关键词： Cytomegalovirus   White matter abnormality   Sensorineural hearing loss   Ganciclovir   Neurodevelopment  

摘要： BackgroundCongenital cytomegalovirus (cCMV) infection leads to sensorineural hearing loss (SNHL) and neurodevelopmental delays. However, the long-term outcomes of cCMV infection with severe neurological manifestations in infancy remain *** presentationThe patient was a one-month-old girl visited owing to abnormalities in neonatal hearing screening. Central nervous system involvement including intracranial calcification and extensive white matter abnormalities was identified. Right SNHL (50dB) was detected by auditory brain response (ABR) testing. The cause of her hearing loss was determined to be cCMV infection by polymerase chain reaction (PCR) using a dried blood spot. At 1.5months of age, the patient was treated with intravenous ganciclovir (GCV) for 5weeks followed by oral valganciclovir (VGCV) for an additional 6weeks. Cytomegalovirus (CMV) loads in her urine continued to be detected until she was 10years old. Fortunately, during this time, her right hearing loss did not deteriorate, and her left hearing remained normal. Furthermore, the extensive abnormal areas of white matter observed at 1month of age mostly disappeared by the time the patient was 9years old. Her neurodevelopmental score was normal, and motor milestones were not delayed as of 10years of ***, we report the 10-year follow-up of a patient with cCMV who showed normal neurodevelopment, no progression of hearing loss, and ameliorating magnetic resonance imaging (MRI) findings, despite having various complications and severe neurological findings during infancy.

关键词： Cerebrum   cancer cell culture   FKBP12 Rapamycin Complex Associated Protein 1   Central Nervous System Diseases   Neurologic Disorders   tumor growth   Cancer Cell Growth   Protein Kinases  

摘要： Mechanistic target of rapamycin (mTOR) promotes cell proliferation, growth, and survival and is overactivated in many tumors and central nervous system disorders. PQR620 (3) is a novel, potent, selective, and brain penetrable inhibitor of mTORC1/2 kinase. PQR620 (3) showed excellent selectivity for mTOR over PI3K and protein kinases and efficiently prevented cancer cell growth in a 66 cancer cell line panel. In C57BL/6J and Sprague-Dawley mice, maximum concentration (C-max) in plasma and brain was reached after 30 min, with a half-life (t(1/2)) > 5 h. In an ovarian carcinoma mouse xenograft model (OVCAR-3), daily dosing of PQR620 (3) inhibited tumor growth significantly. Moreover, PQR620 (3) attenuated epileptic seizures in a tuberous sclerosis complex (TSC) mouse model. In conclusion, PQR620 (3) inhibits mTOR kinase potently and selectively, shows antitumor effects in vitro and in vivo, and promises advantages in CNS indications due to its brain/plasma distribution ratio.

摘要： Manganese superoxide dismutase (MnSOD) lysine acetylation is a critical post-translational modification that regulates its detoxification activity to direct cellular ROS levels and metabolic balance. In this regard, our lab has shown the change in structural configuration and gain of peroxidase function upon MnSOD-K68 acetylation. As such, this study aims to investigate the role of MnSOD-K68 acetylation (K68-Ac) status, as well as its potential biological significance both in vitro and in vivo. To experimentally evaluate the effects of MnSOD acetylation, recombinant mutants were constructed where lysine was substituted with glutamine (Q) or arginine (R), an acetylation or deacetylation mimic, respectively. The results showed that enforced expression of MnSOD^K68Q disrupts mitochondrial metabolism and ultrastructure, and functions as an in vitro oncogene. To examine the physiological significance of MnSOD acetylation, a genetically engineered whole-body MnSOD^K68Q knock-in mouse has been constructed. Biallelic knock-in (MnSOD^K68Q/K68Q) mice around 3 weeks of age display a significant phenotype that includes (1) small size, (2) lean body mass, (3) significant weight loss, and (4) a fatal neurological disorder involving loss of lower extremity movement, tremors, and dyskinesia. Daily injection of GC4419, a Mn-based chemical drug that replaces MnSOD activity by removing superoxide, extended the lifespan (from 25 days to 45 days), partially rescued motor coordination loss (as tested by rotarod) and delayed the onset of the profound neurological symptoms. In addition, electron microscopy identified disrupted mitochondrial structure in multiple tissues including liver, skeletal muscles, and the substantia nigra. Lastly, whole-body monoallelic female mice (MnSOD^WT/K68Q) of six months also display mammary tissue with smaller, disorganized fat cells, characteristics of ductal hyperplasia, and areas of cells consistent with ductal carc

关键词： blood-brain barrier   drug delivery   nanomaterials   nanoparticles   neurological diseases  

摘要： Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood-brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial-based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease-targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial-mediated treatment of neurological diseases.

