Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effec...Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.展开更多
Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrate...Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.展开更多
Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship betwee...Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
Objective Hypoglossal nerve-facial nerve‘side’-to-side neurorrhaphy is a new method for the treatment of potential incomplete facial paralysis after acoustic neuroma.However,there are differences in postoperative ou...Objective Hypoglossal nerve-facial nerve‘side’-to-side neurorrhaphy is a new method for the treatment of potential incomplete facial paralysis after acoustic neuroma.However,there are differences in postoperative outcomes among patients.This study analysed preoperative factors that may influence the treatment outcomes of neurorrhaphy.Methods We performed a retrospective study of 53 patients who were treated by neurorrhaphy for facial paralysis after acoustic neuroma resection.After a one-year follow-up period,the patients were divided into two groups according to facial functional outcome:better recovery or ordinary recovery.We analysed the following factors:gender,age,tumour size,and characteristics,tumour adhesion to the facial nerve,the duration of facial paralysis(DFP)and F wave appearance prior to neurorrhaphy(F wave).Results Univariate analysis showed significant differences between the two groups in DFP(P=0.0002),tumour adhesion to the facial nerve(P=0.0079)and F waves(P=0.0048).Logistic regression analysis of these factors also showed statistical significance with P values of 0.042 for the DFP,0.043 for F waves,and 0.031 for tumour adhesion to the facial nerve.Conclusions Tumour adhesion to the facial nerve,F waves appearance and DFP prior to neurorrhaphy are the predominant factors that influence treatment outcomes.展开更多
BACKGROUND Optic nerve sheath diameter(ONSD)measurement is one of the non-invasive methods recommended for increased intracranial pressure(ICP)monitoring.AIM This study aimed to evaluate the roles of optic nerve sheat...BACKGROUND Optic nerve sheath diameter(ONSD)measurement is one of the non-invasive methods recommended for increased intracranial pressure(ICP)monitoring.AIM This study aimed to evaluate the roles of optic nerve sheath diameter(ONSD)and ONSD/eyeball transverse diameter(ETD)ratio in predicting prognosis of death in comatose patients with acute stroke during their hospitalization.METHODS A total of 67 comatose patients with acute stroke were retrospectively recruited.The ONSD and ETD were measured by cranial computed tomography(CT)scan.All patients underwent cranial CT scan within 24 h after coma onset.Patients were divided into death group and survival group according to their survival status at discharge.The differences of the ONSD and ONSD/ETD ratio between the two groups and their prognostic values were compared.RESULTS The ONSD and ONSD/ETD ratio were 6.07±0.72 mm and 0.27±0.03 in the comatose patients,respectively.The ONSD was significantly greater in the death group than that in the survival group(6.32±0.67 mm vs 5.65±0.62 mm,t=4.078,P<0.0001).The ONSD/ETD ratio was significantly higher in the death group than that in the survival group(0.28±0.03 vs 0.25±0.02,t=4.625,P<0.0001).The area under the receiver operating characteristic curve was 0.760(95%CI:0.637-0.882,P<0.0001)for the ONSD and 0.808(95%CI:0.696-0.920,P<0.0001)for the ONSD/ETD ratio.CONCLUSION The mortality increased in comatose patients with acute stroke when the ONSD was>5.7 mm or the ONSD/ETD ratio was>0.25.Both indexes could be used as prognostic tools for comatose patients with acute stroke.The ONSD/ETD ratio was more stable than the ONSD alone,which would be preferred in clinical practice.展开更多
Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignan...Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;P<0.0001)in patients with IDH-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDHmutant gliomas.展开更多
Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of t...Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury(TBI).In this study,we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI.Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses,including complement and coagulation cascades,as well as chemokine signaling pathways.Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1,RelA,IRF1,STAT1,and Spi1 play pivotal roles in the secondary injury that occurs after TBI,which further corroborates the functional enrichment for inflammatory factors.Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.展开更多
After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been full...After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.展开更多
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 articl...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.展开更多
The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neuro...The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.展开更多
