Involvement of 90-kuD ribosomal S6 kinase in collagen type I expression in rat hepatic fibrosis

AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy.Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell （HSC） line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chainreaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, thencollagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated withor without platelet-derived growth factor （PDGF）-BB at a final concentration of 20μg/L and the cell growthwas determined by MTS conversion.RESULTS： In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significantpositive correlation with collagen type I levels.In HSC-T6 cells transfected with RNAi targeted top90RSK, the expression of collagen type I was down-regulated （61.8% in mRNA, P 〈 0.01, 89.1% inprotein, P 〈 0.01）. However, collagen type ] promoteractivity was not increased with over-expression of p90RSK and not decreased with low expression either,compared with controls in the same cell line （P = 0.076）.Furthermore, p90RSK siRNA exerted the inhibitionof HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation.CONCLUSION： p90RSK is over-expressed in activatedHSCs and involved in regulating the abnormalexpression of collagen type I through initiating theproliferation of HSCs.     

Significant decrease in prevalence of Helicobacter pylori in the Czech Republic

AIM: To study possible decrease in prevalence of Helicobacter pylori (H. pylori) infection in the Czech Republic within a 10-year period.METHODS: A total of 22 centres entered the study. The catchment areas of these centres covered cities and towns with more than 20 000 inhabitants, smaller towns (≤ 20 000 inhabitants) with surrounding villages and rural areas, and were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1 837 subjects (aged 5-98 years) took part in the study, randomly selected out of 38 147 people from the general population. H. pylori infection was investigated by means of a ¹³C-urea breath test. Breath samples in duplicates were analysed using isotope ratio mass spectrometry. The cut-off point was 3.5. Social and demographic characteristics were based on data from self-completed questionnaires.RESULTS: The overall prevalence of H. pylori infection was 23.5% (430/1826), and 4.8% (20/420) in children aged 15 or less. There was no statistically significant difference in prevalence between males (24.3%; 208/857) and females (22.9%, 222/969, P = 0.494). H. pylori infection was strongly associated with higher age, among subjects aged 55+ years, prevalence of H. pylori infection was 39.8% (252/633, P < 0.001). The highest prevalence of H. pylori infection was found among persons aged 55-64 years (43.9%, 97/221) and 75+ years (37.9%, 58/153). Among study subjects aged 15+ years, prevalence of H. pylori infection was significantly increased in those with lowest education (odds risk 3.19, 95% CI 1.87-5.47). Compared to never married (14.1%), the prevalence of H. pylori infection was statistically significantly higher among married (35.4%, 246/694, P < 0.001), divorced (36.8%, 49/133, P < 0.001) and widowed study subjects (40.2%, 45/112, P < 0.001), both in minimally and fully adjusted analysis. There was no significant difference in the prevalence of H. pylori infection between married and widowed subjects (35.4%, 246/694 vs 40.2%, 45/112, P = 0.389). There was little variation in smoking prevalence across categories of smoking and there was no evidence of an increased risk of H. pylori infection among current or past smokers in our data (odds risk 1.04 with 95% CI 0.78-1.40 for current smokers; odds ratio 0.83 with 95% CI 0.60-1.16 for former smokers). The current prevalence of H. pylori in 2011 was significantly lower compared to the prevalence reported from identical geographical areas in 2001 (23.5% vs 41.7%, P < 0.001).CONCLUSION: The overall prevalence of H. pylori infection in the general population has fallen substantially in the Czech Republic over the past 10 years.     

