SLC35A2基因变异致先天性糖基化障碍Ⅱm型3例并文献复习

目的总结SLC35A2基因变异致先天性糖基化障碍Ⅱm型3例患儿的临床特征、基因变异特点、诊断、治疗及预后。方法总结2018—2020年在中南大学湘雅医院儿科就诊的3例确诊为先天性糖基化障碍Ⅱm型(CDG Ⅱm)患儿的临床资料。以"congenital disorders of glycosylation Ⅱm""SLC35A2""先天性糖基化障碍Ⅱm型""CDG Ⅱm"为关键词, 查阅在线人类孟德尔遗传数据库和PubMed数据库、中国知识基础设施工程(CNKI)数据库、万方数据库建库至2022年1月的相关文献, 总结SLC35A2基因变异患者的临床表现、遗传学、治疗及预后特点。结果 3例患儿均为婴儿期起病, 表现为痉挛发作和全面发育落后, 经多种抗癫痫发作药物治疗有暂时和部分好转, 但不能完全控制;先证者2和先证者3出现丙氨酸氨基转移酶、血小板升高, 眼底检查示双眼视网膜色素上皮发育不良, 接受了D-半乳糖治疗后, 临床或生化指标稍有改善。文献检索SLC35A2变异报道共22篇99例, 共报道75个不同变异位点, 均为杂合变异;临床表型主要包括发育迟缓或智力障碍(89/99)、癫痫发作...     

SLC22A18基因启动子甲基化与胶质瘤SLC22A18表达的关系

目的 探讨胶质瘤中SLC2218基因肩动子甲基化与其表达的关系.方法 选取上海交通大学医学院附属第三人民医院神经外科自2006年9月至2009年6月、武汉大学中南医院神经外科自2002年9月至2005年6月间手术切除的胶质瘤标本30例,另选10例行内减压术颅脑损伤患者的正常脑组织作为对照.采用甲基化特异性聚合酶链反应(MSP)检测标本中SLC22A18基因启动子甲基化的状态,RT-PCR和Westem blotting分别检测SLC22A18 mRNA和蛋白的表达.体外培养胶质瘤U251细胞于含2 μmol/L去甲基化药物5-aza-2-deoxycytidine的培养液(实验组1中,同时设普通培养液作对照,培养3、5、7 d后进行细胞计数并应用Western blotting检测SLC22A18蛋白的表达.结果 MSP检测结果显示15例胶质瘤组织出现甲基化,对照脑组织均表现出非甲基化;15例甲基化胶质瘤组织中SLC22A18 mRNA、蛋白的表达明显低于对照脑组织.培养5、7 d实验组U251细胞计数少于对照组,差异有统计学意义(P＜0.05).培养7 d Western blotting检测结果发现实验组细胞SLC22A18蛋白的表达明显高于对照组.结论 SLC22A18基因启动子甲基化导致其表达下调;去甲基化药物能恢复U251细胞SLC22A18的表达,并抑制U251细胞增殖.

Abstract：

Objective To investigate the relationship between aberrant methylation of SLC22A18 gene promoter and SLC22A18 expression in human glioma. Methods Thirty patients with glioma and 10 patients with craniocerebral injury performed decompression were chosen in our study;their tissue samples were prepared. Methylation-specific PCR (MSP) was used to detect the methylation status of SLC22A18 gene promoter;and Western blotting and RT-PCR were employed to measure the protein and mRAN expressions of SLC22A18 in these tissue samples. U251 cells were cultured in vitro with demethylating agent 5-aza-2-deoxycytidine (experimental group, 2μmol/L) and common medium (control group), resepectively;the re-expression of SLC22A18 in U251 cells was measured by Western blotting and cell growth suppression induced by 5-aza-2-deoxycytidine was also observed 3, 5 and 7 d after the culture. Results The methlylation of SLC22A18 gene promoter existed in glioma tissues of 15 patients (50%) but that did not exist in the tissues of patients with craniocerebral injury. The protein and mRAN expressions of SLC22A18 in the tissue samples of these 15 patients were significantly decreased as compared with those in patients with craniocerebral injury (P<0.05);cell counting of U251 cells in the experimental group on the 5th and 7th d of culture was significantly decreased as compared with that of those in the control group (P<0.05). On the 7ht d of culture, Western blotting indicated that the protein b expression level of SLC22A18 in the experimental group was obviously higher than that in the control group. Conclusion The aberrant methylation of SLC22A18 gene promoter plays a key role in down-regulating SLC22A18 expression, and demethylation agents can restore the SLC22A18 expression and suppress the growth of U251 cells.     

