Background:Ischemic stroke (IS) induces profound dysregulation of the neuro-molecular innate immune-vascular network, yet the molecular immune states and regulatory mechanisms of key cellular subpopulations remain insufficiently defined. Although traditional Chinese medicine (TCM) exhibits multi-target immunomodulatory potential, its cell-type and cell-state-specific actions within the ischemic brain microenvironment at single-cell resolution remain unclear. Methods:Single-cell RNA sequencing was used to construct a cellular atlas of the ischemic mouse brain, followed by integrative bioinformatic analyses to characterize innate immune-related neural cell subpopulations and their regulatory networks. Network pharmacology and molecular docking were applied to identify salidroside (SAL), a major active compound of Rhodiola, and predict its potential molecular targets. In vivo experiments were performed to validate cellular and molecular changes associated with SAL treatment. Results:In a mouse model of IS, ischemic injury induced pronounced imbalances across multiple immune and glial cell subpopulations. A transcriptionally defined Notch1+ Hes5+ astrocyte (ASC), enriched for progenitor-like and reparative gene signatures, was markedly reduced after ischemic injury, whereas reactive SerpinA3N+ ASC and pro-inflammatory Sell+ microglia (MG) were expanded. Additionally, alterations were observed in immune-regulatory cell populations, including Cxcl12+ endothelial cells (ECs) and Gpr34+ Ptgs1+ MG. In vivo validation showed that SAL treatment was associated with modulation of Notch1/Hes5 signaling in ASC, reduced reactive ASC features, and partial normalization of ECs alterations, accompanied by changes consistent with attenuated neuroimmune activation. These effects coincided with altered intercellular communication, particularly involving NOTCH signaling. Conclusions:This study provides single-cell-level insights into innate immune microenvironment remodeling following IS and identifies a Notch1+ Hes5+ ASC subpopulation with transcriptional features associated with reparative-related programs and responsiveness to SAL. The findings suggest that SAL-associated neuroprotection was accompanied by modulation of ASC states and immune-glial communication, highlighting the potential of SAL-associated immunoregulatory effects at the single-cell level in IS.

BACKGROUND:Volatile organic compounds (VOCs) are widespread environmental pollutants that can cause oxidative stress and hepatocellular damage. However, epidemiological evidence linking VOC exposure to liver fibrosis and the underlying molecular mechanisms remains limited. METHODS:Data were obtained from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Liver fibrosis was defined using the NAFLD fibrosis score (NFS > 0.676). Weighted logistic regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) models were applied to evaluate individual and combined associations of nine blood VOCs with liver fibrosis after adjusting for demographic, lifestyle, and biochemical covariates. To explore potential mechanisms, network toxicology and molecular docking were conducted. RESULTS:VOCs were moderately correlated, indicating common co-exposure sources. The WQS model revealed a positive overall association between mixed VOC exposure and liver fibrosis, with 1,4-Dichlorobenzene contributing the greatest weight. In fully adjusted models, higher blood 1,4-Dichlorobenzene levels were significantly associated with increased odds of liver fibrosis (p-trend < 0.05). RCS analysis showed a nonlinear dose-response relationship between 1,4-Dichlorobenzene and liver fibrosis risk. Network toxicology identified 176 overlapping targets enriched in PI3K-AKT and MAPK signaling pathways, with SRC, AKT1, AKT3, PIK3CA, and PIK3CD as hub genes. Molecular docking confirmed stable binding between 1,4-Dichlorobenzene and these proteins, with binding energies ranging from -7.5 to -8.5 kcal/mol. CONCLUSION:Blood 1,4-dichlorobenzene exposure is positively associated with an increased risk of liver fibrosis in the U.S. population, potentially through PI3K-AKT and MAPK pathway activation. This integrative approach provides new insights into VOC-induced hepatic fibrosis.

