多指标联合检测对类风湿关节炎的临床诊断价值[J].pdf

G21论G21G21著G21多指标联合检测对类风湿关节炎的临床诊断价值潘秋荣G28G23孙肖依G29G21G28G2B南京中医药大学附属常州中医院检验科G23江苏常州G29G28G26G22G22G26G2AG29G2B江苏大学京江学院医学检验系G23江苏镇江G29G28G29G22G22G22G22G21G21摘G21要G23目的G21探讨类风湿因子G21G36G5BG22G24葡萄糖G32G21G32磷酸异构酶G21G3AG35G25G22G24抗突变型瓜氨酸波形蛋白G21G39G24G47G22抗体G21抗G39G24G47G22和抗环瓜氨酸肽G21G24G24G35G22抗体G21抗G24G24G35G22联合检测对类风湿关节炎G21G36G34G22的临床诊断价值G27方法G21以G28G22G27例G36G34患者G21G36G34组G22及G27G21例非G36G34患者G21非G36G34组G22为研究对象G23检测G36G5BG24G3AG35G25G24抗G39G24G47和抗G24G24G35血清浓度G27结果G21G33个指标检测结果在G36G34组和非G36G34组间的差异有统计学意义G21G3EG28G22G2BG22G2AG22G2A任意G29项及其以上指标联合诊断G36G34的敏感度G24特异性G24阳性预测值G24阴性预测值G24诊断效率G24G45G4DG4BG4AG41G30指数G24受试者工作特征曲线下面积分别为G2CG31G2BG29G24G28G22G22G2BG22G24G28G22G22G2BG22G24G28G22G22G2BG22G24G2CG27G2BG27G24G22G2BG2CG31和G22G2BG2CG27G33G27结论G21上述G33个指标的联合检测有助于提高诊断G36G34的灵敏度和特异性G23可弥补单指标检测的不足G23从而有效避免漏诊和误诊G27关键词G23类风湿因子G2AG21葡糖G32G21G32磷酸异构酶G2AG21关节炎G23内风湿G2AG21抗突变型瓜氨酸波形蛋白抗体G2AG21抗环瓜氨酸肽抗体G21G22G23G2AG28G22G2BG26G2CG21G2CG2BG2DG2BG2EG2FG2FG30G2BG28G21G31G26G32G33G28G26G22G2BG29G22G28G28G2BG28G26G2BG22G28G21文献标识码G23G34文章编号G23G28G21G31G26G32G33G28G26G22G21G29G22G28G28G22G28G26G32G28G33G26G21G32G22G29G4DG40G2FG2DG37G31G33G31G2DG43G2CG37G35G2FG3FG3EG2DG3FG3DG2BG31G33G2FG3CG3CG2FG2EG2FG2DG2EG31G3FG33G3FG3EG3BG4FG21G50G39G23G21G2CG33G2EG31G2AG29G3AG51G2CG33G3CG2CG33G2EG31G2AG3AG3AG39G2CG33G2EG31G2BG3FG3CG38G31G33G3CG31G2CG34G33G3FG32G31G32G3FG3EG30G40G2FG35G3DG2CG2EG3FG31G3CG2CG30G2EG40G30G31G2EG31G32G3EG27G29G49G26G24G33G23G29G2EG28G21G41G24G29G25G26G27G23G2CG26G29G28G28G30G2BG31G32G27G33G34G28G31G29G34G23G35G36G2FG26G29G26G37G27G2FG2AG27G38G23G33G27G34G23G33G2CG21G36G22G27G29G2EG3AG22G23G24G36G22G26G29G31G3CG31G47G33G27G40G26G34G26G23G29G27G2FG3DG31G40G26G37G27G2FG2DG23G3CG32G26G34G27G2FG4EG35G35G26G2FG26G27G34G31G40G34G23G36G22G26G29G31G3CG31G47G33G27G40G26G34G26G23G29G27G2FG3DG31G40G26G37G27G2FG42G29G26G43G31G33G3CG26G34G2CG23G35G4FG27G29G4CG26G29G2EG21G50G26G27G29G2EG3CG24G29G28G26G22G22G26G21G36G22G26G29G27G2DG29G30G2BG31G32G27G33G34G28G31G29G34G23G35G36G2FG26G29G26G37G27G2FG2AG27G38G23G33G27G34G23G33G2CG