Discovery of hydrocarbon source rocks in the Permian Xinxing Formation in the southern Zhangguangcai range,Northeast China

1.Objective The study area is located at the southern Zhangguangcai range,which is thought to be the eastern part of the Central Asian Orogenic Belt(CAOB).The study area is closed to the eastern margin of the Songliao basin(Fig.1a).No petroleum exploration or related research work have been conducted in this area by far.Based on our most recent geological mapping,numerous hydrocarbon source rocks were firstly discovered within the Xinxing Formation,which is widely exposed from the central Jilin Province to the southeastern Heilongjiang province.The Xinxing Formation covers an area of nearly 1000 km2 with a total thickness of more than 1481 m(Regional Geology of Heilongjiang Province,1993).Therefore,the Xinxing Formation has huge potential to form oil and gas resources.This new discovery of hydrocarbon source rocks within the Xinxing Formation could provide critical clues for oil and gas resources’investigation in Northeast China,also may has important economic significance.

Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

Background Myelin oligodendrocyte glycoprotein(MOG)antibody-associated disease(MOGAD)is an autoimmune demy-elinating disorder of the central nervous system.Methods Extracted proteins from 34 cerebrospinal fluid(CSF)samples[patients with MOGAD(MOG group,n=12);healthy controls(HC group,n=12);patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases(IND group,n=10)]were processed and subjected to label-free quantitative proteomics.Supervised partial least squares-discriminant analysis(PLS-DA)and orthogonal PLS-DA(O-PLS-DA)models were also performed based on proteomics data.Functional analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and Genomes.An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD.Results Four hundred and twenty-nine DEPs(149 upregulated and 280 downregulated proteins)were identified in the MOG group compared to the HC group according to the P value and fold change(FC).Using the O-PLS-DA model,872 differentially abundant proteins were identified with variable importance projection(VIP)scores>1.Five proteins(gamma-glutamyl hydrolase,cathepsin F,interalpha-trypsin inhibitor heavy chain 5,latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1)overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired.Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades,cell adhesion,axon guidance,and glycosphingolipid biosynthesis compared to the HC group.Conclusion The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

缺血性卒中后感染介导了低密度脂蛋白胆固醇与全因死亡风险之间的U形曲线关系

在缺血性卒中急性期,尚不清楚低水平的低密度脂蛋白胆固醇(LDL-C)的病理生理意义,本研究旨在评估LDL-C水平、卒中后感染和全因死亡间的关系.研究共纳入804,855名缺血性卒中患者.通过多元logistic回归模型分析LDL-C水平、感染和死亡之间的关系,采用基于反事实框架的中介分析,以阐明卒中后感染的中介效应,研究发现LDL-C与死亡风险之间呈U形曲线关系,死亡风险最低的LDL-C水平为2.67mmol/L.经多因素校正后,与LDL-C=2.50~2.99mmol/L相比,LDL-C<1.0mmol/L患者的死亡风险比值比(OR)为2.22(95%置信区间(CI):1.77~2.79),LDL-C5.0mmol/L患者的OR为1.22(95%CI:0.98~1.50).LDL-C与死亡之间关联的38.20%(95%CI:5.96~70.45,P=0.020)由感染介导:在逐步剔除存在心血管危险因素的患者后,LDL-C与全因死亡间的U形曲线关系及感染的中介效应与主要分析一致,而死亡风险最低时的LDL-C水平逐渐升高.在缺血性卒中急性期,LDL-C水平与全因死亡之间存在U形曲线关系,其被卒中后感染介导。

Temporal trends and rural-urban disparities in cerebrovascular risk factors,in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015:a nationwide serial cross-sectional survey

