Vimentin as a potential target for diverse nervous system diseases

Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.

Ameliorative effects of standardized extract from Trigonella foenum-graecum L.seeds on painful peripheral neuropathy in rats

Objective:To evaluate the effects of the standardized extract of fenugreek(Trigonella foenumgraecum L.Family:Leguminasae) seed(IND01) in animal models of peripheral neuropathy. Methods:IND01 was prepared from fenugreek seeds and standardized by high performance liquid chromatography to a marker compound,trigonelline.The effects of daily oral administration of IND01(50,100 and 200 mg/kg) were studied in rats after partial sciatic nerve ligation(PSNL) and sciatic nerve crush injury(SNCI) during 30-days period.The measurements on thermal hyperalgesia(TH),motor function test(MFT) score and motor nerve conduction velocity (MNCV) were recorded.Results:IND01 offered sustained protection against TH and deranged MFT scores in both models from 7-day onwards.Fifteen days of daily oral administration of IND01 restored MNCV reduction in rats with SNCI but not with PSNL.Conclusions:IND01 was found to be effective in rat models of painful peripheral neuropathy.

Glymphatic system:a gateway for neuroinflammation

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

Traditional Chinese Medicine syndrome analysis on oxaliplatin-induced peripheral neuropathy and clinical efficacy of Bushen Yiqi formula(补肾益气方):a prospective randomized controlled study

OBJECTIVES:To analyze the distribution characteristics of Traditional Chinese Medicine(TCM)syndromes in patients with oxaliplatin-induced peripheral neuropathy(OIPN)and observe the clinical efficacy of Bushen Yiqi formula(补肾益气方,BSYQF)in treating patients with OIPN.METHODS:A total of 89 patients with OIPN were enrolled in this study.The TCM syndrome characteristics were investigated by frequency analysis methodology after collecting and analyzing the TCM syndrome elements of the patients with the OIPN TCM syndrome element scale.Further,62 cases of cold-dampness obstruction syndrome and kidney-Qi deficiency and cold syndrome were selected and randomly divided into the control group(n=31)and the treatment group(n=31).The patients in the treatment group were treated with modified BSYQF,while those in the control group were treated with mecobalamin tablets for 3 weeks.The Levi sensory neurotoxicity score and the neuro-electrophysiological changes were observed before and after the treatment in both groups.RESULTS:The distribution of TCM syndrome types in 89 patients with OIPN were in order of kidney-Qi deficiency and cold syndrome(44 cases),cold-dampness obstruction syndrome(18 cases),Yin deficiency of liver and kidney syndrome(11 cases),blood stasis obstruction syndrome(7 cases),and dampness-heat obstruction syndrome(5 cases).Improvement in Levi sensory neurotoxicity score:After 3-week treatment,the total effective rate in the treatment group was higher than that in the control group(P<0.05).The subgroup analysis showed that the total effective rate in the treatment group of patients with kidney-Qi deficiency and cold syndrome was higher than that in the control group before and after treatment(P<0.05).Improvement in nerve conduction velocity:The sensory nerve conduction velocity of bilateral ulnar nerves improved in the control group after treatment compared with that before treatment(P<0.05).The sensory and motor nerve conduction velocities of the bilateral ulnar and bilateral peroneal nerves improved in the treatment group compared with those before treatment and after treatment in the control group(P<0.05).CONCLUSIONS:The modified BSYQF had a definite therapeutic effect on the OIPN in patients with kidney-Qi deficiency and cold syndrome and those with cold-dampness obstruction syndrome.It could effectively reduce the grade of peripheral nerve toxicity and improve nerve conduction velocity,and its curative effect was better than that of mecobalamin tablets.

电针防治长春碱类药物所致的周围神经毒性及对生存质量影响的临床观察

目的观察电针治疗肿瘤患者长春碱类药物所致的周围神经毒性反应的疗效及其对生存质量的影响。方法选取60例肿瘤患者,随机分为电针治疗组和针刺对照组各30例。两组均采用长春碱类药物进行化疗,电针治疗组在常规化疗的同时,予以电针治疗;针刺对照组予以针刺穴位,但不通电流治疗。观察两组患者长春碱类药物所致周围神经毒性防治情况及生存质量。结果电针治疗组周围神经毒性的发生率为60.0%(18/30),而针刺对照组为90.0%(27/30),两组比较差异有统计学意义(P<0.05)。两组体质量和卡氏评分情况比较,电针治疗组治疗后体质量比治疗前增加(P<0.05),针刺对照组治疗前、后比较差异无统计学意义(P>0.05);电针治疗组治疗后卡氏评分比治疗前增加(P<0.05),针刺对照组治疗前、后无变化(P>0.05)。结论电针能有效改善及降低长春碱类药物的神经毒性,增加患者体质量,提高生存质量。

Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome

BACKGROUND：Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome （MODS） has been reported to be related to damage to interstitial cells of Cajal （ICC）. In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE：To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE＇I-FING：The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS：Escherichia coli （E. colistrain O127 H6） and bovine serum albumin were purchased from Sigma, USA.METHODS：A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES：Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS：Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group （P 〈 0.01）. The enteric nerve-ICC network were disrupted.CONCLUSION：There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.