21G50G26G29G2EG4CG26G27G29G2EG36G23G2FG2FG31G2EG31G23G35G50G26G27G29G2EG3CG24G42G29G26G43G31G33G3CG26G34G2CG21G21G22G31G29G4CG26G27G29G2EG21G50G26G27G29G2EG3CG24G29G28G29G22G22G22G21G36G22G26G29G27G29G41G2BG32G2EG30G2CG2DG2EG2AG22G2BG42G2FG2DG2EG31G43G2FG21G3BG4DG41G54G51G40G4DG42G41G3FG4EG41G3EG40G2EG30G2EG3EG53G3DG40G4BG41G4DG55G3EG4DG50G49G2EG30G41G4AG4AG41G3FG41G3EG3FG2EG4DG30G4DG55G42G4EG41G4BG50G3DG3FG4DG2EG4AG55G3DG3EG3FG4DG42G28G36G5BG29G21G4CG40G4BG3EG4DG2FG41G32G21G32G51G4EG4DG2FG51G4EG3DG3FG41G2EG2FG4DG50G41G42G32G3DG2FG41G28G3AG35G25G29G21G3DG30G3FG2EG32G50G4BG3FG3DG3FG41G4AG3EG2EG3FG42G4BG40G40G2EG30G3DG3FG41G4AG53G2EG50G41G30G3FG2EG30G3DG30G3FG2EG49G4DG4AG4FG28G3DG30G3FG2EG32G39G24G47G29G3DG30G4AG3DG30G3FG2EG32G3EG4FG3EG40G2EG3EG3EG2EG3FG42G4BG40G40G2EG30G3DG3FG41G4AG51G41G51G3FG2EG4AG41G3DG30G3FG2EG49G4DG4AG4FG28G3DG30G3FG2EG32G24G24G35G29G2EG30G3FG4EG41G4AG2EG3DG4CG30G4DG2FG2EG2FG4DG55G42G4EG41G4BG50G3DG3FG4DG2EG4AG3DG42G3FG4EG42G2EG3FG2EG2FG28G36G34G29G2BG29G2FG2EG40G3FG3CG32G21G28G22G27G3EG3DG2FG41G2FG4DG55G51G3DG3FG2EG41G30G3FG2FG56G2EG3FG4EG36G34G28G36G34G4CG42G4DG4BG51G29G21G27G21G3EG3DG2FG41G2FG4DG55G51G3DG3FG2EG41G30G3FG2FG56G2EG3FG4EG4DG4BG3FG36G34G28G30G4DG30G32G36G34G4CG42G4DG4BG51G29G21G2AG33G3EG3DG2FG41G2FG4DG55G4EG41G3DG40G3FG4EG4FG3EG4DG30G3FG42G4DG40G2FG56G41G42G41G41G30G42G4DG40G40G41G4AG3DG30G4AG4AG41G3FG41G3EG3FG41G4AG55G4DG42G2FG41G42G4BG50G3EG4DG30G3EG41G30G3FG42G3DG3FG2EG4DG30G4DG55G36G5BG21G3AG35G25G21G3DG30G3FG2EG32G39G24G47G3DG30G4AG3DG30G3FG2EG32G24G24G35G2BG3BG2FG32G35G37G2EG32G21G3BG4EG41G42G41G56G41G42G41G2FG2EG4CG30G2EG55G2EG3EG3DG30G3FG4AG2EG55G55G41G42G41G30G3EG41G2FG4DG55G3FG4EG41G2FG41G42G4BG50G40G41G53G41G40G2FG4DG55G3FG4EG41G55G4DG4BG42G51G3DG42G3DG50G41G3FG41G42G2FG49G41G3FG56G41G41G30G36G34G4CG42G4DG4BG51G3DG30G4AG30G4DG30G32G36G34G4CG42G4DG4BG51G28G3EG28G22G2BG22G2AG29G2BG3BG4EG41G2FG41G30G2FG2EG3FG2EG53G2EG3FG4FG21G2FG51G41G3EG2EG55G2EG3EG2EG3FG4FG21G51G4DG2FG2EG3FG2EG53G41G3DG30G4AG30G41G4CG3DG3FG2EG53G41G51G42G41G4AG2EG3EG3FG2EG53G41G53G3DG40G4BG41G21G4AG2EG3DG4CG30G4DG2FG3FG2EG