Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise....Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise.In China,the average age of firsttime stroke patients is 66.4 years,and the intravenous thrombolysis rate using recombinant tissue plasminogen activator within 3 h of onset is only 16%.Given this fact,there is a pressing need for real‐time predictive tools,particularly for elderly individuals at home,that can provide early warnings for potential strokes.Methods:We collected continuous monitoring data from nonintrusive smart beds and multimodal temporal data from electronic medical records at the National Center for Neurological Disorders.The data included smart bed monitoring indicators,laboratory tests,nurse observations,and static data as potential predictors,with stroke as the outcome.We applied feature representation and feature selection techniques and then input the predictors into machine learning models.Additionally,deep learning models were used after preprocessing the irregular temporal data.Finally,we evaluated the performance of the stroke prediction models and assessed the importance of the features.We used continuously updated vital signs and clinical data during hospitalization to generate timely stroke risk alerts during the same period of admission.Results:A total of 37,041 samples were analyzed,of which 7020 patients were diagnosed with stroke.When only the smart bed features were used for prediction,the model achieved an area under the receiver operating characteristic curve(AUROC)of 0.59−0.63,with an accuracy ranging from 60%−65%.Among the four artificial intelligence algorithms,the random forest model demonstrated the best performance.After all the available features were incorporated,the AUROC increased to 0.94,and the accuracy improved to 92%.Conclusions:In this study,the occurrence of stroke was successfully identified by integrating multimodal temporal data from electronic medical records.Noncontact monitoring of respiration and heart rate offers a promising approach for daily stroke surveillance in home‐based populations,particularly for elderly individuals living alone.展开更多
Neurological disorders pose a severe public health challenge in China,with substantial impacts on mortality,disability,and socioeconomic burden,especially in the context of population aging.This study synthesizes key ...Neurological disorders pose a severe public health challenge in China,with substantial impacts on mortality,disability,and socioeconomic burden,especially in the context of population aging.This study synthesizes key findings from the China Neurological Disorders Report 2024(compiled by the National Center for Neurological Disorders)to systematically outline the epidemiology of ten major neurological disorders in China,including cerebrovascular disease,dementia/Alzheimer's disease(AD),Parkinson's disease,epilepsy,central nervous system(CNS)tumors,traumatic brain injury(TBI),multiple sclerosis(MS),myasthenia gravis(MG),headache and pain syndromes,and amyotrophic lateral sclerosi(ALS).Cerebrovascular disease remains a leading cause of death,with ischemic stroke accounting for approximately 72.8% of stroke cases and distinct north-south geographic disparities in China.AD and related dementias affect 16.99 million Chinese(29.8% of the global total),with higher prevalence and mortality in females.Parkinson's disease prevalence is rising rapidly,with an estimated 3.62 million current patients and forecasts of 4.79 million by 2030.Epilepsy impacts over nine million people,while CNS tumors,TBI,MS,and MG exhibit unique demographic patterns.Notable trends include increasing disease burdens from neurodegenerative disorders linked to aging,sex disparities(higher female prevalence in AD,higher male incidence in Parkinson's disease and CNS tumors),and regional variations.These standardized,multi-source data address gaps in fragmented prior research,providing a robust scientific basis for healthcare resource allocation,clinical practice optimization,and policy development.Future efforts should focus on expanding data coverage,long-term cohort studies,and interdisciplinary research to enhance precise prevention and management of neurological disorders in China.展开更多
Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroa...Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.展开更多
Major advances have been made over the past few decades in identifying and managing disorders of consciousness(DOC)in patients with acquired brain injury(ABI),bringing the transformation from a conceptualized definiti...Major advances have been made over the past few decades in identifying and managing disorders of consciousness(DOC)in patients with acquired brain injury(ABI),bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration.Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools,sophisticated neuroimaging,and electrophysiological techniques,a considerably higher diagnostic accuracy rate of DOC may now be reached.During the treatment of patients with DOC,a variety of intervention methods are available,including amantadine and transcranial direct current stimulation,which have both provided class II evidence,zolpidem,which is also of high quality,and non-invasive stimulation,which appears to be more encouraging than pharmacological therapy.However,heterogeneity is profoundly ingrained in study designs,and only rare schemes have been recommended by authoritative institutions.There is still a lack of an effective clinical protocol for managing patients with DOC following ABI.To advance future clinical studies on DOC,we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC.We propose a preliminary clinical decision protocol,which could serve as an ideal reference tool for many medical institutions.展开更多
