Abstract The incidence of emotional disorders in patients with idiopathic pulmonary fibrosis (IPF) is substantially higher than that in the general population, severely compromising their quality of life. However, the underlying mechanisms remain poorly understood. In this study with multi-omics, we demonstrated that sphingosine-1-phosphate (S1P) derived from IPF lungs drive anxiety and depressive-like behaviors. Mechanistically, circulating S1P in the blood bound to hippocampal S1PR1 to regulate the PI3K/PKA/CREB signaling pathway, leading to synapse damage, the activation of microglia and astrocytes, neuroinflammation and ferroptosis in the hippocampus. Pharmacological inhibition of Sphk1, a key enzyme in S1P synthesis, reduced serum S1P levels and alleviated IPF-induced anxiety and depressive-like behaviors. Similarly, selective inhibition of hippocampal S1P receptor signaling using Fingolimod also attenuated neuroinflammation and ferroptosis and ameliorated mood disorders in IPF models. Collectively, these findings demonstrate that metabolite S1P from fibrotic lungs serves as a mediator of lung-to-brain functional influence, providing new insights into the IPF comorbid mood disorders and potential therapeutic targets.

Background:High-resolution magnetic resonance vessel wall imaging (HR-VWI) offers enhanced visualization of vascular structures, thereby facilitating the deep learning (DL) network's acquisition of more extensive and detailed image information. This study aimed to develop a high-precision integrated model leveraging DL with an attention mechanism based on HR-VWI for predicting recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). Methods:A retrospective study was conducted involving 363 sICAS patients who underwent HR-VWI, with data divided into a training set (n=254) from Center 1 (The First Affiliated Hospital of Xinxiang Medical University) and a test set (n=109) from Center 2 (The Sixth People's Hospital of Shanghai Jiao Tong University). Two convolutional neural network (CNN) models, ResNet50 and DenseNet169, were employed as feature extractors to capture image information from culprit plaques in HR-VWI. Integrating the Transformer attention mechanism, an advanced ensemble model, Trans-CNN, was constructed to predict stroke recurrence in sICAS patients. Model performance was evaluated using receiver operating characteristic (ROC) curves, with DeLong's test for comparing models. Additionally, decision curve analysis (DCA) and calibration curves were utilized to assess the model's practical and clinical value. Results:Trans-CNN demonstrated superior predictive performance, outperforming other models in both the training and test sets. Specifically, in the training set, Trans-CNN achieved an area under the curve (AUC) of 0.951 [95% confidence interval (CI): 0.923-0.974], accuracy of 0.880 (95% CI: 0.797-0.937), sensitivity of 0.900 (95% CI: 0.836-1.000), and specificity of 0.882 (95% CI: 0.757-0.948). Similarly, in the test set, it achieved an AUC of 0.912 (95% CI: 0.839-0.969), accuracy of 0.858 (95% CI: 0.743-0.936), sensitivity of 0.880 (95% CI: 0.693-1.000), and specificity of 0.810 (95% CI: 0.690-0.976). The AUC improvement of Trans-CNN over all other models was statistically significant (DeLong's test, P<0.05). Calibration curve analysis revealed good agreement between predicted probabilities and observed outcomes in both sets. DCA further underscored the potential value of Trans-CNN in guiding clinical decision-making. Conclusions:The integrated model combining DL with an attention mechanism based on HR-VWI exhibits excellent performance in assessing the risk of stroke recurrence in sICAS patients. This advancement holds significant potential in assisting clinicians in diagnosis and developing individualized treatment strategies.

The blood-retina barrier (BRB) serves as a critical interface that separates the retina from the circulatory system, playing an essential role in preserving the homeostasis of the microenvironment within the retina. Specialized tight junctions and limited vesicle trafficking restrict paracellular and transcellular transport, respectively, thereby maintaining BRB barrier properties. Additionally, transcytosis of macromolecules through retinal vascular endothelial cells constitutes a primary mechanism for transporting substances from the vascular compartment into the surrounding tissue. This review summarizes the fundamental aspects of transcytosis including its function in the healthy retina, the biochemical properties of transcytosis, and the methodologies used to study this process. Furthermore, we discuss the current understanding of transcytosis in the context of pathological BRB breakdown and present recent findings that highlight significant advances in drug delivery to the retina based on transcytosis.

