Xun Ye

BACKGROUND: Intracranial aneurysms (IAs) are localized dilations of cerebral arteries that pose a significant threat of rupture, leading to fatal subarachnoid hemorrhage. The inflammation driven by immune cell infiltration is believed to be a key driver for the pathogenesis of IAs; however, the detailed immune cell landscape and spatial composition of immune cells remain unclear. METHODS: In this study, we employed an integrated multi-omics approach using human IA tissues, including single‑cell RNA sequencing, spatial transcriptomics, microarray data, and multiplex immunofluorescence, to construct a comprehensive immune cell atlas of IAs, providing a systematic characterization of their immune composition and spatial architecture. Findings were further validated in a mouse model of IA. RESULTS: We identified, for the first time, tertiary lymphoid structures within the aneurysm wall and demonstrated that their presence strongly correlates with rupture. Furthermore, we observed a significant expansion of a specific T-cell subset, C-X-C motif chemokine legand 13 (CXCL13)-positive T-follicular helper cells. These cells were critical for B-cell recruitment and the structural organization of the tertiary lymphoid structures. In the IA mouse model, CXCL13 neutralization effectively suppressed both aneurysm formation and rupture. CONCLUSIONS: Our finding establishes tertiary lymphoid structures and CXCL13 ⁺ T follicular helper cells as central elements in IA progression and highlight the CXCL13 signaling axis as a promising therapeutic target for preventing aneurysm advancement.

Read as associations rather than intervention evidence. Its contribution is more specific: it places post-stroke cognition within the patient's daily activity range and emotional state, rather than treating cognition as a direct consequence of the infarct alone.Liao et al. focused on serum uric acid to serum creatinine ratio (SUA/SCr) in acute ischemic stroke and early-onset post-stroke cognitive impairment (PSCI). Lower SUA/SCr was independently associated with PSCI assessed within 2 weeks after stroke. The result supports further testing of routine metabolic indices as early cognitive risk markers, but its predictive strength and clinical thresholds require validation before clinical use.Luo et al. extended this biomarker-oriented discussion to cerebral small vessel disease (CSVD). In a cross-sectional cohort, blood urea nitrogen to albumin ratio (BAR) was independently associated with CSVD and with ischemic imaging markers, including white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS), but not lacunes. This finding connects an accessible laboratory index with MRI-defined structural injury. The absence of an association with lacunes narrows the interpretation of BAR, suggesting that its relationship with CSVD may differ across imaging features. BAR is best presented as a laboratory marker associated with selected CSVD imaging findings, with its clinical use still requiring prospective validation.Yang et al. investigated surgically treated patients with spontaneous intracranial hemorrhage (ICH) stratified by type 2 diabetes mellitus (DM). In 688 patients, DM was associated with higher rates of postoperative major adverse cerebrovascular events, including ischemic and hemorrhagic events, as well as 30-day mortality after adjustment for confounders. Li et al. focused on basal ganglia hemorrhage and perioperative hemoglobin (HB) indices. Lower preoperative, postoperative, and mean HB levels were independently associated with unfavorable 6-month functional outcomes, and an HB-integrated model showed stronger predictive performance than single HB indicators. Read together, these studies support perioperative assessment that considers vascular comorbidity, dynamic laboratory measures, and functional endpoints, rather than hematoma location or volume alone (Li et al., 2025;Yang et al., 2025). The collection points to a limitation of lesion-centered assessment: vascular anatomy and lesion burden alone do not fully account for cognitive and functional heterogeneity after cerebrovascular disease. The next step is not simply to validate single markers, but to evaluate cognitive testing, MRI or perfusion markers, laboratory indices, clinical phenotypes, and functional endpoints in shared prospective datasets. This would make it easier to separate markers useful for surveillance from factors that can be targeted through rehabilitation planning, perioperative management, or long-term cognitive care.Butnariu, I., Cojocaru, F.-M., Lăptoiu, V.-I., Bidea, A., Mitrică, I.-A. M., Tuță, S., et al. (2026).Hemilingual edema as a warning sign for internal carotid artery dissection-a case report and literature review. Front. Med. 13, 1765232. doi: 10.3389/fmed.2026.1765232 Huang, H., Wang, C., Hua, H., Zhang, Y., Zhao, B., andWan, D. (2025). Case report: dyke-davidoff-masson syndrome resulting from a rare combination of hypoplastic left posterior cerebral artery and ipsilateral fetal-type posterior communicating artery. Front. Hum. Neurosci. 19, 1629156. doi: 10.3389/fnhum.2025.1629156 Lai, W., andHu, J. (2026). Acute-phase clinical phenotyping stratifies long-term cognitive and functional outcomes in cerebral venous sinus thrombosis. Front. Neurol. 17, 1754770. doi: 10.3389/fneur.2026.1754770 Li, X., Zhang, L., Yang, Z., Ding, J., Yu, Y., Yang, S., et al. (2025) Yang, J., Wang, S., Ji, X., Sun, Y., Feng, J., Liu, B., et al. (2025). Risk of postoperative major adverse cerebrovascular events in patients with spontaneous intracranial hematoma stratified by type 2 diabetes mellitus. Front. Hum. Neurosci. 19, 1654763. doi: 10.3389/fnhum.2025.1654763 Zhang, Y., Yang, X., Gu, Q., Pan, J., Mao, J., Lu, D., et al. (2025). Multiple mediators of anxiety and depression between living space and cognitive function among elderly patients with ischemic stroke. Front. Psychiatry 16, 1682799. doi: 10.3389/fpsyt.2025.1682799