强迫症与5-羟色胺转运体基因多态的关联分析

目的 探索汉族人群中5-羟色胺转运体SLC6A4基因多态与强迫症发病的关系。方法采用聚合酶链反应扩增片段长度多态技术测定120例强迫症患者(强迫症组)和130名健康人(对照组)的SLC6A4基因型。结果 强迫症组SLC6A4第2内含子及启动子的基因型多态分布与对照组间的差异有显著性(X2=6.70,P=0.035;X2=6.35,P=0.042);第2内含子等位基因频数分布与对照组之间的差异有非常显著性(X2=7.54,P=0.006);第2内含子的等位基因10,12/10基因型和启动子的L/L基因型与强迫症存在显著正关联[比数比(OR)值分别为2.24,2.12和3.57,P<0.05];强迫症组及对照组内不同性别间基因型分布的差异均无显著性(P>0.05)。结论 在汉族人群中SLC6A4基因可能与强迫症存在遗传关联,第2内含子的等位基因10和12/10基因型、启动子的L/L基因型可能是强迫症的风险因子。     

成人Ⅱ型瓜氨酸血症一例临床特征分析

目的 总结1例成人Ⅱ型瓜氨酸血症( CTLN2)的临床资料,提高临床医生对该病早期诊断、早期治疗和随访重要性的认识.方法 收集患者临床资料,仔细询问病史并进行体格检查和各项辅助检查.对患者及其女儿进行SLC25A13基因检测.结果 患者女性,27岁,因反复头晕、呕吐2年余,伴发作性意识模糊1年半就诊,肝脏B超、MRI及肝活体组织检查均示肝硬化.脑电图示异常尖波.血氨基酸检测示瓜氨酸升高,SLC25A13基因检测示851 del4纯合突变,患者女儿系851del4杂合突变.结论 对于成人不明原因的脂肪肝及肝硬化,特别是伴神经精神症状的患者应考虑到CTLN2,SLC25A13基因检测可帮助早期诊断.     

低级别胶质瘤SLC12A5的表达及临床意义的生信分析

目的 探讨溶质载体家族12成员5（SLC12A5）在低级别胶质瘤（LGG）中的表达及临床意义。方法 利用GEPIA数据库分析SLC12A5在LGG的表达以及SLC12A5表达与LGG病人预后的关系;通过GEMEMANIA和SDTRING数据库构建SLC12A5的相互作用网络;筛选50个与SLC12A54存在强相关关系的基因并进行功能富集分析。结果 SLC12A5在LGG组织中表达显著下调,Kaplan-Meier生存曲线显示SLC12A5低表达与LGG病人不良生存预后有关。相互作用网络结果显示SLC12A5可能与STK39存在相互作用关系。功能富集分析发现,SLC12A5及其共表达基因主要参与化学突触传递、突触小泡周期、认知、细胞连接组织、突触小泡回收以及体液水平的调节等生物学过程。结论 SLC12A5在LGG中呈低表达,与病人不良预后相关。     

中国汉族人群SLC6A11基因多态性与耐药性癫痫的相关性研究

目的探索中国汉族人群SLC6A11基因多态性与耐药性癫痫的相关性。方法据入选标准和排除标准收集在湘雅医院门诊的480例癫痫患者,应用Illumina Golden Gate定制芯片对288例药物敏感癫痫患者和192例药物耐药癫痫患者进行SLC6A11基因型鉴定,分析单位点基因型频率和单体型与耐药性癫痫的相关性。结果敏感组与耐药组之间SLC6 A11基因14个SNP位点的基因型频率差异无统计学意义(P0.05);耐药性癫痫患者单倍型5的频率高于敏感组(1%vs.4%;OR=2.56[0.107-0.763];P=0.01),经过Bonferroni多重检验后单倍型5的频率在两组间无显著差异。结论 SLC6A11基因的14个SNP多态性可能与中国汉族人群的癫痫耐药性无关。     

