难治性丙型肝炎研究新进展

随着聚乙二醇化干扰素(IFN)的普及应用和慢性丙型肝炎规范化治疗的开展,其治愈率不断提高.但疗效不佳的慢性丙型肝炎患者不断积累,难治性慢性丙型肝炎患者成为临床医生必须面对的挑战.难治性丙型肝炎患者应当分为两类,第一类为“难治疗”性慢性丙型肝炎患者,该类患者由于宿主条件限制,不能耐受IFN联合利巴韦林(RBV)的标准治疗,如儿童和老年人、慢性肾功能衰竭患者等.第二类为“难治愈”性慢性丙型肝炎患者,该类患者可以耐受标准治疗方案,但按照应答指导的治疗原则(RGT)治疗后,效果仍然不佳或复发.本文就近年关于难治性丙型肝炎的研究进展,从难治性丙型肝炎的定义、机制、治疗诸方面作一综述.     

CXCR4和CXCR7在甲状腺癌中的表达及病理意义

研究甲状腺癌组织中趋化因子4受体（CXCR4）和趋化因子7受体（CXCR7）的表达情况及临床病理意义。应用免疫组织化学PV-6000法及Westernblot法检测CXCR4与CXCR7在甲状腺癌中的表达。二者在甲状腺癌与甲状腺良性疾病组织的差异均具有统计学意义（P〈0．05）,在甲状腺癌中表达仅与淋巴结转移有关（P〈0．05）,CXCR4与CXCR7之间呈正相关。Westernblot结果提示二者在甲状腺癌中的表达率高于癌旁及甲状腺腺瘤。CXCR4和CXCR7的表达水平与淋巴结转移相关,可作为甲状腺癌预后的判断指标。     

Lenin,Hegel and Western Marxism: From the 1920s to 1953

I would like to thank the following people for helpful comments and criticisms: Janet Afary, Paul Buhle, Bud Burkhard, Olga Domanski, Nigel Gibson, Peter Hudis, Martin Jay, Douglas Kellner, Andrew Kliman, Pierre Lantz, Heinz Osterle, Jim Thomas, Lou Turner, and Alan Wald.     

Global Model Analysis of Cognitive Variability

Residual fluctuations produced in typical experimental methodologies are examined as correlated noises. The effective range of the correlations was assessed by determining whether the decay over look-back time is better described as a power law or exponential. Both of these decay laws contain free parameters and it is argued that it is not possible to distinguish their models on the basis of simple measures of goodness-of-fit. Global analyses that evaluate models on the basis of how well they generalize are conducted. The models are examined in terms of three constructs that all bear on generalization: cross-validity, flexibility, and representativeness. Quantitative assessment of a large ensemble of data suggests that the correlations decay over time as a power law. The conclusion is that human residual fluctuation is a correlated fractal.     

探讨人乳头瘤病毒L1蛋白功能及其临床意义

高危型别人乳头瘤病毒（HPV）感染在宫颈癌发生发展中具有重要作用。由于HPV L1蛋白结构特征及其精确的抗原特性,在粘附宿主细胞、识别病毒受体、协助病毒DNA的入胞转运中均发挥重要作用。检测患者宫颈损伤组织中L1蛋白的表达将有助于对患者是否具有传染性进行评估。本文将深刻思考HPV L1功能及其在感染机体并引发癌变的机制,以期更好的解读宫颈癌发病原理并最终应用于,强床治疗。     

Interference with reelin signaling in the lateral entorhinal cortex impairs spatial memory

