Background: Cordyceps polysaccharides (CSP) have shown neuroprotective potential in models of ischemic stroke, but the underlying mechanisms remain to be clarified. Methods: In this study, the effects of CSP were evaluated in MCAO rats and OGD-exposed BV-2 cells. Results: CSP significantly attenuated ischemic injury and inflammatory responses in both in vivo and in vitro models. Mechanistically, CSP decreased CMPK2 expression, increased TFAM levels, and reduced 8-OHdG expression, suggesting attenuation of oxidative DNA damage and mitochondrial DNA-associated stress. EdU staining further showed that OGD-induced DNA synthesis-related signals were predominantly extranuclear, supporting the possibility of mtDNA-associated alterations under ischemia-like conditions. Moreover, CSP suppressed the upregulation of NLRP3, Caspase-1, N-GSDMD, IL-1β, and IL-18, and reduced LDH release following OGD exposure, suggesting inhibition of inflammasome-associated pyroptotic signaling. Conclusions: These findings suggest that the neuroprotective effects of CSP in ischemic stroke models may be related to the modulation of CMPK2/mtDNA/NLRP3 inflammasome pathway and reduced pyroptosis.

The pathogenesis of diabetic retinopathy DR is highly complex, and in recent years, increasing attention has been directed toward the role of the gut in its development. Evidence suggests that intestinal barrier dysfunction is a frequent pathological feature in both DR patients and animal models, facilitating the translocation of gut microbiota and their metabolites into the systemic circulation. On one hand, these translocated microbial components and metabolites activate intestinal immune cells, promoting the migration of gut-derived immune cells to the retina or choroid, thereby contributing to retinal neuroinflammation. On the other hand, they may compromise the integrity of the blood-retina barrier, disrupting the retinal microenvironment. This review explores the influence of the gut on DR pathogenesis through several key mechanisms: alterations in gut microbiota and their metabolites, impairment of intestinal barrier integrity, dysregulated gut immune responses, translocation routes of gut-derived components (including immune cells, microbes, and metabolites) to the retina, and the resulting retinal pathology and microglial-mediated neuroinflammation. By elucidating the pathological mechanisms underlying the gut-retina axis, we aim to identify critical molecular and cellular targets involved in DR progression and to provide new insights for the development of innovative therapeutic strategies.

Cordyceps polysaccharide (CSP) has been shown to exhibit anti-inflammatory and antioxidant effects, with potential applications in ischemic stroke. This work is to explore the interventional potential of CSP in MCAO rats and the effects on the intestinal and cerebral IL-23/IL-17 axis. We conducted pharmacological experiments and mechanism exploration in MCAO rats. Our research showed that CSP improved the neurological function and cerebral pathological morphology, reduced cerebral infarction volume and water content in MCAO rats. We also found that CSP significantly decreased the IL-1 beta, TNF-alpha and IL-6 in the ischemic brain and enhanced the ability of MCAO rats to resist oxidative stress. Additionally, CSP improved intestinal barrier, inhibited the activation of the TLR4/Myd88/NF-kappa beta signaling pathway and IL-23/IL-17 axis. The study results demonstrated the effectiveness of CSP in interfering with MCAO rats. The mechanism appears to be related to protecting the intestinal barrier and inhibiting the IL-23/IL-17 axis.

Objective: To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions: WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

目的 系统评价复方玄驹胶囊(CXC)治疗慢性前列腺炎(CP)的临床有效性与安全性.方法 检索中国知网、万方数据库、维普数据库、PubMed中CXC治疗CP的随机对照试验,检索时限自2007年1月至2022年8月29日.由两名研究人员按照上述方法进行文献查阅,并对文献进行纳入和排除的筛选.采用RevMan 5.4软件进行数据分析.结果 共纳入21篇文献,累计3401例样本.Meta分析结果显示,CXC治疗后总有效率明显升高(RR=1.32,95％CI为1.26～1.38,P<0.00001),美国国立卫生研究院慢性前列腺炎症状指数(NIH-CPSI)显著降低(MD=-6.16,95％CI为-7.56～-4.76,P<0.00001),但对不良反应无显著影响(RR=0.82,95％CI为0.50～1.33,P=0.42).结论 基于本研究,CXC可改善CP症状,对CP具有显著的临床疗效,但仍需更多高质量、大样本的随机对照试验进一步验证.