Serum pepsinogen Ⅱ is a better diagnostic marker in gastric cancer

AIM:To investigate screening makers for gastric cancer,we assessed the association between gastric cancer and serum pepsinogens(PGs).METHODS:The subjects comprised 450 patients with gastric cancer,111 individuals with gastric atrophy,and 961 healthy controls.Serum anti-Helicobacter pylori(H.pylori) immunoglobulin G(IgG),PGⅠand PG Ⅱ were detected by enzyme-linked immunosorbent assay.Gastric atrophy and gastric cancer were diagnosed by endoscopy and histopathological examinations.Odds ratios and 95%CIs were calculated using multivariate logistic regression.RESULTS:Rates of H.pylori infection remained high in Northeastern China.Rates of H.pylori IgG positivity were greater in the gastric cancer and gastric atrophy groups compared to the control group(69.1% and 75.7% vs 49.7%,P 0.001).Higher levels of PG Ⅱ(15.9 μg/L and 13.9 μg/L vs 11.5 μg/L,P 0.001) and lower PGⅠ/PG Ⅱ ratio(5.4 and 4.6 vs 8.4,P 0.001) were found in patients with gastric cancer or gastric atrophy compared to healthy controls,whereas no correlation was found between the plasma PGⅠconcentration and risk of gastric cancer(P = 0.537).In addition,multivariate logistic analysis indicated that H.pylori infection and atrophic gastritis were independent risk factors for gastric cancer.Lower plasma PGⅠ/PG Ⅱ ratio was associated with higher risks of atrophy and gastric cancer.Furthermore,plasma PG Ⅱ?level?significantly?correlated?with?H.pyloriinfected gastric cancer.CONCLUSION:Serum PG Ⅱ concentration and PG Ⅰ/PG Ⅱ ratio are potential biomarkers for H.pyloriinfected gastric disease.PG Ⅱ is independently associated with risk of gastric cancer.     

Helicobacter pylori infection is associated with gallstones: Epidemiological survey in China

AIM: To elucidate the prevalence and risk factors for gallstones, primarily focusing on Helicobacter pylori(H. pylori) infection. METHODS: A total of 10016 Chinese subjects, who had undergone physical examination, fasting 13 C urea breath test and abdominal ultrasonography, had sufficient blood test data, and had finished a questionnaire, were included in this cross-sectional study. Participants(n = 1122) who had previous eradication of H. pylori were studied separately. RESULTS: Gallstones were discovered in 9.10% of men and 8.58% of women, with no significant sex difference. Multivariate analyses displayed that age, aspartate aminotransferase, total cholesterol, H. pylori infection, hepatitis C virus(HCV) infection, and fattyliver had a significant association with gallstones(P 0.05). Successive multiple logistic regression analysis including index of odds ratio(OR) and standardized coefficient(β) indicated that older age(OR/β = 1.056/0.055), H. pylori infection(OR/β = 1.454/0.109), HCV infection(OR/β = 1.871/0.123), and fatty liver(OR/β = 1.947/0.189) had a significant positive association with gallstones. After age stratification, H. pylori infection and fatty liver still had a significant positive association with gallstones in any age-specific groups, whereas HCV infection had a significant positive association in patients aged 40 years. The prevalence of gallstones among H. pylori-positive, H. pylori-eradicated, and H. pylori-negative subjects was 9.47%, 9.02%, and 8.46%, respectively. The matched analysis showed that gallstones among H. pylori eradicated subjects was significantly lower compared with H. pylori-positive subjects(P 0.05).CONCLUSION: H. pylori infection and fatty liver have a significant positive association with gallstones. H. pylori eradication may lead to prevention of gallstones.     

Isolation and diagnosis of Helicobacter pylori by a new method: Microcapillary culture