3EG41G55G55G2EG3EG2EG41G30G3EG4FG21G45G4DG4BG4AG41G30G2EG30G4AG41G54G3DG30G4AG3DG42G41G3DG4BG30G4AG41G42G42G41G3EG41G2EG53G41G42G4DG51G41G42G3DG3FG2EG30G4CG3EG4EG3DG42G3DG3EG3FG41G42G2EG2FG3FG2EG3EG3EG4BG42G53G41G56G41G42G41G2CG31G2BG29G21G28G22G22G2BG22G21G28G22G22G2BG22G21G28G22G22G2BG22G21G2CG27G2BG27G21G22G2BG2CG31G3DG30G4AG22G2BG2CG27G33G42G41G2FG51G41G3EG3FG2EG53G41G40G4FG2BG3AG3FG33G2DG37G35G32G31G3FG33G21G24G4DG50G49G2EG30G41G4AG4AG41G3FG41G3EG3FG2EG4DG30G4DG55G3FG4EG41G55G4DG4BG42G51G3DG42G3DG50G41G3FG41G42G2FG3EG4DG4BG40G4AG4EG3DG53G41G4CG42G41G3DG3FG3EG40G2EG30G2EG3EG53G3DG40G4BG41G2EG30G3FG4EG41G4AG2EG3DG4CG30G4DG2FG2EG2FG4DG55G36G34G2BG44G2FG38G45G3FG30G3CG32G2AG42G4EG41G4BG50G3DG3FG4DG2EG4AG55G3DG3EG3FG4DG42G2DG21G4CG40G4BG3EG4DG2FG41G32G21G32G51G4EG4DG2FG51G4EG3DG3FG41G2EG2FG4DG50G41G42G3DG2FG41G2DG21G3DG42G3FG4EG42G2EG3FG2EG2FG21G42G4EG41G4BG50G3DG3FG4DG2EG4AG2DG21G3DG30G3FG2EG32G50G4BG3FG3DG3FG41G4AG3EG2EG3FG42G4BG40G40G2EG30G3DG3FG41G4AG53G2EG50G41G30G3FG2EG30G2DG21G3DG30G3FG2EG3EG4FG3EG40G2EG3EG3EG2EG3FG42G4BG40G40G2EG30G3DG3FG41G4AG51G41G51G3FG2EG4AG41G3DG30G3FG2EG49G4DG4AG2EG41G2FG21G21类风湿关节炎G28G42G4EG41G4BG50G3DG3FG4DG2EG4AG3DG42G3FG4EG42G2EG3FG2EG2FG21G36G34G29是较为常见的致畸性自身免疫性疾病G21患者发病G29年即出现不可逆转的骨关节破坏G21进而丧失运动能力G23现行的诊断标准主要为临床表现G22G63线检查以及类风湿因子G28G42G4EG41G4BG50G3DG3FG4DG2EG4AG55G3DG3EG3FG4DG42G21G36G5BG29检测G21符合此标准的患者常已出现骨关节破坏G21且G36G5B检测缺乏特异性G21不利于早期诊断和及时治疗G23因此G21寻找特异性检测指标对G36G34进行早期诊断十分必要G23笔者对G33个与G36G34相关的检测指标进行了分析G21以明确其临床诊断价值G23结果报道如下G23G24G21资料与方法G24G2BG24G21一般资料G21G28G28G29试验组G2A本院G36G34患者G28G22G27例G21其中男G26G29例G21女G31G21例G21年龄G27G21G31G27岁G21平均G28G33G2AG2BG29G69G28G2AG2BG28G29岁G2D均符合美国风湿病学会G28G2CG27G31年修订的诊断分类标准G23G28G29G29对照组G2A本院非G36G34患者G27G21例G21其中男G29G31例G21女G2AG2C例G21年龄G2CG21G31G33岁G21平均G28G33G2AG2BG2CG69G28G2AG2BG33G29岁G2D其中系统性红斑狼疮G28G2FG4FG2FG3FG41G50G2EG3EG40G4BG51G4BG2FG41G42G4FG3FG4EG41G32G50G3DG3FG4DG2FG4BG2FG21G23G44G43G29G26G22例G22系统性硬化病G28G2FG4FG2FG3FG41G50G2FG3EG40G41G42G41G4AG41G50G3DG21G23G23G3EG29G26例G21多发性肌炎G2B皮肌炎G28G51G4DG40G4FG50G4FG4DG2FG2EG3FG2EG2FG2BG4AG41G42G50G3DG3FG4DG50G4FG