Bidirectional communication between central nervous system (CNS) and intestine is mediated by nerve, endocrine, immune and other pathways in gut-brain axis. Many diseases of CNS disturb the homeostasis of intestine and gut microbiota. Similarly, the dysbiosis of intestinal and gut microbiota also promotes the progression and deterioration of CNS diseases. IL-23/IL-17 axis is an important inflammatory axis which is widely involved in CNS diseases such as experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), and ischemic stroke (IS). Attributing to the long anatomically distances between ischemic brain and gut, previous studies on IL-23/IL-17 axis in IS are rarely focused on intestinal tissues. However, recent studies have found that IL-17+T cells in CNS mainly originate from intestine. The activation and migration of IL-17+T cells to CNS is likely to be affected by the altered intestinal homeostasis. These studies promoted the attention of IL-23/IL-17 axis and gut-brain axis. IS is difficult to treat because of its extremely complex pathological mechanism. This review mainly discusses the relationship between IL-23/IL-17 axis and IS from the perspective of gut-brain axis. By analyzing the immune pathways in gut-brain axis, the activation of IL-23/IL-17 axis, the roles of IL-23/IL-17 axis in gut, CNS and other systems after stoke, this review is expected to provide new enlightenments for the treatment strategies of IS. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".

Objective: To explore the therapeutic potential of Cordyceps sinensis（Berk.） Sacc.（C. sinensis, Dong Chong Xia Cao） in an ischemic stroke（IS） model and predict its possible mechanism through network pharmacology.Methods: Thirty-three Sprague—Dawley rats were randomly divided into the Sham, model, and C. sinensis groups. After 5 days of pre-treatment, the model group and the C. sinensis group were subjected to middle cerebral artery occlusion（MCAO） modeling. Effect of C. sinensis on MCAO rats was evaluated by comparing cerebral infarct size, neurological function, cerebral water content, pathological changes, and certain biochemical indicators. Intersection targets between C. sinensis and IS was screened using network pharmacology analysis. Relationship among core components, targets and pathways of C. sinensis in treating IS was constructed through network pharmacology analysis and further verified by molecular docking. Finally, the DAVID v8.8 database was used for performing GO analysis and KEGG pathway enrichment analysis by importing the intersection targets.Results: Compared with the model group, C. sinensis significantly reduced the volume of cerebral infarction（P =.026）, the cerebral water content（P =.0013）, the m NSS score（P ＜.001）, and the levels of IL-17（P =.031）, TNF-a（P =.016）, MDA（P =.014）, and glutamate（P =.014） in serum, while upregulating the level of SOD in serum and improving the pathological morphology in MCAO rat ischemic brains. The results of network pharmacology analysis showed that core targets（such as CASP3, PTGS2, and PPARG）and the main enrichment pathways（IL-17, AGE-RAGE, and TNF signaling pathways） were regulated by 30chemical components of C. sinensis, which effectively treated IS in MCAO rats.Conclusion: The results of this study showed that C. sinensis effectively interfered with MCAO rats, and the mechanism may be related to the regulation of blood lipids and to anti-apoptosis and antiinflammatory effects.

Ischemic stroke (IS) has complex pathological mechanisms, and is extremely difficult to treat. At present, the treatment of IS is mainly based on intravenous thrombolysis and mechanical thrombectomy, but they are limited by a strict time window. In addition, after intravenous thrombolysis or mechanical thrombectomy, damaged neurons often fail to make ideal improvements due to microcirculation disorders. Therefore, finding suitable pathways and targets from the pathological mechanism is crucial for the development of neuroprotective agents against IS. With the hope of making contributions to the development of IS treatments, this review will introduce (1) how related targets are found in pathological mechanisms such as inflammation, excitotoxicity, oxidative stress, and complement system activation; and (2) the current status and challenges in drug development.