INTRODUCTION:The inhibition of microglia-mediated inflammatory responses is of great importance for the treatment of neurodegenerative diseases. Mume Fructus total flavonoids (MFTF) are one of the major bioactive components of Mume Fructus, a traditional food and medicinal herb in China. This study aimed to clarify the anti-inflammatory effect of MFTF on lipopolysaccharide (LPS)-induced microglial inflammation and to elucidate its underlying mechanism. METHODS:Ultra-high-performance liquid chromatography coupled with Quadrupole Time-offlight mass spectrometry was used to analyze the chemical composition of MFTF. BV2 cells were stimulated with LPS (100 ng/mL) for 24 h to establish an in vitro inflammatory model. Cell viability was tested by the Cell Counting Kit-8 assay. Cell proliferation was assessed by the 5- Ethynyl-2'-deoxyuridine assay. Cell polarization and miR-145-3p expression were analysed by real-time quantitative PCR. The expression of apoptosis- and inflammation-related proteins was analyzed by Western Blotting. RNA sequencing was used to explore the potential mechanisms by which MFTF regulates the inflammation of BV2. RESULTS:A total of 379 compounds have been identified in MFTF. MFTF promoted the proliferation, downregulated the expression of pro-inflammatory markers (iNOS, IL-1β, and CD86), and upregulated the expression of anti-inflammatory markers (Arg-1, IL-10, and CD206) of BV2 cells following LPS stimulation. In addition, MFTF inhibited the expression of pro-apoptotic protein Bad and inflammatory mediators COX-2 and iNOS, while promoting the anti-apoptotic protein Bcl-2. Further, MFTF unregulated miR-145-3p expression in LPS-stimulated BV2 cells, and inhibition of miR-145-3p partially abolished the anti-inflammatory, anti-apoptotic, and proproliferative effects of MFTF. RNA sequencing results showed MFTF may inhibit the inflammation in BV2 cells by regulating the Toll-like receptor signalling pathway, NOD-like receptor signalling pathway, and NF-κB signalling pathway. DISCUSSION:Our findings demonstrated that MFTF inhibited pro-inflammatory polarization (M1) while promoting proliferation and anti-inflammatory polarization (M2) of microglia, potentially through the upregulation of miR-145-3p. These results indicated that MFTF could attenuate microglial inflammation, thereby supporting our hypothesis that MFTF may have therapeutic potential in alleviating neurodegenerative diseases. CONCLUSION:These results uncovered a potential mechanism underlying the antineuroinflammatory effects of MFTF and provide a theoretical basis for its therapeutic application in neuroinflammatory disorders.

Background:Intractable temporal lobe epilepsy (ITLE) poses ongoing therapeutic challenges due to resistance to antiseizure medications and limited improvements in patient quality of life. Although neuroimaging studies have identified both functional and structural abnormalities in ITLE, their combined analysis and relevance to treatment refractoriness remain unclear. Methods:We collected longitudinal rs-fMRI and DTI data from 29 patients with ITLE (pre-/post-treatment) and 25 healthy controls and extracted ALFF/ReHo and FA/MD/AD/RD features. Primary inferences were based on conventional group and longitudinal analyses, while exploratory random-forest classification and UMAP visualization were used to compare functional and structural discriminative patterns. Results:Post-treatment functional measures in ITLE patients showed partial normalization toward healthy control levels, whereas white matter abnormalities-especially reduced fractional anisotropy in the Fornix (crus)/Stria terminalis-remained persistent. In exploratory classification analyses, structural features continued to distinguish ITLE from controls after treatment, while functional features more frequently classified post-treatment ITLE cases as healthy, consistent with a structural-functional dissociation. Conclusions:These findings suggest that persistent white matter microstructural alterations may contribute to treatment resistance in ITLE despite apparent functional normalization. Exploratory machine-learning and low-dimensional visualization offered converging, quantitative support for this dissociation and may help prioritize candidate targets for future validation in larger cohorts.

The rapid accumulation of lactate following cerebral ischemia has been well documented, however, the pathophysiological mechanisms underlying hyperlactate-induced lactylation in modulating neurological injury and prognosis of acute ischemic stroke (AIS) remain to be fully elucidated. We constructed transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 60 AIS patients and 60 healthy controls using the Illumina sequencing platform. Unsupervised consensus clustering based on 56 lactylation-related genes (LRGs) was applied to stratify AIS molecular subtypes. Single-cell sequencing data analysis was conducted to evaluate the regulatory effects of LRGs enrichment on inter-neuronal communication. 265 differentially expressed genes (DEGs), including 162 upregulated and 103 downregulated, were identified between AIS patients and healthy controls. And DEGs were found to be enriched in natural killer cell-mediated cytotoxicity, cytokine-cytokine receptor interaction, and TGF-β signaling pathways. Unsupervised consensus clustering stratified AIS into two subtypes, with AIS2 exhibiting more severe neuronal injury and inflammatory responses. Single-cell sequencing analysis revealed that LRGs were predominantly enriched in NK T cells following cerebral ischemia. Cell communication analysis further suggested that LRGs might regulate interactions between NK T cells and neural cells via the Nampt-Insr and Tnf-Tnfsf1b ligand-receptor pair. LASSO regression selected four prognosis-related genes (SUMO2, SUB1, LSP1, EEF1G) with robust diagnostic efficacy for prognosis prediction (AUC value = 0.805, sensitivity = 0.875, specificity = 0.706). Our findings reveal significant correlations between LRGs in AIS patients and both neurological deficit severity and inflammatory status, highlighting LRGs as potential prognostic biomarkers for AIS.