Background Stroke is the leading cause of mortality in China,with limited evidence of in-hospital burden obtained from nationwide surveys.We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors,management and outcomes from 2005 to 2015.Methods We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005,2010 and 2015.We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach.We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.Results We analysed 28277 ischaemic stroke admissions from 189 participating hospitals.From 2005 to 2015,the estimated national hospital admission rate for ischaemic stroke per 100000 people increased(from 75.9 to 402.7,Ptrend<0.001),and the prevalence of risk factors,including hypertension,diabetes,dyslipidaemia and current smoking,increased.The composite score of diagnostic tests for stroke aetiology assessment(from 0.22 to 0.36,Ptrend<0.001)and secondary prevention treatments(from 0.46 to 0.70,Ptrend<0.001)were improved.A temporal decrease was found in discharge against medical advice(DAMA)(from 15.2%(95%CI 13.7%to 16.7%)to 8.6%(8.1%to 9.0%);adjusted Ptrend=0.046),and decreases in in-hospital mortality(0.7%in 2015 vs 1.8%in 2005;adjusted OR(aOR)0.52;95%CI 0.32 to 0.85)and the composite outcome of in-hospital mortality or DAMA(8.4%in 2015 vs 13.9%in 2005;aOR 0.65;95%CI 0.47 to 0.89)were observed.Disparities between rural and urban hospitals narrowed;however,disparities persisted in in-hospital management(brain MRI:rural-urban difference from−14.4%to−11.2%;cerebrovascular assessment:from−20.3%to−16.7%;clopidogrel:from−2.1%to−10.3%;anticoagulant for atrial fibrillation:from−10.9%to−8.2%)and in-hospital outcomes(DAMA:from 2.7%to 5.0%;composite outcome of in-hospital mortality or DAMA:from 2.4%to 4.6%).Conclusions From 2005 to 2015,improvements in hospital admission and in-hospital management for ischaemic stroke in China were found.A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed.Disparities between rural and urban hospitals generally narrowed but persisted.

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.

Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism(SPACE)trial:rationale and design

Backgrounds Embolic stroke is one of the main mechanisms of ischaemic stroke.Even if treated with recommended antithrombotic agents,stroke recurrence remains high.The Shuxuetong injection,a purified extract of traditional Chinese medicine widely used for thrombus diseases in clinical practice in China,could be a promising agent to prevent stroke recurrence.Aims To describe the design of the Shuxuetong injection for prevention of recurrence in acute ischaemic stroke with embolism mechanisms.Design The Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism(SPACE)trial is a multicentre,randomised,double-blind,placebo-controlled,parallel-group,superiority trial to evaluate the efficacy and safety of Shuxuetong injection in reducing recurrence or silent new ischaemic lesions on patients with acute embolic stroke within 10 days.An estimated 2416 patients with embolic stroke within 72 hours of symptom onset from 80 hospitals will be randomly assigned to one of two groups receiving Shuxuetong injection or placebo injection for 10 days.The primary endpoint is symptomatic or asymptomatic new cerebral infarction within 10 days after randomisation.Conclusion The SPACE Trial will provide valuable evidence for the efficacy and safety of Shuxuetong injection for the prevention of stroke recurrence in patients with imaging-defined embolic stroke.

Impact of Libido at 2 Weeks after Stroke on Risk of Stroke Recurrence at 1-Year in a Chinese Stroke Cohort Study

Background： There were few studies on the relation between changes in libido and incidence of stroke recurrence. The aim of this study was to investigate the relationship between libido decrease at 2 weeks after stroke and recurrent stroke at 1-year. Methods： It is a multi-centered, prospective cohort study. The 14th item of the Hamilton Depression Rating Scale-17 was used to evaluate changes of libido in poststroke patients at 2 weeks. Stroke recurrence was defined as an aggravation of former neurological functional deficit, new local or overall symptoms, or stroke diagnosed at re-admission. Results： Among 2341 enrolled patients, 1757 patients had completed follow-up data, 533 （30.34%） patients had decreased libido at 2 weeks, and 166 （9.45%） patients had recurrent stroke at l-year. Multivariate logistic regression analysis showed that, compared with patients with normal libido, the odds ratio （OR） of recurrent stroke in patients with decreased libido was reduced by 4 l% （OR = 0.59, 95% confidence interval [CI]： 0.40-0.87）. The correlation was more prominent among male patients （OR = 0.52, 95% CI： 0.31 0.85） and patients of≥60 years of age （OR = 0.57, 95% CI： 0.35-0.93）. Conclusions： One out of three stroke patients in China's Mainland has decreased libido at 2 weeks after stroke. Decreased libido is a protective factor for stroke recurrence at 1-year, which is more prominent among older male patients.

