Previous studies evaluating the association between antidiabetic drugs and the risk of ischemic stroke have yielded inconsistent results. This study employed a Mendelian randomization (MR) approach to preliminarily explore the potential causal associations of major antidiabetic drugs with the risk of ischemic stroke and its subtypes, and performed validation using independent European and Asian population data. Methods: Genetic variants associated with the targets of sulfonylureas (ABCC8/KCNJ11), GLP-1 analogs (GLP1R), thiazolidinediones (PPARG), insulin and its analogs (INSR), and metformin were extracted from published studies as instrumental variables (all instrument F-statistics>10). The primary analysis was conducted using MEGASTROKE European population data. Inverse variance weighting (IVW) or the Wald ratio method was used to estimate the causal effects of drug targets on acute ischemic stroke (AIS), large artery atherosclerosis stroke (LAS), cardioembolic stroke (CES), and small vessel stroke (SVS). External validation consisted of: (1) validation of overall AIS using independent European population data from FinnGen; (2) an exploratory analysis of stroke subtypes using GIGASTROKE East Asian population data. This study was exploratory in nature; no corrections were made for multiple comparisons, and a P-value < 0.05 was used as the statistical criterion for nominal association. Results: The primary analysis (MEGASTROKE) showed that sulfonylureas (rs757110) had a nominal association with reduced AIS risk (OR=0.05, 95% CI 0.01-0.29, P=0.001), although the effect was extreme; metformin showed a suggestive association with LAS (OR=0.47, P=0.047); and the multi-single nucleotide polymorphism (SNP) instrument for sulfonylureas (KCNJ11/ABCC8) showed a suggestive association with CES (OR=0.09, P=0.046). External validation: In FinnGen, none of the associations between the drugs and AIS were statistically significant (rs757110: OR=0.53, P=0.601; all others P>0.05). In the exploratory analysis of the East Asian population, none of the original positive signals for stroke subtypes showed a nominal association [metformin with LAS: OR=1.22, P=0.715; sulfonylureas (ABCC8/KCNJ11) with CES: OR=1.68, P= 0.871]; the associations were not replicated, and the confidence intervals were extremely wide, suggesting insufficient statistical power. Conclusion: The positive signals for antidiabetic drugs on ischemic stroke observed in the primary analysis were not supported by independent external validation. The extreme protective effect of the sulfonylurea SNP-rs757110 was judged as a false positive. The suggestive associations of metformin with LAS and sulfonylureas with CES were not replicated in external validation and should be considered only as exploratory hypotheses. The current genetic evidence does not support the clinical application of any antidiabetic drug for ischemic stroke or its subtypes.

To compare the efficacy and safety of bridging therapy (intravenous thrombolysis plus endovascular treatment) versus direct endovascular treatment (EVT) in patients with acute posterior circulation large vessel occlusion (PC-LVO). Methods: This was a single-center, retrospective cohort study. A total of 110 eligible patients with PC-LVO were enrolled, comprising 66 in the bridging group (receiving intravenous rt-PA within 4.5 hours of onset followed by EVT) and 44 in the direct EVT group [with onset-to-puncture time (OPT) extendable up to 24 hours). Clinical data were collected and compared between the two groups, including baseline characteristics such as age, sex, hypertension, diabetes, history of atrial fibrillation, admission National Institutes of Health Stroke Scale (NIHSS) score, anesthesia method, OPT, and time window stratification. The primary efficacy endpoint was the proportion of patients with a modified Rankin Scale (mRS) score of 0-3 at 90 days (good outcome). Safety indicators included the incidence of symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. Multivariate Logistic regression analysis was performed to evaluate the association between bridging therapy and good outcome (mRS≤3), adjusting for baseline differences and time factors. Results: There were no statistically significant differences in baseline characteristics between the two groups except for OPT (P>0.05); the bridging group had a shorter OPT [200 (150, 240) min vs 480 (320, 720) min, P< 0.001]. The 90-day good outcome rate was 53.0% (35/66) in the bridging group and 40.9% (18/44) in the direct group, with no statistically significant difference (P=0.16). The incidence of sICH in the bridging group was slightly higher than that in the direct group (9.1% vs 4.5% , P=0.38). The 90-day mortality was 25.8% in the bridging group and 18.2% in the direct group (P=0.34). Multivariate Logistic regression analysis showed no significant association between bridging therapy and a good 90-day outcome (P=0.30). A high NIHSS score was an independent risk factor for poor outcome (P<0.01), while older age showed only a trend toward adverse prognosis (P=0.20). Prolonged OPT was significantly associated with poor outcome (per 1-hour delay, OR≈0.61, P= 0.04). The results of the sensitivity analysis (considering only patients with OPT≤6 hours) were consistent with the main analysis. Conclusion: In this retrospective cohort, there were no statistically significant differences in functional outcome and mortality between the bridging therapy group and the direct EVT group in patients with PC-LVO. Future large-sample randomized studies are needed to further validate the role of bridging therapy in posterior circulation stroke.

