产后抑郁症患者听感觉门控P50的研究

目的：探讨产后抑郁症患者感觉门控P50 的变化特征,为产后抑郁患者的早期预防提供参考依据。方法：采用配对听觉条件（S1）、测试（S2）刺激范式,对本院2011 年1 月至2012 年6 月收治的26 例产后抑郁症患者（实验组）进行听觉诱发电位P50检测,测量P50 的潜伏期、波幅,并与25 例健康被试者（对照组）的结果进行比较。结果：（1） 与对照组相比,实验组S1-P50 潜伏期[（56.62± 17.42） ms vs. （49.86 ± 15.21） ms],S2-P50 潜伏期[（57.36 ± 15.42） ms vs. （50.04 ± 16.27） ms]的差异均无统计学意义（P〉0.05）;（2）与对照组相比,实验组S1-P50 波幅[（3.58 ± 1.72） μV vs. （1.13 ± 0.91） μV]显著降低,差异有统计学意义（P〈0.05）;S2-P50 波幅[（1.32 ± 1.16） μV vs. （1.48 ± 1.05） μV]差异无统计学意义（P〉0.05）;（3） 与对照组相比,实验组S2/S1 波幅比值[（1.17 ± 0.26） vs.（0.41 ± 0.13）]显著升高,差异有统计学意义（P〈0.05）。结论：产后抑郁症患者感觉门控抑制能力有缺陷,P50 受损指标可能为评估产后抑郁症患者的潜在生物学指标。     

产后与非产后抑郁症患者事件相关电位P300的对比研究

目的:探讨产后抑郁症与非产后抑郁症患者事件相关电位P300的差异,为产后抑郁症的预防提供参考指标。方法:选择2011年1月~2012年10月解放军第三医院精神科收治的35例产后抑郁症患者(产后组)和36例非产后抑郁症患者(非产后组)为研究对象,并检测其事件相关电位P300,并与36名健康志愿者(对照组)的结果进行比较。结果:(1)与对照组相比,产后组、非产后组P2、N2、P3潜伏期均显著延迟,P2、N2、P3波幅均明显降低,差异均有统计学意义(P0.05)。(2)与产后组相比,非产后组P2、N2、P3潜伏期差异均无统计学意义(P0.05)。P2、N2波幅均偏高,差异均有统计学意义(P2[(5.0±2.1)ms vs.(3.9±1.8)μV],N2[(3.2±1.7)μV vs.(2.1±1.0)μV],P0.05),P3波幅差异无统计学意义(P0.05)。结论:产后与非产后抑郁症患者认知功能均受损,非产后抑郁患者受损程度大于产后抑郁患者;产后抑郁的外界感知能力和早期注意受损程度大于非产后抑郁患者。     

孤独症谱系障碍儿童听觉脑干反应特征分析

摘要 目的：探讨孤独症谱系障碍(autism spectrum disorder,ASD)儿童听觉脑干反应(auditory brainstem response,ABR)各波潜伏期和波间期特征与ASD行为表型间的关联。方法：对2019年7月-2020年12月来我科就诊的26例明确诊断的2~6岁ASD儿童的患儿进行声导抗,听性脑干反应,畸变产物耳声发射及多频稳态听觉诱发电位测试,以38例正常儿童为对照组,进行同样的测试,并对其测试结果进行统计分析。分析ASD儿童左右耳各波潜伏期,波间期特征及与ASD临床表型的关联。结果：ASD儿童左右耳Ⅰ,Ⅲ,Ⅴ波潜伏期分别为(1.42±0.09)ms,(3.67±0.09)ms,(5.65±0.13)ms;(1.45±0.11)ms,(3.69±0.08)ms,(5.62±0.15)ms。ASD组的右耳I,III波的潜伏期均值大于正常组 (P 值均＜0.05);ASD儿童两组间左耳III-V,右耳III-V,右耳I-V的波间期分别是(1.97±0.07)ms,(1.93±0.10)ms,(4.15±0.14)ms;ASD组的左耳III-V,右耳III-V,右耳I-V波间期均小于正常组(P 值均＜0.05);ASD组中小于等于3岁组与大于3岁组间ABR波间期差异不具有统计学意义。关联性分析发现,ASD儿童语言能力与右耳III波潜伏期,右耳最小阈值V波潜伏期负相关;社会行为能力与右耳I-III波间期负相关;社会生活能力与左耳最小阈值V波潜伏期负相关;而ABC评分与ASD儿童右耳III波潜伏期,左耳I-III波间期,右耳I-III波间期正相关。结论：ASD儿童存在异常的听觉脑干反应特征,且异常程度与 ASD 儿童语言,社会行为能力,社会生活能力的严重程度存在明显关联。     