AIM:To investigate the performance of the microcapillary culture method(MCM) in Helicobacter pylori(H.pylori) isolation and diagnosis.METHODS:Microcapillary culture(MC),classical culture(CC),rapid urease(CLO) test,and histopathologic examination(HE) were performed with biopsy samples.Homogenized biopsy samples were loaded into capillary tubes and incubated for 48 h at 37 ℃ without providing a microaerophilic environment.Additionally,three or four loops of the homogenized sample were inoculated in a ready-to-use selective medium(Becton Dickinson,Helicobacter Agar,Modified) specific for the isolation of H.pylori and incubated at 37 ℃ in a microaerophilic atmosphere provided by Campy Gen(Becton Dickinson,Gas Pack).Bacteria reproducing in microcapillary tubes were evaluated in an inverted microscope and also were evaluated after performing a CC with the content.Results obtained by CC,CLO test,and HE were compared with those of MC.The diagnostic performances of the methods used in this study were evaluated for specificity,sensitivity,positive predictive value(PPV),negative predictive value(NPV),and CI.RESULTS:H.pylori was found positive by CLO test +HE and/or CC culture in 26 patient antrum and corpus biopsy samples.In 25(25/26) patient biopsy samples,H.pylori was isolated by MCM,whereas in only 14(14/26) patient biopsy samples,H.pylori was isolatedby CC.CLO test and HE were found positive in 17(17/26) patient biopsy samples.Comparing the results of the isolation of H.pylori by MCM,CC,CLO test,and HE,the sensitivity of the MCM was found as 96%,the specificity as 80%,the PPV as 83%,the NPV as 95%,and the 95%CI as 0.76(χ2 =31.51,P < 0.01) whereas the sensitivity of the CC was found as 54%(χ2 =19.15,P < 0.01),and the sensitivity of the CLO test and HE were found as 65%(χ2 =25.26,P < 0.01).CONCLUSION:This new microcapillary cultivation method for H.pylori has high diagnostic sensitivity compared with CC,HE,and CLO tests.     

Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells

AIM: To investigate the potential mechanism of Arg-Gly-Asp (RGD) peptide-labeled liposome loading oxymatrine (OM) therapy in CCl₄-induced hepatic fibrosis in rats.METHODS: We constructed a rat model of CCl₄-induced hepatic fibrosis and treated the rats with different formulations of OM. To evaluate the antifibrotic effect of OM, we detected levels of alkaline phosphatase, hepatic histopathology (hematoxylin and eosin stain and Masson staining) and fibrosis-related gene expression of matrix metallopeptidase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-1 as well as type I procollagen via quantitative real-time polymerase chain reaction. To detect cell viability and apoptosis of hepatic stellate cells (HSCs), we performed 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and flow cytometry. To reinforce the combination of oxymatrine with HSCs, we constructed fluorescein-isothiocyanate-conjugated Arg-Gly-Asp peptide-labeled liposomes loading OM, and its targeting of HSCs was examined by fluorescent microscopy.RESULTS: OM attenuated CCl₄-induced hepatic fibrosis, as defined by reducing serum alkaline phosphatase (344.47 ± 27.52 U/L vs 550.69 ± 43.78 U/L, P < 0.05), attenuating liver injury and improving collagen deposits (2.36% ± 0.09% vs 7.70% ± 0.60%, P < 0.05) and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type I procollagen (P < 0.05). OM inhibited cell viability and induced apoptosis of HSCs in vitro. RGD promoted OM targeting of HSCs and enhanced the therapeutic effect of OM in terms of serum alkaline phosphatase (272.51 ± 19.55 U/L vs 344.47 ± 27.52 U/L, P < 0.05), liver injury, collagen deposits (0.26% ± 0.09% vs 2.36% ± 0.09%, P < 0.05) and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type I procollagen (P < 0.05). Moreover, in vitro assay demonstrated that RGD enhanced the effect of OM on HSC viability and apoptosis.CONCLUSION: OM attenuated hepatic fibrosis by inhibiting viability and inducing apoptosis of HSCs. The RGD-labeled formulation enhanced the targeting efficiency for HSCs and the therapeutic effect.     

Centralized isolation of Helicobacter pylori from multiple centers and transport condition influences

