Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.

The potential bidirectional association between Helicobacter pylori infection and gallstone disease in adults: A two-cohort study.

BACKGROUND: Previous studies have suggested that Helicobacter pylori (H. pylori) may act as a precipitating factor in gallstone formation, and the potential association between H. pylori infection and gallstone disease (GD) is still unclear and controversial. This study aimed to clarify the potential bidirectional relationship between H. pylori infection and GD. METHODS: This retrospective cohort study was performed in a population that underwent health checkups at the hospital between 2013 and 2018. H. pylori infection status was evaluated by urea breath test (UBT), and GD was diagnosed via ultrasound. Cox regression and propensity score matching (PSM) were used. RESULTS: Among 1011 participants without H. pylori infection at baseline, 134 participants were infected with H. pylori. Among 1192 participants without gallstones or cholecystectomy at baseline, 60 participants developed gallstones or cholecystectomy. The hazard ratio (HR) (95% CI) for incident H. pylori infection comparing the GD versus the no GD group was 1.84 (1.19, 2.85). The age- and sex-adjusted HR (95% CI) for incident GD comparing H. pylori-positive subjects to H. pylori-negative subjects was 1.74 (1.01, 2.98). Consistent results were also found with PSM and multivariate analysis. CONCLUSIONS: This cohort study demonstrated a potential bidirectional association between H. pylori infection and GD, which provides a basis for indicating the risk of GD and implementing the clinical strategies for GD. For the prevention and treatment of GD, H. pylori infection should be carefully considered and evaluated.

Antibiotic Resistance of Helicobacter pylori Isolated from Patients after Partial Gastrectomy: A Retrospective Study.

BACKGROUND: To determine the prevalence of Helicobacter pylori infection and the antibiotic susceptibility of H. pylori in patients after partial gastrectomy. METHODS: Patients who underwent gastroscopy from January 2009 to November 2017 and had a history of partial gastrectomy were retrospectively enrolled in the remnant stomach group. Contemporary non-gastrectomized patients with an endoscopic diagnosis of chronic gastritis were enrolled in the non-operated stomach group. The detection of H. pylori infection was performed by culture and histology. The in vitro antimicrobial susceptibility was examined by the agar dilution method on strains from gastric biopsies. RESULTS: In this study, a total of 728 gastrectomized and 5035 non-gastrectomized patients were included. There was a significantly lower prevalence of H. pylori infection in the gastric-remnant patients (8.65%) than in the non-gastrectomized patients (17.76%) (P < .001) with the diagnostic method of culture. In the gastric-remnant patients, the H. pylori strains had resistance rates to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone of 100%, 20.63%, 22.22%, 0%, and 0%, respectively. In the nongastrectomized patients, H. pylori resistance to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone was 90.49%, 24.61%, 21.70%, 0.22%, and 0.11%, respectively. Gastric-remnant patients had a significantly higher metronidazole resistance rate than non-gastrectomized patients (P = .005). Moreover, no significant changes in the resistance to 5 antibiotics were observed among the gastric-remnant patients from different age, gender, and surgical indication groups. CONCLUSION: Patients after partial gastrectomy showed a lower prevalence of H. pylori infection. Gastric-remnant patients were more likely to harbor metronidazole-resistant H. pylori strains.

Current status of Helicobacter pylori eradication and risk factors for eradication failure.

BACKGROUND: The Helicobacter pylori (H. pylori) eradication rate is decreasing in the general population of China. AIM: To evaluate the H. pylori eradication status in real-world clinical practice and to explore factors related to eradication failure. METHODS: Patients with H. pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Multivariate analysis was performed to identify predictors of eradication failure. RESULTS: Of 2610 patients enrolled, eradication was successful in 1999 (76.6%) patients. Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens (83.0% vs 69.0%, P < 0.001). The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate (83.5%). Primary therapy had a higher eradication rate than rescue therapy (78.3% vs 66.5%, P < 0.001). In rescue therapy, the amoxicillin- and furazolidone-containing regimens achieved the highest eradication rate (80.8%). Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors (81.8% vs 74.9%, P = 0.001). Multivariate regression analysis found that older age, prior therapy, and use of omeprazole or pantoprazole were associated with an increased risk of eradication failure. CONCLUSION: The total eradication rate is 76.6%. Amoxicillin-containing regimens are superior to other regimens. Age, prior therapy, and use of omeprazole or pantoprazole are independent risk factors for eradication failure.

