INTRODUCTION:Ischemic Stroke (IS) shows high rates of mortality and disability, with a rising incidence. Persicae Semen (TaoRen), a traditional Chinese medicine, is known to promote blood circulation and resolve stasis. This study aimed to screen its active components and identify their anti-IS targets. METHODS:Transcriptome and single-cell data of IS were obtained from the GEO database. TaoRen's active components and targets were predicted using TCMSP and SwissTargetPrediction. Differentially Expressed Genes (DEGs) were screened using the limma package. The predicted target genes of TaoRen were intersected with these IS-related DEGs to identify the candidate key therapeutic targets. Subsequently, a regulatory network was constructed and visualized using Cytoscape. Functional enrichment analysis was performed using GSEA to explore the biological pathways involved. Molecular docking was performed using AutoDockTools to validate the binding affinity between the active components and the core targets. Finally, single-cell transcriptomic data were analyzed using the Seurat package. RT-qPCR, CCK-8, flow cytometry, and commercial kits were used to identify the protective effect of Hederagenin (HE) against OGD/R damage on PC12 cells. RESULTS:Four active ingredients (α1-sitosterol, Hederagenin (HE),β-sitosterol, campesterol) of TaoRen were identified. FABP4, which was highly expressed in IS samples, was identified as a key target involved in ROS and mitochondrial pathways. Molecular docking confirmed strong binding between FABP4 and HE. Single-cell analysis showed that FABP4 is predominantly expressed in vascular smooth muscle and brain endothelial cells. HE treatment downregulated FABP4 expression, protected PC12 viability, and suppressed apoptosis and oxidative stress. DISCUSSION:This study identified HE,β-sitosterol, and campesterol as key components of TaoRen that target FABP4, demonstrating neuroprotection against IS through oxidative stress and mitochondrial pathways. However, limitations such as insufficient validation and potential challenges to cross-species translatability should be addressed. CONCLUSION:This study identified four bioactive compounds from TaoRen and verified FABP4 as a potential target for IS, contributing to the development of TaoRen-derived therapeutic agents for IS treatment.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system with a growing global burden. While traditionally considered rare in Asia, China rising MS prevalence and disproportionate disability present major public health challenges. Comprehensive cross-regional comparisons between China, the group of 20 (G20), and global aggregates remain limited. Using data from the global burden of disease 2021 study, we quantified MS incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in China, G20 countries, and worldwide from 1990 to 2021. Temporal trends were analyzed with joinpoint regression, drivers of burden were decomposed into epidemiological change, population aging, and population growth, and future trajectories were forecast to 2050 using autoregressive integrated moving average (ARIMA) models. To evaluate healthcare system performance, we further constructed a Quality of Care Index (QCI) based on composite ratios of incidence, prevalence, mortality, and DALYs. From 1990 to 2021, MS prevalence and DALYs increased substantially in all regions, with China exhibiting faster growth in DALYs than G20 or global averages, particularly among women and working-age adults. In contrast, the G20 showed a more pronounced aging of MS burden. Decomposition analysis revealed that population aging and epidemiological change were the primary drivers of China rising burden. Forecasting predicts continued growth of cases and DALYs through 2050. QCI analysis demonstrated global improvement in MS care quality, with China achieving marked progress, especially among elderly groups; however, persistent disparities remain, with lower QCI values in children, older adults, and women, showing a consistent "middle-high, both-ends-low" pattern across regions. The MS burden in China has expanded more rapidly than in the G20 or globally, with disproportionate impacts on women and working-age populations. Although care quality has improved, inequities by age and sex persist. These findings highlight the urgent need for earlier diagnosis, equitable access to disease-modifying treatments, and targeted interventions for vulnerable groups to mitigate the future burden of MS.

BackgroundPost-stroke depression (PSD) is a common neuropsychiatric complication affecting 30–50% of stroke survivors, impairing rehabilitation, quality of life, and prognosis.Main bodyThis narrative review synthesizes recent evidence on PSD pathogenesis (neurotransmitter dysregulation, neuroinflammation, impaired neuroplasticity; psychosocial factors such as stress and social support deficits; gene–environment interactions including 5-HTT and BDNF polymorphisms), clinical interventions (pharmacotherapy with SSRIs/SNRIs, psychotherapy including CBT, neuromodulation via rTMS/tDCS/ECT, novel agents such as ketamine, and multidisciplinary models), and prevention (risk stratification, early screening with PHQ-9/HAMD, personalized biological/psychosocial strategies, and digital monitoring).ConclusionDespite gaps in long-term data and validated biomarkers, multidisciplinary integrated care and precision medicine approaches offer promising avenues to optimize screening, early intervention, prevention, and long-term outcomes for stroke survivors.

