Advances in the differentiation of pluripotent stem cells into vascular cells

Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

Change of MicroRNA-134,CREB and p-CREB expression in epileptic rat

Objective:To To investigate the changes of MicroRNA-134,CREB and p-CREB expression in epileptic rat brains in order to elucidate the molecular mechanisms of epilepsy,providing new ideas for clinical treatment.Methods:Sixty-four Spraque-Dawley(SD)rats were divided into groups randomly,including control group,six hours after seizure group,24-hour group,threeday group,one-week group,two-week group,four-week group,and eight-week group.All groups were placed under a pilocarpine-induced epilepsy model except the control group,and all rats were decapitated in different points of time.Brain specimens were taken for quantitative PCR experiments,immunohistochemistry and Western blot experiments.The results of the epilepsy model groups and the control group were compared.Results:There were no significant differences between the six hours after seizure group,the 24-hour group and the control group about the MicroRNA-134 levels.MicroRNA-134 in the hippocampus tissue of the three-day group significantly reduced compared with the control group;same result was observed with the one-week,two-week,four-week and eight-week groups.The CREB and p-CREB levels in the three-day group's rat hippocampus significantly increased compared with the control group;and the high levels of CREB and p-CREB were constantly maintained in the one-week,two-week,four-week and eight-week groups.Conclusions:The MicroRNA-134 level of the epileptic rat hippocampus is significantly lower than normal after three days,and continues to maintain a low level:while CREB and p-CREB levels are rsignificantly increased after three days,and continue to remain at a high level.MicroRNA-134 plays a role in inhibiting synaptic plasticity by inhibiting CREB and p-CREB expressions.

Construction of neuron specific vector of human antisense noggin gene expression

Thenoggin gene is present in the central nervous system in embryonic and postnatal mammals, and plays an important role in maintaining nervous system development and physiological function A 0.76-kb sequence of human noggin gene was cloned by polymerase chain reaction with the digestion site of Hind Ill and Xba I on the 5＇ end. The cloned fragment was reversely inserted into pCS2＋[Tal]-GFP plasmid, an neural cell-specific antisense eukaryotic expression vector. The plasmid expresses antisense for human noggin specifically in neurons, which may facilitate understanding of the physiological function of noggin.

Early diagnosis, treatment, and outcomes of five patients with acute thallium poisoning

BACKGROUND Thallium poisoning is rare and difficult to recognize.Early diagnosis and treatment of thallium-poisoned patients are essential to prevent morbidity and mortality.AIM To evaluate the efficacy of treatments and outcomes of five patients with early diagnosis of acute thallium poisoning.METHODS Five patients who consumed a thallium-contaminated meal were hospitalized in succession,and underwent clinical examinations such as blood tests and electromyography tests.Urine and blood tests confirmed the diagnosis of thallotoxicosis,revealing the occurrence of food poisoning.All patients underwent detoxification treatment,including hemoperfusion(HP)and treatment with Prussian blue(PB).A 24-mo follow-up was performed to evaluate the long-term outcomes on the patients after discharge.RESULTS Initially,the patients presented with symptoms of acute thallium poisoning including hyperalgesia of the limbs and abdominalgia,which may differ from common peripheral neuropathy.Accompanying symptoms such as hepatic damage and alopecia were observed in all the patients,which further confirmed the diagnosis of poisoning.Treatment with chelating agents was ineffective,while HP and treatment with PB drastically decreased the thallium concentration in the urine and blood.With early diagnosis and intervention,four patients had a good prognosis and no permanent sequelae.One patient developed blindness and disability during the 24-mo follow-up period.CONCLUSION Identification of incident cluster and characteristic symptoms is extremely important for early diagnosis of acute thallium poisoning.HP plus PB is essential to improve the prognosis of thallium-poisoned patients.