Background: Moyamoya disease (MMD) is characterized by progressive arterial stenosis and abnormal collateral formation, but the spatial organization of vessel-wall abnormalities remains incompletely understood. Methods: We combined Xenium in situ spatial transcriptomics and multiplex immunofluorescence in superficial temporal artery samples from patients with MMD and controls, and performed gain- and loss-of-function experiments in human brain microvascular endothelial cells (HBMECs). Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), tube-formation, Transwell migration, and cell scratch assays were used to assess signaling and endothelial phenotypes. Results: MMD vascular tissue showed intimal hyperplasia, altered spatial cellular architecture, and enrichment of extracellular matrix- and proteoglycan-related programs, with upregulation of sulfatase 1 (SULF1). In HBMECs, SULF1 knockdown reduced, whereas SULF1 overexpression enhanced, vascular endothelial growth factor A165 (VEGF-A165)-induced vascular endothelial growth factor receptor 2 (VEGFR2), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (AKT) phosphorylation, migration, tube formation, and angiogenesis- and adhesion-related gene expression. Heparinase III attenuated the signaling effects associated with SULF1 overexpression. Conclusion: These findings suggest that SULF1-associated extracellular matrix alterations may contribute to local vessel-wall remodeling and enhanced endothelial responsiveness in MMD. Graphical

Background: The cellular composition and molecular mechanisms of the pathological arteries in Moyamoya disease (MMD) remain poorly understood. To improve our understanding of pathogenesis in MMD, we aimed to comprehensively map the cellular composition and molecular alterations within the pathological arteries of patients with MMD. Methods: Superficial temporal artery samples were collected from patients with MMD (n=2) and healthy controls (n=3), yielding a total of 26 371 cells that were used for single‐cell RNA sequencing. Differentially expressed genes, pathway enrichment, and cell–cell communication analyses were performed to examine disease‐related changes. In vitro experiments were performed to validate the changes in endothelial cells (ECs) and smooth‐muscle cells (SMCs), as well as the interactions between immune cells and ECs and SMCs. Results: We identified 8 major cell types in the human superficial temporal artery. We observed an increased proportion of SMCs in the superficial temporal artery of MMD. Two distinct SMC clusters, SMC1 and SMC2, were identified and exhibited different gene expression. Immune profiling revealed significant upregulation of genes in natural killer T cells, suggesting increased immune activity in MMD. Cell–cell communication analysis highlighted the role of the macrophage migration inhibitory factor pathway in promoting interactions between immune cells, SMCs, and ECs. In vitro experiments confirmed that the colocalization of CD74 with CD44 or CXCR4 in ECs promotes EC proliferation and angiogenesis. Natural killer T cells can promote cytoskeletal enlargement in ECs and SMCs, enhancing their migratory and proliferative capacities, as well as promoting angiogenesis in ECs. Conclusions: This study provides a single‐cell transcriptomic map of the superficial temporal artery in MMD, revealing key immune and vascular cell populations. Immune cells, particularly natural killer T cells, play a critical role in promoting SMC and EC proliferation and migration, contributing to vascular occlusion. These findings make contributions to understanding the pathogenesis of MMD and suggest potential therapeutic targets.