AIM:To evaluate the efficacy of centralized culture and possible influencing factors.METHODS:From January 2010 to July 2012,66452 patients with suspected Helicobacter pylori(H.pylori) infection from 26 hospitals in Zhejiang and Jiangsu Provinces in China underwent gastrointestinal endoscopy.Gastric mucosal biopsies were taken from the antrum for culture.These biopsies were transported under natural environmental temperature to the central laboratory in Hangzhou city and divided into three groups based on their transport time:5,24 and 48 h.The culture results were reported after 72 h and the positive culture rates were analyzed by a χ2 test.An additional 5736 biopsies from H.pylori-positive patients(5646 rapid urease test-positive and 90 14C-urease breath test-positive) were also cultured for quality control in the central laboratory setting.RESULTS:The positive culture rate was 31.66%(21036/66452) for the patient samples and 71.72%(4114/5736) for the H.pylori-positive quality control specimens.In the 5 h transport group,the positiveculture rate was 30.99%(3865/12471),and 32.84%(14960/45553) in the 24 h transport group.In contrast,the positive culture rate declined significantly in the 48 h transport group(26.25%; P 0.001).During transportation,the average natural temperature increased from 4.67 to 29.14℃,while the positive culture rate declined from 36.67%(1462/3987) to 24.12%(1799/7459).When the temperature exceeded 24℃,the positive culture rate decreased significantly,especially in the 48 h transport group(23.17%).CONCLUSION:Transportation of specimens within 24 h and below 24℃ is reasonable and acceptable for centralized culture of multicenter H.pylori samples.     

Different risk factors influence peptic ulcer disease development in a Brazilian population

AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P 0.0001) and intestinal metaplasia (OR = 1.0520, P 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P 0.0001) and with the incidence of DU (OR = 3.6077, P 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU.     

Abnormal DNA-PKcs and Ku 70/80 expression may promote malignant pathological processes in gastric carcinoma

AIM:To determine the expression of the catalytic subunit of DNA-dependent protein kinase(DNA-PKcs)and the Ku70/Ku80 heterodimer(Ku 70/80)in gastric carcinoma.METHODS:Gastric biopsies were obtained from 146gastric carcinoma patients[Helicobacter pylori(H.pylori)-negative:89 and H.pylori-positive:57]and 34from normal subjects(H.pylori-negative:16 and H.pylori-positive:18)via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University.Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system.An‘‘in-house’’rapid urease test and modified Giemsa staining were employed to detect H.pylori infection.The expression of DNA-PKcs and the Ku 70/80protein was detected by immunohistochemistry.RESULTS:Overall,the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer(χ2=133.04,P<0.001 for DNA-PKcs andχ2=13.06,P<0.01 for Ku)compared with normal gastric mucosa.There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa,and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0%(0/34),whereas the rate in gastric cancer(GC)was 93.8%(137/146).The difference between the two groups was statistically significant.Additionally,the positive rate of Ku 70/80 was79.4%(27/34)in normal gastric mucosa and 96.6%(141/146)in gastric cancer.The DNA-PKcs protein level was significantly increased in gastric cancer(MannWhitney U=39.00,P<0.001),compared with normal gastric mucosa.In addition,there was a significant difference in the expression of Ku 70/80(Mann-Whitney U=1117.00,P<0.001)between gastric cancer and normal gastric mucosa.There was also a significant difference in Ku70/80 protein expression between GC patients with and without H.pylori infection(P<0.05).Spearman analysis showed a negative correlation between tumor differentiation and DNA-PKcs expression(r=-0.447,P<0.05).Moreov     

MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults

AIM:To evaluate the association between Helicobacter pylori(H.pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability(MSI).METHODS:The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction(MSPPCR) in gastric biopsy samples from uninfected or H.pylori-infected children(n = 50),from adults with chronic gastritis(n = 97) and from adults with gastric cancer(n = 92).MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene(β actin).MSI analysis was performed by screening MSI markers at 4 loci(Bat-25,Bat-26,D17S250 and D2S123) with PCR;PCR products were analysed by single strand conformation polymorphism followed by silver staining.Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher’s exact test,and statistical significance for expression analysis was assessed using an unpaired Student’s t-test.RESULTS:Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children,regardless of H.pylori infection status.The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H.pylori infection(P < 0.05);this region was methylated in 66% of gastric cancer patients,and the difference in the percentage of methylated samples between these patients and those from H.pylori-infected chronic gastritis patients was statistically significant(P < 0.05).MLH1 methylation frequencies among H.pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%,respectively.We observed methylation of the MLH1 promoter(39%) and increased MSI levels(68%) in samples from gastric cancer patients in comparison to samples from H.pylori-infected adult chronic gastritis patients(P < 0.001 and P < 0.01,respectively).The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H.pylori-positiv     

