Identification of microRNAs and messenger RNAs involved in human umbilical cord mesenchymal stem cell treatment of ischemic cerebral infarction using integrated bioinformatics analysis

In recent years,a large number of differentially expressed genes have been identified in human umbilical cord mesenchymal stem cell(hUMSC)transplants for the treatment of ischemic cerebral infarction.These genes are involved in various biochemical processes,but the role of microRNAs(miRNAs)in this process is still unclear.From the Gene Expression Omnibus(GEO)database,we downloaded two microarray datasets for GSE78731(messenger RNA(mRNA)profile)and GSE97532(miRNA profile).The differentially expressed genes screened were compared between the hUMSC group and the middle cerebral artery occlusion group.Gene ontology enrichment and pathway enrichment analyses were subsequently conducted using the online Database for Annotation,Visualization,and Integrated Discovery.Identified genes were applied to perform weighted gene co-suppression analyses,to establish a weighted co-expression network model.Furthermore,the protein-protein interaction network for differentially expressed genes from turquoise modules was built using Cytoscape(version 3.40)and the most highly correlated subnetwork was extracted from the protein-protein interaction network using the MCODE plugin.The predicted target genes for differentially expressed miRNAs were also identified using the online database starBase v3.0.A total of 3698 differentially expressed genes were identified.Gene ontology analysis demonstrated that differentially expressed genes that are related to hUMSC treatment of ischemic cerebral infarction are involved in endocytosis and inflammatory responses.We identified 12 differentially expressed miRNAs in middle cerebral artery occlusion rats after hUMSC treatment,and these differentially expressed miRNAs were mainly involved in signaling in inflammatory pathways,such as in the regulation of neutrophil migration.In conclusion,we have identified a number of differentially expressed genes and differentially expressed mRNAs,miRNA-mRNAs,and signaling pathways involved in the hUMSC treatment of ischemic cerebral infarction.Bioinformatics and interaction analyses can provide novel clues for further research into hUMSC treatment of ischemic cerebral infarction.

Chinese Stroke Center Alliance:a national effort to improve healthcare quality for acute stroke and transient ischaemic attack:rationale,design and preliminary findings

Background In June 2015,the Chinese Stroke Association(CSA)initiated the Chinese Stroke Center Alliance(CSCA)to establish the national hospital-based stroke care quality assessment and improvement platform.This article outlines its objectives,operational structure,patient population,quality improvement(QI)intervention tools,data elements,data collection methodology and current patient and hospital data.Methods The CSCA is a national,hospital-based,multicentre,voluntary,multifaceted intervention and continuous QI initiative.This multifaceted intervention includes stroke centre development,written care protocols,workshops and a monitoring/feedback system of evidencebased performance measures.The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital.results As of July 2017,1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433264 patients with acute stroke/transient ischaemic attacks(TIA),including 352572(81.38%)acute ischaemic stroke,30362(7.01%)TIA,42080(9.71%)spontaneous intracranial haemorrhage,5505(1.27%)subarachnoid haemorrhage and 2745(0.63%)not specified stroke.Conclusion The CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and,ultimately,improve patient outcomes.It supports the CSA mission to reduce stroke burden in China.

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.

Vascular protection and regenerative effects of intranasal DL-3-N butylphthalide treatment after ischaemic stroke in mice

Objective To investigate the effects of DL-3-N butylphthalide(NBP)via intranasal delivery after ischaemic stroke in mice.Methods C57BL/6 mice were divided into three groups:sham,stroke with vehicle and stroke with NBP treatment.Ischaemic stroke was induced by permanent ligation of right middle cerebral artery with 7 min common carotid artery occlusion.NBP(100 mg/kg)or vehicle was intranasally administered at 1 hour after stroke and repeated once a day until sacrifice.Bromodeoxyuridine(BrdU)(50 mg/kg/day)was given from the third day until sacrifice.Sensorimotor function was tested during 1-21 days after stroke.Local cerebral blood flow in the ischaemic and peri-infarct regions was measured using laser Doppler flowmetry before,during and 3 days after ischaemia.Expressions of vascular endothelial growth factor(VEGF)and endothelial nitric oxide synthase as well as regenerative marker BrdU in the peri-infarct region were analysed by western blotting and immunohistochemical methods.Results Compared with the vehicle group,NBP treatment significantly increased the VEGF expression in the poststroke brain.Stroke mice that received NBP showed significantly less vascular damage after stroke and more new neurons and blood vessels in the peri-infarct region at 21 days after stroke.In the adhesive removal test,the sensorimotor function of stroke mice treated with NBP performed significantly better at 1,3 and 7 days after stroke compared with vehicle controls.Conclusion Daily intranasal NBP treatment provides protective and neurogenic/angiogenic effects in the poststroke brain,accompanied with functional improvements after a focal ischaemic stroke in mice.

