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Abstract Cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity globally. Studies have shown that infections especially bacteraemia and sepsis are associated with increased risks for endothelial dysfunction and related CVDs including atherosclerosis. Extracellular vesicles (EVs) are small, sealed membrane‐derived structures that are released into body fluids and blood from cells and/or microbes and are critically involved in a variety of important cell functions and disease development, including intercellular communications, immune responses and inflammation. It is known that EVs‐mediated mechanism(s) is important in the development of endothelial dysfunction in infections with a diverse spectrum of microorganisms including Escherichia coli, Candida albicans, SARS‐CoV‐2 (the virus for COVID‐19) and Helicobacter pylori. H. pylori infection is one of the most common infections globally. During H. pylori infection, EVs can carry H. pylori components, such as lipopolysaccharide, cytotoxin‐associated gene A, or vacuolating cytotoxin A, and transfer these substances into endothelial cells, triggering inflammatory responses and endothelial dysfunction. This review is to illustrate the important role of EVs in the pathogenesis of infectious diseases, and the development of endothelial dysfunction in infectious diseases especially H. pylori infection, and to discuss the potential mechanisms and clinical implications.

Abstract Background The sensitivity of RT-PCR in diagnosing COVID-19 is only 60–70%, and chest CT plays an indispensable role in the auxiliary diagnosis of COVID-19 pneumonia, but the results of CT imaging are highly dependent on professional radiologists. Aims This study aimed to develop a deep learning model to assist radiologists in detecting COVID-19 pneumonia. Methods The total study population was 437. The training dataset contained 26,477, 2468, and 8104 CT images of normal, CAP, and COVID-19, respectively. The validation dataset contained 14,076, 1028, and 3376 CT images of normal, CAP, and COVID-19 patients, respectively. The test set included 51 normal cases, 28 CAP patients, and 51 COVID-19 patients. We designed and trained a deep learning model to recognize normal, CAP, and COVID-19 patients based on U-Net and ResNet-50. Moreover, the diagnoses of the deep learning model were compared with different levels of radiologists. Results In the test set, the sensitivity of the deep learning model in diagnosing normal cases, CAP, and COVID-19 patients was 98.03%, 89.28%, and 92.15%, respectively. The diagnostic accuracy of the deep learning model was 93.84%. In the validation set, the accuracy was 92.86%, which was better than that of two novice doctors (86.73% and 87.75%) and almost equal to that of two experts (94.90% and 93.88%). The AI model performed significantly better than all four radiologists in terms of time consumption (35 min vs. 75 min, 93 min, 79 min, and 82 min). Conclusion The AI model we obtained had strong decision-making ability, which could potentially assist doctors in detecting COVID-19 pneumonia.

Background:Helicobacter pylori (H.pylori) infection is an important factor in the occurrence of human gastric diseases, but its pathogenic mechanism is not clear. N6-methyladenosine (m6A) is the most prevalent reversible methylation modification in mammalian RNA and it plays a crucial role in controlling many biological processes. However, there are no studies reported that whether H. pylori infection impacts the m6A methylation of stomach. In this study, we measured the overall level changes of m6A methylation of RNA under H. pylori infection through in vitro and in vivo experiment.Methods: The total quantity of m6A was quantified in gastric tissues of clinical patients and C57 mice with H. pylori infection, as well as acute infection model [H. pylori and GES-1 cells were cocultured for 48 h at a multiplicity of infection (MOI) from of 10:1 to 50:1]. Furthermore, we performed m6A methylation sequencing and RNA-sequencing on the cell model and RNA-sequencing on animal model.Results: Quantitative detection of RNA methylation showed that H. pylori infection group had higher m6A modification level. M6A methylation sequencing identified 2,107 significantly changed m6A methylation peaks, including 1,565 upregulated peaks and 542 downregulated peaks. A total of 2,487 mRNA was upregulated and 1,029 mRNA was downregulated. According to the comprehensive analysis of MeRIP-seq and RNA-seq, we identified 200 hypermethylation and upregulation, 129 hypermethylation but downregulation, 19 hypomethylation and downregulation and 106 hypomethylation but upregulation genes. The GO and KEGG pathway analysis of these differential methylation and regulatory genes revealed a wide range of biological functions. Moreover, combining with mice RNA-seq results, qRT- PCR showed that m6A regulators, METTL3, WTAP, FTO and ALKBH5, has significant difference; Two key genes, PTPN14 and ADAMTS1, had significant difference by qRT- PCR.Conclusion: These findings provide a basis for further investigation of the role of m6A methylation modification in H. pylori-associated gastritis.