Dysregulation of long non-coding RNAs (lncRNAs) is implicated in the pathophysiology of ischemic stroke (IS). However, the molecular mechanism of the lncRNA SERPINB9P1 in IS remains unclear. Our study aimed to explore the role and molecular mechanism of the lncRNA SERPINB9P1 in IS. This study revealed downregulation of the lncRNA SERPINB9P1 in the peripheral blood of IS patients, which was corroborated by the GSE140275 dataset. Furthermore, high lncRNA SERPINB9P1 expression was associated with lower National Institutes of Health Stroke Scale (NIHSS) scores and favorable outcome. Clinically, lncRNA SERPINB9P1 expression was correlated with inflammation and coagulation parameters in IS patients. Furthermore, lncRNA SERPINB9P1 silencing inhibited cell viability, induced apoptosis and inflammatory response under oxygen–glucose deprivation/reperfusion ; however, these effects were reversed upon its overexpression. Additionally, Chromatin Isolation by RNA Purification and mass spectrometry (CHIRP-MS) and western blot confirmed that the lncRNA SERPINB9P1 was involved in the pathological process of IS through binding to heat shock protein 2 (HSPA2). HSPA2 was upregulated in IS patients, and its protein interaction network was significantly enriched in IS-related pathways. In conclusion, the lncRNA SERPINB9P1 may ameliorate neurological injury in IS patients by interacting with the HSPA2 protein and engaging in IS-related pathways, providing new insights into treatment strategies for IS.

Difficulty in resisting gravity is a common leg motor impairment in stroke patients, significantly impacting daily life. Automated clinical-level quantification of motor-leg videos based on the National Institutes of Health Stroke Scale is crucial for consistent and timely stroke diagnosis and assessment. However, real-world applications are challenged by interference impacting motion representation and decision-making, leading to performance instability. To address this, we propose a causality debiasing graph convolutional network. This model systematically reduces interference in both motor and non-motor body parts, extracting causal representations from human skeletons to ensure reliable decision-making. Specifically, an intra-class causality enhancement module is first proposed to resolve instability in motor-leg representations. This involves separating skeletal graphs with the same score, generating unbiased samples with similar discriminative features, and improving causal consistency. Subsequently, an inter-class non-causality suppression module is designed to handle biases in non-motor body parts. By decoupling skeletal graphs with different scores, this module constructs biased samples and enhances decision stability despite non-causal factors. Extensive validation on the clinical video dataset highlights the strong performance of our method for motor-leg scoring, achieving an impressive correlation above 0.82 with clinical scores, while independent testing at two additional hospitals further reinforces its stability. Furthermore, performance on another motor-arm scoring task and an additional Parkinsonian gait assessment task also successfully confirmed the method’s reliability. Even when faced with potential real-world interferences, our approach consistently shows substantial value, offering both clinical significance and credibility. In summary, this work provides new insights for daily stroke assessment and telemedicine, with significant potential for widespread clinical adoption.

