Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Malignant tumors(commonly referred to as cancer)represent a major global public health challenge and contribute significantly to the worldwide disease burden.Early screening plays a critical role in improving detection rates,enabling timely intervention,and enhancing pa-tient survival rates.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifical-ly rational,multi-cancer screening approach offers several advantages:it optimizes the use of bio-logical samples,reduces time costs for participants,enhances the efficiency and comprehensive-ness of screening,and minimizes overall expenses.Such an approach also facilitates the rational allocation of healthcare resources,ultimately helping to reduce the societal burden of cancer.To address this need,the Cancer Epidemiology Committee of the Chinese Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers in China.This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and interna-tional researches on cancer screening,early detection,and treatment for prevalent malignancies.Drawing upon China's unique demographic and healthcare context,as well as practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the principles and methodologies established by the World Health Organization(WHO),aiming to:enhance the effectiveness of combined cancer screening in China,improve early detec-tion rates,and provide a scientific foundation for national cancer prevention and control strategies.

Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Malignant tumors (commonly referred to as cancer) represent a major global public health challenge and contribute significantly to the worldwide disease burden. Early screening plays a critical role in improving detection rates, enabling timely intervention, and enhancing patient survival rates. However, current cancer screening guidelines primarily focus on site-specific screening, which may not fully address the need for comprehensive early detection. A scientifically rational, multi-cancer screening approach offers several advantages: it optimizes the use of biological samples, reduces time costs for participants, enhances the efficiency and comprehensiveness of screening, and minimizes overall expenses. Such an approach also facilitates the rational allocation of healthcare resources, ultimately helping to reduce the societal burden of cancer. To address this need, the Cancer Epidemiology Committee of the Chinese Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers in China. This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and international researches on cancer screening, early detection, and treatment for prevalent malignancies. Drawing upon China's unique demographic and healthcare context, as well as practical screening experiences, the consensus provides evidence-based recommendations on target populations, screening technologies, and procedural workflows for multi-cancer screening. These guidelines align with the principles and methodologies established by the World Health Organization (WHO), aiming to enhance the effectiveness of combined cancer screening in China, improve early detection rates, and provide a scientific foundation for national cancer prevention and control strategies.

Malignant tumors(commonly referred to as cancers)represent a major global public health challenge and contribute substan-tially to the global disease burden.Early screening plays a crucial role in improving detection rates,enabling timely intervention,and enhan-cing patient survival.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifically rational,multi-cancer screening approach offers several advantages:it optimizes the use of biological samples,reduces the time burden for participants,enhances the efficiency and comprehensiveness of screening,and min-imizes overall expenses.Moreover,this approach facilitates rational allocation of healthcare resources,ultimately helping to reduce the soci-etal burden of cancer.To address gap,the Cancer Epidemiology Committee of the China Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers.This consensus integrates multidisciplinary expertise and synthesizes the latest do-mestic and international researches on cancer screening,early detection,and treatment of prevalent malignancies.Drawing upon China's unique demographic and healthcare context and practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the prin-ciples and methodologies established by the World Health Organization(WHO),aiming to enhance the effectiveness of combined cancer screening in China,improve early detection rates,and provide a scientific foundation for national cancer prevention and control strategies.

With the rapid advancement and iterative development of new artificial intelligence technologies, there remains a regulatory vacuum in corresponding governance measures among governments worldwide. Simultaneously, a technological and governance gap exists between developing countries and developed economies. In response, the World Health Organization (WHO) has released "Ethics and Governance of Artificial Intelligence for Health: Guidance on Large Multi-Modal Models" to assist governments in strengthening governance capabilities in this field. This paper provides an in-depth analysis of the Guidance, aiming to identify challenges and risks associated with the application of multimodal large models in healthcare. Guided by ethical principles for advancing health through artificial intelligence, the paper examines the three-tier governance framework and recommendations outlined in the Guidance. Additionally, it evaluates the current state of AI governance in China, offering insights and reference points for improving AI governance in China′s healthcare sector.

Objective:To study the impact of fluoride exposure through drinking water on the risk of hypertension among residents in Jishan County, Shanxi Province.Methods:From March to April 2023, a cluster sampling method was used to select permanent residents aged ≥18 years and residing for ≥10 years in 12 villages in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province as the survey subjects. A questionnaire survey, physical examination, and morning urinary fluoride level testing were conducted. The least absolute shrinkage and selection operator (Lasso) regression were used to analyze the key influencing factors of hypertension. Restricted cubic spline was used to evaluate the linear relationship between urinary fluoride and hypertension. Logistic regression was used to analyze the impact of urinary fluoride on hypertension.Results:Finally, 2 453 survey subjects were included, aged (62 ± 10) years, including 1 565 patients (63.80%) with hypertension. There were significant differences in the distribution of age, gender, education level, annual household income, body mass index (BMI), and the level and distribution of urinary fluoride between hypertension group and normal blood pressure group ( P < 0.05). The Lasso regression results showed that age, education level, BMI, and urinary fluoride were the key influencing factors of hypertension, with coefficients of 1.04, - 0.12, 0.24 and 0.01, respectively. The results of the restricted cubic spline showed that there was a linear relationship between urinary fluoride and hypertension after adjusting for age, education level, and BMI ( Poverall = 0.018, Pnonlinear = 0.482). The logistic regression results showed that after adjusting for age, education level, and BMI, urinary fluoride > 4.68 mg/L was a risk factor for hypertension ( OR = 1.42, 95% CI: 1.10 - 1.84, P = 0.007). Conclusion:High urinary fluoride is a risk factor for hypertension in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province.

