[This corrects the article DOI: 10.3389/fneur.2025.1733441.].

Alcohol consumption and depression commonly co-occur, and most current research has focused on the associations between either alcohol consumption or depression alone with mortality risk. However, the association of the comorbidity of heavy alcohol consumption and depression on the risk of all-cause and cause-specific mortality remains unclear in the U.S. population. The objective of our study was to analyze the risks of all-cause and cause-specific mortality in participants who have heavy alcohol consumption alone, depression alone, or both, by conducting a prospective cohort study with a sample in the National Health and Nutrition Examination Survey (NHANES) database. For this cohort study, we included 11,590 U.S. adults aged ≥ 20 years from a nationally representative sample. Data on depression and alcohol consumption were extracted from the NHANES conducted between 2005 and 2018, and mortality information was obtained from the NHANES Linked Mortality File through December 31, 2019. Drinking and depression were classified into four groups: only heavy alcohol consumption, only depression, both present, and neither present. By adjusting for confounding factors, we applied the Cox proportional hazards model to investigate the risk of all-cause mortality associated with alcohol consumption and depressive states, including cardiovascular disease (CVD), cancer, and other causes. The log-rank test and Kaplan-Meier (K-M) survival analysis were applied to investigate differences in survival probabilities. Additionally, we examined the correlation between heavy alcohol consumption and depression by assessing additive interaction using the synergy index (SI), the attributable proportion due to interaction (AP), and the relative excess risk due to interaction (RERI). The adjusted HR (aHR) for all-cause mortality, as well as mortality due to CVD, cancer, and other causes, were highest among individuals with comorbid heavy alcohol consumption and depression (HR 2.68[95

Epileptic seizures are sudden, brief episodes of abnormal brain activity that can be detected through electroencephalography (EEG), which records both normal and abnormal electrical activity in the brain. Previous studies have achieved significant success in detecting seizures using convolutional neural networks (CNNs) to automatically extract seizurespecific features from EEG signals. However, substantial variability in multi-channel seizure waveforms across different patients poses challenges to model generalization and cross-patient recognition. To this end, we introduce a novel Temporal-Focal Attention Network (TFANet), designed to capture channel-specific activations associated with crosspatient seizure patterns. TFANet enhances focal responses learned from high-resolution temporal signals during convolution, effectively capturing channel-specific seizure representations across patients. Extensive experiments on a self-curated dataset demonstrate that TFANet outperforms existing methods, achieving a state-of-the-art Kappa score of 93.19% for cross-patient seizure detection. The code is available at https://github.com/fjssharpsword/EEG-BCI.

The Midasin AAA (ATPase associated with various activities) ATPase 1 (MDN1) gene, a member of the AAA protein family, plays a crucial role in ribosome maturation. MDN1 is expressed in the human brain throughout life, especially during early development and adulthood. However, MDN1 variants have not been previously reported in patients with epilepsy. This study aims to explore the association between MDN1 variants and epilepsy. Trios-based whole-exome sequencing was performed in a cohort of patients with epilepsy susceptibility from the China Epilepsy Gene 1.0 Project. The excess, damaging effects, and molecular subregional implications of variants, as well as the spatio-temporal expression of MDN1, were analyzed to validate the gene-disease association. Compound heterozygous variants in MDN1 were identified in five unrelated patients with febrile seizures or secondary epilepsy. Three patients presented with febrile seizures/epilepsy with febrile seizures plus, while two patients developed epilepsy secondary to brain damage (five or seven years after). These variants were either absent or present at low frequencies in the control group, and exhibited statistically significant higher frequencies in the case group compared to controls. All the missense variants were predicted to be damaging by at least one in silico tool. In each pair of compound heterozygous variants, one allele was located in the AAA2-AAA3 domains, while the other allele was located in the linker domain or its vicinity. In contrast, most of the variants from the asymptomatic control group were located outside the AAA domains, suggesting a molecular subregional implication of the MDN1 variants. MDN1 is potentially a susceptibility gene for epilepsy.