Objective. The complex interplay between inflammatory cytokines and sepsis is not well understood. This study employs Mendelian Randomization (MR) to investigate the causal relationships between various inflammatory cytokines and sepsis, aiming to elucidate the underlying mechanisms and potential therapeutic targets. Methods. This study employed a bidirectional MR approach to investigate the causal effects of inflammatory cytokines on sepsis and vice versa. Genetic variants from genome-wide association studies (GWAS) were used as instrumental variables (IVs). Key MR methods included Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median. SNPs were filtered using a p-value threshold of <5e-08, with linkage disequilibrium exclusions (r2<0.001). We analyzed 41 inflammatory cytokines, utilizing leave-one-out analysis and MR-PRESSO to address pleiotropy. Results. The MR analysis revealed significant causal relationships between specific cytokines and sepsis. CTACK (OR=1.102, P=0.031), MIF (OR=1.071, P=0.036), and TRAIL (OR=1.053, P=0.036) were identified as risk factors, while MIP1-(3 (OR=0.933, P=0.039) and TGF-alpha (OR=0.957, P=0.029) emerged as protective factors. Additionally, sepsis increased the risk for IL-2 (OR=1.455, P<0.01), IL-6 (OR=1.151, P= 0.012), and MCSF (OR=1.272, P=0.028), while showing a protective effect on NGF-(3 (OR=0.78, P=0.012) and SCF (OR=0.86, P=0.02). Conclusion. This study reveals novel causal relationships between specific inflammatory cytokines and sepsis, suggesting that CTACK, MIF, and TRAIL are risk factors, while MIP1-(3 and TGF-alpha are protective. Additionally, sepsis influences various cytokines, indicating complex bi-directional interactions. These find-ings provide valuable insights for developing targeted therapeutic strategies to manage sepsis and inflam-matory responses.

Radiotherapy, as a key component of the comprehensive treatment system for malignant tumors, not only facilitates precise tumor destruction but also necessitates the strategic use of radioprotective agents to regulate immune responses and mitigate toxicity in normal tissues. Revealing the molecular biological mechanisms of ionizing radiation damage, such as DNA double-strand breaks, oxidative stress responses, and abnormal cell cycle regulation is critical for the development of clinically effective radioprotective drugs. Such advancements hold dual significance in enhancing patient outcomes and improving clinical efficacy. This paper explores the classification of radioprotective agents, and their diverse mechanisms of action, including free radical scavenging, regulation of redox enzyme systems, suppression of ionizing radiation-induced inflammation, and apoptosis-related immune damage. And, it also examines the challenges and prospects of their clinical translation. This study aims to provide important theoretical framework for the development of radioprotective agents to contribute to future advancements in radiation therapy.

Background: Dementia is caused by cognitive decline that interferes with daily living. It is often considered a syndrome rather than a single disease. The causes of dementia are diverse, including brain degeneration and cerebrovascular disease, but the pathogenic mechanisms remain unclear. Alzheimer's disease (AD) and vascular dementia (VaD) are the most common forms of dementia. As dementia cases continue to rise worldwide, investigating dementia has become increasingly important. Early-stage AD and VaD may cause amnestic mild cognitive impairment (MCI). Therefore, elucidating the relationship among AD, VaD, and MCI is crucial. This study aimed to analyze the correlations among AD, VaD, and MCI, and differences in these three diseases using bioinformatics methods on gene expression omnibus (GEO) databases, to provide information. Methods: Gene set enrichment (GSE) 18309 and GSE122063 were utilized to identify differentially expressed mRNAs among AD, VaD, and MCI. The gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these mRNAs. Results: The main functions of the identified mRNAs were revealed, with phosphatidylinositide 3 kinases-protein kinase B (PI3KAkt) signaling and hypoxia-inducible factor-1 (HIF-1) signaling showing the highest frequency. Conclusion: Bioinformatics analyses of public databases provide insights into the relationship and differences among AD, VaD, and MCI based on differential mRNA expression and pathway enrichment, laying the foundation for future mechanistic studies. The identified pathways such as PI3K-Akt and HIF-1 signaling represent promising targets for further investigation and therapeutic development.