目的:利用网络药理学和分子对接技术探究核心组方治疗精液不液化的作用机制.方法:利用中药系统药理学数据库与分析平台(TCMSP)和Uniprot数据库对王琦院士的核心组方药物进行成分和靶点的处理收集,再借助Gene Cards数据库、在线人类孟德尔遗传数据库(OMIM)对疾病靶点进行收集,与药物靶点取"药物-疾病"交集,获得核心靶点,使用String数据库绘制核心靶点蛋白质-蛋白质相互作用(PPI)网络.运用R语言平台进行基因本体(GO)和京都基因和基因组百科全书(KEGG)信号通路富集分析,构建核心组方"成分-靶点-疾病"通路图.对关键成分与核心靶点进行分子对接,最后通过造模和药物对大鼠进行干预后,利用酶联免疫吸附试验(ELISA)检测各组大鼠前列腺中细胞因子水平,实时荧光定量-聚合酶链反应(RT-PCR)法检测IL-17mRNA的表达量,对核心作用靶点及信号通路进行动物实验验证.结果:核心组方中有活性成分29个,对应靶点194个,与疾病靶点交集靶点24个,关键成分有槲皮素、山柰酚、β-谷甾醇等,核心靶点涉及肿瘤坏死因子(TNF)、纤溶酶原激活物抑制因子(SERPINE1)、白细胞介素6(IL-6)等.主要通过糖尿病并发症AGE-RAGE信号通路及IL-17炎症通路等发挥药效.核心组方中的槲皮素、β-谷甾醇等核心靶点之间具有较强的结合活性.核心组方能显著降低模型组大鼠前列腺组织中TNF、SERPINE1、IL-6、IL-1β的水平及IL-17 mRNA的表达量(P<0.01).结论:王琦院士所拟核心组方中的关键成分槲皮素、β-谷甾醇等可能通过作用于TNF、SERPINE1等靶点调节多条通路,可能通过抑制炎症反应、抗氧化和调节纤维蛋白等作用治疗精液不液化.

目的 回顾性探究基于案例教学法(case-based learning,CBL)的半翻转课堂教学模式在病理生理学本科生线上教学中的应用.方法 选取北京中医药大学2017—2020年病理生理学授课学习的所有本科生,分为对照组(2017—2019年以传统课堂模式教学的本科生)和实验组(2020年基于CBL的半翻转课堂教学的本科生),教学完成后,针对学生的教学满意度等问卷调查、期末考试成绩以及教学督导专家意见进行总结.结果 与传统的教学模式相比,学生对基于CBL的半翻转课堂线上教学模式中教师的教学以及学生的学习效果评价较好[自主学习能力(3.96±0.93)分、满足个人学习要求(3.95±0.86)分、知识掌握情况(3.80±0.86)分];与其他线上平台相比,利用微信授课易被学生接受[(3.87±1.03)分];线上授课[实验组2020年成绩为85.0(81.0,89.0)分]的学生期末考试成绩较传统课堂教学模式[对照组:2017年、2018年、2019年成绩分别为75.0(66.5,83.5)分、73.0(67.0,80.0)分、76.0(67.5,84.5)分]明显提高(P<0.001);教学督导专家也有积极的评价.结论 基于CBL的半翻转课堂在病理生理学本科生线上教学效果好,学生满意度高,是一种值得尝试的教学模式.