OBJECTIVE: This study was conducted to explore the role of serum amyloid A2 (SAA2) protein in the phenotype changes of vascular smooth muscle cells (VSMCs) in moyamoya disease (MMD). METHODS: Between January 2020 and August 2022, individuals with diagnosed MMD were identified through a combination of their neuroradiological assessments and medical history. Control participants consisted of healthy adult volunteers who did not have MMD or any preexisting diseases. Data-independent acquisition (DIA) mass spectrometry was used to identify differentially expressed proteins in the serum of 40 MMD patients and 20 healthy controls (HCs), a discovery cohort of 60 patients. These proteins were validated with an enzyme-linked immunosorbent assay using the serum of another 15 MMD patients and 15 HCs plus 5 randomly selected samples each from the MMD patients and the HCs in the discovery cohort, bringing the validation cohort to 20 MMD patients and 20 HCs. In vitro experiments, including western blotting, flow cytometry, scratch tests, and cell proliferation assays, were performed to explore the effects and mechanisms of these proteins on smooth muscle cells. RESULTS: Proteomic analysis showed significant upregulation of SAA2 protein in the MMD serum compared to that in the HC serum (log ₂ FC [MMD/HC] = 2.797, p < 0.05). SAA2 increased the proportion of VSMCs in the S phase and promoted their proliferation, migration, and contractile-to-synthetic phenotypic switching. Aspirin reversed SAA2-induced changes in VSMCs. Mechanistic studies revealed that the ERK1/2 and AKT signaling pathways play a major role in SAA2-induced changes in VSMCs. CONCLUSIONS: This study revealed that SAA2 is upregulated in the serum of MMD patients. The overexpression of SAA2 in MMD patients and in subsequent in vitro experiments suggests that the SAA2 protein promotes phenotypic changes in VSMCs and is related to cerebrovascular intimal thickening in MMD, with diagnostic and therapeutic ramifications.

Background This study aimed to investigate the natural history of re-rupture in ruptured brain arteriovenous malformations (AVMs) and to provide comprehensive insights into its associated factors and prevention. Methods This study included 1712 eligible ruptured AVMs from a nationwide multicenter prospective collaboration registry between August 2011 and September 2021. The natural rupture risk before intervention and the annual rupture risk after intervention were both assessed. Cox proportional hazard regression models and Kaplan–Meier survival curves were used to explore independent factors associated with AVM re-rupture. The correlation between these factors and AVM re-rupture was verified in multiple independent cohorts, and the prevention effect of intervention timing and intervention strategies on AVM re-rupture was further analyzed. Results The annual re-rupture risk in ruptured AVMs was 7.6%, and the cumulative re-rupture risk in the first 1, 3, 5, and 10 years following the initial rupture were 10%, 25%, 37.5%, and 50%, respectively. Cox proportional hazard regression analysis confirmed adult patients, ventricular system involvement, and any deep venous drainage as independent factors associated with AVM re-rupture. The intervention was found to significantly reduce the risk of AVM re-rupture (annual rupture risk 11.34% vs 1.70%, pConclusions The risk of re-rupture in ruptured AVMs is high. Adult patients, ventricular system involvement, and any deep venous drainage are independent risk factors for re-rupture. Applying the results universally to all ruptured AVM cases may be biased. Intervention could effectively reduce the risk of re-rupture.