4DG2FG2EG3FG2EG2FG21G35G39G2BG38G39G29G2A例G22原发性干燥综合征G28G51G42G2EG50G3DG42G4FG23G2DG4DG4CG42G41G30G2FG4FG30G4AG42G4DG50G41G21G51G23G23G29G28G33例G22未分化结缔组织病G28G4BG30G4AG2EG55G55G41G42G41G30G3FG2EG3DG3FG41G4AG3EG4DG30G30G41G3EG3FG2EG53G41G3FG2EG2FG2FG4BG41G4AG2EG2FG41G3DG2FG41G21G5DG24G3BG38G29G21例G22强直性脊柱炎G28G3DG30G5AG4FG40G4DG2FG2EG30G4CG2FG51G4DG30G4AG4FG40G2EG3FG2EG2FG21G34G23G29G28G2C例G22血清阴性脊柱关节病G28G2FG41G42G4DG30G41G4CG3DG3FG2EG53G41G2FG51G4DG30G4AG4FG40G4DG3DG42G32G3FG4EG42G4DG51G3DG3FG4EG2EG41G2FG21G23G51G34G29G2C例G21均符合国内或国际相应的诊断标准G2EG28G2FG23G28G26G29健康对照组G2A本院体检健康者G2AG33例G21其中男G28G21例G22女G26G27例G21年龄G27G21G31G29岁G21平均G28G33G21G2BG21G69G28G2AG2BG31G29岁G23G24G2BG25G21仪器与试剂G21G28G28G29试剂G2A速率散射免疫比浊法G36G5B定量检测试剂盒G28西门子G21德国G29G2D双抗体夹心酶联免疫吸附法G28G41G30G58G4FG50G41G40G2EG30G5AG41G4AG2EG50G50G4BG30G4DG2FG4DG42G49G41G30G3FG3DG2FG2FG3DG4FG21G43G44G25G23G34G29葡萄糖G32G21G32磷酸异构酶G28G4CG40G4BG3EG4DG2FG41G32G21G32G51G4EG4DG2FG51G4EG3DG3FG41G2EG2FG4DG50G41G42G3DG2FG41G21G3AG35G25G29半定量检测试剂盒G28北加G21中国G29G21G3AG35G25G25G22G2BG29G22G50G4CG2BG44时判为阳性G2D抗突变型瓜氨酸波形蛋白G28G50G4BG3FG3DG30G3FG3EG2EG3FG42G4BG40G40G2EG30G3DG3FG41G4AG53G2EG50G41G30G3FG2EG30G3DG30G3FG2EG49G4DG4AG4FG21G39G24G47G29抗体G28抗G39G24G47G29G43G44G25G23G34试剂盒G28G64G36G3AG43G37G3BG43G24G21德国G29G21抗G39G24G47G25G2AG22G5DG2BG50G44时判为阳性G2D抗环瓜氨酸肽G28G3EG4FG3EG40G2EG3EG3EG2EG3FG42G4BG40G40G2EG30G3DG3FG41G4AG51G41G51G32G3FG2EG4AG41G3DG30G3FG2EG49G4DG4AG4FG21G24G24G35G29抗体G28抗G24G24G35G29G43G44G25G23G34试剂盒G28G43G4BG42G4DG2EG50G32G50G4BG30G41G21德国G29G23G28G29G29仪器G2AG3CG37G27型特种蛋白仪G28德灵G21美国G29G22G39G4DG4AG41G40G21G27G22型酶标仪G28G3CG25G64G32G36G3DG4AG21美国G29G23G24G2BG26G21方法G21各组受试对象均抽取非抗凝晨起空腹静脉血G26G50G44G21G26G22G22G22G4C离心G2AG50G2EG30G21分离血清后严格按试剂盒说明书进行G36G5BG22G3AG35G25G22抗G39G24G47和抗G24G24G35检测G23G24G2BG27G21统计学处理G21用G23G35G23G23G28G27G2BG22统计软件进行统计学分析G23根据各指标在不同浓度时诊断G36G34的灵敏度和特异性G21计算受试者操作特征曲线G28G42G41G3EG41G2EG53G41G42G4DG51G41G42G3DG3FG2EG30G4CG3EG4EG3DG42G3DG3EG3FG41G42G2EG2FG3FG2EG3EG3EG4BG42G53G41G21G36G64G24G29及G36G64G24曲线下面积G28G3DG42G41G3DG4BG30G4AG41G42G36G64G24G21G34G5DG24G29G23以G34