Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models.

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Metal-Organic Framework Based Mucoadhesive Nanodrugs for Multifunction Helicobacter Pylori Targeted Eradication, Inflammation Regulation and Gut Flora Protection.

The prevalence of drug-resistant bacteria presents a significant challenge to the antibiotic treatment of Helicobacter pylori (H. pylori), while traditional antimicrobial agents often suffer from shortcomings such as poor gastric retention, inadequate alleviation of inflammation, and significant adverse effects on the gut microbiota. Here, a selenized chitosan (CS-Se) modified bismuth-based metal-organic framework (Bi-MOF@CS-Se) nanodrug is reported that can target mucin through the charge interaction of the outer CS-Se layer to achieve mucosal adhesion and gastric retention. Additionally, the Bi-MOF@CS-Se can respond to gastric acid and pepsin degradation, and the exposed Bi-MOF exhibits excellent antibacterial properties against standard H. pylori as well as clinical antibiotic-resistant strains. Remarkably, the Bi-MOF@CS-Se effectively alleviates inflammation and excessive oxidative stress by regulating the expression of inflammatory factors and the production of reactive oxygen species (ROS), thereby exerting therapeutic effects against H. pylori infection. Importantly, this Bi-MOF@CS-Se nanodrug does not affect the homeostasis of gut microbiota, providing a promising strategy for efficient and safe treatment of H. pylori infection.

Etiological Changes and Prognosis of Hospitalized Patients with Acute Pancreatitis Over a 15-Year Period.

BACKGROUND: The worldwide incidence of acute pancreatitis (AP) is increasing, but the dominant etiology of AP may vary by country. Mixed etiologies are involved in the increase in the number of AP patients. AIMS: This study was to analyze the etiological changes and prognosis of AP patients and explore the prognosis of AP patients with mixed etiologies. METHODS: Using a retrospective analysis method, AP patients hospitalized from January 2007 to December 2021 were selected from a pancreatic center in Nanchang, China. Trends in the main etiologies were analyzed, and the severity and prognosis of different etiologies were compared. RESULTS: A total of 10,071 patients were included. Cholelithiasis (56.0%), hyperlipidemia (25.3%), and alcohol (6.5%) were the top three etiologies. The proportion of acute biliary pancreatitis (ABP) showed a decreasing trend, while the proportion of hypertriglyceridemic pancreatitis (HTGP) and alcoholic AP showed an increasing trend (all ptrend < 0.001). The incidence of organ failure and necrotizing pancreatitis was higher in patients with HTGP than in those with AP induced by other etiologies (all p < 0.05). There was no statistically significant difference in mortality among patients with different etiologies. Patients with AP due to a mixed hypertriglyceridemia-alcoholic etiology had higher ICU admission rates and were more severe than those with AP induced by other mixed etiologies. CONCLUSION: In the past 15 years, the proportion of ABP has trended downward, while those of HTGP and alcoholic AP have risen. Among patients with mixed etiologies, those with a mixed hypertriglyceridemia-alcoholic etiology had a worse prognosis.

Vonoprazan and amoxicillin dual therapy as the first-line treatment of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Recent clinical trials have evaluated the efficacy of vonoprazan-amoxicillin (VA) dual therapy as the first-line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. MATERIALS AND METHODS: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium-competitive acid blocker" OR "P-CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention-to-treat and per-protocol analysis. The secondary outcomes were adverse events and compliance. RESULTS: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention-to-treat and per-protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors-based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan-containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7-day VA dual therapy showed lower eradication rates than 10-day (χ2 = 24.09, p < 0.01) and 14-day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth-containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. CONCLUSION: VA dual therapy, a novel regimen, showed high efficacy as the first-line treatment for H. pylori eradication, which should be optimized before application in different regions.

Investigation of the prevalence and risk factors of Helicobacter pylori infection and the value of different gastric cancer screening methods in a low-risk region of gastric cancer in China.

BACKGROUND: The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods. METHODS: An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis. RESULTS: A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18-1.77, p < 0.001), loss of appetite (OR: 1.71, 95% CI: 1.29-2.26, p < 0.001), PG II >37.23 ng/mL (OR: 2.11, 95% CI: 1.50-2.97, p < 0.001), G-17 > 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93-3.30, p < 0.001), and G-17 > 5.7 pmol/L (OR: 1.96, 95% CI: 1.48-2.60, p < 0.001) were risk factors of H. pylori infection, while alcohol consumption (OR: 0.70, 95% CI: 0.54-0.91, p = 0.006) was a protective factor. According to the new gastric cancer screening method, the prevalence of low-grade intraepithelial neoplasia in the low-risk group, medium-risk group and high-risk group was 4.4%, 7.7% and 12.5% respectively (p < 0.001). CONCLUSIONS: In a low-risk area of gastric cancer in China, the infection rate of H. pylori is relatively low. Low income, loss of appetite, high PG II, and high G-17 were risk factors for H. pylori infection, while alcohol consumption was a protective factor. Moreover, the new gastric cancer screening method better predicted low-grade intraepithelial neoplasia than the ABC method and the new ABC method.

Elevated CK-MB levels are associated with adverse clinical outcomes in acute pancreatitis: a propensity score-matched study.

Aim: Cardiac injury, reflected by the measured concentrations of chemicals released from injured cardiac muscle, is common in acute pancreatitis (AP). However, there is no adequate evidence assessing the impact of cardiac injury on AP-related outcomes. Creatine kinase-myocardial band (CK-MB) mainly exists in the myocardium. Therefore, we sought to evaluate the relationship between the increase in CK-MB and the adverse clinical outcomes of AP. Methods: This propensity score-matched study analyzed AP patients admitted to the Department of Gastroenterology in the First Affiliated Hospital of Nanchang University from June 2017 to July 2022. Propensity score matching and multivariate logistic regression analysis were used to explore the relationship between CK-MB elevation and AP outcome variables. Results: A total of 5,944 patients were screened for eligibility, of whom 4,802 were ultimately enrolled. Overall, 896 (18.66%) of AP patients had elevated (>24 U/ml) CK-MB levels, and 895 (99.89%) were paired with controls using propensity score matching. The propensity score-matched cohort analysis demonstrated that mortality (OR, 5.87; 95% CI, 3.89-8.84; P < 0.001), severe acute pancreatitis (SAP) (OR, 2.74; 95% CI, 2.23-3.35; P < 0.001), and infected necrotizing pancreatitis (INP) (OR, 3.40; 95% CI, 2.34-4.94; P < 0.001) were more frequent in the elevated CK-MB (>24 U/ml) group than in the normal CK-MB (≤ 24 U/ml) group. Using the multivariate logistic regression analysis, elevated CK-MB levels were independently associated with increased mortality (OR, 2.753, 95% CI, 2.095-3.617, P < 0.001), SAP incidence (OR, 2.223, CI, 1.870-2.643, P < 0.001), and INP incidence (OR, 1.913, 95% CI, 1.467-2.494, P < 0.001). CK-MB elevation was an independent risk factor for adverse clinical outcomes in AP patients. Conclusion: CK-MB elevation was significantly related to adverse outcomes in AP patients, which makes it a potentially useful laboratory parameter for predicting adverse clinical outcomes of AP.

TikTok and Bilibili as sources of information on Helicobacter pylori in China: A content and quality analysis.

BACKGROUND: Helicobacter pylori (H. pylori) is closely associated with gastric diseases and has a high prevalence in China. Public platforms are considered common and important tools to publicize H. pylori-related information. This study aimed to assess and compare the content and quality of H. pylori-related videos on TikTok and Bilibili. MATERIALS AND METHODS: A search was performed on the TikTok and Bilibili platforms using the keyword "H. pylori". The source of upload was categorized as for-profit organizations, general users, health professionals, news agencies, nonprofit organizations, and science communicators. The Journal of American Medical Association (JAMA), Global Quality Scale (GQS), and modified DISCERN scores were used to evaluate the quality of the included videos. RESULTS: A total of 93 TikTok videos and 79 Bilibili videos were included and analyzed. TikTok videos had a significantly shorter duration than Bilibili videos (64 vs. 149 s, respectively; p < 0.001). The duration of the video showed a positive correlation with the modified DISCERN and GQS scores (p < 0.001, r = 0.388 and r = 0.437, respectively). The JAMA and modified DISCERN scores of the TikTok video were significantly higher in health professionals and nonprofit organizations than in other sources (p < 0.05). For Bilibili, science communicators had a significantly higher JAMA score than the other video sources (p < 0.001). The videos uploaded by news agencies received more views, comments, shares, and favorites than any other organization or individual (p < 0.001). CONCLUSIONS: In China, H. pylori-related videos from TikTok and Bilibili tended to provide the information regarding the transmission and eradication of H. pylori. However, many videos scored an average rating in content and quality and need to be improved. We recommend that the public obtain H. pylori-related information through videos uploaded by health professionals, nonprofit organizations, and science communicators.

Research trends on vonoprazan-based therapy for Helicobacter pylori eradication: A bibliometric analysis from 2015 to 2023.

BACKGROUND: Vonoprazan is an emerging option for the treatment of Helicobacter pylori infection. We aimed to assess the research trends and hotspots of vonoprazan-based therapy for H. pylori eradication through bibliometric analysis. MATERIALS AND METHODS: Vonoprazan-based studies for eradicating H. pylori published from 2015 to 2023 were extracted from the Web of Science using a combination of the search terms "H. pylori" and "vonoprazan." Each study was weighted according to the number of included patients. RESULTS: A total of 65 studies were included. Japan was the most productive and cooperative country, accounting for 69.2% of publications. Vonoprazan in combination with amoxicillin and clarithromycin (41.8%) was most used for eradicating H. pylori, followed by vonoprazan in combination with amoxicillin (20.4%) and vonoprazan in combination with amoxicillin and metronidazole (19.4%). The eradication rates for first-line vonoprazan-based therapies by intention to treat were: dual therapy (82.9%, 95% CI: 77.7%-88.0%), triple (83.3%, 95% CI: 79.7%-86.8%) and quadruple therapy (91.5%, 95% CI: 85.5%-97.4%), and per protocol: dual therapy (86.1%, 95% CI: 81.5%-90.7%), triple (89.3%, 95% CI: 87.9%-90.6%) and quadruple therapy (94.0%, 95% CI: 88.6%-99.4%). Vonoprazan was superior to proton pump inhibitors in triple therapy regarding empirical therapy (RR = 1.18, 95% CI, 1.14-1.22, p < 0.01) and clarithromycin-resistant group (RR = 1.71, 95% CI, 1.33-2.20, p < 0.01), but there is no significant difference between triple therapy and dual therapy (RR = 1.02, 95% CI, 0.98-1.07, p = 0.33). CONCLUSIONS: Vonoprazan has been widely used for H. pylori eradication. Further studies are needed to optimize the best duration and dosage of vonoprazan-based regimens in different regions.

Albumin infusion may decrease the mortality of hypoalbuminemia patients with severe acute pancreatitis: a retrospective cohort study.

BACKGROUND: At present, the relationship between severe acute pancreatitis (SAP) and albumin infusion is not clear. We aimed to identify the impact of serum albumin on the prognosis of SAP and the association between albumin infusions and mortality for hypoalbuminemia patients. METHODS: This was a retrospective cohort study that analyzed 1000 patients with SAP who were admitted to the First Affiliated Hospital of Nanchang University between January 2010 and December 2021 using data from a prospectively maintained database. Multivariate logistic regression analysis was conducted to reveal the relationship between serum albumin within 1 week after admission and poor prognosis of SAP. Propensity score matching (PSM) analysis was adopted to evaluate the effect of albumin infusion for hypoalbuminemia patients with SAP. RESULTS: The prevalence of hypoalbuminemia (≤ 30 g/L) was 56.9% within 1 week after admission. Multivariate logistic regression identified that age (OR: 1.02; 95% CI: 1.00-1.04; P = 0.012), serum urea (OR: 1.08; 95% CI: 1.04-1.12; P < 0.001), serum calcium (OR: 0.27; 95% CI: 0.14-0.50; P < 0.001), lowest albumin level within 1 week after admission (OR: 0.93; 95% CI: 0.89-0.97; P = 0.002), and APACHE II score ≥ 15 (OR: 1.73; 95% CI: 1.19-2.51; P = 0.004) were independently associated with mortality. The PSM analysis demonstrated that mortality (OR: 0.52, 95% CI: 0.29-0.92, P = 0.023) was less common in albumin-infused than non-albumin-infused hypoalbuminemia patients. In subgroup analyses, doses > 100 g within 1 week after admission for hypoalbuminemia patients with albumin infusions was associated with lower mortality than doses ≤ 100 g (OR: 0.51, 95% CI: 0.28-0.90, P = 0.020). CONCLUSIONS: Hypoalbuminemia in early-stage SAP is significantly related to poor prognosis. However, albumin infusions could significantly decrease mortality in hypoalbuminemia patients with SAP. Additionally, infusing sufficient albumin within a week after admission may decrease mortality in hypoalbuminemia patients.