Objectives: Ischemic stroke (IS) is a leading cause of morbidity and mortality globally. This study aimed to investigate the role of exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) treated with Musk Ketone (Mus treated-Exo) in the development of IS injury. Methods: BMSCs were pretreated with 10 mu M Mus for 36 h, and Exo derived from these Mus-treated BMSCs (Mustreated Exo) were extracted. Rats with middle cerebral artery occlusion (MCAO) were administered either 2 mg/ kg of control Exo (Ctrl-Exo), 2 mg/kg of Mus treated-Exo, or 10 mu M Mus. Neurological deficit and cerebral infarction in the MCAO rats were assessed utilizing neurological scores and TTC staining. Neuronal apoptosis, activation of microglia/macrophages, and inflammation were evaluated through TUNEL staining, immunofluorescence staining, and western blot analysis, respectively. Results: Our findings revealed that Mus-treated Exo possessed a more pronounced neuroprotective effect on MCAO rats when compared to Ctrl-Exo and Mus treatment alone. Specifically, Mus treated-Exo effectively ameliorated neurological function, reduced the volume of cerebral infarction, and diminished hemispheric swelling in MCAO rats. Moreover, it inhibited neuronal apoptosis and activation of microglia/macrophages, promoted the expression of the anti-apoptotic protein Bcl-2 while decreasing the expression of pro-apoptotic protein Bax, Cleaved-caspase 3, and pro-inflammatory factors IL -6 and COX-2. Conclusions: The findings imply that Mus treated-Exo could confer neuroprotection in rats affected by IS, potentially by attenuating apoptosis and neuroinflammation. The underlying mechanisms, however, warrant further investigation. Mus treated-Exo shows potential as a new therapeutic strategy for IS.

铁死亡是一种铁依赖的、多不饱和脂质过氧化导致的细胞膜结构损伤的调控性细胞死亡方式,与缺血性脑卒中密切相关,可作为缺血性脑卒中治疗的潜在靶点.多种中药活性成分可减轻缺血性脑卒中病人的铁死亡.综述中药治疗缺血性脑卒中铁死亡作用机制的研究进展,以期为中药治疗缺血性脑卒中铁死亡提供依据.

Traditional Chinese medicine has emerged as promising targets for ischemic stroke (IS) therapy, yet the mech-anism remains elusive. The current study was performed with an aim to investigate the action and mechanism of Tongqiao Huoxue decoction (TQHXD) affecting the neurological impairment secondary to IS based on network pharmacology. Based on network pharmacology and bioinformatics analysis, target genes and pathways involved in the treatment of TQHXD against IS were predicted. Serum containing TQHXD was prepared through blood collection from C57BL/6 mice after intragastric administration of TQHXD. The main results exhibited that Prostaglandin-endoperoxide synthase 2 (PTGS2) exhibited an abundance in IS and enrichment in the NF-kappa B signaling pathway, holding the potential as targets related to TQHXD treatment for IS. TQHXD was found to rescue cell viability, inhibit apoptosis, and alleviate inflammation under oxygen and glucose deprivation and reoxygenation (OGD/R) exposure. Furthermore, our in vivo experiment validated the protective function of TQHXD in ischemic brain damage stimulated by middle cerebral artery occlusion (MCAO). This protective action of TQHXD could be attenuated by overexpressing nuclear factor (NF)-kappa B, which was dependent on PTGS2. Collectively, TQHXD was demonstrated to ameliorate IS-induced neurological impairment by blocking the NF-kappa B signaling pathway and down-regulating PTGS2.

多发性硬化(MS)是常见的神经内科疾病,具有高复发率和高致残率,是仅次于创伤性疾病的中青年致残主要原因.近年来,中医药对MS的相关研究逐渐成为热点.中医学"治未病"理论是中医预防医学的精髓和概括性总结."治未病"理念一方面体现在疾病预防层面,另一方面体现在病中的积极治疗和病后康复层面.在神经系统自身免疫性疾病如MS的防治过程中,"治未病"理念体现的尤为丰富和深刻.通过讨论"治未病"思想在MS不同阶段的防治目标及防治策略,以期为中医药防治MS提供思路和理论支持,促进MS防治水平的提高.