Edaravone dexborneol (EDB) is widely recognized for its anti-inflammatory and antioxidant properties and is clinically applied in the treatment of acute cerebral infarction. Ferroptosis is a critical process in the pathophysiology of brain injury following intracerebral hemorrhage (ICH). However, it remains unclear whether EDB can ameliorate ICH through the modulation of ferroptosis. This study aimed to evaluate the function and mechanism of EDB in treatment of ICH. With a male rat ICH model, animal behavior tests, histopathological staining, magnetic resonance imaging and evans blue staining were used to evaluate the neural protective function of EDB on ICH rats. The potential molecular mechanism was investigated using RNA sequencing. With the administration of Fer-1, a range of ferroptosis-related biomarkers, including Fe2+, 4-hydroxynonenal, malondialdehyde, etc., were analyzed to ascertain whether EDB confers neuroprotective effects through the modulation of P53/GPX4 pathways to inhibit ferroptosis. Finally, the findings were further corroborated using an in vitro ICH model with a P53 inhibitor. EDB has the potential to markedly enhance nerve and motor function, mitigate pathological damage, facilitate hematoma clearance, and repair BBB injury in ICH rats. KEGG analysis revealed that the differentially expressed genes were associated with signaling pathways, including P53 and ferroptosis. Both EDB and Fer-1 substantially reduced the concentrations of Fe2+, 4-hydroxynonenal, malondialdehyde, increased the amount of anti-oxidants, decreased the expression of P53, and concurrently upregulated the expression of GPX4. Besides, the P53 inhibitor PFT-α was observed to significantly reduce the levels of 4-HNE and lipid peroxides, while concurrently increasing the expression of GPX4. This investigation has shed light on the crucial neuroprotective role of EDB by regulating ferroptosis in ICH disease, which provided a theoretical basis for the clinical application of EDB in the treatment of ICH.

BACKGROUND:Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS:The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. RESULTS:We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS:With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Background and objectiveTo investigate the use of high-resolution magnetic resonance imaging (HR-MRI) to identify the characteristics of culprit plaques in intracranial arteries, and to evaluate the predictive value of the characteristics of culprit plaques combined with the modified Essen score for the recurrence risk of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) patients.MethodsA retrospective analysis was conducted on 180 patients with HR-NICE at the First Affiliated Hospital of Xinxiang Medical University, including 128 patients with no recurrence (non-recurrence group) and 52 patients with recurrence (recurrence group). A total of 65 patients with HR-NICE were collected from the Sixth Affiliated Hospital of Shanghai Jiaotong University as a validation group, and their modified Essen scores, high-resolution magnetic resonance vessel wall images, and clinical data were collected. The culprit plaques were analyzed using VesselExplorer2 software. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for recurrence, and a nomogram was constructed using R software to evaluate the discrimination of the model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to evaluate the model performance. Calibration curves and Decision Curve Analysis (DCA) were used to evaluate the model efficacy.ResultsIntra-plaque hemorrhage (OR = 3.592, 95% CI = 1.474–9.104, p = 0.006), homocysteine (OR = 1.098, 95% CI = 1.025–1.179, p = 0.007), and normalized wall index (OR = 1.114, 95% CI = 1.027–1.222, p = 0.015) were significantly higher in the recurrent stroke group than in the non-recurrent stroke group, and were independent risk factors for recurrent stroke. The performance of the nomogram model (AUC = 0.830, 95% CI: 0.769–0.891; PR-AUC = 0.628) was better than that of the modified Essen scoring model (AUC = 0.660, 95% CI: 0.583–0.738) and the independent risk factor combination model (AUC = 0.827, 95% CI: 0.765–0.889). The nomogram model still had good model performance in the validation group (AUC = 0.785, 95% CI: 0.671–0.899), with a well-fitting calibration curve and a DCA curve indicating good net benefit efficacy for patients.ConclusionHigh-resolution vessel wall imaging combined with a modified Essen score can effectively assess the recurrence risk of HR-NICE patients, and the nomogram model can provide a reference for identifying high-risk populations with good clinical application prospects.