Objective (background)The aim of this study is to analyze the current research status and future prospects of the field of developmental and epileptic encephalopathy (DEE) and gene through bibliometric methods. It aims to explore the trends and potential developments in this field.MethodsA systematic search of the DEE and gene literature from 2001 to 2025.2 was conducted using the Web of Science core collection database. Supplementary PubMed searches for this field’s clinical research trends ensured verified data comprehensiveness and methodological rigor. Quantitative analysis of co-authorship networks was performed using VOSviewer and CiteSpace tools.ResultsA total of 1,022 articles related to the field of DEE and gene were included in this study, authored by 8,355 researchers affiliated with 7,238 institutions across 315 countries. United States emerged as the leading research countries in this field, with the National Institute of Health and Medical Research. Professor Ingrid Scheffer had the highest number of publications in this field, and the journal Epilepsy had the highest citation count. The research hotspots in this field revolved around epilepsy, mutations, epileptic encephalopathy, de novo mutations, and seizure.ConclusionThe research on DEE and gene is currently experiencing rapid growth. The field is expanding, and the research is becoming more in-depth.

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations. However, the ability of retinal vasculature changes, specifically focusing on retinal vessel diameter, to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively. While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events, they have not incorporated this information into a predictive model. Therefore, this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke. Additionally, we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors. We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University. All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years. We found that, after adjusting for related risk factors, patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin (MAD0.5-1.0DD) of ≥ 74.14 μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin (MVD0.5-1.0DD) of ≥ 83.91 μm tended to experience recurrent cerebrovascular events. We established three multivariate Cox proportional hazard regression models: model 1 included traditional risk factors, model 2 added MAD0.5-1.0DD to model 1, and model 3 added MVD0.5-1.0DD to model 1. Model 3 had the greatest potential to predict subsequent cerebrovascular events, followed by model 2, and finally model 1. These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke, and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.

INTRODUCTION:Symtomatic hemorrhagic transformation(sHT) was defined as any intracerebral hemorrhage that combined with clinical deterioration. While recent studies showed low rates of sHT in large core ischemic strokes treated with endovascular thrombectomy (EVT), the specific impact of core size on overall hemorrhagic transformation (HT) remains unclear. We aim to investigate the relationship between ischemic core size and development of HT post thrombectomy. METHODS:This prospective study enrolled acute ischemic stroke (AIS) patients with anterior large vessel occlusion undergoing EVT who had baseline MRI from 2017 to 2019. Pre-EVT Arterial Spin Labeling (ASL) and Diffusion-Weighted Imaging (DWI) scans were performed for volume calculations. Primary outcome was HT assessed within 72 h post EVT. Multivariable logistic regression was used to analyze the associations between baseline DWI and ASL volumes and HT occurrence. Discriminative ability for HT was compared using receiver operating curve analysis (c-statistic). RESULTS:We included 101 patients (median age: 64 [IQR 56-74] years, baseline NIHSS 13 [IQR 9-16]). Median DWI and ASL volume were 21.0 ml [IQR 8.3-47.2] and 105 ml [59.5-172.9], respectively. 16.8 % recieved intravenous thrombolysis before EVT. HT occurred in 36.6 % of patients, including 16.8 % with sHT. Baseline DWI volume was independently associated with HT (OR = 1.030, 95 % CI 1.008 to 1.053, P = 0.009), while ASL volume wasn't statistically significant(P = 0.330). The DWI model was superior to ASL model in predicting HT within 72 h (c-statistic, 0.787).Neither DWI (P = 0.149) nor ASL volume (P = 0.834) effectively indicated sHT. CONCLUSIONS:DWI-based ischemic core volume correlates significantly with HT within 72 h post successful thrombectomy. This highlights the potential clinical utility of DWI in guiding treatment decisions for this population.

The active hemorrhage surrounding the hematoma is caused by the infiltration of blood into the cerebral parenchyma through the ruptured vessel, including the compromised blood–brain barrier (BBB). This process is thought to be mainly driven by inflammation and serves as a significant pathological characteristic that contributes to the neurological deterioration observed in individuals with intracerebral hemorrhage (ICH). Heat shock protein 90 (HSP90) exhibits abnormally high expression levels in various diseases and is closely associated with the onset of inflammation. Here, we found that blocking HSP90 effectively alleviates the inflammatory damage to BBB and subsequent bleeding around the hematoma. We have observed increased HSP90 levels in the serum of patients with ICH and the perihematoma region in ICH rats. Treatment with anti-HSP90 drugs (Geldanamycin and radicicol) effectively reduced HSP90 levels, resulting in enhanced neurological outcomes, decreased hematoma volume, and prevented peripheral immune cells from adhering to the BBB and infiltrating the brain parenchyma surrounding the hematoma in ICH rats. Mechanistically, anti-HSP90 therapy alleviated BBB injury caused by ICH-induced inflammation by suppressing TLR4 signaling. The study highlights the potential of anti-HSP90 therapy in mitigating BBB disruption and hemorrhage surrounding the hematoma, providing new insights into the management of ICH by targeting HSP90.

Intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT) have been widely used in minor ischemic stroke (MIS) treatment. However, the clinical outcomes and safety of these two treatments have not been compared within the early thrombolytic time window. Here, we conducted a multicenter, ambispective cohort study involving patients with MIS presenting within 4.5 h of symptom onset at 3 affiliated hospitals of Jinan University from 2018–2022. The patients were divided into the IVT group and DAPT group. The primary outcome was a 90-day excellent outcome (mRS ≤ 1). A total of 1,026 patients were enrolled, of whom 492 were assigned to the IVT group and 534 were assigned to the DAPT group. The IVT group had better 90-day excellent outcomes (mRS ≤ 1) than the DAPT group (OR 1.69, 95

Background. There is insufficient evidence about the suitability of dual-antiplatelet therapy (DAPT) for different stroke subtypes. We aimed to determine the relationship between DAPT and early neurological deterioration (END) in patients with minor stroke of undetermined cause. Methods. We retrospectively collected data on patients with minor stroke treated with aspirin alone or in combination with clopidogrel and aspirin. Efficacy was the incidence of END defined as the National Institutes of Health Stroke Scale score increase of ≥2 within 7 days after admission. Safety was defined as the rate of any bleeding event. These were investigated in subtypes including the stroke of undetermined cause (SUC), large artery atherosclerosis (LAA), cardioembolism (CE), and small artery occlusion (SAO). Results. 442 patients were assigned to the SUC ( n = 91 ), LAA ( n = 157 ), CE ( n = 30 ), and SAO ( n = 164 ) groups. The incidences of END were not significantly different between patients treated with dual- versus single-antiplatelet therapy in any stroke subtypes: LAA, 17.6% vs. 12.1% ( P = 0.348 ); CE, 0% vs. 20.0% ( P = 0.224 ); SAO, 8.8% vs. 2.4% ( P = 0.093 ); and SUC, 13.6% vs. 2.1% ( P = 0.053 ). Multivariable analysis showed that after adjusting for confounding factors, DAPT was the independent factor associated with END (odds ratio 13.39, 95% confidence interval (1.16-154.81), P = 0.038 ) in the SUC group, rather than the LAA, CE, and SAO groups. Conclusion. Combined clopidogrel and aspirin is a risk factor for the rate of END only in minor stroke patients with the SUC subtype. This suggests that cryptogenic stroke may not be suitable for DAPT in the acute phase.

Background Stroke-related pneumonia (SAP) is a common complication in acute ischemic stroke (AIS) patients, and it has adverse effects on the clinical outcomes and increases the burden on patients' families and society. Early identification and individualized care are necessary to reduce the incidence of SAP. Objective The present study aimed to explore the effect of nurse-led hierarchical management care based on the acute ischemic stroke-associated pneumonia score (AIS-APS) scale in AIS patients. Methods A quasi-intervention pilot study design was adopted for the present study. A total of 120 AIS patients were enrolled and assigned to the intervention group and the control group, with 60 subjects in each group in a tertiary hospital in Guangzhou, China. The control group received routine care, whereas the intervention group was given nurse-led hierarchical management care based on the AIS-APS scale. The intervention duration was more than 7 days, and the incidence of SAP, neurological function, swallowing function, and activities of daily living (ADLs) at discharge were observed. The outcomes were assessed at baseline and at outpatient time. Results A total of 120 participants were enrolled in our study. A significant decrease was found in the incidence of SAP in the intervention group (18.3%) compared with that in the control group (41.7%). Positive outcomes were shown in neurology function, swallowing function, and ADL in the intervention group. Conclusion Nurse-led hierarchical management care based on AIS-APS can reduce the incidence of SAP, promote AIS patients' neurological function, and maintain patients' ADL. The results of our study indicated that nurse-led hierarchical management care is feasible for AIS patients and provides individualized interventions for patients with different levels of SAP risk. Nurse-led hierarchical management care could be incorporated into routine nursing practice. Further study is needed and expected to solve more clinical problems.