Mitochondrial and nuclear damages and caspase-3 expression in the hippicampal CA3 region of rats with kainic acid induced statuse pilepticus

BACKGROUND: Some scholars believed that the neuronal injury after status epilepticus is apoptosis, the main evidence is the changes of expressions of various apoptosis related genes, such as immediate-early gene, p53 gene and genes of bcl-2 family, etc. But there is still no ultrastructural evidence for apoptosis. OBJECTIVE: To observe the ultrastructural damages of mitochondrion and nucleus and the changes of caspase expression in neurons of hippocampal CA3 region in rats with status epilepticus induced by kainic acid. DESIGN: A randomized controlled study. SETTING: Department of Anesthesiology and Department of Neurology, Qilu Hospital of Shandong University. MATERIALS: Seventy-five adult male Wistar rats of 250-300 g, clean degree, were provided by the experimental animal center of Shandong University. Kainic acid was purchased from Sigma Company (USA); rabbit anti-rat polyclonal antibody caspase-3 from Santa Cruz Company (USA). METHODS: The experiments were carried out in the Department of Anesthesiology, Qilu Hospital of Shandong University from October 2005 to February 2006. ① The 75 rats were randomly divided into experimental group (n =45) and control group (n =30). ② Model establishment, convulsion grading and the judging standards for status epilepticus: Rats in the experimental group were given intraperitoneal injection of kainic acid (10 mg/kg), and those in the control group were injected with saline of the same volume. The time of seizure was recorded and their behavioral manifestations were observed, and the seizure was terminated by intraperitoneal injection of diazepam (10 mg/kg). ③ Observation under electron microscope: At 3, 12 and 24 hours after status epilepticus respectively, bilateral hippocampal tissues were taken out, semithin sections of about 75 nm were prepared after fixation, dehydration and embedding, and then observed under H-800 transmission electron microscope. ④ Immunohistochemical detection: Bilateral hippocampi were removed at 3, 12 and 24 hours after status epilepticus respectively, the fixation, dehydration, transparence, wax immersion and embedding were performed, then serial sections of CA3 region were immunohistochemically determined by the SABC method. Leica QWinV3 image analytical software was applied, then the average number and average gray value of positive cells were calculated. MAIN OUTCOME MEASURES: Results of observation under electron microscope, that of immunohistochemical staining of neurons in hippocampal CA3 region; Comparison of number of caspase-3 positive cells and gray value. RESULTS: All the 75 Wistar rats were involved in the analysis of results. ① Results of observation under electron microscope: At 3 hours after status epilepticus, swelling crista and membranous disintegration were observed under electron microscope. At 24 hours, obvious nuclear changes occurred, and manifested as the side-aggegation of chromatins. ② Results of immunohistochemical detection: In the experimental group, the number of caspase-3 positive cells at 3 hours after status epilepticus had no obvious difference as compared with that in the control group (P > 0.05); At 12 hours, the number and gray value of caspase-3 positive cells in the experimental group were higher than those in the control group (10.49±0.68 vs. 5.33±0.43; 45.57±2.27 vs. 19.79±0.33, P < 0.05), the same results were also observed at 24 hours (37.36±0.57 vs. 5.12±0.47; 115.24±1.22 vs. 18.73±0.42, P < 0.01). CONCLUSION: In the rat models of status epilepticus induced by kainic acid, mitochondrial damage was earlier than the increase of caspase-3 expression and nuclear changes, which suggested that mitochondrion was the key link for the neuronal death after status epilepticus.

Injury of mitochondria and the expressions of fas and bax mRNA in the hippocampus of epileptic rats of different latency

