BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

Objective To explore the methods of preparing whole blood control of seven trace elements (magnesium,manganese,iron,copper,zinc,lead,calcium) in laboratory and evaluate its performance.Methods Heparin sodium anticoagulant calf whole blood was used as substrateMetal salt or standard solution with target concentration of each element was added.And whole blood control product was made after process of anticorrosion,mixing and sub-packaging.Antibacterial effect was observed,uniformity and stabilitywasevaluatedaccording to CNAS-GL03 and matrix effects was evaluatedaccording to CLSI EP14.SDI (standard deviation index) and detection coefficient of variation (CV)were calculated to evaluateapplication effectiveness.Results Laboratory preparation of whole blood control reached target concentration,sterility tests was qualified,results of uniformity and stability indicated that the substrate was even and stable at least for one year.Besides,matrix effects of other six elements can be ignored except lead.Historical and inter-laboratory comparisons had shown that laboratory preparation of whole blood control has no obvious difference with commercial ones in performance.Conclusion The formulation and evaluation scheme of whole blood control of seven trace elements (magnesium,manganese,iron,copper,zinc,lead,calcium) was feasible and can be used as commercial ones for elementary tests in medical laboratory.

Objective To report a case of superficial white onychomycosis caused by Nigrospora sphaerica. Methods Natl specimens were obtained from the patient and examined by direct microscopy, fungal culture and histopathology. Subsequently, the isolate was subjected to DNA sequencing analysis, gelatin liquefaction test, antifungal susceptibility test and nail-plate invasion test. Results A 21-year-old male presented with a 5-month history of whitening of the right hallux. Direct microscopy of nail scrapings showed spores, hyphae and lobiform conidiophores, and histopathology of decalcifying nail clippings revealed the presence of fungal elements including numerous spores and hyphae. A black woolly colony was formed in Sabouraud's dextrose agar (SDA). DNA sequencing analysis showed that the isolate was highly consis-tent with genus Nigrospora. Also, the isolate possessed the ability to liquefy gelatin and to invade normal nail plate. Antifungal susceptibility test showed that the isolate was highly susceptible to itraconazole, clotrimazole, amphotericin B and nystatin. The onychomycosis was cured after 5-month treatment with oral itra-conazole pulse therapy. Conclusions The isolate is identified as Nigrospora sphaerica by morphological features and DNA sequencing analysis. It is the first reported case of superficial white onychomycosis caused by N. Sphaerica in China, and it was effectively treated by itraeonazolc.