BACKGROUND： The differential diagnosis of many neurodegenerative disorders depends primarily on clinical symptoms together with imaging methods. Recently, increased importance has been placed on the use of biomarkers...BACKGROUND： The differential diagnosis of many neurodegenerative disorders depends primarily on clinical symptoms together with imaging methods. Recently, increased importance has been placed on the use of biomarkers for diagnosing various neurodegenerative disorders. OBJECTIVE： To assess the feasibility of tau-protein, phosphorylated tau-protein, beta-amyloid 42 （Aβ42）, and 14-3-3 protein as biomarkers for diagnosing several neurodegenerative diseases complicated by cognitive deficits. DESIGN, TIME AND SETTING： A non-randomized, concurrent, case-control investigation was performed in three medical centers in the Czech Republic （Department of Neurology at the University Hospital in Hradec Kralove, Department of Neurology at the 2rd Medical Faculty, and the University Hospital Motol） between October 2000 and November 2006. PARTICIPANTS： Eighteen patients with probable AIzheimer＇s disease, 4 patients with Creutzfeldt-Jakob disease, 10 patients with frontotemporal dementia, 9 patients with clinically isolated syndrome suggestive of multiple sclerosis, and 7 patients with multiple sclerosis, as well as 38 race-, nationality-, and age-matched cognitively intact controls, were included in the study. Diagnoses were established based on the following criteria： the criteria for Alzheimer＇s disease proposed by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer＇s Disease and Related Disorders Association, WHO criteria for Creutzfeldt-Jakob disease, Neary criteria for frontotemporal dementia, and McDonald＇s criteria for multiple sclerosis. All included patients were confirmed to suffer from various degrees of dementia. METHODS： Enzyme-linked immunosorbent assay was used to measure concentrations of tau-protein, phosphorylated tau-protein, and Aβ42 in cerebrospinal fluid （CSF） samples collected by standard lumbar puncture from each patient. Moreover, 14-3-3 protein was assessed by Western blot in CSF of Creutzfeldt-Jakob disease patients. Cognitive status was assessed using the Mini Mental Scale Examination （MMSE） in all subjects. MAIN OUTCOME MEASURES： Establishment of biomarkers with greatest specificity and sensitivity for the investigated disorders according to Receiver Operating Characteristic curves, which were based on values from patients and controls; correlation between concentrations of given biomarkers and demographic parameters, diagnosis, duration of disease, and level of cognitive deficit. RESULTS： Increased concentrations of total tau protein and phosphorylated tau protein, and decreased levels of Aβ42, in CSF of Alzheimer＇s disease patients reached the required sensitivity/specificity ratio of 80% or greater. A marked elevation in CSF concentrations of total tau protein showed even greater sensitivity than 14-3-3 protein in Creutzfeldt-Jakob disease. There was no association between selected biomarkers and frontotemporal dementia or multiple sclerosis. Phosphorylated tau-protein was the only biomarker that noticeably correlated with MMSE scores for Alzheimer＇s disease.CONCLUSION： Levels of total tau protein, phosphorylated tau protein, and A!342 in the CSF could differentiate patients with Alzheimer＇s disease and Creutzfeldt-Jakob disease from healthy controls and patients with other neurodegenerative disorders. The diversity of absolute values demonstrates the necessity to establish a specific standard for each laboratory.展开更多