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity.

BACKGROUND: Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM: To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS: Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS: The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION: Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.

Antagonizing circRNA_002581-miR-122-CPEB1 axis alleviates NASH through restoring PTEN-AMPK-mTOR pathway regulated autophagy.

Circular RNAs (circRNAs) have been shown to play critical roles in cancer biology, but their functions in nonalcoholic steatohepatitis (NASH) remain unexplored. Full length of circRNA_002581 was amplified and sequenced, followed by RNA immunoprecipitation, RNA-Fluorescence in Situ Hybridization and dual luciferase reporter gene analysis to confirm the existence of the circRNA_002581-miR-122-CPEB1 regulatory axis in vitro. CircRNA_002581 knockdown was used to study its roles in high concentration of free fatty acids-induced NASH-like cell model and a methionine and choline deficiency (MCD) diet-induced NASH mice model. Autophagy flux and related potential PTEN-AMPK-mTOR pathway were tested by western blot. CircRNA_002581 overexpression significantly relieved the inhibitory role of miR-122 on its target CPEB1 by sponging miR-122. CircRNA_002581 knockdown markedly attenuated lipid droplet accumulation, reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), pro-inflammatory cytokines, apoptosis, H2O2, and increased ATP level in both mice and cellular models of NASH. Mechanistically, circRNA_002581 interference significantly rescue the defective autophagy evidenced by increased autophagosome number, upregulated LC3-II/I level, and decreased p62 level. Further chloroquine-mediated total autophagy inhibition antagonizes the protective effect of circRNA_002581 knockdown. Finally, CPEB1-PTEN-AMPK-mTOR pathway is shown to link the autophagy and circRNA_002581 knockdown-mediated NASH alleviation. CircRNA_002581-miR-122-CPEB1 axis actively participates in the pathogenesis of NASH through PTEN-AMPK-mTOR pathway-related autophagy suppression. Targeting circRNA_002581 is a potential therapeutic strategy for NASH through partial autophagy restoration.

Cost-Effectiveness Analysis of Helicobacter pylori Eradication Therapy for Prevention of Gastric Cancer: A Markov Model.

BACKGROUND: Helicobacter pylori (H. pylori) eradication can reduce the prevalence of gastric cancer. However, whether H. pylori eradication therapy should be performed in infected patients, especially in asymptomatic cases, is still controversial. AIMS: The aims of this study were to determine whether H. pylori screening and eradication could prevent gastric cancer in a cost-effective way, and further whether eradication therapy should be administered to asymptomatic individuals. METHODS: Cost-effectiveness analysis was performed using a Markov model. We established two groups, each with 10,000 hypothetical Chinese individuals at the age of 40 years. Clinical outcomes and cost of H. pylori eradication were compared between the eradication and control groups. RESULTS: There was a lower morbidity with gastric cancer in the eradication group than in the control group, which was most significant after running the model for 15 years. The eradication group experienced an average of 34.64 quality-adjusted life years (QALYs) per person, and the average cost was US $1706.52 per person. The control group exhibited an average of 32.63 QALYs per person, and the average cost was US $2045.10 per person. The cost-effectiveness analysis showed that eradication saved $1539 per LY per person and $168.45 per QALY per person. CONCLUSIONS: H. pylori screening and eradication therapy effectively reduces the morbidity of gastric cancer and cancer-related costs in asymptomatic infected individuals. Therefore, we believe that H. pylori eradication can prevent gastric cancer in a cost-effective way.

Is Helicobacter pylori associated with Behçet's syndrome? A meta-analysis.