Ethnopharmacological relevance Tackling phlegm and improving blood circulation is vital in the treatment of ischemic stroke (IS), culminating in the development of Zhongfeng Decoction (ZFD), a method grounded in this approach and serving as an effective therapy for IS. Nonetheless, the defensive mechanism of the ZFD in preventing cerebral ischemia-reperfusion damage remains ambiguous. Aim of the study Determine the active ingredients in ZFD that have neuroprotective effects, and identify its mechanism of action against IS. Materials and methods A cerebral ischemia model in rats was developed, utilizing TTC, Nissl staining, and an oxidative stress kit to evaluate the neuroprotective impact of ZFD on this rat model. Following this, an amalgamation of LC-MS and network pharmacology techniques was employed to pinpoint potential active components, primary targets, and crucial action mechanisms of ZFD in treating IS. Finally, key targets and signaling pathways were detected using qRT-PCR, ELISA, Western blotting, electron microscopy, and other methods. Results Through LC-MS and network analysis, 15 active ingredients and 6 hub targets were identified from ZFD. Analysis of pathway enrichment revealed that ZFD predominantly engages in the AGE-RAGE signaling route. Kaempferol, quercetin, luteolin, baicalein, and nobiletin in ZFD are the main active ingredients for treating IS. In vivo validation showed that ZFD can improve nerve damage in cerebral ischemic rats, reduce the mRNA expression of IL6, SERPINE1, CCL2, and TGFB1 related to inflammation. Furthermore, we also confirmed that ZFD can inhibit the protein expression of AGEs, RAGE, p-IKBα/IKBα, p-NF-κB p65/NF-κB p65, reduce autophagy levels, and thus decrease neuronal apoptosis. Conclusions The mechanism of action of ZFD in treating IS primarily includes inflammation suppression, oxidative stress response alleviation, post-stroke cell autophagy and apoptosis regulation, and potential mediation of the AGE-RAGE signaling pathway. This study elucidates how ZFD functions in treating IS, establishing a theoretical basis for its clinical application.

Leg agility is a key indicator of bradykinesia, which in turn is a cardinal manifestation of Parkinson’s disease (PD). In fact, automated video assessment of the leg-agility task is critically required for improving the efficiency and objectivity of PD diagnosis. Therefore, we propose a causality-informed graph convolutional network to extract discriminative clinically-meaningful motion features from human skeletons in videos, finally achieving stable leg-agility 5-point scoring. The proposed scheme systematically mines causal features of each skeleton graph from graph node, structure, and representation levels. Specifically, we firstly developed a causality-informed node selection mechanism to mine the graph nodes representing the discriminative features, and thus identify nodes causally correlated to the clinical assessment aspects and suppress the interference from other nodes. Afterwards, a causality-informed structure generation mechanism was designed to generate a graph structure encoding the connections between the discriminative nodes, hence maintaining the discriminability of features associated with these causality-informed nodes. Finally, we employed a clinically-driven self-supervised learning scheme to embed clinical prior knowledge into the proposed model and hence boost the clinical significance of the causality-informed graph nodes, structures, and representations. The proposed method achieved a 71.11% accuracy and a 98.93% acceptable accuracy on a large clinical video dataset. Its effectiveness was also confirmed on an independent test set, and the obtained results exhibited interpretability from modeling and clinical perspectives. In conclusion, our method provides a highly stable scheme for objective video quantification of bradykinesia. Our source code will be released at https://github.com/SJTUBME-QianLab/PD-CIGCN.

China has experienced a heavy public health burden due to the increasing incidence of ischemic stroke (IS). Few studies have evaluated the relationship between particulate matter (PM) exposure and acute ischemic stroke (AIS) in relatively less-polluted areas, and the results have been inconsistent. As a result, this study aimed to investigate and evaluate the association between PM exposure and hospitalizations for AIS in an area with less air pollution. Through collecting daily AIS hospitalizations, air pollution data and meteorological data from July 1, 2017 to June 30, 2020 in Nanning, this paper explored the association between short-term exposure to PM (PM2.5, PM10 and PMc) and daily hospital admissions for AIS using a distributed lag non-linear model based on time-series. To further identify the susceptible populations, stratified analyses were performed by age and gender. During the study period, a total of 2382 patients were admitted to hospital with AIS, with the ratio of male to female reached 2.03: 1. No statistical association was found between PM exposure and AIS admissions in the total population. Subgroup analysis showed that PM2.5, PM10 and PMc exposures were significantly associated with AIS admissions in male at lag29-lag30, lag27-lag30 and lag25-lag27, respectively. In addition, PMc exposure was also relevant to admissions for AIS with aged < 65 years at lag18-lag23. Short-term exposure to ambient PM was not associated with hospital admissions for AIS in the general population, but males and young adults (aged < 65 years) were more susceptible to PM exposure. Even in areas with relatively low air pollution, appropriate measures should be adopted to intervene in the adverse effects of air pollution on vulnerable populations.

