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Background: H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. Methods: One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. Results: The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1–6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001). Conclusions: The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The treatment of trigger finger so far has heavily relied on clinicians' evaluations for the severity of patients' symptoms and the functionality of affected fingers. However, there is still a lack of pathological evidence supporting the criteria of clinical evaluations. This study's aim was to correlate clinical classification and pathological changes for trigger finger based on the tissue abnormality observed from microscopic images.Methods: Tissue samples were acquired, and microscopic images were randomly selected and then graded by three pathologists and two physicians, respectively. Moreover, the acquired images were automatically analyzed to derive two quantitative parameters, the size ratio of the abnormal tissue region and the number ratio of the abnormal nuclei, which can reflect tissue abnormality caused by trigger finger. A self-developed image analysis system was used to avoid human subjectivity during the quantification process. Finally, correlations between the quantitative image parameters, pathological grading, and clinical severity classification were assessed.Results: One-way ANOVA tests revealed significant correlations between the image quantification and pathological grading as well as between the image quantification and clinical severity classification. The Cohen's kappa coefficient test also depicted good consistency between pathological grading and clinical severity classification.Conclusions: The criteria of clinical classification were found to be highly associated with the pathological changes of affected tissues. The correlations serve as explicit evidence supporting clinicians in making a treatment strategy of trigger finger. In addition, our proposed computer-aided image analysis system was considered to be a promising and objective approach to determining trigger finger severity at the microscopic level. [ABSTRACT FROM AUTHOR]

Background: Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls., Methods: A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls., Results: The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p < 0.05). In contrast, the female T2DM patients had higher chronic inflammatory scores in the antrum than the controls (p < 0.05). In T2DM patients, the males had significantly higher rates of CGI than the females (p < 0.05). Multivariate logistic regression analysis showed that male patients (odds ratio: 2.28, 95% confidence interval: 1.11-4.69, p = 0.025) and non-insulin users (odds ratio: 0.33, 95% confidence interval: 0.15-0.74, p = 0.007) were independent factors for the presence of CGI in the H. pylori-infected patients with type 2 diabetes mellitus., Conclusions: Patients with type 2 diabetes mellitus and H. pylori infection had more severe corpus gastric inflammation than non-diabetic controls. Moreover, male gender and non-insulin users of T2DM patients were predisposed to have corpus-predominant gastritis after H. pylori infection., Trial Registration: ClinicalTrial: NCT02466919 , retrospectively registered may 17, 2015.

Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM)., Results: There were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR[95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10(-4)), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10(-4))., Conclusions: The SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication.

Background: Intragenomic recombination between babA and babB mediates antigenic variations and may help H. pylori colonization. This study determined whether variable genotypes of babA and babB correlate to different clinical disease outcomes, and can distribute over the different gastric niches., Results: This study enrolled 92 clinical strains (45 from peptic ulcer, 27 from gastritis, and 20 from gastric cancer) to detect whether the babA and babB are at locus A or B by PCR reactions using the primers designed from the upstream and variable region of the babA and babB genes. Four genotypes of babA and babB (A B, AB B, A AB, AB AB) were found. The distribution of the 4 genotypes in 92 clinical strains was significantly different among patients with different gastric diseases (p < 0.05). The isolates from gastric cancer patients had a higher rate of AB AB genotype than those from non-cancer patients (40.0% vs. 9.7%, p < 0.05). The AB AB genotype was associated with a higher intensity of intestinal metaplasia (p < 0.05), but did not correlate with a higher inflammation and colonization density in gastric histology (p > 0.05). Besides, the study enrolled 19 patients to verify whether variable genotypes of babAB existed in the different gastric niches. Among the patients infected with more than one babAB genotypes over antrum and corpus, there were higher rate of genotypes as A B or AB AB in isolates from antrum than in those from corpus (75.0 % vs. 16.7%, p < 0.05)., Conclusions: The H. pylori isolate with the AB AB genotype correlates with an increased gastric cancer risk, and colonize in an antrum predominant manner.

Background: H. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways., Results: Challenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100) of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting., Conclusions: H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

Background: Nearly all Taiwanese H. pylori stains are cagA-genopositive and encode CagA protein. In this study, we evaluated whether different intensity of tyrosine phosphorylated-CagA (p-CagA) had an impact on the clinical diseases and histological outcomes in this area., Results: We enrolled 469 dyspeptic patients and prospectively obtained the gastric biopsy specimens and the H. pylori isolates. These patients were categorized according to the clinical diseases, such as duodenal ulcer, gastric ulcer, gastric cancer, and gastritis with or without intestinal metaplasia. Their gastric specimens were reviewed by the updated Sydney's system. Furthermore, a total of 146 patients were randomly selected from each clinical category for evaluation of their isolates' p-CagA intensity by in vitro AGS cells co-culture. The p-CagA was sparse in 30 (20.5%), weak in 59 (40.5%), and strong in 57 (39%) isolates. The isolates from the patients of gastric cancer or gastritis with intestinal metaplasia had stronger p-CagA intensity than those of gastritis without intestinal metaplasia (p ≤ 0.002). Moreover, the patients infected with isolates with strong or weak p-CagA intensity had a higher risk of gastric intestinal metaplasia (p < 0.05, odds ratio 3.09~15.26) than those infected with sparse p-CagA isolates., Conclusions: Infection with H. pylori stains with stronger p-CagA intensity may lead to an increased risk of gastric intestinal metaplasia and cancer.