The continuous development of various gene therapies has brought new light to the treatment of genetic diseases.Among them,therapies targeting monogenic diseases are relatively progressive and promising due to the exp...The continuous development of various gene therapies has brought new light to the treatment of genetic diseases.Among them,therapies targeting monogenic diseases are relatively progressive and promising due to the explicit and clear pathogenesis.The discovery and development of clustered regularly interspaced short palindromic repeats/associated nuclease(CRISPR/Cas)and related technologies was undoubtedly an extraordinary leap forward for gene therapy.展开更多
Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter rel...Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.展开更多
The anomalous activation of glycolysis and subsequent accumulation of L-lactate under aerobic conditions,known as the Warburg effect,are prominent metabolic hallmarks of cancer1.Extensive research has revealed that la...The anomalous activation of glycolysis and subsequent accumulation of L-lactate under aerobic conditions,known as the Warburg effect,are prominent metabolic hallmarks of cancer1.Extensive research has revealed that lactate acts not only as an energy-supplying substrate but also as a signaling molecule in glioma2.In addition,lactate accumulation contributes to the formation of a suppressive immune microenvironment in glioma,owing to its acidifying effects.However,emerging findings regarding the lysine lactylome indicate that the roles of lactate extend beyond these functions3。展开更多
Amyotrophic lateral sclerosis(ALS)is an idiopathic and fatal neurodegenerative disorder leading to progressive muscle atrophy,dysarthria,dysphagia,and respiratory failure[1].More than 80 different drugs have been test...Amyotrophic lateral sclerosis(ALS)is an idiopathic and fatal neurodegenerative disorder leading to progressive muscle atrophy,dysarthria,dysphagia,and respiratory failure[1].More than 80 different drugs have been tested since the 198Os,but only two.展开更多
Background:The integration of 7 Tesla(7T)magnetic resonance imaging(MRI)with advanced multimodal artificial intelligence(AI)models represents a promising frontier in neuroimaging.The superior spatial resolution of 7TM...Background:The integration of 7 Tesla(7T)magnetic resonance imaging(MRI)with advanced multimodal artificial intelligence(AI)models represents a promising frontier in neuroimaging.The superior spatial resolution of 7TMRI provides detailed visualizations of brain structure,which are crucial forunderstanding complex central nervous system diseases and tumors.Concurrently,the application of multimodal AI to medical images enables interactive imaging-based diagnostic conversation.Methods:In this paper,we systematically investigate the capacity and feasibility of applying the existing advanced multimodal AI model ChatGPT-4V to 7T MRI under the context of brain tumors.First,we test whether ChatGPT-4V has knowledge about 7T MRI,and whether it can differentiate 7T MRI from 3T MRI.In addition,we explore whether ChatGPT-4V can recognize different 7T MRI modalities and whether it can correctly offer diagnosis of tumors based on single or multiple modality 7T MRI.Results:ChatGPT-4V exhibited accuracy of 84.4%in 3T-vs-7T differentiation and accuracy of 78.9%in 7T modality recognition.Meanwhile,in a human evaluation with three clinical experts,ChatGPT obtained average scores of 9.27/20 in single modality-based diagnosis and 21.25/25 in multiple modality-based diagnosis.Our study indicates that single-modality diagnosis and the interpretability of diagnostic decisions in clinical practice should be enhanced when ChatGPT-4V is applied to 7T data.Conclusions:In general,our analysis suggests that such integration has promise as a tool to improve the workflow of diagnostics in neurology,with a potentially transformative impact in the fields of medical image analysis and patient management.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.展开更多
Background:Spontaneous intracerebral hemorrhage(ICH)is a severe neurological emergency with high morbidity and mortality.The effectiveness of surgical intervention remains controversial,partly due to significant heter...Background:Spontaneous intracerebral hemorrhage(ICH)is a severe neurological emergency with high morbidity and mortality.The effectiveness of surgical intervention remains controversial,partly due to significant heterogeneity among patients.Traditional clinical criteria often fail to identify those most likely to benefit from surgery.Methods:This nationwide retrospective study in China included 2,167 ICH patients from 31 hospitals.Using machine learning techniques,we integrated clinical and radiomic data to perform unsupervised clustering and identify distinct phenogroups.Dimensionality reduction and cross-validation were applied to minimize overfitting.External validation was conducted using data from the INTERACT3 trial,and a prospective cohort was used to assess real-world applicability.Results:Three phenogroups were identified.Among them,only Phenogroup 1-characterized by older age,moderate hematoma volume,and intermediate Glasgow Coma Scale scores-showed significant benefit from early surgical intervention,with a 42%reduction in 3-month mortality and improved functional outcomes.In contrast,surgery did not significantly affect outcomes in Phenogroups 0 and 2.These findings were consistent across multiple machine learning models and validated externally.Conclusion:Machine learning-driven phenotypic stratification can effectively identify ICH patients who are most likely to benefit from surgical treatment.This approach supports personalized treatment strategies and may improve clinical decision-making in ICH management.Further validation in diverse populations is warranted.展开更多
Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting th...Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting the nerve roots has been shown to improve motor function by enhancing nerve conduction in the injured spinal cord and restoring the synaptic ultrastructure of both the sensory and motor cortex.However,our understanding of the neurophysiological mechanisms by which nerve root magnetic stimulation facilitates motor function recovery in the spinal cord is limited,and its role in neuroplasticity remains unclear.In this study,we established a model of spinal cord injury in adult male Sprague–Dawley rats by applying moderate compression at the T10 vertebra.We then performed magnetic stimulation on the L5 nerve root for 3 weeks,beginning on day 3 post-injury.At day 22 post-injury,we observed that nerve root magnetic stimulation downregulated the level of interleukin-6 in the injured spinal cord tissue of rats.Additionally,this treatment reduced neuronal damage and glial scar formation,and increased the number of neurons in the injured spinal cord.Furthermore,nerve root magnetic stimulation decreased the levels of acetylcholine,norepinephrine,and dopamine,and increased the expression of synaptic plasticity-related m RNA and proteins PSD95,GAP43,and Synapsin II.Taken together,these results showed that nerve root magnetic stimulation alleviated neuronal damage in the injured spinal cord,regulated synaptic plasticity,and suppressed inflammatory responses.These findings provide laboratory evidence for the clinical application of nerve root magnetic stimulation in the treatment of spinal cord injury.展开更多
Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its...Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its safety and effectiveness in China.Methods We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke(AIS)within 4.5 hours of onset between 1 March 2019 and 1 October 2023,from 18 stroke centres in China.Using propensity score matching(PSM),TNK-treated patients were matched 1:1 with alteplase-treated patients.The primary outcome was the rate of symptomatic intracranial haemorrhage(sICH)within 72 hours post-thrombolysis.Secondary outcomes comprised the rate of parenchymal haemorrhage type 2,any intracranial haemorrhage,any systematic bleeding and mortality at 90 days,as well as 24-hour National Institutes of Health Stroke Scale(NIHSS),early neurological improvement at 24 hours,modified Rankin Scale(mRS)shift,percentage of mRS 0-1 and mRS 0-2 at 90 days.Results We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase.Following PSM,1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase.No significant differences were observed in rates of sICH(1.8%vs 1.98%,p=0.864)or other safety outcomes.Moreover,TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage(OR:0.51,95%CI:0.31 to 0.86,p=0.012).A higher proportion of patients achieving early neurological improvement at 24 hours(OR:1.76,95%CI:1.48 to 2.09,p=0.000),better 90-day mRS(OR:0.67,95%CI:0.57 to 0.79,p=0.000)as well as higher percentages of 90-day mRS 0-1(OR:1.27,95%CI:1.05 to 1.54,p=0.012)and mRS 0-2(OR:1.41,95%CI:1.14 to 1.75,p=0.001)compared with alteplase.Conclusions Thrombolysis with TNK is not associated with an increased risk of sICH,and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.展开更多
Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension a...Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.展开更多
Totheeditor:Major depressive disorder(MDD)is a principal cause of disability worldwide and is often associated with high morbidity and mortality rates.Although there are several therapies available for the treatment o...Totheeditor:Major depressive disorder(MDD)is a principal cause of disability worldwide and is often associated with high morbidity and mortality rates.Although there are several therapies available for the treatment of depression,about one-third of patients with MMD will not respond to two or more antidepressant drugs with different mechanisms;the patients are then referred to as having treatment-resistant depression(TRD).Patients with TRD have a poorer quality of life,greater economic burden and increased suicidal behaviours.Therefore,new antidepressant treatments that are effective,safe,long-lasting and tolerable are needed.Ketamine infusion,intranasal esketamine and transcranial magnetic stimulation(TMS)have been used to treat early stage TRD.’A recent review suggests that electroconvulsive therapy(ECT)may be superior to ketamine for reducing depression severity in the acute treatment of TRD.展开更多
