Objective: To understand the prevalence of dental caries and its influencing factors among primary and middle school students in the Xinjiang Production and Construction Corps (hereinafter referred to as "the Corps"), so as to provide a reference for formulating targeted prevention strategies and promoting oral health of primary and middle school students. Methods: Primary and middle school students in the Corps were selected as survey subjects by a multi-stage stratified random cluster sampling method in September 2023. Basic information and dietary behaviors were collected through questionnaire surveys, and dental caries status was examined by oral health technicians. Multivariable logistic regression model was used to analyze the influencing factors of dental caries among primary and middle school students. Results: A total of 80 370 primary and middle school students were investigated, including 40 582 males (50.49%) and 39 788 females (49.51%). There were 37 608 primary school students (46.79%), 34 612 junior high school students (43.07%), and 8 150 senior high school students (10.14%). There were 26 669 students with dental caries, with a prevalence rate of 33.18%. Multivariable logistic regression analysis showed that the risk of dental caries was higher among female students (OR=1.170, 95%CI: 1.136-1.206), students in suburban counties (OR=1.212, 95%CI: 1.166-1.258), boarding students (OR=1.306, 95%CI: 1.257-1.357), and those with a frequency of fried food intake ≥1 time per day (OR=1.175, 95%CI: 1.084-1.273). Conversely, the risk of dental caries was lower among middle school students (OR=0.542, 95%CI: 0.524-0.560), high school students (OR=0.661, 95%CI: 0.620-0.705), and those with a frequency of vegetable intake ≥1 time per day (1 time per day, OR=0.900, 95%CI: 0.838-0.967), (≥2 time per day, OR=0.879, 95%CI: 0.819-0.944), and those who sometimes ate breakfast (OR=0.907, 95%CI: 0.874-0.942). Conclusions The prevalence of dental caries among primary and middle school students in the Corps is relatively high, and is influenced by various factors such as gender, school stage, area, boarding status, and dietary behaviors. It is suggested to strengthen oral health knowledge education among students, conduct regular oral health examinations, and improve the overall level of oral health.

As a novel long-acting glucagon-like peptide-1 （GLP-1） receptor agonist， semaglutide plays a pivotal role in the treatment of obesity and related metabolic diseases. This article systematically reviews the research progress of semaglutide in the treatment of obesity and related metabolic diseases from three aspects： mechanism of action， clinical applications， and existing challenges. It is found that its mechanism of action involves multi-organ synergistic regulation and metabolic intervention. Its clinical applications encompass the treatment of obesity， diabetes， polycystic ovary syndrome， and liver-related metabolic syndromes， and it demonstrates groundbreaking value in cardiovascular and renal protection. However， it still faces multiple challenges in terms of adverse reactions， individualized treatment， economic accessibility， ethical controversies， and risks. In the future， it is essential to further accumulate long-term safety data on semaglutide， optimize combination treatment regimens， and address key issues such as individualized medication for special populations， in order to fully realize its clinical application value.

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

Neurodegenerative disorders (NDDs) are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations. Increasing evidence suggested that mitochondrial quality control (MQC) serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria. Herein, we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs, emphasizing mitochondrial dynamic stability, the clearance of damaged mitochondria, and the generation of new mitochondria. In addition, traditional Chinese medicines (TCMs) and their active monomers targeting MQC in NDD treatment have been demonstrated. Consequently, we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC, aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

Objective To draw the genome-wide distribution and remodeling characteristics of H3K27me3 silencers in signet-ring cell carcinoma of the stomach(SRCC)through epigenetic sequencing technology,and to investigate their roles in transcriptional regulation in order to elucidate the regulatory mechanism of SRCC malignant progression.Methods The study was conducted on 35 gastric samples obtained by gastroendoscopic biopsy(15 normal and 20 SRCC tissues)from Department of Gastroenterology of Army Medical Center of PLA between January 2021 and December 2023.Multi-omics analyses,including assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq),cleavage under targets and tagmentation(CUT&Tag)and transcriptome sequencing(RNA-seq),were performed to identify chromatin accessibility,H3K27me3 silencer regions,and transcriptional changes,with aid of Illumina NovaSeq 6000.H3K27me3 related differentially expressed genes(|Log2FC|>1,FDR<0.05)were screened using DESeq2.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were employed to analyze the enrichment function,and Homer was employed to identify transcription factor motifs.A regulatory network was constructed using Cytoscape,and then validated using immunohistochemistry to explore its regulatory mechanism.Results H3K27me3 silencers were primarily located in distal intergenic regions(37.06%)in SRCC.Compared with the normal tissues,SRCC showed a significant reduction in H3K27me3 silencer signals(95%CI:1.34～2.30,P=0.007)with 6 257 lost sites(FDR<0.01).Integrating CUT&Tag and RNA-seq revealed 380 up-regulated immune-related genes,particularly in T cell receptor signaling(OR=4.2,95%CI:2.8～6.3,P=0.002).Immunohistochemistry confirmed elevated expression of transcription factor EHF(P<0.05).Conclusion There is the remodeling of H3K27me3 silencers in SRCC,and EHF may potentially play a crucial role in the SRCC malignant progression.