SLC6A1基因变异导致神经发育障碍的家系分析

目的 探讨SLC6A1基因突变导致的儿童癫痫及其他神经发育障碍的临床特征和基因变异特点。方法 对2021年1月-2022年10月在华中科技大学同济医学院附属同济医院儿科住院及门诊随访的1例SLC6A1基因变异导致的肌阵挛-失张力癫痫患儿的临床表现和基因变异特点进行回顾性分析，并检索文献，总结SLC6A1基因突变患者的临床表型及基因突变特点。结果 患儿，女，1岁8月龄出现频繁腿抖，独站不稳及摔跤，伴有频繁眨眼。于2岁3月龄因仍不能独立行走开始康复训练。不会说话，不愿意理人。视频脑电图提示背景节律慢化；醒睡期见双侧前头部、后头部或广泛性高波幅慢波、棘慢波或节律发放。头部MRI提示双侧额叶斑点状高T₂ Flair信号灶。Gesell发育评估量表发育商64,发育年龄为21月龄，儿童孤独症评定量表提示目前无明显孤独症表现。基因突变分析发现患儿SLC6A1基因存在一处杂合变异c. 889G>A(p. Gly297Arg),突变来自母亲及外婆，其母亲及外婆幼时有抽搐史。总结既往文献，SLC6A1基因突变相关的神经发育障碍的主要临床表型为癫痫(失神、失张力、肌阵挛及肌阵挛-...     

钠/钙交换蛋白SLC24A6在实验性颅内出血导致脑损伤过程中的作用及机制研究

目的探究钾依赖钠/钙交换蛋白-6(SLC24A6)参与大鼠脑出血后继发性脑损伤的作用和可能机制。方法建立SD大鼠脑出血模型,检测大鼠脑出血后尾状核SLC24A6表达及其介导的细胞内钙浓度([Ca~(2+)]_i)随时间变化的情况,观察SLC24A6在正常氧浓度和低氧条件下对[Ca~(2+)]_i的调控。结果脑出血早期,尾状核SLC24A6蛋白和SLC24A6mRNA水平均降低,在脑出血后3 d降至最低水平,5和7 d后轻微升高。脑出血后早期,[Ca~(2+)]_i增加,于脑出血后3 d达最高水平,5和7 d时逐步下降。正常氧浓度下,转染SLC24A6导致HEK293[Ca~(2+)]_i升高。结论 SLC24A6通过抑制钙超载在脑出血后脑损伤中起保护作用。     

肌酸转运载体缺乏一家系临床与遗传学分析

目的报道由SLC6A8基因突变导致肌酸转运载体缺乏(creatine transporter deficiency,CRTR-D)一家系的临床和遗传特点。方法对2018年9月山西省儿童医院神经内科收治的1例全面性发育迟缓伴癫痫患儿及家系进行临床分析与遗传学检查,分析其致病基因突变情况。结果先证者男性,3岁3个月,走路不稳,不会说话,频繁抽搐,尿肌酸/肌酐比值升高,磁共振波谱提示脑肌酸峰值降低。先证者舅舅与患儿症状相似,先证者母亲仅表现出学习困难,先证者父亲、姐姐及外祖父母均无症状。测序发现患儿SLC6A8基因(NM_005629)TTC缺失突变[c.1222_1224del(p.Phe408del)],诊断为X-连锁CRTR-D;患儿母亲及外祖母为杂合突变,患儿舅舅携带同样的半合子突变,先证者父亲、姐姐及外祖父未发现该突变。结论SLC6A8基因突变导致CRTR-D的病例家系中具有相同突变的2名女性携带者临床表现不一,存在表型变异,对研究CRTR-D基因型-表型相关性有重要意义。     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

帕金森病运动症状进展分析

目的分析帕金森病(PD)患者运动症状进展特点。方法采用PD统一评分量表(UPDRS)Ⅲ对912例PD患者进行评估。结果与病程1年的患者比较,除病程1~2年的患者外,其他病程患者的UPDRSⅢ评分、强直分、姿势或步态异常分、轴性症状总分、言语分、步态分显著升高(均P0.05),病程5~6年及14年患者的震颤分,病程5~6年、7~8年、9~13年、14年患者的运动迟缓分、姿势分显著升高(P0.05~0.01)。轴性症状进展速度高于UPDRSⅢ评分。结论 PD患者病程早期UPDRSⅢ评分进展快,震颤症状进展独立于其他症状,轴性症状评分较UPDRSⅢ更敏感地反映疾病加重趋势。     

Frequency of accumulation of filaments in adaxonal cytoplasm of Schwann cells of myelinated fibers of rat spinal roots

Summary The frequency of accumulation of 6-nm filaments in the adaxonal cytoplasm of Schwann cells in the 6th lumbar dorsal and ventral roots was evaluated in 4-, 8-, 26- and 45-week-old Sprague-Dawley rats. The frequency was higher in 4- and 8-week-old (growing) rats than in 26- and 45-week old (mature) rats, and also higher in ventral than in dorsal roots in 4-, 8- and 26-week old rats. There were no clusters on certain groups of myelinated fibers according to the size of transverse axonal area, in both the ventral and dorsal roots. Therefore, this accumulation may reflect certain functions of the adaxonal cytoplasm of Schwann cell during natural growth and maturation of the axon and myelin sheath.     

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.     