BACKGROUND: Preceding studies have reported the relationship between Helicobacter pylori (H pylori) and Behçet's syndrome (BS), but there still exists controversy. In this study, we firstly conducted a meta-analysis to clarify the relationship of these two diseases. METHODS: Articles published until July 1, 2019, in the PubMed, MEDLINE, and Embase databases with restriction of English-language studies were searched and reviewed. According to the inclusion criteria, relevant statistical data were extracted and analyzed. RESULTS: Six articles were finally included. The result showed that BS individuals were 1.39 times more susceptible to H pylori infection (OR = 1.39, 95% CI = (1.03, 1.87)). In addition, it found that oral ulceration (OR = 27.98, 95% CI = (3.49, 224.49)), genital ulceration (OR = 3.15, 95% CI = (1.51, 6.56)), and cutaneous lesions (OR = 4.29, 95% CI = (2.14, 8.61)) were alleviated after H pylori eradication. Publication bias and sensitivity analysis showed no statistical heterogeneity. CONCLUSIONS: BS patients had higher rate of H pylori infection, and clinical symptoms including oral ulceration, genital ulceration, and cutaneous lesions can be improved after H pylori eradication. The results indicated that H pylori may be an etiological factor to BS.

Serological characteristics of autoimmune pancreatitis and its differential diagnosis from pancreatic cancer by using a combination of carbohydrate antigen 19-9, globulin, eosinophils and hemoglobin.

Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19-9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P<0.05), while hemoglobin and tumor marker CA19-9 levels were lower (P <0.05). The combination of these markers identified patients with AIP with 92% sensitivity and 79% specificity, which indicated relatively high diagnostic value. Elevated serum eosinophils, globulin, together with decreased hemoglobin level can be used as a preoperative indicator for AIP and can help to initiate diagnosis of AIP in time.

ω-3 Fatty acids reverse lipotoxity through induction of autophagy in nonalcoholic fatty liver disease.

OBJECTIVE: The aim of this study was to evaluate the effect of ω-3 fatty acids on nonalcoholic fatty liver disease concerning hepatocyte lipid accumulation as well as apoptosis induced by free fatty acids (FFAs) and to explore the underlying mechanism involving autophagy. METHODS: Hepatocytes were incubated with a mixture of free fatty acids (FFAs) to mimic in vitro lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of autophagy and genetic deficit cells, as well as ω-3 fatty acids were used as intervention. The autophagic role of ω-3 fatty acids was investigated using Western blot and immunofluorescence. The underlying mechanism of ω-3 fatty acids involving autophagy was preliminarily explored by quantitative real-time polymerase chain reaction and Western blot. RESULTS: FFAs induce lipid accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of autophagy increases lipid accumulation induced by FFA, whereas induction acts inversely. ω-3 Fatty acids reduced lipid accumulation and inhibited apoptosis induced by FFA. ω-3 Fatty acids induced autophagy by downregulating stearoyl-CoA desaturase 1 expression in hepatocytes. CONCLUSION: ω-3 Fatty acids exert protective effects on hepatocytes against lipotoxicity through induction of autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis.

Association of Salivary Helicobacter pylori Infection with Oral Diseases: a Cross-sectional Study in a Chinese Population.

OBJECTIVE: The aim of this study was to detect the prevalence of oral H.pylori among adults and to investigate the correlation between H.pylori infection and common oral diseases. STUDY DESIGN: A cross-sectional study was performed among adults Chinese who took their annual oral healthy examination at The First Affiliated Hospital, Zhejiang University School of Medicine, China. RESULTS: The study included 1050 subjects in total and oral H.pylori infection occurred in 60.29% of the subjects. The prevalence rates of oral H.pylori in patients with periodontal diseases (63.42%) and caries (66.91%) were significantly increased than those without oral diseases (54.07%), respectively (P < 0.05), while the difference between subjects with recurrent aphthous stomatitis and controls was not significant. In addition, the differences of positive rates of H.pylori with or without history of gastric ulcer were statistically significant (69.47% vs 58.26%, P<0.05). Presenting with periodontal diseases (OR 1.473;95% CI 1.021 to 2.124), caries (OR 1.717; 1.127 to 2.618), and having history of gastric ulcer (OR 1.631; 1.164 to 2.285) increased the risk of H.pylori infection. CONCLUSIONS: Oral H.pylori infection is common in adult Chinese, which is significantly associated with oral diseases including periodontal diseases and caries.

Is national socioeconomic status related to prevalence of irritable bowel syndrome?

