two-sample Mendelian randomization was employed to test the causality for the key factors. All the analyses were conducted with data stratification by sex and the socio-demographic index (SDI). The global age-standardized disability-adjusted life years (DALYs) rate showed an increasing trend in both males (average annual percentage change [AAPC]=+0.34%) and females (AAPC=+0.05%). Decomposition analysis revealed that population growth was the primary driver of the global increase in DALYs, while population aging contributed to 52.37% of male deaths in high-SDI regions. Health inequality analysis showed a concentration index of -0.05 for DALYs in 2021, indicating a concentration of burden among low-SDI populations. Machine learning identified smoking (relative importance=100%) and advanced age (70-74 years: 60%) as the most critical predictors of mortality, and the model demonstrated good fit on the test set (R²=0.98). SDI-stratified analysis showed smoking and aging are the top two predictors across all SDI regions. Mendelian randomization further confirmed positive causal associations of smoking initiation (OR=1.35, PP<0.05) with NAFLD risk. NAFLD burden is heavy globally with significant sex and socioeconomic inequalities. Smoking and advanced age are key risk factors for NAFLD, calling for integrated interventions for tobacco control, geriatric health management, and health equity promotion.

Introduction: Colorectal cancer (CRC) remains a globally prevalent and lethal malignancy, with ferroptosis emerging as a novel cell death mechanism. This study aimed to elucidate the role of key genes in ferroptosis regulation and their impact on CRC malignancy.Methods: Using bioinformatics and experimental methods, we identified TIMP1 as an oncogene that may promote CRC progression via ferroptosis, a pathway implicated in diverse diseases. TIMP1 expression was analyzed in TCGA CRC datasets and validated using the UALCAN database.Results: TIMP1 was demonstrated as a critical ferroptosis-related gene in CRC, with elevated expression correlating with advanced pathological staging. Immunohistochemistry demonstrated significantly higher TIMP1 levels in CRC tissues compared to healthy controls. Functional assays revealed that TIMP1 knockdown enhanced ferroptosis sensitivity, suppressed CRC cell proliferation and migration, and reduced expression of ferroptosis regulators GPX4 and SLC7A11.Conclusion: These findings indicate that TIMP1 drives CRC malignancy through ferroptosis modulation, positioning TIMP1 as a potential therapeutic target and offering novel insights for CRC-targeted therapies.

Cardiac microvascular endothelial cells (CMECs) are important cells surrounding the cardiomyocytes in the heart that maintain microenvironment homeostasis. Salvianic acid A sodium (SAAS) has been reported to prevent myocardial infarction (MI) injury. However, the role of SAAS on CMEC proliferation remains unclear. CEMCs exposed to oxygen glucose deprivation (OGD) were used to explore the angiogenic abilities of SAAS. In vivo, C57BL/6 mice were divided into three groups: sham, MI and SAAS + MI groups. Compared to OGD group, SAAS led to a reduction in the apoptotic rate and an increase of the proliferation in vitro. Additionally, SAAS increased the protein levels of Bcl2, HIF‐1α and vascular endothelial growth factor (VEGF) with the reduction of Bax. In terms of the specific mechanisms, SAAS might inhibit HIF‐1α ubiquitination and enhance the HIF‐1α/VEGF signalling pathway to increase CMEC proliferation. Furthermore, SAAS increased the density of vessels, inhibited myocardial fibrosis and improved cardiac dysfunction in vivo. The present study has revealed that SAAS could potentially be used as an active substance to facilitate CMEC proliferation post‐MI.

探究UBE2S在肝癌微环境不同细胞类型的特异性表达及对肝癌细胞干性的影响。 使用TCGA数据库分析肝癌中UBE2S转录水平及其启动子甲基化水平差异，使用CPTAC数据库分析UBE2S蛋白水平差异。使用TISCH单细胞测序数据挖掘UBE2S在不同细胞类型中的表达，并分析细胞通讯的强度以及细胞群各自的关键转录因子。免疫组化验证UBE2S在肝癌组织中的表达；多色免疫荧光检测UBE2S在肝癌细胞以及T细胞的表达情况。利用shRNA敲低肝癌细胞HCC-LM3中的UBE2S，分为shCtrl（对照组）、shUBE2S-1（敲低组1）、shUBE2S-2（敲低组2）3个组，利用克隆形成实验、悬浮成球实验检测UBE2S敲低对HCC-LM3干性影响。 UBE2S在TCGA数据库中非配对肿瘤组织中高表达（P < 0.001），配对肿瘤组织中也高表达（P < 0.001），随着肿瘤分级增高，转录水平逐渐增高（P < 0.001）；在CPTAC数据库中肝癌组织UBE2S蛋白水平表达也增高（P < 0.001）；肝癌中UBE2S启动子甲基化水平降低（P < 0.001）；TP53突变组UBE2S转录水平更高（P < 0.001）。单细胞测序结果显示，UBE2S在T细胞等细胞群高表达；内皮与上皮及成纤维细胞之间的细胞交互强度较高，SMAD1等转录因子可能是Tprolif细胞关键转录因子。与正常组织相比，UBE2S在肝癌组织高表达；且在肝癌细胞和T细胞中均有较高表达。克隆形成实验显示：与shCtrl组相比，敲低UBE2S能减少肝癌细胞克隆形成数目（shUBE2S-1，P < 0.05、P < 0.01；shUBE2S-2，P < 0.01、P < 0.05）；悬浮成球实验显示：与shCtrl组相比，敲低UBE2S能减少肝癌细胞肿瘤球形成数目（shUBE2S-1，P < 0.05、P < 0.01；shUBE2S-2，P < 0.01、P < 0.01）。 UBE2S在肝癌组织T细胞中高表达，与预后不良相关，且其能促进肝癌细胞干细胞特性。

Objective: To investigate the characteristics of workers with occupational benzene poisoning in Jiangsu Province during 2006-2018, find out the susceptible population of occupational benzene poisoning and provide some evidence for establishing some exposure standards for workers. Methods: Questionnaire is the tool that we adopt to collect basic information of workers. Benzene detector is applied to detect the concentration of benzene in the working environments. Statistical description and analysis was conducted to analyze the prevalence of occupational benzene poisoning in Jiangsu Province during 2006-2018. Results: The number of cases of occupational benzene poisoning in these years was 145, and 28 of them were diagnosed with benzene induced leukemia; the patients mainly worked in manufacturing industry (89.7%); most of cases were distributed in small factories (43.4%) and private companies (46.2%). Male workers took a major part in the cases of acute benzene poisoning(80%)while female workers had a higher proportion of the chronic benzene poisoning (65%). Most cases were distributed in the 30-49 age group (80%). There was no evident differences among these seniority groups, most of the cases were in the working age of 1-19 years old (82.9%); concentration of benzene of chronic benzene poisoning workers were mostly under 0.6mg/m³ (40%). Conclusions: The departments of occupational disease prevention should heighten the benzene surveillance of small-scale private companies in manufacturing industry, regular physical examination and health education should be conducted in the workers of low concentration of benzene exposure, safety protection measures should be taken to reduce the incidence of occupational poisoning. Keywords: occupational disease; occupational benzene poisoning; benzene induced leukemia