Background Stroke remains a leading cause of mortality and adult disability in China, imposing a substantial disease and socioeconomic burden on society, yet nationally representative epidemiological and real-world inpatient care data remain insufficient. Methods This study integrated data from the Global Burden of Disease 2023, the Hospital Quality Monitoring System (7536 hospitals) in 2023, and the 2021 National Mortality Surveillance System to systematically assess the epidemiology, disease burden, inpatient care patterns, clinical outcomes and average costs of stroke per hospitalisation in China. Results In 2023, China reported 4.23 million incident cases, 26.68 million prevalent cases and 2.05 million deaths from stroke. Despite declining age-standardised incidence and mortality, ischaemic stroke (IS) prevalence continued to increase, while haemorrhagic stroke remains the principal contributor to disability-adjusted life years. Real-world inpatient data showed that males and older adults accounted for higher proportions of stroke admissions. Stroke admissions were predominantly concentrated in tertiary public hospitals with marked regional variation. Haemorrhagic stroke has substantially higher in-hospital mortality (intracerebral haemorrhage, ICH: 4.23%; subarachnoid haemorrhage, SAH: 4.08% vs IS: 0.49%) and adverse discharge outcomes than IS. Tertiary hospitals exhibited higher mortality (1.19% vs 0.62%) but lower 0–31-day readmission rates (1.19% vs 1.63%) than secondary hospitals, whereas private hospitals showed longer hospital stays (10.54 vs 9.86 days) and higher readmission rates (1.88% vs 1.34%) than public institutions. The mean hospitalisation cost was RMB13 927 (US$1900) per admission, with substantially higher costs for SAH and ICH than for IS. Conclusions This nationwide analysis provides comprehensive real-world evidence on the epidemiological burden, inpatient care patterns, clinical outcomes and hospitalisation costs of stroke in China, identifying substantial national, regional and hospital-level variations that may inform future research and quality improvement efforts.

Background The pathological and physiological state of patients with intracerebral hemorrhage (ICH) after minimally invasive surgery (MIS) is a dynamic evolution, and the traditional models cannot dynamically predict prognosis. Clinical data at multiple time points often show the characteristics of different categories, different numbers, and missing data. The existing models lack methods to deal with imbalanced data. Objective This study aims to develop and validate a dynamic prognostic model using multi–time point data from patients with ICH undergoing MIS to predict survival and functional outcomes. Methods In this study, 287 patients who underwent MIS for ICH were retrospectively collected on the day of surgery, days 1, 3, 7, and 14 after surgery, and the day of drainage tube removal. Their general information, vital signs, laboratory test findings, neurological function scores, head hematoma volume, and MIS-related indicators were collected. In addition, this study proposes a multistep attention model, namely the MultiStep Transformer. The model can simultaneously output 3 types of prediction probabilities for 30-day survival probability, 180-day survival probability, and 180-day favorable functional outcome (modified Rankin Scale [mRS] 0-3) probability. Five-fold cross-validation was used to evaluate the performance of the model and compare it with mainstream models and traditional scores. The main evaluation indexes included accuracy, precision, recall, and F1-score. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves; its calibration was assessed via calibration curves; and its clinical utility was examined using decision curve analysis (DCA). Attributable value analysis was conducted to assess the key predictive features. Results The 30‑day survival rate, 180‑day survival rate, and 180‑day favorable functional outcome rate among 287 patients were 92.3%, 88.8%, and 52.3%, respectively. In terms of predictive efficacy for survival and functional outcomes, the MultiStep Transformer model showed a remarkable superiority over traditional scoring systems and other deep learning models. For these three outcomes, the model achieved areas under the receiver operating characteristic curves (AUROCs) of 0.87 (95% CI 0.82-0.92), 0.85 (95% CI 0.77-0.93), and 0.75 (95% CI 0.72-0.78), with corresponding Brier scores of 0.1041, 0.1115, and 0.231. DCA confirmed that the model provided a definite clinical net benefit when threshold probabilities ranged within 0.06-0.26, 0.04-0.5, and 0.21-0.71. Conclusions The MultiStep Transformer model proposed in this study can effectively use imbalanced data to construct a model. It possesses good dynamic prediction ability for short-term and long-term survival and functional outcome of patients with ICH undergoing MIS, providing a novel tool for individualized assessment of prognosis among patients with ICH undergoing MIS.