检验分析相关比较差异G21以G3EG28G22G2BG22G2A为差异有统计学意义G23G2CG21G26G33G28G2C国际检验医学杂志G29G22G28G28年G27月第G26G29卷第G28G26期G21G25G30G3FG48G44G3DG49G39G41G4AG21G34G4BG4CG4BG2FG3FG29G22G28G28G21G47G4DG40G2BG26G29G21G37G4DG2BG28G26G25G21结G21G21果G25G2BG24G21各组G36G5BG22G3AG35G25G22抗G39G24G47和抗G24G24G35检测结果G21G33个指标检测结果在G36G34组和非G36G34组间的差异具有统计学意义G28G3EG28G22G2BG22G2AG29G23各组G36G5BG22G3AG35G25G22抗G39G24G47和抗G24G24G35检测结果见表G28G23G25G2BG25G21G36G5BG22G3AG35G25G22抗G39G24G47和抗G24G24G35诊断性能评价G21各组G33个检测指标的阳性率见表G29G21由表G29计算获得的各检测指标诊断性能评价指标结果见表G26G23表G28G21G21G36G5BG29G3AG35G25G29抗G39G24G47和抗G24G24G35检测结果G24G46G69G3CG26组别G29G36G5BG28G25G5DG2BG50G44G29G3AG35G25G28G50G4CG2BG44G29抗G39G24G47G28G5DG2BG50G44G29抗G24G24G35G28G36G5DG2BG50G44G29G36G34组G28G22G27G26G28G2AG2BG2CG69G28G28G21G2BG29G22G28G2BG29G31G69G22G2BG33G27G22G26G2AG21G2BG33G69G28G22G2AG2BG26G22G28G33G29G2BG2AG22G69G2AG28G2BG33G22非G36G34组G27G21G29G28G2BG21G69G28G28G2BG26G22G2BG33G26G69G22G2BG29G21G29G31G2BG21G69G28G28G2BG26G26G2BG33G28G69G28G2BG2AG2C健康对照组G2AG33G28G22G2BG31G69G2AG2BG2CG22G2BG28G28G69G22G2BG22G33G29G28G21G2BG27G69G33G2BG31G29G2BG22G28G69G28G2BG29G27G21G21G22G2AG3EG28G22G2BG22G2AG21与非G36G34组比较G23表G29G21G21各指标检测阳性率G27G29或G29G24G57G26G28组别G29G36G5BG32G25G4CG39G3AG35G25抗G39G24G47抗G24G24G35任意G29项或G29项以上G36G34组G28G22G27G27G29G28G31G2AG2BG2CG29G27G21G28G31G2CG2BG21G29G27G26G28G31G21G2BG2CG29G31G27G28G31G29G2BG29G29G28G22G2AG28G2CG31G2BG29G29非G36G34组G27G21G28G28G28G28G29G2BG27G29G28G33G28G28G21G2BG29G29G31G28G27G2BG28G29G2AG28G2AG2BG27G29G21G22G28G22G2BG22G29健康对照组G2AG33G29G28G26G2BG31G29G26G28G2AG2BG21G29G29G28G26G2BG31G29G28G28G28G2BG2CG29G21G22G28G22G2BG22G29表G26G21G21G36G5BG29G3AG35G25G29抗G39G24G47和抗G24G24G35诊断性能评价指标灵敏度G28G57G29特异性G28G57G29阳性预测值G28G57G29阴性预测值G28G57G29诊断效率G28G57G29G45G4DG4BG4AG41G30指数G34G5DG24G36G5BG31G2AG2BG2CG2CG29G2BG28G27G21G2BG26G27G26G2BG29G27G2AG2BG28G22G2BG21G27G22G2BG27G2AG31G3AG35G25G31G2CG2BG21G27G31G2BG2CG27G26G2BG2AG27G33G2BG27G27G33G2BG26G22G2BG21G27G22G2BG27G2AG28抗G39G24G47G31G21G2BG2CG2CG26G2BG21G2CG22G2BG29G27G33G2BG22G27G21G2BG26G22G2BG31G28G22G2BG27G31G2A抗G24G24G35