Prognostic value of admission hyperglycemia on outcomes of thrombolysis in ischemic stroke patients with or without diabetes

Thrombolytic therapy within 4.5 h from symptom onset is a recognized effective and standard therapy for acute ischemic stroke(AIS),but some patients still have a poor clinical outcome.The evaluation and control of predictors for AIS poor clinical outcomes is integral to achieving optimal treatments,but the prognostic value of admission blood glucose(ABG)for this purpose is unclear and still under debate.ABG evaluated in patients without diabetes mellitus(DM)often suggests acute stress hyperglycemia,while ABG may have a close relationship with long-term blood glucose control in patients with DM.However,in most studies about the influence of ABG on the prognosis of recombinant tissue-type plasminogen activator(rtPA)therapy after AIS,patients were not classified into those with and without DM.The present study was designed to investigate the prognostic value of ABG for clinical outcomes of AIS after thrombolysis according to DM status in a Chinese population.

China Stroke Statistics 2019:A Report From the National Center for Healthcare Quality Management in Neurological Diseases,China National Clinical Research Center for Neurological Diseases,the Chinese Stroke Association,National Center for Chronic and Non-communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations

China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading causes of death behind malignant tumours and heart disease.The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100000 population and 246.8 per 100000 person-years,respectively.According to the Global Burden of Disease Study 2017,the years of life lost(YLLs)per 100000 population for stroke increased by 14.6%;YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.The absolute numbers and rates per 100000 population for all-age disability-adjusted life years(DALYs)for stroke increased substantially between 1990 and 2017,and stroke was the leading cause of all-age DALYs in 2017.The main contributors to cerebrovascular diseases include behavioural risk factors(smoking and alcohol use)and pre-existing conditions(hypertension,diabetes mellitus,dyslipidaemia and atrial fibrillation(AF)).The most prevalent risk factors among stroke survivors were hypertension(63.0%-84.2%)and smoking(31.7%-47.6%).The least prevalent was AF(2.7%-7.4%).The prevalences for major risk factors for stroke are high and most have increased over time.Based on the latest national epidemiological data,26.6%of adults aged≥15 years(307.6 million adults)smoked tobacco products.For those aged≥18 years,age-adjusted prevalence of hypertension was 25.2%;adjusted prevalence of hypercholesterolaemia was 5.8%;and the standardised prevalence of diabetes was 10.9%.For those aged≥40 years,the standardised prevalence of AF was 2.31%.Data from the Hospital Quality Monitoring System showed that 3010204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.Of those,2466785(81.9%)were ischaemic strokes(ISs);447609(14.9%)were intracerebral haemorrhages(ICHs);and 95810(3.2%)were subarachnoid haemorrhages(SAHs).The average age of patients admitted was 66 years old,and nearly 60%were male.A total of 1555(0.1%),2774(0.6%)and 1347(1.4%)paediatric strokes(age<18 years)were identified among IS,ICH and SAH,respectively.Over one-third(1063892(35.3%))of the patients were covered by urban resident basic medical insurance,followed by urban employee basic medical insurance(699513(23.2%))and new rural cooperative medical schema(489361(16.3%)).The leading risk factor was hypertension(67.4%for IS,77.2%for ICH and 49.1%for SAH),and the leading comorbidity was pneumonia or pulmonary infection(10.1%for IS,31.4%for ICH and 25.2%for SAH).In-hospital death/discharge against medical advice rate was 8.3%for stroke inpatients,ranging from 5.8%for IS to 19.5%for ICH.The median and IQR of length of stay was 10.0(7.0-14.0)days,ranging from 10.0(7.0-13.0)in IS to 14.0(8.0-22.0)in SAH.Data from the Chinese Stroke Center Alliance demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS,ICH and SAH were 0.77±0.21,0.72±0.28 and 0.59±0.32,respectively.

