Gastritis Patients Research Articles

Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation.

ABSTRACTA known virulence factor of Helicobacter pylori that augments gastric cancer risk is the CagA cytotoxin. A carcinogenic derivative strain, 7.13, that has a greater ability to translocate CagA exhibits much higher hydrogenase activity than its parent noncarcinogenic strain, B128. A Δhyd mutant strain with deletion of hydrogenase genes was ineffective in CagA translocation into human gastric epithelial AGS cells, while no significant attenuation of cell adhesion was observed. The quinone reductase inhibitor 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO) was used to specifically inhibit the H2-utilizing respiratory chain of outer membrane-permeabilized bacterial cells; that level of inhibitor also greatly attenuated CagA translocation into AGS cells, indicating the H2-generated transmembrane potential is a contributor to toxin translocation. The Δhyd strain showed a decreased frequency of DNA transformation, suggesting that H. pylori hydrogenase is also involved in energizing the DNA uptake apparatus. In a gerbil model of infection, the ability of the Δhyd strain to induce inflammation was significantly attenuated (at 12 weeks postinoculation), while all of the gerbils infected with the parent strain (7.13) exhibited a high level of inflammation. Gastric cancer developed in 50% of gerbils infected with the wild-type strain 7.13 but in none of the animals infected with the Δhyd strain. By examining the hydrogenase activities from well-defined clinical H. pylori isolates, we observed that strains isolated from cancer patients (n = 6) have a significantly higher hydrogenase (H2/O2) activity than the strains isolated from gastritis patients (n = 6), further supporting an association between H. pylori hydrogenase activity and gastric carcinogenesis in humans.

Metabolomic Analysis of Gastric Cancer Progression within the Correa's Cascade Using Ultraperformance Liquid Chromatography-Mass Spectrometry.

Gastric cancer (GC) is among the most common cancers worldwide. Gastric carcinogenesis is a multistep and multifactorial process beginning with chronic gastritis induced by Helicobacter pylori (H. pylori) infection. This process is often described via a sequence of events known as Correas's cascade, a stepwise progression from nonactive gastritis, chronic active gastritis, precursor lesions of gastric cancer (atrophy, intestinal metaplasia, and dysplasia), and finally adenocarcinoma. Our aim was to identify a plasma metabolic pattern characteristic of GC through disease progression within the Correa's cascade. This study involved the analysis of plasma samples collected from 143 patients classified in four groups: patients with nonactive gastritis and no H. pylori infection, H. pylori infected patients with chronic active gastritis, infected or noninfected patients with precursor lesions of gastric cancer, and GC. Independent partial least-squares-discriminant binary models of UPLC-ESI(+)-TOFMS metabolic profiles, implemented in a decision-directed acyclic graph, allowed the identification of tryptophan and kynurenine as discriminant metabolites that could be attributed to indoleamine-2,3-dioxygenase upregulation in cancer patients leading to tryptophan depletion and kynurenine metabolites generation. Furthermore, phenylacetylglutamine was also classified as a discriminant metabolite. Our data suggest the use of tryptophan, kynurenine, and phenylacetylglutamine as potential GC biomarkers.

Polymorphisms in HLA-DQ genes, together with age, sex, and Helicobacter pylori infection, as potential biomarkers for the early diagnosis of gastric cancer.

Polymorphisms in inflammation-related genes are factors associated with the development of gastroduodenal diseases in Helicobacter pylori-infected individuals. We aimed to analyze polymorphisms in HLA-DQ, together with other host and H.pylori variables as risk factors for precancerous and cancerous gastric lesions. 1052 individuals were studied, including nonatrophic gastritis (NAG), intestinal metaplasia (IM), gastric cancer (GC) or duodenal ulcer (DU) patients, and healthy volunteers. Patients with alleles DQA*01:01 (OR 0.78), *01:02 (OR 0.29), *01:03 (OR 0.31), and DQB*02:01/02 (OR 0.40) showed a reduced risk for GC. A multivariate logistic regression analyses showed that patients with homozygote genotypes DQA1*03:01 (OR 7.27) and DQA1*04:01 (OR 8.99) and DQB1*05:01:01 (OR 12.04) were at significantly increased risk for GC. Multivariate analyses also demonstrated that age (OR>10.0) and gender (OR>2.0) were variables that influenced significantly the risk for GC, while H.pylori infection (OR>2.5) increased the risk for IM. We identified HLA-DQ alleles associated with IM and GC, and confirm that age, sex, and H.pylori infection are variables that also influence the risk for disease. The use of multiple markers, HLA-DQ alleles, age, sex, and H.pylori infection may be useful biomarkers for the early diagnosis of patients with IM and GC.