G31G29G2BG29G2CG2AG2BG31G2CG29G2BG2CG27G28G2BG31G27G2AG2BG2AG22G2BG21G27G22G2BG27G2AG21任意G29项或G29项以上G2CG31G2BG29G28G22G22G2BG22G28G22G22G2BG22G28G22G22G2BG22G2CG27G2BG27G22G2BG2CG31G22G2BG2CG27G33G26G21讨G21G21论本研究显示各指标在诊断G36G34时都有一定的诊断价值G21但各性能指标存在一定的差异G2D各指标的灵敏度及特异性不是太理想G21存在较大的漏诊率和误诊率G2D通过多指标联合检测G21可明显提高诊断灵敏度和特异性等G23G36G5B是诊断G36G34的血清学指标G21其检测方法简便G22快速G23本研究显示G21其诊断灵敏度低G28G31G2AG2BG2CG57G29G21但特异性相对较高G28G2CG29G2BG28G57G29G23除G36G34G22G23G44G43外G21G36G5B在其他自身免疫性疾病患者中的阳性率也较高G21甚至在部分传染性疾病患者以及老年人中也有较高的阳性率G21因此不能作为G36G34早期诊断的独立指标G23G3AG35G25在G36G34患者血清中的浓度异常增高G21被认为是极有希望广泛应用于G36G34诊断及判断疾病活动性的检测指标之一G2EG29G2FG23苏娜等G2EG26G2F的研究发现G21G36G34患者血清G3AG35G25浓度较其他风湿病患者及健康者显著增高G21提示G3AG35G25可以作为G36G34的诊断指标之一G21也可用于判断疾病活动性G23本研究中G21G3AG35G25用于G36G34诊断的敏感度G22特异性及诊断效率与参考文献G2EG33G2F报道的结果相近G23波形蛋白G28原命名为G23G3D抗原G29的瓜氨酸修饰残基的异常暴露可引起自身免疫反应G21诱导抗G39G24G47的产生G2EG2AG32G31G2FG23本项研究发现G21抗G39G24G47用于G36G34诊断的灵敏度可达G31G21G2BG2CG57G21特异性可达G2CG26G2BG21G57G21可用于G36G34和其他自身免疫性疾病的鉴别诊断G21与国外研究结果相近G2EG27G32G28G22G2FG23随着G36G34血清学特异性标记物研究的深入G21抗核周因子G28G3DG30G3FG2EG32G51G41G42G2EG30G4BG3EG40G41G3DG42G55G3DG3EG3FG4DG42G21G34G35G5BG29G22抗角蛋白抗体G28G3DG30G3FG2EG32G5AG41G42G3DG3FG2EG30G3DG30G32G3FG2EG49G4DG4AG4FG21G34G5EG34G29G22抗G24G24G35等逐渐引起研究人员的重视G23G34G5EG34虽对G36G5B的诊断特异性高达近G28G22G22G57G21但由于难以制备和保存其抗体底物G21所采用的检测方法为间接免疫荧光法G21结果判断受多种人为因素干扰G21缺乏标准化检测方法G21使其难以在临床中推广应用G23抗G24G24G35G22G34G5EG34和G34G35G5B在化学结构上具有关联性G21其靶抗原均为上皮细胞分化终末阶段的细胞骨架成分中间丝相关蛋白G21而瓜氨酸是该蛋白的组成成分之一G21因此被统称为瓜氨酸相关自身免疫系统G2EG28G28G2FG23抗G24G24G35检测具有以下优势G2A在G36G34发病早期G21甚至在临床症状出现前G21抗G24G24G35即可出现阳性G21可用于G36G34的早期诊断G2D抗G24G24G35阳性的G36G34患者较阴性者更有可能发展为侵袭性疾病G21在判断关节破坏等方面也具有一定的临床意义G21可用于G36G34的预后判断G2EG28G29G32G28G26G2FG2D以化学方法合成的G24G24G35作为抗原G21采用G43G44G25G23G34检测抗G24G24G35G21既具有良好的重复性和稳定性G21便于实现标准化操作G21能够保证检测结果的可信度G23因此G21已有研究人员提出将抗G24G24G35列入G36G34分类诊断标准之中G2EG28G33G2FG23G36G64G24曲线是将诊断试验的结果划分为若干个临界点G21在以敏感度为纵坐标G22G28G28G67特异度G29为横坐标的坐标图中连接每个临界点而得出的曲线G21所以G34G5DG24能够综合反映多个临界点的敏感度G22特异性G21从而全面反映诊断试验的诊断性能G23本研究中G34G5DG24计算结果显示各指标对G36G34的诊断都有一定的临床价值G21但联合检测的诊断价值更高G23参考文献G2EG28G2F陈灏珠G21丁训杰G21翁心华G21等G2B实用内科学G2EG39G2FG2BG28G