胶质细胞球形包涵体Tau蛋白病的颅脑影像学特点

胶质细胞球形包涵体Tau蛋白病(GGT)是一种4R-Tau蛋白病,发病罕见,其临床表现和神经病理具有异质性,与阿尔茨海默病、额颞叶痴呆及进行性核上性麻痹等多种神经变性疾病具有重叠之处,诊断困难,目前主要依赖于尸检。迄今为止,由于详细报道GGT影像学表现的文献数量有限,对该病影像学上的认识多局限于额颞叶萎缩、白质高信号等非特异性征象。因此,文章对近5年报道的GGT病例的影像学资料进行回顾,提取相对特异性的影像学征象,以期为临床识别GGT提供一定的参考价值。     

家族性和散发性额颞型痴呆及其他Tau蛋白相关疾病中Tau蛋白突变的发生率

在与17号染色体连锁的额颞型痴呆合并帕金森综合征患者(FTDP-17)的谱系中发现,不溶性Tau蛋白合并有Tau蛋白基因的突变,这在神经病理学中已得到证实。其他的神经变性疾病,如进行性核上性麻痹(PSP)和皮质基底节变性等都会有不溶性Tau蛋白的产生。本研究旨在阐明患神经变性疾病的一个先证者队列中,Tau基因突变的本质及突变发生率。对64例患者进行了3年以上的研究,其临床表现均符合额颞型痴呆(FTD)或其他Tau蛋白相关疾病的特征。其中30%的患者证实有神经病理性损害。采用PCR产物直接测序法,对Tau基因的编码区和侧翼内含子区进行了突变的…     

额颞叶变性的研究进展

额颞叶变性(frontotemporal lobar degeneration,FTLD)是以局限性额叶/颞叶变性为特征的非阿尔茨海默病(Alzheimer disease,AD)痴呆综合征.近年的研究发现它与tau蛋白的变性有关,并与皮质基底节变性(corticobasal ganglionic degeneration,CBD)、进行性核上性麻痹(progressive supranuclear palsy,PSP)、运动神经元病(motor neuron disease,MND)相关或重叠.本文就FTLD的病因、病理、遗传学、临床分型以及诊断标准等方面的研究进展作一综述.     

载脂蛋白Eε4是tau蛋白病、共核蛋白病及额颞叶变性中阿尔茨海默型病变特征的决定因素

目的:确定载脂蛋白E4是否影响tau蛋白病、共核蛋白病及额颞叶变性中阿尔茨海默型病变特征的发生频率,以及该病变特征在共核蛋白病中的发生率是否与tau蛋白病和额颞叶变性相似。方法:对年龄在75.1±9.3岁,病理证明患有神经变性疾病(包括弥散性和移行性Lewy小体病、额颞叶变性、进行性核上性麻痹、皮质基底节变性和多系统萎缩)的285例患者进行遗传学和病理学分析。疾病被分为tau蛋白病(进行性核上性麻痹和皮质基底节变性)、共核蛋白病(Lewy小体病和多系统萎缩)以及额颞叶变性3组。使用Braak神经纤维缠结分期和老年斑定量评分作为确定每一病…     

Tau蛋白过度磷酸化与阿尔茨海默病

阿尔茨海默病(AD)是最常见的痴呆类型,Tau蛋白异常过度磷酸化是其主要的发病机制之一。Tau蛋白是脑内一种微管相关蛋白,受蛋白激酶(磷酸化)和蛋白磷酸酯酶(脱磷酸化)的调节。Tau蛋白功能异常改变可能是神经元功能障碍和死亡的必要环节。该文对Tau蛋白的结构与功能,Tau蛋白过度磷酸化,Tau蛋白磷酸化调节及Tau蛋白、β淀粉样蛋白与AD的关系进行阐述。     

Tau蛋白高度磷酸化致阿尔茨海默病动物模型研究进展

阿尔茨海默病(Alzheimer’s disease, AD)是老年人中最常见的神经退行性疾病,以过度磷酸化tau蛋白为核心形成的神经原纤维缠结为AD的主要病理特征之一。近年来对tau蛋白磷酸化的研究备受关注。在AD的实验研究中,探索理想的AD动物模型对于明确AD的病因、发病机制及药物的研发等方面起关键作用。本文对Tau蛋白磷酸化致AD主要动物模型的研究进展进行了综述,包括Tau转基因动物模型、激酶和磷酸化酶系统失衡致Tau 蛋白过度磷酸化损伤模型、降低Tau蛋白糖基化致Tau过度磷酸化模型等。     

