关键词： 新型冠状病毒肺炎   神经病学   在线对分课堂   教学模式  

摘要： 在新型冠状病毒肺炎疫情突发背景下,教育部作出了“停课不停教、停课不停学”统一部署。本科神经病学面临着怎样开展高质量网络教学工作的难题。我们尝试将对分课堂与互联网结合用于神经病学网络教学,取得了较好的教学效果。本文分析了在线对分课堂的实施背景和意义,并基于讲授、独学、讨论和对话4个基本环节介绍了在线对分课堂具体实现方法和教学效果,最后总结了在线对分课堂的组织与实施中需要注意的问题,为突发公共卫生事件期间医学教育与在线对分课堂的结合及应用提供相应参考。

关键词： COVID-19   Influence on therapy   Neuroinvasive mechanisms   Neurological symptoms   SARS-CoV-2 infection  

摘要： In this paper, the neurological aspects of COVID-19 are presented, which may be of significance for physicians. Knowledge about the neurological symptoms of COVID-19 infection should help physicians in diagnoses and in taking appropriate precautions, as some manifestations can appear before typical pulmonary symptoms. Various mechanisms of SARS-CoV-2 neuroinvasion are discussed and symptoms are described, which can be subdivided into manifestations of the central nervous system (CNS) (headache, dizziness, stroke, impaired consciousness, encephalitis, meningitis, seizures) and peripheral nervous system (PNS) (characteristic hyposmia and hypogeusia, Guillain Barre syndrome, myalgia). Additionally, the implications of COVID-19 infection for treatment of patients with common neurological diseases and their management is presented. It can be concluded that neurological symptoms are part of a clinical spectrum of COVID-19 infection, involving the CNS and PNS. COVID-19 may influence decisions regarding the treatment of neurological disorders, especially those with an immune background.

关键词： HAND   HIV-1 Nef   Autophagy   Exosome  

摘要： Despite adherence to treatment, individuals living with HIV have an increased risk for developing cognitive impairments, referred to as HIV-associated neurological disorders (HAND). Due to continued growth in the HIV population, particularly amongst the aging cohort, the neurobiological mechanisms of HAND are increasingly relevant. Similar to other viral proteins (e.g. Tat, Gp120, Vpr), the Negative Factor (Nef) is associated with numerous adverse effects in the CNS as well as cognitive impairments. In particular, emerging data indicate the consequences of Nef may be facilitated by the modulation of cellular autophagy as well as its inclusion into extracellular vesicles (EVs). The present review examines evidence for the molecular mechanisms by which Nef might contribute to neuronal dysfunction underlying HAND, with a specific focus on autophagy and EVs. Based on the these data, we propose an integrated model by which Nef may contribute to underlying neuronal dysfunction in HAND and highlight potentially novel therapeutic targets for HAND.

关键词： brain injury   intergenerational transmission   neurological deficits   postural asymmetry   pregnant rat  

摘要： Effects of environmental factors may be transmitted to the following generation, and cause neuropsychiatric disorders including depression, anxiety, and posttraumatic stress disorder in the offspring. Enhanced synaptic plasticity induced by environmental enrichment may be also transmitted. We here test the hypothesis that the effects of brain injury in pregnant animals may produce neurological deficits in the offspring. Unilateral brain injury (UBI) by ablation of the hindlimb sensorimotor cortex in pregnant rats resulted in the development of hindlimb postural asymmetry (HL-PA), and impairment of balance and coordination in beam walking test in the offspring. The offspring of rats with the left UBI exhibited HL-PA before and after spinal cord transection with the contralesional (i.e., right) hindlimb flexion. The right UBI caused the offspring to develop HL-PA that however was cryptic and not-lateralized;it was evident only after spinalization, and was characterized by similar occurrence of the ipsi- and contralesional hindlimb flexion. The HL-PA persisted after spinalization suggesting that the asymmetry was encoded in lumbar spinal neurocircuits that control hindlimb muscles. Balance and coordination were affected by the right UBI but not the left UBI. Thus, the effects of a unilateral brain lesion in pregnant animals may be intergenerationally transmitted, and this process may depend on the side of brain injury. The results suggest the existence of left-right side-specific mechanisms that mediate transmission of the lateralized effects of brain trauma from mother to fetus.

