目的建立基于同位素稀释液相色谱串联质谱技术(liquid phase chromatography tandem mass spectrometry,LC-MS/MS)的血清25羟维生素D3[25-hydroxy vitamin D3,25(OH)D3]的候选参考测量程序。方法采用同位素标准溶液为内标,液液萃取进行...目的建立基于同位素稀释液相色谱串联质谱技术(liquid phase chromatography tandem mass spectrometry,LC-MS/MS)的血清25羟维生素D3[25-hydroxy vitamin D3,25(OH)D3]的候选参考测量程序。方法采用同位素标准溶液为内标,液液萃取进行前处理,正离子电喷雾模式进行监测。参照美国临床实验室标准化协会(Clinical and Laboratory Standards Institute,CLSI)C62-A和EP15-A3等文件,对方法的正确度、精密度、线性范围、定量限、检测下限、相对基质效应等进行验证。采用候选参考测量程序和质谱常规程序检测40份临床血清样本,评价两种方法的一致性。结果候选方法的分析时间为15 min,通过色谱的等度洗脱可有效分离同分异构体3-epi-25(OH)D3,特异度好。测定参考实验室室间比对(RELA)样本,偏倚低于1.5%。批内精密度和批间精密度分别为0.75%~2.31%和1.28%~2.01%。定量限和检测下限分别为0.85 ng/ml和1.84 ng/ml。在2.5~220ng/ml浓度范围内线性良好。无相对基质效应和携带污染。质谱常规程序与候选参考程序的相关性较好(r=0.982),但低浓度样本处的偏差超出卫健委临检中心室间质评的允许总误差±25%。结论成功建立了基于LC-MS/MS技术的血清25(OH)D3的候选参考测量程序,分析性能符合要求,可用于临床常规方法的量值溯源。展开更多
目的:观察不同滴度谷氨酸脱羧酶抗体(GADA)成人隐匿性自身免疫性糖尿病(LADA)患者25羟维生素D3[25(OH)D3]水平及T淋巴细胞亚群的变化,探讨其与胰岛β细胞功能的关系。方法:在成人糖尿病(DM)患者中筛查获得GADA阳性患者,根据GADA滴度水...目的:观察不同滴度谷氨酸脱羧酶抗体(GADA)成人隐匿性自身免疫性糖尿病(LADA)患者25羟维生素D3[25(OH)D3]水平及T淋巴细胞亚群的变化,探讨其与胰岛β细胞功能的关系。方法:在成人糖尿病(DM)患者中筛查获得GADA阳性患者,根据GADA滴度水平分为低滴度组和高滴度组,对照组为普通2型糖尿病(T2DM)患者。检测空腹血糖(FBG)、血脂、肝肾功能,糖化血红蛋白(HbA1c)、空腹血清C肽(FCP)、25(OH)D3和T淋巴细胞亚群(CD3^(+)、CD4^(+)和CD8^(+))。计算胰岛素抵抗指数[Homa-IR(CP)]和胰岛功能指数[Homa-islet(CP)]。结果:与T2DM组比较,高滴度组体重指数(BMI)、25(OH)D3水平、FCP、餐后2 h C肽(2 hCP)、Homa-IR(CP)和Homa-islet(CP)均降低,差异有统计学意义(P<0.05),同时合并有较低的总胆固醇(TC)、三酰甘油(TG)、尿酸(UA)水平,差异有统计学意义(P<0.05);低滴度组也表现出BMI、25(OH)D3水平、FCP、2 hCP、Homa-IR(CP)和Homa-islet(CP)降低,伴低TC水平,差异有统计学意义(P<0.05)。高滴度组CD4^(+)/CD8^(+)T比值高于低滴度组,差异有统计学意义(P<0.05),LADA患者CD4^(+)/CD8^(+)比值与GADA滴度呈正相关(r=0.37,P<0.01),25(OH)D3水平与Homa-islet(CP)呈正相关(r=0.32,P=0.02)。结论:低25(OH)D3水平及T淋巴细胞亚群比例失衡与胰岛β细胞功能损伤有关并参与LADA病程的进展。展开更多
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
文摘目的建立基于同位素稀释液相色谱串联质谱技术(liquid phase chromatography tandem mass spectrometry,LC-MS/MS)的血清25羟维生素D3[25-hydroxy vitamin D3,25(OH)D3]的候选参考测量程序。方法采用同位素标准溶液为内标,液液萃取进行前处理,正离子电喷雾模式进行监测。参照美国临床实验室标准化协会(Clinical and Laboratory Standards Institute,CLSI)C62-A和EP15-A3等文件,对方法的正确度、精密度、线性范围、定量限、检测下限、相对基质效应等进行验证。采用候选参考测量程序和质谱常规程序检测40份临床血清样本,评价两种方法的一致性。结果候选方法的分析时间为15 min,通过色谱的等度洗脱可有效分离同分异构体3-epi-25(OH)D3,特异度好。测定参考实验室室间比对(RELA)样本,偏倚低于1.5%。批内精密度和批间精密度分别为0.75%~2.31%和1.28%~2.01%。定量限和检测下限分别为0.85 ng/ml和1.84 ng/ml。在2.5~220ng/ml浓度范围内线性良好。无相对基质效应和携带污染。质谱常规程序与候选参考程序的相关性较好(r=0.982),但低浓度样本处的偏差超出卫健委临检中心室间质评的允许总误差±25%。结论成功建立了基于LC-MS/MS技术的血清25(OH)D3的候选参考测量程序,分析性能符合要求,可用于临床常规方法的量值溯源。
文摘目的:观察不同滴度谷氨酸脱羧酶抗体(GADA)成人隐匿性自身免疫性糖尿病(LADA)患者25羟维生素D3[25(OH)D3]水平及T淋巴细胞亚群的变化,探讨其与胰岛β细胞功能的关系。方法:在成人糖尿病(DM)患者中筛查获得GADA阳性患者,根据GADA滴度水平分为低滴度组和高滴度组,对照组为普通2型糖尿病(T2DM)患者。检测空腹血糖(FBG)、血脂、肝肾功能,糖化血红蛋白(HbA1c)、空腹血清C肽(FCP)、25(OH)D3和T淋巴细胞亚群(CD3^(+)、CD4^(+)和CD8^(+))。计算胰岛素抵抗指数[Homa-IR(CP)]和胰岛功能指数[Homa-islet(CP)]。结果:与T2DM组比较,高滴度组体重指数(BMI)、25(OH)D3水平、FCP、餐后2 h C肽(2 hCP)、Homa-IR(CP)和Homa-islet(CP)均降低,差异有统计学意义(P<0.05),同时合并有较低的总胆固醇(TC)、三酰甘油(TG)、尿酸(UA)水平,差异有统计学意义(P<0.05);低滴度组也表现出BMI、25(OH)D3水平、FCP、2 hCP、Homa-IR(CP)和Homa-islet(CP)降低,伴低TC水平,差异有统计学意义(P<0.05)。高滴度组CD4^(+)/CD8^(+)T比值高于低滴度组,差异有统计学意义(P<0.05),LADA患者CD4^(+)/CD8^(+)比值与GADA滴度呈正相关(r=0.37,P<0.01),25(OH)D3水平与Homa-islet(CP)呈正相关(r=0.32,P=0.02)。结论:低25(OH)D3水平及T淋巴细胞亚群比例失衡与胰岛β细胞功能损伤有关并参与LADA病程的进展。
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