Intracerebral hemorrhage (ICH) is a leading cause of mortality and disability in the Chinese population. Neurorestorative treatments represent effective therapeutic strategies for patients with ICH. In recent years, significant advancements have been achieved in ICH neurorestoration. However, the absence of established standards and guidelines presents a major challenge in both clinical practice and fundamental research. To address this issue, the Chinese Association of Neurorestoratology (CANR; Preparatory), together with the China Committee of the International Association of Neurorestoratology (IANR-China Committee), convened a panel of experts to consolidate various neurorestorative approaches and develop comprehensive clinical guidelines for the diagnosis and management of ICH neurorestoration. These guidelines provide diagnostic criteria and staging for ICH, as well as therapeutic strategies for neurorestoration at different stages of the condition, aiming to improve patient survival rates and quality of life.

Abstract Background Neuroinflammation is a critical pathogenic driver in a wide spectrum of neurological disorders, contributing to significant morbidity and presenting a formidable therapeutic challenge. Among emerging regenerative approaches, mesenchymal stem cells (MSCs) have garnered significant attention for their potent capacity to modulate this detrimental immune response, offering hope for conditions ranging from acute brain injury to chronic neurodegeneration. Objective This review aims to comprehensively synthesize the current understanding of how MSCs and their secretome, particularly extracellular vesicles (EVs), therapeutically modulate neuroinflammation. We seek to elucidate the key molecular and cellular mechanisms of action and to critically evaluate the evidence for these therapies across various neurological disease models. Evidence review This review synthesizes the evolving literature on MSC-mediated immunomodulation, highlighting the therapeutic transition from cell replacement to secretome-based strategies. We examine pivotal studies elucidating the molecular mechanisms by which MSCs and their secretome regulate glial phenotypes and inflammatory pathways, preserve blood-brain barrier integrity, and modulate peripheral immune responses. Furthermore, we critically analyze therapeutic efficacy across preclinical models of acute and chronic neurological disorders and assess the current status of clinical translation. Findings The primary therapeutic action of MSCs is mediated by their paracrine secretome, not cell replacement. Key findings demonstrate that MSC-derived EVs deliver bioactive cargo (e.g., microRNAs, TSG-6) that actively reprograms microglia and astrocytes from a pro-inflammatory to a neuroprotective phenotype and suppresses critical inflammatory signaling pathways, such as TLR4/NF-κB and the NLRP3 inflammasome, thereby reducing neuronal damage, preserving blood-brain barrier integrity, and fostering an environment conducive to endogenous repair. Conclusion MSCs and their cell-free secretome represent a promising therapeutic platform for neurological disorders by directly targeting neuroinflammation. While clinical translation is advancing, significant challenges in standardization, manufacturing, and regulatory approval must be addressed. Future progress will depend on developing next-generation, potentially bioengineered, secretome-based products with defined potency to bring this regenerative strategy from the laboratory to the clinic.

Intracerebral hemorrhage (ICH) leads to significant neuronal loss and glial scar formation, but the regenerative capacity of the adult brain remains limited. Although small-molecule-induced astrocyte-to-neuron (AtN) conversion has shown promise in vitro, in vivo applications—particularly under pathological conditions—are still scarce. We aimed to develop and validate a small-molecule cocktail for inducing astrocyte-to-neuron reprogramming in vivo following ICH. We identified a seven-compound cocktail (DFGKLRV) capable of converting astrocytes into neurons under both physiological and ICH conditions. Using immunostaining, RT‒qPCR, electrophysiology, RNA sequencing, neural circuit tracing, and behavioral assessment, we assessed the identity and functionality of induced neurons. In vivo reprogramming was achieved via continuous intracerebral infusion of the cocktail using osmotic pumps. Lineage tracing with aldehyde dehydrogenase 1 family member L1 (Aldh1l1)-CreERT2/Rosa-CAG-tdTomato mice confirmed the astrocytic origin of the reprogrammed neurons. Additionally, we monitored ferroptosis dynamics during reprogramming and evaluated the effect of ferroptosis inhibition on conversion efficiency. DFGKLRV successfully reprogrammed astrocytes into functional, electrophysiologically active neurons. This reprogramming was effective both in vitro and in vivo, including in the hemorrhagic brain environment. Pharmacological inhibition of ferroptosis significantly improved reprogramming efficiency. Mechanistically, ferroptosis inhibition promoted astrocyte-to-neuron conversion at least in part through suppression of the TGF-β/SMAD3/SOX9 axis, whereas exogenous TGF-β1 treatment or Sox9 overexpression reversed this pro-reprogramming effect. Our findings demonstrate that the DFGKLRV cocktail enables efficient in vivo astrocyte-to-neuron reprogramming following ICH. Moreover, ferroptosis represents a key regulatory mechanism and potential therapeutic target for enhancing chemical reprogramming strategies.