Background: Metal exposure has long been considered a significant risk factor for ischemic stroke. However, existing data on the effects of metal exposure on brain function in ischemic stroke are limited. Therefore, this study aimed to explore the correlation between exposure to various metals and changes in resting-state functional connectivity (rs-FC) in ischemic stroke patients. Methods: This study included 28 acute ischemic stroke patients with hemiplegia and 28 matched healthy controls (HCs). All participants underwent T1-weighted MRI and 3.0 T resting-state functional magnetic resonance imaging (fMRI). After MRI acquisition, the rs-FC between 137 cortical and subcortical regions was extracted and preprocessed. Plasma levels of 19 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). The Bayesian kernel machine regression (BKMR) model and the weighted quantile sum regression (WQS) model were used to assess the overall effect of metal mixture exposure. The severity of neurological deficits in each acute ischemic stroke patient was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Additionally, the associations between exposure to various metals and modifications in brain functional connectivity were determined using Pearson or Spearman correlation analysis. Results: Bilateral brain connectivity was significantly decreased compared to controls and was associated with neurological impairment in ischemic stroke. In patients with ischemic stroke, the plasma concentrations of Cr (p < 0.001), Cu (p = 0.004), As (p = 0.010), Cs (p = 0.046), Rb (p = 0.041), and Sb (p = 0.001) were significantly higher than those in the HCs, whereas the plasma Tl concentrations (p = 0.022) were significantly lower. The results of the BKMR and WQS models showed that combined exposure to metal mixtures was linked to a higher risk of ischemic stroke. Cr was positively correlated with the rs-FC between the left Rolandic_Oper and the left Supp_Motor_Area (r = 0.414, p = 0.029), while negatively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal (r = -0.398, p = 0.037). Cu was negatively correlated with the rs-FC between the left paracentral lobule and the left thalamus (r = -0.409, p = 0.031). Tl was positively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal cortex (r = 0.590, p = 0.001). A negative correlation was observed between Cs and rs-FC between the right Cingulate_Mid and left Occipital_Sup (r = -0.429, p = 0.024). Sb was negatively correlated with the rs-FC between the left Parietal_Inf and the right SupraMarginal (r = -0.384, p = 0.044), the right Parietal_Inf and the left SupraMarginal (r = -0.583, p = 0.001), and the left SupraMarginal and the right SupraMarginal (r = -0.377, p = 0.048). Conclusion: Plasma levels of Cr, Cu, Tl, Cs, and Sb were associated with altered rs-FC in brain regions related to motor control, sensory integration, executive function, language processing, and emotional regulation in ischemic stroke patients with basal ganglia infarction.

Circular RNAs are involved in intervention strategies for treating ischemic stroke (IS). However, circCNOT6L (hsa_circ_0006168) has not yet been reported in IS. Thus, we aimed to explore the potential role of circCNOT6L and its molecular mechanism in IS. In this study, we first found that the expression of both exosomal circCNOT6L ( P = 0.0006) and plasma circCNOT6L ( P = 0.0054) was down-regulated in IS patients compared with controls. Clinically, a negative correlation was observed between the relative expression level of circCNOT6L and the National Institutes of Health Stroke Scale (NIHSS) score and infarct volume of the brain. Simultaneously, the relative expression level of circCNOT6L was negatively associated with multiple risk factors for IS, such as mean platelet volume (MPV), red cell distribution width (RDW), very low-density lipoprotein (VLDL), and serum potassium, whereas it was positively correlated with high-density lipoprotein (HDL). In vitro, circCNOT6L silencing blocked cell viability and proliferation, while it promoted cell apoptosis of astrocytes undergoing oxygen–glucose deprivation/reperfusion (OGD/R) treatment. Mechanistically, the RNA antisense purification (RAP) assay and luciferase reporter assay revealed that circCNOT6L acts as a miRNA sponge to absorb miR-99a-5p and then regulates the expression of serine proteinase inhibitor (SERPINE1). In the further rescue experiment, overexpressing SERPINE1 could rescue the cell apoptotic signals due to circCNOT6L depletion. In conclusion, CircCNOT6L attenuated the cell apoptotic signal of astrocytes via the miR99a-5p/SERPINE1 axis and then alleviated injury after hypoxia induced by ischemic stroke.