Entorhinal neurons receive extensive intracortical projections, and form the primary input to the hippocampus via the perforant pathway. The glutamatergic cells of origin for the perforant pathway are distinguished by their expression of reelin, a glycoprotein involved in learning and synaptic plasticity. The functional significance of reelin signaling within the entorhinal cortex, however, remains unexplored. To determine whether interrupting entorhinal reelin signaling might have consequences for learning and memory, we administered recombinant receptor-associated protein (RAP) into the lateral entorhinal cortex (LEC) of young Long-Evans rats. RAP prevents reelin from binding to its receptors, and we verified the knockdown of reelin signaling by quantifying the phosphorylation state of reelin’s intracellular signaling target, disabled-1 (DAB1). Effective knockdown of reelin signaling was associated with impaired performance in the hippocampus-dependent version of the water maze. Moreover, inhibition of reelin signaling induced a localized loss of synaptic marker expression in the LEC. These observations support a role for entorhinal reelin signaling in spatial learning, and suggest that an intact reelin signaling pathway is essential for synaptic integrity in the adult entorhinal cortex.     

Whose Gene Is It? A Case Discussion About Familial Conflict over Genetic Testing for Breast Cancer

A multidisciplinary group of genetic and other professionals discuss a complex case of familial conflict over access to genetic information. One twin wishes to know the results of her deceased mother's tests for BRCA1 mutations; a second twin objects to researchers making this information available. As the case discussion unfolds, the apparent facts of this case are called into question and the lines of ethical certainty become less clear.     

The pathological left-handedness syndrome

A clinical syndrome of pathological left-handedness (PLH) is proposed to identify the pattern of correlative changes in lateral development associated with early brain injury in some manifest left-handers. This syndrome is believed to be caused by a hemispheric lesion that is predominantly left-sided (or bilateral asymmetric), which onsets before Age 6, and which encroaches upon the critical speech zones of the frontotemporal/frontoparietal cortex. The pattern of changes may include any or all of the following features: shifts in manual dominance, trophic changes in the extremities, transfer of hemispheric speech, and/or intrahemispheric reorganization of visuospatial cognitive functions. Although some of these correlates of PLH have long been known, they have not been recognized as an interrelated pattern of traits that constitute a clinical syndrome. Identification of these individuals, all manifest left-handers, will be shown to have implications for diagnosis/remediation and for models of recovery of function.     

Children's affective,behavioral, and cognitive responses to social comparison

Relative outcomes in social commerce with peers are potent determinants of cognitions and behavior in young children. Although there has been considerable attention given to the behavioral consequences of social comparisons following the receipt of rewards, there has been less concern with cognitive or affective consequences. Additionally, little is known about the accrued effects of multiple social comparison experiences that may be consistent or inconsistent with one another. In the present study, young children received a constant level of reward but the amount they saw a peer receive was varied. There were two sequences of reward distribution, and in a given sequence children received either the same number of rewards as the peer (=), more (+), or fewer (?). In a 3 × 3 factorial design all possible combinations occurred. A negative inequality in reward distribution, no matter where it fell in a sequence, made children sad and inclined children to distribute fewer rewards to peers. When a sequence contained an initial experience of positive inequality, children decreased subsequent levels of self-reward. Experiencing a comparison that revealed a negative inequality in reward distribution also disrupted children's accuracy in appraising the overall distribution of rewards: even when an initial negative inequality was completely offset by an equivalent experience of positive inequality, children inaccurately concluded that they had received fewer rewards than their peers.     

不同特质焦虑水平的选择性注意偏向

高特质焦虑个体常表现出对威胁性刺激的选择性注意偏向的特点。然而其潜在的神经机制目前仍不清楚。通过记录高、低特质焦虑者各17名进行情绪加工时的ERP,比较了两组个体在选择性注意偏向发生的时间进程和相关的神经反应的差异。结果发现,高特质焦虑者诱发出更大的N1,进一步发现恐惧图片比中性图片诱发更大的N1;而低特质焦虑者诱发了更大的N2,特质焦虑得分越低, N2波幅越大。结果初步说明高特质焦虑者加工早期对恐惧图片分配了较多的注意资源,并且其抑制执行功能可能受损;而低特质焦虑者较晚开始区分恐惧图片和中性图片。这些结果提供了支持认知-动机模型的新证据。