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Background: Helicobacter pylori (H. pylori), prevalent in developing regions, is a key factor in gastrointestinal diseases. Despite the common use of bismuth-based quadruple therapy, its drawbacks have prompted the search for alternatives. Recently, vonoprazan, a novel acid suppressant, has shown promise in combination with antibiotics as a dual therapy for H. pylori eradication. This study aimed to assess the therapeutic outcomes and adverse events of vonoprazan-amoxicillin dual therapy compared to quadruple therapy. Methods: A randomized controlled trial (RCT) enrolled H. pylori-infected patients at Zhejiang Hospital. Participants were randomly assigned to dual and quadruple therapy groups. The primary endpoints were H. pylori eradication and adverse events. Results: Of the 400 patients studied from April 2022 to June 2023, In the intention-to-treat (ITT) analysis, the eradication rates of H. pylori in vonoprazan-amoxicillin dual therapy group and quadruple therapy group were 94.0% and 87.0%, respectively, p = 0.017. In the per-protocol (PP) analysis were 97.9% and 93.0%, p = 0.022. Additionally, the dual therapy group had a significantly lower incidence of adverse events (19%) compared to the quadruple therapy group (53%) (p < 0.001). Conclusion: Vonoprazan-amoxicillin dual therapy demonstrates superior eradication efficacy and reduced adverse events compared to quadruple therapy in H. pylori-infected patients, suggesting its potential for clinical application and promotion. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a recurring inflammatory bowel disease, in which oxidative stress plays a role in its progression, and regulation of the oxidative/antioxidative balance has been suggested as a potential target for the treatment of UC. The aim of this study was to evaluate the protective effect of andrographolide against UC and its potential antioxidant properties by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Dextran sulfate sodium (DSS) -induced UC mice and the LPS-induced HT29 inflammatory cell model were established to uncover the potential mechanisms of andrographolide. ML385, a Nrf2 inhibitor, was used in both models to assess whether andrographolide exerts a protective effect against UC through the Nrf2/HO-1 pathway. The in vivo experiment showed that andrographolide ameliorated the symptoms and histopathology of DSS-induced mice and restored the expressions of ZO-1, Occludin-1 and Claudin-1. Meanwhile, DSS-induced oxidative stress and inflammation were suppressed by andrographolide treatment, along with the upregulation of key proteins in the Nrf2/HO-1 pathway. In vitro experiments showed that andrographolide attenuated LPS-induced excessive generation of ROS in HT29 cells, reduced inflammatory factors, and upregulated the expression of proteins related to tight junctions and Nrf2/HO-1 pathway. In addition, ML385 abolished the beneficial effect of andrographolide. In conclusion, the protective effect of andrographolide against UC may involve the suppression of oxidative stress and inflammation via the Nrf2/HO-1 pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shu, Fu, Pi, Feng, Dong, Si, Li, Zhu, Zheng and Zhu.)

Background: The pathogenesis of extraesophageal symptoms of gastroesophageal reflux disease is complex, and esophageal motility and reflux may be involved in it. In this study, we aimed to compare esophageal motility and reflux characteristics in gastroesopha- geal reflux disease patients with and without extraesophageal symptoms by high-resolution manometry and multichannel intraluminal impedance-pH monitoring., Methods: We retrospectively studied gastroesophageal reflux disease patients between January 2014 and December 2018. All patients had undergone high-resolution manometry and multichannel intraluminal impedance-pH monitoring. The results were compared and analyzed., Results: A total of 59 patients were included in this study. Patients were divided into 3 groups according to their main complaint: only typical symptoms (group A, n = 11), both typical and extraesophageal symptoms (group B, n = 33), and only extraesophageal symp- toms (group C, n = 15). Compared with group A, the lower esophageal sphincter basal pressure, integrated residual pressure, and lower esophageal sphincter length were lower, and the proximal reflux percentages of a weak acid and non-acid reflux were higher in group B and group C (P < .017). The positive rate of esophageal motility disorders was lower in group A than in other groups (P < .05). The propor- tion of patients with multiple rapid swallows/single swallow-distal contractile integral ratio greater than 1-was higher in group A than in other groups (P < .05)., Conclusions: Decreased lower esophageal sphincter pressure and lower esophageal sphincter length, increased proximal esophageal reflux of weak acid and non-acid reflux, esophageal motility disorders, and decreased peristaltic reserve are involved in the pathogenesis of extraesophageal symptoms of gastroesophageal reflux disease.

Ulcerative colitis (UC) is a chronic and nonspecific intestinal inflammatory disease, which may increase the risk of colon cancer. Andrographolide is a main active component of Andrographis paniculata . The anti-inflammatory ability of andrographolide suggested its potential therapeutic effect against UC. In the present study, elevated serum concentrations of proinflammatory factors, including (TNF)-α, interleukin (IL)-1β, IL-6 and IL-23, as well as increased percentages of Th17 cells (IL-17+CD4+ cells) in CD4+ cells were detected in UC patients compared to that in healthy donors. These data suggested that Th17 immune responses may involve in the pathogenesis of UC. Experimental colitis mouse model was then established. The results of hematoxylin and eosin staining demonstrated the therapeutic effect of andrographolide on colitis. Enzyme-linked immunosorbent assay (ELISA), flow cytometry and western blotting analyses showed that andrographolide could decreased the levels of proinflammatory factors TNF-α, IL-1β, IL-6 and IL-17A in the serum and in the colon tissues, reduced the percentages of Th17 cells in CD4+ cells, and suppressed the levels of IL-23, IL-17A, ROR-γt (key transcription factor of Th17 cells) and p-STAT3 in the colon tissues. Further, peripheral blood mononuclear cells (PBMCs) were isolated from UC patients and treated with various concentrations of andrographolide (0, 10, 20 and 30 μg/ml). Andrographolide also showed inhibitory effects on the levels of proinflammatory factors, the percentages of Th17 cells and the expression of relative proteins. Similar results were obtained in lipopolysaccharide-treated normal PBMCs. These data suggested that andrographolide may inhibit Th17 immune response via STAT3 signaling. In conclusion, we demonstrated that andrographolide inhibited the activity of IL-23/IL-17 axis and down-stream pro-inflammatory factors so as to suppress inflammation response, resulting in the relieving of UC., Competing Interests: None.