Functional near-infrared spectroscopy quantifies cerebral hemodynamic signals by capturing oxygenation-dependent changes in hemoglobin in a noninvasive, portable, and ecologically valid manner, providing a unique insight into neurovascular coupling. However, functional imaging biomarkers with high ecological validity for neurological disorders such as stroke, Parkinson's disease, dementia, amyotrophic lateral sclerosis, epilepsy, spinal cord injury, and traumatic brain injury are lacking, limiting the mechanistic understanding, treatment evaluations, and individualized interventions. The aim of this review is to systematically summarize evidence from the past decade on the use of functional near-infrared spectroscopy under the aforementioned conditions, synthesize its value for revealing neural mechanisms and assessing therapeutic responses, and identify current technical bottlenecks and future directions for advancement. Collectively, the findings demonstrate that functional near-infrared spectroscopy possesses substantial and far-reaching potential for uncovering the neural mechanisms underlying disease and for evaluating treatment-induced changes in brain function. Equipped with wearable probes, functional near-infrared spectroscopy can continuously and noninvasively monitor brain activity in naturalistic environments for extended periods, thereby overcoming the limitations of conventional imaging modalities that can only acquire data under restricted settings. This capability can furnish unprecedented objective neuroimaging evidence for neuroregenerative therapy research. Moreover, the portability of functional near-infrared spectroscopy allows it to be integrated into neurofeedback training systems: hemoglobin signals can be fed back to participants within milliseconds, enabling targeted, individualized, closed-loop modulation of brain function and considerably expanding the scope of hemodynamics-based neurofeedback. When combined with other brain function assays (such as electroencephalography) and intervention techniques (such as transcranial magnetic stimulation and transcranial direct current stimulation), functional near-infrared spectroscopy also supplies high-temporal-resolution hemodynamic information, laying a critical foundation for the construction of high-precision noninvasive brain-computer interfaces, real-time cognitive-state decoding, and adaptive neuromodulation. Admittedly, almost all existing functional near-infrared spectroscopy studies are still observational and have small sample sizes, short follow-ups, and insufficient controls-shortcomings that together produce low-grade evidence. Therefore, there is still a significant gap before clinical translation can be achieved. Technically, the limited penetration depth of functional near-infrared spectroscopy restricts sampling to the superficial cortex, leaving deep nuclei largely unreachable. In addition, no consensus exists across devices regarding optode layout, light-source choice, motion-artifact correction, or analytical pipelines, creating pronounced heterogeneity that undermines reproducibility. With artificial intelligence and big data analytics advancing rapidly, functional near-infrared spectroscopy embedded within multimodal fusion frameworks is now poised to systematically map aberrant brain function signatures of neurological disorders, identify pathological regions suitable for targeted intervention, and provide real-time assessments of functional changes produced by neuroregenerative therapies.