BackgroundThe increasing antibiotic resistance is the main issue causing Helicobacter pylori (H. pylori) eradication failure. As a nutritional supplement, Egg Yolk Antibody (Ig Y) provides a new approach for H. pylori infection rescue therapy.MethodsIn this randomized, controlled study, 100 H. pylori-positive patients with previous H. pylori eradication treatment were included. All individuals received standard bismuth-containing quadruple therapy twice daily (5 mg ilaprazole, 100 mg doxycycline, 500 mg clarithromycin or 1 g amoxicillin or 100 mg furazolidone, and 220 mg colloidal bismuth tartrate) for 14 days and were randomized to receive either twice daily 7 g Ig Y-H. pylori treatment (study group) or not (control group). 4 weeks after the end of treatment, urea breath tests were used to assess the H. pylori eradication rate. All participants scored by the Global Overall Symptom scale (GOS) and recorded adverse events during the trial.ResultsThe H. pylori eradication rates were 84.0% (95% CI 73.5–94.5%) vs. 80.0% (95% CI 68.5–91.5%) in the study and control groups at intention-to-treat (ITT) analysis and 85.7% (95% CI 75.6–95.9%) vs. 80.0% (95% CI 68.5–91.5%) at per-protocol (PP) analysis, respectively. The number of over 80% symptom relief after treatment in the two groups was 27 (60%) and 12 (29.2%) (p < 0.05), and the incidences of adverse events were 4 (8%) and 6 (12%), respectively.ConclusionBoth groups achieved satisfactory eradication efficiency in H. pylori rescue therapy and Ig Y-H. pylori effectively alleviates the symptoms with good compliance and fewer adverse effects.

Abstract Background The chronic infection with Helicobacter pylori (H. pylori), especially cytotoxin-associated gene A-positive (CagA+) strains, has been associated with various extragastric disorders. Evaluating the potential impacts of virulence factor CagA on intestine may provide a better understanding of H. pylori pathogenesis such as colitis. The intestinal mucosal barrier is essential for maintaining its integrity and functions. However, how persistent CagA+ H. pylori colonization influences barrier disruption and thereby affects chronic colitis is not fully understood. Results Chronic colitis models of CagA+ H. pylori-colonized mice treated with 2% Dextran sulphate sodium (DSS) were established to assess the disease activity and pertinent expression of tight junction proteins closely related to mucosal integrity. The aggravating effect of CagA+ H. pylori infection on DSS-induced chronic colitis was confirmed in mouse models. In addition, augmented Claudin-2 expression was detected in CagA+ H. pylori infection conditions and selected for mechanistic analysis. Next, GES-1 human gastric epithelial cells were cultured with CagA+ H. pylori or a recombinant CagA protein, and exosomes isolated from conditioned media were then identified. We assessed the Claudin-2 levels after exposure to CagA+ exosomes, CagA− exosomes, and IFN-γ incubation, revealing that CagA+ H. pylori compromised the colonic mucosal barrier and facilitated IFN-γ-induced intestinal epithelial destruction through CagA-containing exosome-mediated mechanisms. Specifically, CagA upregulated Claudin-2 expression at the transcriptional level via a CDX2-dependent mechanism to slow the restoration of wounded mucosa in colitis in vitro. Conclusions These data suggest that exosomes containing CagA facilitate CDX2-dependent Claudin-2 maintenance. The exosome-dependent mechanisms of CagA+ H. pylori infection are indispensable for damaging the mucosal barrier integrity in chronic colitis, which may provide a new idea for inflammatory bowel disease (IBD) treatment.

