Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology

BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD.     

基于网络药理学研究黄连解毒汤抗幽门螺杆菌感染作用机制

目的运用网络药理学方法预测黄连解毒汤抗Hp感染的主要有效成分、靶点及信号通路,挖掘其潜在作用机制,为后续实验研究提供依据。方法应用TCMSP筛选黄连解毒汤中黄连、黄芩、黄柏、栀子4味中药的主要有效成分及其潜在作用靶点。通过GeneCards数据库和人类孟德尔遗传数据库(OMIM)筛选Hp感染相关靶点,并取药物和疾病的交集靶点。将交集靶点导入Cytoscape 3.7.2构建有效成分和Hp感染相关靶点网络,并进行拓扑学分析。应用STRING在线分析平台构建靶蛋白相互作用(PPI)网络并进行分析。运用R语言在线检索Bioconductor平台对靶点进行GO功能富集;通过DAVID数据库对靶点进行KEGG通路富集分析。结果黄连解毒汤中共筛选出85个有效成分,主要包括槲皮素、小檗碱、山柰酚、汉黄芩素、黄芩素等。对应靶点112个,疾病相关靶点1960个,药物疾病共同靶点71个。网络中度值最高的有效成分为槲皮素,度值最高的靶点为环加氧酶1(PTGS1)。PPI网络中69个节点中度值较高的靶蛋白包括半胱氨酸蛋白酶3(CASP3)、IL6、MAPK8、原癌基因(MYC)、VEGFA、表皮生长因子受体(EGFR)等。GO功能富集分析共获得89个条目,KEGG通路富集分析共筛选12条存在显著差异的信号通路,其中发挥主要作用的有癌症通路、ErbB信号通路、p53信号通路、凋亡、黏附斑等。结论黄连解毒汤可通过多成分、多靶点、多通路发挥对Hp的治疗作用,可通过抗肿瘤机制调控胃癌进程,本研究可为其有效成分研究和抗Hp机制研究提供依据。     

幽门螺杆菌感染相关因素的研究进展

幽门螺杆菌（HP）是革兰阴性微需氧的螺旋样杆菌，主要通过口-口途径在人-人之间感染传播。HP的发现加深了人类对慢性感染、炎症和癌症之间关系的认识。其特定的螺旋形体型、鞭毛及动力、尿素酶和黏附素活性，以及细胞毒素基因A（cagA）、空泡细胞毒素基因A（vacA）等是影响HP感染研究较多的相关致病因素。HP感染在胃癌的发生、发展中可能具有重要作用，但尚未确切证实HP感染是导致胃癌的主因。文章概述了HP感染相关致病因素的研究进展。     

白光胃镜下内镜征象诊断幽门螺杆菌感染的临床研究

ObjectiveTo investigate the clinical value of endoscopic signs for diagnosing Helicobacter pylori(Hp) infection by white light endoscopy.     

双歧杆菌四联活菌片联合四联疗法对HP阳性胃溃疡患者血清TGF-β1、G17、PGI的影响

目的探讨双歧杆菌四联活菌片联合四联疗法对幽门螺旋杆菌(HP)阳性胃溃疡患者血清转化生长因子-β1(TGF-β1)、胃泌素17(G17)、胃蛋白酶原I(PGI)的影响。 方法选取HP阳性胃溃疡患者98例,随机均分为对照组和联合组。对照组采用四联疗法,联合组采用双歧杆菌四联活菌片联合四联疗法治疗。比较两组临床疗效、胃黏膜组织学评分、血清TGF-β1、PGI、G17、胃动素(MTL)、不良反应等情况。 结果联合组治疗总有效率高于对照组(P＜0.05)。与治疗前比较,治疗后两组胃黏膜组织学各项评分、TGF-β1、G17、PGI均降低,MTL升高,且联合组较对照组更为显著(P＜0.05)。联合组不良反应总发生率低于对照组(P＜0.05)。 结论双歧杆菌四联活菌片联合四联疗法治疗HP阳性胃溃疡患者疗效满意,可调节胃肠激素水平,安全性良好,具有临床应用价值。     

High-definition optical magnification with digital chromoendoscopy detects gastric mucosal changes in dyspeptic-patients