OC-020 Is Taking Histological Biopsies in Patients With Gastritis A Waste of Time and Money?

Introduction The clinical usefulness of taking gastric biopsies in patients with endoscopic gastritis is unclear. There are international recommendations in support of this but the cost effectiveness is questionable and there is little evidence that biopsies influence patient management. 1 Methods In 2014, 1109 patients were identified as having endoscopic gastritis based on a retrospective review of the hospital’s Endoscopy database. Of these patients, 610 had a urease test, 90 had both urease testing and gastric histology, 378 just had histology and 31 had neither test. A more detailed review of the patient’s clinical notes and histology was undertaken for 114 consecutive gastritis patients who had gastric biopsies sent for histological analysis over a 3 month period (Aug-Oct). Results 56% of the patients were female (64/114) with an average age of 65 years (range 17–91). 76% of these patients were taking a PPI at the time of endoscopy. Dyspepsia/reflux (43%) was the commonest primary indication, followed by anaemia/GI bleeding (24.5%), dysphagia (10.5%), nausea/vomiting (6%) and miscellaneous others. 88.5% of patients had at least 2 antral biopsies taken. 17.5% of patients had both antral and corpus biopsies. 6% of patients had both urease testing and histology. No serious pathology was found on any of the histological samples. The commonest histological diagnosis was chemical, reactive or inflammatory gastritis (70%), followed by normal (17%), Helicobacter pylori (Hp) gastritis (10.5%), intestinal metaplasia (1%) and fundic gland polyp (1%). Conclusion Despite recommendations to the contrary, 1 we found 42% of patients with uncomplicated gastritis still have gastric biopsies sent for histopathological analysis. The reasons why an Endoscopist chooses to request histology rather than a urease test are not clear. We suspect decision-making is influenced by whether the patient is taking a PPI with a perception that this may reduce the sensitivity of urease testing. However the manufacturer of Endosc-Hp™ reports a sensitivity of 94.4% in detecting Hp even if the patient is taking a PPI (email comm). Consequently there would seem to be no additional value in sending histology in this group of patients. The cost savings are considerable. Even in a DGH serving a population of 220,000, the annual cost savings of carrying out urease testing rather than histology in patients with uncomplicated gastritis would amount to at least £37000. This study supports the Royal College of Pathologists contention that “biopsy for histological classification of gastritis is unlikely to change management” and taking biopsies for patients with uncomplicated gastritis “is not recommended.” 1 Reference 1 Loughrey MB, Johnston BT. Frontline Gastroenterology 2014; 5 :88–95. Disclosure of Interest None Declared

Effect of IL-1 Polymorphisms, CYP2C19 Genotype and Antibiotic Resistance on Helicobacter pylori Eradication Comparing Between 10-day Sequential Therapy and 14-day Standard Triple Therapy with Four-Times-Daily-Dosing of Amoxicillin in Thailand: a Prospective Randomized Study.

Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.

The application value in diagnosis of chronic atrophic gastritis using the magnifying endoscopy and narrow-band imaging

Objective To explore the application value in diagnosis of chronic atrophic gastritis using the magnifying endoscopy and narrow-band imaging. Methods A total of 98 cases of chronic atrophic gastritis patients was selected, and carried out the ordinary white light endoscopy, magnifying endoscopy and narrow-band imaging(ME-NBI) and pathological examination in file, followed by comparison of the results. Results The sensitivity and specificity of chronic atrophic gastritis by magnifying endoscopy and narrow-band imaging mode were 74.07% and 82.35%, respectively; which were significantly higher than that obtained by conventional endoscopy, which were 48.15% and 64.71% (P<0.05). In magnifying endoscopy and narrow-band imaging endoscopy group, 60 patients were positive, which intestinal metaplasia accounted for 35%, while in conventional endoscopy group, 39 patients were positive which was only 17.95% (P<0.05). Conclusions Magnifying endoscopy and narrow-band imaging can improve the diagnostic accuracy of chronic atrophic gastritis. Key words: Endoscopy/MT; Gastritis, atrophic/DI

Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China.

Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy. Infection with vacA s1, i1 and m1 strains increases the risk for progression of gastric premalignant lesions and for gastric carcinoma. However, in East Asian countries most of the H. pylori strains are vacA s1, regardless of the patients’ clinical status, and the significance of the vacA i1 and m1 genotypes for gastric carcinoma in this geographic area remains to be fully elucidated. The aim of the present study was to investigate this relationship in 290 patients from Macau, China. Using very sensitive and accurate genotyping methods, we detected infection with vacA i1 and with vacA m1 strains in, respectively, 85.2% and 52.6% of the patients that were infected with single genotypes. The prevalence of cagA-positive strains was 87.5%. No significant associations were observed between vacA genotypes or cagA and gastric carcinoma. It is worth noting that 37.5% of the infected patients had coexistence of H. pylori strains with different vacA genotypes. Additional studies directed to other H. pylori virulence factors should be performed to identify high risk patients in East Asia.

Su1252 Utility of Bile Acid Scintigraphy in the Diagnosis of Remnant Gastritis in Patients With Roux-en-Y Gastric Bypass

Su1252 Utility of Bile Acid Scintigraphy in the Diagnosis of Remnant Gastritis in Patients With Roux-en-Y Gastric Bypass

An Observational Study on Aberrant Methylation of Runx3 With the Prognosis in Chronic Atrophic Gastritis Patients.

The aim of this study is to discuss whether the methylation levels of Runx3 could be used as the early biomarker for predicting the prognosis in chronic atrophic gastritis (CAG) patients. A total of 200 subjects including 60 controls without CAG (Group 1), 70 patients with mild CAG (Group 2), and 70 patients with moderate and severe CAG (Group 3) were recruited for this cross-sectional investigation in the Department of Gastroenterology in Daqing Oilfield General Hospital from July 2013 to May 2014. The MlALDI-TOF-MS was used to measure the methylation levels of Runx3 in all of the subjects. Real-time quantitative reverse transcription polymerase chain reaction and western blotting were chosen to determine the expression levels of Runx3. The correlations between methylation levels of Runx3 among these CAG patients and their prognosis were shown by logistic regression models. The results demonstrated that the methylation levels of CpG13, CpG14, and CpG15 in Runx3 were higher in Group 3 than those in Groups 1 and 2 (P <0.05), whereas the mRNA and protein expression levels of Runx3 were lower in Group 3 than those in Groups 1 and 2 (P <0.05). There were significantly negative correlations between the methylation levels of Runx3 with its expression and the healing prognosis of CAG patients. In brief, this study proved that the hypermethylation modifications of CpG13, CpG14, and CpG15 in the promoter region of Runx3 could result in the down regulation of Runx3 expression to affect the prognosis of CAG. So the methylation levels of these CpG sites in Runx3 in the peripheral blood can be used as the biomarker for predicting the healing prognosis of CAG patients.

CLINICAL, ENDOSCOPIC AND PATHOLOGICAL RESPONSES AFTER ERADICATION WITH RACM REGIMEN IN PATIENTS OF HELICOBACTER PYLORI-RELATED CHRONIC GASTRITIS

