Metabolomics-based comparative analysis of the effects of host and environment on Viscum coloratum metabolites and antioxidative activities.

Viscum coloratum (Kom.) Nakai is a well-known medicinal hemiparasite widely distributed in Asia. The synthesis and accumulation of its metabolites are affected by both environmental factors and the host plants, while the latter of which is usually overlooked. The purpose of this study was to comprehensively evaluate the effects of host and habitat on the metabolites in V. coloratum through multiple chemical and biological approaches. The metabolite profile of V. coloratum harvested from three different host plants in two habitats were determined by multiple chemical methods including high-performance liquid chromatography-ultraviolet (HPLC-UV), gas chromatography-flame ionization detector (GC-FID) and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF/MS). The differences in antioxidant efficacy of V. coloratum were determined based on multiple in vitro models. The multivariate statistical analysis and data fusion strategy were applied to analyze the differences in metabolite profile and antioxidant activity of V. coloratum. Results indicated that the metabolite profile obtained by various chemical approaches was simultaneously affected by host and environment factors, and the environment plays a key role. Meanwhile, three main differential metabolites between two environment groups were identified. The results of antioxidant assay indicated that the environment has greater effects on the biological activity of V. coloratum than the host. Therefore, we conclude that the integration of various chemical and biological approaches combined with multivariate statistical and data fusion analysis, which can determine the influences of host plant and habitat on the metabolites, is a powerful strategy to control the quality of semi-parasitic herbal medicine.

High-dose dual therapy versus culture-based susceptibility-guided therapy as a rescue regimen for Helicobacter pylori infection: a randomized controlled trial.

Background: Although the Maastricht VI/Florence consensus report recommended high-dose proton pump inhibitor-amoxicillin dual therapy as possible rescue therapy for Helicobacter pylori infection, clinical evidence of its efficacy was lacking. Objectives: To compare the efficacy, safety, patient compliance, and cost between high-dose dual therapy (HDDT) and culture-based susceptibility-guided therapy (CB-SGT) as a rescue regimen for H. pylori infection. Design: A single-center, open-label, randomized controlled clinical trial. Methods: In all, 146 patients with a history of eradication failure were enrolled and randomly assigned to receive HDDT or CB-SGT. HDDT consisted of esomeprazole 20 mg and amoxicillin 750 mg, both given four times per day (qid). CB-SGT consisted of esomeprazole 20 mg twice daily (bid), amoxicillin 1000 mg bid plus clarithromycin 500 mg bid, metronidazole 400 mg bid, or levofloxacin 500 mg daily (qd) for sensitive patients, in that order. For patients with triple resistance, a bismuth-containing regimen with a high dose of metronidazole was chosen, including esomeprazole 20 mg bid, bismuth 220 mg bid, amoxicillin 1000 mg bid, and metronidazole 400 mg qid. All regimens were given for 14 days. Results: The eradication H. pylori rates achieved with HDDT in the intention-to-treat (ITT), per-protocol, and modified ITT analyses were all 84.9% [62/73, 95% confidence interval (CI): 76.5-93.9%], compared with 83.6% (61/73, 95% CI: 74.9-92.3%), 84.7% (61/72, 95% CI: 76.2-93.2%), and 84.7% (61/72, 95% CI: 76.2-93.2%) with CB-SGT, respectively. For patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, the eradication rates of HDDT and CB-SGT were 90.70% (39/43, 95% CI: 77.86-97.41%) and 84.21% (32/38, 95% CI: 68.75-93.98%), respectively. The difference between groups was 6.49% (95% CI: -8.00% to 20.97%), and the non-inferiority p value was 0.0128. For patients with a treatment interval of more than 3 months, the eradication rates of the two regimens reached 88.71% (95% CI: 78.11-95.34%) and 71.97% (95% CI: 70.02-90.64%). The difference between groups was 6.74% (95% CI: -5.71% to 19.20%), with a non-inferiority p value of 0.0042. Patient adherence was high in both groups. The HDDT had a lower cost and rate of side effects (p < 0.001) compared with CB-SGT. Conclusions: HDDT can reach an eradication rate of 85% in treatment-experienced patients of H. pylori infection and 91% in patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, with good compliance, lower side effects and costs, and less use of antibiotics. In conclusion, HDDT offers an effective rescue regimen for H. pylori infection. Registration: This clinical trial was registered at the Chinese Clinical Trail Registry (trail registration number: ChiCTR1900025044).

Efficacy and safety of high-dose esomeprazole and amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori infection: a multicenter, randomized controlled clinical trial.

