静止性脑梗死风险预测量表的构建和验证

【摘要】
目的 调查与静止性脑梗死（silent brain infarction，SBI）相关的独立影响因素，构建SBI风险预测量
表并验证。
方法 在单中心横断面研究中，前瞻性连续纳入无神经系统疾病既往史的体检者，收集其人口学
信息，高血压、糖尿病等血管危险因素，血脂、糖化血红蛋白、血浆同型半胱氨酸等化验结果录入数
据库。采用标准影像学操作规范进行头颅MRI扫描，并由影像学医师盲法判读，将受试者分为SBI组
和无SBI组。将所有受试者按照3∶1比例随机分为训练集和验证集，在训练集中采用单因素和多因素
Logistic回归分析SBI的独立影响因素，构建SBI预测量表。在训练集和验证集中应用ROC曲线检验量表
的区分度，应用Hosmer-Lemeshow分析检验量表的校准度。
结果 共有633例研究对象纳入研究，平均年龄52.0±10.5岁，女性272例（43.0%）。训练集（475
例）和验证集（158例）两个样本集合的基线特征均衡。校正混杂因素后多因素分析显示，年龄≥45
岁（OR 8.37，95%CI 1.12～62.80，P =0.039），高血压（OR 2.30，95%CI 1.08～4.90，P =0.032），同型半
胱氨酸（Q2～Q3：OR 6.89，95%CI 0.89～53.10，P =0.064；Q4：OR 13.6，95%CI 1.74～105.87，P =0.013）
与SBI风险独立相关。根据OR 值构建SBI危险评分（SBI risk score，SBI-RS）量表，量表赋值为：年龄
≥45岁赋值8分；有高血压赋值2分；同型半胱氨酸根据四分位分层分别赋值为0分、7分和14分。SBIRS
在训练集和验证集中ROC曲线显示曲线下面积分别为0.77（95%CI 0.69～0.84，P＜0.001）和0.76
（95%CI 0.63～0.88，P＜0.001），区分度良好。Hosmer-Lemeshow相关分析提示SBI-RS具有较好的校准度
（P＞0.05）。
结论 在健康体检人群中，SBI -RS具有较好的区分度和校准度，可以帮助识别SBI高危人群。     

无症状性脑梗死患者的心理功能测评

随着高敏度的脑成像技术如ＣＴ、ＭＲＩ在临床的广泛应用 ,发现了许多临床上无明显症状、体征或症状、体征与既往卒中史不相关的梗死灶 ,称之为无症状性脑梗死 (ａｓｙｍｐｔｏｍａｔｉｃｉｎｆａｒｃｔ)或静止性脑梗死(ｓｉｌｅｎｔｃｅｒｅｂｒａｌｉｎｆａｒｃｔｉｏｎ ,ＳＣＩ)。虽然这些病人经传统的神经系统检查未发现明显的异常 ,但有学者认为他们存在明显的认知功能障碍、精细运动障碍及情感障碍等。本文对 38例ＳＣＩ及 30例对照组进行了认知功能、记忆、精细运动、感知觉及情感等方面的评价 ,有利于ＳＣＩ以及血管性痴呆的早期防…     

Spatial arrangements of responses by cells in the cat visual cortex to light and dark bars and edges

Summary Detailed examination is made of the responses of visual cortical cells (area 17, border 17–18 and adjacent area 18) in the anaesthetized cat to stationary flashing bars and to bars (lines) and edges moving at their optimal velocities. Particular attention is given to the receptive field organization of cells in the simple family. While there is good general agreement between the main receptive field subregions revealed by stationary and moving stimuli, the responses to moving light and dark bars, supplemented by the responses to moving light and dark edges, provide a much more rapid, accurate and complete guide to the spatial organization of the receptive fields than do the response profiles to a stationary flashing bar. Moving light and dark bars between them generally reveal more subregions in the receptive fields of simple cells than is evident from the response profiles to a stationary flashing bar, particularly when the receptive fields have many subregions. In addition the responses to moving edges provide a rapid guide to spatial summation across the width of a subregion and the possible antagonistic effects of the next subregion in sequence.Two subclasses of cells in the simple family have been recognized: ordinary simple and fast simple cells. Two cell classes (A-cells and silent periodic cells) having properties intermediate between simple and complex types are discriminated and their properties described.     