Age, smoking and overweight contribute to the development of intestinal metaplasia of the cardia

AIM: To assess the role of Helicobacter pylori (H. pylori), gastroesophageal reflux disease (GERD), age, smoking and body weight on the development of intestinal metaplasia of the gastric cardia (IMC).METHODS: Two hundred and seventeen patients scheduled for esophagogastroduodenoscopy were enrolled in this study. Endoscopic biopsies from the esophagus, gastroesophageal junction and stomach were evaluated for inflammation, the presence of H. pylori and intestinal metaplasia. The correlation of these factors with the presence of IMC was assessed using logistic regression.RESULTS: IMC was observed in 42% of the patients. Patient age, smoking habit and body mass index (BMI) were found as potential contributors to IMC. The risk of developing IMC can be predicted in theory by combining these factors according to the following formula: Risk of IMC = a + s - 2B where a = 2,…6 decade of age, s = 0 for non-smokers or ex-smokers, 1 for < 10 cigarettes/d, 2 for > 10 cigarettes/d and B = 0 for BMI < 25 kg/m² (BMI < 27 kg/m² in females), 1 for BMI > 25 kg/m² (BMI > 27 kg/m² in females). Among potential factors associated with IMC, H. pylori had borderline significance (P = 0.07), while GERD showed no significance.CONCLUSION: Age, smoking and BMI are potential factors associated with IMC, while H. pylori and GERD show no significant association. IMC can be predicted in theory by logistic regression analysis.     

First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

AIM: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or ¹³C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642).RESULTS: The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population.CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs.     

Helicobacter pylori infection in patients with selective immunoglobulin E deficiency

AIM: To investigate the prevalence and clinical characteristics of Helicobacter pylori(H.pylori)-infected dyspeptic patients with selective immunoglobulin E deficiency(IgE d).METHODS: All individuals who underwent serum totalimmunoglobulin E(Ig E) measurement at the Leumit Healthcare Services(Israel) in 2012 were identified in an electronic database search(n = 18487).From these,selected case group subjects were ≥ 12 years of age and had serum total Ig E 2 k IU/L(n = 158).The control group was selected from a random sampling of the remaining subjects ≥ 12 years of age to obtain a case-control ratio of 1:20(n = 3160).Dyspeptic diseases,diagnosed no more than 5 years before serum total Ig E testing,were identified and retrieved from the electronic database using specific International Classification of Diseases diagnostic codes.Results of C13-urea breath tests were used to identify subjects infected with H.pylori.Categorical variables between case and control subjects were analyzed using Fisher's exact tests,whereas continuous variables were analyzed using χ2 tests.RESULTS: Dyspepsia was present in 27.2%(43/158) of case subjects and 22.7%(718/3160) of controls.Of these,significantly more case subjects(32/43,74.4%) than controls(223/718,31.1%) were positive for H.pylori(P 0.01).Esophagogastroduodenoscopy was performed in 19 case and 94 control subjects,revealing that gastritis was more prevalent in IgE d case subjects than in controls(57.9% vs 29.8%,P 0.05).Furthermore,a significantly greater proportion of case subjects presented with peptic duodenal ulcers(63.2% vs 15.9%,P 0.01).Histopathologic examination showed marked chronic inflammation,lymphoid follicle formation and prominent germinal centers,with polymorphonuclear cell infiltration of gastric glands,that was similar in case and control biopsy tissues.Finally,Ig Ed case subjects that underwent esophagogastroduodenoscopy were more likely to exhibit treatment-refractory H.pylori infections that require second-line triple antibiotic therapy(47.4% vs 11.7%,P 0.01).CONCLUSION: IgE d is associated with higher rates ofH.pylori-associated gastritis and peptic duodenal ulcers.     

Gastric precancerous lesions are associated with gene variants in Helicobacter pylori -susceptible ethnic Malays

AIM: To identify genes associated with gastric pre-cancerous lesions in Helicobacter pylori (H. pylori )susceptible ethnic Malays. METHODS: Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as "cases". Thirtyseven Malay subjects who were H. pylori negative and had no precancerous lesions were included as "controls". Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ2 P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers. RESULTS: Of the 23 H. pylori -positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in "cases" vs "controls" for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively. CONCLUSION: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.     