BACKGROUND： It has been confirmed that Fas and Bax respectively mediate the exogenous and endogenous pathways of neuronal apoptosis, and then mediate the neuronal injury after status epilepticus. OBJECTIVE： To comparatively observe the injury of mitochondrial ultrastructure and the expressions of fas and bax in hippocampal tissue of rats with status epilepticus of different latency.DESIGN： A randomized control study.SETTING ： Department of Anesthesiology and Department of Neurology, Qilu Hospital of Shandong University. MATERIALS： Totally 110 male adult SD rats of 260-300 g were used. Kainic acid was purchased from American Sigma Company. METHODS： The experiment was carried out in the Pathological Laboratory of Shandong Academy of Medical Sciences between March and July 2005.① Totally 100 SD rats were divided into. two groups according to the random number table method： intraperitoneal injection group and caudal venous injection group. The rats were given kainic acid injected intraperitoneally （12 mg/kg） and through caudal vein （10 mg/kg） respectively. Each group was observed at 3, 6, 24, 48 and 72 hours after status epilepticus respectively. Ten rats were selected for each time point, including 2 for examination of electron microscope and 8 for the diction of the fas and bax mRNA expressions. The time and manifestations of seizure were observed, and the seizure was lasted for 2 hours, and then it was terminated by intraperitoneal injection of diazepam （10 mg/kg）. Another 10 rats were used as the normal control group, and the materials were taken at 24 hours after status epilepticus, 2 of rats for the examination of electron microscope and 8 of them for the reverse transcription-polymerase chain reaction （RT-PCR）.② The ultrastructure of hippocampal neurons and its mitochondria were observed with transmission electron microscope. ③ The fas and bax mRNA expressions were detected with reverse transcription-polymerase chain reaction （RT-PCR）. MAIN OUTCOME MEASURES： The complete form of hippocampal neurons, changes of mitochondrial structure, and the expression of fas and bax mRNA after status epilepticus were observed. RESULTS： All the 110 rats were involved in the analysis of results.①In the intraperitoneal injection group, the average latency of the occurrence of status epilepticus was （97±11） minutes, mitochondrial swelling in hippocampus was observed under electron microscope, neurons showed apoptosis; In the caudal venous injection group, the latency was （48±13） minutes, hippocampal mitochondria swelled and accompanied by the membranous disintegration, and neurons showed necrosis.② In the caudal venous injection group, no obvious increases of fas and bax mRNA expressions were observed as compared with the control group （P 〉 0.05）. In the intraperitoneal injection group, the fas and bax mRNA expressions began to increase at 6 hours after status epilepticus （0.13±0.042, 0.29±0.016）, reached the peak values at 48 hours （0.78±0.063, 1.04±0.061 ）, and lasted to 72 hours （0.64±0.063, 0.97±0.069） （P 〈 0.05-0.01 ）. CONCLUSION ： The mitochondrial injury of hippocampal neurons in rats with longer latency of status epilepticus is mainly the manifestation of apoptosis, which is milder than in the rats with shorter latency manifested by necrosis, and the fas and bax mRNA expressions in hippocampus are higher than in those with shorter latency.

Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy

Background:Given that seizures may be triggered by vaccination,this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy(PWE)after being vaccinated against coronavirus disease 2019(COVID-19).Methods:This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China.We divided the PWE into two groups as follows:(1)patients who developed seizures within 14 days of vaccination were assigned to the SAV(with seizures after vaccination)group;(2)patients who were seizure-free within 14 days of vaccination were assigned to the SFAV(seizure-free after vaccination)group.To identify potential risk factors for seizure reccurence,the binary logistic regression analysis was performed.Besides,67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence,and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal.Results:The study included a total of 407 patients;of which,48(11.8%)developed seizures within 14 days after vaccination(SAV group),whereas 359(88.2%)remained seizure-free(SFAV group).The binary logistic regression analysis revealed that duration of seizure freedom(P<0.001)and withdrawal from anti-seizure medications(ASMs)or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures(odds ratio=7.384,95%confidence interval=1.732–31.488,P=0.007).In addition,32 of 33 patients(97.0%)who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination.A total of 92(22.6%)patients experienced non-epileptic adverse reactions after vaccination.Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal(P=0.143).Conclusions:PWE need protection from the COVID-19 vaccine.PWE who are seizure-free for>3 months before vaccination should be vaccinated.Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19.Finally,PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.

A feasible strategy for focal cerebral ischemiareperfusion injury: remote ischemic postconditioning

It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperftlsion injury model was established using three cycles of remote ischernic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the in- farct area and attenuated brain edema. In addition, inflammatory nuclear factor-KB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the ce- rebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.

Study of an integrated non-motor symptoms questionnaire for Parkinson＇s disease

Background Although the validity of non-motor symptoms screening questionnaire （NMSQuest） for Parkinson＇s disease has been verified in several recent researches, the specificity of the questionnaire is still in doubt. This study aimed to compare the non-motor symptoms （NMS） in Parkinson＇s disease （PD） with a medically ill control group. Methods In this study, the first comprehensive clinic-based NMS screening questionnaire for PD developed by the Parkinson＇s Disease Non-Motor Group （PDNMG） was used. Data from 90 PD patients and 270 sex-and age-matched control subjects, including stroke （n=90）, heart disease （n=-90） and diabetes （n=-90） were analyzed. Results Compared with control group, NMS was more common in PD; on an average, most PD patients reported more than 12 non-motor items. There was a correlation of total NMS score in PD patients with Hoehn ＆ Yahr Staging, but not with age, sex distribution, disease duration, or age at disease onset. Additionally, depression, constipation and impaired olfaction which occurred prior to the motor symptoms of PD were reported in this study. Conclusions NMS are more common in PD patients. There are some NMS that occurred at the preclinical stage of PD and might predict the onset of motor symptoms of PD patients.