心梗大鼠离体心脏的动作电位和不应期电生理研究

目的对比观察正常大鼠和心梗大鼠离体心脏动作电位和有效不应期的特点。方法用离体灌流吸附电极记录单向动作电位,常规电生理方法测量最大动作电位幅度(APA)、复极90%(MAP90)、复极50%(MAP50)、复极20%(MAP20)、有效不应期(ERP)。结果(1)和正常大鼠相比,心梗大鼠离体心脏左心房电生理参数MAP90(56.3±2.7vs.64.5±8.7,P<0.05)显著延长,ERP MAP90(0.89±0.2vs.0.78±0.3,P<0.05)减小,基础周期为250ms;右心室的电生理参数MAP90(67.6±14.1vs.134.1±26.7,P<0.001),ERP(55.0±3.53vs.69.0±8.9,P<0.05)明显延长,ERP MAP90(0.79±0.1vs.0.60±0.1,P<0.05)减小,基础周期为250ms;左心室的电生理参数MAP90(87.2±15.7vs.168.8±31.2,P<0.001)也呈显著延长,ERP(59.0±4.2vs.90.0±17.7,P<0.001),ERP MAP90(0.65±0.081vs.0.54±0.090,P<0.05)呈显著减小基础周期为250ms;(2)与正常大鼠相比,心梗大鼠的MAP90离散度[(LVMAP90-RVMAP90)(17.0±6.5vs.51.4±28.7,P<0.001)]、ERP离散度[(LVERP-RVERP)(4.0±2.2vs.20.0±7.9)P<0.001]显著增加,基础周期为250ms。结论心梗大鼠心脏不同部位的MAP的复极时间都显著性延长,MAP90和ERP离散度增加,这些电生理特点是促进折返形成、造成心律失常的主要原因。     

一氧化氮增加常氧和缺氧豚鼠心室肌细胞持续性钠电流

运用全细胞膜片钳记录缺氧条件下豚鼠心室肌持续性钠电流(INa.P)的变化及施加药物对其的影响,以探讨 INa.P 的本质及缺氧增大 INa.P 的机制。结果显示:(1)在常氧条件下,一氧化氮(NO)前体 L- 精氨酸(L-Arg)和供体硝普钠(SNP)浓度依赖性地增大INa.P; (2)INa.P 随缺氧时间延长而增大, 缺氧15 min 后施加 NO 合酶(NOS)抑制剂L- 硝基精氨酸甲酯(L-NAME), 不能使增大的INa.P 明显回复[(1.344 ±0.320) vs (1.301 ±0.317) pA/pF, P>0.05, n=5]; (3)缺氧时含L-NAME 的灌流液可使INa.P 明显减小,与单纯缺氧相比有显著差异[(0.914 ± 0.263), n=5 vs (1.344 ± 0.320) pA/pF, n=6, P<0.05], 但仍比常氧条件下增大[(0.914 ±0.263) vs (0.497 ±0.149) pA/pF, P<0.05, n=5]; (4)还原剂1,4-二硫代苏糖醇(DTT)不但可使L-Arg 及缺氧后施加SNP 增大的 INa.P 回复[(1.449 ± 0.522) vs (0.414 ± 0.067) pA/pF, P<0.01, n = 6 和(0.436 ± 0.141) vs (1.786 ± 0.636) pA/pF,P<0.01, n=5],而且使正常的 INa.P 减小[(0.396 ± 0.057) pA/pF vs (0.442 ± 0.056) pA/pF, P<0.01, n=6]。本实验结果表明缺氧可增大心室肌细胞的INa.P, 其作用机制可能是缺氧时心肌产生的NO 通过氧化细胞膜上钠通道蛋白所致,正常INa.P 的产生     