To explore the related risk factors for the onset of post-stroke spasticity (PSS). Methods: Medical records of stroke patients hospitalized in the Rehabilitation Center of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from April 1, 2022, to December 31, 2023, were enrolled. Patients were divided into the PSS group and the non-PSS (NPSS) group based on the presence or absence of PSS. Univariate and multivariate logistic analyses were used to analyze potential risk factors. Results: Multivariate logistic regression analysis revealed six risk factors for the occurrence of PSS, including a disease course longer than 2 weeks, right cerebral hemisphere damage, higher NIHSS scores (ranging from 5 to 20), and lower MBI scores (ranging from 41 to 59). In contrast, older age at stroke onset and high triglyceride levels were found to reduce the incidence of PSS. Conclusion: This study identified a total of six risk factors for PSS.

To investigate the characteristics of peripheral lymphocyte subsets in patients with insomnia disorder (ID) and their associations with cognitive function. Methods: A total of 39 drug-naïve patients with ID and 51 healthy controls (HCs) were recruited from Wuhan First Hospital between April 2022 and March 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Stroop Color-Word Test. Flow cytometry was performed to determine the proportions and absolute counts of peripheral lymphocyte subsets in both groups. Between-group comparisons, correlation analyses, and multivariable linear regression analyses were conducted to evaluate the relationships between peripheral lymphocyte subsets and cognitive function. Results: Compared with HCs, the ID group had significantly lower MoCA total scores and poorer performance in multiple cognitive domains (P<0.05). In the Stroop test, the ID group showed reduced accuracy and prolonged Stroop-D reaction time (P<0.05). In addition, the ID group exhibited significantly increased proportions and absolute counts of T cells, helper T lymphocytes (Th cells), B cells, and total T+B+NK cells (P<0.05), whereas the proportion of NK cells was significantly decreased (P= 0.001). Correlation analyses further showed that the MoCA total score and several domain scores were negatively correlated with the proportions and absolute counts of Th cells and B cells (P<0.05), but positively correlated with the proportion of NK cells (P<0.05). Moreover, the accuracy and reaction time in Stroop-C and Stroop-D were significantly correlated with T-cell- and Th-cell-related parameters (P<0.05). Multivariable linear regression analysis showed that, after adjustment for age, education level, and BMI, Th-cell proportion, Th-cell absolute count, the Th/cytotoxic T lymphocyte (CTL) ratio, B-cell absolute count, NK-cell proportion, and total T+B+NK absolute count were independently associated with the MoCA total score. Conclusion: Patients with ID showed mild multidomain cognitive impairment, predominantly involving executive function, accompanied by a peripheral immune profile characterized by adaptive immune predominance. This imbalance in peripheral lymphocyte subsets was significantly associated with cognitive decline and may represent a potential biomarker of insomnia-related cognitive impairment.