Objective This study aimed to examine the trends in stroke mortality among young and middle-aged adults in China.Methods Data were obtained from the China national vital registration system.Significant changes in mort...Objective This study aimed to examine the trends in stroke mortality among young and middle-aged adults in China.Methods Data were obtained from the China national vital registration system.Significant changes in mortality were assessed by Joinpoint regression.Age-period-cohort analysis was used to explain the reasons for the changes.Future mortality and counts were predicted by the Bayesian age-period-cohort model.Results Between 2002 and 2019,a total of 6,253,951 stroke mortality in young and middle-aged adults were recorded.The age-adjusted mortality rates(AAMRs)of women showed a downward trend.The annual percent changes(APC)were-3.5%(-5.2%,-1.7%)for urban women and-2.8%(-3.7%,-1.9%)for rural women.By contrast,the AAMRs per 100,000 for rural men aged 25–44 years continued to rise from 9.40 to 15.46.The AAMRS for urban men aged 25–44 years and urban and rural men aged 45–64years did not change significantly.Between 2020 and 2030,the projected stroke deaths are 1,423,584 in men and 401,712 in women.Conclusion Significant sex and age disparities in the trends of stroke mortality among young and middle-aged adults were identified in China.Targeted health policy measures are needed to address the burden of stroke in the young generation,especially for rural men,with a focus on the prevention and management of high risk factors.展开更多
For decades,chiral nanomaterials have been extensively studied because of their extraordinary properties.Chiral nanostructures have attracted a lot of interest because of their potential applications including biosens...For decades,chiral nanomaterials have been extensively studied because of their extraordinary properties.Chiral nanostructures have attracted a lot of interest because of their potential applications including biosensing,asymmetric catalysis,optical devices,and negative index materials.Circularly polarized light(CPL)is the most attractive source for chirality owing to its high availability,and now it has been used as a chiral source for the preparation of chiral matter.In this review,the recent progress in the field of CPL-enabled chiral nanomaterials is summarized.Firstly,the recent advancements in the fabrication of chiral materials using circularly polarized light are described,focusing on the unique strategies.Secondly,an overview of the potential applications of chiral nanomaterials driven by CPL is provided,with a particular emphasis on biosensing,catalysis,and phototherapy.Finally,a perspective on the challenges in the field of CPL-enabled chiral nanomaterials is given.展开更多
Stem cells(SCs)are cells with strong proliferation ability,multilineage differentiation potential and self-renewal capacity.SC transplantation represents an important therapeutic advancement for the treatment strategy...Stem cells(SCs)are cells with strong proliferation ability,multilineage differentiation potential and self-renewal capacity.SC transplantation represents an important therapeutic advancement for the treatment strategy of neurological diseases,both in the preclinical experimental and clinical settings.Innovative and breakthrough SC labelling and tracking technologies are widely used to monitor the distribution and viability of transplanted cells non-invasively and longitudinally.Here we summarised the research progress of the main tracers,labelling methods and imaging technologies involved in current SC tracking technologies for various neurological diseases.Finally,the applications,challenges and unresolved problems of current SC tracing technologies were discussed.展开更多
Tripartite motif 21(TRIM21)is an E3 ubiquitin ligase that shows great promise for protein degradation through ubiquitination.Here,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands ...Tripartite motif 21(TRIM21)is an E3 ubiquitin ligase that shows great promise for protein degradation through ubiquitination.Here,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands were fabricated.After conjugated with an NLR family pyrin domain-containing protein 3(NLRP3)antibody(D-NP-a NLRP3 or L-NP-a NLRP3),DNP-a NLRP3 showed effective delivery efficiency of the antibody into microglia and prevented Aβ-mediated microglia senescence,and p16^(ink4a),a marker of senescence,in the microglia was reduced by 90.3%±7.8% while L-NP-a NLRP3 decreased by 48.01%±3.1%.Mechanistic investigations revealed that the D-NP-a NLRP3((1.5±0.3)×10^(7)M^(-1))exhibited sixteen-fold larger binding affinity to transmembrane glycoprotein SLC3A2 than L-type((9.5±2.7)×10^(5)M^(-1)),which led to a high efficiency of antibody delivery and TRIM21-dependent NLRP3 degradation.Notably,the blood-brain barrier(BBB)-crossing ability of chiral NP-a NLRP3 as well as NLRP3 degradation was demonstrated in vivo.The APP/PS1 Alzheimer's disease(AD)model mice experiments exhibited a reduction of 89.7%±6.8% for the NLRP3 protein and 84.2±7.5% for p16^(ink4a)following the intravenous administration of D-NP-a NLRP3 once a week for 60 days.Furthermore,the levels of the AD markers Aβ and phosphorylatedTau in the brains were reduced by 86.2%±8.2% and 81.6%±9.1%;these were 2.1-fold and 1.9-fold higher than those treated with L-NP-a NLRP3,respectively.The studies provide a method to rescue AD-like pathologies and prevent senescence.展开更多