Background: Dl-3-n-Butylphthalide (NBP) has the potential to improve clinical outcomes in acute ischemic stroke patients by improving collateral circulation. We aimed to evaluate the efficacy and safety of NBP in patients with non-disabling minor ischemic stroke and transient ischemic attack (TIA). Methods: The BRIDGE (the observation study on clinical effectiveness of NBP on patients with non-disabling ischemic cerebrovascular disease) is a prospective registry to monitor the efficacy and safety of NBP therapy in acute non-disabling ischemic stroke or high-risk TIA. Non-disabling minor ischemic stroke patients within 48 h were enrolled across 51 stroke centers in China. We divided patients into NBP compliance or non-compliance groups according to their adherence to NBP. The primary outcome was the favorable functional outcome at 90 days, defined as a modified Rankin scale (mRS) <2. Results: Between 10th October 2016 and 25th June 2019, 3,118 patients were included in this analysis. In multivariable analysis, Between 10th October 2016 and 25th June 2019, 3,118 patients were included in this analysis. In multivariable analysis, after adjusting for common risk factors and demographic factors, NBP-compliance group has a higher proportion of favorable functional outcome (92.1 vs. 87.4%, adjusted odds ratio 2.00, 95% confidence interval, 1.50–2.65), and a higher stroke recurrence rate (2.40 vs. 0.31%, adjusted odds ratio 8.86, 95% confidence interval, 3.37–23.30) than the NBP-non-compliance group. There was no significant difference in death and intracranial hemorrhage rate between the two groups. In subgroup analysis, patients with National Institutes of Health Stroke Scale (NIHSS) scores from 3 to 5 who complied to NBP therapy had a higher rate of favorable functional outcomes than the NBP-non-compliance group. [88.82 vs. 76.21%, adjusted odds ratio 2.52 (1.81–3.50), adjusted interaction P = 0.00]. Conclusion: In non-disabling minor ischemic stroke or TIA patients, compliance with NBP therapy led to better 90-day functional outcomes despite a higher risk of recurrence, and this effect seems to be stronger in patients with NIHSS scores of 3-5. Further large randomized, double-blind controlled studies to analyse the association between NBP and functional outcome is warranted in the coming future.

Many hospitals lack facilities for accurate diagnosis of acute ischemic stroke (AIS). Circular RNA (circRNA) is highly expressed in the brain and is closely associated with stroke. In this study, we examined whether the blood-borne circRNAs could be promising candidates as adjunctive diagnostic biomarkers and their pathophysiological roles after stroke. We profiled the blood circRNA expression in mice subjected to experimental focal cerebral ischemia and validated the selected circRNAs in AIS patients. We demonstrated that 128, 198, and 789 circRNAs were significantly altered at 5 min, 3 h, and 24 h after ischemic stroke, respectively. Our bioinformatics analysis revealed that the circRNA-targeted genes were associated with the Hippo signaling pathway, extracellular matrix-receptor interaction, and fatty acid metabolism at 5 min, 3 h and 24 h after ischemic stroke, respectively. We verified that many of these circRNAs existed in the mouse brain. Furthermore, we found that most of the predicted circRNA-miRNA interactions apparently exhibited functional roles in terms of regulation of their target gene expression in the brain. We also verified that many of these mouse circRNAs were conserved in human. Finally, we found that circBBS2 and circPHKA2 were differentially expressed in the blood of AIS patients. These results demonstrate that blood circRNAs may serve as potential biomarkers for AIS diagnosis and reveal the pathophysiological responses in the brain after ischemic stroke.

The present study aimed to assess the expression and functional role of aquaporin-1 (AQP1) in glioblastoma multiforme (GBM) migration, invasion and vasculogenic mimicry (VM). In the primary human gliomas and human glioma‑derived cell lines tested, it was observed that the expression of AQP1 was upregulated. In addition, it was demonstrated that silencing of AQP1 expression resulted in decreased migration and invasion, in addition to vasculogenic mimicry in vitro. It was additionally observed that silencing of AQP1 expression resulted in in vivo inhibition of tumor growth, a decrease in the expression of invasion‑associated protein, and suppression of VM formation. Based on these data, it was concluded that AQP1 may serve a role in GBM migration, invasion and VM formation, and that it may serve as a novel diagnostic/prognostic biomarker and a potential therapeutic target.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases glucose-dependent insulin secretion to reduce the glucose level. Liraglutide, a long-acting GLP-1 analogue, has been found to have neuroprotective action in various experimental models. However, the protective mechanisms of liraglutide in ischaemic stroke remain unclear. Here, we demonstrated that liraglutide significantly decreased the infarct volume, improved neurologic deficits, and lowered stress-related hyperglycaemia without causing hypoglycaemia in a rat model of middle cerebral artery occlusion (MCAO). Liraglutide inhibited cell apoptosis by reducing excessive reactive oxygen species (ROS) and improving the function of mitochondria in neurons under oxygen glucose deprivation (OGD) in vitro and MCAO in vivo. Liraglutide up-regulated the phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinases (ERK) and inhibited the phosphorylation of c-jun-NH2-terminal kinase (JNK) and p38. Moreover, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and/or the ERK inhibitor U0126 counteracted the protective effect of liraglutide. Taken together, these results suggest that liraglutide exerts neuroprotective action against ischaemia-induced apoptosis through the reduction of ROS and the activation of the PI3K/AKT and mitogen-activated protein kinase (MAPK) pathways. Therefore, liraglutide has therapeutic potential for patients with ischaemic stroke, especially those with Type 2 diabetes mellitus or stress hyperglycaemia.