Newly detected atrial fibrillation is associated with cortex-involved ischemic stroke

Background: Both cortical and cortical-subcortical (cortex-involved) lesions are typically associated with embolic stroke, of which atrial fibrillation (AF) is the common cause. The aim of this study was to find out the associations between cortex-involved stroke, vascular risk factors, and the subtypes (discovery time and duration) of AF. Methods: This was an imaging study of the China Atrial Fibrillation Screening in Acute Ischemic Stroke Patients (CRIST) trial. Between October 2013 and June 2015, 1511 acute ischemic stroke or transient ischemic attack (TIA) patients within 7 days after stroke onset at 20 Chinese hospitals were enrolled in this prospective, multicenter cohort, cross-sectional study. The final analysis of this sub-study included 243 patients with AF with required magnetic resonance imaging (MRI) sequences. AF was diagnosed by 6-day Holter monitoring and classified by duration of 24 h. Two stroke specialists blinded to the clinical information reviewed MRI (diffusion-weighted MRI). The third stroke specialists, also blinded to the clinical information, assessed the conflicts. Adjusted large artery atherosclerosis as confounding factor, the associations between cortex-involved lesions, vascular risk factors, and the subtype of AF were evaluated by univariate and multivariate regression analyses. Results: Of 243 acute ischemic stroke patients with AF, 190 were known AF and 53 were newly detected AF. There were 28 patients with AF persistent >24 h and 25 persistent ≤24 h in newly detected AF. Patients with newly detected AF were likely to have a fewer history of stroke or TIA (16.98% vs. 36.31%, P = 0.008) and lower fasting blood glucose (5.91 ± 1.83 mmol/L vs. 6.75 ± 3.83 mmol/L, P = 0.030) than patients with known AF. Among these 243 patients, 102 (41.98%) patients were with cortex-involved lesions. Cortex-involved lesions were significantly related to newly detected AF persistent >24 h (odds ratio [OR]: 4.517, 95% confidence interval [CI]: 1.490–13.696, P = 0.008), proteinuria (OR: 3.431, 95% CI: 1.530–7.692, P = 0.021), and glycosylated hemoglobin (OR: 0.632, 95% CI: 0.464–0.861, P = 0.004). Conclusions: Compared to previously known AF, newly detected AF persistent >24 h was associated with cortex-involved ischemic stroke.

Establishment of an efficient reverse genetic system of Mumps virus S79 from cloned DNA

Background Mumps is a common type of respiratory infectious disease caused by mumps virus(MuV),and can be effectively prevented by vaccination.In this study,a reverse genetic system of MuV that can facilitate the rational design of safer,more efficient mumps vaccine candidates is established.Methods MuV-S79 cDNA clone was assembled into a full-length plasmid by means of the GeneArtTM High-Order Genetic Assembly System,and was rescued via reverse genetic technology.RT-PCR,sequencing,and immunofluorescence assays were used for rMuV-S79 authentication.Viral replication kinetics and in vivo experimental models were used to evaluate the replication,safety,and immunogenicity of rMuV-S79.Results A full-length cDNA clone of MuV-S79 in the assembly process was generated by a novel plasmid assemble strategy,and a robust reverse genetic system of MuV-S79 was successfully established.The established rMuV-S79 strain could reach a high virus titer in vitro.The average viral titer of rMuV-S79 in the lung tissues was 2.68±0.14 log10PFU/g lung tissue,and rMuV-S79 group did not induce inflammation in the lung tissues in cotton rats.Neutralizing antibody titers induced by rMuV-S79 were high,long-lasting and could provide complete protection against MuV wild strain challenge.Conclusion We have established a robust reverse genetic system of MuV-S79 which can facilitate the optimization of mumps vaccines.rMuV-S79 rescued could reach a high virus titer and the safety was proven in vivo.It could also provide complete protection against MuV wild strain challenge.

Attenuated MuV-S79 as vector stably expressing foreign gene

Background To describe mumps virus(MuV)used as a vector to express enhanced green fluorescent protein(EGFP)or red fluorescent protein(RFP)genes.Methods Molecular cloning technique was applied to establish the cDNA clones of recombinant mumps viruses(rMuVs).rMuVs were recovered based on our reverse genetic system of MuV-S79.The properties of rMuVs were determined by growth curve,plaque assay,fluorescent microscopy and determination of fluorescent intensity.Results Three recombinant viruses replicated well in Vero cells and similarly as parental rMuV-S79,expressed heterologous genes in high levels,and were genetically stable in at least 15 passages.Conclusion rMuV-S79 is a promising platform to accommodate foreign genes like marker genes,other antigens and immunomodulators for addressing various diseases.