BACKGROUND:Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS:This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20 mg b.i.d plus amoxicillin 1 g t.i.d) or 14-day of EA therapy (Esomeprazole 40 mg b.i.d plus amoxicillin 1 g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS:A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p = 0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p = 0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p = 0.155). Non-inferiority was confirmed between the two groups (all p < 0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION:For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.
BACKGROUND While numerous studies have examined the associations between dietary polyphenol subclasses (i.e. , flavonoids, phenolic acids, lignans, and stilbenes) and the risk of gastric cancer (GC), evidence regarding their relationships with gastric precancerous lesions (GPL) and their subtypes [i.e. , chronic atrophic gastritis, intestinal metaplasia (IM), and low-grade dysplasia (LGD)] remains extremely limited. AIM To investigate the associations between dietary polyphenol subclasses and both GPL subtypes and GC in a high-risk population. METHODS This cross-sectional study utilized baseline data from the Wuwei Cohort. The intakes of dietary polyphenol subclasses were estimated using a food frequency questionnaire and the Phenol-Explorer database. Gastric diseases were diagnosed via endoscopic screening followed by pathological confirmation and further classified into three distinct groups: Normal control group, GPL group, and GC group. Logistic regression model and restricted cubic spline (RCS) analyses were employed to assess the associations between dietary polyphenol subclasses and the risks of GPL and GC. RESULTS Higher stilbenes intake was associated with lower GPL risk [odds ratio (OR) T3 vs T1 = 0.78, 95% confidence interval (CI): 0.67-0.89]. For specific lesions, strong inverse associations were observed in IM and phenolic acids (ORT3 vs T1 = 0.75, 95%CI: 0.62-0.91), lignans (ORT3 vs T1 = 0.80, 95%CI: 0.66-0.96), and stilbenes (ORT3 vs T1 = 0.58, 95%CI: 0.48-0.69). Flavonoids intake was associated with an increased risk of IM (ORperLog2 = 1.13, 95%CI: 1.02-1.25). RCS analyses revealed a reverse U -shaped relationship between flavonoids and LGD risk (P = 0.022). Regarding GC risk, an inverse association for stilbenes (ORT3 vs T1 = 0.59, 95%CI: 0.42-0.84; ORperLog2 = 0.92, 95%CI: 0.86-0.97) was observed, and a positive association for flavonoids (ORperLog2 = 1.25, 95%CI: 1.02-1.55). However, these associations were attenuated and became non-significant after comprehensive covariate adjustment. CONCLUSION Specific dietary polyphenol subclasses, including stilbenes, lignans, and phenolic acids, are associated with reduced risks of GPL, particularly IM. Flavonoids intake may be associated with increased risks of GPL and GC.
Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori (H. pylori) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.
The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.
幽门螺杆菌(Helicobacter pylori,H.pylori)定植于胃中,与多种消化系统疾病有关,包括慢性胃炎、消化性溃疡病、胆囊炎及胆囊结石、胃黏膜相关淋巴组织淋巴瘤和胃癌等.本文回顾了H.pylori与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)相关性的证据,表明H.pylori也可以在NAFLD发生发展中起作用,但也有相反的观点否认了它们之间的关系.由于NAFLD的病因复杂、病程漫长、发病机制不明确以及临床治疗困难,明确H.pylori感染在NAFLD中的致病性无疑将为NAFLD治疗的新靶点提供证据.本文将综述H.pylori感染与NAFLD的关系及其可能的发病机制,以及根除H.pylori的治疗现状.
BACKGROUND A lack of research on the association of trefoil factors (TFFs) with gastric cancer (GC) and premalignant lesions (PMLs) in the general populations is an important obstacle to the application of TFFs for GC screening. We aimed to analyze the association of TFFs with GC and PMLs in a general population. METHODS We evaluated 3,986 adults residing in Wuwei, China. We collected baseline characteristics and GC risk factors, including TFFs, endoscopic diagnosis, and pathological information. Three logistic regression models were generated to analyze the association between TFFs and GC, as well as PMLs. Adjusted odds ratio (OR) and 95% confidence intervals (95% CI) were calculated to determine the strength of association. RESULTS Compared with pepsinogen (PG) and anti-Helicobacter pylori immunoglobulin G antibody (Hp-IgG), TFFs had significant association with GC and PMLs after adjusting for biomarkers and risk factors (P < 0.05). The ORs [95% CI] for TFF1 (1.67 [1.27-2.20]), TFF2 (2.66 [2.01-3.51]), and TFF3 (1.32 [1.00-1.74]) were larger than the ORs for PGI (0.79 [0.61-1.03]), PGI/II (1.00 [0.76-1.31]) and Hp-IgG (0.99 [0.73-1.35]) in the GC group. In intestinal metaplasia (IM) group, not only the TFF3 serum level was the highest, but also the OR (1.92 [1.64-2.25]) was the highest. CONCLUSIONS Trefoil factor were associated with risk of GC and PMLs. IMPACT Serum TFFs can improve the screening of high-risk populations for GC.
