OBJECTIVE:The aim of this study was to investigate the serum level of microRNA (miR)-21 in patients with osteosarcoma and its correlation with chemosensitivity and prognosis. METHODS: miR-21 levels in sera from 65 patients with osteosarcoma and 30 healthy controls were measured by real-time reverse transcription-polymerase chain reaction. Correlations between serum miR-21 and clinicopathological features in patients with osteosarcoma were determined. The prognostic significance of serum miR-21 was assessed using a Cox proportional hazards model. RESULTS: The serum level of miR-21 was significantly higher in patients with osteosarcoma than in control subjects. High serum miR-21 was significantly correlated with advanced Enneking stage and chemotherapeutic resistance. Univariate and multivariate analyses for overall survival showed that upregulation of serum miR-21 was an independent, unfavourable prognostic factor for patients with osteosarcoma (hazard ratio, 2.325). CONCLUSIONS: miR-21 might be a good candidate for a therapeutic target, and a potential biomarker for the prediction of chemotherapeutic sensitivity and prognosis in patients with osteosarcoma.

Individual components of metabolic syndrome contributed variously to CHD across different glucose tolerance statuses.

Bupivacaine is frequently used for conducting regional anesthesia. When accidentally injected or excessively absorbed into circulation, bupivacaine can induce severe arrhythmia and potentially lead to cardiac arrest. The specific mechanisms underlying this cardiotoxicity, however, remain to be clarified. We transfected HEK-293 cells to express the small conductance calcium-activated potassium type-2 channel (SK2), and used a whole-cell patch clamp method in order to explore how bupivacaine affected these channels. We subsequently used SK2 knockout mice to explore the relevance of SK2 channels in bupivacaine-induced cardiotoxicity in isolating mouse hearts, mounting them on a Langendorff apparatus, and perfusing them with bupivacaine. Using this system, arrhythmia, asystole, and cardiac functions were monitored. We observed dose-dependent inhibition of SK2 channels by bupivacaine: half-maximal inhibitory concentration (IC50) value = 18.6 μM (95% CI 10.8–32.1). When SK2 knockout (SK2 −/−) or wild-type (WT) mice were perfused with Krebs-Henseleit buffer (KHB), we did not observe any instances of arrhythmia. When SK2 −/− mice or WT were perfused with KHB containing bupivacaine (40 μM), the time to arrhythmia (Tarrhythmia) and time to asystole (Tasystole) were both significantly longer in SK2 −/− mice relative to WT mice ( P < 0.001). Similarly, SK2 −/− mice exhibited a significantly longer time to 25%, 50%, and 75% reductions in heart rate (HR) and rate-pressure product (RPP) relative to WT mice following bupivacaine perfusion ( P < 0.001). These results reveal that bupivacaine was able to mediate a dose-dependent inhibition of SK2 channels in HEK-293 cells, and deletion of SK2 channels can delay bupivacaine-induced cardiotoxicity in isolated mouse hearts.