目的:探讨右美托咪定复合超声引导下腹横肌平面(TAP)阻滞麻醉对腹腔镜下腹股沟疝修补术病人血清β-42淀粉样蛋白(Aβ-42)和Tau蛋白的影响。方法:选取行腹腔镜下腹股沟疝修补术病人100例,随机分为对照组和观察组,各50例。对照组行喉罩全...目的:探讨右美托咪定复合超声引导下腹横肌平面(TAP)阻滞麻醉对腹腔镜下腹股沟疝修补术病人血清β-42淀粉样蛋白(Aβ-42)和Tau蛋白的影响。方法:选取行腹腔镜下腹股沟疝修补术病人100例,随机分为对照组和观察组,各50例。对照组行喉罩全麻,观察组采用超声引导下TAP阻滞联合右美托咪定麻醉。记录2组病人切皮时(T1)、手术开始1 h(T2)、手术结束即刻(T3)的平均动脉压和心率(HR)、血氧饱和度。比较2组疼痛视觉模拟评分(VAS)、简易智能状态检查量表(MMSE)评分、术后认知功能障碍(POCD)的发生率及Aβ-42和Tau蛋白表达水平。结果:2组病人术后即刻和术后6、24、48 h VAS评分逐渐降低降低(P<0.05);观察组术后6、24、48 h VAS评分均明显低于对照组(P<0.01)。观察组T2、T3 HR均明显低于对照组(P<0.01),且T2、T3时HR低于T1(P<0.05)。术后观察组POCD的发生率为6.00%(3/50),低于对照组的22.00%(11/50)(P<0.05)。术后1、7 d 2组MMSE评分均低于麻醉前(P<0.05),且观察组MMSE评分明显高于对照组(P<0.01)。术后7 d 2组Tau蛋白水平均高于麻醉前(P<0.05),Aβ-42蛋白水平均低于麻醉前(P<0.05),Tau/Aβ-42值高于麻醉前(P<0.05);且观察组Tau蛋白水平及Tau/Aβ-42值均低于对照组(P<0.05和P<0.01),Aβ-42水平明显高于对照组(P<0.01)。结论:超声引导下TAP阻滞麻醉联合右美托咪定在腹腔镜下腹股沟疝修补术中镇痛效果显著,同时有效改善病人的认知功能,调节术后血清Aβ-42和Tau蛋白水平,降低POCD发生率。展开更多
The study investigated the effects of Qingguang＇an Ⅱ（a Chinese medicinal preparation） on expressions of OX42 protein and interleukin-1β（IL-1β） mRNA of retinal microglia cells of rats with chronic high intraocu...The study investigated the effects of Qingguang＇an Ⅱ（a Chinese medicinal preparation） on expressions of OX42 protein and interleukin-1β（IL-1β） mRNA of retinal microglia cells of rats with chronic high intraocular pressure（IOP）. SD rats were randomly divided into 6 groups, that were： A： blank group; B： model group; C： Qingguang＇an Ⅱ low dose group; D： Qingguang＇an Ⅱ medium dose group; E： Qingguang＇an Ⅱ high dose group; F： Yimaikang disket（a Chinese medicinal preparation） group. Experimental rats in B, C, D, E, F groups were established the model of chronic high IOP by cauterizing of superficial scleral vein. Tissues of eyes were obtained after intragastric administration for 2 and 4 wk. At the time-point of 2 wk, OX42 protein and IL-1β mRNA in group B were statistically expressed in higher level comparing with other groups（P〈0.05）. Moreover, at the time-point of 4 wk, OX42 protein and IL-1β mRNA in groups C, D and E were statistically expressed in lower level comparing with group F（P〈0.05）. Besides, OX42 protein and IL-1β mRNA in groups C and D were statistically expressed in higher level comparing with group E（P〈0.05）. OX42 protein and IL-1β mRNA in groups C and D were expressed in similar level（P〉0.05）. The study indicated that, in the protection of optic nerve of rats with chronic high IOP, the high dose of Qingguang＇an Ⅱ at the time-point of 4 wk was the better choice.展开更多
MgCdc42 （Cdc42 in Magnaporthe grisea）, with high homology to ScCdc42 （Cdc42 in Saccharomyces cerevisiae）, has been demonstrated to involve in the morphogenesis and infection process. To further understand the sign...MgCdc42 （Cdc42 in Magnaporthe grisea）, with high homology to ScCdc42 （Cdc42 in Saccharomyces cerevisiae）, has been demonstrated to involve in the morphogenesis and infection process. To further understand the signaling network, the putative MgCdc42-interacting proteins were analyzed. ScCdc42-interacting protein sequences were first used to BLAST against the M. grisea genome database to retrieve their corresponding analogs. Subsequently, conserved domains of these proteins were compared and expression patterns of their encoding genes in different MgCdc42 mutation states were analyzed by semiquantitative RT-PCR. All retrieved analogs of ScCdc42-interacting proteins from the M. grisea database have conserved domains as those in S. cerevisiae. Expression of their encoding genes increased in MgCdc42CA mutant and decreased in MgCdc42KO mutant. However, MgBeml, Chin1, and MgGicl in MgCdc42DN mutant had the same expression level as that in the wild type, although MgBem4, MgBoi2, MgCdc24, MgGic2, MgRgal, and Mst20 had decreased expression level, as expected. Overall, it is concluded that there may exist a similar Cdc42 signal pathway in M. grisea as in S. cerevisiae and MgCdc42 plays a key role in the pathway.展开更多
