他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎效果观察

摘 要 目的：探讨他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎的临床效果。方法：80例难治性类风湿关节炎患者随机分为观察组和对照组,每组40例。观察组给予他克莫司与甲氨蝶呤联合治疗,对照组给予环磷酰胺与甲氨蝶呤联合治疗,两组均治疗24周。观察两组患者治疗前后关节疼痛指数、关节肿胀指数及晨僵时间的变化,采用视觉模拟评分（VAS ）对患者疼痛情况进行评估;评价两组临床疗效;比较两组患者治疗前后红细胞沉降率（ESR）、C 反应蛋白（CRP）、肿瘤坏死因子α（TNF α）、血管内皮生长因子（VEGF）等指标变化。结果：观察组总缓解率为100.00%,显著高于对照组的67.50%（P<0.05）。治疗后两组关节疼痛指数、关节肿胀指数、晨僵时间及VAS 评分均较治疗前显著降低（P<0.05）,且观察组各项指标均明显低于对照组（P<0.05）。两组治疗后ESR、CRP、TNF α、VEGF均较治疗前显著降低（P<0.05）,且观察组明显低于对照组（P<0.05）。结论：他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎临床疗效好,安全性高,其作用机制可能与降低患者体内炎症反应及下调VEGF水平有关。     

临床药师干预作用对医院药品不良反应监测与上报的影响

摘 要 目的：评价临床药师干预作用对医院药品不良反应（ADR）监测与上报的影响。方法：对我院2007～2016年间药品不良反应监测上报情况进行回顾性分析。以2014年临床药师干预ADR上报为时间界限,比较临床药师干预前后,我院ADR报告总数,新的、严重的 ADR报告数与比例,新的ADR判定错误比例;以及ADR上报来源变化。结果：干预后,ADR报告数,严重ADR报告数及其比例,以及新的ADR的报告数及其比例均较干预前显著增加（P<0.05）,新的ADR判定错误比例则较前明显降低（P<0.05）。干预后药师上报ADR比例较前明显增加（P<0.05）。结论：临床药师干预ADR 监测报告,使我院ADR监测报告数量及质量均得到明显提高。     

药物性肝损伤诊断治疗进展概述

摘 要药物性肝损伤（DILI）是指使用一种或多种药物后,由药物或其代谢产物引起的肝脏损伤。引起DILI最常见的药物包括：中药、抗结核药、抗肿瘤药、解热镇痛药、抗生素等,目前保健品、减肥药、食品添加剂等导致肝功能损伤越来越受到临床医生的重视。DILI可表现为急性或慢性肝损伤,可进展至肝硬化,轻者停药后肝功能可自行恢复,重者可出现黄疸、肝衰竭和各种并发症危及生命。随着生活水平的提高、生活习惯的改变及药物种类的增多,DILI的发病率逐年升高,其病因、诊断和治疗方面的相关问题越来越受到关注。本文将从DILI的诊断、治疗及预后等方面进行综述。     

Endoscopic molecular imaging of early gastric cancer using fluorescently labeled human H-ferritin nanoparticle

Optical imaging technologies improve clinical diagnostic accuracy of early gastric cancer (EGC). However, there was a lack of imaging agents exhibiting molecular specificity for EGCs. Here, we employed the dye labeled human heavy-chain ferritin (HFn) as imaging nanoprobe, which recognizes tumor biomarker transferrin receptor 1 (TfR1), to enable specific EGC imaging using confocal laser endomicroscopy (CLE). TfR1 expression was initially examined in vitro in gastric tumor cells and in vivo through whole-body fluorescence and CLE imaging in tumor-bearing mice. Subsequently, dye labeled HFn was topically applied to resected human tissues for EGC detection. CLE analysis of TfR1-targeted fluorescence imaging allowed distinction of neoplastic from non-neoplastic tissues (P?<?0.0001), and TfR1 expression level was found to correlate with EGC differentiation degrees (P?<?0.0001). Notably, the CLE evaluation correlated well with the immunohistochemical findings (κ-coefficient: 0.8023). Our HFn-nanoprobe-based CLE increases the accuracy of EGC detection and enables visualization of tumor margins and endoscopic resection.     