Background:Serum bilirubin may play a role in preventing antioxidant and cytoprotective effects in physiological conditions. Serum bilirubin levels are inversely correlated with insulin resistance and the prevalence of cardiovascular diseases and diabetes mellitus. However, the correlation between serum bilirubin and nonalcoholic fatty liver disease (NAFLD) is unclear. NAFLD in non-obese participants may lead to serious health problems, calling for prompt recognition and early management. This study aimed at investigating the relationship between the serum bilirubin levels and NAFLD in non-obese Chinese adults. Methods:We evaluated 4,900 non-obese subjects (body mass index <25 kg/m2) residing in Wuwei, China. The subjects received a baseline questionnaire, physical examination, abdominal ultrasonography, and laboratory check-ups. Fasting serum bilirubin was measured with an automated biochemical analyzer. NAFLD was diagnosed based on imaging findings of fatty liver disease on ultrasonography, without excessive alcohol intake and other known causes for chronic liver disease. A logistic regression model was applied to calculate the association between serum bilirubin level and NAFLD in non-obese subjects. Results:NAFLD was diagnosed in 408 (203 men) of the subjects, and they had a mean age of 51-year-old. Non-obese NAFLD patients had lower serum direct bilirubin (DBIL) levels than control group did [2.50 (1.80-3.25) vs. 2.60 (1.90-3.50), P=0.004], but no significant differences in indirect bilirubin (IBIL) and total bilirubin (TBIL) levels of the two groups was seen (both P>0.05). After adjusting confounding factors such as age, gender, body mass index, blood glucose, and blood lipids, multivariate analysis showed serum DBIL (OR: 0.96, 95% CI: 0.83-1.11, P trend =0.6022), IBIL (OR: 1.02, 95% CI: 0.89-1.17, P trend =0.7756), and TBIL (OR: 1.00, 95% CI: 0.87-1.15, P trend =0.991) levels were not associated with NAFLD in the non-obese population. In addition, subgroup analyses (stratified according to age, gender, and medical histories of hypertension, and diabetes mellitus) suggested no independent association between NAFLD and DBIL, IBIL, or TBIL. Conclusions:Our data suggest that serum bilirubin levels are unlikely to be associated with NAFLD in non-obese subjects.
Objective This study aimed to determine the prevalence and risk factors of Helicobacter pylori infection across all age groups in Wuwei City, a high-risk area for gastric cancer in Northwest China. Methods We conducted this study from 2016 to 2017 in an urban and a rural community in Wuwei City. Stool antigen tests targeted individuals aged 0 to 3 years old, and C-13-urea breath tests targeted individuals aged above 3 years. We selected participants based on hierarchical cluster sampling. We assessed the association between variables and H. pylori infection based on logistic regression models. Results Ultimately, the results of 2,163 participants (age: 0 to 77 years old) were included (1,238 minors and 925 adults) in the analysis. The overall prevalence of H. pylori infection was 35.6%. It increased with age, reaching the peak in the 30 to 39 age group, and then began to decline. In multivariate analysis, age was positively associated with prevalence of H. pylori infection, and factors negatively associated with the prevalence were drinking running water, the frequency of yoghurt consumption, and an annual household income of Renminbi ( yen ) 30,000-100,000 or 100,000 above. In the subgroup analyses, however, the same variables associated differently in different age groups. Additionally, we interestingly noticed that boarding, eating at school cafeterias over six times per week, and frequently drinking untreated water were independent predictors of H. pylori infection in junior and senior high school students. Conclusion The prevalence of H. pylori infection is moderate and closely associated with the socioeconomic conditions of Wuwei City, as well as the sanitary situations and dietary habits of the participants in the city. Boarding, eating at school, and drinking untreated water are the main factors explaining the rising infection rate in junior-senior high school students.
BACKGROUND:The diagnostic value of linked color imaging based on endoscopy for gastric intestinal metaplasia has shown variable results. Therefore, this meta-analysis sought to systematically evaluate the value of linked color imaging (LCI) based on the blue laser endoscopy system for the diagnosis of gastric intestinal metaplasia (GIM).METHODS:Literature searches were conducted of electronic databases including PubMed, Embase, the Cochrane Library, and Web of Science to screen diagnostic tests of LCI. The random-effects model was adopted to calculate the diagnostic efficacy of LCI for GIM. Meta-DiSc 1.40 software was applied for the calculation of sensitivity, specificity, and likelihood ratios; symmetric receiver operator characteristic (SROC) curves were drawn, and the areas under the SROC curves (AUCs) were computed. Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool.RESULTS:Six original studies involving 700 participants were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of LCI for diagnosing GIM were 0.87 (0.83-0.91), 0.86 (0.82-0.89), 5.72 (3.63-8.99), and 0.17 (0.08-0.36), respectively. SROC curve analysis showed that the AUC value was 0.9283.DISCUSSION:Our study shows that LCI can be used for the accurate diagnosis of GIM. Considering weaknesses of available studies in terms of design, further studies with rigorous design are in need for further validating the findings of this meta-analysis.