Glioma is the most common and lethal intrinsic primary tumor of the brain.Its controversial origins may contribute to its heterogeneity,creating challenges and difficulties in the development of therapies.Among the co...Glioma is the most common and lethal intrinsic primary tumor of the brain.Its controversial origins may contribute to its heterogeneity,creating challenges and difficulties in the development of therapies.Among the components constituting tumors,glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation.Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor,in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation.Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states,glial,neural,and immune cell populations in the tumor microenvironment.Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy.Here,we discuss the heterogeneity and relevant functions of tumor cell state,microglia,monocyte-derived macrophages,and neurons in glioma,highlighting their bilateral effects on tumors.Finally,we describe potential therapeutic approaches and targets beyond standard treatments.展开更多
Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To invest...Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK Biobank.Social isolation and loneliness were measured using self-report questionnaires.The study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath registries.Results Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or stroke.Loneliness(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not mortality.Social isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and stroke.The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.展开更多
Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer’s disease(AD).In this review,we evaluated the altered audiovisual integrative behavioral...Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer’s disease(AD).In this review,we evaluated the altered audiovisual integrative behavioral symptoms in AD.We further analyzed the relationships between AD pathologies and audiovisual integration alterations bidirectionally and suggested the possible mechanisms of audiovisual integration alterations underlying AD,including the imbalance between energy demand and supply,activity-dependent degeneration,disrupted brain networks,and cognitive resource overloading.Then,based on the clinical characteristics including electrophysiological and imaging data related to audiovisual integration,we emphasized the value of audiovisual integration alterations as potential biomarkers for the early diagnosis and progression of AD.We also highlighted that treatments targeted audiovisual integration contributed to widespread pathological improvements in AD animal models and cognitive improvements in AD patients.Moreover,investigation into audiovisual integration alterations in AD also provided new insights and comprehension about sensory information processes.展开更多
基金supported by the National Natural Science Foundation of China(72204169,82425101,82271516,81801187)Noncommunicable Chronic Diseases‐National Science and Technology Major Project(2023ZD0504800,2023ZD0504801,2023ZD0504802,2023ZD0504803,2023ZD0504804)+2 种基金Beijing Municipal Science&Technology Commission(Z231100004823036)Capital's Funds for Health Improvement and Research(2022‐2‐2045)National Key R&D Program of China(2024YFC3044800,2022YFF1501500,2022YFF1501501,2022YFF1501502,2022YFF1501503,2022YFF1501504,2022YFF1501505).
文摘Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise.In China,the average age of firsttime stroke patients is 66.4 years,and the intravenous thrombolysis rate using recombinant tissue plasminogen activator within 3 h of onset is only 16%.Given this fact,there is a pressing need for real‐time predictive tools,particularly for elderly individuals at home,that can provide early warnings for potential strokes.Methods:We collected continuous monitoring data from nonintrusive smart beds and multimodal temporal data from electronic medical records at the National Center for Neurological Disorders.The data included smart bed monitoring indicators,laboratory tests,nurse observations,and static data as potential predictors,with stroke as the outcome.We applied feature representation and feature selection techniques and then input the predictors into machine learning models.Additionally,deep learning models were used after preprocessing the irregular temporal data.Finally,we evaluated the performance of the stroke prediction models and assessed the importance of the features.We used continuously updated vital signs and clinical data during hospitalization to generate timely stroke risk alerts during the same period of admission.Results:A total of 37,041 samples were analyzed,of which 7020 patients were diagnosed with stroke.When only the smart bed features were used for prediction,the model achieved an area under the receiver operating characteristic curve(AUROC)of 0.59−0.63,with an accuracy ranging from 60%−65%.Among the four artificial intelligence algorithms,the random forest model demonstrated the best performance.After all the available features were incorporated,the AUROC increased to 0.94,and the accuracy improved to 92%.Conclusions:In this study,the occurrence of stroke was successfully identified by integrating multimodal temporal data from electronic medical records.Noncontact monitoring of respiration and heart rate offers a promising approach for daily stroke surveillance in home‐based populations,particularly for elderly individuals living alone.
