Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis

BACKGROUND Helicobacter pylori(H.pylori)infection is a major risk factor for chronic gastritis,affecting approximately half of the global population.H.pylori eradication is a popular treatment method for H.pylori-positive chronic gastritis,but its mecha-nism remains unclear.Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment.However,no clinical study has been conducted on urinary metabolomics of chronic gastritis.AIM To elucidate the urinary metabolic profiles during H.pylori eradication in patients with chronic gastritis.METHODS We applied LC–MS-based metabolomics and network pharmacology to in-vestigate the relationships between urinary metabolites and H.pylori-positive chronic gastritis via a clinical follow-up study.RESULTS Our study revealed the different urinary metabolic profiles of H.pylori-positive chronic gastritis before and after H.pylori eradication.The metabolites regulated by H.pylori eradication therapy include cis-aconitic acid,isocitric acid,citric acid,L-tyrosine,L-phenylalanine,L-tryptophan,and hippuric acid,which were involved in four metabolic pathways:(1)Phenylalanine metabolism;(2)phenylalanine,tyrosine,and tryptophan biosynthesis;(3)citrate cycle;and(4)glyoxylate and dicarboxylate metabolism.Integrated metabolomics and network pharmacology revealed that MPO,COMT,TPO,TH,EPX,CMA1,DDC,TPH1,and LPO were the key proteins involved in the biological progress of H.pylori eradication in chronic gastritis.CONCLUSION Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H.pylori-positive chronic gastritis patients.

Metabolic dynamics in chronic gastritis:Examining urinary profiles post Helicobacter pylori eradication

Chronic gastritis is the persistent and insidious inflammation of the gastric lining.Helicobacter pylori(H.pylori)has been identified as the most common cause of chronic gastritis and consequently elimination of H.pylori can lead to its cure.This editorial explores the use of urinary metabolic profiles before and after eradication to identify biomarkers that can aid in prognosis and treatment.Despite providing promising insights,there are limitations such as a small sample size(17 patients),a narrow treatment period of 2 wk,and treatment heterogeneity,which raise concerns.Nevertheless,these findings have opened a gateway to enhancing the treatment and prognosis of chronic gastritis through urinary metabolomics.

Correlation between CD4, CD8 cell infiltration in gastric mucosa, Helicobacter pylori infection and symptoms in patients with chronic gastritis

AIM: To evaluate the correlation between CD4, CD8 cell infiltration in gastric mucosa, Helicobacter pylori(H pylori)infection and symptoms or the assemblage of symptoms in cases with chronic gastritis.METHODS: Biopsy samples at the gastric antrum were obtained from 62 patients with chronic gastritis. CD4 and CD8 cell infiltration was evaluated by immunohistochemical assays on frozen sections of the biopsy samples. Fifteen symptoms referring to digestion-related activity and nondigestion related activity were observed. The correlation between lymphocyte infiltration and each symptom or symptom assemblage was analyzed by logistic regression and K-mean cluster methods.RESULTS: CD4 cell infiltrations in gastric mucosa were much more in patients with H pylori infection, while CD8 cell infiltrations were similar in patients with or without H pylori infection. Logistic regression analysis showed that the symptoms including heavy feeling in head or body (t= 2.563), and thirst (t= 2.478) were significantly related with CD4 cell infiltration in gastric mucosa (P＜0.05), and cool limbs with aversion to cold were related with CD8cell infiltration (t = 2.872, P＜0.05). Further analysis showed that non-digestive related symptom assemblage could increase the predicted percentage of CD4 and CD8cell infiltration in gastric mucosa, including lower CD4infiltration by 12.5%, higher CD8 infiltration by 33.3%,and also non-H pylori infection by 23.6%.K-means cluster analysis of all symptoms and CD4 and CD8 cell infiltration in gastric mucosa showed a similar tendency to increase the predicted percentage of CD4, CD8 cell infiltration and H pylori infection.CONCLUSION: Based on correlation between the gastric mucosa lymphocyte infiltration, H pylori infection and clinical symptoms, symptoms or symptomatic assemblages play an important role in making further classification of chronic gastritis, which might help find a more specific therapy for chronic gastritis.