关键词： PBL教学模式   神经病学   临床教学  

摘要： 神经病学是一门具有高度抽象性、逻辑性和专业性的临床学科,临床教学是其教学模式的重要组成部分。将PBL教学模式应用于神经病学临床教学中,有利于培养医学生的临床思维,促进其向临床医生角色转变。

关键词： PCGF2   Polycomb Group Ring Finger 2   MEL18   intellectual disability   dysmorphism   polymicrogyria  

摘要： PCGF2 encodes the polycomb group ring finger 2 protein, a transcriptional repressor involved in cell proliferation, differentiation, and embryogenesis. PCGF2 is a component of the polycomb repressive complex 1 (PRC1), a multiprotein complex which controls gene silencing through histone modification and chromatin remodelling. We report the phenotypic characterization of 13 patients (11 unrelated individuals and a pair of monozygotic twins) with missense mutations in PCGF2. All the mutations affected the same highly conserved proline in PCGF2 and were de novo, excepting maternal mosaicism in one. The patients demonstrated a recognizable facial gestalt, intellectual disability, feeding problems, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Computer structural modeling suggests the substitutions alter an N-terminal loop of PCGF2 critical for histone biding. Mutant PCGF2 may have dominant-negative effects, sequestering PRC1 components into complexes that lack the ability to interact efficiently with histones. These findings demonstrate the important role of PCGF2 in human development and confirm that heterozygous substitutions of the Pro65 residue of PCGF2 cause a recognizable syndrome characterized by distinctive craniofacial, neurological, cardiovascular, and skeletal features.

关键词： 翻转课堂   CBT   临床   教学   应用   神经病学  

摘要： 目的探究临床专业学生采用翻转课堂与CBT联合教学模式的效果和作用。方法选择2016级70名临床专业学生作为研究对象。采用抽签法,将其分为实验组与参照组,每组均35名。其中,参照组采用常规小班教学模式,实验组实施翻转课堂与CBT联合教学模式,对比2组学生神经病学考核成绩与教学满意度。结果实验组基础知识、疾病诊断、疾病症状及临床检查考核评分均优于参照组,实验组对教学总满意率(97.14%)高于参照组(77.14%),组间各数据比较,差异均具有意义(P <0.05)。结论翻转课堂结合CBT模式能够吸引学生注意力,学生学习积极性较高,神经病学临床教学质量得以大幅度提升。

关键词： 新型教学模式   神经解剖   三维动画   多媒体教学   三维立体   神经病学  

摘要： 神经病学教学内容繁多、神经解剖结构复杂、抽象且理论性很强,历来是医学教育的重点和难点,新时代下传统的医学教育模式已经不能满足学科教学的发展。而随着多媒体教学的发展,将三维动画应用到神经病学的教学中,能够在有限的时间内从不同角度、不同视点对神经系统的解剖关系进行清晰、准确的展示,使得学生们更容易形成各种三维立体空间结构的概念,可以把抽象、深邃的知识直观地呈现给学生,调动学生学习的积极性,并加深学生对神经病学知识的理解,有利于学生们将解剖结构与临床紧密相联系,培养了学生定位诊断的临床思维与分析问题的能力,从而提高神经病学的教学水平。

关键词： 潍坊市益都中心医院   山东省   中西医结合学会   专业委员会   神经内科   硕士生导师   主任委员   神经病学  

摘要： 牛建一,现任山东省潍坊市益都中心医院理事长兼大神经内科主任。兼任山东省中西医结合学会神经内科专业委员会委员,潍坊市中西医结合学会副会长,潍坊市神经病学专业委员会副主任委员,神经内科专业主任医师、教授、硕士生导师,潍坊名医。

关键词： 临床病理讨论   神经科   北京市   CPC   首都医科大学宣武医院   学术思想   神经病学   国内外  

摘要： 11月3日,2018年神经科临床病理高峰论坛暨北京市神经科临床病理讨论会(CPC)成立40周年纪念会在首都医科大学宣武医院举行。国内外专家与参会代表们济济一堂,共同庆祝CPC成立40周年,同时交流学术思想,共同推动我国神经病学的发展。