Effects of the Solution Treatment on Microstructural Evolution, Mechanical Properties, and Fracture Mechanism of Nickel-Based GH4099 Superalloy

Grain growth, mechanical properties, and fracture mechanism of nickel-based GH4099 superalloy are investigated using heat treatments, tensile tests, optical microscopy (OM), and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS). The OM observation shows that the matrix grains (γ-grains) undergo an apparent growth during the solution treatment. The grain size diameter increases from 100 to 174 μm when the solution temperature rises from 1100℃ to 1160℃ for 30 min. When the holding time increases from 15 to 60 min at 1140℃, the grain size diameter increases from 140 to 176 μm, indicating that the γ-grain growth is more sensitive to temperature than time. Standard deviation, Sv, and the grain size distribution are utilized to characterize the microstructural uniformity. To predict the grain size more accurately, we develop the grain growth kinetics and find that the growth index is close to 5. The yield strength (Rp0.2), tensile strength (Rm), and ductility (Af) are also measured. It is found that the effect decreases in the order cooling rate, solution temperature, time. Rp0.2 reduces by 47% with the increase in the cooling rate from 1℃ to 8000℃/min, while both strength and ductility exhibit little changes with time. The SEM results show that the fracture surfaces have typical mixed brittle and ductile characteristics when specimens are subjected to water quenching and air cooling. However, a complete brittle fracture occurs under furnace cooling conditions. The EDS analysis indicates that the brittle γ' (Ni3Ti) phase precipitates around the γ-grain boundary during the slow cooling process, which is the main factor yielding the complete brittle fracture. Finally, the optimal solution treatment scheme for the GH4099 superalloy is proposed—a temperature of 1140℃ for 30 min followed by air cooling.

Awareness intervention for Beijing neurologists regarding secondary prevention of cerebral infarction/transient ischemia Cross-sectional investigation

BACKGROUND： Stroke prevention guidelines should be made available application to aid in uniformity, timing, preciseness, and acceptance of disease. OBJECTIVE： To investigate the awareness of neurologists in some Beijing secondary prevention of cerebral infarction/transient ischemia. DESIGN： Cross-sectional study. to neurologists for clinical hospitals of intervention in SETTING： Beijing Tiantan Hospital, Beijing Anzhen Hospital, General Hospital of Beijing Military Area, Command of Chinese PLA, Beijing Chuiyangliu Hospital, Beijing 6^th Hospital, Beijing Hepingli Hospital, and Beijing Daxing District Hospital. PARTICIPANTS： A total of 28 （associate） chief physicians, 58 attending physicians, and 54 resident physicians who engaged in clinical treatment of cerebrovascular diseases were selected from 8 hospitals in Beijing from March to April 2007. All physicians provided informed consent. METHODS： Self-made closed questionnaires were provided for data collection, consisting of 16 questions that were single choice or multiple choice. Specifically, questions 1-7 focused on awareness of blood pressure regulation in different patients and first choice of decompression drug; questions 8-12 focused on awareness of lipid regulation; and questions 13-16 focused on awareness of anti-blood platelet drugs applied in secondary prevention. The scores ranged from 0-100 points, and each question was worth 6.25 points. The scores positively correlated with the awareness rate. To test leveling real-time, the survey lasted for a maximum of 20 minutes. One questionnaire was independently finished by each subject in the survey. MAIN OUTCOME MEASURES： Awareness intervention among neurologists during secondary prevention of cerebral infarction/transient ischemia and questionnaire scores. RESULTS： 140 subjects were included in the final analysis. ① The awareness rate among neurologists for intervention during secondary prevention of cerebral infarction/transient ischemia ranged from 0.7-57.9%, the scores ranged between 0-56 points, and the mean score was 26 points.② Scores of resident physicians were 0-56 points with a mean score of 26 points; attending physicians scored 6-50 points, with a mean score of 26 points; and chief physicians scored 6-50 points, with a mean score of 23 points. There were no significant differences among the various physicians （F = 0.771, t = 0.465, P 〉 0.05）. CONCLUSION： Awareness among neurologists of intervention during secondary prevention of cerebral infarction/transient ischemia is not ideal. However, there was no significant difference between professional titles.