Effect of Hewei-Decoction on chronic atrophic gastritis and eradication of Helicobacter pylori

AIM: To demonstrate the effect of Hewei-Decoction (Decoction for regulating the stomach) on chronic atrophic gastritis (CAG) and eradication of Helicobacter pylori. METHODS: Ninety patients with CAG entering the investigation were divided into six differentiation syndromes, based on their major symptoms and signs. Hewei-Decoction was taken by all the patients orally for 4 or 8 wk. The efficacy was assessed by both the composite accumulation of reduced scores of major symptoms and the eradication of H pylori.X2 test was used to compare the efficacy between H pylori-positive and negative cases, and to disclose the relationship between efficacy and eradication of H pylori. RESULTS: In patients with six different syndrome types, the efficacy of Hewei-Decoction was 91.67% (11/12), 92.86% (13/14), 97.22% (35/36), 87.50% (14/16), 75.00% (6/8), 75.00% (3/4) respectively. The rate of highly efficacious was 58.33% (7/12), 50.00% (7/14), 77.78% (28/36), 62.50% (10/16), 12.50% (1/8) and 25.00% (1/4), respectively. The total efficacy was 91.11% (82/90), and the rate of highly efficacious was 60.00% (54/90). The eradication rate of H pylori was 67.86% (38/56). The therapeutic effect of Hewei-Decoction was better in H pylori positive cases than that in H pylori-negative cases with the total effect of 96.43% vs 82.35% (P<0.05). In 56 H pylori positive cases, the therapeutic effect was better in H pylori eradicated cases than that in H pylori-existent cases with the total effect of 97.37% vs 72.22% (P<0.01). CONCLUSION: Hewei-Decoction is effective in most cases of all the syndrome types. The results indicate that eradication of H pylori is one of the important mechanisms for alleviation of symptoms and signs. Also, the decoction is efficacious in H pylori-negative cases.

Innate immunity–the hallmark of Helicobacter pylori infection in pediatric chronic gastritis

BACKGROUND Innate immunity was found to be associated with both persistence of Helicobacter pylori(H.pylori)infection and increased risk of gastric cancer.AIM To identify the risk factors associated with H.pylori infection and to establish the role of TLR9 rs352140 in suppressing or promoting inflammation related to this infection in children.METHODS We performed a study of 155 children with digestive symptoms,who were divided into two groups according to the histopathological exam:Group 1–48 children with H.pylori-induced chronic gastritis,and Group 2–control group.RESULTS Rural area and poor living conditions were significantly associated with H.pylori chronic gastritis(P=0.0042/P<0.0001).Both positive immunoglobulin A anti H.pylori and the rapid urease test were significantly associated with H.pylori infection(P<0.0001).Significantly higher values of leukocytes and neutrophils within the peripheral blood were found in children with H.pylori chronic gastritis(P=0.111/P=0.284).We found a significant positive correlation between the variant TT genotype of TLR9 rs352140 polymorphism and both leucocytes and neutrophils(P=0.0225/P=0.0292).CONCLUSION Variant TT genotype carriers of the TLR9 rs352140 gene polymorphism might have a more severe degree of inflammation.

Asymptomatic Helicobacter pylori infection and its relation to chronic gastritis

Ninety-two asymptomafic subjects were investigated to determine whether they were in-fected with Helicobacter pylori(HP)by means of fiber gastroscopy, urease test andWarthin-Starry silver stain.As a result of this work,49 subjects with HP infection were found.Under gastroscope,24 of 92 subjects had normal gastric mucosa 45 suffered frompiebaldism-like congestion of the gastric mucosa and 23 mucosal erosion,but the differencesamong the detectable rotes of them had no statistical significance(P】0.05).Forty-six of the subjects with HP infection were seen in the 67 patients with gastritis and only 3 in the subjectswith normal mucosa.The positive rates of HP infection in the patients with moderate and serfous gastritis were significant highly(P【0.01),as compared with that in mild gastritis.It could besuggested that HP infection and the gastritis associated with it may universally exist in“healthy persons”without symptom.