关键词： Proenkephalin   Dipeptidyl peptidase 3   Biomarker   Cardiac arrest   Cerebral performance category  

摘要： Background: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuroprognostication no earlier than 72-96 h after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors. Methods: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor longterm neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow coma scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86-0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89-0.97, p < 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic

关键词： RNA processing   Brain development   Neurological disorder   Therapy  

摘要： Gene expression comprises a diverse array of enzymes, proteins, non-coding transcripts, and cellular structures to guide the transfer of genetic information to its various final products. In the brain, the coordination among genes, or lack thereof, characterizes individual brain regions, mediates a variety of brain-related disorders, and brings light to fundamental differences between species. RNA processing, occurring between transcription and translation, controls an essential portion of gene expression through splicing, editing, localization, stability, and interference. The machinery to regulate transcripts must operate with precision serving as a blueprint for proteins and non-coding RNAs to derive their identity. Therefore, RNA processing has a broad scope of influence in the brain, as it modulates cell morphogenesis during development and underlies mechanisms behind certain neurological diseases. Here, we present these ideas through recent findings on RNA processing in development and post-developmental maturity to advance therapeutic discoveries and the collective knowledge of the RNA life cycle.

关键词： Alternative splicing   Comparative genomics   Activity-inducible genes   BDNF   Dominant negative  

摘要： Alternative splicing of genes in the central nervous system is ubiquitous and utilizes many different mechanisms. Splicing generates unique transcript or protein isoforms of the primary gene that result in shortened, lengthened, or reorganized products that may have distinct functions from the parent gene. Learning and memory genes respond selectively to a variety of environmental stimuli and have evolved a number of complex mechanisms for transcriptional regulation to act rapidly and flexibly to environmental demands. Their patterns of expression, however, are incompletely understood. Many activity-inducible genes generate transcripts by alternative splicing that have an unknown physiological or behavioral function. One such gene codes for the protein brain-derived neurotrophic factor (BDNF). BDNF is a neurotrophin whose expression is essential for cellular growth, synaptogenesis, and synaptic plasticity. It is an important model gene because of its complex structure and the variety of transcriptional mechanisms it displays for expression in response to external stimuli. Some of these are unexpected, or non-canonical, transcriptional control mechanisms that require further exploration in an activity-dependent context. In this review, a comparative genomics approach is taken to highlight the different forms of BDNF gene transcription including potential autoregulatory mechanisms. Modes of BDNF control have general implications for understanding the origins of several neurological disorders that are associated with reduced BDNF function.

关键词： Immune checkpoint inhibitor   PD-1   CTLA-4   Neurotoxicity   CNS   Nerve   CAR T cell   Blinatumomab   CD19  

摘要： Immunotherapy has emerged as a powerful therapeutic approach in many areas of clinical oncology and hematology. The approval of ipilimumab, a monoclonal antibody targeting the immune cell receptor CTLA-4, has marked the beginning of the era of immune checkpoint inhibitors. In the meantime, numerous antibodies targeting the PD-1 pathway have expanded the class of clinically approved immune checkpoint inhibitors. Furthermore, novel antibodies directed against other immune checkpoints are currently in clinical evaluation. More recently, bispecific antibodies, which link T cells directly to tumor cells as well as adoptive T cell transfer with immune cells engineered to express a chimeric antigen receptor, have been approved in certain indications. Neurological complications associated with the use of these novel immunotherapeutic concepts have been recognized more and more frequently. Immune checkpoint inhibitors may cause various neurological deficits mainly by alterations of the peripheral nervous system's integrity. These include radiculopathies, neuropathies, myopathies as well as myasthenic syndromes. Side effects involving the central nervous system are less frequent but may result in severe clinical symptoms and syndromes. The administration of chimeric antigen receptor (CAR) T cell is subject to rigorous patient selection and their use is frequently associated with neurological complications including encephalopathy and seizures, which require immediate action and appropriate therapeutic measures. Close clinical monitoring for neurological symptoms is key for early recognition of immunotherapy-related side effects. Comprehensive diagnostic work-up and adequate therapeutic measures are essential to avoid further clinical deterioration and residual neurological deficits.

关键词： Liver transplant   Immunosuppression   Neurological symptoms   Tacrolimus