Background: The clinical, endoscopic and histopathological responses after Helicobacter pylori eradication in patients of chronic gastritis were still inconstant. This study is aimed at: (1) evaluating of clinical variations, endoscopic images six months after Helicobacter pylori eradication by Rabeprazole-Amoxicillin—Metronidazole-Clarithromycin therapy for 14 days. (2) assessing histopathological response six months after H. pylori eradication. Method: prospective, consisting of 83 patients examined and treated in Danang hospital from 4/2014 to 6/2015. Results: There were improvements in clinical symptoms 6 months after H. pylori eradication: epigastric pain 85.5% vs. 7.2%); bloating (97.1% vs. 4.3%); indigestion (47.8% vs. 2.9%); weight loss (17.4% vs. 1.4%); anorexia (23.2% vs. 2.9%) (p&lt; 0.01). However, there were no improvement regarding common lesions on endoscopy, edema (33.3% increase to 71%); flat erosion and elevated erosion (15.9% vs. 8.7%); atrophy (7.2%); haemorrhagic (5.8% vs. 0%); hypertrophic (7.2% vs. 0%); bile reflux (14.5% vs. 4.3%). Regarding histopathology: active inflammation accounted for a high proportion (63.8% vs. 27.5%); non-active inflammation (36.2% increase to 72.5%); atrophy (8.7% vs. 5.8%); dysplasia (26.1% vs. 1.4%), no significant change in intestinal metaplasia was found after treatment. Conclusions: There was an improvement in clinical symptoms and histopathological against inflammatory activity grade, dysplasia at the time before and after 6 months treatment H. pylori eradication. However, no significant change in mucosal atrophy and intestinal metaplasia was found. Key words: chronic gastritis; H. pylori; clinical, endoscopic and pathological responses

CHRONIC HELICOBACTER PYLORI GASTRITIS: THE ERADICATION EFFICACY&amp;NBSP;OF THE&amp;NBSP;BISMUTH-CONTAINING QUADRUPLE REGIMEN (EBMT)

Background: there has not been yet any research on the effectiveness of H. pylori eradication of bismuth-containing quadruple regimen on chronic gastritis patients in our country. Objective: to evaluate H. pylori eradication rate of bismuth-containing quadruple regimen according to intention to treat (ITT), per protocol (PP) analysis, the rate of side effects and medication compliance. Subjects and Methods: from March 2014 to January 2016 we used bismuth-containing quadruple regimen (EBMT) 10 days for H. pylori eradication therapy for 166 chronic gastritis patients diagnosed based on clinical, endoscopic, rapid urease test, histology and culture. Patients were evaluated side effects and medication compliance at the end of treatment (day 11-14). To assess the eradication, repeating endoscopy with both rapid urease test and histological examination were performed at 4 to 8 weeks after stopping treatment course. Results: H. pylori eradication rates on ITT and PP analysis overall, for naïve patients, after one and more two eradication failures were respectively: 80.72-89.33%, 79.51-90.65%, 91.67-91.67% and 75.00-78.95%. Medication adherence rate was 96.99%. The rates of patients experiencing moderate, severe and very severe side effects were: 19.88%, 0.60% and 1.81%. Conclusion: the EBMT 10-day regimen attained high eradication rates in chronic gastritis patients with rare serious side effects and the high compliance rate. We should apply bismuth-containing quadruple regimen in H. pylori eradication therapy for naïve patients or after one eradication failure. Key words: bismuth-containing quadruple regimen, EBMT, eradication, chronic Helicobacter pylori gastritis

Braf, Kras and Helicobacter pylori epigenetic changes-associated chronic gastritis in Egyptian patients with and without gastric cancer.

We aimed to study MLH1 and MGMT methylation status in Helicobacter pylori-associated chronic gastritis in Egyptian patients with and without gastric cancer. 39 patients were included in our study. They were divided into 2 groups; patients without (group I) and with gastric adenocarcinoma (group II). Patients were subjected to clinical examination, abdominal ultrasound and upper endoscopy for gastric biopsy. Biopsies were subjected to urease test, histological examination, and DNA purification. H. pylori, Braf, Kras, MLH1 and MGMT methylation were assessed by quantitative PCR. DNA sequencing was performed to assess Braf and Kras genes mutation. qPCR of H. pylori was significantly higher in patients with adenocarcinoma (group II) than those without adenocarcinoma (group I); with a p<0.001 as well as in patients with age above 50years with a p value=0.008. By applying logistic regression analysis it was reported that the H. pylori qPCR is a significant predictor to the adenocarcinoma with OR=1.025 (95% CI: 1. 002-1.048), with sensitivity of 90% and specificity of 100%. Adenocarcinoma patients had a significantly higher mean age and levels of H. Pylori, Braf, K-ras, methylated MGMT and methylated MLH1 than those of gastritis patients. DNA sequence analysis of Braf (codon 12) and Kras (codon 600) had genes mutation in gastric adenocarcinoma versus chronic gastritis. H. pylori may cause epigenetic changes predisposing the patients to cancer stomach. Estimation of H. pylori by qPCR can be a good predictor to adenocarcinoma. Braf and Kras genes mutation were reveled in gastritis and adenocarcinoma patients.