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...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.展开更多
Objective To investigate cognitive dysfunction in patients with carotid artery stenosis(CAS) and potential risk factors related to cognitive-especially memory-dysfunction. Methods Forty-seven patients with carotid art...Objective To investigate cognitive dysfunction in patients with carotid artery stenosis(CAS) and potential risk factors related to cognitive-especially memory-dysfunction. Methods Forty-seven patients with carotid artery stenosis were recruited into our study cohort. The Mini-Mental State Examination(MMSE) and the Montreal Cognitive Assessment(MoCA) were adopted to assess cognitive function, the Wechsler Memory Scale(WMS) to assess memory function, high-resolution MRI and enhanced ultrasound to evaluate carotid plaques, and computed tomography perfusion(CTP) imaging to evaluate intracranial blood perfusion. Single-factor analysis and multiple-factor regression analysis were used to analyze potential risk factors of cognitive impairment. Results Mini-Mental State Examination test results showed that 22 patients had cognitive impairment, and MoCA test results showed that 10 patients had cognitive impairment. Analysis of various risk factors indicated that the average memory quotient of female patients was higher than that of males(P = 0.024). The cognitive and memory performance of those with an educational background above high school were significantly better than those of participants with high school or lower(P = 0.045). Patients with abnormal intracranial perfusion performed worse on the MMSE test(P = 0.024), and their WMS scores were significantly lower(P = 0.007). The MMSE scores and the memory quotients were significantly lower in patients with a history of cerebral infarction(MMSE, P = 0.047, memory quotient score, P = 0.018). Conclusion A history of cerebral infarction and abnormal cerebral perfusion are associated with decline in overall cognitive function and memory in patients with carotid stenosis. Being female and having an educational background above high school may be protective factors in the development of cognitive dysfunction.展开更多
Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We r...Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We retrospectively examined EGFRvⅢ expression and EGFRvⅢ nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization(WHO) II gliomas, 84 WHO Ⅲ gliomas and 72 glioblastomas(WHO IV). Factors that correlated with EGFRvⅢ and EGFRvⅢ nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.Results: Log-rank tests showed that patient age, Karnofsky performance scale(KPS) score, tumor grade,EGFRvⅢ expression, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, isocitrate dehydrogenase(IDH)mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase(MGMT) status(P<0.05) were significantly correlated with overall survival(OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, and IDH mutation(P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvⅢ nuclear translocation(≥7%) had both significantly shorter OS [hazard ratio(HR): 1.920, 95% confidence interval(95% CI): 1.228-3.003, P=0.004] and progression-free survival(PFS) times(HR: 1.661, 95% CI: 1.116-2.471, P=0.012) than those with a low level of EGFRvⅢ nuclear translocation(<7%).Conclusions: A high level of EGFRvⅢ nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvⅢ expression is not an independent clinical prognostic factor. The level of EGFRvⅢ nuclear translocation maybe a novel and crucial prognostic biomarker in glioma.展开更多
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 S...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.展开更多
The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative st...The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.展开更多
基金supported by the National Natural Science Foundation of China,No.82171270 (to ZL)Public Service Platform for Artificial In telligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People's Republic of China,No.2020-0103-3-1 (to ZL)+3 种基金the Natural Science Foundation of Beijing,No.Z200016 (to ZL)Beijing Talents Project,No.2018000021223ZK03 (to ZL)Beijing Municipal Committee of Science and Technology,No.Z201 100005620010 (to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029 (to YongW)。
文摘Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.
基金supported by the Chongqing Science and Technology CommitteeNatural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0065 (to YL)。
文摘Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.
基金supported by National Natural Science Foundation of China(No.82001239)Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support,code(NO.202112)。
文摘Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
基金supported by grants from the National Natural Science Foundation of China[No.81471239].
