Extracellular vesicles in the diagnosis and treatment of central nervous system diseases

Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems.In many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic proteins.The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases.Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier.Today,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well evidenced.Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative diseases.Depending on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and anti-inflammatory.Due to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain.This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.

Overview of emerging therapies for demyelinating diseases

This paper provides an overview of autoimmune disorders of the central nervous system,specifically those caused by demyelination.We explore new research regarding potential therapeutic interventions,particularly those aimed at inducing remyelination.Remyelination is a detailed process,involving many cell types–oligodendrocyte precursor cells(OPCs),astrocytes,and microglia–and both the innate and adaptive immune systems.Our discussion of this process includes the differentiation potential of neural stem cells,the function of adult OPCs,and the impact of molecular mediators on myelin repair.Emerging therapies are also explored,with mechanisms of action including the induction of OPC differentiation,the transplantation of mesenchymal stem cells,and the use of molecular mediators.Further,we discuss current medical advancements in relation to many myelin-related disorders,including multiple sclerosis,optic neuritis,neuromyelitis optica spectrum disorder,myelin oligodendrocyte glycoprotein antibodyassociated disease,transverse myelitis,and acute disseminated encephalomyelitis.Beyond these emerging systemic therapies,we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries.Despite these aforementioned scientific advancements,this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients’quality of life.

Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases

Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.

Circular RNAs:Diagnostic and Therapeutic Perspectives in CNS Diseases

Circular RNAs(circRNAs)are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends.A growing body of evidence suggests that circRNAs play important roles in physiology and pathology.In particular,accumulating data on circRNA functions in various central nervous system(CNS)diseases and their correlations indicate that circRNAs are critical contributors to the onset and development of brain disorders.In this review,we focus on the regulatory and functional roles of circRNAs in CNS diseases,highlighting their diagnostic and therapeutic potential,with the aim of providing new insights into CNS diseases.

Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases

Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of neurons.ROCKs are also involved in the biological effects of immune cells and glial cells,as well as the development of neurodegenerative disorders such as Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis.Previous studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation,regulating immune imbalance,repairing the blood-brain barrier,and promoting nerve repair and myelin regeneration.Fasudil,the first ROCKs inhibitor to be used clinically,has a good therapeutic effect on neurodegenerative diseases.Fasudil increases the activity of neural stem cells and mesenchymal stem cells,thus optimizing cell therapy.This review will systematically describe,for the first time,the effects of abnormal activation of ROCKs on T cells,B cells,microglia,astrocytes,oligodendrocytes,and pericytes in neurodegenerative diseases of the central nervous system,summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases,and clarify the possible cellular and molecular mechanisms of ROCKs inhibition.This review also proposes that fasudil is a novel potential treatment,especially in combination with cell-based therapy.Findings from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.

Eighty Cases of Injury of the Superior Cluneal Nerve Treated by Electroacupuncture

Injury of the superior cluneal nerve is acommonly encountered affection in clinical practice.The author treated 80 cases of injury of the superiorcluneal nerve by electr0acupuncture from August1991 to August 1998,with other 77 cases treated byacupuncture as the controls.The result is reported asfollow.General Data157 OUtpatients were randomly diVided into thetreatment group and the control group.Among

Global trends of fMRI studies on acupuncture for CNS diseases over the past two decades:A bibliometric analysis

Background:Extensive global research has been conducted to explore the neural mechanisms involved in acupuncture treatment for central nervous system(CNS)disorders.However,there is a lack of bibliometric analysis specifically focusing on functional magnetic resonance imaging(fMRI)studies examining the effects of acupuncture on CNS diseases.Objective:This study aims to fill this gap by offering a theoretical framework for the current clinical application and future research directions.It presents a comprehensive overview of the current state,hotspots,and global trends in fMRI studies on therapeutic applications and potential mechanisms of acupuncture for CNS diseases over the past two decades.Methods:The publications were analyzed using VOSviewer 1.6.18 and CiteSpace 6.1.R6 software running on the Java platform.All publications were acquired from the Science Citation Index-Expanded of the Web of Science Core Collection.The document types were limited to original articles and review articles,with publication dates spanning from October 24,2003 to October 24,2023.Only publications written in the English language were considered for analysis.Results:fMRI has the advantages of non-invasiveness,high spatial resolution,and signals directly from neural activity in the brain.Compared to the other three brain imaging techniques,fMRI has the most significant articles on acupuncture treatment for CNS diseases in the past two decades,with a substantial increase.As of October 24,2023,227 records of fMRI studies on acupuncture for CNS diseases were identified.Notably,a discernible upward trend exists in this domain’s overall number of annual publications.It is worth highlighting that China has emerged as the primary contributor to this field.The five most prominent topics explored in fMRI studies on acupuncture for CNS diseases encompassed the concepts of"acupuncture""fMRI""electroacupuncture""functional connectivity"and"stimulation".Furthermore,the frontier areas of investigation encompassed the topics of"migraine without aura""ischemic stroke""prophylaxis"and"randomized controlled trial".Conclusion:fMRI studies on acupuncture treatment in CNS diseases have potential applications,and the number of publications on this topic is expected to increase rapidly in future research,which may focus on migraine without aura,ischemic stroke,and randomized controlled trials.fMRI studies of acupuncture for CNS diseases have connected various brain areas,focusing on the default mode network.In addition,strengthening collaboration among different academic groups across countries is imperative.