Post-stroke headache (PSH) and its chronic counterpart, persistent post-stroke headache (PPSH), represent significant but frequently overlooked complications of cerebrovascular disease that adversely affect rehabilitation and quality of life. This review provides an updated synthesis of PSH, following its formal classification in the International Classification of Headache Disorders, 3rd edition (ICHD-3). We examine the epidemiology of PSH, noting a prevalence range of 6–44% in ischemic stroke survivors, with risk factors including younger age, female sex, and posterior circulation lesions. The pathophysiology is explored as a complex interplay involving the trigeminovascular system, neurogenic inflammation, and central sensitization, often exacerbated by structural factors such as edema and stroke topography. Clinical phenotypes vary, predominantly presenting as tension-type, though migraine-like features occur. Furthermore, this review highlights the critical role of headache as a sentinel symptom in the differential diagnosis of distinct stroke etiologies such as cervical artery dissection, reversible cerebral vasoconstriction syndrome, and cerebral venous thrombosis. A major finding is the significant gap in evidence-based management; current therapeutic strategies often rely on extrapolating data from primary headache disorders, with unverified safety profiles for newer agents such as triptans and calcitonin gene-related peptide (CGRP) antagonists in the post-stroke population. We conclude by emphasizing the urgent need for randomized controlled trials to establish safe, effective pharmacological and non-pharmacological interventions for this disabling condition.

In the study of electroencephalography (EEG)-based motor imagery (MI) brain-computer interfaces (BCIs), neurorehabilitation technologies hold significant potential for recovering from intracerebral hemorrhage (ICH). However, the rehabilitation process is hindered as the clinical practicality of such systems is reduced considerably due to their lengthy setup procedures caused by excessive number of channels. Accordingly, this study proposes a channel selection method based on an adaptive recursive learning framework, which establishes a comprehensive evaluation metric by combining time-frequency domain features. Experimental results demonstrate that, upon using 37.50% fewer channels, the average accuracy of MI classification increased from 65.44% to 69.28% in healthy subjects and from 65.00% to 67.64% in patients with ICH. This study presents the pioneering EEG-based MI BCI channel selection process specifically designed for ICH patients, paving the way for personalized rehabilitation protocols and facilitating the translation of neurotechnology into clinical practice.

Background: Acute ischemic stroke (AIS) with large vessel occlusion (LVO) carries high morbidity despite endovascular thrombectomy (EVT).Symptomatic hemorrhagic transformation (sHT), a reperfusion-related complication, remains a critical concern. Elevated blood pressure variability (BPV) post-EVT correlates with sHT risk, but traditional BPV assessments lack real-time utility. We propose a machine learning model analyzing continuous blood pressure and heart rate to predict sHT early, enabling timely intervention and improved outcomes. Methods: We conducted a retrospective study including 615 patients with AIS who achieved successful recanalization after EVT across two hospitals. Blood pressure (BP) and heart rate (HR) measurements were recorded at 30-minute or 1-hour intervals during the first 24 hours post-EVT, and non-contrast head CT was performed to determine the presence of sHT. Patients were categorized into symptomatic HT (sHT) and non-sHT groups based on CT findings. We applied deep learning models, including LeNet and Generative Adversarial Networks (GANs), to characterize and compare BP/HR temporal patterns between groups. GAN-based augmentation was used to mitigate class imbalance by generating synthetic sHT cases, and a sliding-window strategy was implemented to support real-time prediction of sHT. Results: Using data from two hospitals, the deep learning framework identified distinct pre-sHT temporal signatures in systolic (SBP), diastolic (DBP), and HR, with SBP exhibiting the largest and most informative fluctuations prior to sHT onset. After GAN-based augmentation to address class imbalance, the model achieved strong discrimination for sHT prediction in both the training and held-out test evaluations. In the independent external validation cohort, the model correctly identified all 73 non-sHT cases and 25 of 28 sHT cases, yielding an AUC of 0.978, an accuracy of 97.0%, a specificity of 100%, and a sensitivity of 89.3%. With a 10-point sliding window, the model provided near–real-time forecasting of sHT in the next measurement interval with high accuracy. Notably, the optimal decision threshold was not identical across hospitals, consistent with inter-site differences in baseline haemodynamics, measurement frequency, and case mix. Therefore, the operating threshold was optimized separately for each hospital on the corresponding test/evaluation cohort using ROC analysis and Youden’s J statistic to balance sensitivity and specificity. In the overall test set, the model showed good generalization, achieving high accuracy in the non-sHT group and substantially improved performance for sHT following GAN-based balancing. Conclusion: Our findings show that deep learning models can anticipate symptomatic haemorrhagic transformation after EVT using early post-procedural blood pressure and heart-rate trajectories. In this framework, LeNet was used for prediction, while a GANs was applied separately to mitigate class imbalance through synthetic case generation. The resulting pipeline supports near–real-time risk estimation with high discriminative performance, offering a clinically actionable strategy for earlier identification of high-risk patients and timely intervention, with operating thresholds calibrated to the intended deployment setting.