BACKGROUND Accurate detection of gastric infection by Helicobacter pylori(H.pylori) and premalignant lesions are important for effective provision of treatment,preventing the development of gastric neoplasia.Optical enhancement systems with optical magnification improved the identification of mucosal superficial and vascular patterns in patients with dyspepsia.AIM To evaluate an optical enhancement system with high-definition magnification,for diagnosis of normal gastric mucosa,H.pylori-associated gastritis,and gastric atrophy.METHODS A cross-sectional,nonrandomized study from November 2015 to April 2016 performed in a single-tertiary academic center from Ecuador.Seventy-two consecutive patients with functional dyspepsia according to the Rome III criteria,were tested for H.pylori using a stool antigen test and were assigned to an Hp+group or an Hp-control group.Esophagogastroduodenoscopy with highdefinition optical magnification and digital chromoendoscopy was performed,and patients were classified into 4 groups,in accordance to the microvasculararchitecture pattern of the mucosa.Interobserver and intraobserver agreement among operators were calculated.RESULTS Of the 72 participants,35 were Hp+ and 37 were Hp-.Among 10 patients with normal mucosal histology in biopsy samples,90% had a Type I pattern of microvascular architecture by endoscopy.Among participants with type IIa and type IIb patterns,significantly more were Hp+ than Hp-(32 vs 8),and most(31 out of 40) had histological diagnoses of chronic active gastritis.Two of the three participants with a histological diagnosis of atrophy had a type III microvascular pattern.The type I pattern predicted normal mucosa,type IIa–IIb predicted H.pylori infection,and type III predicted atrophy with sensitivities of 90.0%,91.4%,and 66.7%,respectively.The intraobserver and interobserver agreements had kappa values of 0.91 and 0.89,respectively.CONCLUSION High-definition optical magnification with digital chromoendoscopy is useful for diagnosis of normal gastric mucosa and H.pylori-associated gastritis with high accuracy,but further studies are needed to determine whether endoscopic diagnosis of gastric atrophy is feasible.     

降逆胃舒汤治疗萎缩性胃炎疗效及对患者病理评分的影响

目的:研究降逆胃舒汤对幽门螺杆菌感染致萎缩性胃炎病理评分的功效。方法:选取238例幽门螺杆菌感染致萎缩性胃炎患者作为本次研究观察对象,入选患者遵循随机数字表法平均分配入对照组与治疗组,对照组以常规西药四联疗法治疗,治疗组在对照组疗法的基础上给予降逆胃舒汤治疗; 治疗3个月后,观察两组患者HP清除率并随访6个月统计复发率,观察两组患者中医证候积分、胃黏膜胃镜征象积分、胃黏膜病理评分及血清胃泌素-17(G-17)、血清胃蛋白酶原Ⅰ、Ⅱ(PGⅠ、PGⅡ)、PGⅠ/PGⅡ比值(PGR)治疗前、后的变化情况。结果:治疗前两组患者各项中医证候、胃黏膜胃镜积分、病理评分及血清指标表达水平比较,差异无统计学意义(P>0.05); 治疗后两组患者各项中医证候、胃黏膜胃镜积分、病理评分及血清指标表达水平比较,差异有统计学意义(P<0.05),治疗组均优于对照组(P<0.05); 治疗后3个月时治疗组HP清除率为88.24%、对照组为73.11%,随访6个月治疗组复发率为3.81%,对照组为18.39%,两组HP根除率、复发率比较,差异有统计学意义(P<0.05)。结论:降逆胃舒汤能够提高幽门螺杆菌清除率并降低复发,更有效缓解幽门螺杆菌感染致萎缩性胃炎的各项中医证候,进一步改善患者胃黏膜病理评分与胃镜征象,更良好的调节患者血清指标。     

Helicobacter pylori infection,chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population-based ESTHER cohort study

Helicobacter pylori (H. pylori) infection is considered as principal cause of gastric cancer. It is further associated with a reduced risk of esophageal adenocarcinomas. In a large prospective population-based cohort study including 9,949 subjects with average observation time of 13.8 years, we assessed the risk of invasive gastric and esophageal cancer according to H. pylori infection and presence of chronic atrophic gastritis (CAG). Incidence rates and hazard ratios (HR) derived by Cox proportional hazards models and adjusted for relevant confounders were derived by seroprevalence of H. pylori and cytotoxin-associated gene A (CagA) antibodies and presence of CAG based on serological markers at baseline, respectively. During follow-up, 30 cases of noncardia gastric cancer and 33 cases of esophageal cancer were observed. Infection by H. pylori without and with expression of CagA was associated with a 5.2-fold (95% confidence interval 1.00–27.1) and an 18.2-fold (4.3–77.4) increase of noncardia gastric cancer incidence. A 0.65-fold decreased risk of esophageal adenocarcinomas (HR 0.35, 0.12–0.97) was observed among H. pylori-infected individuals. In participants infected with CagA expressed H. pylori, the presence of mild/moderate and severe CAG was associated with a 6.4-fold (1.3–31.0) and an 11.8-fold (3.1–45.4) increase of gastric cancer incidence, respectively. The results of this prospective population-based cohort study may contribute relevant evidence to the ongoing research of H. pylori-related cancers. The results may furthermore enhance the empirical basis for risk stratification among H. pylori-infected people and for recommendations regarding H. pylori screening and treatment among older adults in a Western population.