Prevalence and Factors Associated with Intestinal Metaplasia in Chronic Helicobacter pylori Gastritis in a Country with High Endemicity: Ivory Coast Case

Context/Objective: Few studies have been carried out in a country with high endemicity for Helicobacter pylori (H. pylori) infection in Sub-Saharan Africa looking for the association of intestinal metaplasia (IM) with chronic gastritis. We hypothesize that IM is correlated with the intensity of H. pylori infection in a country with high endemicity, Ivory Coast. The objective of this study was to determine the prevalence of intestinal metaplasia in chronic H. pylori gastritis in Ivory Coast. Methods: This was a prospective, cross-sectional, multicenter study, carried out over a period of 5 months, in the reference hospital centers of Abidjan, specialized in Gastroenterology. All patients who had undergone Gastroscopy with biopsies according to the criteria of the Sydney System for the anatomopathological study, those with chronic gastritis and/or H. pylori intestinal metaplasia on histology and in whom all the parameters of the Sydney system classification had been well informed. The quantitative variables were expressed by their means accompanied by their standard deviations and the qualitative variables by their numbers and percentages. Chi-square and Fischer tests were used to look for associations between variables. The significance level was set at 5%. Results: 152 patients were retained. The mean age was 44.9 ± 12.9 years. The prevalence of intestinal metaplasia was 11.8%. In univariate analysis, no significant association was found between clinical and pathological sociodemographic factors (age, sex, ethnicity, educational level, profession) and intestinal metaplasia in chronic Helicobacter pylori gastric cases. In multivariate analysis we found that prolonged use of Proton Pump Inhibitors (PPIs) and a history of Gastroesophageal Reflux Disease (GERD) were significantly associated with the absence of IM. Conclusion: Chronic H. pylori gastritis is the main risk factor for intestinal metaplasia. Prolonged use of PPIs and a history of GERD were significantly identified as factors that would protect against intestinal metaplasia.

Traditional Chinese herbal medicine plus triple therapy in treating Helicobacter pylori-induced chronic atrophic gastritis: a meta-analysis and cumulative meta-analysis

Objectives:To evaluate the benefits of traditional Chinese herbal medicine(TCHM)plus triple therapy(TT)in the management of Helicobacter pylori(H.pylori)-induced chronic atrophic gastritis(CAG).Methods:A comprehensive access and electronic database search were carried out from inception to June 2020.Prospective randomized trials(TCHM plus TT vs.TT)were selected to assess the eradication rate of H.pylori(ER of H.pylori),clinical symptom relief rate(SRR),treatment-related adverse reactions(TRAR)and 95%confidence intervals(CI)in the meta-analysis and cumulative meta-analysis(CMA).Meta-regression analysis was used to analyze heterogeneity between studies and publication bias.Results:33 studies contained 3,226 participants were included.Compared with the TT group,TCHM plus TT group showed a significantly higher ER of H.pylori(OR=4.14,95%CI:3.21-5.35;P=0.000)and SRR(OR=4.50,95%CI:3.59-5.64).Meanwhile,the TRAR of TCHM plus TT remedy was significantly lower than TT monopoly(RR=0.43,95%CI:0.29-0.64;P=0.000).The results of the CMA,sorted by publication year,duration of treatment,and sample size,confirmed that combined treatment remedy was superior to TT monopoly in respect of ER of H.pylori and SRR.Conclusions:The present study obtained reliable and convincing evidence suggesting that TCHM plus TT remedy was efficacious and safe in treating H.pylori-induced CAG.

Presence of the Genes <i>cag</i>A, <i>cag</i>E, <i>vir</i>B11 and Allelic Variation of <i>vac</i>A of <i>Helicobacter pylori</i>Are Associated with the Activity of Gastritis

Non-atrophic active chronic gastritis (ACG) is characterized by the presence of H. pylori in the gastric epithelium, known to be one of the first steps that precede progression to gastric adenocarcinoma. Inactive chronic gastritis (ICG) suggests that the patient has H. pylori gastritis, but this diagnosis is rarely made in routine histopathology. Clinical manifestations associated with H. pylori infection are potentially due to differences in virulence between strains;however, it is unclear if the progression of ACG to ICG depends on the H. pylori strain. The aim of this study was to compare the prevalence of the virulence factors of H. pylori found in patients with ACG and ICG, and its influence on the development of ICG. A significant association was observed between H. pylori detection by histological examination and the activity of gastritis (p 1 year) was reported by 28.6% of the ACG group and 42.5% of the ICG, while no evidence of association between long-term use of PPI and decreased inflammation was found in the patients studied. The genes cagA, cagE and virB11 were statistically associated with ACG (p = 0.01, p vacAs1 allele groups, ACG was associated with the most virulent group (p = 0.0015), while ICG was associated with the less virulent group (p < 0.001). The rate of co-infection was significantly higher in ICG than in ACG cases (p = 0.02). In conclusion, this study points to the role of virulent strains of H. pylori in the non-resolution of gastritis.