缺氧是实体肿瘤普遍存在的一个特征，广泛存在于肿瘤的原发灶及其转移灶。缺氧诱导因子家族(HIFF)在对缺氧的适应性改变中起了重要作用。HIFF共有3个成员，包括缺氧诱导因子(HIF)l、2、3，均是由不同的α亚基(HIF-1α、HIF-2α、HIF-3α)和共同的β亚基构成的异源二聚体转录因子。其中HIF-1α亚基是细胞在缺氧应答反应中起重要作用的调节因子。syndecan-1是细胞膜表面的硫酸乙酰肝素蛋白聚糖家族的成员，许多研究表明，syndecan-1是肿瘤生长和转移的一个重要的促进因子，在许多肿瘤中已被看作是一种与肿瘤发生有关的可能标志物[1-3]。

Objective:To explore the relationship between the expressions of ERRα mRNA and estrogen,progesterone,and to elucidate the function of ERRα in the endometrial carcinoma.Methods:HEC-1B cells were dealt with different concentrations of β-estradiol and progesterone respectively.The proliferation of the cells was measured by MTT assay.The expression levels of ERRα mRNA were examined by real-time quantitive PCR.Results:E2 could promote the proliferation of HEC-1B cells,and the OD values in the groups of high concentration of E2(10-6～10-8mol/L) were increased compared with the control group(P<0.05).The expression levels of ERRα mRNA were significantly up-regulated after stimulated by different concentrations of E2.The maximal effect was observed at the concentration of 10-7mol/L.Progesterone could inhibit the proliferation of HEC-1B cells,which was enhanced with the increasing of dose and treatment time.And the OD values in the group of high concentration of progesterone(10-4～10-6mol/L) were decreased compared with control group(P<0.05).The expression levels of ERRα mRNA were significantly down-regulated after stimulated by different concentrations of progesterone.The maximal effect was observed at the concentration of 10-4mol/L.Positive correlations were found between the proliferation of HEC-1B cells and the expression levels of ERRα mRNA after stimulated by different concentration of E2 and progesterone,which means estrogen could promote the cell proliferation by up regulating the expression levels of ERRα mRNA,while progesterone could inhibit the cell proliferation by down regulating the expression levels of ERRα mRNA in the ERα-negative endometrial carcinoma cell line HEC-1B.Conclusion:ERRα may play a role in the development of endometrial carcinoma.

Objective To invesigate the effect of different approaches of misoprostol and urethral catheter placement in cervical canals used to intenerate cervix in hysteroscope therapy.Methods Three hundred and fouty cases were divided into three groups according to the different period of our hospital to select different way to intenerate cervix;group A:120 cases,were placed misoprostol 1 mg sublingually 2 hours before hysteroscope therapy;group B:120 cases,they were placed misoprostol 1 mg in vagina 2 hours before hysteroscope therapy and group C: 100 cases,placed urethral catheter in cervical canals 12 hours before hysteroscope therapy.The degree of intenerate cervix,the effect of analgesia,hemorrhage during operation,operation time,the adverse reaction including nausea,vomiting and bellyache were observed.Results Effect of intenerate cervix in three groups were 96.66%,84.44%,89.00%,with no significant differences(P0.05).The rate of nausea,vomiting and bellyache in group B were higher than other groups(P0.05).The operation time,hemorrhage during operation in the three group had significant differences.Conclusion The effects of misoprostol placed in vagina or sublingually 2 hours before hysteroscope and urethral catheter placement therapy are all significant.Different administration routes can decrease administration route,but placed misoprostol sublingually 2 hours before hysteroscope therapy may have more gastrointestinal tract reaction,but urethral catheter placement in cervical canals have potential infected chances.