Silent period to transcranial magnetic stimulation: construction and properties of stimulus–response curves in healthy volunteers

Silent period (SP) is widely used in transcranial magnetic stimulation studies. Methodologically, SP is usually elicited at stimulus intensities corresponding to a certain percentage of corticomotor threshold. Because this approach might lead to factitious SP changes, the present study was designed to develop, in a stepwise manner, a method for investigating SP independently of corticomotor threshold. First, stimulus–response (S–R) curves of SP against stimulus intensity (SI) were constructed and quantitatively described in healthy volunteers. Second, various methodological issues such as the optimum model for describing the relationship between SP duration and SI and the importance of the type of stimulating coil were addressed. Finally, the proposed method and a commonly used method (eliciting SPs at 130% MT SI) were directly compared for a group of epileptic patients for whom administration of oxcarbazepine resulted in significant corticomotor threshold elevation. Twenty-one subjects (eleven females, median age, 38 years) were studied. SPs were obtained with a figure-of-eight coil using a standardized procedure (recording, FDI). Pilot experiments indicated that at least four trials were required, at each intensity level, to estimate the mean SP duration within 10% of the true mean. Therefore, SPs were determined from the average of four trials with 5% increments from 5 to 100% maximum SI. In a second set of experiments, SPs were obtained for fifteen subjects using a circular coil. In a third set of experiments, eight epileptic patients were studied before and after administration of oxcarbazepine (mean dose 1553 mg, range 900–1800 mg). The S–R curves were fitted to a Boltzman function and to first-order to fourth-order polynomial and sigmoid functions. The Boltzman function described the data accurately (R²=0.947–0.990). In addition, direct comparison of the six models with an F-test proved the superiority of the first. The best-fit parameters of the reference curve, i.e. the maximum and minimum values, the slope, and V₅₀ (the SI at which SP duration is halfway between Min and Max) were 230.8±3.31 ms (x±SEM), –11.51±3.31 ms, 11.56±0.65%, and 49.82±0.65%, respectively. When the curves obtained with the circular coil were compared with those obtained with the figure-of-eight coil, there were differences between V₅₀ (51.69±0.72 vs 47.95±0.82, P<0.001) and SP threshold (31.15 vs 24.77, P<0.01) whereas the other best-fit values did not differ significantly. Oxcarbazepine increased corticomotor threshold from 45.3±5.8% at baseline to 59.4±10.4% (P<0.001). According to the commonly used method, the drug significantly prolonged SP (from 117.6±42.4 ms to 143.5±46.5 ms, P<0.001) and, consequently, enhanced brain inhibition. In contrast, study of the SP curves led to the conclusion that oxcarbazepine does not affect the Max value and slope but significantly increases V₅₀ and SP threshold (from 54.5±4.9% to 59.9±7.2% and from 29.1±6.4% to 34.6±6.8%, respectively, P<0.01). These findings imply that oxcarbazepine does not enhance brain inhibitory mechanisms. Thus, in situations characterized by significant changes in corticomotor threshold the proposed method provides results clearly different from a commonly used approach. It is concluded that S–R curves obtained with a figure-of-eight coil in 5% increments and fitted to a Boltzman function provide an accurate, comprehensive, and clinically applicable method for exploring SP.Presented in part at the meeting of the EFNS, Helsinki, September 2003     