History of chronic gastritis:How our perceptions have changed

Currently,the diagnostic strategy for chronic gastritis(CG)is aimed not just at fixing the presence of gastric mucosal inflammation,but also at gastric cancer(GC)risk stratification in a particular patient.Modern classification approach with the definition of the stage of gastritis determines the need,activities and frequency of dynamic monitoring of a patient.However,this attitude to the patient suffering from CG was far from always.The present publication is a literature review describing the key milestones in the history of CG research,from the description of the first observations of inflammation of the gastric mucosa,assessment of gastritis as a predominantly functional disease,to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy,assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy,intestinal metaplasia,dysplasia and GC.

Yiwei Xiaoyu granules for treatment of chronic atrophic gastritis with deficiency syndrome of the spleen and stomach

BACKGROUND The Correa sequence,initiated by Helicobacter pylori(H.pylori),commonly progresses to gastric cancer through the stage of chronic atrophic gastritis(CAG).Although eradication of H.pylori only reduces the risk of gastric cancer,it does not eliminate the risk for neoplastic progression.Yiwei Xiaoyu granules(YWXY)are a commonly used composite preparation in Chinese clinics.However,the pursuit of excellence in clinical trials and the establishment of standardized animal experiments are still needed to contribute to full understanding and application of traditional Chinese medicine in the treatment of CAG.AIM To demonstrate the effectiveness of YWXY in patients with CAG and spleenstomach deficiency syndrome(DSSS),by alleviating histological scores,improving response rates for pathological lesions,and achieving clinical efficacy in relieving DSSS symptoms.METHODS We designed a double-blind,randomized,controlled trial.The study enrolled seventy-two H.pylori-negative patients(mean age,52.3 years;38 men)who were randomly allocated to either the treatment group or control group in a 1:1 ratio,and treated with 15 g YWXY or 0.36 g Weifuchun(WFC)tablet combined with the respective dummy for 24 wk.The pre-randomization phase resulted in the exclusion of 72 patients:50 participants did not meet the inclusion criteria,12 participants declined to participate,and 10 participants were excluded for various other reasons.Seven visits were conducted during the study,and histopathological examination with target endoscopic biopsy of narrow-band imaging was requested before the first and seventh visits.We also evaluated endoscopic performance scores,total symptom scores,serum pepsinogen and gastrin-17.RESULTS Six patients did not complete the trial procedures.Treatment with YWXY improved the Operative Link on Gastric Intestinal Metaplasia Assessment(OLGIM)stage,compared with WFC(P<0.05).YWXY provided better relief from symptoms of DSSS and better improvement in serum gastric function,compared with WFC(P<0.05).CONCLUSION YWXY compared with WFC significantly reduced the risk of mild or moderate atrophic disease,according to OLGIM stage,significantly relieved symptoms of DSSS,and improved serum gastric function.

Alteration of sister chromatid exchange frequencies in gastric cancer and chronic atrophic gastritis patients with and without H pylori infection

AIM: To determine, by counting sister chromatid exchange (SCE) frequencies, whether genetic impairment and DNA damage have an effect on the pathogenesis of gastric cancer (GC). METHODS: Analysis of SCE is a cytogenetic technique used to show DNA damage as a result of an exchange of DNA fragments between sister chromatids. We analyzed SCE frequency in 24 patients with GC, 26 patients with chronic atrophic gastritis (CAG), and 15 normal controls. The presence of H pylori was confirmed by urease test, toluidine-blue stain and hematoxylin-eosin stain. RESULTS: SCE was significantly increased in H pylori- negative GC patients, and in H pylori-negative CAG patients compared with controls (7.41 ± 1.36 and 6.92 ± 1.20, respectively, vs 5.54 ± 0.8, P < 0.001). There was no difference in the SCE frequency between H pylori- negative GC patients and H pylori-negative CAG patients (P > 0.05). On other hand, the SCE frequencies in H pylori-positive GC patients were higher than those in H pylori-positive CAG patients (9.20 ± 0.94 vs 7.93 ± 0.81, P < 0.01). Furthermore, H pylori-positive GC patients had a higher SCE frequency than H pylori- negative GC patients (9.20 ± 0.94 vs 7.41 ± 1.36, P < 0.001). Similarly, a significant difference was detected between H pylori-positive CAG patients and H pylori-negative CAG patients (7.93 ± 0.81 vs 6.92 ± 1.20, P < 0.05). CONCLUSION: We suggest the increased SCE in patients reflects a genomic instability that may be operative in gastric carcinogenesis.