Autism spectrum disorder (ASD) involves heterogeneous neurodevelopmental alterations, yet the genetic mechanisms linking ASD to variation in brain structure remain unclear. Imaging-derived phenotypes (IDPs) from large population cohorts offer the opportunity to explore structural features contributing to ASD risk, but the convergence of genetic evidence with structural imaging alterations observed in ASD cohorts has not been systematically investigated. We integrated ASD genome-wide association study (GWAS) summary statistics with 3,935 UK Biobank imaging-derived phenotypes to identify brain structural features with potential causal roles in ASD. Causal inference was performed using inverse-variance weighted Mendelian randomisation (MR) with extensive sensitivity analyses. Genetic sharing was evaluated using Linkage disequilibrium (LD) score regression and local genetic correlation modelling with Local Analysis of Variant Association (LAVA). Independent phenotypic convergence was evaluated in the ABIDE cohort by mapping genetically implicated IDPs onto case–control differences in cortical–subcortical connectivity. Multi-trait co-localisation (HyPrColoc) was conducted across ASD, IDPs, and brain expression quantitative trait loci (eQTL) datasets. Cell-type specificity and transcriptional alterations were examined using single-cell RNA-seq from ASD post-mortem cortex. MR identified 59 IDPs in the combined-sex analysis indicating robust causal associations with ASD after heterogeneity correction. LD score regression revealed 20 of 59 IDPs with significant global genetic correlation with ASD, while LAVA identified 91 loci with significant local genetic correlation. In the Autism Brain Imaging Data Exchange I (ABIDE I) cohort, IDPs identified as genetically causal mapped onto reduced cortical–subcortical connectivity in ASD. Multi-trait co-localisation detected 22 ASD–IDP shared variants, among which rs2668622 showed joint association with ASD, the right anterior thalamic radiation intracellular volume fraction (ICVF), and brain-region–specific gene expression, with LRRC37A emerging as the most consistently supported gene. Single-cell RNA-seq further showed that LRRC37A is enriched in L2/3 and L5/6 corticocortical projection neurons and significantly downregulated in ASD. Together, these multi-omics findings support a model in which genetically mediated alterations in white matter microstructure contribute to ASD and converge with structural connectivity differences. The identification of LRRC37A as a co-localised gene with consistent evidence of genetic, imaging, and cell-type expression highlights a potential molecular effector linking genetic risk to circuit-level alterations. Network perturbation analyses further revealed that LRRC37A dysregulation induces layer-specific disruption of gene regulatory networks, characterised by widespread destabilisation in L2/3 neurons and hub-targeted perturbation in L5/6 corticocortical neurons. This study delineated cross-scale biological pathways underlying ASD and provides a framework for future mechanistic investigation.

Disruption of excitatory/inhibitory (E/I) balance within the basolateral amygdala (BLA) is a critical feature of depressive and anxiety-like states, yet effective circuit-based therapies are lacking. Here, we demonstrate that tactile experience enrichment (TEE)—a noninvasive sensory stimulation—ameliorates depressive- and anxiety-like behaviors in multiple post-stroke depression (PSD) mouse models by engaging a thalamic-amygdala pathway from the reuniens nucleus (Re) to BLA inhibitory neurons (ReExc-BLAInh). Activation of this compensatory circuit re-establishes E/I balance in the BLA through feedforward inhibition of excitatory neurons, thereby bypassing the impaired medial prefrontal cortex-BLA pathway. Both chemogenetic activation of the ReExc-BLAInh pathway and TEE treatment in chronic social defeat stress (CSDS) and chronic restraint stress (CRS) models similarly restore synaptic E/I balance and significantly improve emotional behaviors. These results define a lesion-bypassing circuit mechanism through which tactile input modulates amygdala function in mice and will motivate future studies of translational relevance.