文摘Neurological disorders pose a severe public health challenge in China,with substantial impacts on mortality,disability,and socioeconomic burden,especially in the context of population aging.This study synthesizes key findings from the China Neurological Disorders Report 2024(compiled by the National Center for Neurological Disorders)to systematically outline the epidemiology of ten major neurological disorders in China,including cerebrovascular disease,dementia/Alzheimer's disease(AD),Parkinson's disease,epilepsy,central nervous system(CNS)tumors,traumatic brain injury(TBI),multiple sclerosis(MS),myasthenia gravis(MG),headache and pain syndromes,and amyotrophic lateral sclerosi(ALS).Cerebrovascular disease remains a leading cause of death,with ischemic stroke accounting for approximately 72.8% of stroke cases and distinct north-south geographic disparities in China.AD and related dementias affect 16.99 million Chinese(29.8% of the global total),with higher prevalence and mortality in females.Parkinson's disease prevalence is rising rapidly,with an estimated 3.62 million current patients and forecasts of 4.79 million by 2030.Epilepsy impacts over nine million people,while CNS tumors,TBI,MS,and MG exhibit unique demographic patterns.Notable trends include increasing disease burdens from neurodegenerative disorders linked to aging,sex disparities(higher female prevalence in AD,higher male incidence in Parkinson's disease and CNS tumors),and regional variations.These standardized,multi-source data address gaps in fragmented prior research,providing a robust scientific basis for healthcare resource allocation,clinical practice optimization,and policy development.Future efforts should focus on expanding data coverage,long-term cohort studies,and interdisciplinary research to enhance precise prevention and management of neurological disorders in China.
基金supported by grants(92168103,32171417,2019CXJQ01)from the National Nature Science Foundation of China,Shanghai Municipal GovernmentPeak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.
文摘Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
基金supported by the National Natural Science Foundation of China,Nos.82174496(to NW),82374574(to NW),82302865(to LL)Shanghai Science and Technology Committee Sailing Program,Nos.23YF1403800(to LL),23YF1405200(to YX)Shanghai Hospital Development Center Foundation-Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance,No.SHDC22023304(to YW).
文摘Stroke remains a leading cause of death and disability worldwide,and electroacupuncture has a long history of use in stroke treatment.This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke.The PubMed,EMBASE,Web of Science,CENTRAL,and CINAHL databases were comprehensively searched up to May 1,2024.This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke.Data from 70 eligible studies were analyzed in Stata 18.0,using a random-effects model to calculate the standardized mean difference(Hedge’s g).The risk of bias was assessed using RevMan 5.4 software,and the quality of evidence was rated according to the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)system.Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness.The quality assessment revealed that most studies adequately handled incomplete data and selective reporting.However,several methodological limitations were identified:only 4 studies demonstrated a low risk of allocation concealment,26 achieved a low risk of outcome assessment bias,and 9 had a high risk of randomization bias.Additionally,there was an unclear risk regarding participant blinding and other methodological aspects.The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality.The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways:(1)Electroacupuncture significantly reduced infarct volume and apoptotic cell death(P<0.01)in ischemic stroke models;(2)electroacupuncture significantly decreased the levels of pro-inflammatory factors(P<0.01)while increasing the levels of anti-inflammatory factors(P=0.02);(3)electroacupuncture reduced the levels of oxidative stress indicators(P<0.01)and enhanced the expression of antioxidant enzymes(P<0.01);(4)electroacupuncture significantly promoted nerve regeneration(P<0.01);and(5)electroacupuncture influenced blood flow remodeling(P<0.01)and angiogenesis(P<0.01).Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model(P<0.01)and in post-middle cerebral artery occlusion intervention(P<0.01).Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects(P<0.01),while scalp acupoints demonstrated greater efficacy than body acupoints(P<0.01).The heterogeneity among the included studies was minimal,and sensitivity analyses indicated stable results.Their methodological quality was generally satisfactory.In conclusion,electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis,oxidative stress,inflammation,stroke-induced nerve regeneration,blood flow remodeling,and angiogenesis.The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model,the timing of intervention onset,waveform,and acupoint selection.Despite the moderate to low quality of evidence,these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.
基金supported by the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,Shanghai Center for Brain Science and Brain-Inspired Technology,and National Major Pre-Research Project(pilot project)(IDF151042).