Objective To identify the enhancer profile marked by histone H3K27ac modification in high-grade intraepithelial neoplasia(HGIN)in order to reveal the novel regulatory mechanism of HGIN pathogensis.Methods Gastric tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA between June 2022 and June 2023,including 14 normal gastric tissues(Nor group),31 HGIN tissues(HGIN group)and 17 gastric cancer tissues(GC group).Cleavage under targets and tagmentation(CUT&Tag)technique was employed to capture enhancer regions modified by histone H3K27ac.Multi-omics analysis was performed to identify HGIN-specific active enhancers and their potentially regulated genes.Immunohistochemical profiling was performed to assess differential expression of the gene of interest across clinically stratified specimens,combined with CRISPR-dCas9-mediated ablation of active enhancers to monitor the gene of interest transcriptional dynamics and validate enhancer-mediated regulatory mechanisms.Results Epigenomic sequencing obtained the data with excellent quality,and indicated that obvious remodeling was observed in H3K27ac enhancers in HGIN and GC groups(P<0.05),though no significant difference in the genome-wide distribution of H3K27ac modification among the 3 groups.Combining transcriptome data revealed that enhancer remodeling may up-regulate the expression of the proliferation-related target gene,CD24,in the HGIN tissue;while,inhibiting enhancer activity can notably reduce CD24 expression level(P<0.05).Immunohistochemical assay displayed a positive correlation between the expression levels of CD24 and Ki-67(P<0.001).Conclusion The remodeling of H3K27ac enhancer represents a significant epigenetic feature of the transformation from normal condition to HGIN.Remodeling of H3K27ac enhancer up-regulates CD24,which may facilitate the abnormal proliferation of gastric epithelial cells.

Objective To analyze clinical characteristics of mesenchymal-subtype gastric cancer(Mes-GC)by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.Methods Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023.Transcriptome and genome sequencing were applied for these tissue samples,including 19 cases of diffuse-type gastric cancer,22 cases of intestinal-type gastric cancer,and 23 cases of mixed-type gastric cancer patients.Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer(non-Mes-GC)by integrating data resources including The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and National Genomics Data Center(NGDC).Results Compared to non-Mes-GC patients,Mes-GC ones were characterized by later clinical stages,deeper tumor infiltration,and higher rates of lymph node metastasis.Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time,poor prognosis as well as increased risk of cancer recurrence(P<0.05).Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness,metastasis(P<0.05),and epithelial-mesenchymal transition(EMT).And in the tumor microenvironment,there were significant more myeloid cells,smooth muscle cells,endothelial cells and fibroblasts,with the most pronounced elevation in the proportion of fibroblasts(P<0.05).Moreover,the patients with larger proportion of fibroblasts were associated with poorer prognosis.Conclusion Mes-GC tumor cells exhibit higher stemness and EMT characteristics,and stromal cells such as myeloid cells,endothelial cells,and fibroblasts are enriched in the tumor microenvironment.These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

Objective To determine the expression level of TG-interacting factor 1(TGIF1)in gastric cancer(GC)and its correlation with prognosis,and investigate the characteristics of immune microenvironment of TGIF1-overexpressing GCs and its clinical significance.Methods Integrated analysis was performed using transcriptomic data from The Cancer Genome Atlas(TCGA),Asian Cancer Research Group(ACRG),and our in-house GC transcriptome database.Immunohistochemistry(IHC)assay was employed to compare TGIF1 expression between GC and normal gastric mucosa tissues.Based on Kaplan-Meier Plotter online database,the correlation between TGIF1 expression and clinical prognosis was evaluated.Transcriptomic data were analyzed to identify functional enrichment features of GC with high TGIF1 expression.The GENIE3 toolkit and STRING database were utilized to predict TGIF1-regulated target genes and protein-protein interaction(PPI)networks,respectively to explore the potential immune-related signaling pathways regulated by TGIF1.Single-cell RNA sequencing(scRNA-seq)was applied to analyze the association between TGIF1 expression and tumor microenvironment(TME)disorder.Results Transcriptomic analysis revealed significantly higher TGIF1 expression in GC tissues compared to normal tissues(P<0.01).Patients with high TGIF1 expression exhibited poorer clinical prognosis(P<0.05).IHC assay confirmed elevated TGIF1 expression in GC tissues than normal tissues(P<0.01).GC with high TGIF1 expression was enriched in immune regulatory pathways,including immunosuppressive cytokines such as chemokine C-C motif ligand 20(CCL20).These tumors displayed an immunosuppressive TME,characterized by abundant immunosuppressive NK cells,mast cells,regulatory T cells(Tregs),myeloid cells,and exhausted CD8+T cells.Cell interaction analysis suggested that TGIF1-overexpressing GC cells may engage with Tregs via the CCL20-CCR6 axis.Co-high expression of signature gene sets from these interacting cells was associated with significantly shorter survival in the patients(P<0.05).Conclusion TGIF1 is highly expressed in GC tissues and may serve as a biomarker for immunosuppressive TME and poor prognosis.TGIF1-overexpressing GC cells may interact with multiple immune cells,particularly Tregs,to induce an immunosuppressive microenvironment.

Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33％,including 65 cases(70.65％)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39％),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96％)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00％),and were sensitive to linezolid(100.00％),teicoplanin(100.00％)and rifampicin(100.00％).The sensitivity rate to vancomycin was 98.59％.G-strains were sensitive to ceftazidime(86.36％),ceftizoxime(88.89％)and amikacin(100.00％).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33％in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23％vs.36.36％,P＜0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.