Background and objectiveSymptomatic intracranial atherosclerotic stenosis (SICAS) is the most common etiology of ischemic stroke and one of the main causes of high stroke recurrence. The recurrence of stroke is closely related to the prognosis of ischemic stroke. This study aims to develop a machine learning model based on high-resolution vessel wall imaging (HR-VWI) to predict the risk of stroke recurrence in SICAS.MethodsThis study retrospectively collected data from 180 SICAS stroke patients treated at the hospital between 2020.01 and 2022.01. Relevant imaging and clinical data were collected, and follow-up was conducted. The dataset was divided into a training set and a validation set in a ratio of 7:3. We employed the least absolute shrinkage and selection operator (LASSO) regression to perform a selection on the baseline data, laboratory tests, and neuroimaging data generated by HR-VWI scans collected from the training set. Finally, five machine learning techniques, including logistic regression model (LR), support vector machine (SVM), Gaussian naive Bayes (GNB), Complement naive Bayes (CNB), and k-nearest neighbors algorithm (kNN), were employed to develop a predictive model for stroke recurrence. Shapley Additive Explanation (SHAP) was used to provide visualization and interpretation for each patient. The model’s effectiveness was evaluated using average accuracy, sensitivity, specificity, precision, f1 score, PR curve, calibration curve, and decision curve analysis.ResultsLASSO analysis revealed that “history of hypertension,” “homocysteine level,” “NWI value,” “stenosis rate,” “intracranial hemorrhage,” “positive remodeling,” and “enhancement grade” were independent risk factors for stroke recurrence in SICAS patients. In 10-fold cross-validation, the area under the curve (AUC) ranged from 0.813 to 0.912 in ROC curve analysis. The area under the precision-recall curve (AUPRC) ranged from 0.655 to 0.833, with the Gaussian Naive Bayes (GNB) model exhibiting the best ability to predict stroke recurrence in SICAS. SHAP analysis provided interpretability for the machine learning model and revealed essential factors related to the risk of stroke recurrence in SICAS.ConclusionA precise machine learning-based prediction model for stroke recurrence in SICAS has been established to assist clinical practitioners in making clinical decisions and implementing personalized treatment measures.

Background Neuroinflammation is closely related to the development of Parkinson's disease (PD). Because of the extensive sources, non-invasive and periodical collection method, human menstrual blood-derived endometrial stem cells (MenSCs) have been explored as a promising tool for treatment of PD. This study aimed to investigate if MenSCs could inhibit neuroinflammation in PD rats by regulating M1/M2 polarization and to excavate the underlying mechanisms. Methods MenSCs were co-cultured with 6-OHDA-exposed microglia cell lines. Then the morphology of microglia cells and the level of inflammatory factors were assessed by immunofluorescence and qRT-PCR. After MenSCs were transplanted into the brain of PD rats, animal motor function, the expression of tyrosine hydroxylase, and the level of inflammatory factors in the cerebrospinal fluid (CSF) and serum were detected to evaluate the therapeutic potential of MenSCs. Meanwhile, the expression of M1/M2 phenotype related genes was detected by qRT-PCR. One protein array kit containing 1000 kinds of factors was used to detect the protein components in the conditioned medium of MenSCs. Finally, bioinformatic analysis was performed to analyze the function of factors secreted by MenSCs and the signal pathways involved in. Results MenSCs could suppress 6-OHDA-induced microglia cell activation and significantly decrease inflammation in vitro. After transplantation into the brain of PD rats, MenSCs improved animal motor function, which was indicated by the increased movement distance, ambulatory episodes, exercise time on the rotarod, and less contralateral rotation. Additionally, MenSCs reduced the loss of dopaminergic neurons and down-regulated the level of pro-inflammatory factors in the CSF and serum. Moreover, q-PCR and WB results showed the transplantation of MenSCs significantly down-regulated the expression of M1 phenotype cell markers and meanwhile up-regulated the expression of M2 phenotype cell markers in the brain of PD rats. 176 biological processes including inflammatory response, negative regulation of apoptotic process, and microglial cell activation were enriched by GO-BP analysis. 58 signal pathways including PI3K/Akt and MAPK were enriched by KEGG analysis. Conclusions In conclusion, our results provide preliminary evidence for the anti-inflammation capacity of MenSCs by regulating M1/M2 polarization. We firstly demonstrated the biological process of factors secreted by MenSCs and the signal pathways involved in using protein array and bioinformatic analysis.