Background: A high-dose proton pump inhibitor (PPI)-amoxicillin dual therapy has been investigated for treatment of patients with Helicobacter pylori (H. pylori) infection. Currently, the efficacy of this dual therapy remains inconclusive, with controversial findings from various single-center clinical trials. Objectives: To assess the efficacy and safety of high-dose dual therapy (HDDT) compared with the bismuth-containing quadruple therapy (BQT) in treatment-naive patients with H. pylori infection. Design: A multicenter, open-label, randomized controlled clinical trial. Methods: Three hundred and forty treatment-naïve patients with H. pylori infection were prospectively recruited from seven participating hospitals. The enrolled patients were randomized into one of two treatment groups: the HDDT group (esomeprazole, 20 mg four times daily; amoxicillin, 750 mg four times daily) and the BQT group (esomeprazole, 20 mg, twice daily; bismuth potassium citrate, 600 mg, twice daily; amoxicillin, 1 g, twice daily; metronidazole, 400 mg, four times daily). The primary outcome was eradication rate, and secondary outcomes were safety and patient compliance. Results: The eradication rates in the HDDT group versus the BQT group were 86.47% versus 87.06% on intention-to-treat (ITT) analysis, 91.88% versus 92.50% on modified ITT (MITT) analysis, and 91.77% versus 93.04% on per-protocol (PP) analysis, with no significant differences between the two groups. The patient compliance rates in the HDDT group versus the BQT group were 97.02% versus 95.86%, and no significant difference was found between the two groups. Notably, the HDDT group exhibited significantly lower incidence in the drug-induced adverse events (AEs) compared to the BQT group (16.67% versus 47.94%). Conclusion: HDDT is equally efficacious in eradicating H. pylori infection and resulted in good patient compliance and safety compared with BQT. These findings provide evidence in support of HDDT as a first-line treatment for H. pylori infection. Registration: This clinical trial was registered at The Chinese Clinical Trial Registry (trial registration number: ChiCTR2000039096).

10-Day and 14-day high-dose dual therapy for the treatment of Helicobacter pylori: A propensity score matching analysis.

BACKGROUND: Inconsistent eradication rates for Helicobacter pylori have been reported worldwide with dual therapy, perhaps owing to the difference in dose administration and treatment duration. This retrospective study aimed to determine whether high-dose dual therapy (HDDT) with different regimens leads to different eradication rates. The study compares the efficacy and safety of HDDT 10-day vs 14-day and investigates the factors that might affect the eradication rates. MATERIALS AND METHODS: Two comparable treatment groups were based on propensity score matching (PSM). Patients were divided into two groups based on the therapy they underwent: 10-day HDDT and 14-day HDDT (20 mg esomeprazole and 750 mg amoxicillin, administered four times daily). The eradication rates, adverse events (AEs), patient compliance, CYP2C19 gene polymorphisms, and antibiotic resistance rates of the two groups were compared. RESULTS: The intention to treat (ITT) analysis showed that the eradication rates for 10-day and 14-day groups were 78.4% (95% CI 69.6%-87.2%) and 89.7% (95% CI 83.3%-96.2%; p = .039), respectively, while the per-protocol (PP) eradication rates were 80.0% (95% CI 71.3%-88.7%) and 92.9% (95% CI 87.4%-98.5%; p = .014), respectively. The corresponding drug-related AEs were 6.8% (6/88) and 5.7% (5/88; p = .755). No significant differences were observed between the compliance rates of the two groups. The CYP2C19 gene polymorphism had no effect on the eradication rates of the two groups. CONCLUSION: The results showed that the 14-day HDDT affords a higher H. pylori eradication rate than the 10-day HDDT.

High dose PPI-amoxicillin dual therapy for the treatment of Helicobacter pylori infection: a systematic review with meta-analysis.

BACKGROUND: Helicobacter pylori resistance to amoxicillin remains rare in many regions. Proton pump inhibitor-amoxicillin-containing high dose dual therapy (HDDT) has been proposed to treat H. pylori infection. We aimed to assess the effectiveness and safety of PPI-amoxicillin HDDT for treatment of H. pylori infection in comparison with other regimens. METHODS: Databases, including PubMed, Embase, and the Cochrane Register of Controlled Trials, were searched to find relevant publications. Randomized controlled trials comparing HDDT with control regimens for H. pylori eradication in adult patients were included. The primary outcome was eradication rate by intention-to-treat analysis. Adverse events were analyzed as second outcome. RESULTS: A total of 15 trials with 3818 patients qualified for inclusion. The eradication rate of HDDT was neither significantly inferior nor superior to the recommended regimens such as triple therapy, bismuth quadruple therapy, and non-bismuth quadruple therapy [relative risk (RR): 1.00, 95% confidence interval (CI): 0.96-1.05, p = 0.870]. This finding was robust through subgroup analyses and sensitivity analyses. Trial sequential analysis showed that HDDT was equivalent to control regimens, and further similar trials were unlikely to alter the conclusions of this analysis. The frequency of adverse events was significantly lower in HDDT group (RR: 0.48, 95% CI: 0.37-0.64, p < 0.001). CONCLUSION: HDDT was equivalent to recommended first-line or rescue regimens with fewer adverse effects. The evidence from this meta-analysis supports the use of HDDT as first-line or rescue treatment for H. pylori infection. TRIAL REGISTRATION: PROSPERO CRD42019133002.