To summarize and analyze the neurological manifestations, biochemical and imaging characteristics, treatment methods, and prognosis of patients with central nervous system-hemophagocytic lymphohistiocytosis (CNS-HLH), so as to deepen the clinical understanding of this disease. Methods: A retrospective analysis was conducted on the clinical data of 33 CNS-HLH patients treated at Beijing Friendship Hospital, Capital Medical University, from January 2022 to December 2024. Additionally, the PubMed database was searched for literature reports of 484 CNS-HLH patients published from January 2020 to December 2025. Descriptive statistical analysis was performed on the etiology, clinical manifestations, laboratory and imaging examinations, treatment regimens, and prognosis of the two patient groups. Results: Among the 33 patients from our hospital, the main etiologies were Epstein-Barr virus (EBV) infection (51.5%) and lymphoma (24.2% ). The primary neurological manifestations were alterations in consciousness/mental status (24.2% ) and focal neurological deficits (24.2% ). Cerebrospinal fluid (CSF) examinations most commonly showed elevated pressure (75.8%) and elevated protein levels (60.6%), while the abnormality rate on cranial MRI was 63.3%. In terms of treatment, 87.9% of patients received intrathecal injection, and 51.5% underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a 1-year survival rate of 75.8%. Among the 484 patients reviewed from the literature, the main etiologies were EBV infection (64.9%) and familial genetic defects (50.2% ). Clinical manifestations were predominantly epilepsy (58% ) and disturbance of consciousness (39% ). The CSF abnormality rate was 83.3%, and the cranial MRI abnormality rate reached 85.6% , with lesions most frequently involving the cerebral hemispheres (74.4% ). Regarding treatment, 58% received intrathecal injection, while only 8% underwent allo-HSCT, and the overall mortality rate was 46.3% . Conclusion: The etiology of CNS-HLH is predominantly EBV infection and hereditary immunodeficiency, and its neurological manifestations lack specificity. Biochemical abnormalities in CSF and characteristic changes on cranial MRI are crucial for diagnosis. Early combined immunosuppression, targeted therapy, and intrathecal injection are helpful for controlling the disease. Allogeneic hematopoietic stem cell transplantation is an important means to improve prognosis; however, the overall mortality rate remains high, warranting high clinical vigilance.

To summarize and analyze the organizational structure, operational mechanisms, innovative strategies, and implementation effectiveness of the stroke tiered diagnosis and treatment model in Hubei Province, so as to provide replicable reference experience for the construction of the national stroke prevention and control system. Methods: Based on the policy framework of the“323”Offensive Action, this study systematically analyzed the construction of stroke centers and primary prevention and treatment stations, key treatment time indicators, and the implementation effects of tiered diagnosis and treatment in Hubei Province. This was achieved through policy analysis, administrative data mining, and summarization of typical practices, relying on national and provincial stroke center construction and management platforms. Results: Hubei Province has established a three-level quality control system (“Provincial Stroke Prevention and Control Center - Municipal Center - Medical Institution”) and a five-level linkage organizational architecture covering province, city, county, township, and village. As of the end of 2024, 183 stroke centers (22 tertiary and 161 secondary) and 1,029 primary stroke prevention and treatment stations had been established. The stroke emergency map covers 189 units, achieving full coverage of acute stroke treatment resources at the county level. The compliance rate for door-to-needle time (DNT) ≤ 60 min across the province reached 86.95%, and onset-to-needle time (ONT) was shortened by 40 min. Primary institutions have performed a cumulative total of 5,307 intravenous thrombolysis cases. From 2021 to 2024, the number of intravenous thrombolysis cases in tertiary hospitals increased by 117.3% , and arterial thrombectomy cases increased by 255.1%; in secondary hospitals, intravenous thrombolysis increased by 211.5%, and arterial thrombectomy increased by 696.8% . Through the mechanism of integrating medical care and prevention, high-risk screening has been conducted for approximately 20 million residents aged over 35, 847 brain-heart health managers have been trained, and closed-loop management has been implemented for over 1 million person-times. Stroke mortality rates in some regions were lower than the national and central region averages. Conclusion: By establishing a three-level quality control and five-level linkage tiered diagnosis and treatment system, and promoting technology transfer to primary care and the integration of medical care and prevention, Hubei Province has significantly improved acute stroke treatment efficiency and primary prevention and treatment capabilities. This provides replicable regional experience for the implementation of stroke tiered diagnosis and treatment in China.

Endolymphatic hydrops (EH) serves as a crucial pathological basis for various vestibular disorders and holds particular significance in the diagnosis of Meniere's disease. With the continuous advancement of magnetic resonance imaging (MRI) technology, especially the application of delayed gadolinium-enhanced delayed 3D-FLAIR sequences, the capability for imaging diagnosis of EH has been significantly enhanced. Clinically, the interpretation of inner ear hydrops imaging often relies on experienced experts; however, this process is highly subjective and time-consuming, posing a substantial challenge to the precise diagnosis of peripheral vestibular disorders. In recent years, the application of artificial intelligence (AI), particularly deep learning-based image analysis methods, has provided a novel solution for the rapid and objective assessment of EH. This article reviews the fundamental principles of radiomics and AI in EH diagnosis, the current status of their application in interpreting inner ear hydrops imaging, existing challenges, and future development directions. It aims to provide theoretical support and technical reference for the precise diagnosis and personalized treatment of inner ear diseases.

