Global DNA methylation (LINE-1) associated with exposure to arsenic-contaminated environment and with type of arsenical skin lesions in Thailand

The effects of chronic arsenic exposure mode on DNA methylation and skin lesion type are unclear. These relationships were investigated in an arsenic-contaminated area of southern Thailand. Cases with arsenical skin lesions (n = 131) and lesion-free controls (n = 163) were selected from an arsenic-contaminated sub-district, as well as 105 controls from a non-contaminated area. Type and severity of skin lesions and salivary global DNA methylation (LINE-1) were determined. Arsenic exposure was characterized as occupational, domestic and current (toe-nail arsenic). Associations were explored using logistic regression. Cases and controls had lower LINE-1 methylation and higher toenail arsenic than external controls (74.65% and 74.61% vs 76.05%, p < 0.001 for each). Cases were more likely to have been exposed domestically (OR_total 1.76, 95% ci 1.00, 3.11; and 2.22, 95% ci 1.22, 4.03; P_trend = 0.005 for exposure <36 and ≥36 years). More severe spotty hyperpigmentation was related to higher LINE-1 methylation (P_trend=0.006). LINE-1 methylation was positively associated with toenail arsenic only among non-symptomatic exposed subjects (OR 1.31, 95% ci 1.06, 1.64; p = 0.014). Exposure to an arsenic-contaminated environment results in global DNA hypomethylation. However, among symptomatic subjects, increased global DNA methylation was associated with increased severity of spotty hyperpigmentation.     

幽门螺杆菌感染与细胞自噬的研究进展

幽门螺杆菌(Helicobacter pylori,H. pylori)是一种革兰阴性微需氧病原菌,也是定植于人类胃黏膜上皮中最特异的一种致病菌。它与人消化性溃疡、慢性胃炎、胃癌及胃黏膜相关组织淋巴瘤(MALT)等疾病密切相关。此后又发现H. pylori可能是一种兼性胞内菌,该菌可能通过自噬在胃上皮细胞和巨噬细胞中得以生存、繁殖并引起慢性持续性感染。本文根据近年发表的自噬相关文献,对H. pylori感染不同细胞后自噬对其存活的影响以及H. pylori不同配体引起的自噬调节作一综述。     

Molecular mechanism of therapeutic approaches for human gastric cancer stem cells

Gastric cancer(GC)is a primary cause of cancer-related mortality worldwide,and even after therapeutic gastrectomy,survival rates remain poor.The presence of gastric cancer stem cells(GCSCs)is thought to be the major reason for resistance to anticancer treatment(chemotherapy or radiotherapy),and for the development of tumor recurrence,epithelial–mesenchymal transition,and metastases.Additionally,GCSCs have the capacity for self-renewal,differentiation,and tumor initiation.They also synthesize antiapoptotic factors,demonstrate higher performance of drug efflux pumps,and display cell plasticity abilities.Moreover,the tumor microenvironment(TME;tumor niche)that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor.However,the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential.In this review,we provide up-todate information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development.This information will support improved diagnosis,novel therapeutic approaches,and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy.To date,most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents.However,when used in combination with adjuvant therapy,treatment can improve.By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC,the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy,radiotherapy,or other adjuvant treatment.     

Chronic metformin intake and gastric cancer: A pooled analysis within the Stomach cancer Pooling (StoP) Project

IntroductionThe association between chronic use of metformin and risk of gastric cancer (GC) has been investigated with contradicting results. We aimed to study the association between chronic use of metformin and GC by using data from the Stomach cancer Pooling (StoP) Project, an epidemiological consortium of case-control studies on GC.MethodsData from three studies of the StoP Project with available information on metformin intake were analyzed.Multivariable logistic regression models were used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic use of metformin and GC risk. Analyses were adjusted for sex, age, socioeconomic status, body mass index, smoking status, alcohol drinking status, and history of diabetes. Study-specific ORs and 95% CIs were then pooled with a random-effects model.The dose-response relationship between the duration of metformin intake and GC was assessed with a one-stage logistic model, and the duration of intake was modelled using second-order fractional polynomials.ResultsThe OR of GC in metformin users versus non-users was 1.01 (95% CI=0.61, 1.67). The association between metformin and GC did not change among different strata of study participants’ characteristics or when restricting the analyses to those with a history of diabetes.The dose-response analysis showed a slightly reducing trend in the OR of GC and a borderline significant association with increasing duration of metformin intake.ConclusionsThe results of our study do not clearly support an association between chronic use of metformin and GC, warranting further research.     