文摘BACKGROUND： The differential diagnosis of many neurodegenerative disorders depends primarily on clinical symptoms together with imaging methods. Recently, increased importance has been placed on the use of biomarkers for diagnosing various neurodegenerative disorders. OBJECTIVE： To assess the feasibility of tau-protein, phosphorylated tau-protein, beta-amyloid 42 （Aβ42）, and 14-3-3 protein as biomarkers for diagnosing several neurodegenerative diseases complicated by cognitive deficits. DESIGN, TIME AND SETTING： A non-randomized, concurrent, case-control investigation was performed in three medical centers in the Czech Republic （Department of Neurology at the University Hospital in Hradec Kralove, Department of Neurology at the 2rd Medical Faculty, and the University Hospital Motol） between October 2000 and November 2006. PARTICIPANTS： Eighteen patients with probable AIzheimer＇s disease, 4 patients with Creutzfeldt-Jakob disease, 10 patients with frontotemporal dementia, 9 patients with clinically isolated syndrome suggestive of multiple sclerosis, and 7 patients with multiple sclerosis, as well as 38 race-, nationality-, and age-matched cognitively intact controls, were included in the study. Diagnoses were established based on the following criteria： the criteria for Alzheimer＇s disease proposed by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer＇s Disease and Related Disorders Association, WHO criteria for Creutzfeldt-Jakob disease, Neary criteria for frontotemporal dementia, and McDonald＇s criteria for multiple sclerosis. All included patients were confirmed to suffer from various degrees of dementia. METHODS： Enzyme-linked immunosorbent assay was used to measure concentrations of tau-protein, phosphorylated tau-protein, and Aβ42 in cerebrospinal fluid （CSF） samples collected by standard lumbar puncture from each patient. Moreover, 14-3-3 protein was assessed by Western blot in CSF of Creutzfeldt-Jakob disease patients. Cognitive status was assessed using the Mini Mental Scale Examination （MMSE） in all subjects. MAIN OUTCOME MEASURES： Establishment of biomarkers with greatest specificity and sensitivity for the investigated disorders according to Receiver Operating Characteristic curves, which were based on values from patients and controls; correlation between concentrations of given biomarkers and demographic parameters, diagnosis, duration of disease, and level of cognitive deficit. RESULTS： Increased concentrations of total tau protein and phosphorylated tau protein, and decreased levels of Aβ42, in CSF of Alzheimer＇s disease patients reached the required sensitivity/specificity ratio of 80% or greater. A marked elevation in CSF concentrations of total tau protein showed even greater sensitivity than 14-3-3 protein in Creutzfeldt-Jakob disease. There was no association between selected biomarkers and frontotemporal dementia or multiple sclerosis. Phosphorylated tau-protein was the only biomarker that noticeably correlated with MMSE scores for Alzheimer＇s disease.CONCLUSION： Levels of total tau protein, phosphorylated tau protein, and A!342 in the CSF could differentiate patients with Alzheimer＇s disease and Creutzfeldt-Jakob disease from healthy controls and patients with other neurodegenerative disorders. The diversity of absolute values demonstrates the necessity to establish a specific standard for each laboratory.
