The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype

neurogenetics - Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy with a prevalence of 1 in 2500 individuals worldwide. Here, we report three Turkish siblings from...     

Berberine ameliorates non-steroidal anti-inflammatory drugs-induced intestinal injury by the repair of enteric nervous system

The study was to detect the role of GDNF, PGP9.5 (a neuronal marker), and GFAP (EGCs’ marker) in the mechanism of non-steroidal anti-inflammatory drugs (NSAIDs) related to intestinal injury and to clarify the protective effect of berberine in the treatment of NSAID-induced small intestinal disease. Forty male SD rats were divided randomly into five groups (A–E): Group A: control group; Group B: model group received diclofenac sodium 7.5 mg/(kg*day) for 5 days; Group C–E: berberine low, medium and high dose groups were treated by 7.5 mg/(kg*day) diclofenac sodium for 5 days then received berberine 25 mg/(kg*day), 50 mg/(kg*day), and 75 mg/(kg*day), respectively, between the sixth and eighth day. Intestinal mucosa was taken on the ninth day to observe the general, histological injuries, and to measure the intestinal epithelial thickness. Then, immunohistochemistry was performed to detect the expression of PGP9.5 and GFAP, and Western blot was performed to detect GDNF expression. The histological score and the general score in the model group were, respectively, 5.75 ± 1.04 and 4.83 ± 0.92. Scores in berberine medium and high berberine group were lower compared with the model group (P < 0.05). The intestinal epithelial thickness in the model group was lower than in the control group and the berberine groups (P < 0.05). PGP9.5, GFAP, and GDNF content in the model group and the three berberine groups were significantly lower than in the control groups (P < 0.05). PGP9.5, GFAP, and GDNF content in the control group and the three berberine groups were higher compared with the model groups (P < 0.05). Berberine can protect the intestinal mucosa of NSAID users, and the mechanism is associated with the reparation of the enteric nervous system via upregulating the expression of PGP9.5, GFAP, and GDNF.     

抗γ-氨基丁酸B型受体脑炎五例分析

目的:探讨抗γ-氨基丁酸B型受体(GABA BR)脑炎患者的临床特点、治疗及预后。方法:回顾性总结2017年9月至2019年6月香港大学深圳医院神经内科诊治的5例抗GABA BR脑炎病例,分析其临床资料、辅助检查、治疗经过,随访3.5~23.0个月并评估预后。结果:5例抗GABA BR脑炎患者(19~81岁)均急性起病,以难治性癫痫为主要临床表现,其中4例颅脑磁共振成像显示颞叶及海马为主的T 2/液体衰减反转恢复序列高信号。脑电图均提示慢波或癫痫样放电。4例肺部发现占位,病理均确诊为小细胞肺癌。5例接受一线免疫抑制治疗(激素联合丙种球蛋白或血浆置换)效果均欠佳,3例接受了二线免疫治疗(利妥昔单抗、环磷酰胺),其中2例合并肿瘤者同时接受了肿瘤治疗,接受二线治疗及肿瘤治疗的患者疗效明显好于单纯一线治疗者。结论:抗GABA BR脑炎主要表现为以难治性癫痫为特征的边缘性脑炎综合征。一线治疗效果欠佳的抗GABA BR脑炎尽快启动二线治疗可明显改善预后。     

磁共振成像阴性颞叶癫痫的临床特点分析

目的探讨磁共振成像(MRI)阴性颞叶癫痫(nonlesional temporal lobe epilepsy,TLE-NL)患者的临床特征、记忆水平和影像学特点。方法纳入2012年9月1日至2017年8月31日在浙江大学医学院附属第二医院确诊的44例单侧TLE-NL患者和53例同期就诊单侧颞叶癫痫伴海马硬化(temporal lobe epilepsy with hippocampal sclerosis,TLE-HS)患者,对TLE-NL和TLE-HS的临床特点进行对比。同时纳入20名健康志愿者作为正常对照组。采用韦氏记忆量表评估患者和对照组记忆功能,并通过高分辨率MRI定量分析海马体积及形态,评估TLE-NL和TLE-HS患者记忆水平和海马体积的改变。结果TLE-NL患者比TLE-HS患者发病年龄更晚[(24.3±12.6)岁与(15.8±10.3)岁;t=3.684,P<0.01],癫痫病程更短[4.00(2.00,8.75)年与14.00(7.50,22.00)年;Z=-4.675,P<0.01],热性惊厥史比例[4.5%(2/44)与62.3%(33/53);χ2=32.270,P<0.01)和药物难治性比例更低[47.7%(21/44)与84.9%(45/53);χ2=15.282,P<0.01)。TLE-NL患者在性别比例、癫痫家族史、致痫灶侧别、先兆发生率、症状学类型及发作频率上与TLE-HS患者类似。TLE-NL患者与正常对照组相比无明显记忆损害(记忆商数:105.2±17.4与103.8±16.2;P=1.000),而TLE-HS患者与正常对照组相比存在明显记忆损害(记忆商数:84.5±20.3与103.8±16.2;P<0.01)。TLE-NL患者海马体积和形态与正常对照组相比无明显改变,而TLE-HS患者存在明显致痫灶同侧海马萎缩[(2953±481)mm3与(4431±505)mm3;P<0.01),形态分析结果提示萎缩以海马头及海马体部明显。结论TLE-NL是一类有别于TLE-HS的颞叶癫痫综合征,具有发病年龄晚、病程短、热性惊厥史少、药物难治性癫痫发生率较低、无明显记忆损害及海马萎缩的临床特点。     

