Loss of MD1 Promotes Inflammatory and Apoptotic Atrial Remodelling in Diabetic Cardiomyopathy by Activating the TLR4/NF-κB Signalling Pathway.

INTRODUCTION: Myeloid differentiation protein 1 (MD1), a negative regulator of toll-like receptor 4 (TLR4), is widely expressed in the heart. Recent studies have shown that MD1 plays an important role in cardiac remodelling. However, the effects and potential mechanisms underlying MD1-mediated atrial remodelling in diabetic cardiomyopathy (DCM) remain unclear. Therefore, this study was designed to explore the role of MD1 in DCM-related atrial remodelling. METHODS: MD1 knockout (MD1-KO) mice and wild-type (WT) littermates were injected with streptozotocin (STZ) to establish a diabetic mouse model. These mice were then used to evaluate MD1 expression and its effects on atrial remodelling in vivo. RESULTS: MD1 expression was significantly decreased in STZ-induced diabetic mice. The loss of MD1 aggravated atrial fibrosis, inflammation, and apoptosis in DCM mice and promoted atrial remodelling. MD1-KO diabetic mice also showed higher susceptibility to atrial fibrillation (AF) and worse cardiac function. Mechanistically, the deletion of MD1 promoted the activation of the TLR4/NF-κB signalling pathway, resulting in atrial remodelling in DCM mice via increased p65 phosphorylation. CONCLUSIONS: The deletion of MD1 plays an important role in inflammatory and apoptotic atrial remodelling and increases susceptibility to AF in DCM mice, providing a new target for the preventive treatment of DCM-related atrial remodelling.

Comparison of the effectiveness and safety of topical versus intravenous tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized controlled trials.

BACKGROUND: This study aims to compare the effectiveness and safety of topical versus intravenous tranexamic acid (TXA) in reducing blood loss in primary total knee arthroplasty (TKA). METHODS: PubMed, Embase, the Cochrane Library, Web of Science, Chinese Biomedicine Literature (CBM), Wanfang Database and China National Knowledge Infrastructure (CNKI), and Google Scholar were searched for randomized controlled studies (RCTs) that compared topical versus intravenous TXA in terms of reducing blood loss during TKA from their inception to September 2015. This systematic review and meta-analysis was performed according to PRISMA criteria. RESULTS: Twelve studies reporting 12 RCTs comprising 1130 patients were included. Compared with the intravenous administration of TXA, the topical administration of TXA showed no significant differences in total blood loss (MD 2.08, 95% CI -68.43 to 72.60, P = 0.95), blood loss in drainage (MD 18.49, 95% CI -40.01 to 76.98, P = 0.54), hidden blood loss (MD 4.75, 95% CI -337.94 to 347.44, P = 0.99), need for transfusion (RR = 0.92, 95% CI 0.67~1.25, P = 0.58), hemoglobin (Hb) decline (MD -0.42, 95% CI -0.89 to 0.05, P = 0.08), and DVT occurrence (RR = 1.17, 95% CI 0.55~2.50, P = 0.68). CONCLUSIONS: Compared with intravenous administration TXA, topical administration TXA exhibits comparable effectiveness and safety in terms of reducing blood loss during TKA. Due to the poor quality of the included studies, more high-quality RCTs are needed to identify the optimal method and dose of TXA after TKA.