Autonomic and sensory nerve dysfunction in primary biliary cirrhosis

AIM:Cardiovascular autonomic and peripheral sensoryneuropathy is a known complication of chronic alcoholicand non-alcoholic liver diseases.We aimed to assess theprevalence and risk factors for peripheral sensory nerveand autonomic dysfunction using sensitive methods inpatients with primary biliary cirrhosis (PBC).METHODS:Twenty-four AMA M2 positive female patientswith clinical,biochemical and histological evidence of PBCand 20 age matched healthy female subjects were studied.Five standard cardiovascular reflex tests and 2d-h heartrate variability(HRV)analysis were performed to defineautonomic function.Peripheral sensory nerve function onmedian and peroneal nerves was characterized by currentperception threshold(CPT),measured by a neuroselectivediagnostic stimulator(Neurotron,Baltimore,MD).RESULTS:Fourteen of 24 patients(58%)had at least oneabnormal cardiovascular reflex test and thirteen(54%)had peripheral sensory neuropathy.Lower heart rateresponse to deep breathing(P=0.001),standing(P=0.03)and Valsalva manoeuvre(P=0.01),and more profounddecrease of blood pressure after standing(P=0.03)wasfound in PBC patients than in controls.As a novel findingwe proved that both time domain and frequency domainparameters of 24-h HRV were significantly reduced in PBCpatients compared to controls.Each patient had at leastone abnormal parameter of HRV.Lower CPT values indicatedhyperaesthesia as a characteristic feature at peronealnerve testing at three frequencies(2000 Hz:P=0.005;250 Hz:P=0.002;5 Hz:P=0.004)in PBC compared tocontrols.Correlation of autonomic dysfunction with theseverity and duration of the disease was observed.Lowertotal power of HRV correlated with lower CPT values atmedian nerve testing at 250 Hz(P=0.0001)and at 5 Hz(P=0.002),as well as with those at peroneal nerve testingat 2000 Hz(P=0.01).CONCLUSION:Autonomic and sensory nerve dysfunctionsare frequent in PBC.Twenty-four-hour HRV analysis is moresensitive than standard cardiovascular tests for detectingof both parasympathetic and sympathetic impairments.Ournovel data suggest that hyperaesthesia is a characteristicfeature of peripheral sensory neuropathy and mightcontribute to itching in PBC.Autonomic dysfunction is relatedto the duration and severity of PBC.

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

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.

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.

Mononeuropathy multiplex associated with systemic vasculitis:A case report

BACKGROUND Vasculitis,a systemic disorder with inflammation of blood vessel walls,can develop broad spectrum of signs and symptoms according to involvement of various organs,and therefore,early diagnosis of vasculitis is challenging.We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex,rectal perforation and antiphospholipid syndrome(APS)presented with pulmonary embolism.CASE SUMMARY A 61-year-old woman visited hospital with complaints of myalgia and occasional fever.She was initially diagnosed as proctitis and treated with antibiotics,however,there was no improvement.In addition,she also complained right foot drop with hypesthesia,and left 2^(nd) and 3^(rd) finger tingling sensation.She underwent nerve conduction study for evaluation,and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs.Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy.Based on nerve biopsy and clinical manifestation,she was diagnosed with vasculitis and treated with immunosuppressive therapy.During treatment,sudden rectal perforation and pulmonary thromboembolism occurred,and further laboratory study suggested probable concomitant APS.Emergency Hartmann operation was performed for rectal perforation,and anti-coagulation therapy was started for APS.After few cycles of immunosuppressive therapy,tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary.CONCLUSION Vasculitis can be presented with a variety of signs and symptoms,therefore,clinicians should always consider the possibility of diagnosis.

遗传性压力易感性周围神经病

遗传性压力易感性周围神经病是一种遗传性运动感觉性神经病,呈常染色体显性遗传,以反复发作的肢体麻木、无力为特征表现。在临床工作中,一些患者临床表现轻微或不典型,易致漏诊、误诊。本文对该病的病因、流行病学、临床表现、辅助检查、诊断及鉴别诊断、治疗与预后等方面进行介绍。

糖尿病周围神经病变中医研究进展

糖尿病周围神经病变为糖尿病微血管并发症之一，中医学将该病归于“消渴病痹症”，从络病角度对其进行辨治，治疗在补虚的同时，加用通络药物取得了较好疗效。近年来中医学对本病的研究不断深入，在病因病机、治疗、实验及临床研究等方面均有了新的认识，本文归纳相关文献进行综述。

慢性阻塞性肺疾病合并外周血管疾病研究进展

慢性阻塞性肺疾病(COPD)是一种常见的慢性气流受限性疾病,外周血管疾病是其常见的合并症,COPD合并外周血管疾病患者病情重、病死率高、预后差.COPD合并外周血管疾病主要累及颈动脉、下肢动脉、肺动脉及下肢静脉,其发生与缺氧、氧化应激、全身炎症反应、自主神经功能障碍等多种因素相关.C O PD合并外周血管疾病起病隐匿、临床表现无特异性且不易早期发现,本文对其流行病学、发病机制、早期发现与预防等方面进行综述,为临床工作提供帮助.

Value of sympathetic skin response test in the early diagnosis of diabetic neuropathy

Background Diabetic neuropathy is common in diabetes mellitus. The early stage of diabetic neuropathy is often symptomless and difficult to be treated. The aim of this study was to assess the correlation between the results of the sympathetic skin response (SSR) test and the development of diabetic neuropathy, and explore the use of SSR as an objective basis for the early diagnosis of diabetic neuropathy. Methods The latencies and amplitudes of initiation and of the N and P waves were determined by SSR testing of the extremities of 80 diabetic patients and 30 healthy controls. Results The latencies of initiation and of the N and P waves were significantly (P<0.001) longer in diabetic patients than in the controls, while there was no significant difference in the amplitudes (P>0.05). All but two patients (97.5%) demonstrated abnormal SSR in at least one limb. Conclusions SSR can detect early dysfunction of the small sympathetic fibers in people affected by diabetes mellitus, and may be a useful electrophysiological test for the early diagnosis of diabetic neuropathy.