强迫症团体认知行为治疗与药物治疗的随机对照研究

目的分析团体认知行为治疗(group cognitive-behavioral therapy,GCBT)对强迫症患者的疗效。方法本研究采用随机对照试验设计,与常规抗强迫药物治疗做对照。将符合入组标准的94例未用药强迫症患者,采用Excel软件中的RAND函数产生随机数字表形成随机分组序列的简单随机分组法,随机分为GCBT组(47例)和药物治疗组(47例)。经12周的结构化GCBT治疗和常规抗强迫药物治疗,采用t检验、卡方检验和方差分析比较2组间Y-BOCS、HAMA14和HAMD24平均减分率和减分值的差异。结果(1)2组基线Y-BOCS及HAMA14评分差异无统计学意义(t=0.281,P=0.779;t=0.795,P=0.429),但GCBT组HAMD24评分显著低于药物治疗组(t=2.316,P<0.05)。2组各有16例患者退出治疗,总脱落率为34%(32/94)。(2)12周治疗结束时,2组患者的Y-BOCS评分较基线显著降低,GCBT组和药物治疗组治疗前后Y-BOCS平均减分率[(37.0±27.4)%比(45.5±22.9)%]和平均减分值[(9.0±6.3)分比(11.0±5.8)分]比较差异无统计学意义[F(1,62)=0.069,P=0.794;F(1,62)=0.001,P=0.975]。GCBT组和药物治疗组的有效率和治愈率差异无统计学意义(χ^2=1.653,P=0.199;χ^2=0.088,P=0.767)。(3)GCBT组HAMA14减分率和减分值与药物治疗组治疗前后比较差异无统计学意义(t=-0.922,P=0.362;t=1.082,P=0.286)。(4)GCBT组HAMD24减分率与药物治疗组治疗前后比较差异无统计学意义,但药物治疗组HAMD24减分值显著高于GCBT组(t=2.239,P=0.029)。结论GCBT与常规抗强迫药物治疗强迫症患者的强迫和焦虑症状的疗效相当,常规药物治疗对抑郁症状的疗效优于GCBT。     

α-突触核蛋白聚集及传播模型的构建

目的 建立α-突触核蛋白(α-synuclein,α-syn)聚集及传播的细胞和动物模型,为帕金森病的发病机制研究提供基础。方法 亲和层析法纯化α-syn蛋白,体外诱导其聚集成为α-syn纤维(Preformed fibrils,PFFs); 培养稳定表达GFP-α-syn的HEK293细胞系及原代神经元,转导α-synPFFs后免疫荧光染色法观察细胞内α-syn聚集情况; 小鼠立体定位注射α-syn PFFs,免疫组织化学法检测内源性α-syn的聚集及传播情况。结果 纯化的α-syn可在体外聚集形成聚集体; 在细胞及动物水平观察到α-syn PFFs可诱导内源性蛋白的聚集和传播。结论 本研究建立了α-syn聚集及传播的细胞和动物模型,为帕金森病的相关研究打下了基础。     

阿尔兹海默病发病危险因素概况

本文目的是探讨阿尔兹海默病（AD）可能的危险因素、相关的发病机制及预防策略。阿尔兹海默病的危险因素可分为可控因素和不可控因素，不可控因素主要包括遗传、年龄、性别等，可控因素包括糖尿病、中年时期高血压病史、高脂血症、中年时期肥胖史、缺乏运动锻炼、抑郁、吸烟、低教育水平、睡眠等，此外，还包括环境中的金属元素以及脑创伤、甲状腺功能减退、肠道菌群紊乱等病史，本文对这些危险因素的研究现状及可能的发病机制进行讨论。     

Gypenosides Prevent H2O2-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response

Journal of Molecular Neuroscience - Our previous study demonstrated that gypenosides (Gp) exert protective effects on retinal nerve fibers and axons in a mouse model of experimental autoimmune...