文摘Objective Hypoglossal nerve-facial nerve‘side’-to-side neurorrhaphy is a new method for the treatment of potential incomplete facial paralysis after acoustic neuroma.However,there are differences in postoperative outcomes among patients.This study analysed preoperative factors that may influence the treatment outcomes of neurorrhaphy.Methods We performed a retrospective study of 53 patients who were treated by neurorrhaphy for facial paralysis after acoustic neuroma resection.After a one-year follow-up period,the patients were divided into two groups according to facial functional outcome:better recovery or ordinary recovery.We analysed the following factors:gender,age,tumour size,and characteristics,tumour adhesion to the facial nerve,the duration of facial paralysis(DFP)and F wave appearance prior to neurorrhaphy(F wave).Results Univariate analysis showed significant differences between the two groups in DFP(P=0.0002),tumour adhesion to the facial nerve(P=0.0079)and F waves(P=0.0048).Logistic regression analysis of these factors also showed statistical significance with P values of 0.042 for the DFP,0.043 for F waves,and 0.031 for tumour adhesion to the facial nerve.Conclusions Tumour adhesion to the facial nerve,F waves appearance and DFP prior to neurorrhaphy are the predominant factors that influence treatment outcomes.
文摘BACKGROUND Optic nerve sheath diameter(ONSD)measurement is one of the non-invasive methods recommended for increased intracranial pressure(ICP)monitoring.AIM This study aimed to evaluate the roles of optic nerve sheath diameter(ONSD)and ONSD/eyeball transverse diameter(ETD)ratio in predicting prognosis of death in comatose patients with acute stroke during their hospitalization.METHODS A total of 67 comatose patients with acute stroke were retrospectively recruited.The ONSD and ETD were measured by cranial computed tomography(CT)scan.All patients underwent cranial CT scan within 24 h after coma onset.Patients were divided into death group and survival group according to their survival status at discharge.The differences of the ONSD and ONSD/ETD ratio between the two groups and their prognostic values were compared.RESULTS The ONSD and ONSD/ETD ratio were 6.07±0.72 mm and 0.27±0.03 in the comatose patients,respectively.The ONSD was significantly greater in the death group than that in the survival group(6.32±0.67 mm vs 5.65±0.62 mm,t=4.078,P<0.0001).The ONSD/ETD ratio was significantly higher in the death group than that in the survival group(0.28±0.03 vs 0.25±0.02,t=4.625,P<0.0001).The area under the receiver operating characteristic curve was 0.760(95%CI:0.637-0.882,P<0.0001)for the ONSD and 0.808(95%CI:0.696-0.920,P<0.0001)for the ONSD/ETD ratio.CONCLUSION The mortality increased in comatose patients with acute stroke when the ONSD was>5.7 mm or the ONSD/ETD ratio was>0.25.Both indexes could be used as prognostic tools for comatose patients with acute stroke.The ONSD/ETD ratio was more stable than the ONSD alone,which would be preferred in clinical practice.
基金supported bygrants from the Beijing Hospitals Authority Youth Programme(Grant No.QML20190506)the Capital Health Development Research Project(Grant No.2020-2-1072).
文摘Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;P<0.0001)in patients with IDH-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDHmutant gliomas.
基金supported by the National Natural Science Foundation of China,No. 81771327a grant for the Platform Construction of Basic Research and Clinical Translation of Nervous System Injury,China,No. PXM2020_026280_000002 (both to BYL)
文摘Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury(TBI).In this study,we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI.Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses,including complement and coagulation cascades,as well as chemokine signaling pathways.Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1,RelA,IRF1,STAT1,and Spi1 play pivotal roles in the secondary injury that occurs after TBI,which further corroborates the functional enrichment for inflammatory factors.Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.
基金supported by the National Natural Science Foundation of China,No. 81771327 (to BYL)Construction of Central Nervous System Injury Basic Science and Clinical Translational Research PlatformBudget of Beijing Municipal Health Commission 2020, No. PXM2020_026280_000002 (BYL)。
文摘After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.
基金This work was supported by grants from the Ministry of Science and Technology and the Ministry of Health of the People’s Republic of China(National S&T Major Project of China:2011BAI08B02,2012ZX09303,2013BAI09B14,2013BAI09B03,2015BAI12B02,2015BAI12B04,2017YFC1310900,2017YFC1310901 and 2017YFC1310903)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2013BAI09B03)+1 种基金Beijing Municipal Committee of Science and Technology(D15110700200000,D151100002015001,D151100002015002,Z161100000516223 and Z141107002514125)Beijing Institute for Brain Disorders(BIBD-PXM2013_014226_07_000084).
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.82171346(to YZW)82171269(to JLY)+1 种基金82171471(to HF)Beijing Nova Program,No.Z201100006820076(to JLY).
文摘The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.