The activation of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers pyroptosis proinflammatory cell death in experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanisms of the inflammatory processes of microglia in EAE remain unclear. Our previous studies suggested that interleukin-1 receptor-associated kinase (IRAK)-M down-regulates the toll-like receptor 4/interleukin-1 receptor signaling pathway. Here, we used IRAK-M knockout (IRAK-M-/-) mice and their microglia to dissect the role of IRAK-M in EAE. We found that deletion of IRAK-M increased the incidence rate and exacerbated the clinical symptoms in EAE mice. We then found that IRAK-M deficiency promoted the activation of microglia, activated NLRP3 inflammasomes, and enhanced GSDMD-mediated pyroptosis in the microglia of EAE. In contrast, over-expression of IRAK-M exerted inhibitory effects on neuroinflammation, NLRP3 activation, and pyroptosis. Moreover, IRAK-M deficiency enhanced the phosphorylation of IRAK1, while IRAK-M over-expression downregulated the level of phosphorylated IRAK1. Finally, we found upregulated binding of IRAK1 and TNF receptor-associated factor 6 (TRAF6) in IRAK-M-/- EAE mice compared to WT mice, which was blocked in AAVIRAK-M EAE mice. Our study reveals a complex signaling network of IRAK-M, which negatively regulates microglial NLRP3 inflammasomes and pyroptosis by inhibiting IRAK1 phosphorylation during EAE. These findings suggest a potential target for the novel therapeutic approaches of multiple sclerosis (MS)/EAE and NLRP3-related inflammatory diseases.

帕金森病(PD)是世界上第二大最常见的顽固性神经退行性疾病,给老龄人口带来沉重的身体和经济负担.其病理特征表现为黑质多巴胺能神经元变性死亡和脑干神经元内α-突触核蛋白(α-Syn)积聚形成路易体.目前,大多数的治疗主要侧重于减轻运动障碍,包括运动迟缓、肌肉僵硬、震颤等.但随着疾病进展,治疗效果变得愈发有限.PD早期发生神经炎症,导致多巴胺能神经元损伤.其中,NLRP3 炎症小体在小胶质细胞中表达,在PD的进展中起关键作用.基于此,本文对PD与神经炎症的关系进行综述,旨在进一步揭示PD的发病机制,为PD的治疗新药开发提供理论依据.

缺血性脑卒中作为急性脑血管的一类疾病，是由于血栓将脑动脉血管阻塞或脑血管管腔本身变窄、脑动脉出现粥样硬化改变从而引起大脑供血不足。缺血性脑卒中严重威胁人类生命安全以及使生活质量呈直线下降。由此看来，早期进行溶栓治疗，对挽救缺血性脑卒中患者的生命及脑功能具有至关重要的作用。但溶栓的常见并发症就是溶栓出血，本文就溶栓治疗现状及溶栓出血机制的可能作用做一综述，以期为缺血性脑卒中的诊治方面提供参考。

Background Traditional Chinese medicine (TCM) has become a crucial direction for ischemic stroke treatment. This study sought to explore the underlying roles of YaoYi-moxibustion (YY-moxi) in ischemic stroke. Methods A total of 75 Sprague-Dawley rats were randomly divided into the following 5 groups: (I) the sham-operated group; (II) the middle cerebral artery occlusion model (MCAO) group; (III) the YY-moxi group; (IV) the antioxidant (N-acetylcysteine, NAC) group; and (V) the NAC + YY-moxi group. After the model had been established, the NAC group received intracerebroventricular injections of NAC, the YY-moxi group received YY-moxi, and the NAC + YY-moxi group received a combination of these 2 interventions. The neurological deficit score was confirmed, and the cerebral infarction was examined by triphenyl tetrazolium chloride (TTC) staining. In the ischemia site of stroke, terminal deoxynucleotidyl transferase-mediated Dutp nick end labeling staining was applied to examine the apoptotic cells. Additionally, the apoptosis-associated genes and protein expressions in the ischemic brains were investigated by the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry, and western blot analysis. Results YY-moxi alone and YY-moxi combined with NAC significantly reduced the neurological scores and cerebral infarction area of the MCAO rats. Additionally, YY-moxi alone and the combined application of YY-moxi and NAC improved the pathological status of ischemic brain tissues. Further, we found that YY-moxi alone and YY-moxi in combination with NAC could enhanced the antioxidation ability and reduced the inflammatory response of the MCAO model rats. We also proved that YY-moxi alone and YY-moxi combined with NAC significantly suppressed apoptosis-related proteins in the MCAO model rats. Conclusions These findings indicate that YY-moxi exerts a protective effect on cerebral ischemic injury by reducing apoptosis. The study suggests that the mechanism may be related to its downregulating the expression of nuclear factor kappa B (NK-κB).

