Background: Antifibrinolytic agents have been successfully used to reduce blood transfusion demand in patients undergoing elective knee arthroplasty. The purpose of this study was to investigate different antifibrinolytic agents for patients undergoing total-knee arthroplasty (TKA). Methods: We searched the randomized controlled trials assessing the effect of antifibrinolytic agents on TKA in MEDLINE, PubMed, Embase, and the Cochrane Library. Participants are divided into antifibrinolytic agent group and control group under TKA. Double extraction technology is used and the quality of its methodology is evaluated before analysis. Outcomes analyzed included blood loss, number of blood transfusions, rates of blood transfusion, and deep vein thrombosis (DVT). Results: A total of 28 randomized controlled trials involving 1899 patients were included in this study. Compared with the control group, the antifibrinolytic agents group exhibited significantly reduced the amounts of total blood loss (weighted mean difference [WMD] with 95% confidence interval [CI]: −272.19, −338.25 to −206.4), postoperative blood loss (WMD with 95% CI: −102.83, −157.64 to −46.02), average units of blood transfusion (risk ratio with 95% CI: 0.7, 0.12 to 0.24), and average blood transfusion volumes (WMD with 95% CI: −1.34, −1.47 to −1,21). Antifibrinolytic agents significantly reduced the rate of blood transfusions and did not increase the occurrence risk of intraoperative blood loss and DVT. Several limitations should also be acknowledged such as the heterogeneity among the studies. Conclusion: The application of antifibrinolytic agents can significantly reduce blood loss and blood transfusion requirements. Additionally, these agents did not increase the risk of DVT in patients undergoing TKAs.

Background: The imbalance of proliferation and apoptosis plays an important role in the pathogenesis of osteoporosis. MicroRNAs play an important role in the apoptosis of osteoblasts cells. However, the role and potential mechanism of miR-545-3p in regulating osteoblast apoptosis remain unclear. The purpose of this study was to investigate the effect of miR-545-3p on osteoblast cells apoptosis and explore the mechanism of osteoporosis.Methods: Osteogenic medium was used to induce the differentiation of osteoblasts MC3T3-E1 to construct the osteoporosis model, and the expression of ALP, Runx2, OCN were detected by western blot; miR-545-3p mRNA was detected by RT-PCR. Transfected with miR-545-3p mimics into MC3T3-E1, then flow cytometry was used to detected the changes of apoptosis status. The expression of apoptosis related proteins Bcl-2 and Bax were detected by western blot. Bioinformatics was used to analyze the binding protein of miR-545-3p, and luciferase reporter gene experiment was used to verify whether miR-545-3p directly targets SIRT6; RT-qPCR and western blot were used to detect the expression level of SIRT6 after transfection of miR-545-3p mimics or miR-545-3p inhibitor. After co-transfection of miR-545-3p mimics and pcDNA3.1-SIRT6, the apoptosis status of osteoblasts was analyzed by flow cytometry, and the expression of apoptosis related proteins Bcl-2 and Bax were detected by western blot.Results: The expression of miR-545-3p in patients with osteoporosis was significantly higher than that of normal in GEO database (P<0.05). After osteoblasts were cultured in osteogenic medium, the expression of ALP, Runx2 and OCN was increased, and the expression of miR-545-3p was decreased. Flow cytometry analysis showed that overexpression of miR-545-3p promoted the apoptosis of osteoblasts. Western blot results showed that overexpression of miR-545-3p promoted the expression of Bax and decreased the expression of Bcl-2. Bioinformatics analysis showed that miR-545-3p could target SIRT6. The results of real-time PCR and western blot showed that SIRT6 expression was significantly inhibited by miR-545-3p mimics (P<0.05). Luciferase reporter gene assay showed that miR-545-3p significantly inhibited luciferase activity of wild-type SIRT6-3'UTR plasmid transfected cells (P<0.05), but had no effect on luciferase activity of mutant SIRT6-3'UTR plasmid transfected cells (P<0.05). However, co-transfection of miR-545-3p mimics and pcDNA3.1-SIRT6 could reduce the apoptosis, and western blot results showed that co-transfection promoted the expression of Bcl-2 and decreased the expression of Bax.Conclusions: miR-545-3p can promote the apoptosis of osteoblasts by inhibiting the expression of SIRT6, which provides a certain idea for the treatment of osteoporosis.