针对中国陆地碳汇反演的大气二氧化碳浓度观测网络最优化设计

精准估算陆地生态系统碳汇对中国制定碳减排措施、实现碳中和目标有重要科学支撑作用.大气反演方法基于大气二氧化碳浓度观测数据,可有效估算地面二氧化碳通量的时空分布.目前中国陆地生态系统碳汇的大气反演估算仍有巨大不确定性,其中一个重要瓶颈在于缺乏足够的二氧化碳观测站点.本文研发了针对中国区域的大气反演框架,提出了二氧化碳观测网络的站点布设方案以最大程度降低中国陆地碳汇反演估算的不确定性.研究表明,在现有站点基础上,亟需在生长季植被生产力较高的东南、东北、华北和青藏高原地区增设二氧化碳观测站点.若在中国建设30个大气二氧化碳观测站点可将碳汇估算不确定性从每年10亿吨碳降低至3亿吨碳;建设60个站点可将不确定性进一步降低至每年2亿吨碳.这些站点将是“天-空-地”综合碳观测系统的重要组成部分,服务于中国二氧化碳收支反演和精准核算.

Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke:a prospective cohort study

Background Somatic mutation contributes to clonal haematopoiesis of indeterminate potential(CHIP)is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease.Here,we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke(AIS)cohort and explored the underlying mechanisms.Methods We studied a prospective cohort of 6016 patients who had a first-ever AIS in China.Whole-genome sequencing was performed to identify CHIP.High-sensitivity C reactive protein(hs-CRP)levels above 3 mg/L at baseline were defined as hyperinflammation.Recurrent stroke during the 3-month follow-up was the primary outcome.Results Among the 6016 patients who had a first-ever AIS,with a median age was 62 years(IQR,54.0‒70.0),3.70%were identified as CHIP carriers.The most common mutations occurred in the DNMT3A(30.0%)and TET2(11.4%)genes.During a follow-up of 3 months,the presence of CHIP was associated with recurrent stroke(HR 1.62,95%CI 1.04 to 2.51,p=0.03),recurrent ischaemic stroke(HR 1.64,95%CI 1.04 to 2.58,p=0.03)and combined vascular events(HR 1.58,95%CI 1.02 to 2.44,p=0.04)after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS.Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation(OR 3.10,95%CI 1.92 to 5.00,p<0.001)but not in those without hyperinflammation(OR 0.18,95%CI 0.03 to 1.04,p=0.06,Pinteraction=0.002).Conclusion Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS.Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.

AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells

While neuroblastoma accounts for 15%of childhood tumor-related deaths,treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs.Currently,maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical,especially high-risk patients.However,differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy,unclear mechanism,and few drug options.Through compound library screening,we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691.The protein kinase B(AKT)pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation,yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear.Here,we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines.Further evidence including neurites outgrowth,cell cycle arrest,and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691.Meanwhile,with the introduction of other AKT inhibitors,it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation.Furthermore,silencing AKT was found to have the effect of inducing neuroblastoma differentiation.Finally,confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo,suggesting that Hu7691 is a potential molecule against neuroblastoma.Through this study,we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Constraint of satellite CO_(2)retrieval on the global carbon cycle from a Chinese atmospheric inversion system