Polyautoimmunity in autoimmune gastritis

ObjectivesAutoimmune gastritis may be associated with other organ-specific autoimmune disorders, but the prevalence of this association is not entirely quantified. The aims of this study were to investigate the prevalence of autoimmune disorders and evaluate the factors that might affect this association in patients with autoimmune gastritis. MethodsA total of 320 patients with autoimmune gastritis were retrospectively studied and data on concomitant autoimmune diseases, serum gastrin and chromogranin A levels, anti-Hp IgG, antiparietal cell antibodies, presence of enterochromaffin-like cell hyperplasia and gastric atrophy were gathered for each patient and associations between autoimmune gastritis and studied parameters were explored through descriptive statistics and logistic regression analysis. ResultsOf the 320 atrophic body autoimmune gastritis patients, 171 (53.4%) had an associated autoimmune disorder. Autoimmune thyroiditis was the most common concurrent disease, diagnosed in 116 patients (36.2%). Multivariate analysis showed that, presence of enterochromaffin cell hyperplasia (odds ratio [OR] 9.445, 95% confidence [CI]: 4.42–20.22), serum gastrin (OR 3.1, 95% CI: 1.46–6.60) and serum chromogranin A (OR 4.14, 95% CI: 2.01–8.52) levels remained significantly associated with the coexistence of an autoimmune disease. ConclusionsConcurrent autoimmune diseases are common in patients with autoimmune gastritis. Autoimmune thyroiditis is the most encountered disease. These data suggest that patients with autoimmune gastritis should be investigated for the presence of an autoimmune disease, in particular patients with enterochromaffin cell hyperplasia and those with serum gastrin and chromogranin A levels above cut-off values.

Relationships between autonomic nerve function and gastric emptying in patients with autoimmune gastritis.

Autonomic nervous system dysfunction exists in autoimmune diseases. Symptoms of autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any autonomic dysfunction exists in autoimmune gastritis patients, and if so, to clarify the relationship between the autonomic nervous dysfunction, delayed gastric emptying, and gastrointestinal symptoms. 75 patients (50 women, mean age 56.73±11.77) diagnosed with autoimmune gastritis were investigated by means of autonomic nervous system and gastric emptying tests. All patients underwent a standardized scintigraphic gastric emptying study and five tests evaluating autonomic nervous system. Patients with autonomic nervous system dysfunction were then analyzed and compared by means of existence of delayed gastric emptying and gastrointestinal symptoms. 62 patients had autonomic nervous system dysfunction (14 mild, 40 moderate, and 8 severe autonomic dysfunction). The mean total score of autonomic tests was 3.85±2.35. Total autonomic score of patients (n=60) with delayed gastric emptying was significantly higher than patients (n=15) with normal gastric emptying (4.68±1.7 vs. 1.53±0.58, p<0.001). Mean gastroparesis cardinal symptom index was significantly higher in patients (n=60) with delayed gastric emptying half-time compared to patients (n=15) with normal gastric emptying half-time (1.89±1.16 vs 0.4±0.3, p<0.001). Most of patients with autoimmune gastritis also have autonomic nerve dysfunction. There is a close relationship between autonomic nervous system dysfunction and delayed gastric emptying. Gastroparesis cardinal symptom index has a high sensitivity and specificity in predicting both autonomic nerve function and delay in gastric emptying.