Helicobacter pylori neutrophil-activating protein:From molecular pathogenesis to clinical applications

Helicobacter pylori(H.pylori)neutrophil-activating protein(HP-NAP)was originally identified as a virulence factor of H.pylori for its ability to activate neutrophils to generate respiratory burst by releasing reactive oxygen species.Later on,HP-NAP was also found to be involved in the protection of H.pylori from DNA damage,supporting the survival of H.pylori under oxidative stress.This protein is highly conserved and expressed by virtually all clinical isolates of H.pylori.The majority of patients infected with H.pylori produced antibodies specific for HP-NAP,suggesting its important role in immunity.In addition to acting as a pathogenic factor by activating the innate immunity through a wide range of human leukocytes,including neutrophils,monocytes,and mast cells,HP-NAP also mediates adaptive immunity through the induction of T helper cell typeⅠresponses.The pro-inflammatory and immunomodulatory properties of HP-NAP not only make it play an important role in disease pathogenesis but also make it a potential candidate for clinical use.Even though there is no convincing evidence to link HP-NAP to a disease outcome,recent findings supporting the pathogenic role of HP-NAP will be reviewed.In addition,the potential clinical applications of HP-NAP in vaccine development,clinical diagnosis,and drug development will be discussed.     

Histological changes of gastric mucosa after Helicobacter pylori eradication:a systematic review and meta-analysis

AIM:To systematically review pathological changes of gastric mucosa in gastric atrophy(GA)and intestinal metaplasia(IM)after Helicobacter pylori(H.pylori)eradication.METHODS:A systematic search was made of PubMed,Web of Science,EMBASE,ClinicalTrials.gov,OVID and the Cochran Library databases for articles published before March 2013 pertaining to H.pylori and gastric premalignant lesions.Relevant outcomes from articles included in the meta-analysis were combined using Review Manager 5.2 software.A Begg’s test was applied to test for publication bias using STATA 11software.χ2 and I2 analyses were used to assess heterogeneity.Analysis of data with no heterogeneity(P>0.1,I2<25%)was carried out with a fixed effects model,otherwise the causes of heterogeneity were first analyzed and then a random effects model was applied.RESULTS:The results of the meta-analysis showed that the pooled weighted mean difference(WMD)with 95%CI was 0.23(0.18-0.29)between eradication and non-eradication of H.pylori infection in antral IM with a significant overall effect(Z=8.19;P<0.00001)and no significant heterogeneity(χ2=27.54,I2=16%).The pooled WMD with 95%CI was-0.01(-0.04-0.02)for IM in the corpus with no overall effect(Z=0.66)or heterogeneity(χ2=14.87,I2=0%)(fixed effects model).In antral GA,the pooled WMD with 95%CI was 0.25(0.15-0.35)with a significant overall effect(Z=4.78;P<0.00001)and significant heterogeneity(χ2=86.12,I2=71%;P<0.00001).The pooled WMD with 95%CI for GA of the corpus was 0.14(0.04-0.24)with a significant overall effect(Z=2.67;P=0.008)and significant heterogeneity(χ2=44.79,I2=62%;P=0.0003)(random effects model).CONCLUSION:H.pylori eradication strongly correlates with improvement in IM in the antrum and GA in the corpus and antrum of the stomach.     

Helicobacter pylori and gastric cancer: Indian enigma

Helicobacter pylori(H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade Ⅰ carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.     