BackgroundThe increasing rate of drug resistance often leads to Helicobacter pylori (H. pylori) eradication failure and needs the rescue therapy. Thus, the exploration of new rescue therapeutic regimens is important. The present study was designed to test the beneficial effects of Saccharomyces boulardii (S.boulardii) prior to H. pylori rescue therapy basing on bismuth quadruple.MethodsOne hundred H. pylori-infected patients were randomly divided into two groups: study group and control group. Patients in the study group (n=50) underwent two-stages therapy: patients started with S.boulardii monotherapy for 2 weeks, and then tested for H. pylori infection after resting for 4 weeks without any therapy, patients who were still positive for H. pylori continued with bismuth quadruple eradication therapy. For the control group (n=50), all patients were observed and were not treated with any gastric drugs or antibiotics for 6 weeks, then those who were still positive for H. pylori received the same eradication therapy as the study group. Eradication rate, adverse events and the cost-effectiveness of two regimens were analyzed in this study.ResultsThe H.pylori eradication rate of ITT (intent-to-treat) analysis and PP (per-protocol) analysis in the first phase of treatment were significantly higher in the study group than the control groups respectively (28.0% vs 2.0%, p

Background: Increased antibiotic resistance is one of the major factors contributing to the failure of H. pylori eradication. This study aimed to compare the efficacy and safety of doxycycline and amoxicillin, both critical components for bismuth-based quadruple therapy, for the first-line treatment of H. pylori-infected duodenal ulcers. Methods: An open, randomized case-controlled, multicenter trial was conducted in seven hospitals in China. A total of 184 eligible participants were divided into an IDFB (ilaprazole 5 mg, doxycycline 100 mg, furazolidone 100 mg, and bismuth 220 mg bid) or IAFB (ilaprazole 5 mg, amoxicillin 1000 mg, furazolidone 100 mg, and bismuth 220 mg bid) group for 14 days. Both groups were administrated with ilaprazole 5 mg qd for another 14 days. The main outcome was an H. pylori eradication rate; secondary outcomes were ulcer healing, relief of symptoms, and incidence of adverse effects. Results: The H. pylori eradication rates were 85.9% (95% CI 78.6–93.9) in the IDFB vs. 84.8% (95% CI 77.3–92.3) in the IAFB group in ITT analysis (p > 0.05), and 92.9% (95% CI 87.4–98.5) vs. and 91.8% (95% CI 85.8–97.7) in PP analysis (p > 0.05). The overall ulcer healing rates of IDFB and IAFB were 79.1% and 84.7% (p > 0.05), both effective in relieving symptoms. Only nine participants had adverse reactions in this trial (4/92 in IDFB and 5/92 in IAFB). Conclusion: A bismuth quadruple regimen containing doxycycline or amoxicillin could be an effective and safe treatment for H. pylori eradication, while doxycycline replacement is an alternative for participants with penicillin allergy.

Background Epidemiological studies have suggested an association between Helicobacter pylori (H pylori) infection and atherosclerosis through undefined mechanisms. Endothelial dysfunction is critical to the development of atherosclerosis and related cardiovascular diseases. The present study was designed to test the hypothesis that H pylori infection impaires endothelial function through exosome‐mediated mechanisms. Methods and Results Young male and female patients (18‐35 years old) with and without H pylori infection were recruited to minimize the chance of potential risk factors for endothelial dysfunction for the study. Endothelium‐dependent flow‐mediated vasodilatation of the brachial artery was evaluated in the patients and control subjects. Mouse infection models with CagA+ H pylori from a gastric ulcer patient were created to determine if H pylori infection‐induced endothelial dysfunction could be reproduced in animal models. H pylori infection significantly decreased endothelium‐dependent flow‐mediated vasodilatation in young patients and significantly attenuated acetylcholine‐induced endothelium‐dependent aortic relaxation without change in nitroglycerin‐induced endothelium‐independent vascular relaxation in mice. H pylori eradication significantly improved endothelium‐dependent vasodilation in both patients and mice with H pylori infection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA+ H pylori or serum exosomes from patients and mice with H pylori infection significantly decreased endothelial functions with decreased migration, tube formation, and proliferation in vitro. Inhibition of exosome secretion with GW4869 effectively preserved endothelial function in mice with H pylori infection. Conclusions H pylori infection impaired endothelial function in patients and mice through exosome‐medicated mechanisms. The findings indicated that H pylori infection might be a novel risk factor for cardiovascular diseases.