Effectiveness and safety of rivaroxaban for anticoagulation therapy in COVID-19: A meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.

Uncovering hub genes in sepsis through bioinformatics analysis.

In-depth studies on the mechanisms of pathogenesis of sepsis and diagnostic biomarkers in the early stages may be the key to developing individualized and effective treatment strategies. This study aimed to identify sepsis-related hub genes and evaluate their diagnostic reliability. The gene expression profiles of GSE4607 and GSE131761 were obtained from the Gene Expression Omnibus. Differentially co-expressed genes between the sepsis and control groups were screened. Single-sample gene set enrichment analysis and gene set variation analysis were performed to investigate the biological functions of the hub genes. A receiver operating characteristic curve was used to evaluate diagnostic value. Datasets GSE154918 and GSE185263 were used as external validation datasets to verify the reliability of the hub genes. Four differentially co-expressed genes, FAM89A, FFAR3, G0S2, and FGF13, were extracted using a weighted gene co-expression network analysis and differential gene expression analysis methods. These 4 genes were upregulated in the sepsis group and were distinct from those in the controls. Moreover, the receiver operating characteristic curves of the 4 genes exhibited considerable diagnostic value in discriminating septic blood samples from those of the non-septic control group. The reliability and consistency of these 4 genes were externally validated. Single-sample gene set enrichment analysis and gene set variation analysis analyses indicated that the 4 hub genes were significantly correlated with the regulation of immunity and metabolism in sepsis. The identified FAM89A, FFAR3, G0S2, and FGF13 genes may help elucidate the molecular mechanisms underlying sepsis and drive the introduction of new biomarkers to advance diagnosis and treatment.

Metformin alleviates adriamycin resistance of osteosarcoma by declining YY1 to inhibit MDR1 transcriptional activity.

Chemotherapy resistance hinders the successful treatment of osteosarcoma (OS) to some extent. Previous studies have confirmed that metformin (Met) enhances apoptosis induced by chemotherapeutic drugs, but the underlying mechanism remains unclear. To establish adriamycin (ADM)-resistant MG-63 (MG-63/ADM) cells, the dosage of ADM was progressively increased. The results of qRT-PCR and Western blotting demonstrated that the expression level of Yin Yang 1 (YY1) and multi-drug resistance-1 (MDR1) in MG-63/ADM cells were remarkably increased compared with those in MG-63 cells. Met dramatically enhanced ADM cytotoxicity and accelerated apoptosis of MG-63/ADM cells. Moreover, Met suppressed the expressions of YY1 and MDR1 in MG-63/ADM cells. YY1 promoted its transcriptional expression by directly binding to the MDR1 promoter. Furthermore, the effects of Met on ADM sensitivity in MG-63/ADM cells was reversed due to overexpression of YY1 or MDR1. Collectively, these findings suggested that Met inhibited YY1/MDR1 pathway to reverse ADM resistance in OS, providing a new insight into the mechanism of Met in ADM resistance of OS.

The distance between the anterior and posterior edges of the fibula at a lateral internal rotation of 15° is associated with postoperative malreduction in patients with an ankle joint fracture combined with a lower tibiofibular syndesmosis injury.

BACKGROUND: Malreduction remains a problem in patients with an ankle joint fracture combined with a lower tibiofibular syndesmosis injury. Current methods of malreduction evaluation have many limitations, and novel techniques are required. OBJECTIVES: The aim of the study was to investigate the association between the distance between the anterior and posterior edges of the fibula at a 15° lateral internal rotation and postoperative malreduction in patients with an ankle joint fracture combined with a lower tibiofibular syndesmosis injury. MATERIAL AND METHODS: This prospective observational cohort study enrolled 187 patients diagnosed with an ankle joint fracture combined with a lower tibiofibular syndesmosis injury between January 2020 and January 2022. The patients were divided into 2 groups according to their postoperative malreduction condition: the malreduction group and the non-malreduction group. After tibiofibular syndesmosis reduction, a computed tomography (CT) scan was used to measure the distance between the anterior and posterior edges of the fibula at a standard lateral position and a position with a lateral internal rotation of 15°. Demographic data and basic clinical characteristics were recorded for all patients. RESULTS: The mean distance between the anterior and posterior edges of the fibula was longer in malreduction patients than non-malreduction patients at the standard lateral and 15° lateral internal rotation positions. At a lateral internal rotation of 15°, the distance between the anterior and posterior edges correlated negatively with the postoperative Mazur and American Orthopaedic Foot and Ankle Society (AOFAS) scores, and correlated positively with the length of hospitalization and fracture healing time. Receiver operating characteristic (ROC) curves revealed the potential postoperative malreduction diagnostic value of fibular anterior-posterior edge distance using an internal rotation of 15°. Postoperative AOFAS score, length of hospitalization, fracture healing time, and the distance between the anterior and posterior edges of the fibula at a lateral internal rotation of 15° were independent risk factors of malreduction. CONCLUSIONS: The fibular anterior-posterior edge distance at an internal rotation of 15° is associated with postoperative ankle joint function and the occurrence of malreduction.