自然流产患者绒毛和蜕膜中ZEB1 的差异性表达及意义*

摘要目的：检测锌指结合蛋白（zinc finger E-box-binding protein ,ZEB1）在自然流产患者绒毛和蜕膜组织中的差异性表达。方法： 选取2010 年3 月到2011 年3 月在我院妇产科门诊进行人工流产的患者,分为正常人工流产（对照组50 例）和自然流产（实验组 50 例）两组,两组年龄和孕周间差异无统计学意义（P＞0.05）。用荧光实时定量PCR（qRT-PCR）技术检测在绒毛和蜕膜组织中 ZEB1 mRNA的表达量。结果：自然流产患者绒毛（0.835± 0.047）中ZEB1的表达量低于对照组（1.942± 0.095）,自然流产患者蜕 膜（0.65± 0.058）中ZEB1 的表达量低于对照组（1.13± 0.084）,差异具有统计学意义(P＜0.05)。结论：绒毛及蜕膜组织中ZEB1 的 异常表达可能参与自然流产的发生发展过程。     

腺苷抗豚鼠室性心律失常的电生理研究

实验用全细胞膜片钳技术在单个豚鼠心室肌细胞上研究了腺苷 (Ado)对正常及异丙肾上腺素 (Iso)致豚鼠心室肌细胞动作电位、迟后除极 (DAD)、L 型钙电流 (ICa.L)和短暂内向电流 (Iti)的作用。结果表明 :(1)Ado在2 0～ 10 0 μmol/L时对豚鼠心室肌细胞动作电位和ICa .L无明显直接作用 ,但却可明显降低Iso所致的动作电位时程(APD)延长和ICa .L峰值增大 ,Iso (10nmol/L)使细胞APD50 从 3 40± 2 1ms延长到 486± 2 8ms (P <0 0 1) ,APD90从 3 61± 17ms延长至 5 0 1± 2 9ms (P <0 0 1) ;ICa .L峰值从 - 6 5 3± 1 4pA/pF增大到 - 18 2 8± 2 4pA/pF (P <0 0 1) ,电流电压曲线明显左移和下移 ;Ado (5 0 μmol/L)使APD50 和APD90 降至 40 3± 19ms和 419± 2 6ms ,但并不影响动作电位其它参数 ,使ICa.L峰值降低至 - 10 2± 1 5pA/pF (P <0 0 1)。 (2 )Iso (3 0nmol/L)可诱发心室肌细胞产生DADs,其发生率为 10 0 % ;Ado (5 0 μmol/L)可完全抑制Iso引发DADs;细胞经 - 40～ +2 0mV、时程 2s的除极电压 ,Iso (3 0nmol/L)诱导出Iti,其发生率为 10 0 % ;Ado (5 0 μmol/L)可明显抑制Iso致Iti的发生 ,其发生率降为 14 3 %。研究结果提示 ,Ado对豚鼠心室肌细胞动作电位和ICa.L无明显直接作用 ,但却可显著降低Is     