BACKGROUND:Stroke remains a major global cause of death and disability, with many patients either missing the therapeutic window or responding poorly to current first-line treatments. Consequently, secondary neurological injury, driven predominantly by neuroinflammation, has emerged as a critical therapeutic target. Microglia rapidly sense post-stroke microenvironmental changes and adopt distinct inflammatory phenotypes that shape pathophysiological outcomes. RESULTS:Accumulating evidence, including high-resolution spatial profiling and single-cell omics, positions mitochondrial dysfunction at the core of these responses. This review synthesizes recent findings on microglial mitochondrial dysfunction in stroke, introducing the concept of a microglial mitochondrial "storm center". In this model, reactive oxygen species (ROS) trigger an inflammatory cascade, while impairments in mitochondrial quality control (MQC) exacerbate pathogenic signaling. Metabolic reprogramming further sustains inflammatory polarization, influencing interactions with neurons, astrocytes, and endothelial cells. CONCLUSIONS:This "storm center" provides a conceptual framework for developing strategies to mitigate secondary brain injury. Finally, this review highlights key molecular mechanisms, potential therapeutic targets, and translational opportunities, providing a stronger foundation for future stroke research and therapeutic innovation.

Abstract Background and aims Successful recanalization without functional independence is common after endovascular thrombectomy in stroke. The effect of tirofiban, a glycoprotein IIb/IIIa receptor antagonist, after successful endovascular treatment is unclear. Methods In this multicenter, double-blind, randomized trial at 82 centers in China, patients with anterior-circulation large vessel occlusion stroke achieving successful recanalization (modified Thrombolysis In Cerebral Infarction score 2b-3) after endovascular treatment were assigned to receive tirofiban (intra-arterial bolus, 5 μg/kg, followed by intravenous infusion at 0.1 μg/kg/min for 24 hours) or placebo. The primary efficacy outcome was functional independence, defined as modified Rankin scale (mRS) score of 0–2 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage within 48 hours and death at 90 days. Results A total of 689 patients were assigned to the tirofiban group and 691 to the placebo group. The percentage of patients with a mRS score of 0–2 at 90 days was 49.4% in the tirofiban group and 43.3% in the placebo group (unadjusted risk ratio, 1.14 [95% CI, 1.02-1.28]; P=0.02; adjusted risk ratio, 1.15 [95% CI, 1.03-1.27]; P=0.01). Symptomatic intracranial hemorrhage occurred in 11.9% with tirofiban and 9.4% with placebo (adjusted risk ratio, 1.24 [95% CI, 0.91-1.68]; P=0.17); 90-day mortality was 18.3% and 19.0%, respectively (adjusted hazard ratio, 0.96 [95% CI, 0.75-1.22]; P=0.72). Conclusions In patients with acute anterior-circulation large vessel occlusion stroke achieving successful recanalization, adjunct tirofiban increased the likelihood of functional independence at 90 days without increasing the risk of symptomatic intracranial hemorrhage or mortality. (ClinicalTrials.gov number, NCT06265051.) Conflict of interest