文摘Major advances have been made over the past few decades in identifying and managing disorders of consciousness(DOC)in patients with acquired brain injury(ABI),bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration.Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools,sophisticated neuroimaging,and electrophysiological techniques,a considerably higher diagnostic accuracy rate of DOC may now be reached.During the treatment of patients with DOC,a variety of intervention methods are available,including amantadine and transcranial direct current stimulation,which have both provided class II evidence,zolpidem,which is also of high quality,and non-invasive stimulation,which appears to be more encouraging than pharmacological therapy.However,heterogeneity is profoundly ingrained in study designs,and only rare schemes have been recommended by authoritative institutions.There is still a lack of an effective clinical protocol for managing patients with DOC following ABI.To advance future clinical studies on DOC,we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC.We propose a preliminary clinical decision protocol,which could serve as an ideal reference tool for many medical institutions.
基金supported by grants from the Ministry of Science and Technology of China(2018YFA0107900,92168103,32171417,82001140,2019CXJQ01)the National Nature Science Foundation,and Shanghai Municipal Government,Peak Disciplines(TypeⅣ)of Institutions of Higher Leaning in Shanghai。
文摘The continuous development of various gene therapies has brought new light to the treatment of genetic diseases.Among them,therapies targeting monogenic diseases are relatively progressive and promising due to the explicit and clear pathogenesis.The discovery and development of clustered regularly interspaced short palindromic repeats/associated nuclease(CRISPR/Cas)and related technologies was undoubtedly an extraordinary leap forward for gene therapy.
基金supported by the National Natural Science Foundation of China,No.82201568(to QQ)Capital’s Funds for Health Improvement and Research,No.2024-2-1031(to QQ)Beijing Nova Program,No.20240484566(to QQ).
文摘Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.
基金supported by the National Natural Science Foundation of China(Grant No.82072768)Youth Beijing Scholar(Grant No.055)+1 种基金The Outstanding Young Scientist Program of Beijing Universities(Grant No.JWZQ20240101026)Beijing Municipal Health Commission Research Ward Excellence Clinical Research Program(Grant No.BRWEP2024W032040200).
文摘The anomalous activation of glycolysis and subsequent accumulation of L-lactate under aerobic conditions,known as the Warburg effect,are prominent metabolic hallmarks of cancer1.Extensive research has revealed that lactate acts not only as an energy-supplying substrate but also as a signaling molecule in glioma2.In addition,lactate accumulation contributes to the formation of a suppressive immune microenvironment in glioma,owing to its acidifying effects.However,emerging findings regarding the lysine lactylome indicate that the roles of lactate extend beyond these functions3。
文摘Amyotrophic lateral sclerosis(ALS)is an idiopathic and fatal neurodegenerative disorder leading to progressive muscle atrophy,dysarthria,dysphagia,and respiratory failure[1].More than 80 different drugs have been tested since the 198Os,but only two.
基金Science and Technology Innovation Plan Of Shanghai Science and Technology Commission,Grant/Award Number:21Y21900600Shanghai Zhou Liang Fu Medical Development Foundation,Grant/Award Number:XM00050-2024-3-8+1 种基金National Natural Science Foundation of China,Grant/Award Numbers:82127801,82227806,82272063Science and Technology Innovation 2030-Major Project,Grant/Award Number:2023ZD0511800。
文摘Background:The integration of 7 Tesla(7T)magnetic resonance imaging(MRI)with advanced multimodal artificial intelligence(AI)models represents a promising frontier in neuroimaging.The superior spatial resolution of 7TMRI provides detailed visualizations of brain structure,which are crucial forunderstanding complex central nervous system diseases and tumors.Concurrently,the application of multimodal AI to medical images enables interactive imaging-based diagnostic conversation.Methods:In this paper,we systematically investigate the capacity and feasibility of applying the existing advanced multimodal AI model ChatGPT-4V to 7T MRI under the context of brain tumors.First,we test whether ChatGPT-4V has knowledge about 7T MRI,and whether it can differentiate 7T MRI from 3T MRI.In addition,we explore whether ChatGPT-4V can recognize different 7T MRI modalities and whether it can correctly offer diagnosis of tumors based on single or multiple modality 7T MRI.Results:ChatGPT-4V exhibited accuracy of 84.4%in 3T-vs-7T differentiation and accuracy of 78.9%in 7T modality recognition.Meanwhile,in a human evaluation with three clinical experts,ChatGPT obtained average scores of 9.27/20 in single modality-based diagnosis and 21.25/25 in multiple modality-based diagnosis.Our study indicates that single-modality diagnosis and the interpretability of diagnostic decisions in clinical practice should be enhanced when ChatGPT-4V is applied to 7T data.Conclusions:In general,our analysis suggests that such integration has promise as a tool to improve the workflow of diagnostics in neurology,with a potentially transformative impact in the fields of medical image analysis and patient management.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.