Dual antiplatelet therapy may increase the risk of non-intracranial haemorrhage in patients with minor strokes: a subgroup analysis of the CHANCE trial

Aim:The aim of this study was to explore the difference between haemorrhagic events among those patients on either aspirin or aspirin plus clopidogrel who were enrolled in the Clopidogrel in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events(CHANCE)trial.Methods:This was an ad hoc analysis of the CHANCE trial;data on all patients with any haemorrhagic event were reviewed and analysed.Cox proportional hazards regression was used to determine factors association with any bleeding.Results:In the CHANCE trial,there were a total of 101(2%)haemorrhagic events reported from 50 different hospitals.The clopidogrel–aspirin group had 60(2.3%)cases and the aspirin group had 41(1.6%,p=0.09).Moderate or severe haemorrhagic events occurred in 7 patients(0.3%)in the clopidogrel–aspirin group and in 8(0.3%)in the aspirin group(p=0.73).Of 36(0.7%)cases of intracranial haemorrhages,20(0.4%)were in the clopidogrel–aspirin group and 16(0.3%)in the aspirin group.Each group had 8(0.3%)cases of symptomatic haemorrhagic strokes.Other common haemorrhagic events included 24(0.5%)cases of skin bruises,13(0.3%)gastrointestinal haemorrhages,9(0.2%)gum haemorrhages and 8(0.2%)intraocular haemorrhages.Conclusions:There was no overall significant difference in haemorrhagic events(p=0.29),especially in the rate of intracranial haemorrhages between the 2 treatment groups.However,patients enrolled with minor strokes had an increased risk of haemorrhagic events regardless of treatment group,not seen in patients with high-risk transient ischaemic attacks.Being elderly,of male gender and with a history of aspirin or proton pump inhibitor usage were associated with increased risk of haemorrhage.Patients with higher body mass index had lower risk of haemorrhagic events.

Artificial intelligence in healthcare:past,present and future

Artificial intelligence(AI)aims to mimic human cognitive functions.It is bringing a paradigm shift to healthcare,powered by increasing availability of healthcare data and rapid progress of analytics techniques.We survey the current status of AI applications in healthcare and discuss its future.AI can be applied to various types of healthcare data(structured and unstructured).Popular AI techniques include machine learning methods for structured data,such as the classical support vector machine and neural network,and the modern deep learning,as well as natural language processing for unstructured data.Major disease areas that use AI tools include cancer,neurology and cardiology.We then review in more details the AI applications in stroke,in the three major areas of early detection and diagnosis,treatment,as well as outcome prediction and prognosis evaluation.We conclude with discussion about pioneer AI systems,such as IBM Watson,and hurdles for real-life deployment of AI.

Impact of COVID-2019 on stroke services in China: survey from the Chinese Stroke Association

Background The COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly.We aimed to illustrate how the stroke services were interrupted during the pandemic in China.Methods A 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020.Results A total of 415 respondents completed the online survey after informed consent was obtained.Of the respondents,37.8%,35.2%and 27.0%were from mild,moderate and severe epidemic areas,respectively.Overall,the proportion of severe impact(reduction>50%)on the admission of transient ischaemic stroke,acute ischaemic stroke(AIS)and intracerebral haemorrhage(ICH)was 45.0%,32.0%and 27.5%,respectively.Those numbers were 36.9%,27.9%and 22.3%;36.5%,22.1%and 22.6%;and 66.4%,47.5%and 41.1%in mild,moderate and severe epidemic areas,respectively(all p<0.0001).For AIS,thrombolysis was moderate(20%-50%reduction)or severely impacted(>50%),as reported by 54.4%of the respondents,while thrombectomy was 39.3%.These were 44.4%,26.3%;44.2%,39.4%;and 78.2%,56.5%,in mild,moderate and severe epidemic areas,respectively(all p<0.0001).For patients with acute ICH,39.8%reported the impact was severe or moderate for those eligible for surgery who had surgery.Those numbers were 27.4%,39.0%and 58.1%in mild,moderate and severe epidemic areas,respectively.For staff resources,about 20%(overall)to 55%(severe epidemic)of the respondents reported moderate or severe impact on the on-duty doctors and nurses.Conclusion We found a significant reduction of admission for all types of patients with stroke during the pandemic.Patients were less likely to receive appropriate care,for example,thrombolysis/thrombectomy,after being admitted to the hospital.Stroke service in severe COVID-19 epidemic areas,for example,Wuhan,was much more severely impacted compared with other regions in China.

Tissue window,not the time window,will guide acute stroke treatment

Since the approval of intravenous(IV)tissue plasminogen activator(tPA)to treat patients with acute ischaemic stroke(AIS)within 3 hours of onset in 1996,it took 12 years to expand the treatment time window to 4.5 hours by the European Cooperative Acute Stroke Trial II(ECASS III).1 It took another 10 years to expand the treatment time window to 6 hours with the bridging of IV tPA and intra-arterial(IA)thrombectomy.2 In 2018,22 years later after the approval of IV tPA and less than 3 years from the approval of IA thrombectomy,we have learnt that IA thrombectomy was effective in treating patients with AIS from large vessel occlusion(LVO)type of stroke up to 24 hours.3 This continued expansion of the treatment time window has brought hope to many patients with stroke who will present to the emergency room at a later time.

Fabry disease with acute cerebral infarction onset in a young patient

To the Editor:Fabry disease (FD)is a recessive X-linked hereditary disease.The onset age of the disease is in children and adolescents mostly.The average time from the onset of symptoms to the definite diagnosis needs 13.7 years in male patients and 16.3 years in female patients.FD happens rarely and it is easy to cause diagnosis and treatment delay.Here,we report a case of FD in a 27-year-old man who developed clinical symptoms with acute cerebral infarction onset to improve doctors' understanding of FD.