The Short-Term Efficacy of Bifidobacterium Quadruple Viable Tablet in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: Potentially Mediated by Metabolism Rather Than Diversity Regulation.

INTRODUCTION: The therapeutic effect of probiotics for irritable bowel syndrome (IBS) was controversial. This study aims to evaluate the short-term efficacy of Bifidobacterium quadruple viable tablet in patients with diarrhea-predominant IBS and explore factors associated with response to probiotics. METHODS: A randomized, double-blind, placebo-controlled, multicenter trial was performed in 15 hospitals. A total of 290 patients who fulfilled the eligibility criteria were assigned to the probiotics or placebo group randomly with a ratio of 1:1 for a 4-week treatment and a 2-week follow-up. The primary outcome was the response rate. It was regarded as the proportion of patients with composite responses of improvement in both abdominal pain and diarrhea simultaneously. RESULTS: After 4-week continuous administration, the response rates of the probiotics and the placebo were 67.59% and 36.55%, respectively ( P < 0.001). In the probiotics, those with higher abdominal pain scores (2.674 [1.139-6.279]) were more likely to respond, but responders in placebo had lower Hamilton Depression Scale score (0.162 [0.060-0.439]), lower Hamilton Anxiety Scale score (0.335 [0.148-0.755]), and higher degree of bloating (2.718 [1.217-6.074]). Although the diversity of the microbiota was not significantly changed by probiotics, the abundance of bacteria producing short-chain fatty acids (SCFAs), including Butyricimonas ( P = 0.048), Pseudobutyrivibrio ( P = 0.005), Barnesiella ( P = 0.020), and Sutterella ( P = 0.020), and the concentration of SCFAs including butyric acid ( P = 0.010), valeric acid ( P = 0.019), and caproic acid ( P = 0.046) in feces increased. DISCUSSION: A Bifidobacterium quadruple viable tablet had a significant short-term efficacy for the treatment of diarrhea-predominant IBS and was more effective in patients with higher abdominal pain scores. This kind of probiotics could improve the abundance of several bacteria producing SCFAs and the concentration of fecal SCFAs compared with placebos.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Circular RNA profiling in plasma exosomes from patients with gastric cancer.

Gastric cancer (GC) is among the most common cancer types worldwide with high mortality. Recent studies have shown that exosomes play a crucial role in the tumorigenesis of GC. The present study aimed to investigate the circular RNA (circRNA) profile in plasma exosomes from patients with gastric cancer (GC). Peripheral blood samples were collected from 5 patients with GC and 5 healthy donors, and exosomes were isolated from plasma. The high-throughput RNA sequencing (RNA-seq) method was applied to detect the differently expressed circRNAs (DE circRNAs). Subsequently, sequencing results were confirmed by reverse transcription quantitative (RT-q) PCR. The potential roles of DE circRNAs in GC were identified using Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analysis. Furthermore, MiRanda software was used to predict circRNA-micro-RNA (miRNA) interactions. A total of 67,880 circRNAs were identified in all samples and 1,060 significantly DE circRNAs were screened, including 620 upregulated and 440 downregulated ones. These results were further confirmed by RT-qPCR. GO and KEGG analyses revealed that these circRNAs were significantly associated with 'cell cycle', 'cytoskeleton organization', 'cellular response to DNA damage', 'regulation of GTPase activity', 'phosphatidylinositol signaling pathway', 'MAPK signaling pathway', 'thyroid hormone signaling pathway', 'chemokine signaling pathway' and 'Wnt signaling pathway'. In addition, a circRNA-miRNA-mRNA interaction network was established. Taken together, these findings may help better understanding the underlying mechanisms of GC and identifying new molecular alterations in GC, and allow the enrichment of the circRNA profiling in human GC.

Long Noncoding RNASBF2-AS1 Promotes Gastric Cancer Progression via Regulating miR-545/EMS1 Axis.

OBJECTIVE: Long noncoding RNA (LncRNA) SBF2-AS1 was reportedly to function as an oncogene in several types of cancers, such as hepatocellular carcinoma, nonsmall cell lung cancer, glioma, and colorectal cancer. However, the biological roles and regulatory mechanisms of SBF2-AS1 in gastric cancer (GC) are unknown. METHODS: The expression of SBF2-AS1 and miR-545 were examined in GC tissues and cell lines via real-time quantitative PCR. The relationship of SBF2-AS1 with miR-545 was verified via dual-luciferase reporter gene assay and RNA immunoprecipitation. The influences of SBF2-AS1 on cell proliferation, migration, and invasion were determined using cell counting Kit-8 (CCK-8), wound healing, and transwell invasion assays, respectively. RESULTS: LncRNA SBF2-AS1 expression was upregulated in GC tissues, especially in advanced clinical stage cases. Moreover, increased SBF2-AS1 indicated a poor survival rate. Functionally, the downregulation of SBF2-AS1 by siRNA in GC cells suppressed the proliferation, migration, and invasion. In terms of mechanism, SBF2-AS1 can directly bind to miR-545 and regulate its expression. Moreover, SBF2-AS1 knockdown significantly decreased the expression of EMS1, which was the direct target of miR-545. Importantly, inhibition of miR-545 or overexpression of EMS1 partially reversed SBF2-AS1-depletion-caused suppression on proliferation, migration, and invasion. CONCLUSION: These findings elucidated a crucial role of SBF2-AS1 as a miR-545 sponge in GC cells, suggesting that SBF2-AS1 might be a potential target for GC.

Lifestyle intervention for gastroesophageal reflux disease: a national multicenter survey of lifestyle factor effects on gastroesophageal reflux disease in China.

BACKGROUND: Poor habits can worsen gastroesophageal reflux disease (GERD) and reduce treatment efficacy. Few large-scale studies have examined lifestyle influences, particularly eating habits, on GERD in China, and research related to eating quickly, hyperphagia, and eating hot foods is quite limited. The aim of this study was to evaluate the relationship between GERD pathogenesis and lifestyle factors to produce useful information for the development of a clinical reference guide through a national multicenter survey in China. METHODS: Symptom and lifestyle/habit questionnaires included 19 items were designed. The questionnaire results were subjected to correlation analysis relative to GERD symptom onset. A standard proton pump inhibitor (PPI) was advised to correct patients with unhealthful lifestyle habits. RESULTS: A total of 1518 subjects (832 GERD, 686 non-GERD) enrolled from six Chinese hospitals completed symptom and lifestyle/habit questionnaires. The top lifestyle factors related to GERD were fast eating, eating beyond fullness, and preference for spicy food. Univariate analysis showed that 21 factors, including male gender, a supra-normal body mass index (BMI), smoking, drinking alcohol, fast eating, eating beyond fullness, eating very hot foods, and drinking soup, among others, were associated with GERD (p < 0.05). Logistic multivariate regression analysis revealed the following risk factors for GERD [with odds ratios (ORs)]: fast eating (4.058), eating beyond fullness (2.849), wearing girdles or corsets (2.187), eating very hot foods (1.811), high BMI (1.805), lying down soon after eating (1.544), and smoking (1.521). Adjuvant lifestyle interventions improved outcomes over medication alone (z = -8.578, p < 0.001 Mann-Whitney rank sum test). CONCLUSIONS: Lifestyle interventions can improve medication efficacy in GERD patients. Numerous habits, including fast eating, eating beyond fullness, and eating very hot foods, were associated with GERD pathogenesis. The present results may be useful as a reference for preventive education and treatment.