目的 明确分化抑制因子3(Id3)能否作为缺血性脑卒中(IS)潜在的诊断标志物,并研究免疫细胞浸润在IS病理中的作用.方法 从基因表达综合数据库中下载IS数据集.首先使用R语言软件识别差异表达基因并进行功能相关分析.然后结合最小绝对收缩与选择算子、支持向量机的特征递减消除算法和加权基因共表达网络分析算法筛选IS的诊断标志物并进一步验证,通过受试者工作特征曲线评估标志物对IS的诊断价值.最后,利用反卷积算法评价IS组织中免疫细胞浸润情况,分析诊断标志物与浸润免疫细胞的相关性.结果 本研究总共确定了165个差异表达基因,发现Id3可能是IS的诊断标志物(受试者工作特征曲线下面积0.839,95％置信区间:0.750～0.920).免疫细胞浸润分析表明,中性粒细胞、初始CD4+T淋巴细胞、初始B细胞、CD8+T淋巴细胞、静息CD4+记忆T淋巴细胞、活化CD4+记忆T淋巴细胞、静息树突状细胞、静息肥大细胞、嗜酸性粒细胞与IS的发生进展可能存在关系.结论 Id3可能是IS潜在的诊断基因,免疫细胞浸润对IS的发生发展有重要影响.

外泌体是大多数细胞分泌的纳米级细胞外囊泡,可以穿越血脑屏障,并携带各种生物活性分子内容物在细胞之间进行传递,促进细胞间的通讯,与各种疾病的发生和过程密切相关.环状RNA是一类广泛存在于哺乳动物细胞中的RNA转录物,具有稳定性、丰富性、普遍性等特征,可作为临床中有价值的生物标志物或治疗靶标.外泌体环状RNA在缺血性脑卒中病理和生理过程中发挥重要的生物学作用,可作为缺血性脑卒中理想的生物标志物和治疗靶点.本文就外泌体、环状RNA及外泌体环状RNA在缺血性脑卒中中的研究进行简要综述.

Objective To investigate the associations between the polymorphisms of phosphatidylinositol glycan anchor biosynthesis class M（PIGM） gene rs2275404, ATPase H + transporting V1 subunit B2（ATP6V1B2） gene rs1042426, N-acetylneuraminic acid phosphatase（NANP） gene rs11700338 and ischemic stroke（IS） and its blood lipid level. Methods A total of 1567 subjects were enrolled in the study, including 774 cases of IS and 793 controls. Massarray SNP technique was used for genotyping, and unconditional logistic regression model was used to analyze association between genetic models（additive model, dominant model, and recessive model） and diseases. Results There was no genetic association between the polymorphisms of PIGM gene rs2275404, ATP6V1B2 gene rs1042426 and NANP gene rs11700338 and the susceptibility of IS（all P＞0.05）.After adjusting age and gender, PIGM gene rs2275404 was significantly correlated with the triglyceride level of IS(recessive model: β adj =-0.26, 95% CI=-0.47-0.05, P adj = 0.015);ATP6V1B2 gene rs1042426 was significantly correlated with the apolipoprotein B level of IS(additive model: β adj = 0.06, 95% CI= 7.77×10 -4 -0.12, P adj =0.048;dominant model: β adj =0.07, 95% CI=4.28×10 -3 -0.14, P adj =0.037);and NANP gene rs11700338 was significantly correlated with apolipoprotein A1 level of IS(dominant model: β adj =0.05, 95% CI=2.86×10 -4 -0.09, P adj =0.049). Conclusion The polymorphisms of PIGM gene rs2275404, ATP6V1B2 gene rs1042426, and NANP gene rs11700338 are not associated with the risks of ischemic stroke, but they may affect the blood lipid levels of patients with ischemic stroke.

目的 探讨锌指蛋白(ZNF)260 rs34550124 多态性与缺血性脑卒中痰证、血瘀证及临床生化指标的相关性.方法 采用病例-对照研究.采用实时荧光定量聚合酶链反应(qRT-PCR)实验技术来测定外周血ZNF260 基因的mRNA表达水平,并采用MassARRAYSNP基因分型实验技术对其进行基因分型.采用"研究对象相关信息采集调查表"结合医院信息系统收集血糖、凝血、血压等临床资料.采用Hardy Weinberg遗传平衡检验方法评估样本代表性.采用非条件Logistic回归模型分析各遗传模型(加性模型、显性模型、隐性模型)与疾病的关联;采用一般线性回归分析多态性位点与相关数量性状的关联.结果 ZNF260 基因rs34550124 多态性与缺血性脑卒中痰证[显性模型:OR=0.73,95％CI(0.56～0.95),P=0.022;校正年龄、性别后,OR=0.73,95％CI(0.56～0.95),P=0.021]、痰证和血瘀证发生风险显著相关[显性模型:OR=0.72,95％CI(0.57～0.92),P=0.009;校正年龄、性别后,OR=0.72,95％CI(0.57～0.92),P=0.009].ZNF260 基因rs34550124 多态性与缺血性脑卒中患者的收缩压(SBP)、餐后2h血糖(2 h PG)、凝血标志物[国际标准化比率(INR)、血小板(PLT)、凝血酶原时间(PT)、凝血酶原时间活动度(PTA)]水平显著相关(P＜0.05).结论 ZNF260 基因rs34550124 多态性可能影响缺血性脑卒中痰证及血瘀证发生过程,且ZNF260 基因rs34550124 多态性可能影响缺血性脑卒中患者的血压、血糖及凝血功能.