Male infertility is a major and growing health problem with an estimated global prevalence of 4.2%. The current therapy is limited by the unknown etiology of MI, emphasizing the critical requirement forward to a more efficient method or medication. Through thousands of years, Traditional Chinese Medicine (TCM) has been shown to be effective in treating MI effectively. However, the components, mechanisms and functions of TCM prescriptions on MI are still obscure, severely limiting its clinical application. In order to discover the molecular mechanism of TCM against MI, our study presents a comprehensive approach integrated data mining, network pharmacology, molecular docking, UHPLC-Q-Orbitrap HRMS, and experimental validation. Here, we begin to acquire 289 clinical TCM prescriptions for MI from a TCM hospital's outpatient department. Then, Core Chinese Materia Medica (CCMM) was then retrieved from the TCM Inheritance Support System (TCMISS), which was utilized to discover the underlying rules and connections in clinical prescriptions. After that, 98 CCMM components and 816 MI targets were obtained from ten distinct databases. Additionally, the network pharmacology methods, including network construction, GO and KEGG pathway enrichment, PPI analysis, were utilized to reveal that kaempferol, quercetin, isorhamnetin, and beta-sitosterol are the core components of CCMM in treating MI. The mechanisms and functions of CCMM against MI are hormone regulation, anti-apoptosis, anti-oxidant stress, and anti-inflammatory. Furthermore, the strong connections between four core components and six key targets were verified using a molecular docking method. Following that, the core components of the CCMM extract were identified using UHPLC-Q-Orbitrap HRMS analysis. Finally, in vivo experiments demonstrated that CCMM and four core components could improve the density, motility, viability of sperm, lecithin corpuscle density, decrease the rate of sperm malformation and testis tissue damage, and regulate the protein expressions of AKT1, MAPK3/1, EGFR, and TNF-α in a mouse model of MI. UHPLC-Q-Orbitrap HRMS analysis and in vivo experiments further validated the results of data mining, network pharmacology, and molecular docking. Our study could uncover the components, mechanisms, and functions of TCM prescriptions against MI and develop a new integrative approach to demonstrate TCM's multi-component, multi-target, and multi-pathway approach to disease treatment.

目的 系统评价生精胶囊(片)治疗少弱精子症的有效性.方法 应用计算机检索中国学术期刊全文数据库(CNKI)、万方数据知识服务平台(Wanfang Data)、维普中文期刊全文数据库(VIP)、循证医学图书馆(The Cochrane Library)、美国生物医学期刊文献数据库(PubMed)中生精胶囊(片)治疗少弱精子症的随机对照试验(RCT)文献,检索时限为自建库至2022年8月9日.由2名研究人员按照检索方式进行文献查阅,并对文献进行纳入和排除的筛选.使用RevMan 5.4软件进行Meta分析.结果 共纳入26篇文献,累计2 902例样本.Meta分析结果显示,采用生精胶囊(片)治疗的试验组总有效率高于对照组(RR=1.41,95％CI:1.25～1.60,P＜0.000 01),在改善患者精液量(MD=0.50,95％CI:0.30～0.71,P＜0.000 01)、精液密度(MD=12.39,95％CI:9.19～15.59,P＜0.000 01)、a 级精子率(MD=7.24,95％CI:4.39～10.08,P＜0.000 01)、(a+b)级精子率(MD=9.00,95％CI:3.25～18.15,P＜0.000 01)方面均优于对照组.结论 本文Meta分析研究显示生精胶囊(片)治疗少弱精子症疗效较好,但仍需更多高质量、大样本的RCT提供高级别的循证医学数据.

与传统的线下课堂教学相比,线上教学给教师、学生及网络平台均带来了巨大挑战.本研究针对北京中医药大学2020年中医学实验班二年级120名本科生开展为期一学期的线上病理生理学教学,并从线上教学的挑战性、线上课堂的实施策略、教学问卷调查及学习成绩等方面总结了线上教学实践过程,形成了病理生理学线上教学的经验,为进一步提高医学课程的线上教学水平和医学生的人才培养质量提供参考借鉴.

