Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.

Current status of Helicobacter pylori eradication and risk factors for eradication failure.

BACKGROUND: The Helicobacter pylori (H. pylori) eradication rate is decreasing in the general population of China. AIM: To evaluate the H. pylori eradication status in real-world clinical practice and to explore factors related to eradication failure. METHODS: Patients with H. pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Multivariate analysis was performed to identify predictors of eradication failure. RESULTS: Of 2610 patients enrolled, eradication was successful in 1999 (76.6%) patients. Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens (83.0% vs 69.0%, P < 0.001). The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate (83.5%). Primary therapy had a higher eradication rate than rescue therapy (78.3% vs 66.5%, P < 0.001). In rescue therapy, the amoxicillin- and furazolidone-containing regimens achieved the highest eradication rate (80.8%). Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors (81.8% vs 74.9%, P = 0.001). Multivariate regression analysis found that older age, prior therapy, and use of omeprazole or pantoprazole were associated with an increased risk of eradication failure. CONCLUSION: The total eradication rate is 76.6%. Amoxicillin-containing regimens are superior to other regimens. Age, prior therapy, and use of omeprazole or pantoprazole are independent risk factors for eradication failure.

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity.

BACKGROUND: Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM: To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS: Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS: The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION: Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.

Association of Salivary Helicobacter pylori Infection with Oral Diseases: a Cross-sectional Study in a Chinese Population.

OBJECTIVE: The aim of this study was to detect the prevalence of oral H.pylori among adults and to investigate the correlation between H.pylori infection and common oral diseases. STUDY DESIGN: A cross-sectional study was performed among adults Chinese who took their annual oral healthy examination at The First Affiliated Hospital, Zhejiang University School of Medicine, China. RESULTS: The study included 1050 subjects in total and oral H.pylori infection occurred in 60.29% of the subjects. The prevalence rates of oral H.pylori in patients with periodontal diseases (63.42%) and caries (66.91%) were significantly increased than those without oral diseases (54.07%), respectively (P < 0.05), while the difference between subjects with recurrent aphthous stomatitis and controls was not significant. In addition, the differences of positive rates of H.pylori with or without history of gastric ulcer were statistically significant (69.47% vs 58.26%, P<0.05). Presenting with periodontal diseases (OR 1.473;95% CI 1.021 to 2.124), caries (OR 1.717; 1.127 to 2.618), and having history of gastric ulcer (OR 1.631; 1.164 to 2.285) increased the risk of H.pylori infection. CONCLUSIONS: Oral H.pylori infection is common in adult Chinese, which is significantly associated with oral diseases including periodontal diseases and caries.

Is national socioeconomic status related to prevalence of irritable bowel syndrome?

BACKGROUND AND AIM: There are a multitude of cross-sectional surveys that provide the prevalence of irritable bowel syndrome (IBS) in the community. However, the data regarding the influence of socioeconomic status on prevalence of IBS were sparse. This study is to investigate the possible relation between human development and prevalence of IBS, at national level. METHODS: EMBASE Classic, EMBASE, and MEDLINE were searched (until October 2013) to identify population-based studies that reported prevalence of IBS. Human Development Index (HDI) was chosen to assess socioeconomic status at national level. RESULTS: Firstly, no correlation was observed between prevalence of IBS and national HDI (P = 0.848). Specifically, there was no statistical significance in prevalence between developing and developed countries (P = 0.319). Moreover, prevalence of IBS failed to witness a downtrend in worldwide over the past two decades. Interestingly, the ratio of female/male prevalence was correlated with national HDI according to linear regression analysis (r = 0.395), and the ratio in the developing was significant lower than that in the developed (P = 0.0394). Lastly, except methods of data collection (P < 0.000), it shows no difference between developing and developed countries in diagnostic criteria, IBS subtypes, and age distribution (P = 0.119, 0.327, and 0.845 respectively). CONCLUSIONS: This study is the first time to investigate the relation between IBS prevalence and national socioeconomic status, with consideration of years, gender, and other factors. It demonstrates that national development is not a direct indicator for prevalence of IBS.

NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Doxorubicin-based therapy is not effective for the treatment of hepatocellular carcinomas (HCCs), which often undergo epithelial-mesenchymal transition (EMT) during tumor progression. Activation of signal transducer and activator of transcription 3 (STAT3) is associated with chemosensitivity and may contribute to EMT during HCC chemotherapy. Low doses of NSC 78459 (a novel STAT3 inhibitor) have little effect on HCC cell proliferation, but efficiently inhibit STAT3. HuH-7, Hep3B, and HepG2 cells, with epithelial phenotypes, show significantly enhanced doxorubicin cytotoxicity following co-treatment with NSC 74859, whereas mesenchymal SNU-449 cells show no such enhancement. NSC 74859 inhibits STAT3 activity and suppressed doxorubicin-induced EMT in epithelial HCC cells. siRNA-mediated STAT3 knockdown resulted in EMT inhibition, which led to attenuation of NSC 74859-mediated chemosensitivity. Our data indicate NSC 74859 co-administration enhances doxorubicin cytotoxicity by inhibiting STAT3 in epithelial HCC cells. STAT3 deactivation and associated EMT attenuation contribute to the synergistic anti-tumor effects of combined NSC 74859/doxorubicin therapy.