siRNA下调EZH2 基因对肾癌细胞系769-P增殖的影响

目的：运用小干扰RNA下调果蝇zeste 基因增强子人类同源物（enhancer of zeste homolog 2,EZH2）在肾癌细胞系769-P 中 的表达,明确其对肾癌细胞增殖的影响。方法：将处于对数生长期769-P 细胞分为实验组（experiment group）、阴性对照组(negative group)、空白对照组（blank group）,合成靶向EZH2 基因的小干扰RNA片段（EZH2-siRNA）和无效序列片段后,通过脂质体介导分 别转染至实理组和阴性对照组,空白对照组未做任何处理。以qRealtime-PCR 检测EZH2 基因mRNA 水平的变化情况,以MTT 法检测各组细胞增殖变化;流式细胞术（FCM）检测转染后细胞周期变化情况。结果：实理组中EZH2 在mRNA 表达水平明显受 抑制;MTT实验中第4 天始,实验组中769-P 细胞的增殖能力开始受抑制,第5 天时实验组细胞抑制更明显,与阴性对照组和空 白组比较差异有统计学意义（P < 0.05）。siRNA 转染后实验组中G0/G1 期细胞比例明显增多(81.32± 3.14)%,与阴性对照组 (44.13± 1.52)%和空白对照组(45.71± 2.32)%差异有统计学意义。结论：EZH2-siRNA 可有效下调并抑制肾癌细胞769-P的增殖, EZH2在肾癌的发生、发展中发挥了重要作用,为下一步研究肾癌基因治疗提供了理论支持。     

益生菌制剂对轮状病毒性肠炎患儿肠道菌群和免疫功能的影响

目的观察益生菌制剂辅助治疗儿童轮状病毒性肠炎的临床疗效及对患儿肠道菌群和免疫功能的影响。方法以160例轮状病毒性肠炎患儿为研究对象,随机分为对照组(n=80)和研究组(n=80)。对照组患儿给予消旋卡多曲颗粒联合蒙脱石散治疗,研究组患儿在此基础上联合双歧杆菌乳杆菌三联活菌片治疗。观察患儿治疗期间药物不良反应,患儿腹泻停止时间、发热消退时间和呕吐停止时间。分别于治疗前后检测患儿血清免疫球蛋白水平和肠道菌群状况,评价患儿治疗效果。结果研究组患儿腹泻停止时间[(2.41±0.70)d]、发热消退时间[(1.71±0.52)d]和呕吐停止时间[(2.09±0.62)d]均显著短于对照组(均P<0.05)。研究组患儿轮状病毒性肠炎总体治疗有效率显著高于对照组(95.00% vs 83.75%,χ²=5.331,P=0.021)。研究组患儿治疗后血清IgG和IgM水平[(5.83±0.59)g/L和(1.07±0.16)g/L]显著高于对照组(均P<0.05)。研究组患儿治疗后肠道菌群正常者比例显著高于对照组(92.50% vs 76.25%,χ²=8.012,P=0.005)。两组患儿恶心、便秘、皮疹和嗜睡等药物不良反应总体发生率差异无统计学意义(10.00% vs 8.75%,χ²=0.074,P=0.786)。结论益生菌制剂可有效缩短轮状病毒性肠炎患儿临床症状改善周期,提高疗效,改善患儿免疫功能,纠正肠道菌群失调状况,且不增加药物不良反应,值得临床推广使用。     

瞬目反射对老年人脑干梗死诊断价值的研究

目的：探讨瞬目反射对老年人脑干梗死的诊断价值。方法：采用神经电生理检查方法对100例老年人（50例健康受试者、50例脑干梗死患者）进行BR检测。确定BR正常值,记录各组潜伏期和波幅的变化,与正常对照组比较;并对50例脑干梗死患者行MRI检测,比较MRI与BR对脑干梗死的诊断阳性率。结果：健康对照组BR各波潜伏期的平均值分别是R1为10.9 ms、R2为30.4 ms、R2＇为29.5 ms,波幅的平均值分别是R1为306.3μv、R2为276.7μv、R2＇为257.8μv。脑干梗死组中有44例BR异常,其中6例中脑梗死患者BR正常;36例桥脑梗死患者BR完全异常;8例延髓梗死患者R1正常,结果具有统计学差异（P〈0.01）。BR与MRI检查对脑干梗死的诊断阳性率比较无统计学差异（P〉0.05）。结论：瞬目反射是一种早期诊断脑干梗死的有价值的临床电生理方法,相对于传统MRI检查,其诊断率稍低,但能敏感地反应脑干尤其是脑桥的病变情况,对定位诊断有重要意义。     