Satellite carbon dioxide(CO_(2))retrievals provide important constraints on surface carbon fluxes in regions that are undersampled by global in situ networks.In this study,we developed an atmospheric inversion system to infer CO_(2)sources and sinks from Orbiting Carbon Observatory-2(OCO-2)column CO_(2)retrievals during 2015–2019,and compared our estimates to five other state-of-the-art inversions.By assimilating satellite CO_(2)retrievals in the inversion,the global net terrestrial carbon sink(net biome productivity,NBP)was found to be 1.03±0.39 petagrams of carbon per year(Pg C yr^(-1));this estimate is lower than the sink estimate of 1.46–2.52 Pg C yr^(-1),obtained using surface-based inversions.We estimated a weak northern uptake of 1.30 Pg C yr-1and weak tropical release of-0.26 Pg C yr^(-1),consistent with previous reports.By contrast,the other inversions showed a strong northern uptake(1.44–2.78 Pg C yr-1),but diverging tropical carbon fluxes,from a sink of 0.77 Pg C yr^(-1) to a source of-1.26 Pg C yr^(-1).During the 2015–2016 El Ni?o event,the tropical land biosphere was mainly responsible for a higher global CO_(2)growth rate.Anomalously high carbon uptake in the northern extratropics,consistent with concurrent extreme Northern Hemisphere greening,partially offset the tropical carbon losses.This anomalously high carbon uptake was not always found in surface-based inversions,resulting in a larger global carbon release in the other inversions.Thus,our satellite constraint refines the current understanding of flux partitioning between northern and tropical terrestrial regions,and suggests that the northern extratropics acted as anomalous high CO_(2)sinks in response to the 2015–2016 El Nino event.

Preclinical evaluation of ZL006-05,a new antistroke drug with fast-onset antidepressant and anxiolytic effects

Background Poststroke depression and anxiety,independent predictor of poor functional outcomes,are common in the acute phase of stroke.Up to now,there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke.ZL006-05,a dual-target analgesic we developed,dissociates nitric oxide synthase from postsynaptic density-95 while potentiatesα2-containingγ-aminobutyric acid type A receptor.This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects.Methods Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice.Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride)staining or Nissl staining.Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores.Grid-walking,cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions.Spatial learning was assessed using Morris water maze task.Depression and anxiety were induced by unpredictable chronic mild stress.Depressive behaviours were assessed by tail suspension,forced swim and sucrose preference tests.Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests.Pharmacokinetics,toxicokinetics and long-term toxicity studies were performed in rats.Results Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly,with a treatment window of 12 hours after ischemia,and reduced plasminogen activato-induced haemorrhagic transformation.ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice,had antidepressant and anxiolytic effects in stroke mice.ZL006-05 crossed the blood-brain barrier and distributed into the brain rapidly,and had a high safety profile in toxicokinetics and long-term toxicological studies.Conclusion ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy,safety and targeting of clinical issues.

Endovascular therapy in acute anterior circulation large vessel occlusive patients with a large infarct core(ANGEL-ASPECT):protocol of a multicentre randomised trial

Background The benefit of stroke thrombectomy for large infarct core still lacks robust randomised controlled studies.Aim To demonstrate the design of a clinical trial on endovascular therapy for acute anterior circulation large vessel occlusion(LVO)patients with large infarct core volume.Design ANGEL-ASPECT is a multicentre,prospective,randomised,open-label,blinded End-point trial to evaluate whether best medical management(BMM)combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score(ASPECTS)of 3-5 on non-contrast CT or infarct core volume range of 70-100 mL(defined as rCBF<30%on CT perfusion or ADC<620 on MRI)up to 24 hours from symptom onset or last seen well.Study outcomes The primary efficacy outcome is 90(±7)days modified Rankin Scale.Symptomatic intracranial haemorrhage within 48 hours from randomisation is the primary safety outcome.Discussion The ANGEL-ASPECT trial will screen patients with large infarct core(ASPECTS 3-5 or 70-100 mL)through image evaluation criteria within 24 hours and explore the efficacy and safety of endovascular therapy compared with BMM.

Rationale and design of a randomised double-blind 2×2 factorial trial comparing the effect of a 3-month intensive statin and antiplatelet therapy for patients with acute mild ischaemic stroke or high-risk TIA with intracranial or extracranial atherosclerosis(INSPIRES)