Gastric polyps: Association with Helicobacter pylori status and the pathology of the surrounding mucosa, a cross sectional study

aim:To assess the endoscopic characteristics of gastric polyps and their association with Helicobacter pylori(H.pylori)status in a predominantly Hispanic population.m ETHODS:We conducted a retrospective study of all esophagogastroduodenoscopies performed at our institution.Demographic,endoscopic and histopathological data were reviewed.Categorization of patients into Hispanic and Non-Hispanic was based on selfidentification.Patients without resection/biopsy were not included in the analysis.Identification of polyps type was based on histological examination.One way analysis of variance was used to compare continuousvariables among different polyp types and Fisher’s exact test was used compare categorical variables among polyp types.Unadjusted and adjusted comparisons of demographic and clinical characteristics were performed according to the H.pylori status and polyp type using logistic regressions.RESULTS:Of 7090 patients who had upper endoscopy,335 patients had gastric polyps(4.7%).Resection or biopsy of gastric polyps was performed in 296 patients(88.4%)with a total of 442 polyps removed or biopsied.Of 296 patients,87(29%)had hyperplastic polyps,82(28%)had fundic gland polyps and 5(1.7%)had adenomatous polyps.Hyperplastic polyps were significantly associated with positive H.pylori status compared with fundic gland polyps(OR=4.621;95%CI:1.92-11.13,P=0.001).Hyperplastic polyps were also found to be significantly associated with portal hypertensive gastropathy compared with fundic gland polyps(OR=6.903;95%CI:1.41-33.93,P=0.0174).Out of 296 patients,30(10.1%)had a followup endoscopy with a mean duration of 26±16.3 mo.Interval development of cancer was not noted in any of the patients during follow up period.CONCLUSi ON:Gastric hyperplastic polyps were significantly associated with positive H.pylori status and portal hypertensive gastropathy as compared with fundic gland polyps.

Improved method for inducing chronic atrophic gastritis in mice

BACKGROUND Chronic atrophic gastritis(CAG)is a common disease of the digestive system with pathological characteristics of a decreasing number,or disappearance,of inherent glands of the gastric mucosa.CAG has been defined as a precancerous condition of gastric cancer.Intestinal metaplasia or intraepithelial neoplasia accompanying atrophied glands of the stomach is regarded as one of the most important precancerous lesions of gastric cancer.As a common malignant tumour,gastric cancer remains without a satisfactory therapy and its pathogenesis remains unclear,seriously threatening human life.Therefore,some scholars have proposed to prevent the incidence of gastric cancer by avoiding precancerous lesions.If CAG can be reversed,the incidence of gastric cancer can be substantially reduced.To reverse and prevent CAG and study its pathogenesis and therapy,it is necessary to develop an ideal,safe,stable,animal model.AIM To study a rapid,stable,and safe method of establishing a mouse model of human CAG.METHODS Six-week-old Kunming mice were divided into a phosphate buffered solution control group,a Helicobacter pylori(H.pylori)group,an N-methyl-N'-nitroguanidine(MNNG)group,an ammonia water group,and a group combining H.pylori,MNNG,and ammonia water(hereinafter referred to as the combined group).The mice were administrated with drinking water containing ammonia or infected with H.pylori through gavage.At the 30th,60th,90th,and 120th day after the last H.pylori infection,mice were selected randomly to collect their gastric mucosa for hematoxylin eosin staining,terminal nick-end labelling staining detection,and immunohistochemical staining for Bax and Bcl-2.In addition,H.pylori was isolated,cultured,and identified,and its extent of colonisation calculated.Blood was collected to detect inflammatory factors interleukin(IL)-1β,IL-8,and tumor necrosis factor(TNF)-αand immune function markers CD4 and CD8 to confirm successful establishment of the CAG model.RESULTS The combined group showed slight CAG at the 90th day and moderate CAG at the 120th day,while other groups did not show CAG at that time.CONCLUSION The combination of H.pylori,MNNG,and ammonia is an effective method of developing a mouse model of human CAG.