Sleep deprivation (SD) is a significant contributor to neuroinflammation, oxidative stress, and cognitive dysfunction, with its mechanisms closely linked to astrocyte activation. As key regulators of the central nervous system, astrocytes exhibit dual roles in SD through A1/A2 polarized phenotypes: A1 astrocytes exacerbate neuroinflammation and synaptic damage by releasing pro-inflammatory factors and neurotoxins, whereas A2 astrocytes promote neural repair via secretion of neurotrophic factors and anti-inflammatory mediators. This review systematically summarizes the activation mechanisms of astrocytes in SD and related signaling pathways, including NF-κB, MAPK, SHH and JAK-STAT. Chronic SD induces cognitive impairment through the accumulation of inflammatory mediators and hyperactivation of astrocytes, while modulating their polarization phenotypes (e.g., suppressing A1 or enhancing A2) may serve as novel strategies for intervening in SD-related neural injuries. Future studies should further elucidate the spatiotemporal specificity of astrocyte polarization and interactions within signaling networks to provide a theoretical basis for targeted therapies.

As global population aging intensifies, the rising incidence of neurodegenerative diseases poses a significant public health challenge. TREM2 (triggering receptor expressed on myeloid cells 2), an immune regulatory receptor specifically expressed in microglia, plays a dual role in neurodegenerative diseases by modulating phagocytosis, inflammatory responses, and cell metabolism. TREM2 can recognize damaged neurons and pathological proteins, such as β-amyloid. It then activates downstream signaling pathways like PI3K/Akt, driving microglia to an anti-inflammatory phenotype. This process clears toxic substances and maintains neuronal metabolic homeostasis. However, TREM2 gene mutations can lead to abnormal protein function, substantially increasing Alzheimer’s disease risk. This paper comprehensively reviews TREM2’s role in various neurodegenerative diseases, particularly in Alzheimer’s disease, aiming to underpin the development of TREM2-based therapies with theoretical evidence and novel insights.

Traumatic brain injury (TBI) is a major brain disorder characterized by high mortality and high disability rates. The secondary brain injury caused by TBI has long lacked effective treatment strategies, representing a critical medical challenge that urgently needs to be overcome. Although a substantial amount of research on TBI treatment has been reported and novel therapeutic concepts have emerged, they have not been successfully translated into clinical practice. Therefore, clinical treatment for TBI-induced secondary brain injury remains an area awaiting breakthroughs. This article primarily discusses the current status of TBI diagnosis and treatment, advances in therapeutic research, and the challenges regarding clinical translation, aiming to provide a reference for promoting research into TBI treatment.

In this paper, the molecular mechanism and research progress of insulin-like growth factor-1 (IGF-1) in diabetes and its complications are systematically reviewed. IGF-1 regulates cell proliferation, metabolism and survival by activating multiple signaling pathways such as PI3K/AKT/mTOR and MAPK/ERK. In the development of diabetes, IGF-1 participates in regulating pancreatic beta cell function, insulin sensitivity and glucose homeostasis, and its serum level is closely related to the risk of diabetes and disease progression. In terms of diabetes complications, IGF-1 may play a neuroprotective role in peripheral neuropathy; while in retinopathy and nephropathy, it shows a dual role, which may promote vascular proliferation and disease progression, but also has protective effects under certain conditions. In summary, IGF-1 and its signaling pathways can be used as potential biomarkers and therapeutic targets for diabetes and its complications. Future studies need to further explore tissue-specific mechanisms and clinical transformation to promote the development of individualized diagnosis and treatment strategies.

Traditional intervention methods for fear-related psychological disorders (such as specific phobia and post-traumatic stress disorder) are challenged by drug dependence and insufficient cultural adaptability. Music therapy, with its non-invasive nature and cross-cultural potential, has emerged as a new option, but there is still a gap in the integration of its mechanisms and the fusion of traditional Chinese and Western medical theories. Through a systematic review of recent studies, this paper proposes an integrated model of“Five Elements Music - Neural Plasticity”, which for the first time links the frequency characteristics of the Chinese Yu mode music (40~80 Hz) with the regulation of neurotransmitters (5-HT, GABA) and the functions of the limbic system (amygdala, hippocampus). This paper further constructs a ternary model of“frequency - neurotransmitter – emotion”, providing evidence-based guidance for the setting of music parameters, and proposes the neural mechanism by which group intervention alleviates social anxiety through the mirror neuron system. This paper provides theoretical basis and practical guidance for the standardized treatment of fear-related psychological disorders with music therapy.