Antimyoclonic Effect of Levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A〉G Mutation

Background： Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers （MERRFs） has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects ofmonotherapies, including levetiracetam （LEV）, clonazepam （CZP）, valproic acid （VPA）, and topiramate （TPM） compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures. Methods： Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months oflbllow-up （mean： 82.9 ± 28.1 days）, 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The lbllow-up period was 4-144 months （mean： 66.3 ± 45.3 months）, the effective rates of monotherapy group （17 patients） and combination therapy group （12 patients） were analyzed by Chi-square test. Results： The m.8344 A〉G mutation was detected in all patients. There were lbur patients with partial response （4/17, two in the CZP group and two in the LEV group）, ten patients with stable disease （10/17, six in the CZP group, three in the LEV group, and one in the TPM group）, and three patients with progressive disease （3/18, two in the VPA group and one in the TPM group）. Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance （12/12）, eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy gToup in the efficacy ofantimyoclonic seizures （χ^2 = 13.7, P 〈 0.001 ）. Conclusions： LEV in combination with CZP is an efficient and sale treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A〉G mutation.

Primary angiitis of the central nervous system： a case report

Primary angiitis of the central nervous system is a rare and difficult entity. Here we represented the clinical and pathological features of a patient with little response to steroid before definite diagnosis. The 50-year-old male had a fluctuating disease course for more than 3 years. He presented visual disorders, seizure, cognitive impairment, hypersomnia, unsteady gait, dysphasia, dysphagia, and incontinence. Magnetic resonance imaging showed multiple, supratentorial and infratentorial abnormal signals, while cerebrospinal fluid and cerebral angiography were normal. Magnetic resonance spectrum showed a decrease of N-acetyl-aspartate. Brain biopsy revealed nongranulomatous lymphatic vasculitis with reactive gliosis, cicatrization, demyelination and focal hemorrhages.

Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy: a multi-center registry survey in China's Mainland

Objective:Chronic levodopa(L-dopa)treatment in Parkinson’s disease(PD)is often associated with the development of motor complications,but the corresponding epidemiological data is rare in Chinese PD patients.The present survey was to investigate the prevalence rate of wearing-off(WO)and dyskinesia among the patients with PD in China.Methods:From May 2012 to October 2012,a 3-step registry survey for wearing off(WO)and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.Results:There were 1,558 PD patients fulfilling the inclusion criteria.Among them,1,051 had at least one positive response of 9-item wearing off questionnaire(WOQ-9),724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists,respectively.The overall prevalence rates of WO and dyskinesia were 46.5%(95%CI 44.0%-48.9%)and 10.3%(95%CI 8.8%-11.8%),respectively.The mean score of WOQ-9 for those with WO was 3.8(SD=1.8),with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms.Better improvement of motor symptoms(n=354,87.8%)and long-term disease control and drug selection(n=288,71.5%)were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.Conclusions:This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from China's Mainland.WO prevalence rate among Chinese PD patients was in line with,while dyskinesia prevalence rate was lower than previous reports from other Countries.

The clinical features and meningeal histochemistry of meningeal malignant melanosis

Meningeal malignant melanosis is a meninges tumor that can produce melanin. Primary intracranial neurocutaneous melanosis is rare. It grows fast with a high degree of malignancy and is associated with earlier intracranial hypertension and meningeal irritation. Most of them can not be diagnosed unless by biopsy or autopsy1. lntracranial malignant melanosis is divided into two kinds： primary and secondary which transfers through the lymph or blood. We report one case of meningeal malignant melanosis that was confirmed by meningeal pathology.