28版G2B北京G2A人民卫生出版社G21G29G22G22G33G2AG29G26G28G27G32G29G26G29G31G2BG2EG29G2F罗怡G21张阳根G2B葡萄糖G32G21G32磷酸异构酶与类风湿性关节炎的研究进展G2EG48G2FG2B国际检验医学杂志G21G29G22G28G22G21G26G28G28G29G29G2AG28G33G21G32G28G33G31G2BG2EG26G2F苏娜G21窦存瑞G21谭宝云G21等G2B血清G21G32磷酸葡萄糖异构酶及抗G24G24G35抗体等联合检测对类风湿关节炎临床诊断应用的研究G2EG48G2FG2B国际检验医学杂志G21G29G22G22G2CG21G26G22G28G28G22G29G2AG2CG31G28G32G2CG31G26G2BG2EG33G2F杨永泉G21李薇G21张速林G21等G2BG21G32磷酸葡萄糖异构酶检测对类风湿关节炎的诊断意义G2EG48G2FG2B广东医学G21G29G22G28G22G21G26G28G28G33G29G2AG33G31G2AG32G33G31G21G2BG2EG2AG2FG3CG4DG2EG42G41G3AG21G24G4DG2FG2FG41G3FG3FG41G35G21G4AG41G3CG42G4BG50G32G5BG41G42G30G3DG30G4AG41G2FG34G48G21G41G3FG3DG40G2BG34G30G3FG2EG32G23G3DG3DG30G3FG2EG32G49G4DG4AG2EG41G2FG3DG30G4AG3DG30G3FG2EG49G4DG4AG2EG41G2FG3DG4CG3DG2EG30G2FG3FG3EG4FG3EG40G2EG3EG3EG2EG3FG42G4BG40G40G2EG30G3DG3FG41G4AG28下转第G28G33G33G22页G29G2CG31G26G33G28G2C国际检验医学杂志G29G22G28G28年G27月第G26G29卷第G28G26期G21G25G30G3FG48G44G3DG49G39G41G4AG21G34G4BG4CG4BG2FG3FG29G22G28G28G21G47G4DG40G2BG26G29G21G37G4DG2BG28G26其多克隆位点和G43G3AG5BG35编码区基因之间设计有核糖体进入位点G21确保插入的G4EG3AG44G35G32G28基因与G3AG5BG35编码基因共同转录G21但翻译合成的G4EG3AG44G35G32G28并不与G3AG5BG35融合G21可保证G4EG3AG44G35G32G28的构象与生理活性G23脂质体作为体内和体外输送载体的工具G21其介导的外源基因导入法以无毒G22无免疫原性G21简单高效而备受青睐G2EG2CG2FG23采用以上载体和转染方法即可在保证目的蛋白的天然生理活性G21也可获得较高的转染效率和表达量G23G3AG5BG35观察及细胞培养液G4EG3AG44G35G32G28含量检测结果均提示重组载体成功转染至靶细胞G21且目的基因得以表达G23G22G32G3BG24G32G21细胞是以经G23G47G33G22病毒转染的胰岛细胞为基础构建的G21有较好的稳定性G21能够分泌胰岛素G22胰高血糖素和生长抑素G21对氧化损伤敏感G21可作为研究G3AG44G35G32G28功能的来源细胞G23目前认为G21G34G63G37通过产生超氧自由基G21损伤细胞膜结构而导致胰岛G22细胞受损G23氧自由基可造成细胞膜产生脂质过氧化作用G21线粒体氧化应激使胞内活性氧增加G21进而触发核因子G29G3CG28G30G4BG32G3EG40G41G3DG42G55G3DG3EG3FG4DG42G21G37G5BG32G29G3CG29G22G24G32G48G4BG30氨基端激酶G28G3EG32G48G4BG30G37G32G3FG41G42G50G2EG30G3DG40G5AG2EG32G30G3DG2FG41G21G48G37G5EG29G22丝裂原活化蛋白激酶G51G26G27亚族G28G51G26G27G50G2EG3FG4DG4CG41G30G32G3DG3EG3FG2EG32G53G3DG3FG41G4AG51G42G4DG3FG41G2EG30G5AG2EG30G3DG2FG41G21G51G26G27G39G34G35G5EG29的激活G21从而诱导胰岛G22细胞的凋亡G2EG28G22G2FG23本研究中G21G46G4DG41G3EG4EG2FG3F染色显示G21经诱导后G22G32G3BG24G32G21细胞核体积缩小G21形态变圆G21出现明显的核碎裂现象G21说明G34G63G37可诱导G22G32G3BG24G32G21细胞凋亡G21尽管转染空载体和转染重组载体的细胞均出现了细胞凋亡现象