Chronic atrophic gastritis detection with a convolutional neural network considering stomach regions

BACKGROUND The risk of gastric cancer increases in patients with Helicobacter pylori-associated chronic atrophic gastritis(CAG).X-ray examination can evaluate the condition of the stomach,and it can be used for gastric cancer mass screening.However,skilled doctors for interpretation of X-ray examination are decreasing due to the diverse of inspections.AIM To evaluate the effectiveness of stomach regions that are automatically estimated by a deep learning-based model for CAG detection.METHODS We used 815 gastric X-ray images(GXIs)obtained from 815 subjects.The ground truth of this study was the diagnostic results in X-ray and endoscopic examinations.For a part of GXIs for training,the stomach regions are manually annotated.A model for automatic estimation of the stomach regions is trained with the GXIs.For the rest of them,the stomach regions are automatically estimated.Finally,a model for automatic CAG detection is trained with all GXIs for training.RESULTS In the case that the stomach regions were manually annotated for only 10 GXIs and 30 GXIs,the harmonic mean of sensitivity and specificity of CAG detection were 0.955±0.002 and 0.963±0.004,respectively.CONCLUSION By estimating stomach regions automatically,our method contributes to the reduction of the workload of manual annotation and the accurate detection of the CAG.

Helicobacter pylori infection with intestinal metaplasia: An independent risk factor for colorectal adenomas

AIM To explore the association between Helicobacter pylori (H. pylori) infection status, intestinal metaplasia (IM), and colorectal adenomas. METHODS We retrospectively reviewed 1641 individuals aged >= 40 years who underwent physical examination, laboratory testing, C-13-urea breath testing, gastroscopy, colonoscopy, and an interview to ascertain baseline characteristics and general state of health. Histopathological results were obtained by gastric and colorectal biopsies. RESULTS The prevalence of H. pylori infection and adenomas was 51.5% (845/1641) and 18.1% (297/1641), respectively. H. pylori infection was significantly correlated with an increased risk of colorectal adenomas (crude OR = 1.535, 95% CI: 1.044-1.753, P = 0.022; adjusted OR = 1.359, 95% CI: 1.035-1.785, P = 0.028). Individuals with IM had an elevated risk of colorectal adenomas (crude OR = 1.664, 95% CI: 1.216-2.277, P = 0.001; adjusted OR = 1.381, 95% CI: 0.998-1.929, P = 0.059). Stratification based on H. pylori infection stage and IM revealed that IM accompanied by H. pylori infection was significantly associated with an increased risk of adenomas (crude OR = 2.109, 95% CI: 1.383-3.216, P = 0.001; adjusted OR = 1.765, 95% CI: 1.130-2.757, P = 0.012). CONCLUSION H. pylori-related IM is associated with a high risk of colorectal adenomas in Chinese individuals.

Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population

BACKGROUND Toll-like receptors(TLRs)are the first line of host defense,and are involved in Helicobacter pylori(H.pylori)recognition and activation of both inflammatory and carcinogenic processes.The presence of single nucleotide polymorphisms(SNPs)in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer(GC).Among them,Toll-like receptor 9(TLR9)polymorphisms have emerged with a risk factor of infectious diseases and cancer,however the studies are still inconclusive.AIM To evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis,and its influence on mRNA expression.METHODS A case-control study was conducted to evaluate two TLR9 SNPs(TLR9-1237 TCrs5743836 and TLR9-1486 CT-rs187084)in chronic gastritis(CG)and GC patients.A total of 609 DNA samples of peripheral blood[248 CG,161 GC,and 200 samples from healthy individuals(C)]were genotyped by polymerase chain reaction-restriction fragment length polymorphism.All samples were tested for the H.pylori infection using Hpx1 and Hpx2 primers.Quantitative polymerase chain reaction by TaqMan?assay was used to quantify TLR9 mRNA from fresh gastric tissues(48 GC,26 CG,and 14 C).RESULTS For TLR9-1237,the TC+CC or CC genotypes were associated with a higher risk of GC than C[recessive model odds ratio(OR)=5.01,95%confidence interval(CI):2.52-9.94,P<0.0001],and the CG(recessive model OR=4.63;95%CI:2.44-8.79,P<0.0001)groups.For TLR9-1486,an association between the CT+TT genotypes and increased risk of both GC(dominant model OR=2.72,95%CI:1.57-4.72,P<0.0001)and CG(dominant model OR=1.79,95%CI:1.15-2.79,P=0.0094)was observed when compared to the C group.Moreover,the presence of TLR9-1237 TC/CC+TLR9-1486 CC genotypes potentiate the risk for this neoplasm(OR=18.57;95%CI:5.06-68.15,P<0.0001).The TLR9 mRNA level was significantly higher in the GC group(RQ=9.24,P<0.0001)in relation to the CG group(RQ=1.55,P=0.0010)and normal mucosa(RQ=1.0).When the samples were grouped according to the polymorphic genotypes and the presence of H.pylori infection,an influence of TLR9-1237 TC+CC polymorphic genotypes(P=0.0083)and H.pylori infection(P<0.0001)was observed on the upregulation of mRNA expression.CONCLUSION Our findings show that TLR9 rs5743836 and rs187084 polymorphisms are associated with a higher risk of carcinogenesis gastric,and that TLR9 mRNA levels can be modulated by TLR9-1237 TC+CC variant genotypes and H.pylori infection.