Background: Serum response factor (SRF) is crucial for gastric ulcer healing process. The study determined if gastric ulcer tissues up-regulate SRF and if such up-regulation correlated with co-morbidities and the risk of recurrent bleeding., Methods: Ulcer and non-ulcer tissues were obtained from 142 patients with active gastric ulcers for SRF expression assessed by immunohistochemistry. Based on the degree of SRF expression between these two tissue types, SRF up-regulation was classified as strong, intermediate, and weak patterns. The patients were followed-up to determine if SRF up-regulation correlated to recurrent bleeding., Results: Gastric ulcer tissues had higher SRF expression than non-ulcer tissues (p < 0.05). Patients with strong SRF up-regulation had lower rates of stigmata of recent hemorrhage (SRH) on the ulcer base than the others (p < 0.05). Multivariate logistic regression confirmed that co-morbidities and weak SRF up-regulation were two independent factors of recurrent gastric ulcer bleeding (p < 0.05). Combining both factors, there was an 8.29-fold (95% CI, 1.31~52.62; p = 0.03) higher risk of recurrent gastric ulcer bleeding., Conclusions: SRF expression is higher in gastric ulcer tissues than in non-ulcer tissues. Weak SRF up-regulation, combined with the presence of co-morbidities, increase the risk of the recurrent gastric ulcer bleeding.

Background: This study investigated if the H. pylori dupA genotype and certain host single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), including MMP-3, MMP-7, MMP-9, TIMP-1 and TIMP-2, might correlate with ulcer risk of H. pylori-infected Taiwanese patients., Results: Of the 549 H. pylori-infected patients enrolled, 470 patients (265 with gastritis, 118 with duodenal ulcer, and 87 with gastric ulcer) received SNPs analysis of MMP-3-1612 6A > 5A, MMP-7-181 A > G, MMP-9exon 6 A > G, TIMP-1372 T > C and TIMP-2-418 G > C by PCR-RFLP. The 181 collected H. pylori isolates were detected for the dupA genotype by PCR. The rates of dupA-positive H. pylori infection were similar among patients with duodenal ulcer (22.8%), gastric ulcer (20.0%), and gastritis (25.5%) (p > 0.05). Males had higher rates of duodenal ulcer and gastric ulcer than females (p < 0.01). Of H. pylori-infected patients, the MMP-3 6A6A genotype were more common in patients with duodenal ulcers than in those with gastritis (87.7% vs. 74.9%, p < 0.05) in females. This genotype had a 2.4-fold (95% CI: 1.02-5.66) increased risk of duodenal ulcer, compared to those with the 5A carrier. Combining the MMP-3/TIMP-1 genotype as 6A6A/CC, the risk of duodenal ulcer increased up to 3.6 fold (p < 0.05) in H. pylori-infected females., Conclusions: The MMP-3 promoter polymorphism, but not the dupA-status, may correlate with susceptibility to duodenal ulcer after H. pylori infection in Taiwanese females.

Background: H. pylori infection is less prevalent in childhood. This study validated whether the rates of H. pylori colonization depend on different acquisition ages, and correlate with the different gastric Lewis antigens or cytokine expressions after H. pylori acquisition., Methods: We applied a young (7-day-old) C57BL/6 mice group (n = 50) and adult (6-week-old) C57BL/6 mice group (n = 50). In each group, 30 mice were challenged with H. pylori and 20 mice served as naïve control. The success of H. pylori colonization was assessed on the 2(nd )week and the 8(th )week, respectively. The intensity of the Lewis x, sialylated Lewis x(sialyl-Le(x)), and cytokine expressions, including TNF-α, IFN-γ, IL-6, IL-10, and IL-1β, were immunochemically stained and graded., Results: On the 2(nd )week after H. pylori challenge, the colonization rates of H. pylori were similar between the young mice group and the adult mice group (89% vs. 100%, P > 0.05). However, on the 8(th )week, the H. pylori colonization rate was significantly lower in the young mice group than in the adult mice group (53% vs. 95%, P = 0.003). On the 8(th )week, the young mice with a persistence of H. pylori colonization had higher sialyl-Le(x), higher IL-10, and lower IFN-γ than those of the mice that lost colonization during the 2(nd )to the 8(th )week (P < 0.05)., Conclusion: The persistence of H. pylori colonization could be an acquisition-age determinant process. After H. pylori exposure at an early acquisition age, the host response with a higher sialyl-Le(x )and IL-10, but a lower IFN-γ correlates to the consequent persistence of H. pylori colonization.

This study tested whether there were different expressions of gastric Lewis antigens between children and adults with Helicobacter pylori infection, and whether the difference was related to the infection outcome. About 68 dyspeptic children and 110 dyspeptic adults were enrolled to check H. pylori infection, its colonization density, and the related histology. Gastric Lewis antigens b (Le(b)), x (Le(x)), and sialyl-Lewis x (sialyl-Le(x)) were immunohistochemically stained and scored for the intensity. The H. pylori-infected adults, but not the children, had a lower Le(b) intensity over the antrum (p=0.019) but higher Le(b) intensity over the corpus (p=0.001) than the non-infected ones. Over the antrum, both the H. pylori-infected children and adults had a lower Le(x) and higher sialyl-Le(x) intensity than those non-infected ones (p<0.05). The H. pylori-infected adults had a higher bacterial density (p=0.004) and Le(b) intensity (p=0.016) over the corpus than the H. pylori-infected children. For the H. pylori-infected adults, but not children, the corpus had a higher Le(b) (p=0.038) and lower Le(x) (p=0.005) intensity than the antrum. Furthermore, the H. pylori-infected adults expressed a higher Le(b) and had a higher bacterial density than those with weak Le(b) (antrum, p<0.001; corpus, p=0.001). In conclusion, H. pylori infection is associated with the intensity change of Lewis antigen expressions in the stomach. The changes of gastric Lewis antigen expressions are different between adults and children with H. pylori infection, which may exert different H. pylori colonization over the corpus between adults and children.