N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer

BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric cancer(EBVaGC)is a distinctive molecular subtype of GC.We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC.AIM To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC.METHODS First,The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC(EBVnGC).Second,we identified Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment of m6A-related differentially expressed genes.We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment(TME).Finally,cell counting kit-8 cell proliferation test,transwell test,and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1(IGFBP1)in EBVaGC cell lines.RESULTS m6A methylation regulators were involved in the occurrence and development of EBVaGC.Compared with EBVnGC,the expression levels of m6A methylation regulators Wilms tumor 1-associated protein,RNA binding motif protein 15B,CBL proto-oncogene like 1,leucine rich pentatricopeptide repeat containing,heterogeneous nuclear ribonucleoprotein A2B1,IGFBP1,and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC(P<0.05).The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher(P=0.046).GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC.Compared with EBVnGC,the infiltration of activated CD4+T cells,activated CD8+T cells,monocytes,activated dendritic cells,and plasmacytoid dendritic cells were significantly upregulated in EBVaGC(P<0.001).In EBVaGC,the expression level of proinflammatory factors interleukin(IL)-17,IL-21,and interferon-γ and immunosuppressive factor IL-10 were significantly increased(P<0.05).In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line(SNU719)than in an EBVnGC cell line(AGS)(P<0.05).IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719.Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS.CONCLUSION m6A regulators could remodel the TME of EBVaGC,which is classified as an immune-inflamed phenotype and referred to as a“hot”tumor.Among these regulators,we demonstrated that IGFBP1 affected proliferation,migration,and apoptosis.

Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China

Objective Gastric precancerous conditions such as atrophic gastritis(AG)and intestinal metaplasia(IM)are considered independent risk factors for gastric cancer(GC).The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development.This study investigated the appropriate monitoring interval for AG/IM patients.Methods Totally,957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study.Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia(HGIN)/GC in AG/IM patients,and to determine an appropriate endoscopic monitoring scheme.Results During follow-up,28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia(LGIN)(0.7%),HGIN(0.9%),and GC(1.3%).Multivariate analysis identified H.pylori infection(P=0.022)and extensive AG/IM lesions(P=0.002)as risk factors for HGIN/GC progression(P=0.025).Conclusion In our study,HGIN/GC was present in 2.2%of AG/IM patients.In AG/IM patients with extensive lesions,a 1–2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Destructive effects on endothelial cells of grafts in cytomegalovirus DNA-positive patients after keratoplasty

AIM:To investigate corneal graft survival rate and endothelial cell density(ECD)loss after keratoplasty in cytomegalovirus(CMV)positive patients.METHODS:This was a retrospective cohort study.We analyzed the clinical data of patients who underwent viral DNA detection in aqueous humor/corneal tissue collected during keratoplasty from March 2015 to December 2018 at the Peking University Third Hospital,Beijing,China.To further evaluate the effect of CMV on graft survival rate and ECD loss,patients were divided into three groups:1)CMV DNA positive(CMV+)group;2)viral DNA negative(virus-)group,comprising virus-group eyes pairwise matched to eyes in the CMV+group according to ocular comorbidities;3)control group,comprising virus-group eyes without ocular comorbidities.The follow-up indicators including graft survival rate,ECD,ECD loss,and central corneal thickness(CCT),were analyzed by Tukey honestly significant difference(HSD)test.RESULTS:Each group included 29 cases.The graft survival rate in CMV+group were lowest among the three groups(P=0.000).No significant difference in donor graft ECD was found among three groups(P=0.54).ECD in the CMV+group was lower than the virus-group at 12(P=0.009),and 24mo(P=0.002)after keratoplasties.Furthermore,ECD loss was higher in the CMV+group than in the virus-group in the middle stage(6-12mo)postkeratoplasty(P=0.017),and significantly higher in the early stage(0-6mo)in the virus-group than in the control group(P=0.000).CONCLUSION:CMV reduces the graft survival rate and exerts persistent detrimental effects on the ECD after keratoplasty.The graft ECD loss associate with CMV infection mainly occurrs in the middle stage(6-12mo postoperatively),while ocular comorbidities mainly affects ECD in the early stage(0-6mo postoperatively).

The correlation between socioeconomic status and health self-management in the elderly

Purpose:To determine the correlation between socioeconomic status and health selfmanagement in the elderly and to provide a scientific basis for the promotion of healthy ageing.Methods:We recruited 6173 people aged
60 years from three regions in Hebei Province using the multi-stage stratified cluster sampling method.The participants were surveyed using questionnaires.Results:The health self-management behaviours of elderly people differed with the area of residence,education level,and personal monthly income.An ordered probit model showed that behaviours were better in elderly people who lived in urban areas,who were educated to college level or higher,and with higher monthly incomes(p<0.05).Conclusion:Socioeconomic status plays a decisive role in health self-management in the elderly.We suggest appropriate measures for promoting health self-management among the elderly.

Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice

Background： Mydcetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. Objective： This study was undertaken to investigate the effect of myricetin on high-fat diet （HFD）-induced obesity in C57BL/6 mice. Results： Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly de- creased in myricetin-treated mice. Moreover, obesity-associated oxidative stress （glutathione peroxidase （GPX） activity, total antioxidant capacity （T-AOC）, and malondialdehyde （MDA）） and inflammation （tumor necrosis factor-α （TNF-α）） were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of my- ricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor y （PPARF） and CCAAT/enhancer- binding protein a （C/EBPa）, and lipogenic transcription factor sterol regulatory element-binding protein lc （SREBP-1c）. Conclusions： Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications.