Objective: Infection with Helicobacter pylori (H pylori), especially cytotoxin‐associated gene A‐positive (CagA+) strains, has been associated with various gastrointestinal and extragastric diseases. The aim of this study was to characterize H pylori‐induced alterations in the gastric and tongue coating microbiota and evaluate their potential impacts on human health.Design: The gastric mucosa and tongue coating specimens were collected from 80 patients with chronic gastritis, and microbiota profiles were generated by 16S rRNA gene sequencing. Samples were grouped as H pylori negative (n = 32), CagA‐negative H pylori infection (n = 13), and CagA‐positive H pylori infection (n=35). The comparison of bacterial relative abundance was made using a generalized linear model. Functional profiling of microbial communities was predicted with PICRUSt and BugBase. Microbial correlation networks were produced by utilizing SparCC method.Results: Significant alterations of the gastric microbiota were found in the H pylori+/CagA+ samples, represented by a decrease in bacterial diversity, a reduced abundance of Roseburia, and increased abundances of Helicobacter and Haemophilus genera. At the community level, functions involved in biofilm forming, mobile element content, and facultative anaerobiosis were significantly decreased in gastric microbiome of the H pylori+ subjects. The presence of CagA gene was linked to an increased proportion of Gram‐negative bacteria in the stomach, thereby contributing to an upregulation of lipopolysaccharide (LPS) biosynthesis. The number of bacterial interactions was greatly reduced in networks of both tongue coating and gastric microbiota of the H pylori+/CagA+ subject, and the cooperative bacterial interactions dominated the tongue coating microbiome.Conclusions: Infection with H pylori strains possessing CagA may increase the risk of various diseases, by upregulating LPS biosynthesis in the stomach and weakening the defense of oral microbiota against microorganisms with pathogenic potential.

Background: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease and is closely linked to type 2 diabetes mellitus (T2DM). The pathogenesis of MAFLD involves complex metabolic imbalances, including impaired fatty acid β-oxidation and chronic inflammation. GLP-1 receptor agonists (GLP-1 RAs) have shown promise in improving metabolic outcomes, but their specific effects on MAFLD remain unclear. This study aims to investigate the molecular mechanisms underlying the hepatic benefits of semaglutide, a GLP-1 RA, in T2DM patients with MAFLD using serum proteomics and metabolomics.Methods: We conducted a single-centre, longitudinal, data-driven study involving 75 T2DM patients with MAFLD (pre-treatment, PT) and 100 healthy controls (health control, HC). Patients received semaglutide treatment (0.25 mg/week initially, escalated to 0.5 mg/week) for 12 weeks. Serum proteomic and metabolomic profiles were analyzed using 4D-DIA proteomics and LC-MS before and after treatment. Biomarker discovery involved the identification of differential metabolites and proteins, pathway analysis, and integration of proteomic and metabolomic data. Clinical and biochemical parameters were also assessed.Results: Semaglutide significantly improved metabolic and liver parameters, including HbA1c, BMI, HOMA-IR, liver function, IL-6, and liver stiffness (p < 0.01). Multivariate analysis revealed distinct proteomic and metabolomic profiles between baseline and post-treatment groups. A total of 203 differential metabolites and 61 proteins were identified, with key changes including reductions in long-chain fatty acids and inflammatory mediators, alongside increases in carnitine derivatives and anti-inflammatory proteins. Pathway analysis highlighted effects on fatty acid metabolism, PPAR signaling, and NAFLD-related pathways.Conclusion: Our study provides a comprehensive multi-omics analysis revealing that semaglutide modulates serum proteomic and metabolomic profiles in T2DM-MAFLD patients, potentially through enhancing mitochondrial β-oxidation, reducing lipid toxicity, and suppressing inflammation. These findings offer mechanistic insights into the hepatic benefits of semaglutide and support its potential as a therapeutic agent for MAFLD. This innovative approach advances our understanding of GLP-1 RAs’ multi-organ protective effects and provides a foundation for developing precision medicine strategies for MAFLD.

In the present study, we investigated the potential role of phenolic acids in initiating oxidative damage to microvascular endothelial cells and the underlying mechanism mediating the pro-oxidant action. Male Wistar rats received high doses of phenolic acid [caffeic acid (CA), salvianolic acid B (SAB), chlorogenic acid (ChA) or ferulic acid (FA)]. The creation of reactive oxygen species in mesenteric microcirculation endothelial cells and adherent leukocytes along with venules were assessed using intravital microscopy. The expression levels of NADPH oxidase subunits (Nox4 and p22phox) in terminal ileum tissues were determined by western blot analysis. Intravenous injection of high-dose ChA or CA (7 mg/kg) markedly increased the peroxide production in the venular walls and upregulated the protein expression levels of Nox4 and p22phox in the ileum tissues, while the same dose of CA and SAB made no difference within the observation period. No changes were observed in the number of leukocytes adhering to the venular walls. High-dose ChA and FA led to an imbalance between the oxidant and antioxidant mechanism by boosting the expression levels of NADPH oxidase. Thus, we clarified the rationale behind the adverse effects of a herbal injection containing high levels of phenolic acid compounds.

Background: Nirmatrelvir plus ritonavir (Paxlovid) have been used in the treatment of adult patients with mild-to-moderate coronavirus disease 2019 (COVID-19). This study aimed to evaluate the impact of Paxlovid on in-hospital outcomes and post-COVID-19 condition in Chinese adult patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. Methods: This non-randomized clinical controlled trial recruited patients infected with SARS-CoV-2 Omicron variant from the designated hospital for treating COVID-19 between November 5 and November 28, 2022, in Shijiazhuang, China. Participants were administered Paxlovid (300 mg of nirmatrelvir and 100 mg of ritonavir orally) or standard treatment. The primary outcome was the nucleic acid shedding time and post-COVID-19 condition. Results: A total of 320 patients infected with SARS-CoV-2 Omicron variant were included, with mean age of 29.10 ± 7.34 years old. Two hundred patients received Paxlovid. Compared to patients in the standard treatment group, those in Paxlovid group had a significantly shorter nucleic acid shedding time (3.26 ± 1.80 vs 7.75 ± 3.68 days, P < .001), shorter days until negative swab test (1.74 ± 1.15 vs 5.33 ± 2.91, P < .001), shorter days of first symptoms resolution (4.86 ± 1.62 vs 7.45 ± 2.63, P < .001), higher in nucleic acid test negative rate within 3 days [138 (70.77%) vs 14 (11.67%), P < .001], higher negative rate within 5 days [174 (89.23%) vs 26 (21.67%), P < .001], negative rate within 7 days [185 (94.87%) vs 78 (65.00%), P < .001], and were less likely to have post-COVID-19 condition [32 (18.60%) vs 30 (31.57%), P = .016]. There was no significant difference in duration of post-COVID-19 condition (43.00 ± 26.00 vs 49.00 ± 26.34 days, P = .354) between the 2 groups. Conclusion: Compared to standard treatment, Paxlovid significantly reduced nucleic acid shedding time, days until negative swab test, and days of first symptoms resolution, as well as improved nucleic acid test negative rate and post-COVID-19 condition.

Many individuals experience long COVID after SARS-CoV-2 infection. As microbiota can influence health, it may change with COVID-19. This study investigated differences in oral microbiota between COVID-19 patients with and without long COVID. Based on a prospective follow-up investigation, this nested case-control study evaluated the differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups), which were assessed by 16S rRNA sequencing on tongue coating samples. A predictive model was established using machine learning based on specific differential microbial communities. One-hundred-and-eight patients were included (n=54 Symptomatic group). The Symptomatic group had higher Alpha diversity indices (observed_otus, Chao1, Shannon, and Simpson indices), differences in microbial composition (Beta diversity), and microbial dysbiosis with increased diversity and relative abundance of pathogenic bacteria. Marker bacteria (c__Campylobacterota, o__Coriobacteriales, o__Pseudomonadales, and o__Campylobacterales) were associated with long COVID by linear discriminant analysis effect size and receiver operating characteristic curves (AUC 0.821). There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID. Changes in oral microbiota may indicate long COVID.