Gating of spontaneous somatic sensations by movement

Movement is known to attenuate the perception of tactile stimuli delivered on the moving part of the body, and this gating diminishes the greater the distance from the moving part. However, does it influence the perception of sensations occurring spontaneously without external triggers? In Experiment 1, participants were asked to focus on one hand while moving or not moving their thumb, and thereafter to map and describe the spatial and qualitative attributes of sensations perceived over the remaining, motionless part of the hand. The results show that movement reduces the frequency, spatial extent, and intensity of sensations, but also participants’ confidence about their spatial characteristics. As expected, gating decreased the greater the distance from the moving thumb. Furthermore, gating was greater for distal than proximal segments of the hand, suggesting a hierarchical proximo-distal suppression. Experiment 2 ruled out the possibility that these effects were due to tactile sensations elicited by movement. Possible mechanisms of gating in the case of spontaneous sensations are discussed.     

慢性吗啡给予、戒断及再给药过程中大鼠海马感觉门控的动态变化

药物成瘾被认为是药物长期作用于脑而产生的一种慢性复吸性脑疾病,长期反复的药物（如吗啡）滥用会导致一系列严重后果,如药物依赖、药物耐受、强迫性药物寻求等。本实验利用条件化位置偏好（conditioned place preference,CPP）模型来检测大鼠对吗啡依赖和心理渴求等过程;采用双声刺激听觉诱发电位来研究大鼠在慢性吗啡给予、戒断以及再给药过程中海马感觉门控（N40）的动态变化。吗啡组大鼠注射吗啡（10mg／kg,i．p．）12d,经历第一次戒断12d,再次注射吗啡（2．5mg／kg,i．P．）1d,之后经历第二次戒断2d;对照组大鼠注射同体积生理盐水,其余实验条件与吗啡组相同。CPP实验表明,这种药物给予方法促使大鼠对吗啡产生药物依赖和心理渴求。双声刺激诱发电位实验表明,吗啡组大鼠在吗啡给予期间海马感觉门控受到损伤;第一次戒断期的第1～2天海马感觉门控能力减弱,第3天增强,第4～12天逐渐恢复到正常水平;再次给予吗啡后海马感觉门控能力与对照组相比显著降低,并且随后2d的戒断期内海马感觉门控能力也一直保持较低水平,表明再次给药使大鼠海马感觉门控对吗啡更加敏感化。结果提示,长期反复的吗啡给予及再给药干扰了海马的感觉门控能力,吗啡成瘾对大脑可能产生长期影响。     

Inhibitory deficit in schizophrenia is not necessarily a GABAergic deficit

1. Current evidence strongly supports the idea of an inhibitory deficit as a central pathophysiological mechanism in schizophrenia. This deficit has been well documented in sensory gating and paired-pulse studies and may be related to decreases in inhibitory interneurons found in schizophrenic patients.2. The GABAergic system has been repeatedly postulated to mediate this deficit, but the findings are controversial, at least in some areas, and mostly negative regarding treatment with drugs enhancing GABAergic activity. Therefore, the scope of mediators of this inhibitory deficit should be widened and the neuromodulator adenosine is proposed as a candidate to be further studied.3. A state of adenosinergic hypoactivity in schizophrenia is compatible not only with the inhibitory deficit but also with symptoms, clinical response to antipsychotics, impaired sensory gating, deteriorating course, increased smoking, and sleep alterations reported in schizophrenia.4. It is concluded that although the GABAergic system should be further studied, especially in sensory gating model in humans, emphasis on other inhibitory mechanisms may prove useful and provide more effective treatment.     