Increasing evidence reveals that delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) results from the combined effects of environmental and genetic factors. The main pathological feature of DEACMP was generalized demyelination of cerebral white matter. Myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) and serum samples from DEACMP patients were elevated. This study investigated the association of MBP single nucleotide polymorphisms(SNPs) (rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336) with DEACMP. We genotyped 416 DEACMP patients and 785 age, educational level, and sex-matched ACMP patients for rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336 SNPs using the Agena MassArray. There were no significant differences in the allele frequency distribution, four genetic models, and genotype distributions between the DEACMP and ACMP groups for rs470555, rs470724, rs4890785, and rs595997. However, significant differences were observed for rs76452994 and rs921336. This study revealed that the MBP polymorphisms, rs470555, rs470724, rs4890785, and rs595997, were not associated with DEACMP. Based on the codominant, dominant, and overdominant genetic inheritability patterns, the MBP rs76452994 and rs921366 polymorphisms were associated with DEACMP. Furthermore, the G allele of rs76452994 and T allele of rs921336 could lead to higher DEACMP risk.

The main pathological changes that occur in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are extensive demyelination of brain white matter and neuron damage. Previous studies suggested that demyelination and neuron injury are related to activating the Rho/ROCK signaling pathway. Inhibition of the Rho/ROCK signaling pathway can alleviate neuron injury and promote myelin repair. This study utilized a DEACMP model in which rats were prepared by space injection of CO gas intraperitoneally (CO group), and the association between the Rho/ROCK signaling pathway and DEACMP was investigated. The ROCK2 kinase inhibitor Y-27632 was used to prevent the effects of the DEACMP model to elucidate its protective mechanism. The results demonstrated that the cognitive and motor functions were significantly impaired, and the GFAP, NSE, RhoA, and ROCK2 protein levels were significantly increased in the CO group within three weeks after the model was established. After Y-27632 intervention, the cognitive and motor functions of the CO+Y-27632 group were significantly improved within three weeks after the model was established. In the CO+Y-27632 group, the RhoA, ROCK2, GFAP, and NSE (indicating neuron injury) protein levels decreased significantly, and the MBP protein levels (indicating myelin repair) increased significantly within three weeks after the model was established. These results suggested that the pathogenesis of DEACMP was associated with activation of the Rho/ROCK pathway and that Y-27632 inhibited ROCK2 kinase activity in the CO exposed rats, resulting in improved behavioral deficits, reduced neuron damage, and promotion of myelin repair. Therefore, Y-27632 might be a potentially effective drug for the treatment of DEACMP-induced brain damage.

Background: The hyperactivation of microglia is closely related to the development of Parkinson's disease (PD). Because of the extensive sources, non-invasive and periodical collection method, human menstrual blood-derived endometrium stem cells (MenSCs) have been explored as a promising tool for treatment of PD. This study aimed to investigate if MenSCs could inhibit neuroinflammation in PD rats by regulating M1/M2 polarization and to excavate the underlying mechanisms. Methods: MenSCs was co-cultured with 6-OHDA-exposed microglia cell lines. Then the morphology of microglia cells and the level of inflammatory factors were assessed by immunofluorescence and qRT-PCR. After MenSCs was transplanted into the brain of PD rats, animal motor function, the expression of tyrosine hydroxylase (TH), and the level of inflammatory factors in the cerebrospinal fluid (CSF) and serum were detected to evaluate the therapeutic potential of MenSCs. Meanwhile, the expression of M1/M2 phenotype related genes was detected by qRT-PCR. One protein array kit containing 1000 kinds of factors was used to detect the protein components in