目的 分析并总结国医大师王琦院士治疗精液不液化的组方特点和用药规律,为中医治疗精液不液化提供新的参考.方法 收集并规范王院士门诊收治精液不液化患者病例数据,通过频次分析、关联规则、聚类分析等方法对病例进行数据挖掘和可视化分析,明确核心组方并挖掘潜在新处方.结果 共纳入有效医案28份,处方51首,涉及中药77味,得出高频药物15味,性味以辛温为主,得到核心组方6组,主要有鸡内金-鱼鳔-淡豆豉、麦芽-鸡内金-山楂-淡豆豉、秦皮-车前子-麦芽-金钱草等,获得3首治疗精液不液化的新处方:鸡内金-鱼鳔-淡豆豉-麦芽-山楂、秦皮-车前子-麦芽-金钱草-山楂、菟丝子-延胡索-巴戟天-柴胡-黄芪-徐长卿.结论 王院士治疗精液不液化时强调"扶正祛邪,恢复气化功能"的用药原则,着眼于"肾阴阳失调,气化失常"的病机,临床用药以补虚药、消食药和活血化瘀药为主.

目的:基于网络药理学研究补阳还五汤(buyang huanwu decoction,BYHWD)入脑成分治疗缺血性中风(ischemic stroke,IS)的潜在生物学机制,并通过实验对预测通路进行初步验证.方法:利用TCMSP、化学专业数据库和Swiss数据库筛选BYHWD的作用靶点,通过DiGSeE、OMIM、TTD和DRUGBANK数据库挖掘IS的相关靶点,将BYHWD的作用靶点与IS靶点相映射得到BYHWD作用于IS的潜在靶点,应用STRING数据库构建PPI网络图,借助Metascape对潜在靶点进行GO和KEGG富集分析,将实验动物随机分为对照组、模型组、BYHWD组和依达拉奉组,通过大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)术建立大鼠IS模型,造模7 d后采用Western blot技术对丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)/细胞外调节激酶(extracellular regulated protein kinases,Erk)通路进行验证.结果:获得BYHWD治疗IS的潜在靶点60个,主要富集到白细胞介素(interleukin,IL)-17信号通路、MAPK信号通路等途径.动物实验结果显示,与模型组比较,BYHWD组大鼠缺血侧脑皮质中磷酸化细胞外调节蛋白激酶(phosphorylation extracellular regulated protein kinases,pErk)表达明显降低(P<0.01).结论:BYHWD治疗IS具有多成分、多靶点、多通路的特点,BYHWD治疗IS的潜在机制可能与抑制MAPK/Erk信号通路的活性相关.

Abstract Background: Male infertility (MI) affects almost 5% adult men worldwide, and 75% of these cases are unexplained idiopathic. There are limitations in the current treatment due to the unclear mechanism of MI, which highlight the urgent need for a more effective strategy or drug. Traditional Chinese Medicine (TCM) prescriptions have been used to treat MI for thousands of years, but their molecular mechanism is not well defined. Methods: Aiming at revealing the molecular mechanism of TCM prescriptions on MI, a comprehensive strategy integrating data mining, network pharmacology, and molecular docking verification was performed. Firstly, we collected 289 TCM prescriptions for treating MI from National Institute of TCM Constitution and Preventive Medicine for 6 years. Then, Core Chinese Materia Medica (CCMM), the crucial combination of TCM prescriptions, was obtained by the TCM Inheritance Support System from China Academy of Chinese Medical Sciences. Next, the components and targets of CCMM in TCM prescriptions and MI-related targets were collected and analyzed through network pharmacology approach.Results: The results showed that the molecular mechanism of TCM prescriptions for treating MI are regulating hormone, inhibiting apoptosis, oxidant stress and inflammatory. Estrogen signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway are the most important signaling pathways. Molecular docking experiments were used to further validate network pharmacology results. Conclusions: This study not only discovers CCMM and the molecular mechanism of TCM prescriptions for treating MI, but may be helpful for the popularization and application of TCM treatment.