According to previous studies, circular RNAs (circRNAs) are involved in multiple pathological processes of acute ischemic stroke (AIS). However, the relationship between circFOXP1 and IS has not yet been reported. Here, we found that circFOXP1 expression was significantly decreased in the peripheral blood of AIS patients compared to controls and was associated with the severity and prognosis of AIS. Functionally, knockdown and overexpression of circFOXP1 promoted and inhibited apoptotic signaling, respectively, following oxygen-glucose deprivation/reperfusion (OGD/R) treatment in vitro. Adeno-associated virus (AAV)-mediated circFOXP1 overexpression attenuated neurological deficits and improved functional recovery after transient middle cerebral artery occlusion (tMCAO) treatment in vivo. Mechanistically, decreased QKI expression inhibited circFOXP1 biogenesis under hypoxic conditions. Decreased circFOXP1 expression accelerated signal transducer and activator of transcription 3 (STAT3) protein degradation by binding to and increasing STAT3 protein ubiquitination, ultimately aggravating brain injury after cerebral ischemia by activating apoptotic signaling. In summary, our study is the first to reveal that circFOXP1 alleviates brain injury after cerebral ischemia by regulating STAT3/apoptotic signaling, which provides a potentially novel therapeutic target for AIS.

目的 探索与缺血性脑卒中(IS)凋亡相关的长链非编码RNA(lncRNA)-mRNA网络并预测核心基因.方法 选取 2016 年 1 月至 2017 年 6 月广西中医药大学第一附属医院(以下简称"我院")收治的 10 例IS患者和同期我院社区卫生体检中心10名健康对照者作为研究对象.对微阵列表达谱进行差异分析,使用加权基因共表达网络分析筛选目标模块内的基因,并与凋亡基因取交集.运用STRING网站和Cytoscape软件筛选前 10位差异mRNAs(DEMs),同时与差异lncRNAs(DELs)构建lncRNA-mRNA共表达网络,最后筛选核心基因.结果 获得 3 930个DEMs,模块基因与凋亡基因取交集后得到了 553个与凋亡相关的IS基因.构建的lncRNA-mRNA共表达网络包含 9 个DEMs、277 个DELs,最终筛选出 7 个核心基因G015366、G068382、PIK3CB、BPTF、NR3C1、Akt2和INS.结论 G015366、G068382、PIK3CB、BPTF、NR3C1、Akt2和INS与IS的发生发展相关,可能成为IS诊断标志物.

Objective To investigate the relationship between rs1067 polymorphism of WD repeat domain(WDR)5B gene and traditional Chinese medicine(TCM)syndromes and clinical markers of ischemic stroke(IS).Methods A total of 1 567 patients with IS and healthy controls at the same time were selected.The genotyping of WDR5B gene rs1067 polymorphism was primarily per-formed with the sequenom MassARRAY SNP technology.The TCM syndromes of IS patients were classified according to the TCM Syn-drome Differentiation Diagnostic Criteria for Apoplexy.Results WDR5B gene rs1067 polymorphism was significantly associated with the occurrence of wind syndrome of IS[allelic(A/G):P=0.037;dominant(AA+GA/GG):P=0.043;additive(AA/GG):P=0.041].After adjusting for sex and age,WDR5B gene rs1067 polymorphism was still significantly associated with the risk of IS syndrome[dominant(AA+GA/GG):P=0.032;additive(AA/GG):P=0.032].After adjusting for sex and age,WDR5B gene rs1067 poly-morphism was significantly associated with postprandial 2 h plasma glucose level and high-density lipoprotein level in patients with IS(P<0.05).Conclusions WDR5B gene rs1067 polymorphism might affect the occurrence of wind syndrome of IS.WDR5B rs1067 gene polymorphism might affect postprandial 2 h plasma glucose level and high-density lipoprotein level in IS patients.