Background It remains unclear if intensive antiplatelet and statin treatments begun within 24-72 hours of cerebral ischaemic events from intracranial or extracranial atherosclerosis is effective or safe.Methods The Intensive Statin and Antiplatelet Therapy for High-risk Intracranial or Extracranial Atherosclerosis(INSPIRES)trial is a randomised,double-blind,placebo-controlled,multicentre and 2×2 factorial trial.6100 individuals between the ages of 35 and 80 who have experienced a mild ischaemic stroke or high-risk transient ischaemic attack(TIA)within the previous 72 hours that is attributed to≥50%atherosclerotic stenosis of a major intracranial or extracranial artery or multiple infarctions of atherosclerotic origin will be enrolled in the trial.Eligible subjects will be randomised 1:1:1:1 to one of four groups:(1)intensive antiplatelet therapy(combined clopidogrel and aspirin for days 1-21,then aspirin placebo and clopidogrel for days 22-90)plus immediate intensive statin therapy(atorvastatin at a dose of 80 mg daily for the first 21 days,then 40 mg daily for days 22-90);(2)intensive antiplatelet therapy plus delayed intensive statin therapy(atorvastatin placebo for days 1-3,followed by 40 mg per day of atorvastatin for days 4-90);(3)standard antiplatelet therapy(combination of clopidogrel placebo with aspirin for 90 days)plus immediate intensive statin therapy and(4)standard antiplatelet therapy plus delayed intensive statin therapy.The primary efficacy endpoint is any new stroke(ischaemic or haemorrhagic)within 90 days after randomisation.The primary safety endpoint is moderate to severe bleeding at 90 days.Conclusion The INSPIRES trial will assess the efficacy and safety of intensive antiplatelet therapy and immediate intensive statin therapy begun within 72 hours of onset in decreasing the recurrent stroke at 90 days in patients with acute mild ischaemic stroke or high-risk TIA of intracranial or extracranial atherosclerosis origin.

小卒中或高危TIA双重抗血小板治疗的患者90天内卒中复发的危险因素：CHANCE研究的亚组分析

目的很多接受双重抗血小板治疗的患者仍有卒中复发。我们的目的是研究急性非致残性脑血管事件高危患者氯吡格雷应用（CHANCE）研究中双重抗血小板治疗的患者90天内卒中复发的相关因素。

新型冠状病毒肺炎疫情对中国2020年碳排放的影响

中国的二氧化碳减排工作一直承受着国际社会的压力.新型冠状病毒肺炎疫情(COVID-19,简称"新冠疫情")对全球碳排放产生了显著影响.准确估算新冠疫情对中国二氧化碳排放量及其排放趋势的影响,对评估中国对全球变化的贡献有重要意义.本研究系统构建了基于活动数据的中国省级日碳排放数据库,对涵盖了化石燃料燃烧和水泥生产造成的所有人为源二氧化碳排放进行定量化的动态评估.本研究发现中国各省的碳排放在新冠疫情期间受到不同程度的影响.江苏、湖北和浙江三省的碳排放受疫情影响最严重,其碳排放减少量分别占总排放减少量的19.4%、17.0%和12.5%.青海省和西藏自治区受疫情的影响最小.从排放部门方面看,电力部门是多数省份减排量的主要贡献源,对于湖北、重庆、青海和福建等省份,工业部门是碳减排的主要贡献源.对于北京、天津这样的大城市以及四川和黑龙江两省,新冠疫情对交通部门的减排作用最显著.从疫情对碳排放的时间影响看,江苏省的碳排放在2020年1和2月份下降最多,3月份之后,湖北省的碳排放减少量最为突出.而宁夏回族自治区、新疆维吾尔自治区、福建省、陕西省和云南省受疫情影响较小的地区3月份的碳排放已经率先恢复到2019年同期水平.进入4月份,除湖北省的碳排放相比2019年同期下降4.9 Mt二氧化碳外,其他省份均接近或已经恢复到2019年同期水平.

