关键词： Sjogren's syndrome   Cross-sectional study   Neurological complication   Risk factor   Logistic model  

摘要： Background: To investigated distinct manifestations of Sjogren's syndrome (SS) patients with neurological complications and the potential risk factors associated with neurological complications in SS, and to produce a disease evaluation and neurological involvement prediction for SS. Methods: 566 patients who fulfilled the 2002 classification criteria for SS from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University were included in the cross-sectional study. Clinical, immunological and histological characteristics were surveyed, and potential risk factors for neurological complications were examined by multivariate analysis. Results: Among 566 SS patients, 184 (32.5%) patients had neurological involvement, with more than 10% got limbs pain, limbs numbness and cerebral infarction, respectively. Of these 184 SS patients with neurological complications, secondary SS (sSS) patients had a higher prevalence of peripheral nervous system (PNS) involvement than primary SS (pSS) patients (31.1 vs. 19%). And sSS patients showed higher total ESSPRI score and higher prevalence of xerostomia and low C3, C4 levels with more liver, articular involvement and saliva gland atrophy, and more severe lymphocyte infiltration in salivary glands than pSS patients. As for the specific factors associated with neurological involvement, low C3 level were found to be significant in pSS or sSS patients who were younger 50 year old, and ANA positivity, cardiac involvement, saliva gland atrophy were demonstrated to be associated in elder pSS patients. And xerophthalmia was found to be associated in sSS patients. Conclusion: Low complement (C3) levels, xerophthalmia, ANA positive, cardiac involvement and labial salivary gland histological result were good ways to predict neurological complications in different subgroups of SS, which might provide insight into better clinical decision-making, especially at early stages of the disease.

关键词： disease modeling   neuron regeneration   neuronal degenerative   neuronal differentiation   neuronal trans-differentiation  

摘要： Neuron regeneration from pluripotent stem cells (PSCs) differentiation or somatic cells trans-differentiation is a promising approach for cell replacement in neurodegenerative diseases and provides a powerful tool for investigating neural development, modeling neurological diseases, and uncovering the mechanisms that underlie diseases. Advancing the materials that are applied in neural differentiation and trans-differentiation promotes the safety, efficiency, and efficacy of neuron regeneration. In the neural differentiation process, matrix materials, either natural or synthetic, not only provide a structural and biochemical support for the monolayer or three-dimensional (3D) cultured cells but also assist in cell adhesion and cell-to-cell communication. They play important roles in directing the differentiation of PSCs into neural cells and modeling neurological diseases. For the trans-differentiation of neural cells, several materials have been used to make the conversion feasible for future therapy. Here, the most current applications of materials for neural differentiation for PSCs, neuronal trans-differentiation, and neurological disease modeling is summarized and discussed.

关键词： imaging   nanomaterials   neural stem cells   regenerative medicine   tissue repair  

摘要： Patients are increasingly being diagnosed with neuropathic diseases, but are rarely cured because of the loss of neurons in damaged tissues. This situation creates an urgent clinical need to develop alternative treatment strategies for effective repair and regeneration of injured or diseased tissues. Neural stem cells (NSCs), highly pluripotent cells with the ability of self-renewal and potential for multidirectional differentiation, provide a promising solution to meet this demand. However, some serious challenges remaining to be addressed are the regulation of implanted NSCs, tracking their fate, monitoring their interaction with and responsiveness to the tissue environment, and evaluating their treatment efficacy. Nanomaterials have been envisioned as innovative components to further empower the field of NSC-based regenerative medicine, because their unique physicochemical characteristics provide unparalleled solutions to the imaging and treatment of diseases. By building on the advantages of nanomaterials, tremendous efforts have been devoted to facilitate research into the clinical translation of NSC-based therapy. Here, recent work on emerging nanomaterials is highlighted and their performance in the imaging and treatment of neurological diseases is evaluated, comparing the strengths and weaknesses of various imaging modalities currently used. The underlying mechanisms of therapeutic efficacy are discussed, and future research directions are suggested.

关键词： Microglial cells   Neuroimmunology  

摘要： Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages ( microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral beta-amyloidosis and immune tolerance alleviates it;similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology.

关键词： MicroRNA let-7c-5p   Traumatic brain injury   Microglia   Neuroinflammation  

摘要： MicroRNAs (miRNAs) are a class of non-coding small RNAs that regulate the expression of target genes. They derive from pre-miRNAs that are enzymatically processed by dicer to 22 nucleotide mature miRNAs. Members of the pre-miRNA lethal-7 (let-7) are known to regulate cell proliferation and apoptosis. Here, we showed that the level of let-7c-5p, a key member of the let-7 family, was rapidly reduced in the traumatically injured foci in brains of adult C57BL/6J mice and gradually recovered to the pre-injury level 14 days after traumatic brain injury (TBI) induction. This finding led us to test whether upregulating let-7c-5p in murine cerebral tissue by intracerebroventricular injection (ICV) of let-7c-5p mimic could improve the outcomes of mice subjected to controlled cortical impact (CCI). We found that let-7c-5p overexpression attenuated TBI-induced neurological dysfunction and brain edema. The improvements were attributed to let-7c-5p-mediated inhibiting neuroinflammation and attenuation of microglia/-macrophage activation, both inhibiting M1 polarization and enhancing M2 polarization. In vitro experiments, we observed that let-7c-Sp was decreased in primary microglia activated by LPS treatment or oxygen/glucose deprivation (OGD). Transfection of let-7c-5p mimic suppressed the release of inflammatory mediators in cultured activated primary microglia. In addition, the expressions of caspase-3, a let-7c-5p putative target gene, and the PKC-delta which mediates effect of caspase-3 were inhibited by let-7c-5p in a murine model of TBI. Taken together, these results define the biological activities of cerebral let-7c-5p and delineate its therapeutic potential for improving the neurological outcome of TBI. (C) 2018 Elsevier B.V. All rights reserved.