Defined, low threshold for caesarean section and multidisciplinary team management improves fetal outcome from acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is associated with increased maternal and fetal mortality. OBJECTIVES: We sought to determine whether a low threshold for cesarean section (C-section) in severe acute pancreatitis (SAP) or Predict SAP improves maternal and fetal outcomes in patients with APIP. METHODS: We identified patients with APIP at a single institution from a prospective database and studied fetal and maternal health in APIP before (2005-2014) and after (2015-2019) introduction of multidisciplinary team management with a defined, lowered threshold for C-section. The primary end point was fetal mortality comprising abortion and perinatal death. Risk factors associated with fetal mortality were analyzed by univariable and multivariable logistic regression analysis. RESULTS: A total of 165 patients with APIP were eligible for analysis. There was a highly significant increase in patients undergoing C-section from 37 (30.8%) of 120 during 2005-2014 to 27 (60%) of 45 in 2015-2019 (P = 0.001), with a highly significant fall in fetal mortality from 37 (30.8%) of 120 to 3 (6.7%) of 45 between the same periods (P = 0.001), when maternal mortality fell from 6 to zero (P = 0.19). Maternal early systemic inflammatory response syndrome (SIRS) (odds ratio [OR] 6.98, 95% confidence interval [CI] 1.53, 30.80, P = 0.01) and SAP (OR 3.64, 95%CI 1.25, 10.60, P = 0.02) were two independent risk factors associated with fetal mortality. CONCLUSIONS: Multidisciplinary collaboration and a defined, low threshold for C-section improve fetal outcomes in patients with APIP.

The severity and infection of acute pancreatitis may increase the risk of bleeding in patients undergoing EUS-guided drainage and endoscopic necrosectomy: a large retrospective cohort.

BACKGROUND: There has been great progress in the use of endoscopic ultrasound (EUS)-guided drainage in acute pancreatitis patients using a novel lumen-apposing metal stent (LAMS) in the last decade, but some patients experience bleeding. Our research analyzed the preprocedural risk factors for bleeding. METHODS: From July 13, 2016 to June 23, 2021, we retrospectively analyzed all patients who received endoscopic drainage by the LAMS in our hospital. Univariate and multivariate statistical analyses were used to identify the independent risk factors. We plotted ROC curves based on the independent risk factors. RESULTS: A total of 205 patients were analyzed and 5 patients were excluded. A total of 200 patients were included in our research. Thirty (15%) patients presented with bleeding. In the multivariate analysis, computed tomography severity index score (CTSI) score [odds ratio (OR), 2.66; 95% CI: 1.31-5.38; P = 0.007], positive blood cultures [odds ratio (OR), 5.35; 95% CI: 1.31-21.9; P = 0.02], and Acute Physiology and Chronic Health Evaluation II (APACHE II) score [odds ratio (OR), 1.14; 95% CI: 1. 01-1.29; P = 0.045] were associated with bleeding. The area under the ROC curve of the combined predictive indicator was 0.79. CONCLUSION: Bleeding in endoscopic drainage by the LAMS is significantly associated with the CTSI score, positive blood cultures, and APACHE II score. This result could help clinicians make more appropriate choices.

Alcohol Consumption within 48 hours before Onset Is Associated with Adverse Clinical Outcomes in Hypertriglyceridemic Pancreatitis.

(1) Background: Some patients with hypertriglyceridemic pancreatitis (HTGP) drink occasionally or moderately, but do not meet the diagnostic criteria for alcoholic pancreatitis. This study aims to investigate whether occasional or moderate alcohol consumption affects the clinical outcomes of patients with HTGP. (2) Methods: This retrospective study included 373 patients with HTGP from January 2007 to December 2021. HTGP patients with occasional or moderate alcohol (OMA) consumption before onset were divided into the OMA group, and HTGP patients without alcohol (WA) consumption were divided into the WA group. The OMA group was further divided into two groups: the drinking within 48 h before onset (DW) group, and the without drinking within 48 h before onset (WDW) group. The clinical data of the two groups were compared and multivariable logistic regression was used to analyze independent risk factors for the primary outcomes. (3) Results: The proportion of men (95.7% vs. 67.6%, p < 0.001) and smoking history (61.7% vs. 15.1%, p < 0.001) in the OMA group were higher than those in the WA group. Occasional or moderate alcohol consumption was independently associated with a high incidence of SAP (adjusted odds ratio (AdjOR), 1.57; 95% CI, 1.02-2.41; p = 0.041), and necrotizing pancreatitis (AdjOR, 1.60; 95% CI, 1.04-2.48; p = 0.034). After dividing the OMA group into two subgroups, we found that drinking within 48 h before onset was independently associated with a high incidence of SAP (AdjOR, 3.09; 95% CI, 1.66-5.77; p < 0.001), and necrotizing pancreatitis (AdjOR, 2.71; 95% CI, 1.46-5.05; p = 0.002). (4) Conclusion: Occasional or moderate alcohol consumption is associated with poor clinical outcomes in patients with HTGP, particularly if they drank alcohol within 48 h before the onset of the disease.

Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study.

Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients' quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects' gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.

Serum triglyceride levels are associated with recurrence in patients with acute hypertriglyceridemic pancreatitis.

Aim: To analyze the clinical profile of patients with acute hypertriglyceridemic pancreatitis (HTGP) and explore risk factors for recurrence. Methods: A retrospective observational study was conducted in patients who experienced an attack of HTGP for the first time. Patients were followed until the recurrence of acute pancreatitis (AP) or 1 year. The detailed clinical profile was compared between patients with or without recurrence. Multivariate logistic regression analysis was conducted to explore independent risk factors for recurrence. Results: A total of 108 HTGP patients were included in this study with 73.1% being male, and the median age being 37 (interquartile range, IQR, 30.3-44.8) years. Recurrence occurred in 70 patients (64.8%). Compared with the nonrecurrent group, serum triglyceride (TG) levels before discharge [4.1 (2.8,6.3) mmol/L vs. 2.9 (2.2,4.2) mmol/L; p = 0.002], at 1 month [3.7 (2.3,9.7) mmol/L vs. 2.0 (1.4,2.7) mmol/L; p = 0.001], at 6 months [6.1 (3.1,13.1) mmol/L vs. 2.5 (1.1,3.5) mmol/L; p = 0.003] and 12 months [9.6 (3.5,20.0) mmol/L vs. 2.7 (1.6,5.5) mmol/L; p = 0.001] after discharge were higher in the recurrent group. Poor control of TG levels (TG > 3.1 mmol/l) at the 1-month follow-up after discharge and a high Charlson's Comorbidity Index score (≥ 2 points) increased the risk of recurrence of HTGP. Conclusion: High TG levels during follow-up and Charlson's Comorbidity Index score were independently associated with recurrence in patients with HTGP.

Colloidal bismuth pectin-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection: A multicenter, randomized, double-blind, non-inferiority clinical trial.

BACKGROUND: Bismuth-containing quadruple therapy is an effective regimen for Helicobacter pylori (H. pylori) treatment. No head-to-head comparison trials have been conducted to evaluate the efficacy of colloidal bismuth pectin (CBP) in quadruple therapy for eradicating H. pylori. We aimed to compare the efficacy and safety of CBP quadruple therapy and bismuth potassium citrate (BPC) quadruple therapy for 14 days in the first-line treatment of H. pylori. METHODS: In this multicenter, randomized, double-blind, non-inferiority clinical trial, H. pylori-infected subjects without eradication history were randomized to receive amoxicillin 1 g twice daily, tetracycline 500 mg three time daily, esomeprazole 20 mg twice daily in combination with CBP 200 mg three time daily or BPC 240 mg twice daily for 14 days. 13 C-urea breath tests were used to access the eradication rate at least 4 weeks after treatment. RESULTS: Between April 2021 and July 2022, 406 patients were assessed for eligibility and 339 subjects were randomized. The cure rates (primary outcome) of CBP and BPC quadruple therapy were 90.5% and 92.3% (p = 0.56) by intention-to-treat analysis, respectively, and 96.1% and 96.2% (p = 1.00) by per-protocol analysis, respectively. CBP quadruple therapy was non-inferior to BPC quadruple therapy in the intention-to-treat and per-protocol analysis (p < 0.025). The frequency of adverse events and compliance were not different among the two groups (p > 0.05). CONCLUSIONS: Both CBP and BPC quadruple therapy for 14 days provide high efficacy, good compliance, and safety in the first-line treatment of H. pylori in China.