血管性痴呆是一种常见的痴呆类型,与脑血管疾病密切相关,主要表现为认知功能下降.神经炎症对血管性痴呆有重要影响.肠道菌群可通过调控神经递质和肠道代谢产物调节血管性痴呆的神经炎症;肠道菌群组成异常也会增加肠道屏障的通透性,激活机体免疫系统引发全身炎症反应,进而破坏血脑屏障,加重神经炎症,导致神经细胞凋亡,发生神经退行性病变.益生菌可减轻肠道菌群失衡引起的神经细胞损伤,调节肠道菌群有望成为防治血管性痴呆的一种新方法.

epatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide. Currently, the prevention and treatment of HCC remains a major challenge. As a traditional Chinese medicine (TCM) formula, Ruangan Lidan decoction (RGLD) has been proved to own the effect of relieving HCC symptoms. However, due to its biological effects and complex compositions, its underlying mechanism of actions (MOAs) have not been fully clarified yet. In this study, we proposed a pharmacological framework to systematically explore the MOAs of RGLD against HCC. We firstly integrated the active ingredients and potential targets of RGLD. We next highlighted 25 key targets that played vital roles in both RGLD and HCC disease via a protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, an ingredient-target network of RGLD consisting of 216 ingredients with 306 targets was constructed, and multilevel systems pharmacology analyses indicated that RGLD could act on multiple biological processes related to the pathogenesis of HCC, such as cellular response to hypoxia and cell proliferation. Additionally, integrated pathway analysis of RGLD uncovered that RGLD might treat HCC through regulating various pathways, including MAPK signaling pathway, PI3K/Akt signaling pathway, TNF signaling pathway, and ERBB signaling pathway. Survival analysis results showed that HCC patients with low expression of VEGFA, HIF1A, CASP8, and TOP2A were related with a higher survival rate than those with high expression, indicating the potential clinical significance for HCC. Finally, molecular docking results of core ingredients and targets further proved the feasibility of RGLD in the treatment of HCC. Overall, this study indicates that RGLD may treat HCC through multiple mechanisms, which also provides a potential paradigm to investigate the MOAs of TCM prescription.

多发性硬化(MS)是一种由免疫系统故障引起的神经系统疾病,导致针对脑白质组织抗原的自身免疫反应.高迁移率族蛋白B1(HMGB1)近年来在炎症反应及自身免疫性疾病中的作用得到广泛关注,但是HMGB1对MS的作用机制的报道相对较少.有研究表明,HMGB1可能成为治疗MS的新靶点.现就HMGB1的结构、来源及信号传导通路,HMGB1在MS中的作用及相关机制的研究进展做一综述,以期为MS的诊疗提供新的靶点,为进一步临床和实验研究提供基础.

脑-肾-督脉轴理论把脑、肾、督脉看作一个大的整体，以脊柱与督脉为桥梁使肾脑相济。本文将脑-肾-督脉轴理论以及临床应用进行总结，有利于对古老中医学的继承和创新，以及推动中医临床应用。

脑卒中是由于脑血管痉挛缺血引起的脑功能障碍,其发生与脑血管舒缩功能失调、受损的内皮细胞增殖重构,进而导致脑部再灌注损伤有关.血清内皮素1是血管活性收缩因子,降钙素基因相关肽(CGRP)是血管活性舒张因子,两者共同作用于血管内皮细胞.内皮素1与CGRP释放平衡失调是导致脑卒中的重要原因.本文就内皮素1与CGRP在脑卒中发病机制中的作用研究进展做一综述.

目的 观察熄风祛瘀方在急性缺血性脑卒中治疗中的应用价值及对神经功能恢复的促进作用研究.方法 选取2019年11月-2021年2月医院收治的急性缺血性脑卒中患者116例为研究对象,依据随机对照法将患者分为研究组和参照组,每组58例.参照组患者采用降糖、降压、脑组织保护和脱水治疗,研究组在参照组治疗的基础上,口服熄风祛瘀方辅助治疗.两组均按疗程治疗14 d.比较两组治疗前后中医证候积分和治疗疗效,比较两组治疗前后神志昏蒙、半身不遂、口舌歪斜、言语謇涩、舌黯红和脉细弦中医证候积分变化,比较两组治疗前后mRS积分、NIHSS评分、MoCA评分、血清BNDF和IMA含量、GQOL-74评分.结果 研究组治疗总有效率高于参照组(P＜0.05);研究组治疗后神志昏蒙、半身不遂、口舌歪斜、言语謇涩、舌黯红和脉细弦中医证候积分低于参照组(P＜0.05);研究组治疗后mRS积分、NIHSS评分低于参照组,MoCA评分高于参照组(P＜0.05);研究组治疗后血清BNDF含量高于参照组,IMA含量低于参照组(P＜0.05);研究组治疗后GQOL-74评分高于参照组(P＜0.05).结论 熄风祛瘀方治疗急性缺血性脑卒中疗效肯定,可改善疾病的相关症状,促进受损脑组织的修复,改善神经功能恢复,提高认知能力和生活质量,提高整体治疗效果,值得临床进一步研究探讨.