White matter alterations associated with chromosomal disorders

White matter alterations in chromosomal disorders have been reported mainly in 18q-syndrome. Our aim was to evaluate white matter alterations in patients with chromosomal abnormalities detected through conventional cytogenetic techniques. Forty-four patients with chromosomal abnormalities, excluding trisomy 21, were diagnosed in our hospital between May 1999 and December 2002 (24 males, 20 females; mean age 6 years 4 months [SD 3 years 2 months], range 0 to 18 years). Of the 44 patients, 14 had brain magnetic resonance imaging (12 males, 2 females; mean age 4 years 2 months [SD 4 years 4 months]; five with sex chromosomal disorders [SCD] and nine with autosomal chromosomal disorders [ACD]). Of these 14 patients, eight (four with SCD and four with ACD) had abnormal white matter findings of similar patterns. These patients had pseudonodular, subcortical, and periventricular white matter high signal intensity images in T2, and fluid-attenuated inversion recovery sequences that were isolated or confluent. The images did not correlate with the neurological clinical state. Given that eight of the 14 patients showed these lesions, their prevalence in different chromosomal abnormalities appears to be high, even though they have not been well reported in the literature. To our knowledge, these alterations have never been described in SCD. We concluded that unknown factors related to the myelination processes may be localized in different chromosomes.     

以科学发展观指导军校转制后的发展

军队院校转制要以科学发展观为指导、以人为本,实现平稳过渡,用发展的理念和办法解决转制中的问题.坚持适应市场理念,根据社会需求调整办学结构;坚持服务社会理念,在为地方服务中促进学校发展;坚持开放办学理念,利用社会资源拓宽发展空间;坚持科技创新理念,依托知识资源促进成果转化,打下可持续发展的牢固基础.     

以科学发展观指导高校学风建设

学风是学校的灵魂和生命,学风建设是学校永恒的主题。学风建设必须以科学发展观为指导,坚持以人为本,协调各方面的教育资源,加强师德培养,以教风带学风;坚持德育为先,以德育正学风;改善学生管理,以管理促学风;优化校园文化,以环境育学风。     

鸦胆子油乳在结直肠癌术后辅助化疗中的应用

目的探讨鸦胆子油乳在结直肠癌术后辅助化疗中的作用。方法将96例结直肠癌术后辅助化疗患者随机分为对照组和治疗组。对照组56例,采用FOLFOX方案,包括FOLFOX4和mFOLFOX6。治疗组40例,采用FOLFOX方案联合应用鸦胆子油乳。对比两组患者化疗后的不良反应。结果治疗组的恶心呕吐和白细胞下降发生率明显低于对照组,分别为：20%与39.3%,22.5%与44.6%。且对照组有4例白细胞重度下降,发生率为7.1%。其余不良反应两组比较差异均无统计学意义。结论鸦胆子油乳能减轻辅助化疗引起的毒副反应,提高患者对化疗的耐受能力,且自身毒副反应低。     

Combined open and endovascular repair of acute type A aortic dissection

In 3 patients previously undergoing one and one-half ventricular repair, right ventricular dysfunction progressed for more than 10 years. Their clinical features resembled those seen in patients undergoing the atriopulmonary Fontan procedure, and reoperation was carried out for conversion to total cavopulmonary connection. Hemodynamics improved subsequent to the circulatory renewal. In 2 patients having atrial arrhythmia before conversion, the resected right atrial wall illustrated grossly abnormal histopathology. These patients suffered from persistent sinus nodal dysfunction and eventually needed pacemaker implantation. The third patient died of sepsis 4 months later.     

Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin

Brain-derived neurotrophic factor (BDNF) is known to modulate synapse development and plasticity, but the source of synaptic BDNF and molecular mechanisms regulating BDNF release remain unclear. Using exogenous BDNF tagged with quantum dots (BDNF-QDs), we found that endocytosed BDNF-QDs were preferentially localized to postsynaptic sites in the dendrite of cultured hippocampal neurons. Repetitive neuronal spiking induced the release of BDNF-QDs at these sites, and this process required activation of glutamate receptors. Down-regulating complexin 1/2 (Cpx1/2) expression eliminated activity-induced BDNF-QD secretion, although the overall activity-independent secretion was elevated. Among eight synaptotagmin (Syt) isoforms examined, down-regulation of only Syt6 impaired activity-induced BDNF-QD secretion. In contrast, activity-induced release of endogenously synthesized BDNF did not depend on Syt6. Thus, neuronal activity could trigger the release of endosomal BDNF from postsynaptic dendrites in a Cpx- and Syt6-dependent manner, and endosomes containing BDNF may serve as a source of BDNF for activity-dependent synaptic modulation.Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family of secreted factors, is known to play important regulatory roles in neuronal survival and differentiation, synaptic development and plasticity, as well as many cognitive functions (1, 2). The findings that the synthesis and secretion of neurotrophins are regulated by neuronal activity prompted the suggestion that neurotrophins may regulate activity-dependent neural plasticity in the brain (3). Indeed, there is now substantial evidence indicating that activity-induced BDNF secretion at glutamatergic synapses is essential for long-term potentiation (LTP) (4), a cellular substrate for the learning and memory functions of neural circuits.The BDNF protein is first synthesized in the endoplasmic reticulum as a precursor protein, prepro-BDNF, which is then converted to pro-BDNF by removal of the signal peptide and further cleaved to generate the mature BDNF (5). Immunostaining and electron microscope studies using specific antibodies to the pro- and mature form of BDNF showed that pro-BDNF is colocalized with mature BDNF in secretory granules in presynaptic axon terminals (6), suggesting that the cleavage may occur in the secretory granule. However, under some experimental conditions, the processing of pro-BDNF into mature BDNF may occur extracellularly (7, 8). The secretory granule containing BDNF and pro-BDNF could undergo exocytosis upon neuronal excitation, as readily demonstrated in cell cultures using ELISA or fluorescent protein-tagged BDNF expressed in the neuron (9, 10). Besides secretory granules, neurotrophins within neuronal cytoplasm could also reside in endosomal compartments, resulting from endocytic uptake of extracellular neurotrophins secreted by the neuron itself or other nearby cells. Initially discovered as factors derived by target tissues, neurotrophins exert their actions via binding to neuronal surface receptors, including tropomyosin related kinase B (TrkB) and pan-neurotrophin receptor p75 (11). Neurotrophin binding to its receptor leads to cytoplasmic signaling as well as internalization of the neurotrophin-receptor complexes. These endocytosed neurotrophin-receptor complexes remain active in the form of “signaling endosomes” that could be transported over long distances within neuronal cytoplasm to exert its regulatory functions within the neuron (12–15). In this study, we have examined the possibility that these endosomes may undergo activity-dependent exocytosis at postsynaptic dendrites, thus providing an additional source of synaptic BDNF.To mark endosomes containing BDNF via the endocytic pathway, it is necessary to monitor BDNF trafficking in neurons. Although YFP-tagged BDNF has been used to study internalization of exogenous BDNF (16), such fluorescent protein-labeled BDNF was not suitable for real-time tracking of BDNF-containing endosomes at a high spatiotemporal resolution. In this study, we used BDNF linked to quantum dots (QDs), which are fluorescent nanoparticles with excellent photostability (17) and could be tracked in live cells with high signal-to-noise ratio and over unprecedented duration. This method has been used to examine endocytic recycling of synaptic vesicles (18) and axonal transport of endosomes containing neurotrophins (19, 20). In this study, we used time-lapse imaging of BDNF-QDs within cultured hippocampal neurons to monitor intracellular transport and localization of these endosomes. Furthermore, the sudden disappearance of cytoplasmic QD fluorescence in a solution containing fluorescence quencher was used to indicate the exocytosis of QD-containing endosomes. Previous studies have shown that extracellular false transmitters, soluble fluorescent markers, and membrane-bound fluorescent lipid dyes could be loaded into endosomes, which undergo exocytosis upon membrane depolarization (21–25). However, whether endosomes formed by receptor-mediated endocytosis is similarly regulated by activity remains unclear. Furthermore, the Ca²⁺-dependence and the kinetics of exocytosis of different endosomal vesicle populations may be differentially regulated by distinct vesicle-associated proteins.In the present study, we have explored the role of synaptotagmin (Syt) and complexin (Cpx) in regulating activity-induced exocytosis of BDNF-containing endosomes. As a universal cofactor in all Ca²⁺-triggered vesicular fusion reactions that have been examined (26), Cpx is known to serve both activating and clamping functions for vesicular exocytosis, by interacting with the Ca²⁺ sensor Syt and the assembled SNARE complexes at the plasma membrane (27). Various isoforms of Syt play distinct regulatory roles in various types of neurosecretion, presumably via their differential Ca²⁺ sensitivity. By manipulating the expression of various Syt and Cpx isoforms in cultured hippocampal neurons, we found that Syt6 and Cpx1/2 play essential regulatory roles in activity-dependent exocytosis of BDNF-containing endosomes. These results support the notion that BDNF-containing endosomes may serve as a source of extracellular BDNF for activity-dependent synaptic modulation and that Syt6 specifically regulates the exocytosis of BDNF-containing endosomes.     

以科学发展观指导军校转制后的发展

军队院校转制要以科学发展观为指导、以人为本,实现平稳过渡,用发展的理念和办法解决转制中的问题.坚持适应市场理念,根据社会需求调整办学结构;坚持服务社会理念,在为地方服务中促进学校发展;坚持开放办学理念,利用社会资源拓宽发展空间;坚持科技创新理念,依托知识资源促进成果转化,打下可持续发展的牢固基础.