Tau蛋白异常导致阿尔茨海默病等神经退行性Tau蛋白病的机制与研究进展

Tau蛋白是神经细胞特有的微管相关蛋白,其基本功能是促进微管蛋白组装成微管,维持正常神经轴突运输及微管稳定性。既往基于尸检发现脑部神经纤维缠结（neurofibrillary tangles,NFTs）与神经细胞形态异常及凋亡之间呈良好的平行关系,因而NFTs被认为是引起神经退行性Tau蛋白病的重要原因,并认为与Tau蛋白的过磷酸化有关;但新近发现单纯Tau蛋白磷酸化并不足以形成NFTs,还必须有其他诸如糖基化、脯氨酸异构化、泛素化等翻译后修饰机制的协同,其他如Tau蛋白基因突变、自噬的抑制等也与NFTs形成有关。尤其是最近采用转基因活体动物和多光子影像技术的研究显示,NFTs可能只是疾病晚期的临床表现,而可溶性的Tau蛋白才是启动下游病理反应的关键因素。更为引人注目的是,抑制Tau蛋白还可以阻止Aβ引起的神经细胞凋亡、减轻记忆损害,换言之即Aβ的毒性是Tau蛋白依赖性的。随着近期对Tau蛋白异常介导神经退行性Tau蛋白病及其机制的新认识以及以Aβ为靶点的药物研发宣告失败,人们愈来愈重视以Tau为靶点的药物开发。     

外周胰岛素抵抗对MAPT转基因小鼠认知损害和大脑Tau蛋白磷酸化的影响

目的:探讨长期高脂饮食引起的胰岛素抵抗对pR5株系MAPT Tau转基因小鼠的认知功能和大脑Tau蛋白磷酸化的影响。方法:8周龄雌性pR5 MAPT转基因小鼠分为标准饮食(standard diet,STD)组(pR5 STD, n＝8)和高脂饮食(high-fat diet,HFD)组(pR5 HFD, ...     

叶酸对N2a-APP695细胞Tau蛋白及其Ser396位点磷酸化的调控

目的:研究叶酸对转染人APP695质粒的小鼠成神经瘤细胞(N2a)Tau蛋白的表达及其磷酸化修饰的影响.方法:稳定转染人APP695质粒的N2a细胞根据叶酸不同剂量分为4组,叶酸缺乏组(0μmol/L)、叶酸正常组(10 μmol/L)、叶酸低剂量组(20μmol/L)、叶酸高剂量组(40 μmol/L).各组细胞作用96 h后,用Real-time PCR检测其tau mRNA表达,用Western blot检测Tau总蛋白以及磷酸化Tau蛋白(p-Tau Ser396)的表达.结果:与叶酸正常组相比,叶酸的添加对tau mRNA及总蛋白的表达水平作用不明显;叶酸对Tau蛋白Ser396位点磷酸化有显著的影响,随叶酸剂量的增加Tau Ser396位点去磷酸化逐渐增强.结论:添加叶酸能对Alzheimer's disease(AD)模型细胞中磷酸化Tau蛋白Ser396位点有显著的去磷酸化作用,提示叶酸对AD可能具有一定的治疗作用.     

远志对阿尔茨海默病大鼠海马神经元Tau蛋白磷酸化的影响

目的:研究远志对阿尔茨海默病(Alzheimer′s disease,AD)大鼠模型海马神经元Tau蛋白磷酸化的影响。方法:将32只雄性健康Wistar大鼠随机分为对照组,模型组,远志1组,远志2组。用脑立体定位技术给大鼠海马注射Aβ1-40与apoE4的混悬液构建AD模型。将大鼠断头取脑,分离海马,采用免疫组化染色法检测大鼠海马神经元Tau蛋白磷酸化的情况。结果:①与对照组比较,模型组、远志1组、2组磷酸化Tau蛋白的平均灰度值明显降低(P<0.01)。②与模型组比较,远志1组、2组磷酸化Tau蛋白的平均灰度值明显升高(P<0.01)。远志2组与远志1组比较,磷酸化Tau蛋白的平均灰度值明显升高(P<0.01)。结论:远志对可溶性Aβ1-40与apoE4联合注射所致AD大鼠模型海马CA1区神经细胞内Tau蛋白过度磷酸化有明显的改善作用。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.