康力欣胶囊联合FOLFOX4方案对中晚期胃癌患者免疫功能、生活质量和血清肿瘤标志物的影响

目的:观察康力欣胶囊联合奥沙利铂、亚叶酸钙、5-氟尿嘧啶(FOLFOX4)方案对中晚期胃癌患者免疫功能、生活质量和血清肿瘤标志物的影响。方法:前瞻性选取2018年7月~2021年1月期间来我院接受治疗的胃癌患者80例,根据抽签分为对照组和观察组两组,各为40例。对照组接受FOLFOX4方案治疗,观察组接受康力欣胶囊联合FOLFOX4方案治疗,以3周为1个疗程,治疗2个疗程。观察两组治疗2个疗程后的疗效、生活质量以及治疗期间不良反应状况,对比两组治疗前、治疗2个疗程后的肿瘤标志物和免疫功能指标变化情况。结果:观察组治疗2个疗程后的总有效率高于对照组(P<0.05)。治疗2个疗程后,观察组的肿瘤相关物质群(TSGF)、糖类抗原-199(CA-199)、癌胚抗原(CEA)低于对照组(P<0.05)。治疗2个疗程后,观察组的CD3;、CD4;、自然杀伤细胞(NK)、CD4;/CD8;高于对照组,CD8;低于对照组(P<0.05)。治疗2个疗程后,观察组的生活质量总改善率、卡氏评分(KPS)评分高于对照组(P<0.05)。两组不良反应发生率组间对比无统计学差异(P>0.05)。结论:中晚期胃癌患者采用康力欣胶囊联合FOLFOX4方案治疗,在阻止疾病进展、改善生活质量、提高免疫功能方面均效果确切,优于单纯化疗效果。     

G蛋白偶联胆汁酸受体1促进胃癌细胞的增殖、迁移和侵袭的实验研究

目的:探讨G蛋白偶联胆汁酸受体1(G-protein coupled bile acid receptor 1,GPBAR1/TGR5)对胃癌细胞增殖、迁移和侵袭的影响。方法:免疫组织化学染色方法(Immunohistochemistry,IHC)检测胃癌及癌旁组织芯片中TGR5表达情况;qRT-PCR及Western blot检测胃癌细胞系中TGR5表达水平;小干扰RNA处理AGS、MKN-45胃癌细胞后构建TGR5敲减细胞系,慢病毒载体转染胃癌SGC-7901细胞构建TGR5过表达细胞系;CCK-8实验、平板克隆形成实验、裸鼠皮下移植瘤实验检测TGR5对细胞增殖的影响;流式细胞仪检测TGR5对细胞周期及凋亡的影响;Tanswell实验检测TGR5对胃癌细胞迁移及侵袭的影响;Western blot检测上皮间充质转化(Epithelial-mesenchymal transition,EMT)相关分子β-连环蛋白(β-catenin)、锌脂蛋白转录因子(Snail)、E盒结合锌指蛋白(Zinc finger E-box binding homeobox 1,ZEB)1在AGS、MKN-45及SGC-7901胃癌细胞中的表达。结果:TGR5在胃癌及癌旁组织中均有表达,胃癌组织TGR5高表达率(41.0%)显著高于癌旁组织(9.5%),伴肠化生癌旁组织TGR5高表达率(50%)显著高于不伴肠化生的癌旁组织(0%),胃癌组织TGR5表达与肿瘤大小相关。TGR5在正常人胃上皮永生化细胞株GES-1及各胃癌细胞系中均有表达。TGR5表达敲低的AGS和MKN-45细胞增殖能力减弱、凋亡率显著升高、侵袭和迁移能力显著降低。过表达TGR5的SGC-7901细胞增殖能力增强、克隆形成能力提高、凋亡率明显减低、侵袭和迁移能力显著升高。此外,TGR5过表达显著上调了间质细胞标志物β-catenin、Snail、ZEB1的表达水平。结论:TGR5能够增强胃癌细胞增殖及迁移能力,并抑制细胞凋亡。TGR5可能通过EMT途径介导胃癌细胞转移。     

淀粉样蛋白A、D-二聚体、肌酸激酶同工酶联合检测对川崎病患儿冠状动脉损伤的诊断价值分析

摘要 目的：探讨血清淀粉样蛋白A(SAA)、D-二聚体(D-D)、肌酸激酶同工酶(CK-MB)联合检测对川崎病患儿冠状动脉损伤(CAL)的诊断价值。方法：选取2018年9月～2021年5月我院收治的80例川崎病患儿,根据是否合并CAL分为CAL组(n=34)和NCAL组(n=46)。收集患儿基础资料,并检测SAA、D-D、CK-MB水平。多因素Logistic回归分析川崎病患儿CAL影响因素,受试者工作特征（ROC）曲线分析血清SAA、D-D、CK-MB水平对川崎病患儿CAL的诊断价值。结果：与NCAL组比较,CAL组C反应蛋白(CRP)、红细胞沉降率(ESR)、SAA、D-D、CK-MB水平升高(P＜0.05)。多因素Logistic回归分析显示,CRP、ESR、SAA、D-D、CK-MB为川崎病患儿CAL独立影响因素(P＜0.05)。SAA、D-D、CK-MB、三项联合诊断川崎病患儿CAL的曲线下面积（AUC）分别为0.661、0.687、0.746、0.799,联合应用的诊断效能最高。结论：血清SAA、D-D、CK-MB是川崎病患儿CAL独立影响因素,且联合检测以上指标可辅助诊断川崎病患儿CAL。