BACKGROUND:Successful reperfusion after endovascular thrombectomy does not consistently result in functional independence in acute ischaemic stroke. We aimed to assess the efficacy and safety of tirofiban, a glycoprotein IIb/IIIa receptor antagonist, given to patients with acute ischaemic stroke who had had a successful endovascular reperfusion. METHODS:This multicentre, double-blind, randomised controlled trial at 82 hospitals in China included patients with acute ischaemic stroke due to anterior-circulation large-vessel occlusion who had had a successful reperfusion after thrombectomy. Eligible patients were randomly assigned (1:1) to receive either tirofiban (intra-arterial bolus 5 μg/kg followed by intravenous infusion 0·1 μg/kg per min for 24 h) or placebo (administered with the same volume and according to the same bolus and infusion procedures as tirofiban), using computer-generated randomisation with fixed blocks stratified by study site. Patients, treating clinicians, investigators, and outcome assessors were masked to group assignments. The primary efficacy outcome was functional independence at 90 days (with a modified Rankin Scale score of 0-2), assessed in all randomly assigned participants (intention-to-treat population). Safety outcomes were symptomatic intracranial haemorrhage within 48 h, any evidence of intracranial haemorrhage on imaging within 48 h, and death within 90 days, and they were assessed in patients having received the study treatment with at least one safety evaluation. The Adjunct Tirofiban Treatment after Successful Endovascular Thrombectomy Recanalisation in Acute Anterior Circulation Ischaemic Stroke (ATTRACTION) trial is registered with ClinicalTrials.gov, NCT06265051 and is now completed. FINDINGS:Of 1686 patients assessed, 1380 were randomly assigned to either the tirofiban group (689 patients) or the placebo group (691 patients) between April 9, 2024, and Sept 29, 2025. Median age was 71 years (IQR 62-77), 591 (43%) patients were female and 789 (57%) were male, and 1367 (99%) were of Han Chinese ethnicity. No patients were lost to follow-up at 90 days. Functional independence at 90 days was recorded in 340 (49%) of 689 patients in the tirofiban group and 299 (43%) of 691 patients in the placebo group (unadjusted absolute risk difference 6·1 percentage points, 95% CI 0·8-11·3, p=0·023; adjusted risk ratio 1·15, 95% CI 1·03-1·27, p=0·0092). There was no significant difference between study groups in the proportion of patients with symptomatic intracranial haemorrhage within 48 h (82 [12%] of 687 patients in the tirofiban group vs 65 [9%] of 691 patients in the placebo group), the proportion with any intracranial haemorrhage within 48 h (235 [34%] patients vs 219 [32%] patients), and 90-day mortality (126 [18%] patients vs 131 [19%] patients). INTERPRETATION:In patients with acute ischaemic stroke due to anterior-circulation large-vessel occlusion achieving successful reperfusion, adjunctive tirofiban increased the likelihood of functional independence compared with placebo. Although symptomatic intracranial haemorrhage occurred numerically more often with tirofiban, the between-group difference was not significant, and this finding warrants caution when weighing potential benefit against bleeding risk. FUNDING:Tongji Hospital Clinical Research Fund.

Background: Muscle RING finger-1 (MuRF-1) serves as a marker of muscle atrophy. However, we have previously shown that MuRF-1 primarily accumulates in regenerating myofibers in muscles from patients with immune-mediated necrotizing myopathy (IMNM). This study was designed to further investigate the underlying mechanisms of MuRF-1 involved in skeletal muscle regeneration. Methods: MuRF-1 expression and muscle regeneration in muscle biopsies from patients with IMNM were detected using immunostaining and real-time quantitative polymerase chain reaction (RT-qPCR). Biopsies from dermatomyositis (DM), dysferlinopathy, and healthy controls were selected for comparison. Short interfering RNA (siRNA) technique, RT-qPCR, western blot, flow cytometry analysis, and immunostaining were performed to explore the roles of MuRF-1 in human myoblast proliferation and differentiation. Results: Muscle regeneration was activated in muscles of IMNM, DM, and dysferlinopathy, especially in IMNM and DM, compared with healthy controls. MuRF-1 expression strongly correlated with myofiber regeneration. MuRF-1-positive myofibers co-localized with regenerating fibers and highly expressed the myogenic transcription factor MyoG. Moreover, satellite cells (muscle stem cells) were enriched on the surface of these myofibers. In vitro experiments further demonstrated that MuRF-1 expression was upregulated during myogenic differentiation. MuRF-1 knockdown inhibited myoblast proliferation, differentiation, and fusion. Moreover, the expression of cell cycle protein Cyclin A and the myogenic regulatory factor MyoG was significantly decreased. Conclusions: MuRF-1 is involved in muscle regeneration by regulating myoblast proliferation and differentiation, which may contribute to muscle injury repair in IMNM. This finding provides new insights into the pathophysiological roles of MuRF-1 in muscular disorders.

The incidence and mortality of stroke have decreased in China in the past decade; however, the prevalence of stroke continues to rise because of population ageing. In alignment with the Healthy China 2030 blueprint, there has been a strategic reorientation of health-care services towards the prevention of major diseases, including stroke. Along with the establishment of a nationwide network of stroke centres to enhance the delivery of stroke care and research, progress has also been made in understanding stroke aetiology, screening for and control of risk factors, and promoting early diagnosis and treatment. Evidence from high-quality randomised trials in China supports the wide adoption of reperfusion therapies for ischaemic stroke, early blood pressure lowering after intracerebral haemorrhage, individualised approaches to secondary prevention, and the research evaluation of traditional Chinese medicine and neuroprotective agents. Future efforts should focus on promoting a healthy lifestyle, public education on awareness of stroke prevention and timely access to stroke services, training of stroke clinicians on evidence-based stroke care, and improvements in both pre-hospital and post-hospital stroke services.

