Progranulin correlated with rapid progressive interstitial lung disease in dermatomyositis with anti-melanoma differentiation-associated gene 5 antibody

Clinical Rheumatology - This study aimed to detect the expression of progranulin (PGRN) and elucidate associations with clinical features in dermatomyositis (DM) patients with anti-melanoma...     

An Update on the Clinical Development of Proprotein Convertase Subtilisin Kexin 9 Inhibitors,Novel Therapeutic Agents for Lowering Low‐Density Lipoprotein Cholesterol

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in the degradation of low‐density lipoprotein C (LDL‐C) receptors, and PCSK9 inhibitors have recently emerged as a potential treatment option to reduce LDL‐C. Our paper reviewed the current available Phase II clinical trials of PCSK9 inhibitors for the treatment of dyslipidemia. A second objective of this review was to evaluate the potential clinical role of PCSK9 inhibitors in the management of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9 inhibitors in patients with dyslipidemia were included. The monoclonal antibodies REGN727/SAR236553 and AMG145 have the most published clinical data. Seven phase II trials were retrieved that evaluated the efficacy and safety of REGN727/SAR236553 or AMG145 in patients with either hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). These two agents significantly decreased LDL‐C levels either as monotherapy or in combination with other lipid‐lowering agents. REGN727/SAR236553 and AMG145 have been well tolerated. The ongoing phase III trials of these two agents are summarized. REGN727/SAR236553 and AMG145 have demonstrated the potential to further decrease LDL‐C levels when added to conventional lipid‐lowering therapy. Morbidity and mortality data are required to define their roles in clinical practice.     

A novel performance monitoring framework for health research systems: experiences of the National Institute for Health Research in England

Background  

The National Institute for Health Research (NIHR) was established in 2006 with the aim of creating an applied health research system embedded within the English National Health Service (NHS). NIHR sought to implement an approach for monitoring its performance that effectively linked early indicators of performance with longer-term research impacts. We attempted to develop and apply a conceptual framework for defining appropriate key performance indicators for NIHR.     

地震救援中流动医院手术室医院感染控制的难点及对策

目的 应对地震灾害救援中流动医院手术室消毒灭菌的难点,探讨其适合灾难救援的对策.方法 医院选址前应将感染控制做到实处,把握环境、物资、消毒灭菌等管理要点,确保医疗救援任务的圆满完成.结果 通过对医院选址、消毒灭菌管理、医疗废物处理等方面的有效管理,确保在历次地震救援中所完成的43例手术,其中包括Ⅰ类切口手术27例,无一例发生医院感染.结论 加强流动医院手术室医院感染控制管理,对于在灾害救援中做好医疗救援工作,增加手术成功率、有效降低感染率具有积极意义.     

Rosuvastatin-regulated post-translational phosphoproteome in human umbilical vein endothelial cells

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are widely prescribed as cholesterol-lowering drugs. Statins have recently been found to have pleiotropic effects that are independent of their lipid-lowering properties. Phosphorylation of serine, threonine, and tyrosine residues of functional proteins are considered to be important in the endothelial signaling cascade. In this study, protein phosphorylation status in human umbilical vein endothelial cells (ECs) after rosuvastatin treatment was examined. The proteins were collected from rosuvastatin-treated ECs and then the phosphorylated peptides purified by a Fe³⁺-immobilized metal-affinity chromatography bead system were examined by liquid chromatography–tandem mass spectrometry analysis. Alterations of the phosphorylation status of proteins were noticed after rosuvastatin treatment. There were 277 and 530 phosphorylated proteins identified from the control and rosuvastatin-treated ECs, respectively. Among those proteins, T78, in addition to S156 of the Ras-GTPase-activating protein, was phosphorylated after rosuvastatin treatment. Rosuvastatin reduced the phosphorylation of Y455 in HSP90 protein. Decreased phosphorylation of T211 with a concurrent increase in the T291 phosphorylation of Akt1 was observed under rosuvastatin treatment. Increased S633 phosphorylation was detected in endothelial nitric oxide synthase. Western blot analysis further showed an earlier and greater S633 phosphorylation than that of S1177 in endothelial nitric oxide synthase after rosuvastatin treatment. Changes in the phosphorylation status of these proteins may alter the protein’s function and affect endothelial physiology. The current study provides new insights leading to a better understanding of the pleiotropic effects of statins on the vascular system.