Background: The clinical outcome of mitral valve repair (MVP) is considerably more favorable than that of mitral valve replacement (MVR) in patients with degenerative mitral disease. However, rheumatic heart disease (RHD) is still the predominant cause of mitral valve surgery in developing countries and the advantages of MVP in RHD have still not been definitely proven. The aim of this meta-analysis was thus to evaluate the suitability of MVP in patients with RHD. Considering the difference between mechanical and biological valves, we distinguished them from each other and compared them with MVP individually. Methods: A comparison of clinical outcomes of MVP and MVR in patients with RHD was performed based on clinical trial data. Relevant articles published from January 1, 1990 until March 1, 2020 were identified in Pubmed, Cochrane Library, and China National Knowledge Infrastructure database (CNKI). Studies that lacked direct comparisons between MVP and MVR were excluded. Results: A total of 16 studies with 8659 patients were included in the analysis. The MVP group displayed lower early and long-term mortality, and fewer valve-related events and major adverse events. However, this patient group required more reoperations compared with the MVR group. Similar results were observed after distinguishing between mechanical and bioprosthetic valves to compare MVP with MVR (mech-valves), but no statistically significant difference was identified in the reoperation rate between MVP and MVR (bio-valves). MVP was further associated with increased risk of mitral reoperation in patients undergoing concomitant aortic valve replacement (AVR) surgery but without any improved early and long-term survival. Conclusions: MVP and MVR are beneficial for patients with RHD. For skilled surgeons, MVP can be performed for some suitable patients with RHD and is preferred for elderly patients or patients with contraindications of anticoagulation. However, MVR is more appropriate when concomitant AVR is needed.

Background: To evaluate circulating T follicular helper (cTfh) cells and characterize their function in chronic-phase recipients after heart transplantation. Methods: Participants were divided into healthy control (HC, n=40), preoperative (Pre, n=40), and post-transplantation chronic-phase recipient (1-year, n=40) groups. The percentages of cTfh cell subsets and CD19⁺ B cell subsets were measured using flow cytometry. In vitro co-culture experiments were performed using cTfh cells and B cells isolated by fluorescence-activated cell sorting. Plasma concentrations of IL-21, chemokine ligand 13 (CXCL13), immunoglobulin G1 (IgG1), and immunoglobulin G3 (IgG3) were quantified using enzyme-linked immunosorbent assays (ELISA). Results: cTfh and programmed cell death protein 1-positive (PD-1⁺) cTfh cells, the cTfh17/cTfh ratio, and class-switched memory B cells in peripheral blood were significantly increased in the 1-year group versus the HC and Pre groups (P<0.01), whereas the cTfh1/cTfh ratio and number of naïve B cells were significantly decreased in the 1-year group. Co-culture experiments showed that cTfh cells promoted B cell differentiation to plasmablasts. In the 1-year group, cTfh and PD-1⁺ cTfh cell numbers were positively correlated with plasmablasts in CD19⁺ B cells (P<0.01). The cTfh17/cTfh ratio was positively correlated with IgG3 concentrations in plasma (P<0.01). The plasma concentrations of interleukin-21 (IL-21) and CXCL13 in the 1-year group were increased compared to the HC and Pre groups (P<0.05). Chronic-phase recipients had increased proportions of CD4⁺CXCR5⁺ and CD4⁺CXCR5⁺PD-1⁺ cTfh cells, with a cTfh1-to-cTfh17 subtype conversion. An increased number of cTfh cells was positively correlated with B cell differentiation to plasmablasts, class-switched memory B cells, and greater IgG production. Conclusions: During the chronic phase, the proportion of cTfh cells increased and enhanced B cell responses. The cTfh-related soluble factors CXCL13 and IL-21 may regulate the immunopathogenesis of chronic immune injury. Thus, cTfh cells may drive long-term immune rejection in chronic-phase recipients after heart transplantation.

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.