Efficacy of modified esomeprazole-amoxicillin dual therapies for Helicobacter pylori infection: an open-label, randomized trial.

OBJECTIVE: The prevalence of Helicobacter pylori resistance to amoxicillin was less than 5% in most countries. Proton pump inhibitor (PPI)-amoxicillin dual therapy dosing four times daily (q.i.d.) for 14 days could achieve an eradication rate of more than 85%. It is unclear whether dual therapy with shorter treatment duration or lower dosing frequency could also attain a satisfactory cure rate. We conducted a randomized controlled trial to assess the efficacy and safety of two modified esomeprazole-amoxicillin dual therapies, 10-day q.i.d. and 14-day three times daily (t.i.d.) dual therapy, and investigate the factors that might affect the eradication rates. PARTICIPANTS AND METHODS: A total of 253 patients were screened for eligibility and 208 patients were randomly assigned to 10-day dual therapy (esomeprazole 20 mg and amoxicillin 750 mg, all given four times daily) or 14-day dual therapy (esomeprazole 20 mg and amoxicillin 1000 mg, all given three times daily). RESULTS: In the intention-to-treat analysis, the eradication rates for 10-day and 14-day groups were 79.8% [95% confidence interval (CI): 70.2-87.4%] and 83.5% (95% CI: 74.3-90.5%) as first-line therapies; and 80% (95% CI: 44.4-97.5%) and 76.9% (95% CI: 46.2-95.0%) as rescue therapies. The adverse event rates were 5.9% and 5.0% for 10-day and 14-day groups, respectively. Smoking and compliance significantly affected the efficacy of PPI-amoxicillin dual therapies. CONCLUSION: The eradication rate of 10-day q.i.d. dual therapy was unacceptable, while that of the 14-day t.i.d. dual therapy was borderline acceptable for first-line therapy. The two dual therapies were well tolerated with few adverse effects.

Sex Differences Associated With Circulating PCSK9 in Patients Presenting With Acute Myocardial Infarction.

A limited number of studies have explored whether the role of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of acute myocardial infarction (AMI) is sex specific. The purpose of the present study was to examine sex differences in plasma PCSK9 in Chinese patients with AMI. In this study, a total of 281 records from patients presenting with AMI were analyzed.We compared hospital data and plasma PCSK9 levels by sex difference for inpatients presenting with AMI. After 1 year of follow-up, major adverse cardiac events(MACE) were recorded. A Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. We found that, compared with male groups, PCSK9 levels were higher in female patients not only for overall patients with AMI but also for patients with ST-elevation myocardial infarction (STEMI) (median: 273.6 [215.6-366.8] vs. 325.1 [247.5-445.3] ng/ml, P = 0.0136; 273.4 [215.6-369.7] vs. 317.1 [249.6-450.1], P = 0.0275, respectively). The cumulative incidence of cardiac death and 1-year MACE were significantly higher in the female group compared with male group (10% vs. 2.74%, P = 0.025; 15% vs. 4.11%, P = 0.0054, respectively). On multivariate Cox regression analysis, female sex, total triglyceride, glycosylated hemoglobin A, and homocysteic acid were independent risk factors of 1-year MACE. There was no significant correlation between PCSK9 and 1-year MACE in total AMI patients. In conclusion, PCSK9 levels and 1-year MACE were higher in women with AMI than in men with AMI, however, female sex but not PCSK9 were significant correlated with the 1-year MACE. The clinical implications of this finding are worthy of further investigations and must be confirmed in larger cohorts.

Stiffness of various pin configurations for pediatric supracondylar humeral fracture: a systematic review on biomechanical studies.

To compare the biomechanical stability of various pin configurations for pediatric supracondylar humeral fractures under varus, internal rotation, and extension conditions. After electronic retrieval, 11 biomechanical studies were included. Stiffness values of pin configurations under different loading conditions were extracted and pooled. There were no statistically significant differences between two cross pins and two divergent lateral pins on the basis of the 'Hamdi method' (P=0.249-0.737). An additional pin did not strengthen two-pin construct (P=0.124-0.367), but better stabilized fractures with medial comminution (P<0.01). Isolated lateral pins are preferable because of a better balance of a lower risk of nerve injury and comparable fixation strength. Limitations such as differences in experimental setup among recruited studies and small sample size may compromise the methodologic power of this study.