Targeting brain-derived neurotrophic factor in the treatment of neurodegenerative diseases:A review

Neurodegenerative diseases,marked by the gradual death of neurons,present a significant and growing public health challenge.Brain-derived neurotrophic factor(BDNF)is crucial for the survival,development,and synaptic plasticity of neurons.Studies have consistently demonstrated that perturbed BDNF communication pathways are associated with the development and progression of neurodegenerative conditions,underscoring their potential as therapeutic targets.This review aimed to summarize the existing findings regarding BDNF expression,metabolism,and signaling transduction.Furthermore,we reviewed the intricate roles of BDNF signaling pathways in neurodegenerative diseases,elucidating their contributions to disease onset and progression.The latest advancements in targeting BDNF for the treatment of neurodegenerative diseases,including the development of small molecules,nucleic acid-based therapeutics,and antibody-based approaches,were also summarized.Despite recent strides,challenges persist,including a lack of comprehensive understanding of BDNF modulation across diverse neurodegenerative contexts and the absence of clinically approved BDNF-targeted drugs.

针刺奇穴为主治疗中枢性顽固性呃逆疗效观察

目的观察针刺奇穴为主治疗中枢性顽固性呃逆的临床疗效。方法将74例中枢性顽固性呃逆患者随机分为治疗组和对照组,每组37例。治疗组采用针刺奇穴为主治疗,对照组采用肌肉注射盐酸甲氧氯普胺注射液及盐酸氯丙嗪注射液治疗。比较两组患者的临床疗效和治疗前后呃逆症状评分变化。结果治疗组总有效率和治愈率分别为94.6%和81.1%,对照组分别为62.2%和29.7%,两组比较差异均具有统计学意义(P<0.01)。两组治疗3 d、5 d后呃逆症状评分与同组治疗前比较,差异均具有统计学意义(P<0.01,P<0.05)。治疗组治疗3 d、5 d后呃逆症状评分与对照组比较,差异均具有统计学意义(P<0.01)。结论针刺奇穴为主治疗能有效改善中枢性顽固性呃逆患者的呃逆症状。

常规理疗联合针刺对重症手足口病中枢神经系统受损致神经肌肉系统功能异常患儿运动功能障碍的干预效果

背景手足口病(HFMD)是一种好发于5岁以下婴幼儿的急性发疹性传染病,可由20多种肠道病毒感染引起,以发热及手、足、口腔、臀部等部位出现疱疹、斑丘疹或溃疡为主要临床症状,大多经治疗后可缓解,不留后遗症,但重症HFMD可造成周围神经麻痹、中枢神经系统损伤,甚至危及患儿的生命,因此,采取有效的干预措施是非常必要的。目的研究常规理疗联合针刺对重症HFMD中枢神经系统受损致神经肌肉系统功能异常患儿运动功能障碍的干预效果。方法选取2014年6月—2017年12月在郑州大学附属儿童医院就诊的重症HFMD中枢神经系统受损致神经肌肉系统功能异常患儿88例。将患儿随机分为对照组和观察组,每组44例。两组患儿均给予常规西医治疗(包括抗病毒、抗感染、促受损神经恢复及维持水、电解质和酸碱平衡),对照组加用常规理疗,观察组加用常规理疗联合针刺治疗,两组治疗周期均为1个月。比较两组临床疗效,治疗前后粗大运动功能量表(GMFM)、Berg平衡量表(BBS)评分,中枢神经系统受损的相关症状(包括呕吐、易惊、肢体抖动、肌无力、嗜睡)消失时间,治疗前后生化指标[白介素6(IL-6)、超敏C反应蛋白(hs-CRP)、白细胞计数(WBC)、肌酸激酶(CK)水平]及不良反应发生情况。结果观察组临床疗效优于对照组(P<0.05)。治疗后,观察组GMFM、BBS评分高于对照组(P<0.05);治疗后两组GMFM、BBS评分高于本组治疗前(P<0.05)。观察组呕吐、易惊、肢体抖动、肌无力、嗜睡消失时间短于对照组(P<0.05)。治疗后,观察组IL-6、hs-CRP、WBC、CK水平低于对照组(P<0.05);治疗后两组IL-6、hs-CRP、WBC、CK水平低于本组治疗前(P<0.05)。两组治疗期间未出现明显的不良反应。结论常规理疗联合针刺治疗重症HFMD中枢神经系统受损致神经肌肉系统功能异常患儿,可显著改善患儿运动功能,缩短病程,减轻炎性反应,且无明显不良反应。

