ObjectivesTo systematically review the efficacy and safety of new oral anticoagulants (Apixaban, Rivaroxaban, or Dabigatran) after joint replacement.MethodsCNKI, WanFang Data, VIP, CBM, PubMed, EMbase and The Cochrane Library databases were electronically searched to collect randomized controlled trials (RCTs) on new oral anticoagulants after joint replacement from inception to October, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, and then meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 13 RCTs were included. The results of meta-analysis showed that compared to Enoxaparin, the new oral anticoagulant significantly reduced the incidence of asymptomatic deep vein thrombosis (DVT) (RR=0.60, 95%CI 0.46 to 0.78, P<0.000 1) and symptomatic DVT (RR=0.40, 95%CI 0.28 to 0.58, P<0.000 1), while the incidence of symptomatic pulmonary embolism (PE) during treatment (RR=0.91, 95%CI 0.59 to 1.39, P=0.65) and mortality (RR=1.00, 95%CI 0.40 to 1.76, P=0.99) were not reduced. Major bleeding (RR=1.05, 95%CI 0.81 to 1.35, P=0.72) and clinically relevant non-major bleeding events (RR=0.99, 95%CI 0.73 to 1.33, P=0.94) with new oral anticoagulants were not statistically different from Enoxaparin.ConclusionsCurrent evidence shows that new oral anticoagulants can effectively reduce the incidence of DVT in patients after joint replacement without increasing the risk of adverse events such as bleeding. Due to limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusions.
ObjectiveTo investigate the effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), a hypoxia-inducible factor-1α (HIF-1α) inhibitor, on hypoxia induced rat pulmonary arterial adventitial fibroblasts (AFs) proliferation and collagen synthesis, and explore the molecular mechanism.MethodsUnder hypoxic condition, rat AFs were cultured in DMEM medium supplemented with 10% fetal bovine serum in vitro. The cells were divided into five groups, ie. a normoxia group, a hypoxia group and three hypoxia+YC-1 groups (treated with YC-1 at concentration of 0.01, 0.05 and 0.1 mmol/L, respectively). The cells proliferation was determined by MTT method. Collagen synthesis of AFs was measured by 3H-proline incorporation assay. The expression of HIF-1α in AFs in different conditions was measured by Western blot, and the mRNA expression of transforming growth factor-β1 (TGF-β1) was measured by reverse-transcription polymerase chain reaction.ResultsThe proliferation rate and the incorporation data of 3H-proline in the hypoxia group were significantly increased as compared with those in the control group (both P<0.01). YC-1 significantly reduced the proliferation rate and incorporation data of3H-proline induced by hypoxia in a dose-dependent manner. YC-1 could also down-regulate the expressions of HIF-1α and TGF-β1 mRNA significantly (both P<0.01). Compared with the hypoxia group, the expressions of HIF-1α and TGF-β1 mRNA decreased respectively by 65% and 61% in the hypoxia+YC-1 (0.1 mmol/L) group (bothP<0.01).ConclusionsYC-1 can inhibit hypoxia-induced AFs proliferation and collagen synthesis in a dose-dependent manner. The mechanism may relate to YC-1’s inhibitory effect on expressions of HIF-1α and TGF-β1 mRNA.