Amino-functionalized core-shell magnetic mesoporous composite microspheres for Pb(Ⅱ) and Cd(Ⅱ) removal

Amino-functionalized Fe3O4@mesoporous SiO/ core-shell composite microspheres NH2-MS in created in multiple synthesis steps have been investigated for Pb（Ⅱ） and Cd（Ⅱ） adsorption. The microspheres were characterized by transmission electron microscope （TEM）, scanning electron microscope （SEM）, N2 adsorption-desorption, zeta potential measurements and vibrating sample magnetometer. Batch adsorption tests indicated that NH2-MS exhibited higher adsorption affinity toward Pb（Ⅱ） and Cd（Ⅱ） than MS did. The Langmuir model could fit the adsorption isotherm very well with maximum adsorption capacity of 128.21 and 51.81 mg/g for Pb（Ⅱ） and Cd（Ⅱ）, respectively, implying that adsorption processes involved monolayer adsorption. Pb（Ⅱ） and Cd（Ⅱ） adsorption could be well described by the pseudo second-order kinetics model, and was found to be strongly dependent on pH and humic acid. The Pb（Ⅱ）- and Cd（Ⅱ）-loaded microspheres were effectively desorbed using 0.01 mol/L HC1 or EDTA solution. NH2-MS have promise for use as adsorbents in the removal of Pb（Ⅱ） and Cd（Ⅱ） in wastewater treatment processes.

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.

The Third China National Stroke Registry (CNSR-Ⅲ) for patients with acute ischaemic stroke or transient ischaemic attack: design, rationale and baseline patient characteristics

Background and purpose Stroke is the leading cause of mortality and disability in China.Precise aetiological classification,imaging and biological markers may predict the prognosis of stroke.The Third China National Stroke Registry(CNSR-Ⅲ),a nationwide registry of ischaemic stroke or transient ischaemic attack(TIA)in China based on aetiology,imaging and biology markers,will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.Methods Between August 2015 and March 2018,the CNSR-Ⅲrecruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China.Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews.Patients were followed for clinical outcomes at 3 months,6 months and 1-5 year annually.Brain imaging,including brain MRI and CT,were completed at baseline.Blood samples were collected and biomarkers were tested at baseline.Results A total of 15166 stroke patients were enrolled,among which 31.7%patients were women with the average age of 62.2±11.3 years.Ischaemic stroke was predominant(93.3%,n=14146)and 1020(6.7%)TIAs were enrolled.Conclusions CNSR-Ⅲis a large scale nationwide registry in China.Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.

Safety and efficacy of Edaravone Dexborneol versus edaravone for patients with acute ischaemic stroke: a phase Ⅱ, multicentre, randomised, double-blind, multiple-dose, active-controlled clinical trial

Background Edaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and(+)-borneol,a food additive with an anti-inflammatory effect in animal ischaemic stroke models.This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke(AIS).Methods In this multicentre,randomised,double-blind,multiple-dose,active-controlled,phaseⅡclinical trial,patients with AIS within 48 hours after stroke onset were randomly assigned(1:1:1:1)to low-dose(12.5 mg),medium-dose(37.5 mg)or high-dose(62.5 mg)Edaravone Dexborneol groups,and an active control group with edaravone(30 mg)by 30 min intravenous infusion every 12 hours,for 14 consecutive days.The primary efficacy outcome was the proportion of modified Rankin Scale(mRS)score≤1 at 90 days and National Institutes of Health Stroke Scale(NIHSS)score change from baseline to 14 days after randomisation.The safety outcome included any adverse event during 90 days after treatment.Results Of 385 patients included in the efficacy analysis,94 were randomised to low-dose group,97 to medium-dose group,98 to high-dose group and 96 to the control group.No significant difference was observed among the four groups on mRS score(mRS≤1,p=0.4054)at 90 days or NIHSS score change at 14 days(p=0.6799).However,a numerically higher percentage of patients with mRSscore≤1 at 90 days in the medium-dose(69.39%)and high-dose(65.63%)groups was observed than in the control group(60.64%).No significant difference in severe adverse events was found among the four groups(p=0.3815).Conclusions Compared with edaravone alone,Edaravone Dexborneol was safe and well tolerated at all doses,although no significant improvement in functional outcomes was observed at 90days.

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.