Objective:To investigate the predictive value of tumor morphology in hepatoce-llular carcinoma (HCC) immunotherapy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinical data of 227 HCC patients who underwent immunotherapy in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to December 2023 were collected. There were 203 males and 24 females, aged (57±11)years. Of the 227 patients, 93 patients with regular tumor morphology of HCC evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) were divided into the regular morphology group, and 134 patients with irregular tumor morphology of HCC evaluated by CT or MRI were divided into the irregular morphology group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) analysis of factors affecting prognosis of patients; (3) prognosis of patients after propensity score matching. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The Log-rank test was used for survival analysis. The Cox proportional hazards regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, with a caliper value of 0.02. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 227 HCC patients undergoing immunotherapy, 164 cases were successfully matched, including 82 cases in the regular morphology group and 82 cases in the irregular morphology group. After propensity score matching, the elimination of patients who underwent radical surgical resection in the past, tumor number and alpha fetoprotein confounding bias ensured comparability between the two groups. (2) Analysis of factors affecting prognosis of patients. Results of multivariate analysis showed that body mass index ≥25 kg/m 2 and irregular tumor morphology were independent risk factors affecting overall survival time of patients ( hazard ratio=0.891, 1.870, 95% confidence interval as 0.825-0.963, 1.151-3.038, P<0.05). (3) Prognosis of patients after propensity score matching. After propensity score matching, the median progression-free survival time was 11.9(95% confidence interval as 9.2-16.1)months for patients in the regular tumor morphology group and 6.4(95% confidence interval as 4.4-8.1)months for patients in the irregular tumor morphology group, the 1-year progress-free survival rate was 48.48% for patients in the regular tumor morphology group and 22.25% for patients in the irregular tumor morphology group. There was a significant difference in progress-free survival between patients in the regular tumor morphology group and the irregular tumor morphology group ( χ2=16.000, P<0.05). The median overall survival time was 27.2(95% confidence interval as 23.7-not reached)months for patients in the regular tumor morphology group and 18.1 (95% confidence interval as 15.8-20.8)months for patients in the regular tumor morphology group, the 1-year overall survival rate was 83.27% for patients in the regular tumor morphology group and 66.98% for patients in the irregular tumor morphology group. There was a significant difference in overall survival between patients in the regular tumor morphology group and the irregular tumor morphology group ( χ2=13.400, P<0.05). Conclusions:Tumor morphology has a predictive value for the efficacy of immunotherapy for HCC. Compared with HCC patients of regular tumor morphology, immunotherapy is less effective in patients with irregular tumor morphology.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

Objective To map the super-enhancers remodeling of intestinal gastric cancer and reveal the tumor biological functions of the super-enhancers and the downstream target genes that may be activated.Methods A total of 31 normal gastric mucosal tissues,23 intestinal gastric cancer tissues and 9 intestinal gastric cancer organoids were collected from the Department of Gastroenterology of Army Medical Center of PLA from January to December 2022.Chromatin targeting histone H3K27ac modified chromatin targeting cleavage under targets and tagmentation(CUT&Tag)sequencing was conducted on above tissues.The remodeling profiles of super-enhancers in intestinal gastric cancer were analyzed and the key target genes were identified based on bioinformation tools.CRISPRi technology was used to intervene with the super-enhancers,the expression of target genes was detected with Western blotting,and the proliferation,migration and invasion abilities were detected by CCK-8 assay and Transwell chambers in the control group and the intervention group.Results There was a significant difference in the signal of super-enhancers between intestinal gastric cancer tissues and normal gastric mucosal tissues(P<0.05),and the active super-enhancers in cancer tissues may be involved in biological processes such as negative regulation of the immune system and cell adhesion.The expression of up-regulated cell migration-inducing protein(CEMIP)in tumor cells was regulated by the super-enhancers,and intervening the super-enhancers down-regulated the expression of CEMIP(P<0.05),and inhibited the cell proliferation,invasion and migration abilities of tumor cells(P<0.05).Conclusion Super-enhancer remodeling is observed in intestinal gastric cancer,and they can up-regulate the expression of CEMIP gene and promote the growth,migration and invasion of cancer cells.