隐性心肌缺血者血脂及血液流变学指标的检测及意义

目的:观察隐性心肌缺血者血脂及血液流变指标的变化,为早期发现和防治冠心病提供实验室依据。方法:选择性别和年龄大致相同的隐性心肌缺血者和心电图正常的健康对照人群,同时进行血脂和血液流变学指标检测,比较两组两类指标的差异。结果:隐性心肌缺血者的总胆固醇、甘油三酯和血液低、中、高切粘度及红细胞聚集指数、变形指数均明显高于正常对照组,每项指标的异常率在两组间相差明显。结论::血脂和血液流变学检测结果可作为隐性心肌缺血和冠心病早期诊断的实验室指标。     

The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study

This study was designed to examine the effects of nisoldipine(relative to placebo), a new dihydropyridine calcium entry blockingagent, in the treatment of silent ischaemia in conventionaldoses. A total of 409 patients with proven coronary artery diseasewere screened and of this 64 had at least six episodes or atotal duration of 30 mm of ST segment depression (1 mm lastingat least 1 min) over 48 h. Fifty-two patients ultimately completeda randomized double-blind cross-over study comparing nisoldipine5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and numberof episodes of ST segment depression when compared to placeboon treatment with nisoldipine 5 mg twice a day and nisoldipine10 mg daily. However, the confidence limits were wide and crossedthe no-treatment effect line. In addition, the nisoldipine dosesneither affected the circadian distribution of ischaemic episodesnor caused an alteration of the workload achieved either atpeak exercise or at 1 mm ST segment depression measured 24 hafter nidoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients withproven coronary artery disease is relatively uncommon, it accountsfor approximately 16% of patients with positive exercise. Inthese patients nisoldipine, given as 5mg twice a day and 10mg daily, showed no significant therapeutic effects, eitheron the frequency or severity of silent ischaemia. New formulationsof slow release nisoldipine are consequently being developedso that a fuller 24 h therapeutic profile may be obtained.     

Brain-derived neurotrophic factor requirement for activity-dependent maturation of glutamatergic synapse in developing mouse somatosensory cortex

The maturation of cortical circuitry critically depends on experience. Recently, a model of silent synapse has been proposed as a mechanism of activity-mediated transition of immature synapse to mature synapse. It is not clear, however, how activity could regulate this transition. Here, we show the evidence that endogenous brain-derived neurotrophic factor (BDNF) is required for the maturation of glutamatergic synapse in developing mouse somatosensory cortex. Field potential recordings of thalamocortical glutamatergic synaptic activity with brain slices from the BDNF mutant mice showed that AMPA receptor responses are low, but NMDA receptor responses remain high in layer 4, thus, the relative contribution of AMPA receptor response is significantly lower compared to the age-matched wild-type mouse. Furthermore, optical images of development of thalamocortical connectivity with a voltage-sensitive dye showed that NMDA receptor-dominant synapse is established first in layer 4 and layer 5/6 then AMPA receptor response appears later in concomitant with reduction of NMDA receptor response in layer 4 and that the maturation of the silent synapse is impaired in the BDNF mutant mice. In layer 5/6, NMDA receptor response was suppressed without upregulation of AMPA receptor response. This process also required BDNF function. Interestingly, whisker-trimming of the wild-type mouse from just after birth showed quite similar results with the homozygous mutant of their whiskers left intact. Therefore, we would propose that BDNF is a critical mediator for the maturation of glutamatergic synapse in developing mouse somatosensory cortex.     

沉默信息调节蛋白1在缺血性脑损伤中的神经保护作用

近年来，沉默信息调节蛋白1（silent information regulator protein 1，SIRT1）作为依赖NAD+ 的组蛋白去乙酰化酶被广泛地研究。SIRT1存在于机体各组织细胞中，通过去乙酰化修饰，调节细胞 的多种生理过程，在能量守恒、细胞氧化、衰老及凋亡等方面发挥重要作用。目前认为，SIRT1在缺血 性脑损伤中起到神经保护作用，可能通过调控细胞能量代谢，抗炎性反应、抗细胞凋亡等方面发挥 作用。本文主要综述了SIRT1在缺血性脑损伤中的神经保护作用。