EFFICACY OF RACM REGIMEN ON HELICOBACTER PYLORI ERADICATION IN PATIENTS OF CHRONIC GASTRITIS

Background: H. pylori eradication still remains a challenge to clinicians, especially with the increasing antibiotic-resistant H. pylori. Concomitant therapy showed effective, even in some multiresistant population, but data in Vietnam is still very limited. The study ''Study of Helicobacter pylori eradication with RACM regimen in chronic gastritis patients at Da Nang Hospital from 1/4/2014 to 30/6/2015, is aimed at: (1) Evaluating the results of Helicobacter pylori eradication of Amoxicillin-Clarithromycin-Rabeprazole-Metronidazole therapy for 14 days.(2) Assessing some side effects of this regimen.Method: prospective, consisting of 83 patients examined and treated in Danang hospital from1/ 4/2014 to 30/6/2015, H.pylori was tested by rapid Urease test; H.pylori positive patients received RACM for 14 days. Results: H.pylori eradication rate was 83.1%. H. pylori eradication rates in different locations: antrum 63.8%, higher than corpus (17.4%), antrum and corpus (18.8%), with statistical significance at p&lt;0.05. Common side effects was nausea (27.7%), diarrhea (19.3%). Abdominal pain, lightheadedness, dizziness, insomnia, headache account for low percentage: 8%; 6%; 3,6% and 2.4% respectively. Conclusion: The effect of 14 day RACM regimen for H. pylori eradication was 83.1%, common side effects are nausea (27.7%), diarrhea (19.3%). Key words: chronic gastritis;H. pylori; eradication of H. pylori(ITT); RACM regimen.

Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.

Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-β stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF-β.

Helicobacter pylori Infection Increases Frequency of PDCA-1+ (CD317+) B-cell Subsets

As a newly discovered B-cell subset, PDCA-1(+) Bcells have been shown to participate in the immune clearance of invading pathogens. The prominence of PDCA-1(+) Bcell immunity in the pathogenesis of Helicobacter pylori infection prompted us to explore the potential role of this subset in gastric H. pylori infection. H. pylori infection was determined by (14)C-urea breath test and Western blot. The frequency of the different sub-compartments of PDCA-1(+) Bcells and their relation to serum cytokines was determined in 33 H. pylori-infected and 14 uninfected patients and in 12 healthy controls (HC). In comparison to uninfected individuals, there was a significantly increased frequency of PDCA-1(+) Bcells, PDCA-1(+)IgM(+) Bcells, CD93(+)PDCA-1(+) Bcells, CD93(+)PDCA-1(+)IgM(+) Bcells, CD137(+)PDCA-1(+) Bcells and CD137(+)PDCA-1(+)IgM(+) Bcells were detected in patients with H. pylori infection, corresponding to increased levels of serum IFN-α and IgM in this group. Compared with H. pylori-positive (HP(+)) chronic non-atrophic gastritis patients, a larger proportion of PDCA-1(+) Bcells, CD93(+)PDCA-1(+) Bcells and CD137(+)PDCA-1(+) Bcells were observed in HP(+) patients suffering from atrophic gastritis or HP(+) peptic ulcers. The frequency of the PDCA-1(+) Bcell compartment is increased during H. pylori infection. Our data support the potential role of this B-cell subset in the pathogenesis of H. pylori-dependent gastritis.

Quadruple regimens using domestically manufactured drugs in gastritis and duodenal ulcer patients for Helicobacter pylori eradication: a perspective, multicenter, randomized controlled trial