Eradication of Helicobacter pylori increases childhood growth and serum acylated ghrelin levels

AIM: To determine whether Helicobacter pylori (H. pylori)-infected children have reduced body weight (BW) and height (BH) growth, and if H. pylori eradication may restore growth while improving serum acylated ghrelin.METHODS: This longitudinal cohort study with one-year follow-up enrolled 1222 children aged 4 to 12 years old into an observation cohort (18 with and 318 without H. pylori) and intervention cohort (75 with and 811 without). The 7-d triple therapy was used for eradication in the intervention cohort. The net increases of BW and BH as well serum acylated ghrelin after one-year follow-up were compared between successful eradicated H. pylori-infected children and controls.RESULTS: In the observation cohort, the H. pylori-infected children had lower z score of BW (-1.11 ± 0.47 vs 0.35 ± 0.69, P = 0.01) and body mass index (BMI) (0.06 ± 0.45 vs 0.44 ± 0.73, P = 0.02) at enrollment and lower net BW gain after one-year follow-up (3.3 ± 2.1 kg vs 4.5 ± 2.4 kg, P = 0.04) than the non-infected controls. In the intervention cohort, the H. pylori-infected children had lower z score of BMI (0.25 ± 1.09 vs 0.68 ± 0.87, P = 0.009) and serum acylated ghrelin levels (41.8 ± 35.6 pg/mL vs 83.6 ± 24.2 pg/mL, P < 0.001) than the non-infected controls. In addition to restoring decreased serum ghrelin levels (87.7 ± 38.0 pg/mL vs 44.2 ± 39.0 pg/mL, P < 0.001), the H. pylori-infected children with successful eradication had higher net gains (P < 0.05) and increase of z scores (P < 0.05) of both BW and BH as compared with non-infected controls after one-year follow-up.CONCLUSION: H. pylori-infected children are associated with low serum acylated ghrelin and growth retardation. Successful eradication of H. pylori restores ghrelin levels and increases growth in children.     

Typical and atypical symptoms of gastro esophageal reflux disease: Does Helicobacter pylori infection matter?

AIM: To analyze whether the presence of Helicobacter pylori(H. pylori) infection could affect the quality of symptoms in gastro-esophageal reflux disease(GERD) patients. METHODS: one hundred and forty-four consecutive patients referred to our Unit for suspected GERD were recruited for the study. All patients underwent esophageal p H-metric recording. For those with a positive test, C13 urea breath test was then performed to assess the H. pylori status. GERD patients were stratified according to the quality of their symptoms and classified as typical, if affected by heartburn and regurgitation, and atypical if complaining of chest pain, respiratory and ears, nose, and throat features. H. pylori-negative patients were also asked whether they had a previous diagnosis of H. pylori infection. If a positive response was given, on the basis of the time period after successful eradication, patients were considered as "eradicated"(E) if H. pylori eradication occurred more than six months earlier or "recently eradicated" if the therapy had been administered within the last six months. Patients without history of infection were identified as "negative"(N). χ2 test was performed by combining the clinical aspects with the H. pylori status.RESULTS: one hundred and twenty-nine of the 144 patients, including 44 H. pylori-positive and 85 H. pylori-negative(41 negative, 21 recently eradicated, 23 eradicated more than 6 mo before), were eligible for the analysis. No difference has been found between H. pylori status and either the number of reflux episodes(138 ± 23 vs 146 ± 36, respectively, P = 0.2, not significant) or the percentage of time with pH values 4(6.8 ± 1.2 vs 7.4 ± 2.1, respectively, P = 0.3, not significant). The distribution of symptoms was as follows: 13 typical(30%) and 31 atypical(70%) among the 44 H. pylori-positive cases; 44 typical(52%) and 41 atypical(48%) among the 85 H. pylori-negative cases,(P = 0.017 vs H. pylori +; OR = 2.55, 95%CI: 1.17-5.55). Furthermore, clinical signs in patients with recent H. pylori eradication were similar to those of H. pylori-positive(P = 0.49; OR = 1.46, 95%CI: 0.49-4.37); on the other hand, patients with ancient H. pylori eradication showed a clinical behavior similar to that of H. pylori-negative subjects(P = 0.13; OR = 0.89, 95%CI: 0.77-6.51) but different as compared to the H. pylori-positive group(P 0.05; OR = 3.71, 95%CI: 0.83-16.47).CONCLUSION: Atypical symptoms of GERD occur more frequently in H. pylori-positive patients than in H. pylori-negative subjects. In addition, atypical symptoms tend to decrease after H. pylori eradication.