基金supported by the Shanghai Municipal Health Commission(201840063,201801075)the Science and Technology Commission of Shanghai Municipality(18441903300).
文摘Background:Spontaneous intracerebral hemorrhage(ICH)is a severe neurological emergency with high morbidity and mortality.The effectiveness of surgical intervention remains controversial,partly due to significant heterogeneity among patients.Traditional clinical criteria often fail to identify those most likely to benefit from surgery.Methods:This nationwide retrospective study in China included 2,167 ICH patients from 31 hospitals.Using machine learning techniques,we integrated clinical and radiomic data to perform unsupervised clustering and identify distinct phenogroups.Dimensionality reduction and cross-validation were applied to minimize overfitting.External validation was conducted using data from the INTERACT3 trial,and a prospective cohort was used to assess real-world applicability.Results:Three phenogroups were identified.Among them,only Phenogroup 1-characterized by older age,moderate hematoma volume,and intermediate Glasgow Coma Scale scores-showed significant benefit from early surgical intervention,with a 42%reduction in 3-month mortality and improved functional outcomes.In contrast,surgery did not significantly affect outcomes in Phenogroups 0 and 2.These findings were consistent across multiple machine learning models and validated externally.Conclusion:Machine learning-driven phenotypic stratification can effectively identify ICH patients who are most likely to benefit from surgical treatment.This approach supports personalized treatment strategies and may improve clinical decision-making in ICH management.Further validation in diverse populations is warranted.
基金supported by the National Natural Science Foundation of China,Nos.81772453(to DX),81974358(to DX),81973157(to JZ),82173646(to JZ),82302866(to YZ)。
文摘Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting the nerve roots has been shown to improve motor function by enhancing nerve conduction in the injured spinal cord and restoring the synaptic ultrastructure of both the sensory and motor cortex.However,our understanding of the neurophysiological mechanisms by which nerve root magnetic stimulation facilitates motor function recovery in the spinal cord is limited,and its role in neuroplasticity remains unclear.In this study,we established a model of spinal cord injury in adult male Sprague–Dawley rats by applying moderate compression at the T10 vertebra.We then performed magnetic stimulation on the L5 nerve root for 3 weeks,beginning on day 3 post-injury.At day 22 post-injury,we observed that nerve root magnetic stimulation downregulated the level of interleukin-6 in the injured spinal cord tissue of rats.Additionally,this treatment reduced neuronal damage and glial scar formation,and increased the number of neurons in the injured spinal cord.Furthermore,nerve root magnetic stimulation decreased the levels of acetylcholine,norepinephrine,and dopamine,and increased the expression of synaptic plasticity-related m RNA and proteins PSD95,GAP43,and Synapsin II.Taken together,these results showed that nerve root magnetic stimulation alleviated neuronal damage in the injured spinal cord,regulated synaptic plasticity,and suppressed inflammatory responses.These findings provide laboratory evidence for the clinical application of nerve root magnetic stimulation in the treatment of spinal cord injury.
基金National Natural Science Foundation of China(82271352)the Science and Technology Commission of Shanghai Municipality(20Z11900802)the Shanghai Municipal Health Commission(2022XD022).
文摘Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its safety and effectiveness in China.Methods We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke(AIS)within 4.5 hours of onset between 1 March 2019 and 1 October 2023,from 18 stroke centres in China.Using propensity score matching(PSM),TNK-treated patients were matched 1:1 with alteplase-treated patients.The primary outcome was the rate of symptomatic intracranial haemorrhage(sICH)within 72 hours post-thrombolysis.Secondary outcomes comprised the rate of parenchymal haemorrhage type 2,any intracranial haemorrhage,any systematic bleeding and mortality at 90 days,as well as 24-hour National Institutes of Health Stroke Scale(NIHSS),early neurological improvement at 24 hours,modified Rankin Scale(mRS)shift,percentage of mRS 0-1 and mRS 0-2 at 90 days.Results We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase.Following PSM,1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase.No significant differences were observed in rates of sICH(1.8%vs 1.98%,p=0.864)or other safety outcomes.Moreover,TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage(OR:0.51,95%CI:0.31 to 0.86,p=0.012).A higher proportion of patients achieving early neurological improvement at 24 hours(OR:1.76,95%CI:1.48 to 2.09,p=0.000),better 90-day mRS(OR:0.67,95%CI:0.57 to 0.79,p=0.000)as well as higher percentages of 90-day mRS 0-1(OR:1.27,95%CI:1.05 to 1.54,p=0.012)and mRS 0-2(OR:1.41,95%CI:1.14 to 1.75,p=0.001)compared with alteplase.Conclusions Thrombolysis with TNK is not associated with an increased risk of sICH,and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.
