Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial

Abstract Background Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. Methods In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. Results In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was − 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and − 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of − 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were − 1.47 (p = 0.18) in 24-h diastolic BP, − 2.86 (p = 0.13) and − 2.74 (p = 0.03) in daytime systolic and diastolic BP, and − 0.45 (p = 0.82) and − 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). Conclusions The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. Trial registration ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018

The glycosylated extracellular domain of MUC1 protects against SARS-CoV-2 infection at the respiratory surface

Mucins play an essential role in protecting the respiratory tract against microbial infections. The heavily O-glycosylated gel-forming mucins MUC5AC and MUC5B eliminate pathogens by mucociliary clearance while transmembrane mucins MUC1, MUC4, and MUC16 restrict microbial invasion at the apical surface of the epithelium. In this study, we determined the impact of host mucins and mucin glycans on SARS-CoV-2 spike-mediated epithelial entry. Human lung epithelial Calu-3 cells have endogenous expression of the SARS-CoV-2 entry receptor ACE2 and express high levels of glycosylated MUC1 on the surface but not MUC4 and MUC16. Removal of the MUC1 extracellular domain (ED) using the O-glycan-specific mucinase StcE greatly enhanced spike binding and viral infection. By contrast, removal of mucin glycans sialic acid and fucose did not impact viral invasion. This study implicates the glycosylated ED of MUC1 as an important component of the host defense that restricts the severity of SARS-CoV-2 infection

The association between socioeconomic status and osteoporotic fracture in population-based adults : a systematic review

Summary : Although socioeconomic status (SES) is inversely related to most diseases, this systematic review showed a paucity of good quality data examining influences of SES on osteoporotic fracture to confirm this relationship. Further research is required to elucidate the issue and any underlying mechanisms as a necessary precursor to considering intervention implications. Introduction : The association between socioeconomic status (SES) and musculoskeletal disease is little understood, despite there being an inverse relationship between SES and most causes of morbidity. We evaluated evidence of SES as a risk factor for osteoporotic fracture in population-based adults. Methods : Computer-aided search of Medline, EMBASE, CINAHL, and PsychINFO from January 1966 until November 2007 was conducted. Identified studies investigated the relationship between SES parameters of income, education, occupation, type of residence and marital status, and occurrence of osteoporotic fracture. A best-evidence synthesis was used to summarize the results. Results : Eleven studies were identified for inclusion, which suggested a lack of literature in the field. Best evidence analysis identified strong evidence for an association between being married/living with someone and reduced risk of osteoporotic fracture. Limited evidence exists of the relationship between occupation type or employment status and fracture, or for type of residence and fracture. Conflicting evidence exists for the relationship between osteoporotic fracture and level of income and education. Conclusion : Limited good quality evidence exists of the role SES might play in osteoporotic fracture. Further research is required to identify whether a relationship exists, and to elucidate underlying mechanisms, as a necessary precursor to considering intervention implications. <br /

Free-standing Fe2O3 nanomembranes enabling ultra-long cycling life and high rate capability for Li-ion batteries

With Fe(2)O(3) as a proof-of-concept, free-standing nanomembrane structure is demonstrated to be highly advantageous to improve the performance of Li-ion batteries. The Fe(2)O(3) nanomembrane electrodes exhibit ultra-long cycling life at high current rates with satisfactory capacity (808 mAh g(−1) after 1000 cycles at 2 C and 530 mAh g(−1) after 3000 cycles at 6 C) as well as repeatable high rate capability up to 50 C. The excellent performance benefits particularly from the unique structural advantages of the nanomembranes. The mechanical feature can buffer the strain of lithiation/delithiation to postpone the pulverization. The two-dimensional transport pathways in between the nanomembranes can promote the pseudo-capacitive type storage. The parallel-laid nanomembranes, which are coated by polymeric gel-like film and SEI layer with the electrolyte in between layers, electrochemically behave like numerous “mini-capacitors” to provide the pseudo-capacitance thus maintain the capacity at high rate