阿尔茨海默病多中心独立的、可重复的海马影像组学标志物:早期识别、纵向进展和生物学基础

脑内海马结构的形态学变化是阿尔茨海默病(AD)的影像学标记之一.海马的影像组学特征是否可以作为AD早期识别的生物标记以及是否可以预测轻度认知损害(MCI)的转化尚需进一步验证,并且海马影像组学特征是否有其神经生物学基础也需要进一步探索.本文的主要目的是研究海马的影像组学特征是否可以作为AD早期识别的影像学标记.为此,我们利用最常用的多变量分类器对AD(261例)和正常人(231例)进行独立中心识别的交叉验证,6个中心的平均准确率为88.21%,更进一步,利用完全独立的ADNI数据集(1228例被试)也验证了这一结果.通过对MCI人群的系统研究发现,部分重要海马影像组学特征与被试的生物学评分(主要包括APOE基因型、多基因风险分数、脑脊液的生物标记物Aβ和Tau,以及认知能力的变化等)具有显著的相关性.更为重要的是,通过5年左右的纵向跟踪研究发现影像组学特征的变化与认知水平的变化具有高度一致性.本研究结果表明海马的影像组学特征有希望用于早期识别AD,具有预测MCI病人是否会转化为AD的潜在能力.综上,研究结果将有可能应用于MCI和AD的早期辅助识别,具有重要的临床意义.

ASAF: altered spontaneous activity fingerprinting in Alzheimer’s disease based on multisite fMRI

Several monocentric studies have noted alterations in spontaneous brain activity in Alzheimer's disease (AD), although there is no consensus on the altered amplitude of low-frequency fluctuations in AD patients. The main aim of the present study was to identify a reliable and reproducible abnormal brain activity pattern in AD. The amplitude of local brain activity (AM), which can provide fast mapping of spontaneous brain activity across the whole brain, was evaluated based on multisite rs-fMRI data for 688 subjects (215 normal controls (NCs), 221 amnestic mild cognitive impairment (aMCI) 252 AD). Two-sample t-tests were used to detect group differences between AD patients and NCs from the same site. Differences in the AM maps were statistically analyzed via the Stouffer's meta-analysis. Consistent regions of lower spontaneous brain activity in the default mode network and increased activity in the bilateral hippocampus/parahippocampus, thalamus, caudate nucleus, orbital part of the middle frontal gyrus and left fusiform were observed in the AD patients compared with those in NCs. Significant correlations (P?<?0.05, Bonferroni corrected) between the normalized amplitude index and Mini-Mental State Examination scores were found in the identified brain regions, which indicates that the altered brain activity was associated with cognitive decline in the patients. Multivariate analysis and leave-one-site-out cross-validation led to a 78.49% prediction accuracy for single-patient classification. The altered activity patterns of the identified brain regions were largely correlated with the FDG-PET results from another independent study. These results emphasized the impaired brain activity to provide a robust and reproducible imaging signature of AD.

Endovascular therapy for Acute ischemic Stroke Trial (EAST): study protocol for a prospective, multicentre control trial in China

Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.

Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo

Background:Abnormal expression of major histocompatibility complex class I(MHC-I)is increased in dopaminergic(DA)neurons in the substantia nigra(SN)in Parkinson’s disease(PD).Low-molecular-mass protein 7(β5i)is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells.Methods:In this study,we investigated the role of β5i in DA neurons using a 6-hydroxydopamine(6-OHDA)model in vitro and vivo.Results:We showed that 6-OHDA upregulatedβ5i expression in DA neurons in a concentration-and time-dependent manner.Inhibition and downregulation ofβ5i induced the expression of glucose-regulated protein(Bip)and exacerbated 6-OHDA neurotoxicity in DA neurons.The inhibition of β5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA.β5i also activated transporter associated with antigen processing 1(TAP1)and promoted MHC-I expression on DA neurons.Conclusion:Taken together,our data suggest that β5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.

Progressive Venous Thrombosis in an 18-Year-Old Man with Down Syndrome

To the Editor： Cerebral venous thrombosis （CVT） indicates occlusion of the main sinus/sinuses or cortical veins, resulting in vascular congestion and neurological lesions. Juveniles with Down syndrome （DS） are more likely to develop thrombosis. However, the association between thrombosis and DS has not been reported widely.