Background: Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke in young adults, which can lead to severe neurological impairment. The registry of Multimodality treatment for brain ArTeriovenous malformation in mainland CHina (MATCH) is a national prospective registry to identify the natural history of AVMs in Asian population; to investigate traditional and emerging hemorrhagic predictors; and to explore the superiority of the multidisciplinary assessment in improving the long-term outcomes. Methods: Consecutive AVM patients will be enrolled from 52 participating hospitals in mainland China. Baseline demographic, clinical and imaging data will be collected prospectively. Conservation, microsurgery, embolization, stereotactic radiosurgery (SRS), and multimodal strategies are all included in this study. Patients will be divided into experimental and control group according to whether the treatment protocols are formulated by multidisciplinary team. Neurofunctional status, subsequent hemorrhage, seizure, and novel neurofunctional deficit will be queried at 3 months, annually (1 and 2 years), 3 years, and 10 years follow-up. Results: Between August 2011 and April 2021, 3241 AVMs were enrolled in 11 participating sites. Among them, 59.0% were male with an average age of 28.4 ± 14.6 years, 61.2% had rupture history and 2268 hemorrhagic events occurred before admission. The median Spetzler-Martin grade and Lawton-Young grade was 3 and 5, respectively. Microsurgery is the dominant strategy (35.7%), with a similar proportion of embolization, SRS, and a combination of both (12.7%; 14.8%; 11.8%; respectively). Among them, 15.43% underwent multidisciplinary assessment and received standardized treatment. At the most recent follow-up, 7.8% were lost and the median follow-up duration was 5.6 years. Conclusions: The MATCH study is a large-sample nationwide prospective registry to investigate multimodality management strategy for AVMs. Data from this registry may also provide the opportunity for individualized risk assessment and the development of optimal individual management strategies. Trial registration: ClinicalTrials.gov Registry (NCT04572568).

Background. The association of DNA methylation with the pathogenesis of adult ischemic moyamoya disease (MMD) is unknown. Here, we investigated the genome‐wide DNA methylation profiles in patients with MMD and identified the genes related to the pathogenesis of MMD. Methods. Whole blood samples were collected from 20 individuals, including 10 patients with ischemic moyamoya disease without any underlying disease and 10 healthy individuals. Genome‐wide DNA methylation analysis was performed using Illumina 850K microarrays. Transcriptional correlation was verified using quantitative reverse transcription‐polymerase chain reaction. In vitro experiments were used to analyze the association of functional defects with candidate epigenetic markers. Results. The genome‐wide methylation level in the whole blood of adults with ischemic MMD was higher than that in the healthy individuals. In total, 759 methylation probes differed significantly between the case and control. The hypermethylated regions were mostly concentrated in the gene spacer regions. Among genes with the highest degree of the differential expression, KCNMA1 and GALNT2 were upregulated, whereas SOX6 and RBM33 were downregulated. Conclusions. This is the first study showing that the low expression of genes associated with epigenetic regulation, such as SOX6 and RBM33, may be related to vascular occlusion in MMD, whereas the overexpression of KCNMA1 and GALNT2 may be related to the vascular hyperplasia. The results suggest that DNA methylation was involved in the pathogenesis of MMD, and new pathogenic genes were proposed as biological markers.

Delayed anastomotic occlusion occurred in a considerable proportion of hemorrhagic moyamoya disease (MMD) patients undergoing direct revascularization. This study aimed to investigate the predictors and outcomes of delayed anastomotic occlusion in adult hemorrhagic MMD. The authors retrospectively reviewed 87 adult hemorrhagic MMD patients. Univariate and multivariate logistic regression analyses were performed. After an average of 9.1 ± 6.9 months of angiographic follow-up, the long-term graft patency rates were 79.8%. The occluded group had significantly worse angiogenesis than the non-occluded group (p < 0.001). However, the improvement of dilated anterior choroidal artery–posterior communicating artery was similar (p = 0.090). After an average of 4.0 ± 2.5 years of clinical follow-up, the neurological statues and postoperative annualized rupture risk were similar between the occluded and non-occluded groups (p = 0.750; p = 0.679; respectively). In the multivariate logistic regression analysis, collateral circulation Grade III (OR, 4.772; 95% CI, 1.184–19.230; p = 0.028) and preoperative computed tomography perfusion (CTP) Grade I–II (OR, 4.129; 95% CI, 1.294–13.175; p = 0.017) were independent predictors of delayed anastomotic occlusion. Delayed anastomotic occlusion in adult hemorrhagic MMD might be a benign phenomenon. Good collateral circulation (Grade III) and compensable preoperative intracranial perfusion (CTP Grade I–II) are independent predictors for this phenomenon. Moreover, the delayed anastomotic occlusion has no significant correlations with the long-term angiographic and neurological outcomes, except neoangiogenesis.