基金supported by the National Natural Science Foundation of China,Nos.82274611(to LZ),82104419(to DM)Capital Science and Technology Leading Talent Training Project,No.Z191100006119017(to LZ)+3 种基金Beijing Hospitals Authority Ascent Plan,No.DFL20190803(to LZ)Cultivation Fund of Hospital Management Center in Beijing,No.PZ2022006(to DM)R&D Program of Beijing Municipal Education Commission,No.KM202210025017(to DM)Beijing Gold-Bridge Project,No.ZZ20145(to DM)。
文摘Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.
基金supported by the National Natural Science Foundation of China(82371490)the National Key R&D Program of China(2022YFC2503901,2022YFC2503900)+1 种基金the Beijing Hundred,Thousand,and Ten Thousand Talents Project(2017-CXYF-09)Beijing Health System Leading Talent Grant(2022-02-10).
文摘Totheeditor:Major depressive disorder(MDD)is a principal cause of disability worldwide and is often associated with high morbidity and mortality rates.Although there are several therapies available for the treatment of depression,about one-third of patients with MMD will not respond to two or more antidepressant drugs with different mechanisms;the patients are then referred to as having treatment-resistant depression(TRD).Patients with TRD have a poorer quality of life,greater economic burden and increased suicidal behaviours.Therefore,new antidepressant treatments that are effective,safe,long-lasting and tolerable are needed.Ketamine infusion,intranasal esketamine and transcranial magnetic stimulation(TMS)have been used to treat early stage TRD.’A recent review suggests that electroconvulsive therapy(ECT)may be superior to ketamine for reducing depression severity in the acute treatment of TRD.
基金supported by the National Key Research and Development Program of China(2020YFA0804200)the National Natural Science Foundation of China(82073166,82273203)+2 种基金a Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)supported by the Program for Professors of Special Appointment(Eastern Scholar)at the Shanghai Institutions of Higher Learning(SSF151005)supported by the Student Scientific Research Program(Fuqing Scholar)of Shanghai Medical College,Fudan University(FQXZ202117C).
文摘Glioma is the most common and lethal intrinsic primary tumor of the brain.Its controversial origins may contribute to its heterogeneity,creating challenges and difficulties in the development of therapies.Among the components constituting tumors,glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation.Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor,in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation.Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states,glial,neural,and immune cell populations in the tumor microenvironment.Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy.Here,we discuss the heterogeneity and relevant functions of tumor cell state,microglia,monocyte-derived macrophages,and neurons in glioma,highlighting their bilateral effects on tumors.Finally,we describe potential therapeutic approaches and targets beyond standard treatments.
基金funded by the National Natural Science Foundation of China(32100880)Guangzhou Municipal Key Discipline in Medicine(2021-2023)Guangzhou High-level Clinical Key Specialty and Guangzhou Research-oriented Hospital.
文摘Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK Biobank.Social isolation and loneliness were measured using self-report questionnaires.The study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath registries.Results Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or stroke.Loneliness(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not mortality.Social isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and stroke.The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.
基金supported by the National Key Research and Development Program of China(2022YFC3602600)National Natural Science Foundation of China(82220108009,81970996)STI2030-Major Projects(2021ZD0201801).
文摘Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer’s disease(AD).In this review,we evaluated the altered audiovisual integrative behavioral symptoms in AD.We further analyzed the relationships between AD pathologies and audiovisual integration alterations bidirectionally and suggested the possible mechanisms of audiovisual integration alterations underlying AD,including the imbalance between energy demand and supply,activity-dependent degeneration,disrupted brain networks,and cognitive resource overloading.Then,based on the clinical characteristics including electrophysiological and imaging data related to audiovisual integration,we emphasized the value of audiovisual integration alterations as potential biomarkers for the early diagnosis and progression of AD.We also highlighted that treatments targeted audiovisual integration contributed to widespread pathological improvements in AD animal models and cognitive improvements in AD patients.Moreover,investigation into audiovisual integration alterations in AD also provided new insights and comprehension about sensory information processes.