In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus Fe3O4‐TiO2 nanoparticles in human liver cells

Recent studies show that Janus Fe₃O₄‐TiO₂ nanoparticles (NPs) have potential applications as a multifunctional agent of magnetic resonance imaging (MRI) and photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However, little work has been done on their biological effects. To evaluate the toxicity and underlying molecular mechanisms of Janus Fe₃O₄‐TiO₂ nanoparticles, an in vitro study using a human liver cell line HL‐7702 cells was conducted. For comparison, the Janus Fe₃O₄‐TiO₂ NPs parent material TiO₂ NPs was also evaluated. Results showed that both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs decreased cell viability and ATP levels when applied in treatment, but increased malonaldehyde (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC‐1 staining assay showed that mitochondrial membrane permeability injury occurred in both NPs treated cells. Cell viability analysis showed that TiO₂ NPs induced slightly higher cytotoxicity than Fe₃O₄‐TiO₂ NPs in HL7702 cells. Western blotting indicated that both TiO₂ NPs and Fe₃O₄‐TiO₂ NPs could induce apoptosis, inflammation, and carcinogenesis related signal protein alterations. Comparatively, Fe₃O₄‐TiO₂ NPs induced higher signal protein expressions than TiO₂ NPs under a high treatment dose. However, under a low dose (6.25 μg/cm²), neither NPs had any significant toxicity on HL7702 cells. In addition, our results suggest both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs could induce oxidative stress and have a potential carcinogenetic effect in vitro. Further studies are needed to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe₃O₄‐TiO₂ NPs.     

Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.     

江苏省噪声作业工人职业体检异常情况分析

目的分析噪声作业工人疑似职业病和职业禁忌证的检出水平及其分布特征。方法依据GBZ 188-2014《职业健康监护技术规范》、GBZ 49-2014《职业性噪声聋的诊断》和GBZ/T 260-2014《职业禁忌证界定导则》,收集江苏省2015年1月1日至2015年12月31日重点职业病监测的149 271名噪声作业工人职业健康检查个案资料,对检查结果进行判定,计算出职业禁忌证和疑似职业性噪声聋检出率,分析检出率在不同性别、年龄、工龄、行业、企业规模等的分布特点。结果噪声作业工人职业禁忌证检出率为2.08%,疑似职业病检出率为2.03%。疑似职业性噪声聋检出率离岗时(2.13%)略高于在岗期间(2.03%)。职业禁忌证检出率在年龄≤20岁、41~50岁以及接触噪声工龄<1年组较高(分别为2.64%、2.48%、5.35%);疑似职业性噪声聋检出率;随年龄、工龄增长而升高(均P<0.05)。职业禁忌证检出率最高的行业是科学研究和技术服务行业(10.46%);疑似职业性噪声聋检出率最高的行业是交通运输、仓储和邮政业(5.88%)。职业禁忌证检出率最高的企业规模是中型企业(2.27%),最低的是微型企业(1.60%);疑似职业性噪声聋检出率最高的企业规模是大型企业(3.21%),最低的是微型企业(1.33%)。 结论应按规范加强噪声作业工人上岗前职业禁忌证以及在岗期间、离岗时疑似噪声聋的筛检。提高对非传统噪声行业噪声危害防治的重视程度和防治力度。     

Delivery of anti-platelet-endothelial cell adhesion molecule single-chain variable fragment-urokinase fusion protein to the cerebral vasculature lyses arterial clots and attenuates postischemic brain edema

Efficacy and safety of current means to prevent cerebrovascular thrombosis in patients at high risk of stroke are suboptimal. In theory, anchoring fibrinolytic plasminogen activators to the luminal surface of the cerebral endothelium might arrest formation of occlusive clots in this setting. We tested this approach using the recombinant construct antiplatelet-endothelial cell adhesion molecule (PECAM) single-chain variable fragment (scFv)-urokinase-type plasminogen activator (uPA), fusing low-molecular-weight single-chain urokinase-type plasminogen activator with a scFv of an antibody directed to the stably expressed endothelial surface determinant PECAM-1, implicated in inflammation and thrombosis. Studies in mice showed that scFv-uPA, but not unconjugated uPA 1) accumulates in the brain after intravascular injection, 2) lyses clots lodged in the cerebral arterial vasculature without hemorrhagic complications, 3) provides rapid and stable cerebral reperfusion, and 4) alleviates post-thrombotic brain edema. Effective and safe thromboprophylaxis in the cerebral arterial circulation by anti-PECAM scFv-uPA represents a prototype of a new paradigm to prevent recurrent cerebrovascular thrombosis.     

司法鉴定技术专业“鉴教融合、校所共培”人才培养模式实践探索

司法鉴定体制改革的深入推进对司法鉴定职业教育人才培养提出了更高要求。构建“鉴教融合、校所共培”司法鉴定技术专业人才培养模式,校所合作,一体化设计人才培养方案,搭建线上线下学习资源共享平台,探索课程融合、师资融合、实践融合、评价融合和服务融合的新路径,创新司法鉴定助理人才培养模式,有效提升人才培养质量。