ObjectiveTo investigate the therapeutic effects and pharmacological mechanisms of Yishen Xingyang capsule (YXC) in oligoasthenospermia (OA) rats.MethodsForty-eight male Sprague–Dawley rats were randomly divided into eight groups of six rats each: normal control (NC); model control (MC); three different positive drug (PD); and low-, medium-, and high-dose YXC groups. A rat model of OA was established by administering glucosides of Tripterygium wilfordii Hook. F (GTW). After YXC administration, penile erectile function was observed. The epididymis, blood, and testes of the rats were harvested for analysis of sperm quality, sex hormone levels, mitochondrial membrane potential, and the transforming growth factor (TGF)-β1/Smad signaling pathway.ResultsCompared with that in the MC group, penile erectile function in the YXC groups and three PD groups increased (all P < .01). Moreover, sperm quality in the YXC groups and three PD groups improved (all P < .001). The levels of testosterone, follicle stimulating hormone, and luteinizing hormone in the three PD and YXC groups increased (all P < .05). The mitochondrial membrane potential in the three PD and YXC groups significantly improved (all P < .001). Furthermore, the YXC and three PD groups showed decreased TGF-β1 expression (all P < .05) compared with the MC group. The high-dose YXC group and three PD groups improved Smad2 and Smad4 expression (all P < .05).ConclusionYXC improved penile erectile function and sperm quality in OA rats, and the underlying mechanism included increase in sex hormones, inhibition of sperm apoptosis, and regulation of the TGF-β1/Smad signaling pathway. Meanwhile, this study provides a new effective drug option for the treatment of OA, which is beneficial to male reproductive health and social harmony.

随着中医药在全球地位的提升,中医院校的留学生数量也在增加.病理生理学是医学基础学科之一,是医学生必修课程,同时也是紧密联系基础与临床的桥梁学科之一.提高病理生理学教学质量是留学生基础教学的重要方面,将对其今后的临床工作有很大的帮助.课堂教学中,教师灵活运用包括思维导图、案例式教学、问题导入法等多种教学方法和手段,使抽象的病理生理学内容变得生动而具体,有助于提高中医院校留学生病理生理学的教学质量,提升教学效果.

男性不育症是一种常见的男科疾病,对全球12％以上男性的生活质量造成了严重影响.枸杞子是茄科植物宁夏枸杞的干燥成熟果实,作为传统中药材,在中医领域被广泛应用,有关研究表明枸杞子可用于治疗男性不育症,但相关综述极少.本文通过检索近15年来枸杞子治疗男性不育症方面的国内外文献,针对相关作用机制进行综述,为进一步开发枸杞子提供参考.

[目的]探究并分析王琦院士临床治疗前列腺增生症的组方规律及用药特点,为中医临床治疗该病提供思路和参考.[方法]收集并整理2016年9月—2019年6月期间王琦院士门诊收治前列腺增生症的临床病例,经过纳入和排除标准筛选及数据规范化处理后,由3人录进"中医传承辅助平台系统(V2.5)"软件并核对,采用平台大数据算法进行组方挖掘和分析.[结果]共纳入方剂75首,涉及中药154味.统计前列腺增生症治疗药物的使用频次、性味归经、关键药物、药物组合关联规则及新方组合.使用频次居前8位的中药依次为水蛭、王不留行、乌药、桃仁、赤芍、桂枝、茯苓、牡丹皮,可见其为桂枝茯苓丸加味.四气频次由高到低依次为寒、平、温、凉、热.五味频次由高到低依次为苦、甘、辛、咸、涩、酸.挖掘出12组药物核心组合,在此基础上演变得到6首新处方.[结论]王琦院士在临床治疗前列腺增生症时紧抓本虚标实的病机特点,提出"肾气亏虚、瘀血阻滞"的病机理论,灵活运用"主病主方"与分期论治的思想.王琦院士治疗前列腺增生症以"疏通"为治则,以散瘀血、消癥积、通水道三法并用为治法,用药以益气活血消癥、化痰软坚利水为主.