Store-operated calcium entry modulates neuronal network activity in a model of chronic epilepsy

Store-operated Ca²⁺ entry (SOCE) over the plasma membrane is activated by depletion of intracellular Ca²⁺ stores and has only recently been shown to play a role in CNS processes like synaptic plasticity. However, the direct effect of SOCE on the excitability of neuronal networks in vitro and in vivo has never been determined. We confirmed the presence of SOCE and the expression of the calcium sensors STIM1 and STIM2, which convey information about the calcium load of the stores to channel proteins at the plasma membrane, in neurons and astrocytes. Inhibition of SOCE by pharmacological agents 2-APB and ML-9 reduced the steady-state neuronal Ca²⁺ concentration, reduced network activity, and increased synchrony of primary neuronal cultures grown on multi-electrode arrays, which prompted us to elucidate the relative expression of STIM proteins in conditions of pathologic excitability. Both proteins were increased in brains of chronic epileptic rodents and strongly expressed in hippocampal specimens from medial temporal lobe epilepsy patients. Pharmacologic inhibition of SOCE in chronic epileptic hippocampal slices suppressed interictal spikes and rhythmized epileptic burst activity. Our results indicate that SOCE modulates the activity of neuronal networks in vitro and in vivo and delineates SOCE as a potential drug target.     

合理进行均值比较——随机区组设计定量资料多元方差分析

本文目的是介绍与随机区组设计定量资料多元方差分析有关的基本概念、计算方法、一个实例以及SAS实现。基本概念包括区组因素、如何选定区组因素、随机区组设计和不完全随机区组设计;计算方法涉及一般统计量和检验统计量;一个实例涉及“长期饲喂高锌日粮对断奶仔猪免疫机能影响的动物试验及其多元定量资料”。借助SAS实现随机区组设计定量资料的一元方差分析和多元方差分析。并讨论当区组因素对结果的影响无统计学意义时,合理的统计分析方法是不考虑区组因素,直接采用单因素多水平设计一元和多元定量资料方差分析。     

5例世界首报不育男性异常染色体核型分析

目的:对发现的5例世界首报不育男性染色体异常核型进行研究探讨。方法:对本中心就诊的男性不育患者采用外周血淋巴细胞培养,常规G显带,目测结合计算机软件进行染色体核型分析,计数100个核型,分析30个核型(核型异常者加倍计数和分析)。结果:检出5例国内外首报异常染色体核型,分别是46,XY,t(1;6)(q21;q23);46,XY,t(1;17)(q21;q25);46,XY,t(2;5)(q14.2;q15);46,XY,t(8;12)(q13;q12);46,XY,t(15;19)(p10;p10)。结论:染色体异常是导致男性不育的重要遗传因素,对不育男性患者应常规进行染色体检查,并提供遗传咨询和生育指导,以有效避免各种遗传缺陷向子代传递。     

Blonanserin, a novel atypical antipsychotic agent not actively transported as substrate by P-glycoprotein

Although blonanserin, a novel atypical antipsychotic agent with dopamine D(2)/serotonin 5-HT(2A) antagonistic properties, displays good brain distribution, the mechanism of this distribution has not been clarified. P-glycoprotein [(P-gp) or multidrug resistance protein 1 (MDR1)] is an efflux transporter expressed in the brain and plays an important role in limiting drug entry into the central nervous system (CNS). In particular, P-gp can affect the pharmacokinetics and efficacy of antipsychotics, and exacerbate or soothe their adverse effects. In this study, we conducted in vitro and in vivo experiments to determine whether blonanserin is a P-gp substrate. Risperidone and its active metabolite 9-hydroxyrisperidone, both of which are P-gp substrates, were used as reference drugs. Affinity of blonanserin, risperidone, and 9-hydroxyrisperidone for P-gp was evaluated by in vitro transcellular transport across LLC-PK1, human MDR1 cDNA-transfected LLC-PK1 (LLC-MDR1), and mouse Mdr1a cDNA-transfected LLC-PK1 (LLC-Mdr1a). In addition, pharmacokinetic parameters in the brain and plasma (B/P ratio) of test compounds were measured in mdr1a/1b knockout (KO) and wild-type (WT) mice. The results of in vitro experiments revealed that P-gp does not actively transport blonanserin as a substrate in humans or mice. In addition, blonanserin displayed comparable B/P ratios in KO and WT mice, whereas B/P ratios of risperidone and 9-hydroxyrisperidone differed markedly in these animals. Our results indicate that blonanserin is not a P-gp substrate and therefore its brain distribution is unlikely to be affected by this transporter.     