BACKGROUND:Spontaneous intracerebral hemorrhage (sICH) remains associated with high mortality and long-term disability worldwide. Since the publication of the Surgical Trial in Intracerebral Haemorrhage (STICH) in 2005, numerous randomized controlled trials have evaluated surgical, pharmacological, and physiological interventions, yet most have not demonstrated consistent improvements in functional outcomes. METHODS:We critically reviewed major randomized controlled trials and influential studies of acute sICH treatment published over the past two decades, with particular attention to surgical strategies, physiological and pharmacological interventions, treatment timing, patient selection, and sex-related biological heterogeneity. RESULTS:Most conventional surgical and single-target medical interventions yielded neutral or modest results. Recent trials suggest that carefully selected surgery, early intervention, and bundled protocolized care may provide greater benefit. However, optimal treatment timing and sex-specific biological differences remain insufficiently investigated. CONCLUSIONS:Further progress in acute sICH treatment will require time-sensitive, mechanism-informed, anatomically tailored, and sex-aware multimodal treatment strategies rather than isolated interventions.

The incidence and mortality of stroke have decreased in China in the past decade; however, the prevalence of stroke continues to rise because of population ageing. In alignment with the Healthy China 2030 blueprint, there has been a strategic reorientation of health-care services towards the prevention of major diseases, including stroke. Along with the establishment of a nationwide network of stroke centres to enhance the delivery of stroke care and research, progress has also been made in understanding stroke aetiology, screening for and control of risk factors, and promoting early diagnosis and treatment. Evidence from high-quality randomised trials in China supports the wide adoption of reperfusion therapies for ischaemic stroke, early blood pressure lowering after intracerebral haemorrhage, individualised approaches to secondary prevention, and the research evaluation of traditional Chinese medicine and neuroprotective agents. Future efforts should focus on promoting a healthy lifestyle, public education on awareness of stroke prevention and timely access to stroke services, training of stroke clinicians on evidence-based stroke care, and improvements in both pre-hospital and post-hospital stroke services.

OBJECTIVE:Precise localization of the epileptogenic zone (EZ) is crucial for epilepsy surgery success. Optically pumped magnetometer magnetoencephalography (OPM-MEG) is a promising noninvasive technique requiring rigorous clinical validation. METHODS:In this prospective diagnostic study, 68 patients with refractory epilepsy underwent 90-min interictal OPM-MEG. Dipoles were fitted to interictal epileptiform discharges for localization. The primary objective was to evaluate the spatial concordance between OPM-MEG and the EZ defined by intracranial electroencephalography (iEEG; stereo-EEG or electrocorticography), assessed at the sublobar level using Gwet AC1. The secondary objective was to evaluate the diagnostic value of OPM-MEG for surgical outcome. This analysis included 51 patients who underwent curative intervention (resection or thermocoagulation). The reference standard was a composite of the treated brain region and seizure freedom (International League Against Epilepsy [ILAE] class 1 or Engel class I) at ≥12-month follow-up, from which sensitivity, specificity, and diagnostic odds ratio (OR) were calculated. RESULTS:OPM-MEG showed almost perfect agreement with iEEG-based EZ localization overall (AC1 = .885, concordance rate = 90.0%), with substantial agreement in temporal (80.1%, AC1 = .723) and almost perfect agreement in extratemporal regions (92.0%, AC1 = .926). The Euclidean centroid distance between OPM-MEG and iEEG localizations was significantly shorter in concordant versus discordant cases. In the assessment of diagnostic value, OPM-MEG demonstrated a sensitivity of 85.7% and specificity of 65.2% (OR = 11.25) under ILAE criteria, and a sensitivity of 73.0% and specificity of 64.3% (OR = 4.86) under Engel criteria. SIGNIFICANCE:OPM-MEG demonstrates high concordance with iEEG for EZ localization and provides robust diagnostic value for predicting postoperative seizure freedom, supporting its utility in the presurgical evaluation of refractory epilepsy.