Background: Mechanical prostheses and bioprosthetic prostheses have their own advantages and disadvantages. Mechanical ones are recommended for younger patients (70 years old). There is still debate regarding which kind of prosthesis is better for middle-aged patients (50 to 70 years old) receiving aortic valve replacement (AVR). To solve this problem, we conducted this meta-analysis. Given that only one randomized controlled trial (RCT) study was included, we conducted a subgroup analysis of RCT and propensity score matching (PSM) retrospective studies to reduce the bias. Methods: We systematically searched articles related to clinical outcomes of mechanical and bioprosthetic prostheses in middle-aged patients receiving AVR in the PubMed, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases. The published date was up to 1 October 2022. Studies were excluded if not only middle-aged patients were included, or if they lacked direct comparisons between mechanical and bioprosthetic prostheses. Results: In total, 22 studies with 32,298 patients were included in the final analysis. The results show that patients aged between 50 and 70 receiving AVR with mechanical prostheses achieved better long-term survival and fewer reoperations and valve-related events but suffered more with bleeding events. No significant difference could be found in terms of early mortality and long-term cardiac death. The same results could be observed in the subgroup analysis of RCT and PSM retrospective studies. Conclusion: Both mechanical and bioprosthetic prostheses are beneficial to middle-aged patients undertaking AVR procedures. However, mechanical prostheses show better clinical outcomes in long-term survival and comorbidities. Individual recommendation is still necessary.

Objectives: Calcific aortic valve disease (CAVD) is most common in the aging population and is without effective medical treatments. Brain and muscle ARNT-like 1 (BMAL1) is related to calcification. It has unique tissue-specific characteristics and plays different roles in different tissues’ calcification processes. The purpose of the present study is to explore the role of BMAL1 in CAVD. Methods: The protein levels of BMAL1 in normal and calcified human aortic valves and valvular interstitial cells (VICs) isolated from normal and calcified human aortic valves were checked. HVICs were cultured in osteogenic medium as an in vitro model, and BMAL1 expression and location were detected. TGF-β and RhoA/ROCK inhibitors and RhoA-siRNA were applied to detect the mechanism underlying the source of BMAL1 during HVICs’ osteogenic differentiation. ChIP was applied to check whether BMAL1 could directly interact with the runx2 primer CPG region, and the expression of key proteins involved in the TNF signaling pathway and NF-κ B pathway was tested after silencing BMAL1. Results: In this study, we found that BMAL1 expression was elevated in calcified human aortic valves and VICs isolated from calcified human aortic valves. Osteogenic medium could promote BMAL1 expression in HVICs and the knockdown of BMAL1 induced the inhibition of HVICs’ osteogenic differentiation. Furthermore, the osteogenic medium promoting BMAL1 expression could be blocked by TGF-β and RhoA/ROCK inhibitors and RhoA-siRNA. Meanwhile, BMAL1 could not bind with the runx2 primer CPG region directly, but knockdown of BMAL1 led to decreased levels of P-AKT, P-IκBα, P-p65 and P-JNK. Conclusions: Osteogenic medium could promote BMAL1 expression in HVICs through the TGF-β/RhoA/ROCK pathway. BMAL1 could not act as a transcription factor, but functioned through the NF-κ B/AKT/MAPK pathway to regulate the osteogenic differentiation of HVICs.