BTFE与e-THRIVE序列在后颅窝微血管减压术前的应用价值

目的 探讨双激发式稳态自由进动序列(BTFE)与增强T1高分辨率各向同性容积激发序列(e-THRIVE)联合应用在原发性三叉神经痛与面肌痉挛微血管减压术前MR成像中的临床应用价值. 方法 回顾性分析自2009年4月至2011年12月广东省第二人民医院收治的121例神经微血管压迫患者(三叉神经痛74例,面肌痉挛47例)的影像资料,患者均采用PHILIPS公司ACHIEVA NOVA DUAL A-serial 1.5T磁共振扫描仪成像,成像序列除头颅常规序列外,特别进行了BTFE序列及e-THRIVE序列成像. 结果 全部患者均经微血管减压术证实.74例患者的三叉神经及47例患者的面神经全部显示清楚.121例患者中共118例(98％)找到责任微血管:74例三叉神经痛患者中有52例(70％)为小脑上动脉压迫;47例面肌痉挛患者中有29例(62％)为小脑前下动脉压迫;压迫方式多呈斜行交叉、平行及垂直交叉相贴. 结论 联合应用BTFE、e-THRIVE序列可清楚显示三叉神经、面神经及后颅窝微血管,再结合空间Link功能及多平面重建技术,可以找寻到责任微血管,为三叉神经痛及面肌痉挛患者行微血管减压术提供术前影像学指导.     

论DRGs和平衡计分卡在住院医疗服务管理中的作用

目的 建立患者住院医疗服务的战略规划,从而提高医疗行业整体价值.方法 战略地图勾勒出当地政府要实施的目标;同时采用诊断相关组(DRGs)使住院产出得到标准化分类并对各病例组赋予权重;将战略地图的目标和DRGs结果转化为平衡计分卡;再在此基础上确定行动计划,完成战略任务图.结果 在客户、内部流程、学习与成长、财务4个方面建立了16个目标、23项指标和13项任务.结论 战略地图有助于实现一个地区完整的住院医疗服务战略规划;诊断相关组是落实以患者为中心服务产出的管理核心工具;平衡记分卡有助于实现北京市住院医疗服务从宏观到微观的持续改进.     

基于平衡计分卡的医院绩效管理体系构建

目的通过绩效管理体系的完善,改善管理中存在的问题,激发员工积极性,提高医疗质量和医疗水平。方法分析存在的问题,借鉴成熟的平衡计分卡绩效管理理论和KPI方法,提出以BSC理论为基础的KPI绩效管理体系设计方法,有效应用于医院管理实践。结果依据医院管理模式及实际情况,建立以临床、医技、护理、职能等四个职系的基于平衡计分卡的分类、分层的三级KPI绩效考核体系。结论绩效体系的实施使得存在的问题得到明显改善,并在实践应用中不断总结,得出有效推行绩效管理体系的关键因素。     

染色体微阵列产前诊断8q13.3微缺失一例

目的应用染色体微阵列分析(chromosome microarray analysis,CMA)技术对1例超声结构异常胎儿进行全基因组拷贝数变异(copy number variations,CNVs)检测,探讨CMA在超声结构异常胎儿产前诊断中的意义。方法应用常规G显带染色体核型分析胎儿及其父母的染色体核型,应用CMA技术分析胎儿及其父母的CNVs。结果G显带核型分析显示胎儿核型与母亲一致,为46,XN,t(8;11)(q21.2;q13)mat,父亲核型正常;父母CMA检测结果均未见异常;胎儿的检测结果为arr[GRCh37]8q13.3(71314082-73322915)×1,提示一条8号染色体的8q13.3区域发生2.00 Mb缺失。结论超声结构异常胎儿染色体核型分析检出的平衡易位,需借助CMA等技术进一步确定是否存在微缺失微重复。     

Ten new cases of Balanced Reciprocal Translocation Mosaicism (BRTM): Reproductive implications,frequency and mechanism

Chromosomal anomalies are well known to be an important cause of infertility, sterility and pregnancy loss. Balanced Reciprocal Translocation Mosaicism (BRTM) is an extremely rare phenomenon, mainly observed in subjects with a normal phenotype accompanied by reproductive failure. To date the mechanism of origin and the incidence of BRTM are poorly defined.Here we describe 10 new cases of BRTM. In 9 cases chromosome analysis revealed the presence of two different cell lines, one with a normal karyotype and the second with an apparently balanced reciprocal translocation. In the remaining case, both cell lines showed two different, but apparently balanced, reciprocal translocations.We document the clinical implications of BRTM, discuss its frequency in our referred population and suggest that carrier individuals might be more frequent than expected.