Effects of prevention of afferentation of the development of the chick optic lobe

BONDY, S. C., M. E. HARRINGTON AND C. L. ANDERSON. Effects of prevention of afferentation on the developmentof the chick optic lobe. BRAIN RES. BULL. 3(5) 411–413, 1978.—The effects of unilateral extirpation of the right optic cup of the three-day incubated chick embryo upon the rate of synthesis and the stability of DNA in the non-innervated optic lobe, have been studied. This surgical procedure prevents innervation of the optic lobe contralateral to the removed eye, while the other optic lobe is normally innervated by retinal ganglion cells of the remaining eye. At the 20th day of incubation, the DNA content of the non-innervated lobe was below that of the paired lobe receiving normal innervation. This deficiency of cell number was caused by two events; death of an excess number of neurons formed early in embryogenesis and a reduced rate of glial proliferation in the later stages of incubation.     

Modelling of movement of the lamprey: Control of oscillators

This article discusses the control methods of the central pattern generator (CPG). First a control model of the CPG is presented using 2 oscillators, and we suggest that phasic modulation to the CPG by means of phasic information is effective for controlling the phase difference between oscillators. Next, two models for controlling the CPG of a lamprey are proposed. One model describes a control system from the brain stem, in which the reticulospinal neurons control the CPG by receiving feedback signals and sending control signals to the neck region of the CPG. The other is a model for learning an localized control system to generate a desired motor pattern. By means of these models, a role of the efference copy is suggested.     

利培酮对精神分裂症患者生活质量的影响

目的：比较利培酮与氟哌啶醇对精神分裂症患者生活质量的影响。方法：对门诊72例服用氟哌啶醇及74例服用利培酮的精神分裂症患者用生活质量综合评定问卷（GQOLI）、阳性与阴性症状量表（PANSS）、副反应量表（TESS）进行评定。结果：利培酮组患者治疗后生活质量有所提高,而氟哌啶醇组患者生活质量有所下降。结论：利培酮治疗有利于患者提高生活质量。     

腺垂体功能减退症临床特征变化分析

目的探讨腺垂体功能减退症患者的病因结构变化及临床表现。方法回顾性分析我院2013-01—2016-12住院及门诊78例腺垂体功能减退症患者的临床资料。结果男32例(41.03%),女46例(58.97%);诊断时年龄11~89岁,平均62.5岁;鞍区占位(包括术前及术后)52例(66.67%),席汉综合征8例(10.26%),空泡蝶鞍9例(11.65%),病因不明8例(10.26%),垂体-下丘脑发育不良1例(1.28%)。首次就诊科室:纳差厌食、恶心呕吐就诊于消化内科36例(46.15%)最常见。ACTH+TSH+Gn+G激素缺乏为19例最多,占24.36%,ACTH+TSH+Gn缺乏15例,占19.23%。结论腺垂体功能减退症病因结构发生变化,发病人群、首发症状及受累激素也不同,患者女性多于男性,发病年龄偏高,症状不典型,分布于临床多个科室,其中以低钠血症为首发临床表现就诊消化内科最多。     

Standards of instrumentation of EMG

Standardization of Electromyography (EMG) instrumentation is of particular importance to ensure high quality recordings. This consensus report on “Standards of Instrumentation of EMG” is an update and extension of the earlier IFCN Guidelines published in 1999. First, a panel of experts in different fields from different geographical distributions was invited to submit a section on their particular interest and expertise. Then, the merged document was circulated for comments and edits until a consensus emerged.The first sections in this document cover technical aspects such as instrumentation, EMG hardware and software including amplifiers and filters, digital signal analysis and instrumentation settings. Other sections cover the topics such as temporary storage, trigger and delay line, averaging, electrode types, stimulation techniques for optimal and standardised EMG examinations, and the artefacts electromyographers may face and safety rules they should follow. Finally, storage of data and databases, report generators and external communication are summarized.     

Effect of high simple dose of cisplatinum and of radiation on the brain of rabbit

Abstract

In former studies of intracarotid and intravenous administration of cisplatinum, separate and combined with brain irradiation, we found no cerebral damage. In this study! gradually increasing high doses (above the therapeutic ones) of cisplatinum were administered intravenously to one series of rabbits arid increasing high amounts of irradiation (above the therapeutic amounts) were given to another series. Although the rabbits that received highest doses of irradiation developed areas of alopecia and skin ulcers on the head! the general clinical and histopathologic examination of the rabbits brains in both series was normal. The purpose of this study was to establish the effects of high doses of intravenous cisplatinum and irradiation on the rabbits brains. [Neural Res 1997; 19: 216–218]