Background: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. Objective: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. Methods: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. Results: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P 5 .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. Conclusions: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population. (

BackgroundSevere acute kidney injury (AKI) after cardiac surgery is associated with poor clinical outcomes. This study evaluated the potential use of miR-21 as a risk marker for postoperative AKI progression and other poor outcomes.Methodology/Principal FindingsThe study included 120 adult patients undergoing cardiac surgery: 40 non-AKI controls, 39 patients with progressive AKI, and 41 with non-progressive AKI. Urine and plasma levels of miR-21 were assessed by quantitative real-time PCR (RT-qPCR). Associations between miR-21 levels and AKI progression were determined by estimating areas under receiver operating characteristic curves (AUC). We demonstrated that up-regulated urine and plasma levels of miR-21 in patients with AKI were both associated with AKI progression. The AUCs for urine and plasma levels of miR-21 associated with established AKI were 0.68 (95%CI: 0.59–0.78) and 0.80 (95%CI: 0.73–0.88), respectively. Multiple logistic regression analysis, adjusting for clinical variables, indicated that the prognostic predictive power of urine and plasma miR-21 levels for AKI progression were represented by AUCs of 0.81 (95%CI: 0.72–0.91) and 0.83 (95%CI: 0.74–0.92), respectively. Urinary and plasma miR-21 levels also predicted the need for postoperative renal replacement therapy (RRT), development of Acute Kidney Injury Network (AKIN) stage 3 AKI, 30-day in-hospital mortality and prolonged stay in hospital or ICU. Urine miR-21 was a better outcome predictor than plasma miR-21, being associated with higher (1.4- to 2.6-fold) unadjusted odds ratio for progression of AKI and other poor outcomes.ConclusionsUrinary and plasma miR-21 are associated with severe AKI and other poor postoperative outcomes of cardiac surgery, indicating their potential use as prognostic markers.

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Paraplegia is a disastrous complication after operations of descending and thoracoabdominal aortic aneurysm. Regional hypothermia protects against spinal cord ischemia although the protective mechanism is not well know. The objective of this study is to examine whether hypothermia protects the spinal cord by preventing apoptosis of nerve cell and also investigate a possible mechanism involved in hypothermia neuroprotection. Cell apoptosis with necrosis was evident in the spinal cord 24 h after 30 min of ischemia. Moderate hypothermia decreased the incidence of apoptotic nerve cells. Both cell apoptosis and necrosis were attenuated by hypothermia. p53 expression increased and bcl-2 expression declined after ischemia, while hypothermia mitigated these changes. This study suggests that apoptosis contributes to cell death after spinal cord ischemia, and that moderate hypothermia can prevent nerve cell apoptosis by a mechanism associated with bcl-2 and p53 genes.

An efficient electromechanical coupling model is developed to analyze the effect of the interfacial properties on the mechanical behaviors of piezoelectric/elastic composite smart beams. The interface of the composite smart beams is assumed to be imperfectly bonded and is modeled by the shear-lag model. An asymptotic expansion approximation is employed to construct the electric potential distribution in the piezoelectric layer. The governing equation is derived for the piezoelectric/elastic composite smart beams taking into account the electromechanical coupling effect and the interfacial imperfection. In the numerical analysis, both the mechanical and the electrical loadings are considered. The mechanical behaviors of the composite smart beams are illustrated graphically for three types of boundary conditions: (a) clamped supported–freely supported (C-F), (b) clamped supported–hinged supported (C-H), and (c) hinged supported–hinged supported (H-H). The results show that the interfacial properties have significant effect on the mechanical behaviors of the piezoelectric/elastic composite smart beams. For mechanically actuated case, a larger interfacial imperfection causes a larger transverse deflection, while it is contrary for electrically actuated case.

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A model based on linear electromechanical coupling theory is developed to analyze the performance of a piezoelectric cantilevered energy harvester (PCEH) with an imperfectly bonded interface. The PCEH is made of a piezoelectric layer bonded to a metallic layer and works in flexural mode. The imperfectly bonded interface is modeled by the shear-lag model. A sixth-order governing differential equation is derived and its analytical solution is obtained. The effect of the interfacial property on the dynamic behaviors and the electrical power output of the vibration-based PCEH is investigated. The presented results demonstrate that the interfacial property plays a critical role in the performance characteristics of the PCEHs.

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