Stenting for symptomatic intracranial arterial stenosis in China:1-year outcome of a multicentre registry study

background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable.However,it remained uncertain whether the low event rate could be of a long term.We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Methods Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid,middle cerebral,intracranial vertebral or basilar arteries combined with poor collaterals were enrolled.Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators.The primary outcome was the rate of 30-day stroke,transient ischaemic attack and death,and 12-month ischaemic stroke within the same vascular territory,haemorrhagic stroke and vascular death after stenting.results From September 2013 to January 2015,300 patients(ages 58.3±9.78 years)were recruited.Among them,159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent.During the 1-year follow-up,25 patients had a primary end point event.The probability of primary outcome at 1 year was 8.1%(95% CI 5.3% to 11.7%).In 76 patients with digital subtraction angiography follow-up,27.6%(21/76)had re-stenosis≥50% and 18.4%(14/76)had re-stenosis≥70%.No baseline characteristic was associated with the primary outcome.Conclusion The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Further randomised trial of comparing individually tailored stenting with best medical therapy is needed.

The efficacy and safety of nimodipine in acute ischemic stroke patients with mild cognitive impairment: a double-blind, randomized,placebo-controlled trial

Nimodipine might be effective in subcortical vascular dementia(VaD). Its benefit in preventing further cognitive decline in patients with acute ischemic stroke(AIS) and vascular mild cognitive impairment(VaMCI) remains to be established. In this multicenter, double-blind trial, we randomly assigned 654 eligible patients to nimodipine 30 mg three times a day or placebo. The primary outcome was any cognitive decline defined by the changes on the Mini-Mental State Examination(DMMSE à3) or vascular AD assessment scale cognitive subscale(DADAS-cog ! 4) at 6 months. Secondary outcomes included any distribution shift of DADAS-cog, DMMSE or cognitive improvement defined by DADAS-cog à2, or DMMSE ! 0. The primary outcome in the nimodipine group and placebo group were similar for DMMSE à3(4.18% and 7.22%, respectively, P = 0.15) and DADAS-cog ! 4(8.36% and 8.93% respectively,P = 0.88). The distribution shift of DADAS-cog and DMMSE differed significantly between the two groups(P = 0.03 and P = 0.05 respectively). Cognitive improvement occurred in 55.4% in the nimodipine group and 43.6% in the placebo group measured by DADAS-cog à2(Odds Ratio, 1.54; 95% confidence interval[CI] 1.10–2.14, P < 0.01) or 84.0% and 74.6% respectively by DMMSE ! 0(Odds Ratio, 1.79; 95% CI 1.18–2.70, P < 0.01). Nimodipine was associated with better cognitive function in the memory domain. The adverse events rate was similar in two groups. This study is registered with ClinicalTrials.gov,NCT01220622. Nimodipine did not show benefit to prevent cognitive decline in AIS patients with VaMCI, but improved cognition moderately, especially measured in the memory domain.

Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study

Background Tenecteplase(TNK)possesses several pharmacological characteristics superior to conventional alteplase(rt-PA),with well-established safety and efficacy profile in Caucasians.There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic stroke(AIS).Current study aimed to determine the safety dose range of recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)for patients with AIS in China.Methods This multicentre,prospective,randomised,open-label,blinded end-point,phase II study compared three tiers of 0.1,0.25,0.32 mg/kg rhTNK-tPA(to a maximum of 40 mg)with standard 0.9 mg/kg rt-PA(to a maximum of 90 mg)in patients who were eligible for intravenous thrombolysis.The safety outcome were symptomatic intracranial haemorrhage(sICH)within 36 hours.Results Between May 2018 and February 2020,240 patients were randomly assigned to four group,4 of whom did not receive study treatment.The intention-to-treat analysis included 236 patients.There was no difference in the improvement on National Institutes of Health Stroke Scale at day 14 in the 3 tiers and control group(63.3%,77.2%,66.7%vs 62.7%).The number of sICH was 3 of 60(5.0%)in the 0.1 mg/kg group,none in the 0.25 mg/kg group,2 of 60(3.3%)in the 0.32 mg/kg group and 1(1.7%)of 59 in the rt-PA group.There were no significant between-group differences in severe adverse events.Conclusions Similar to the Caucasians,rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset.The dose-efficacy profile of rhTNK-tPA needs to be established with future investigations.