Evaluation of the Gastric Microbiome in Patients with Chronic Superficial Gastritis and Intestinal Metaplasia

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis(CSG)and intestinal metaplasia(IM)and investigate the influence of Helicobacter pylori(H.pylori)on the gastric microbiome.Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM,and the patients were classified into the following four groups based on the state of H.pylori infection and histology:H.pylori-negative CSG(n=24),H.pylori-positive CSG(n=14),H.pylori-negative IM(n=11),and H.pylori-positive IM(n=5).The gastric microbiome was analyzed by 16S rRNA gene sequencing.Results H.pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM.In H.pylori-positive subjects,the bacterial abundance and diversity were significantly lower than in H.pylori-negative subjects.The H.pylori-negative groups had similar bacterial composition and bacterial abundance.The H.pylori-positive groups also had similar bacterial composition but different bacterial relative abundance.The relative abundance of Neisseria,Streptococcus,Rothia,and Veillonella were richer in the I-HP group than in G-HP group,especially Neisseria(t=175.1,P<0.001).Conclusions The gastric microbial abundance and diversity are lower in H.pylori-infected patients regardless of CSG and IM.Compared to H.pylori-positive CSG group and H.pylori-positive IM,the relative abundance of Neisseria,Streptococcus,Rothia,and Veillonella is higher in H.pylori-positive patients with IM than in H.pylori-positive patients with CSG,especially Neisseria.

Usefulness of vonoprazan,a potassium ion-competitive acid blocker,for primary eradication of Helicobacter pylori

AIM To investigate usefulness of triple therapy with vonoprazan,a potassium ion-competitive acid blocker and antibiotics,for Helicobacter pylori(H.pylori) eradication.METHODS The H.pylori eradication rate was examined in 2507 patients(2055 undergoing primary eradication and 452 undergoing secondary eradication,excluding patients with subtotal gastrectomy) at the Japanese Red Cross Kyoto Daiichi Hospital from March 2013 to September 2015.For patients treated from March 2013 to February 2015,a proton pump inhibitor(PPI) was used to reduce acid secretion,while vonoprazan was used after March 2015.The success rates of the 2 regimens(PPI + amoxicillin + clarithromycin/metronidazole,or vonoprazan + amoxicillin + clarithromycin/metronidazole) were compared.RESULTS The success rate of primary H.pylori eradication was significantly higher in the vonoprazan group.When stratified by the underlying disease,a significant increase of the H.pylori eradication rate was observed in patients with chronic gastritis.A significantly lower H.pylori eradication rate was observed in younger patients compared to older patients in the PPI group,but there was no difference according to age in the vonoprazan group.On the otherhand,the success rate of secondary eradication was similar at approximately 90% in both groups.CONCLUSION Vonoprazan is very useful for primary eradication of H.pylori,and may become a first-line acid secretion inhibitor instead of PPIs.

Detection and evaluation of antibodies against neutrophil-activating protein of Helicobacter pylori in patients with gastric cancer

AIM： To detect and evaluate the antibodies against Helicobacter pylori （H pylori） neutrophil-activating protein （HP-NAP） in patients with gastric cancer and other gastroduodenal diseases.METHODS： Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coll. Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 （IL-8） and growth-related oncogene （GROα） cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected.RESULTS： The serum positivity and mean absorbancevalue of HP-NAP-specific antibodies in the gastriccancer group （97.7% and 1.01 ± 0.24） were significantly higher than those in the chronic gastritisgroup （85.7% and 0.89 ± 0.14, P 〈 0.005） and healthy control group （27.7% and 0.65 ± 0.18, P 〈 0.001）. The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly upregulate IL-8 production in gastric epithelial cell lines but had no effect on GROα production.CONCLUSION： Infection with virulent H py/ori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma, rHP-NAP- based ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.