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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.

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: Although some epidemiological studies have shown a positive relationship between high intake of ultra-processed food (UPF) and risk of colorectal cancer (CRC), the results remain inconsistent. Therefore, we conducted this systematic review and meta-analysis to clarify the association between UPF intake and CRC risk., Methods: PubMed/MEDLINE, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI) and Wan fang databases were used to search the relevant studies published up to February 2023. The summary relative risks (RRs) with the corresponding 95% confidence intervals (CIs) were estimated by comparing the highest category vs. the lowest category of UPF intake, using the random-effects models (DerSimonian-Laird method). Heterogeneity between studies was explored using the Cochran's Q test and I-square (I 2 ). Publication bias was assessed by examining the funnel plots, and quantified by Begg's or Egger's tests., Results: A total of seven articles (three cohort and four case-control studies), involving 18,673 CRC cases and 462,292 participants, were included in our study. Combining nine effect sizes from seven articles, an increased risk of CRC was shown in the highest compared with the lowest category of UPF intake (RR = 1.26; 95%CI:1.14-1.38, p  < 0.0001). Subgroup analyses showed a positive association between UPF intake and CRC risk in case-control studies (RR = 1.41; 95%CI: 1.22-1.63, p  < 0.0001). When we conducted analyses separately by study area, there was a significant association between UPF intake and CRC risk in developed countries (RR = 1.20; 95%CI: 1.11-1.30, p  < 0.0001)., Conclusion: Our results show that high UPF intake is significantly associated with a higher risk of CRC, in the absence, however, of a dose-response association. Further studies in particular of large prospective cohort studies are necessary to confirm these results., 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 © 2023 Shu, Huang, Si, Zhu, Zheng and Zhang.)

Ulcerative colitis (UC) is the most prevalent form of chronic inflammatory bowel disease, the etiology of which is poorly understood. This study investigated the role of miR-151-5p on UC and explored the role of brain-derived neurotrophic factor (BDNF) in a UC mouse model and cell model. A UC mouse model was engineered by dextran sulfate sodium (DSS) induction. Primary mouse intestinal epithelial cells (IECs) were isolated. Colitis mice were intraperitoneally injected with miR-151-5p antagomir and antagomir negative control, and weight loss, disease activity index, and colon length of mice were measured. Colon tissues of mice were histologically analyzed. A UC cell model was constructed by treating MODE-K cells with DSS. miR-151-5p expression in the cell model was modulated by transfection. The exogenous BDNF effect on the UC cell model and intestinal cell apoptosis, viability and proliferation was detected by flow cytometry, CCK-8 and EdU experiment. The expression of miR-151-5p and apoptosis-related proteins was assessed through q-PCR and western blotting. miR-151-5p was upregulated in the colon tissues and primary IECs of colitis mice. miR-151-5p directly inhibited the expression of BNDF. miR-151-5p upregulation promoted apoptosis in UC MODE-K cells. miR-151-5p upregulation repressed the viability of UC MODE-K cells. Exogenous BNDF treatment reversed the effect of miR-151-5p on UC MODE-K cells. miR-151-5p knockdown improved UC symptoms in mice, including alleviating weight loss, reducing disease activity index and improving colon length and damaged colon tissues. miR-151-5p contributed to intestinal epithelial cells apoptosis in colitis mice via inhibiting BNDF expression.

Introduction: Falls are the leading cause of injury-related morbidity and mortality among older adults (aged ≥65 years) worldwide. However, previous studies examining sleep and falls were confined to community subpopulations, and few studies included both sleep quality and sleep duration when discussing risk factors of falls. This nationwide representative study aimed to examine the links between sleep duration, sleep quality and falls among Chinese community-dwelling older adults., Method: Cross-sectional analyses were conducted with 14,681 older individuals (aged ≥65 years) from 23 Chinese provinces from the Chinese Longitudinal Healthy and Longevity Study (CLHLS) in 2018. Individual variables, including sociodemographic factors, lifestyle, and behavioral factors, were measured using a self-reported questionnaire. Falls were confirmed through face-to-face interviews. Three multivariate logistic regression models were conducted to assess the association between sleep duration and sleep quality with falls., Results: There were 21.7% (95%CI: 21.0-22.4%) participants who had experienced falls in the past year. After controlling demographic and individual variables, falls in older adults were associated with self-reported sleep quality and self-reported sleep duration. Those who reported poor sleep quality were more likely to fall (OR = 1.149; 95%CI = 1.004,1.316). Participants who reported sleep duration that was too short (<5) (OR = 1.349; 95% CI = 1.191 to 1.528) or too long (>8) (OR = 1.267; 95% CI = 1.151 to 1.394) were both associated with higher fall prevalence., Conclusion: Nearly one-fifth of older adults in this study had experienced falls in the past year. The study found that falls were significantly associated with less sleep duration, longer sleep duration, and overall poor sleep quality among the old Chinese population., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