针刺治疗中枢性呃逆68例疗效观察

目的:探讨针刺治疗中枢性呃逆的临床疗效。方法:118例中枢性呃逆患者随机分为针刺组及对照组,针刺组采用针刺穴位进行治疗,对照组采用一般常规方法进行治疗,对比两组治疗效果。结果:针刺组治愈率(83.8%)、总有效率(97.0%)均明显高于对照组(16.0%、42.0%),差异有统计学意义(P均<0.01)。结论:针刺治疗中枢性呃逆疗效满意,具有推广价值。

Review of systematic reviews of acupuncture for diabetic peripheral neuropathy

Objective:To review the systematic reviews of acupuncture for diabetic peripheral neuropathy(DPN)and to provide evidence for clinical decisions.Methods:Published systematic reviews targeting acupuncture treatment of DPN were searched using computer through both Chinese and English databases till July 1,2019.Two researchers screened the papers based on inclusion and exclusion criteria and conducted report quality evaluation,methodological quality assessment and evidence quality grading using the preferred reporting items for systematic reviews and meta-analyses(PRISMA),assessment of multiple systematic review 2(AMSTAR 2)and grading of recommendations assessment,development and evaluation(GRADE).Results:Ten systematic reviews were included,involving 11 outcome measures.According to PRISMA,6 items were sufficiently reported while 1 item was not;AMSTAR 2 appraised that all the included systematic reviews were of low quality in the methodological evaluation;according to GRADE,of the 30 clinical evidences,only 5 were graded moderate while the remained were graded low or extremely low.Descriptive analysis showed that acupuncture can significantly improve DPN symptoms,accelerate the conduction velocities of sensory and motor nerves,and up-regulate the content of plasma nitric oxide(NO),while the adverse reaction rate was low.Conclusion:Acupuncture can produce satisfactory clinical efficacy in treating DPN,but the existing problems,such as low-quality evidence,unitary outcome measures,poor methodological quality of systematic reviews and nonstandard reporting,need to be treated cautiously;meanwhile,more high-quality clinical trials are required to elevate the level of evidence.

针灸治疗急性脑血管病致中枢性呃逆的研究进展

在急性后循环缺血的卒中患者中,呃逆常常为伴生症状,其主要的危害在于膈肌强烈痉挛容易引发应激性溃疡与食物返流,甚至导致上消化道出血,影响相关溶栓、抗凝、抗板等治疗的实施。因此,早期纠正呃逆对于预防应激性溃疡与卒中相关性吸入性肺炎的发生具有重要的临床意义。针灸作为治疗呃逆常见的一种方式,其优势在于无需经过口服药物进入胃肠道,杜绝口服药物吸收缓慢的弊端。本文现就针灸治疗呃逆的相关机制及临床治疗意义进行综述。这将为临床上使用针灸治疗急性脑血管病致中枢性呃逆提供指导。

Brief introduction to Professor Gao Wei-bin's needling technique of ‘Ten Acupuncture Skills'

‘Ten Acupuncture Skills＇ refers to ten types of needling techniques for difficult and intractable neurological diseases. It has been summarized by Prof. Gao Wei-bin, a famous traditional Chinese medicine expert in China, based upon his clinical experience for years, including neck acupuncture for bulbar palsy, neck acupuncture for laryngeal muscular paralysis, stuck needling technique for ocular muscular paralysis, electric field therapy at Jiaji（EX-B 2） points for incomplete spinal paraplegia, electroacupuncture（EA） for urination disorder, electric neck acupuncture for waking up and treating various cerebral and nuchal diseases, EA at Jiaji（EX-B 2） points for intractable hiccup, EA at Jiaji（EX-B 2） points for cervical and lumbar spondylopathy, antagonistic EA for post-apoplectic hemiplegia, and EA for facial paralysis. The ten acupuncture skills are summarized in order to guide the clinical application.

Structured Literature Review of Acupuncture Treatment for Peripheral Neuropathy

Objective： To summarize existing evidence on acupuncture treatment for peripheral neuropathy （PN） and potentially generate a meta-analysis by performing a structured literature review. Methods： Literature searches were conducted on 11 databases. All identified clinical studies of acupuncture and electroacupuncture for peripheral neuropathy due to diabetes, chemotherapy, human immunodeficiency virus （HIV） and unknown cause were included. Study criteria such as sample size, randomization, controls, blinding, acupuncture patterns and outcome measurements were examined for the requirements of the meta-analysis. Results： Among the 26 studies included, no high quality randomized clinical trial was found. There were methodical limitations in all studies. Small sample size was found in 9 studies, lack of randomization in 25, lack of controls in 8, inadequate controls in 11, and lack of blinding in 24 studies, as well as a high variability of acupuncture patterns and outcome measurements. Conclusion： Nearly all acupuncture pilot studies on peripheral neuropathy give positive results encouraging further investigation, but a meta-analysis is not possible on the existent data. Randomized, controlled, blinded clinical trials with adequate design and significance still have to be performed.