Cross-modal modulation gates nociceptive inputs in Drosophila

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Fast and slow voltage sensor movements in HERG potassium channels

HERG encodes an inwardly-rectifying potassium channel that plays an important role in repolarization of the cardiac action potential. Inward rectification of HERG channels results from rapid and voltage-dependent inactivation gating, combined with very slow activation gating. We asked whether the voltage sensor is implicated in the unusual properties of HERG gating: does the voltage sensor move slowly to account for slow activation and deactivation, or could the voltage sensor move rapidly to account for the rapid kinetics and intrinsic voltage dependence of inactivation? To probe voltage sensor movement, we used a fluorescence technique to examine conformational changes near the positively charged S4 region. Fluorescent probes attached to three different residues on the NH₂-terminal end of the S4 region (E518C, E519C, and L520C) reported both fast and slow voltage-dependent changes in fluorescence. The slow changes in fluorescence correlated strongly with activation gating, suggesting that the slow activation gating of HERG results from slow voltage sensor movement. The fast changes in fluorescence showed voltage dependence and kinetics similar to inactivation gating, though these fluorescence signals were not affected by external tetraethylammonium blockade or mutations that alter inactivation. A working model with two types of voltage sensor movement is proposed as a framework for understanding HERG channel gating and the fluorescence signals.     

A Neural Basis for Categorizing Sensory Stimuli to Enhance Decision Accuracy

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P50 Sensory Gating in Infants

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood disorder, and schizophrenia. There has been increasing interest in the neurodevelopmental components of these attentional deficits; neurodevelopmental meaning that while the deficits become clinically prominent in childhood or adulthood, the deficits are the results of problems in brain development that begin in infancy or even prenatally. Despite this interest, there are few methods for assessing attention very early in infancy. This report focuses on one method, infant auditory P50 sensory gating.Attention has several components. One of the earliest components of attention, termed sensory gating, allows the brain to tune out repetitive, noninformative sensory information. Auditory P50 sensory gating refers to one task designed to measure sensory gating using changes in EEG. When identical auditory stimuli are presented 500 ms apart, the evoked response (change in the EEG associated with the processing of the click) to the second stimulus is generally reduced relative to the response to the first stimulus (i.e. the response is "gated"). When response to the second stimulus is not reduced, this is considered a poor sensory gating, is reflective of impaired cerebral inhibition, and is correlated with attentional deficits.Because the auditory P50 sensory gating task is passive, it is of potential utility in the study of young infants and may provide a window into the developmental time course of attentional deficits in a variety of neuropsychiatric disorders. The goal of this presentation is to describe the methodology for assessing infant auditory P50 sensory gating, a methodology adapted from those used in studies of adult populations.     

A neuropeptidergic circuit gates selective escape behavior of Drosophila larvae

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Multiple modalities converge on a common gate to control K2P channel function

Members of the K_2P potassium channel family regulate neuronal excitability and are implicated in pain, anaesthetic responses, thermosensation, neuroprotection, and mood. Unlike other potassium channels, K_2Ps are gated by remarkably diverse stimuli that include chemical, thermal, and mechanical modalities. It has remained unclear whether the various gating inputs act through separate or common channel elements. Here, we show that protons, heat, and pressure affect activity of the prototypical, polymodal K_2P, K_2P2.1 (KCNK2/TREK‐1), at a common molecular gate that comprises elements of the pore‐forming segments and the N‐terminal end of the M4 transmembrane segment. We further demonstrate that the M4 gating element is conserved among K_2Ps and is employed regardless of whether the gating stimuli are inhibitory or activating. Our results define a unique gating mechanism shared by K_2P family members and suggest that their diverse sensory properties are achieved by coupling different molecular sensors to a conserved core gating apparatus.