To observe the effects and safety of quadruple regimens including domestically manufactured rabeprazole used as first line/initial therapy for Helicobacter pylori(H.pylori) eradication in gastritis and duodenal ulcer patients, and to investigate the effects of extended use of bismuth after the quadruple therapy on eradication of H. pylori. From January to August 2013, 430 patients with chronic gastritis or duodenal ulcer who were confirmed as H. pylori positive in gastroscopy for upper gastrointestinal symptoms were enrolled from 12 centers in China for initial treatment using quadruple regimens for H. pylori eradication. The study was a prospective, multicenter, randomized double-blinded double-dummy parallel-controlled clinical trial. The 310 chronic gastritis patients were divided into 2 groups: group A1 was given quadruple regime (rabeprazole+ amoxicillin+ clarithromycin+ bismuth potassium citrate) for 10 days followed by bismuth-placebo for 21 days; group A2 was given the quadruple regimen for 10 days and then bismuth potassium citrate for 21 days. The duodenal ulcer patients were given the quadruple for 10 days, then rabeprazole for 14 days. All the patients took (13)C urea breath test to detect H. pylori 28 days after medicine withdrawal. Altogether 428 cases were enrolled and 404 completed the trial. The total eradication rate in the chronic gastritis patients was 85.1% (262/308, intention-to-treat (ITT)analysis), which was 81.7% (125/153, ITT) in the A1 group and 88.4% (137/155, ITT) in the A2 group; the eradication rate in the duodenal ulcer patients was 85.8% (103/120, ITT). No severe adverse effects were reported. The symptoms (pain, burning sensation, reflux, belching, nausea, and vomiting) improvement status was similar among A1 and A2 groups. The quadruple regimen using rabeprazole manufactured in China and administered for 10 days as first line/initial therapy in chronic gastritis and duodenal ulcer patients could achieve good H. pylori eradication rate. The extended use of bismuth after 10-day quadruple regimen might further improve the eradication rate. The regimens containing proton-pump inhibitor and bismuth may be well tolerated and safe in clinical application.

Detection of Helicobacter pylori by immunoblot: a multiple-center study

To evaluate the accuracy and effectiveness of Helicobacter pylori(H.pylori)antibody detection kit (immunoblot) in typing H. pylori strains, and to investigate the relationship between characteristics of H. pylori strains and clinical outcomes. A total of 378 patients with upper gastrointestinal symptoms who had received gastroscopy and had pathological results within the period from March to August 2012 were collected from 6 centers in China.In all the patients, H. pylori antibody detection kit was used to detect and type serum H. pylori antibodies.The sensitivity, specificity, and accuracy of immunoblot in diagnosing H. pylori infection were evaluation in comparison to (13)C urea breath test (UBT) as the"gold standard". The results were also compared with those colloidal gold method.The relationship between H. pylori typing and clinical conditions was analyzed. Totally 378 patients were enrolled, in which 257 had H. pylori-positive (13)C UBT results, and 121 were negative.With (13)C UBT as the"gold standard", the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of H. pylori antibodies detection kit(immunoblot)were 97.7%, 86.8%, 94.0%, 94.6%, and 94.2%, respectively; the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of colloidal gold method were 84.4%, 92.6%, 96.0%, 73.7%, and 87.0%, respectively.In patients diagnosed as H. pylori-positive by (13)C UBT and immunoblot, 93.0%(53/57) in H. pylori eradication failure patients and 93.8%(182/194)in untreated patients were infected with type Ⅰ H. pylori as detected by immunoblot, with no statistically significant difference (P=0.764). The type Ⅰ strains positive rate was 94.2%(65/69), 89.9%(62/69)and 98.2% (55/56) in non-atrophy gastritis, atrophy gastritis, and duodenal ulcer untreated patients, respectively, the positive rate of type Ⅰ strains higher in duodenal ulcer cases than in gastritis ones, but with no statistically significant difference(P=0.185). Compared with the"gold standard"(13)C UBT, the accuracy of H. pylori antibody detection kit (immunoblot) and that of colloidal gold method are both fairly high.Different H. pylori strains may have significantly different potential in causing diseases, as typeⅠtrain appeared to be more virulent than type Ⅱ strain, especially in causing peptic ulcer.There was no obvious difference between eradication failure and untreated patients in terms of positive rate of type Ⅰ H. pylori strains, hence further study is needed to explore the relationship between type Ⅰ H. pylori and eradication rates.

Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients

ABSTRACTBackground Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Methods Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Results Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean ± SD of hs-CRP among men and women were 2.85 ± 2.84 mg/dl and 2.80 ± 4.80 mg/dl (p = 0.047) respectively. Mean ± SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83 ± 3.80 mg/dl, 3.52 ± 5.1 mg/dl, 2.22 ± 2.3 mg/dl and 5.3 ± 5.04 mg/dl respectively. Relationship between hs-CRP and inflammation activities (p < 0.01) was significant. A significant relationship between dysplasia and hs-CRP (p < 0.04) was revealed. A significant relationship between age and hs-CRP was detected (p < 0.05). Conclusion Although serum hs-CRP is not a specific biomarker for gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis.