Ischemic stroke (IS) remains a leading cause of global mortality and neurological disability, with neuronal mitochondrial dysfunction as a central pathological mechanism. Astrocytes, the metabolic custodians of the central nervous system, exert neuroprotection by transferring functional mitochondria to compromised neurons via tunneling nanotubes (TNTs), extracellular vesicles (EVs), connexin 43 (Cx43) mediated gap junctions, and membrane fusion. These transfers replenish neuronal energy reserves, mitigate oxidative stress, and enhance synaptic plasticity. This review systematically delineates the molecular mechanisms of astrocyte-mediated mitochondrial transfer, its regulatory roles in oxidative stress, calcium dyshomeostasis, and ferroptosis, and its therapeutic potential in IS. Experimental models demonstrate that pharmacological enhancement of mitochondrial transfer or exogenous transplantation significantly reduces infarct volume and improves neuronal survival. However, clinical translation faces challenges including low mitochondrial viability, immune rejection, and inefficient delivery. Future research should integrate gene-editing tools, nanocarrier systems, and organoid models to optimize mitochondrial dynamics and develop precision therapies. By bridging mechanistic insights with translational innovations, astrocytic mitochondrial transfer emerges as a groundbreaking strategy for ischemic stroke treatment.

Vascular dementia (VaD), a primary cognitive disorder caused by cerebrovascular pathology, features significant white matter damage from chronic cerebral hypoperfusion strongly correlated with cognitive decline. Myelin integrity disruption represents a core pathological foundation in VaD, with dysfunctional oligodendrocytes (OLs) and microglia (MG) forming a critical pathogenic nexus. OLs govern myelin formation and maintenance while MGs modulate myelination through cerebral microenvironment regulation. In the central nervous system, precise communication and synergistic interaction between cells are the basis for maintaining homeostasis and cognitive function. The complement system, cytokine network, and extracellular vesicles together form its core communication axis. The complement system is at the forefront of the rapid innate immune response, cytokines dynamically regulate the initiation and resolution of inflammation, as carriers of functional molecules between cells, extracellular vesicles target and deliver information of bioactive molecules, upgrading intercellular communication to an active and programmed network regulation system. The three work together to maintain the homeostasis of the neural microenvironment. Their dysregulation can lead to uncontrolled neuroinflammation and tissue damage, which is the core pathological link in diseases such as VaD. This review examines the interplay between OLs and MG in VaD demyelination, detailing their complex communication networks via the complement system (including C1q, C3, C5 fragments), key cytokines (TNF-α, IL-1β, IL-4, IL-10), and extracellular vesicle signaling. Notably, these pathways exhibit bidirectionality: moderate activation promotes repair mechanisms, whereas excessive responses exacerbate injury. Future research should elucidate the spatiotemporal dynamics of OLs-MG interactions and identify precise therapeutic targets to restore cellular equilibrium, thereby informing novel VaD intervention strategies.

Ischemic stroke (IS) is caused by temporary or permanent obstruction of the brain's blood supply. The disruption in glucose and oxygen delivery that results from the drop in blood flow impairs energy metabolism. A significant pathological feature of IS impaired energy metabolism. Astrocytes, as the most prevalent glial cells in the brain, sit in between neurons and the microvasculature. By taking advantage of their special anatomical location, they play a crucial part in regulating cerebral blood flow (CBF) and metabolism. Astrocytes can withstand hypoxic and ischemic conditions better than neurons do. Additionally, astrocytes are essential for maintaining the metabolism and function of neurons. Therefore, the "neurocentric" perspective on neuroenergetics is gradually giving way to a more comprehensive perspective that takes into account metabolic interaction between astrocytes and neurons. Since neurons in the core region of the infarct are unable to undergo oxidative metabolism, the focus of attention in this review is on neurons in the peri-infarct region. We'll go over the metabolic crosstalk of astrocytes and neurons during the acute phase of IS using three different types of metabolites: lactate, fatty acids (FAs), and amino acids, as well as the mitochondria. After IS, astrocytes in the peri-infarct zone can produce lactate, ketone bodies (KBs), glutamine (Gln), and l-serine, shuttling these metabolites, along with mitochondria, to neurons. This process helps maintain the energy requirements of neurons, preserves their redox state, and regulates neurotransmitter receptor activity.

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke, which promotes neuronal death and inhibits nerve tissue regeneration. As the first immune cells to be activated after an ischemic stroke, microglia play an important immunomodulatory role in the progression of the condition. After an ischemic stroke, peripheral blood immune cells (mainly T cells) are recruited to the central nervous system by chemokines secreted by immune cells in the brain, where they interact with central nervous system cells (mainly microglia) to trigger a secondary neuroimmune response. This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke. We found that, during ischemic stroke, T cells and microglia demonstrate a more pronounced synergistic effect. Th1, Th17, and M1 microglia can co-secrete pro-inflammatory factors, such as interferon-γ, tumor necrosis factor-α, and interleukin-1β, to promote neuroinflammation and exacerbate brain injury. Th2, Treg, and M2 microglia jointly secrete anti-inflammatory factors, such as interleukin-4, interleukin-10, and transforming growth factor-β, to inhibit the progression of neuroinflammation, as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury. Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation, which in turn determines the prognosis of ischemic stroke patients. Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke. However, such studies have been relatively infrequent, and clinical experience is still insufficient. In summary, in ischemic stroke, T cell subsets and activated microglia act synergistically to regulate inflammatory progression, mainly by secreting inflammatory factors. In the future, a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells, along with the activation of M2-type microglia. These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

This study aims to provide new insights into PM2.5-induced lung diseases through a focus on the pulmonary epithelial barrier and epithelial-mesenchymal transition (EMT). Firstly, we analyzed the mechanisms by which PM2.5 damages the airway epithelial barrier, including inflammatory responses, immune imbalance, oxidative stress, apoptosis, and autophagy. Subsequently, we investigated the mechanisms by which PM2.5 induces EMT, which involve the synergistic effect of oxidative stress and inflammation, the activation of key signaling pathways, and the regulatory role of non-coding RNAs. Furthermore, we explored the interaction between the airway epithelial barrier and EMT, especially the induction of EMT by epithelial barrier damage and the impact of EMT on epithelial barrier repair. Regarding lung injury diseases, we focused on the roles of the epithelial barrier and EMT in the development of pulmonary fibrosis and lung cancer, providing evidence from in vitro and in vivo studies. Emphasizing the translational prospects from basic research to clinical applications, and we proposed new ideas for treating PM2.5-related lung diseases from four aspects-anti-inflammatory and antioxidant drugs, signaling pathway inhibitors, non-coding RNA-targeted therapies, and gene editing and cell therapies-by focusing on the two key links of the airway epithelial barrier and EMT.

BACKGROUND:Stroke, especially ischemic stroke (IS), represents a major global health challenge due to its high incidence, disability, mortality, recurrence, and economic impact. The limited therapeutic window for thrombolysis underscores the need for new treatments. The blood-brain barrier (BBB), which protects the brain, becomes compromised following ischemia-reperfusion injury, allowing peripheral immune cell infiltration and subsequent neuroinflammation. Huang-Lian-Jie-Du Decoction (HLJDT), a traditional formula with significant neuroprotective effects demonstrated in preliminary studies and literature reviews, has not yet been fully explored for its potential to inhibit peripheral immune cell infiltration through BBB protection. PURPOSE:This study aims to: (1) Evaluate the efficacy of HLJDT in treating MCAO. (2) Observe the regulatory effect of HLJDT on the infiltration of CD4+ T cells into the central nervous system. (3) Investigate the effect of HLJDT on the Wnt/β-Catenin Signaling Pathway. METHODS:A focal MCAO reperfusion model will be used to evaluate HLJDT's effects on neurological function (Zea Longa and Garcia scores), infarction volume (TTC staining), and pathological changes (HE and NISSL staining). Immune-inflammatory responses will be assessed using ELISA for cytokines, flow cytometry for T lymphocyte distribution, and immunofluorescence staining for CD4+ T cell infiltration. The interaction of T cell antigens (LFA-1) and endothelial adhesion molecules (ICAM-1) will be studied with ELISA and immunofluorescence. BBB protection will be evaluated with Evans blue staining and transmission electron microscopy. Mechanisms of T cell infiltration will be examined using transmission electron microscopy and Western blotting (WB) for key proteins. Additionally, the impact of HLJDT on the Wnt/β-catenin pathway will be assessed with WB. RESULTS:HLJDT significantly improves neurological scores, reduces infarction volume, and mitigates pathological damage. It balances CD4+ T cell responses by inhibiting pro-inflammatory cytokines and enhancing anti-inflammatory ones, reducing CD4+ T cell CNS infiltration. HLJDT inhibits LFA-1/ICAM-1 interactions. It can also inhibit CD4+ T cell infiltration by repairing paracellular and transcellular structures of the BBB, with the Wnt/β-catenin signaling pathway playing a key role in this process. CONCLUSION:We have innovatively demonstrated for the first time that HLJDT can regulate the balance between peripheral and central immune inflammation. It inhibits LFA-1/ICAM-1-mediated cell adhesion and, by modulating the Wnt/β-catenin pathway, improves the paracellular and transcellular structures of the blood-brain barrier, thereby suppressing CD4+ T cell infiltration and providing multifaceted protective effects for MCAO rats.

BACKGROUND:Ischemic stroke (IS) is the main cause of disability worldwide, and glial scar can impair neurological recovery during the post-stroke period. Refined qingkailing (RQKL) has been demonstrated to be neuroprotective after IS. PURPOSE:The purpose of our study was to investigate the effect of RQKL on glial scar after IS. METHODS:In this work, rats were used as the model subjects for middle cerebral artery occlusion (MCAO), with 7 and 14 days serving as the critical observational intervals. The treatments of oxygen and glucose deprivation/reoxygenation (OGD/R) were applied to primary astrocytes and an astrocyte-neuron co-culture model. RESULTS:RQKL was effective in improving neurological dysfunction, brain histopathologic manifestations, and reducing the degree of brain atrophy at different stages of glial scar. It also decreased the expression of glial fibrillary acidic protein (GFAP), neurocan, and brevican, and increased the expression of microtubule associated protein 2 (MAP2). In primary astrocyte culture, RQKL reduced the activation and proliferation of astrocytes. In an astrocyte and neuron co-culture model, RQKL decreased the expression of GFAP and brevican in astrocytes, and increased the expression of MAP2 and NF200 in neurons. Epidermal growth factor receptor (EGFR) and p-PLCγ expression was strongly increased following IS, according to both in vivo and in vitro tests, while RQKL decreased EGFR and p-PLCγ expression. CONCLUSION:When considered collectively, these findings imply that the EGFR/PLCγ signaling pathway is crucial for the activation of astrocytes and the formation of glial scars following IS. Also, RQKL affects neurons by blocking the EGFR/PLCγ signaling pathway on astrocytes, which diminishes the activation of astrocytes and the development of glial scars.

This study aimed to investigate the potential protective properties of a traditional Chinese medicine (TCM) herbal product, Siraitia grosvenorii granules (SGG) against PM2.5-induced lung injury, as well as their active constituents and underlying mechanisms. The chemical composition of SGG, such as wogonin (MOL000173), luteolin (MOL000006), nobiletin (MOL005828), naringenin (MOL004328), acacetin (MOL001689), were identified via ultra-high-performance liquid chromatography-Q Exactive (UHPLC-QE) Orbitrap/MS. The specific targets and pathways through which the compounds exert their effects on acute lung injury were then predicted via network pharmacology. The lung-protective effects of SGG against particulate matter (PM2.5) were investigated via in vivo experiments. Results showed that PM2.5-induced lung damage was associated with oxidative stress, suppression of PI3K/AKT/Nrf2 pathway, and increased levels of certain alarmins & cytokines in blood and bronchial alveolar lavage fluid (BALF). However, SGG reversed these changes, particularly tissue damage and oxidative stress, suggesting that lung protection is mediated by the antioxidant effect, which mitigates the release of alarmin and inflammation.

目的 总结东汉至今大黄及不同炮制品的临床用量规律,为大黄的临床应用提供依据.方法 选取东汉至今具有代表性的医学著作92部,采用Excel 2016软件录入数据,包括含有大黄的方剂、炮制方法、药量,建立历代大黄剂量数据库.将大黄根据不同的炮制方式分为净制、酒制、醋制、炒炭、生炭混用及无明确归类6类,统计历代大黄及不同炮制方式的使用频次,临床用量的最小值、最大值、常用剂量及常用范围.结果 东汉、唐代、宋代大黄常用剂量分别为55.2g、41.40g、41.30 g,常用范围为13.8～82.6 g;金元时期大黄常用剂量为38.10g,常用范围为3.81～38.10g;明代、清代大黄常用剂量分别为7.46g、3.73g;民国和现代大黄常用剂量为9.39 g、6.00g.净制大黄使用总频次高达971次,且用量范围在0.38～206.60 g;酒制大黄在明清时期盛行,频次为73次;现代达到高峰,频次为115次;醋制及炒炭大黄记录少,醋制大黄共2次,炒炭大黄共50次,常用量均在15g之内.结论 大黄在历代临床用量呈现出的主要特点是汉唐宋时期大黄常用剂量大、范围广,而在金元时期常用剂量小、范围较窄,且自明清开始,大黄的常用范围与现代接近;历代净制大黄频率高、用量大,酒制大黄的使用在明清兴盛,现代达到高峰,醋制及炒炭大黄使用少、用量低.

Since the proposal of the neurovascular unit (NVU) theory, it has become almost mandatory for neuroprotective medicines against ischaemic stroke (IS) to focus on this unit. Refined Qingkailing (RQKL) is a compound composed of hyodeoxycholic acid, geniposide, baicalin and cholic acid, which has shown great potential in the treatment of IS, but its effect on NVU has not been fully studied. The purpose of this study was to investigate the potential biological pathways that underlie the protective effects of RQKL against NVU damage induced by oxygen-glucose deprivation and re-oxygenation (OGD/R). Using in vitro OGD/R models, we looked into whether RQKL protects the NVU. In order to create an in vitro NVU that resembles IS, we created an OGD/R injury model using primary cultures of brain microvascular endothelial cells, neurons, and astrocytes. Based on our results, we present evidence, for the first time, that RQKL treatment of the injury caused by OGD/R significantly (1) kept the blood brain barrier (BBB) functioning and maintained the architecture of the neurons, (2) mitigated the oxidative stress damage, inflammatory cytokine release, and neuronal death, and (3) upregulated the expression of neurotrophic factors generated from glial cells and the brain in the in vitro model. Therefore, RQKL has a variety of preventive effects against NVU damage caused by OGD/R. RQKL may be a suitable medication for treating IS in a clinical setting.

Vascular and neurological damage are the typical outcomes of ischemic strokes. Vascular endothelial cells (VECs), a substantial component of the blood-brain barrier (BBB), are necessary for normal cerebrovascular physiology. During an ischemic stroke (IS), changes in the brain endothelium can lead to a BBB rupture, inflammation, and vasogenic brain edema, and VECs are essential for neurotrophic effects and angiogenesis. Non-coding RNAs (nc-RNAs) are endogenous molecules, and brain ischemia quickly changes the expression patterns of several non-coding RNA types, such as microRNA (miRNA/miR), long non-coding RNA (lncRNA), and circular RNA (circRNA). Furthermore, vascular endothelium-associated nc-RNAs are important mediators in the maintenance of healthy cerebrovascular function. In order to better understand how VECs are regulated epigenetically during an IS, in this review, we attempted to assemble the molecular functions of nc-RNAs that are linked with VECs during an IS.

目的 总结半夏自东汉至今的临床用量规律,并分析原因,为该药临床合理使用提供参考.方法 汇总前人从东汉至今对半夏临床用量的研究结果,归纳其最常用量及其范围,最大用量及最小用量,并与《中华人民共和国药典》(以下简称《药典》)规定用量作比较,从中总结规律并分析原因.结果 半夏的常用量及其范围呈汉唐用量大、范围宽,宋金元用量下降、范围骤缩,明清至今用量增、范围扩大的变化规律,剂型、炮制、煎服法是主要影响因素;半夏超大剂量与极小剂量应用在历代均属少数,大剂量与所治病证有关,小剂量与用药人群有关.结论 《药典》规定半夏用量(3～9 g)与古代医家的用药用量经验有一脉相承之处,常规情况应遵循.对于失眠、恶性肿瘤、痰浊重证可适当增加用量,大剂量用药过程中需注重防控相关不良反应.对于低龄、高龄、孕妇、阴虚血燥或肝肾功异常等特殊人群,需适当减少用量.

A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world’s population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood–brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.

补法是通过补益人体气血阴阳来治疗各种虚弱证候的一类治法.张仲景对补法的运用炉火纯青,在其著作《伤寒杂病论》中多次论及补法之运用,为后世医家运用补法治疗疾病提供了重要参考.仲景补法之运用可概括为清补与温补、峻补与缓补、通补与涩补、间补与正补,具有深刻的内涵和临床指导价值.

目的:应用数据挖掘技术对国家专利数据库中治疗胃食管反流病的中药配伍规律进行研究,为临床治疗、中药新药研发提供依据.方法:计算机检索中华人民共和国国家知识产权局网站建库至2020年8月1日治疗胃食管反流病的中药复方专利数据.采用中医传承辅助平台(V2.5)进行证候统计、四气五味归经统计、频次统计、关联规则、复杂网络、复杂系统熵聚类、无监督的熵层次聚类等分析.结果:最常见的主治证候为肝胃郁热证(45.16％),其次为肝胃不和证(37.63％);高频药物四气为温、寒;高频药物五味为苦、辛、甘;高频药物归经为胃、脾、肝、肺;高频单味药物有甘草(45.16％)、黄连(31.18％)、吴茱萸(26.88％)等;高频对药有“黄连-吴茱萸”(18.28％);高频角药有“黄连-柴胡-吴茱萸”(9.68％);通过关联规则发现的常用药物组合“黄连-柴胡→吴茱萸”(置信度0.90);通过复杂网络发现核心药物有吴茱萸、黄连、柴胡、甘草等;新处方有“白术、代赭石、茯苓、山药”“枳壳、吴茱萸、柴胡、茯苓、炙甘草”等.结论:对于胃食管反流病的临床治疗与新药开发过程中,可选择苦、辛、甘昧药物,着眼于五行生克制化,通过调整脾、胃、肝、肺之气机,达到治疗效果,代表组方有左金丸.

乌梅丸出自《伤寒论》,是厥阴病代表方,建国之后,众多医家对乌梅丸之组方持“上热下寒、寒热错杂”论,笔者通过查阅文献,梳理了不同时期医家对于乌梅丸认识的差异,从脏腑辨证角度对乌梅丸“上热下寒、寒热错杂”病机提出疑问,并发现从肝阳虚的角度分析乌梅丸,则能解释其组方特点.乌梅丸“寒热错杂”病机是在肝脏阳气虚馁的脏寒基础上,又有相火内郁化热而成,其寒与热均与肝有关,无上下之分.临床应用乌梅丸需抓住脉、症两点:一是脉弦不任重按或弦而无力,二是出现肝经循行部位的症状,根据病证寒热虚实偏颇,调整药物,取温肝阳、益肝体、清郁火之法,可扩展乌梅丸的应用范围.

[目的]研究反流高敏感(RH)、功能性烧心(FH)与非糜烂性反流病(NERD)患者食管功能及反流特点的差别.[方法]选取于2017年12月～2019年5月在首都医科大学附属北京中医医院消化科同时行胃镜、高分辨率食管测压以及24 h多通路腔内阻抗联合pH监测的141例患者,根据症状及检查结果分为NERD组(42例)、RH组(58例)、FH组(41例),比较3组患者食管测压、24 h食管pH及pH-阻抗情况.[结果]FH组LES静息压、同步收缩百分比显著高于RH组(P＜0.05);LES长度、LESP下降例数、LES残余压、UES静息压、UES残余压、波幅平均值、无效食管动力、蠕动断裂、DCI平均值、远端收缩延迟、提前收缩百分比、快速收缩百分比3组之间差异均无统计学意义(P＞0.05);3组间DeMeester评分、总反流次数、立位酸暴露时间占比、近端酸反流次数、远端酸反流次数比较,差异有统计学意义(P＜0.05).NERD组总反流时间、长反流次数、最长反流时间、总酸暴露时间占比、卧位酸暴露时间占比显著高于RH组、FH组(P＜0.05).NERD组、RH组近端反流次数显著高于FH组(P＜0.05).RH组远端弱酸反流次数、近端弱酸反流次数中显著高于FH组(P＜0.05).3组远端非弱酸反流事件差异无统计学意义(P＞0.05).[结论]3组患者均存在不同程度的食管动力异常,可通过弱酸反流增加、近端反流比率升高将RH、FH精准区分开来.