Effect of Lactobacillus plantarum P9 on defecation, quality of life and gut microbiome in individuals with chronic diarrhoea: Protocol for a randomized, double-blind, placebo-controlled clinical trial.

Background: Probiotics may be an ideal choice for these patients, given it can improve the defecation and quality of life of individuals with chronic diarrhoea. However, evidence-based medical research is still limited to support its use as a diarrhoea agent. Method: A randomized, double-blind, placebo-controlled clinical trial is designed to pinpoint the efficiency and possible action modes of probiotics for chronic diarrhoea. 200 eligible volunteers with chronic diarrhoea are randomly assigned to a probiotic group (orally taking Lactobacillus plantarum p9 probiotics powder) or a placebo group. Except an independent project administrator who will be responsible for unblinding, the other researchers are blinded. Primary outcome is diarrhoea severity score, and secondary outcomes include weekly mean frequency of defecation, weekly mean stool appearance score, weekly mean stool urgency score, emotional state score, gut microbiome, and faecal metabolome. Each outcome measure will be assessed at the timepoints of pre-administration (day 0), administration (day 14 and/or 28), and post-administration (day 42) to identity inter- and intra-groups differences. Adverse events will be recorded to evaluate the safety of L. plantarum p9. Discussion: The study protocol will provide high-quality evidence for the use of probiotics as a diarrhoea agent when it is strictly conducted out, providing evidence regarding whether and to what extent L. plantarum p9 can improve the defecation and well-being of individuals with chronic diarrhoea. Trial registration: Chinese Clinical Trial Registry (ChiCTR) (NO. ChiCTR2000038410). Registered on November 22, 2020, https://www.chictr.org.cn/showproj.aspx?proj=56542.

YAP and ß-catenin cooperate to drive H. pylori-induced gastric tumorigenesis.

H. pylori infection is the strongest known risk factor for gastric carcinoma. The activation of the yes-associated protein 1 (YAP) and ß-catenin pathways has been associated with multiple tumor types. In this study, we investigated the crosstalk between the YAP and ß-catenin pathways in H. pylori-associated gastric tumorigenesis. Immunohistochemical analysis of YAP and ß-catenin expression was performed in human gastric cancer tissues. The small molecules Super-TDU and KYA1797K, pharmacological inhibitors of YAP and ß-catenin, respectively, were used to investigate the role of these signaling pathways in H. pylori-induced gastric carcinogenesis in murine models of infection. The common downstream targets of YAP and ß-catenin signaling were evaluated by RNA sequencing (RNA-seq). Western blot, immunofluorescence, luciferase, RT-PCR, immunoprecipitation, cell counting kit-8 (CCK8), EdU and spheroid assays were used. H. pylori infection promoted YAP and ß-catenin nuclear accumulation and transcriptional activity in gastric epithelial cells and transgenic insulin-gastrin (INS-GAS) mice, whereas silencing of both YAP and ß-catenin synergistically inhibited H. pylori-induced cell proliferation and expansion. In addition, YAP was found to directly interact with ß-catenin and knockdown of YAP suppressed H. pylori-induced nuclear translocation of ß-catenin. Moreover, downstream genes caudal-type homeobox 2 (CDX2), leucine-rich repeat containing G protein-coupled receptor 5 (LGR5) and RuvB like AAA ATPase 1 (RUVBL1) were shared by both YAP and ß-catenin signaling. Furthermore, treatment with the YAP inhibitor Super-TDU or ß-catenin inhibitor KYA1797A significantly alleviated gastric inflammation and epithelial DNA damage in H. pylori-infected mice. Finally, the elevation of gastric YAP was positively correlated with ß-catenin expression in human gastric cancer tissues. These findings indicate that YAP and ß-catenin synergistically promote H. pylori-induced gastric carcinogenesis via their physical interaction and reveal that CDX2, LGR5 and RUVBL1 are the downstream genes shared by both the YAP and ß-catenin signaling pathways, and potentially contribute to H. pylori pathogenesis.