Abstract Background: The lack of effective biomarkers for screening gastric cancer (GC) and premalignant lesions (PMLs) is a significant roadblock in the prevention and early intervention of GC. We aimed to identify noninvasive biomarkers to improve the screening of high-risk populations. Methods: We evaluated 25,000 adults residing in Wuwei. We collected baseline characteristics, GC risk indicators, including trefoil factors (TFF1–3), endoscopy diagnosis, and pathological information. We analyzed the data to determine the association of risk biomarkers with the progression of GC and the prediction capacities of these biomarkers using odds ratio (OR)-adjusted models and receiver operating characteristic (ROC) curve analyses. Results: TFF1 and TFF2 serum levels showed incremental changes from the PMLs to the GC group, with the highest serum TFF3 levels reported in the intestinal metaplasia group. TFF1 and TFF2 had significant predictive values in the PMLs and GC in the three OR-adjusted models but not in the non-atrophic gastritis group. Similar results were obtained after adjusting for all biomarkers and risk factors wherein the ORs (95 % confidence intervals) of TFF1 and TFF2 in the GC group were 2.71 (1.57–4.67) and 2.87 (1.75–4.71), respectively (P < 0.001). The combination of TFF1–3 showed the largest area under the curve across all four groups (chronic atrophic gastritis [0.74], intestinal metaplasia [0.79], low-grade intraepithelial neoplasia/dysplasia [0.79], and GC [0.84]), making it the best-fit ROC. Conclusions: TFF1, TFF2, and the combination of TFF1–3 can serve as sensitive, specific, and noninvasive biomarkers for detecting GC and PMLs, facilitating the early identification of these lesions.
目的 研究幽门螺杆菌(Hp)通过Wnt/β-catenin信号通路对胃癌细胞侵袭及血管新生因子的作用.方法 收集手术切除的胃癌组织并检测Wnt1、Wnt3a、β-catenin、MMP-7、N-cadherin、E-cadherin、VEGF、bFGF、Ang-2 mRNA的相对表达量.培养胃癌细胞株SGC-7901,分为对照组、Hp组、Hp+ICG-001组.对照组用不含细菌及药物的DMEM处理,Hp组用含有Hp的DMEM处理,Hp+ICG-001组用含有Hp及Wnt/β-catenin信号通路抑制剂ICG-001的DMEM处理.采用Western blotting检测Wnt1、Wnt3a、β-catenin、MMP-7、N-cadherin、E-cadherin蛋白的相对表达量.采用Transwell检测侵袭数目.采用酶联免疫吸附试验检测VEGF、bFGF、Ang-2的含量.结果 与Hp阴性胃癌组织比较,Hp阳性胃癌组织中Wnt1、Wnt3a、β-catenin、MMP-7、N-cadherin、VEGF、bFGF、Ang-2的mRNA相对表达量均增加(P<0.05),E-cadherin的mRNA相对表达量降低(P<0.05);Hp组Wnt1、Wnt3a、β-catenin、MMP-7、N-cadherin蛋白相对表达量、侵袭数目、VEGF、bFGF、Ang-2的含量高于对照组(P<0.05),E-cadherin的相对表达量低于对照组(P<0.05);Hp+ICG-001组Wnt1、Wnt3a、β-catenin、MMP-7、N-cadherin蛋白相对表达量、侵袭数目、VEGF、bFGF、Ang-2的含量低于Hp组(P<0.05),E-cadherin的相对表达量高于Hp组(P<0.05).结论 Hp通过Wnt/β-catenin信号通路促进胃癌细胞的侵袭及血管新生因子生成.
胆囊结石为肝胆系统常见的良性疾病,胆囊切除术是胆囊结石的首选临床治疗方法.然而,胆囊结石/胆囊切除术后胆汁组分构成比及胆流动力学的改变,可能与肝癌、直肠癌、胰腺癌等消化系统肿瘤的发病有关.胃癌是世界范围内发病率较高的恶性肿瘤之一,与多因素的共同作用相关,胆囊结石或胆囊切除后暴露因素与胃癌发病风险的相关性尚不清楚,可能的致病机制包括胆汁酸盐介导的炎症损伤、基因突变、激素代谢紊乱以及两者共同的症状和危险因素等,可能为临床提供新的胃癌预防指导.
Objectives To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer. Methods Helicobacter pylori infection was analysed in 21 291 adults by C-14-urea breath test, and H. pylori antibody were detected in 9183 serum samples by latex immunoturbidimetric method. The correlation of H. pylori infection with demographic-economic, lifestyle factors and medical history among the participants was determined by questionnaire. The antibodies against H. pylori urease, VacA and CagA in serum were determined by dot immunobinding assay. Results The infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P < 0.05). Conclusion The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.