Objective. The purpose of this study was to analyze the relationship between cadherin gene single-nucleotide polymorphisms (SNPs) and the risk of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Materials and Methods. A total of 416 patients with DEACMP and 754 patients with acute carbon monoxide poisoning (ACMP) were recruited. We used the Sequenom MassARRAY® system to detect cadherin gene SNPs related to DEACMP. Using different genetic analysis models, we evaluated the relationship between the cadherin gene polymorphisms and risk of DEACMP. Results. We found that rs1944294 in the N-cadherin (CDH2) gene showed significant differences in genotype frequencies between the two groups under codominant and dominant inheritance models. Similarly, rs2513796 in the cadherin-17 (CDH17) gene showed significant differences under the codominant, dominant, and overdominant genetic models. And the T allele frequency of rs1944294 in the DEACMP group was significantly higher than that in the ACMP group (P=0.023). Conclusions. Cadherin gene SNPs (rs1944294, rs2513796) are associated with an increased risk of DEACMP in the Chinese population.

Stem cell-based regenerative therapies have recently become promising and advanced for treating stroke. Mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) have received the most attention for treating stroke because of the outstanding paracrine function of MSCs and the three-germ-layer differentiation ability of iPSCs. However, the unsatisfactory homing ability, differentiation, integration, and survival time in vivo limit the effectiveness of MSCs in regenerative medicine. The inherent tumorigenic property of iPSCs renders complete differentiation necessary before transplantation, which is complicated and expensive and affects the consistency among cell batches. Multilineage differentiating stress-enduring (Muse) cells are natural pluripotent stem cells in the connective tissues of nearly every organ and thus are considered nontumorigenic. A single Muse cell can differentiate into all three-germ-layer, preferentially migrate to damaged sites after transplantation, survive in hostile environments, and spontaneously differentiate into tissue-compatible cells, all of which can compensate for the shortcomings of MSCs and iPSCs. This review summarizes the recent progress in understanding the biological properties of Muse cells and highlights the differences between Muse cells and other types of stem cells. Finally, we summarized the current research progress on the application of Muse cells on stroke and challenges from bench to bedside.

By using a mixed-ligand approach, a new Co(II)-bearing coordination polymer (CP) with the chemical formula of [{Co(BINDI)0.5(bpa)0.5(H2O)}·4H2O]n (1, H4BINDI = N,N′-bis(5-isophthalic acid)naphthalenediimide, bpa = 1,2-bis(4-pyridyl)ethane) has been synthesized by room temperature self-assembly and structurally characterized successfully. Furthermore, a process of sonochemistry with oleic acid treatment at 453 K was used to produce the nanostructure 1 (denoted as nano 1 hereafter). The inhibitory effect of nano 1 on cervical cancer cells was determined. Firstly, the CCK-8 assay was performed. The Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay was performed and the relative expression levels of miR-16-1 were determined. Then, the western blotting detection was conducted and the Bcl-2 expression level after nano 1 treatment was evaluated.

目的 探讨肌球蛋白ⅦA基因2个单核苷酸多态性(SNP)位点(rs1052030,rs4945149)的多态性与老年急性一氧化碳中毒(ACMP)后迟发性脑病(DEACMP)的潜在关联.方法 选择2006年11月～2017年12月河南省豫北地区汉族老年ACMP昏迷后抢救成功且已完成90 d以上随访人群.共收集DEACMP患者外周血标本196例,ACMP患者外周血标本347例.其中包含rs1052030位点,DEACMP患者194例(DEACMP1组);ACMP患者344例(ACMP1 组).其中包含 rs4945149位点,DEACMP 患者 192例(DEACMP2组);ACMP 患者340例(ACMP2组).肌球蛋白ⅦA基因多态性采用Sequenom分型技术检测,并分析其与DEACMP遗传易感性.DEACMP患者病情最严重期间应用常识-记忆力-注意力测验量表(IMCT)及日常生活活动能力量表(ADL)评分.结果 DEACMP1组与ACMP1组基因型及等位基因频率比较,差异无统计学意义(P＞0.05).DEACMP2组与ACMP2组基因型及等位基因频率比较,差异无统计学意义(P＞0.05).DEACMP1组CC、TC、TT基因型患者ADL和IMCT评分比较,差异无统计学意义(P＞0.05).DEACMP2组CC、TC、TT基因型患者IMCT和ADL评分比较,差异有统计学意义[(3.12±0.90)分vs(2.37±1.32)分vs(1.71±0.97)分,P=0.000;(55.45±4.86)分 vs(60.48±2.66)分vs(64.81±1.99)分,P=0.001].结论 肌球蛋白 Ⅶ A 基因2个 SNP 位点(rs1052030,rs4945149)与DEACMP发病无遗传关联性.