关键词： nitric oxide   mitochondria   peroxynitrite   mitochondrial fragmentation   parthanatos   neurologic diseases  

摘要： Mitochondria are key cellular organelles that play crucial roles in the energy production and regulation of cellular metabolism. Accumulating evidence suggests that mitochondrial activity can be modulated by nitric oxide (NO). As a key neurotransmitter in biologic systems, NO mediates the majority of its function through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S-nitrosylation of a variety of proteins involved in cellular functioning including those involved in mitochondrial biology. Moreover, excess NO or the formation of reactive NO species (RNS), e.g., peroxynitrite (ONOO-), impairs mitochondrial functioning and this, in conjunction with nuclear events, eventually affects neuronal cell metabolism and survival, contributing to the pathogenesis of several neurodegenerative diseases. In this review we highlight the possible mechanisms underlying the noxious effects of excess NO and RNS on mitochondrial function including (i) negative effects on electron transport chain (ETC);(ii) ONOO- -mediated alteration in mitochondrial permeability transition;(iii) enhanced mitochondrial fragmentation and autophagy through S-nitrosylation of key proteins involved in this process such as dynamin-related protein 1 (DRP-1) and Parkin/PINK1 (protein phosphatase and tensin homolog-induced kinase 1) complex;(iv) alterations in the mitochondrial metabolic pathways including Krebs cycle, glycolysis, fatty acid metabolism, and urea cycle;and finally (v) mitochondrial ONOO -induced nuclear toxicity and subsequent release of apoptosis-inducing factor (AIF) from mitochondria, causing neuronal cell death. These proposed mechanisms highlight the multidimensional nature of NO and its signaling in the mitochondrial function. Understanding the mechanisms by which NO mediates mitochondrial (dys) function can provide new insights into the treatment of neurodegenerative diseases. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

关键词： Wilson disease   Disability evaluation   Neurological manifestations   Unified Wilson's Disease Rating Scale (UWDRS)  

摘要： Background: Wilson disease is a rare genetic disorder in which impaired copper excretion results in toxic copper levels and tissue damage. Manifestations are primarily hepatic and/or neuropsychiatric, with a variety of neurological phenotypes. The aim of this study was to characterize neurological signs of Wilson disease in newly diagnosed patients and to determine whether they correlated with disability, liver function, and copper metabolism. Methods: Fifty-three treatment-naive patients recently diagnosed with Wilson disease who exhibited neurological symptoms were included. Neurological manifestations were characterized by examination in terms of symptom type and degree of neurological impairment (Unified Wilson's Disease Rating Scale [UWDRS] Part III) and correlated with degree of disability (UWDRS Part II), abnormalities in copper parameters and hepatic status. Results: Most patients (62.3%) exhibited tremor and ataxia, whereas 15.1% were dystonic, and 11.3% had parkinsonism. Discrete or unclassified signs only were observed in 11.3% of patients. A good correlation between disability (UWDRS Part II) and neurological impairment (UWDRS Part III) was observed (Pearson r = 0.84). However, there was a lack of correlation when either disability or neurological impairment were analyzed with copper parameters or liver impairment. Conclusions: The predominant neurological manifestations in this cohort of newly diagnosed Wilson disease patients were ataxia and tremor. Neurological impairment measured was highly correlated with the level of disability. However, hepatic manifestations of Wilson disease and copper levels did not appear to be correlated with neurological status and disability. These results highlight the challenges faced when assessing Wilson disease with its highly variable symptomatology.

关键词： PBL教学模式   神经病学   教学  

摘要： 为促进神经病学学科的发展,尝试如何改革医学生培养模式,我们拟以PBL教学方法为其基础,对医学生培养模式及知识结构体系做出调整,着力推进多学科融合。通过多学科融合结合PBL教学模式在神经病学教学中的组织实施,争取为医学生培养机制找到一种有效的新方法。目前,国内外还未见过在神经病学教学中进行多学科融合结合PBL教学的尝试。此次研究尝试在临床医学专业学生神经病学教学中开展多学科融合结合PBL教学模式,并对教学实践进行一些初步总结和探讨。

关键词： 复旦大学附属华山医院   国家级继续教育项目   神经免疫学   学习班   临床   神经内科   医院教育   神经病学  

摘要： 由复旦大学附属华山医院神经内科、复旦大学神经病学研究所和复旦大学附属华山医院教育处举办的国家级继续教育项目＂第四届华山医院临床神经免疫学新进展学习班＂将于2018年8月23~26日在上海召开。学习班主旨为＂探索神经风湿病学＂。