文摘Objective This study aimed to examine the trends in stroke mortality among young and middle-aged adults in China.Methods Data were obtained from the China national vital registration system.Significant changes in mortality were assessed by Joinpoint regression.Age-period-cohort analysis was used to explain the reasons for the changes.Future mortality and counts were predicted by the Bayesian age-period-cohort model.Results Between 2002 and 2019,a total of 6,253,951 stroke mortality in young and middle-aged adults were recorded.The age-adjusted mortality rates(AAMRs)of women showed a downward trend.The annual percent changes(APC)were-3.5%(-5.2%,-1.7%)for urban women and-2.8%(-3.7%,-1.9%)for rural women.By contrast,the AAMRs per 100,000 for rural men aged 25–44 years continued to rise from 9.40 to 15.46.The AAMRS for urban men aged 25–44 years and urban and rural men aged 45–64years did not change significantly.Between 2020 and 2030,the projected stroke deaths are 1,423,584 in men and 401,712 in women.Conclusion Significant sex and age disparities in the trends of stroke mortality among young and middle-aged adults were identified in China.Targeted health policy measures are needed to address the burden of stroke in the young generation,especially for rural men,with a focus on the prevention and management of high risk factors.
基金financially the National Natural Science Foundation of China(51902136)the Fundamental Research Funds for the Central Universities(JUSRP12003,JUSRP622026)Natural Science Foundation of Jiangsu Province(BK20211236)。
文摘For decades,chiral nanomaterials have been extensively studied because of their extraordinary properties.Chiral nanostructures have attracted a lot of interest because of their potential applications including biosensing,asymmetric catalysis,optical devices,and negative index materials.Circularly polarized light(CPL)is the most attractive source for chirality owing to its high availability,and now it has been used as a chiral source for the preparation of chiral matter.In this review,the recent progress in the field of CPL-enabled chiral nanomaterials is summarized.Firstly,the recent advancements in the fabrication of chiral materials using circularly polarized light are described,focusing on the unique strategies.Secondly,an overview of the potential applications of chiral nanomaterials driven by CPL is provided,with a particular emphasis on biosensing,catalysis,and phototherapy.Finally,a perspective on the challenges in the field of CPL-enabled chiral nanomaterials is given.
基金by National Science Foundation of China(81801199,81830038,81971094,91949208)Beijing Municipal Science&Technology Commission(Z181100001818001).
文摘Stem cells(SCs)are cells with strong proliferation ability,multilineage differentiation potential and self-renewal capacity.SC transplantation represents an important therapeutic advancement for the treatment strategy of neurological diseases,both in the preclinical experimental and clinical settings.Innovative and breakthrough SC labelling and tracking technologies are widely used to monitor the distribution and viability of transplanted cells non-invasively and longitudinally.Here we summarised the research progress of the main tracers,labelling methods and imaging technologies involved in current SC tracking technologies for various neurological diseases.Finally,the applications,challenges and unresolved problems of current SC tracing technologies were discussed.
基金supported by the National Natural Science Foundation of China(22274067,82071187)the Natural Science Foundation of Jiangsu Province(BK20230043)the Fundamental Research Funds for the Central Universities(JUSRP622009)。
文摘Tripartite motif 21(TRIM21)is an E3 ubiquitin ligase that shows great promise for protein degradation through ubiquitination.Here,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands were fabricated.After conjugated with an NLR family pyrin domain-containing protein 3(NLRP3)antibody(D-NP-a NLRP3 or L-NP-a NLRP3),DNP-a NLRP3 showed effective delivery efficiency of the antibody into microglia and prevented Aβ-mediated microglia senescence,and p16^(ink4a),a marker of senescence,in the microglia was reduced by 90.3%±7.8% while L-NP-a NLRP3 decreased by 48.01%±3.1%.Mechanistic investigations revealed that the D-NP-a NLRP3((1.5±0.3)×10^(7)M^(-1))exhibited sixteen-fold larger binding affinity to transmembrane glycoprotein SLC3A2 than L-type((9.5±2.7)×10^(5)M^(-1)),which led to a high efficiency of antibody delivery and TRIM21-dependent NLRP3 degradation.Notably,the blood-brain barrier(BBB)-crossing ability of chiral NP-a NLRP3 as well as NLRP3 degradation was demonstrated in vivo.The APP/PS1 Alzheimer's disease(AD)model mice experiments exhibited a reduction of 89.7%±6.8% for the NLRP3 protein and 84.2±7.5% for p16^(ink4a)following the intravenous administration of D-NP-a NLRP3 once a week for 60 days.Furthermore,the levels of the AD markers Aβ and phosphorylatedTau in the brains were reduced by 86.2%±8.2% and 81.6%±9.1%;these were 2.1-fold and 1.9-fold higher than those treated with L-NP-a NLRP3,respectively.The studies provide a method to rescue AD-like pathologies and prevent senescence.