Xuejing Yue Lixia Liu Haiqing Yan Yongkun Gui Jun Zhao Ping Zhang 1School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, People’s Republic of China Background: IL-12 inhibition of the endothelial cell functions and angiogenesis is mediated by the cross-talk between the lymphocyte and the endothelial cells, which plays a key role in inhibiting the process of angiogenesis in the eyeballs and in malignant tumors. Methods: We established the intracerebral hemorrhage (ICH) rat model, and IL-12 receptor beta monoclonal antibody was injected into the ICH rats. Western blot, immunofluorescence and RT-qPCR were used to detect the gene expression. Brain water content, EB staining, Garcia test, Beam walking test and wire hanging test were used to assess the injury of brain in ICH rats. Results: IL-12 gene was significantly increase in hematoma border tissue of ICH rats, and IL-12 protein mainly localized in monocytes. Anti-IL-12 treatment with IL-12 monoclonal antibodies could not only significantly decrease the brain water content and EB content in brain tissues of ICH rats, but also significantly increase the score of the Garcia, Beam balance and the Wire hanging test in ICH rats. Moreover, anti-IL-12 treatment significantly decrease the expression of pro-inflammatory gene, inflammatory gene, p-JAK2/JAK2 and p-STAT4/STAT4 protein, but significantly increase the expression anti-inflammatory gene and CD31 protein, and M2 macrophage ratio in hematoma border tissues of ICH rats. In vitro, rmIL-12 inhibited the tube formation of brain microvascular endothelial cells (BMVES) in BMVES and bone marrow-derived monocytes (BMDM) co-culture systems, but not work in a separately cultured BMVES system. In addition, Fedratinib not only reduced p-JAK2/JAK2 and p-STAT4/STAT4 protein expression in BMDM after treating with b-FGF and rmIL-12, but also significantly increased the tube formation of BMVES in BMVES and BMDM co-culture systems after treating with b-FGF and rmIL-12. Conclusion: Blockade of IL-12 receptor attenuated brain injury after ICH in rat by promoting angiogenesis, and the mechanism might be related to blocking IL-12 could inhibit M2 cell activation via the JAK2/STAT4 pathway.

目的 探讨托吡酯与卡马西平单药治疗癫痫部分性发作的疗效和安全性.方法 计算机检索PubMed、Cochrane、Embase、中国知网、万方数据库和中国生物医学文献数据库中,建库—2019年01月31日关于托吡酯与卡马西平单药治疗癫痫部分性发作患者的临床对照试验文章.对其进行文献筛选,数据提取,文献质量及风险偏倚评估,并交叉核对,使用Meta分析专用软件Revman 5.3进行数据分析.结果 初检文献459篇,最终纳入文献12篇,共2348例患者,其中托吡酯组1075例,卡马西平组1273例.其中高质量文献3篇,低质量文献9篇.Meta分析结果显示:托吡酯组完全控制540例,占52.38％(540/1031);卡马西平组完全控制546例,占45.73％(546/1194),两组差异有统计学意义[OR=1.53,95％CI(1.05,2.24),P<0.05].托吡酯组有效204例,占37.02％(204/551);卡马西平组有效326例,占47.52％(326/686),两组差异无统计学意义[OR=0.91,95％CI(0.70,1.19),P>0.05].托吡酯组出现不良反应372例,占39.45％(372/943);卡马西平组出现不良反应466例,占44.72％(466/1042),两组差异有统计学意义[OR=0.75,95％CI(0.56,1.00),P<0.05].结论 托吡酯单药治疗癫痫部分性发作的疗效及安全性优于卡马西平.