Objective: TMEM119 is a member of transmembrane proteins family, which is abnormally expressed in human cancers and associated with tumorigenesis. In this study, we focused on the expression of TMEM119 and its role in cell invasion and migration in gastric cancer., Methods: Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed to examine the expression of TMEM119 in gastric cancer tissues and cell lines. After transfection with TMEM119 siRNA or recombined TMEM119-expressing vector, the invasion and migration ability of MKN45 and SGC-7901 cells was measured by transwell assay. The expression of TMEM119, p-STAT3, STAT3, VEGF, MMP2, and MMP9 proteins in SGC-7901 and MKN45 cells treated with TMEM119 siRNA, TMEM119-expressing vector, or AG490 was measured by Western blotting., Results: We found that higher TMEM119 expression was found in gastric cancer tissues and cell lines and was associated with lower survival rate. TMEM119 knockdown inhibited SGC-7901 cell invasion and migration, along with the expression of p-STAT3, VEGF, MMP2, and MMP9. TMEM119 overexpression promoted MKN45 cell invasion and migration, along with the expression of p-STAT3, VEGF, MMP2, and MMP9. Additionally, AG490 treatment significantly corrected TMEM119-induced MKN45 cell migration and invasion and expression of p-STAT3, VEGF, MMP9, and MMP2 proteins., Conclusion: The results indicated that TMEM119 promotes gastric cancer cell migration and invasion through activation of STAT3 signaling pathway, and TMEM119 may therefore act as a novel therapeutic target for gastric cancer., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease of the colon. T cell responses have been associated with the pathology of UC. Andrographis paniculata (AP) extract has been previously reported as an effective treatment of UC. The present study aimed to explore the effects of andrographolide, the primary active component of AP, on the T cell responses of patients with UC. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with UC and treated with various concentrations of andrographolide (0, 10, 20 and 30 µg/ml). Andrographolide decreased interferon γ, interleukin (IL)‑23 and IL‑17A, however it increased IL‑4 in a dose‑dependent manner, as indicated by ELISA assay. Andrographolide treatment resulted in a decreased percentage of T helper (Th)1 and Th17 cells and an increased proportion of Th2 cells, as demonstrated by flow cytometry analysis. T‑bet (a Th1‑specific transcription factor) and RAR‑related orphan receptor γt (key transcription factor of Th17 cells) expression was decreased, but GATA‑3 (Th2 lineage‑specific transcription factor) expression was increased following andrographolide treatment as indicated by western blot analysis. These results demonstrated the inhibitory effects on Th1/Th17 responses and the promoting effects on Th2 responses of andrographolide. Experiments on IL‑23‑treated PBMCs from healthy donors revealed similar effects of andrographolide on Th1/Th2/Th17 responses. In summary, these results suggest that andrographolide may be an effective candidate for the treatment of IL‑23‑mediated diseases.

Gastric cancer is the second major cause of death associated with cancer and ranks among the top four cancers diagnosed worldwide. Previous findings identified the association of transmembrane proteins (TMEMs) with tumorigenesis of various types of cancer, including breast, liver and kidney cancer. However, the expression and the biological function of TMEMs, especially TMEM119, and its possible molecular mechanism in gastric cancer remain less understood. CCK-8 and flow cytometric analysis was employed to examine the viability and apoptosis of gastric adenocarcinoma SGC-7901 and AGS cells, gastric carcinoma MKN45 cells, as well as gastric epithelial cell lines GES-1 after transfection with TMEM119-siRNA (siTMEM119), respectively. Quantitative PCR, western blot analysis and immunohistochemistry was performed to detect the expression levels of TMEM119, Bax, Bcl-2 and caspase-3. The results showed that, TMEM119 was elevated with the highest expression detected in SGC-7901 cells compared to AGS cells, MKN45 cells, as well as GES-1. TMEM119 silencing in the gastric cancer cell line, SGC-7901, significantly inhibited cell viability and induced apoptosis. The downregulation of TMEM119 exhibited reduced levels of Bcl-2 and higher levels of Bax and caspase-3 in SGC-7901 cells. These results suggest that TMEM119 is useful in the treatment of gastric cancer.

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.

Background: The effect of whole diet on the development of stroke has recently achieved much interest by various prospective studies, but with inconclusive results. Herein, we carried this meta-analysis to identify the potential associations between different dietary patterns and the risk of stroke by pooling available data from existing studies., Methods: PubMed and EBSCO were searched for pertinent articles that identify dietary patterns published from January 1991 to November 2014, with the following keywords: dietary pattern, dietary patterns, food pattern, eating pattern, alcohol drinking, alcohol consumption, and stroke., Results: A total of 21 studies met the inclusion criteria and were included in this meta-analysis. A decreased risk of stroke was shown for the highest compared with the lowest categories of healthy dietary pattern (odds ratio [OR] = .77; 95% confidence interval [CI] = .63-.93; P < .00001) and light-moderate drinking pattern (OR = .80; 95% CI = .72-.90; P = .0002). There was evidence of the increase in the risk of stroke in the highest compared with heavy alcohol-drinking pattern (OR = 1.25; 95% CI = 1.17-1.33; P < .00001), whereas no significant association with Western-style dietary pattern was observed (OR = 1.05; 95% CI = .82-1.35; P = .70)., Conclusions: The results of this meta-analysis indicated that some dietary patterns may be associated with the risk of stroke., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)