基金Simcere Pharmaceutical Group supported the present study
文摘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.
基金supported by the capital health research and development of special project [2016-2-2043]the ‘13th Five-Year Plan’ National Science and Technology supporting plan [2015BAI12B04]+4 种基金the National Key Technology Research and Development Program of the Ministry of Science and Technology of China [2013BAI09B03]Beijing Municipal Administration of Hospitals’ Mission Plan [SML20150501]Beijing Institute for Brain Disorders [BIBD-PXM2013_014226_07_000084]the Program of Beijing Municipal Science and Technology Commission [Z13110200680000]the Program of the National Natural Science Foundation of China [81371292]
文摘Objective To investigate cognitive dysfunction in patients with carotid artery stenosis(CAS) and potential risk factors related to cognitive-especially memory-dysfunction. Methods Forty-seven patients with carotid artery stenosis were recruited into our study cohort. The Mini-Mental State Examination(MMSE) and the Montreal Cognitive Assessment(MoCA) were adopted to assess cognitive function, the Wechsler Memory Scale(WMS) to assess memory function, high-resolution MRI and enhanced ultrasound to evaluate carotid plaques, and computed tomography perfusion(CTP) imaging to evaluate intracranial blood perfusion. Single-factor analysis and multiple-factor regression analysis were used to analyze potential risk factors of cognitive impairment. Results Mini-Mental State Examination test results showed that 22 patients had cognitive impairment, and MoCA test results showed that 10 patients had cognitive impairment. Analysis of various risk factors indicated that the average memory quotient of female patients was higher than that of males(P = 0.024). The cognitive and memory performance of those with an educational background above high school were significantly better than those of participants with high school or lower(P = 0.045). Patients with abnormal intracranial perfusion performed worse on the MMSE test(P = 0.024), and their WMS scores were significantly lower(P = 0.007). The MMSE scores and the memory quotients were significantly lower in patients with a history of cerebral infarction(MMSE, P = 0.047, memory quotient score, P = 0.018). Conclusion A history of cerebral infarction and abnormal cerebral perfusion are associated with decline in overall cognitive function and memory in patients with carotid stenosis. Being female and having an educational background above high school may be protective factors in the development of cognitive dysfunction.
基金supported by the National Natural Science Foundation of China (No. 81771309)
文摘Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We retrospectively examined EGFRvⅢ expression and EGFRvⅢ nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization(WHO) II gliomas, 84 WHO Ⅲ gliomas and 72 glioblastomas(WHO IV). Factors that correlated with EGFRvⅢ and EGFRvⅢ nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.Results: Log-rank tests showed that patient age, Karnofsky performance scale(KPS) score, tumor grade,EGFRvⅢ expression, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, isocitrate dehydrogenase(IDH)mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase(MGMT) status(P<0.05) were significantly correlated with overall survival(OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, and IDH mutation(P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvⅢ nuclear translocation(≥7%) had both significantly shorter OS [hazard ratio(HR): 1.920, 95% confidence interval(95% CI): 1.228-3.003, P=0.004] and progression-free survival(PFS) times(HR: 1.661, 95% CI: 1.116-2.471, P=0.012) than those with a low level of EGFRvⅢ nuclear translocation(<7%).Conclusions: A high level of EGFRvⅢ nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvⅢ expression is not an independent clinical prognostic factor. The level of EGFRvⅢ nuclear translocation maybe a novel and crucial prognostic biomarker in glioma.
基金This study was supported by grants from the Ministry of Science and Technology of the People’s Republic of China(2016YFC0901001,2016YFC0901002,2017YFC1310901,2017YFC1310902,2018YFC1311700 and 2018YFC1311706)grants from Beijing Municipal Commission of Health and Family Planning(No.2016-1-2041,SML20150502).
文摘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.
基金supported by the National Natural Science Foundation of China, Nos.81471238, 81771327(both to BYL)Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform, Budget of Beijing Municipal Health Commission 2020, No.PXM2020_026280_000002(to BYL)。
文摘The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.