BACKGROUND AND AIM: There are a multitude of cross-sectional surveys that provide the prevalence of irritable bowel syndrome (IBS) in the community. However, the data regarding the influence of socioeconomic status on prevalence of IBS were sparse. This study is to investigate the possible relation between human development and prevalence of IBS, at national level. METHODS: EMBASE Classic, EMBASE, and MEDLINE were searched (until October 2013) to identify population-based studies that reported prevalence of IBS. Human Development Index (HDI) was chosen to assess socioeconomic status at national level. RESULTS: Firstly, no correlation was observed between prevalence of IBS and national HDI (P = 0.848). Specifically, there was no statistical significance in prevalence between developing and developed countries (P = 0.319). Moreover, prevalence of IBS failed to witness a downtrend in worldwide over the past two decades. Interestingly, the ratio of female/male prevalence was correlated with national HDI according to linear regression analysis (r = 0.395), and the ratio in the developing was significant lower than that in the developed (P = 0.0394). Lastly, except methods of data collection (P < 0.000), it shows no difference between developing and developed countries in diagnostic criteria, IBS subtypes, and age distribution (P = 0.119, 0.327, and 0.845 respectively). CONCLUSIONS: This study is the first time to investigate the relation between IBS prevalence and national socioeconomic status, with consideration of years, gender, and other factors. It demonstrates that national development is not a direct indicator for prevalence of IBS.

Deep sequencing-based analysis of the Cymbidium ensifolium floral transcriptome.

Cymbidium ensifolium is a Chinese Cymbidium with an elegant shape, beautiful appearance, and a fragrant aroma. C. ensifolium has a long history of cultivation in China and it has excellent commercial value as a potted plant and cut flower. The development of C. ensifolium genomic resources has been delayed because of its large genome size. Taking advantage of technical and cost improvement of RNA-Seq, we extracted total mRNA from flower buds and mature flowers and obtained a total of 9.52 Gb of filtered nucleotides comprising 98,819,349 filtered reads. The filtered reads were assembled into 101,423 isotigs, representing 51,696 genes. Of the 101,423 isotigs, 41,873 were putative homologs of annotated sequences in the public databases, of which 158 were associated with floral development and 119 were associated with flowering. The isotigs were categorized according to their putative functions. In total, 10,212 of the isotigs were assigned into 25 eukaryotic orthologous groups (KOGs), 41,690 into 58 gene ontology (GO) terms, and 9,830 into 126 Arabidopsis Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 9,539 isotigs into 123 rice pathways. Comparison of the isotigs with those of the two related orchid species P. equestris and C. sinense showed that 17,906 isotigs are unique to C. ensifolium. In addition, a total of 7,936 SSRs and 16,676 putative SNPs were identified. To our knowledge, this transcriptome database is the first major genomic resource for C. ensifolium and the most comprehensive transcriptomic resource for genus Cymbidium. These sequences provide valuable information for understanding the molecular mechanisms of floral development and flowering. Sequences predicted to be unique to C. ensifolium would provide more insights into C. ensifolium gene diversity. The numerous SNPs and SSRs identified in the present study will contribute to marker development for C. ensifolium.

NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Doxorubicin-based therapy is not effective for the treatment of hepatocellular carcinomas (HCCs), which often undergo epithelial-mesenchymal transition (EMT) during tumor progression. Activation of signal transducer and activator of transcription 3 (STAT3) is associated with chemosensitivity and may contribute to EMT during HCC chemotherapy. Low doses of NSC 78459 (a novel STAT3 inhibitor) have little effect on HCC cell proliferation, but efficiently inhibit STAT3. HuH-7, Hep3B, and HepG2 cells, with epithelial phenotypes, show significantly enhanced doxorubicin cytotoxicity following co-treatment with NSC 74859, whereas mesenchymal SNU-449 cells show no such enhancement. NSC 74859 inhibits STAT3 activity and suppressed doxorubicin-induced EMT in epithelial HCC cells. siRNA-mediated STAT3 knockdown resulted in EMT inhibition, which led to attenuation of NSC 74859-mediated chemosensitivity. Our data indicate NSC 74859 co-administration enhances doxorubicin cytotoxicity by inhibiting STAT3 in epithelial HCC cells. STAT3 deactivation and associated EMT attenuation contribute to the synergistic anti-tumor effects of combined NSC 74859/doxorubicin therapy.