G21但多数转染空载体的细胞已处于核碎裂阶段G21而多数转染重组载体的细胞都处于核固缩状态G23G59G23G3BG32G28在电子耦合剂存在的情况下G21可以将线粒体内的部分脱氢酶还原为橙黄色的甲月替G28G55G4DG42G50G3DG30G58G3DG30G29G23细胞增殖越快G21颜色越深G21细胞毒性越大G21颜色越浅G2D颜色的深浅与吸光度值成正比G23本研究中G21G59G23G3BG32G28实验结果显示G21转染重组载体后细胞的毒性作用减低G23综上所述G21经重组载体转染后的细胞毒性减低G21凋亡率下降G23体外实验表明G21若在诱导大鼠胰岛细胞G36G25G37G50G2AG55凋亡的同时将G3AG44G35G32G28加入细胞培养液中G21G36G25G37G50G2AG55细胞内抗凋亡基因G3CG3EG40G32G29表达增加G21而凋亡基因G3CG34G63表达下降G21说明G3AG44G35G32G28对胰岛细胞的抗凋亡作用源于其对凋亡相关基因的调控G2EG28G28G2FG23也有研究发现G21G3AG44G35G32G28能够通过抑制G37G5BG32G29G3C的表达G21而抵抗由白介素G32G28G22介导的大鼠胰岛素细胞G25G37G23G32G28的凋亡G2EG28G29G2FG23本研究采用基因转染的方式G21将G29G5FG47G3DG40G29G32G4EG3AG44G35G32G28成功转染入G34G63G37诱导凋亡的G22G32G3BG24G32G21细胞G21并使其分泌G21发现G4EG3AG44G35G32G28的表达对胰岛G22细胞的凋亡具有一定的影响G23笔者将在后续实验中在细胞内基因表达水平对G4EG3AG44G35G32G28抗凋亡机制进一步研究G21为糖尿病的基因治疗提供一定的实验基础G23参考文献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李晓丽G21刘振G21张志珍G2B人胰高血糖素样肽G32G28类似物基因克隆及真核表达载体构建G2EG48G2FG2B中国现代医学杂志G21G29G22G22G2CG21G28G2CG28G31G29G2AG26G22G33G21G32G26G22G33G2CG2BG2EG2AG2F李明G21王超G21刘跃平G21等G2B糖尿病主要临床化学检测指标应用G2EG48G2FG2B国际检验医学杂志G21G29G22G28G22G21G26G28G28G29G29G2AG28G2CG2CG32G29G22G22G2BG2EG21G2F冯春颜G21张永顶G21胡纪文G2B免疫印迹法检测G24型糖尿病自身抗体的临床应用G2EG48G2FG2B国际检验医学杂志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张蕾G21郭克民G21温洪涛G21等G2BG3CG3EG40G32G63G40基因反义寡合甘酸诱导食管癌细胞凋亡的研究G2EG48G2FG2B中华检验医学杂志G21G29G22G22G2AG21G29G27G28G2CG29G2AG2CG2AG26G32G2CG2AG21G2BG2EG28G22G2FG45G41G45G44G21G45G4BG3DG30G5CG45G21G23G4EG41G30G3CG21G41G3FG3DG40G2BG38G2EG3DG49G41G3FG41G2FG50G4DG4BG2FG41G50G4DG4AG41G40G50G3DG4AG41G49G4FG3DG40G32G40G4DG54G3DG30G2EG48G2FG2BG44G3DG49G34G30G2EG50G3DG40G23G3EG2EG34G4AG50G2EG30G2FG3FG42G3DG3FG21G29G22G22G28G21G28G27G28G29G29G2AG2AG33G32G2AG2CG2BG2EG28G28G2F崔岱G21刘超G21唐伟G2BG3AG44G35G32G28对大鼠胰岛细胞增殖及凋亡的影响G2EG48G2FG2B中国糖尿病杂志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收稿日期G2AG29G22G28G28G32G22G28G32G28G26G29G28上接第G28G33G26G31页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晋淑慧G21王艾丽G21王娟G21等G2B抗G23G3DG22抗G5EG34G22抗G36G34G2AG33抗体和G36G5B联合检测对类风湿性关节炎诊断的意义G2EG48G2FG2B临床检验杂志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