文摘目的:探讨右美托咪定复合超声引导下腹横肌平面(TAP)阻滞麻醉对腹腔镜下腹股沟疝修补术病人血清β-42淀粉样蛋白(Aβ-42)和Tau蛋白的影响。方法:选取行腹腔镜下腹股沟疝修补术病人100例,随机分为对照组和观察组,各50例。对照组行喉罩全麻,观察组采用超声引导下TAP阻滞联合右美托咪定麻醉。记录2组病人切皮时(T1)、手术开始1 h(T2)、手术结束即刻(T3)的平均动脉压和心率(HR)、血氧饱和度。比较2组疼痛视觉模拟评分(VAS)、简易智能状态检查量表(MMSE)评分、术后认知功能障碍(POCD)的发生率及Aβ-42和Tau蛋白表达水平。结果:2组病人术后即刻和术后6、24、48 h VAS评分逐渐降低降低(P<0.05);观察组术后6、24、48 h VAS评分均明显低于对照组(P<0.01)。观察组T2、T3 HR均明显低于对照组(P<0.01),且T2、T3时HR低于T1(P<0.05)。术后观察组POCD的发生率为6.00%(3/50),低于对照组的22.00%(11/50)(P<0.05)。术后1、7 d 2组MMSE评分均低于麻醉前(P<0.05),且观察组MMSE评分明显高于对照组(P<0.01)。术后7 d 2组Tau蛋白水平均高于麻醉前(P<0.05),Aβ-42蛋白水平均低于麻醉前(P<0.05),Tau/Aβ-42值高于麻醉前(P<0.05);且观察组Tau蛋白水平及Tau/Aβ-42值均低于对照组(P<0.05和P<0.01),Aβ-42水平明显高于对照组(P<0.01)。结论:超声引导下TAP阻滞麻醉联合右美托咪定在腹腔镜下腹股沟疝修补术中镇痛效果显著,同时有效改善病人的认知功能,调节术后血清Aβ-42和Tau蛋白水平,降低POCD发生率。
基金Supported by the National Natural Science Foundation of China(No.81273807)Key Projects of Graduate Innovation Fund of Hunan Province(No.CX2017B434+5 种基金No.CX2017B426)Projects of Hunan Educational Research Foundation(No.17C1221)225 Engineering Project of High Lever Health Professionals of Hunan ProvinceKey Discipline Project of Ophthalmology of Traditional Chinese Medicine of State Administration of TCMKey Discipline Project of Otorhinolaryngology of TCM of Hunan ProvinceHunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine(No.2017TP1018)
文摘The study investigated the effects of Qingguang＇an Ⅱ（a Chinese medicinal preparation） on expressions of OX42 protein and interleukin-1β（IL-1β） mRNA of retinal microglia cells of rats with chronic high intraocular pressure（IOP）. SD rats were randomly divided into 6 groups, that were： A： blank group; B： model group; C： Qingguang＇an Ⅱ low dose group; D： Qingguang＇an Ⅱ medium dose group; E： Qingguang＇an Ⅱ high dose group; F： Yimaikang disket（a Chinese medicinal preparation） group. Experimental rats in B, C, D, E, F groups were established the model of chronic high IOP by cauterizing of superficial scleral vein. Tissues of eyes were obtained after intragastric administration for 2 and 4 wk. At the time-point of 2 wk, OX42 protein and IL-1β mRNA in group B were statistically expressed in higher level comparing with other groups（P〈0.05）. Moreover, at the time-point of 4 wk, OX42 protein and IL-1β mRNA in groups C, D and E were statistically expressed in lower level comparing with group F（P〈0.05）. Besides, OX42 protein and IL-1β mRNA in groups C and D were statistically expressed in higher level comparing with group E（P〈0.05）. OX42 protein and IL-1β mRNA in groups C and D were expressed in similar level（P〉0.05）. The study indicated that, in the protection of optic nerve of rats with chronic high IOP, the high dose of Qingguang＇an Ⅱ at the time-point of 4 wk was the better choice.
基金the National Natural Science Foundation of China to Wang Zonghua （30070030, 30470066）.
文摘MgCdc42 （Cdc42 in Magnaporthe grisea）, with high homology to ScCdc42 （Cdc42 in Saccharomyces cerevisiae）, has been demonstrated to involve in the morphogenesis and infection process. To further understand the signaling network, the putative MgCdc42-interacting proteins were analyzed. ScCdc42-interacting protein sequences were first used to BLAST against the M. grisea genome database to retrieve their corresponding analogs. Subsequently, conserved domains of these proteins were compared and expression patterns of their encoding genes in different MgCdc42 mutation states were analyzed by semiquantitative RT-PCR. All retrieved analogs of ScCdc42-interacting proteins from the M. grisea database have conserved domains as those in S. cerevisiae. Expression of their encoding genes increased in MgCdc42CA mutant and decreased in MgCdc42KO mutant. However, MgBeml, Chin1, and MgGicl in MgCdc42DN mutant had the same expression level as that in the wild type, although MgBem4, MgBoi2, MgCdc24, MgGic2, MgRgal, and Mst20 had decreased expression level, as expected. Overall, it is concluded that there may exist a similar Cdc42 signal pathway in M. grisea as in S. cerevisiae and MgCdc42 plays a key role in the pathway.
