Background The incidence of comorbidity between myocardial infarction (MI) and anxiety disorders is increasing. However, the biological association between them has not been fully understood. Objective This study aims to investigate the molecular mechanisms of comorbidity between MI and anxiety disorders and to predict their key genes and potential therapeutic drugs. Methods We searched Gene Expression Omnibus databases and performed differential analyses using the limma package to identify the functional enrichment of differential genes. Next, we constructed regulatory networks to investigate the relationship between hub genes and autophagy, ferroptosis, and immunity. Furthermore, we predicted transcription factors by R package, constructed a miRNA network, performed the single-cell analysis of key gene expression, and predicted drug targeting of differential genes using the Connectivity Map database. Results The datasets for MI and anxiety disorders were analyzed for up and down-regulated differential genes, resulting in 35 intersecting differential genes. The top 10 feature genes from each dataset were intersected using Random Forest, resulting in the identification of three intersecting genes: STK17B, AKIRIN2, and WDR77. Validation of the above key genes was carried out by in vitro experiments. We examined the gene expression of STK17B, WDR77 and AKIRIN2 in the hippocampus and myocardial infarction border zone respectively by qPCR and WB, and the results confirmed that the above are the key genes for myocardial infarction and anxiety. There is a significant correlation between the comorbidity mechanism of myocardial infarction and anxiety disorders with ferroptosis and immunity. The construction of the miRNA network revealed that miR-205 and let-7 had higher average connectivity among the three hub genes. The single-cell analysis revealed significant expression of key genes in Endothelial cells, Cardiomyocytes, Macrophages, and Fibroblasts datasets. Cd274 showed a higher correlation with key genes in myocardial infarction and anxiety disorders. Conclusion Validation by multiple datasets and in vitro experiments showed that STK17B, AKIRIN2, and WDR77 are the key genes in the comorbidity of myocardial infarction and anxiety disorders, and ferroptosis and immunity are the key links in the comorbidity mechanism of myocardial infarction and anxiety disorders.

BackgroundPatients with myocardial infarction (MI) have a high incidence of depression, which deteriorates the cardiac function and increases the risk of cardiovascular events. Shuangxinfang (Psycho-cardiology Formula, PCF) was proved to possess antidepressant and cardioprotective effects post MI. However, the compounds of PCF remain unidentified, and the pertinent mechanism is still not systematic. The purpose of this study is to determine the ingredients of PCF, further to probe the underlying mechanism for MI with depression.MethodsThe compounds of PCF were qualitatively identified by LC-MS/MS. The optimal dosage for lavage with the PCF solution in rats was determined to be 1 mL/100 g/day for a duration of 5 days. We also detected the PCF components migrating to blood in the control and model rats. Then the targets of PCF compounds were searched on Swiss target database, and the targets of depression and MI were predicted on TTD, OMIM, GeneCards, DrugBank and PharmGkb database. All the targets were intersected to construct the Protein-Protein Interaction (PPI) network on Metascape platform and the herb-compound-target (HCT) network on Cytoscape, to identify the hub targets. GO and KEGG pathway enrichment analysis were conducted on DAVID platform. Molecular docking was modeled on AutoDock Vina software.ResultsThere were 142 bioactive compounds from PCF acting on 270 targets in a synergistic way. And a total of seven components migrating to blood were identified, including Miltionone I, Neocryptotanshinone, Danshenxinkun A, Ferulic acid, Valerophenone, Vanillic acid and Senkyunolide D. Then SRC and MAPK3 were obtained as the hub proteins by degree value in PPI network, and P2RY12 was picked out as seed proteins ranked by scores from MCODES. Further analysis of biological process and signaling pathways also revealed the significance of ERK/MAPK. Statistical analyses (e.g., GO and KEGG pathway enrichment, PPI network analysis) demonstrated the significance of the identified targets and pathways (p < 0.05). Molecular docking results showed that the binding energies were all less than −5 kcal/mol. The stability of Neocryptotanshinone possessed the lowest binding energy to MAPK3.ConclusionWe identified PCF’s bioactive compounds and predicted its therapeutic mechanism for MI with depression using LC-MS/MS and bioinformatics. Key targets SRC, MAPK3, and seed protein P2RY12 were crucial for PCF’s cardio-neuroprotective effects. Neocryptotanshinone showed the strongest binding to MAPK3, suggesting it as a pivotal active ingredient. These findings offer new insights and targets for future research on PCF.

BACKGROUND:Depression post-myocardial infarction (MI) is becoming more prevalent. The gut-brain axis (GBA), influenced by the gut microbiota, is a critical component in understanding depression post-MI. Despite the well-established connection between gut microbiota and depression post-MI, this relationship remains incompletely understood. METHODS AND ANALYSIS:This protocol will follow the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) 2020 statement. Beginning from inception to October 2023, a systematic search will be conducted across eight electronic databases, including PubMed, MEDLINE, Scopus, Embase, Cochrane Clinical Trials Database, Web of Science, China National Knowledge Infrastructure, and China Biomedical Literature Database. Pre-selected studies will be independently assessed by two researchers following a standard inclusion, data extraction and quality assessment protocol. The primary outcome measures are differences in the profile of gut microbiota and rating scale scores for depression. Fixed-effects models will be used when both clinical heterogeneity and statistical heterogeneity are low, otherwise random-effects models will be used. Furthermore, subgroup analyses will be conducted on the depression severity of the participants using the same psychiatric scales employed, study type and geographic region. Random forest plot runs and research-related statistical analyses will be carried out using Rev Man V.5.3 software. EXPECTED RESULTS:This study will identify the association between the gut microbiota and the onset of depression post-MI, and provide evidence for the use of probiotics as an adjunctive treatment for depression post-MI. TRIAL REGISTRATION:Prospero registration number: CRD42023444026.

EDITORIAL article Front. Psychiatry, 05 January 2024Sec. Aging Psychiatry Volume 14 - 2023 | https://doi.org/10.3389/fpsyt.2023.1349818

Depression exists with high prevalence and heavy disease burden. Stress events play a key role in the occurrence of depression, but the pathological mechanism has not been fully clarified by reason of the complexity and heterogeneity. In recent years, neuroinflammation as a pathological mechanism of depression has received extensive attention. The activated microglia is regarded as the marker of neuroinflammation, which is an important link of stress-induced depression. Stress might induce microglia activation through pattern recognition receptors(PRR), intestinal flora, hypothalamic-pituitary-adrenal(HPA) axis, and other pathways. Cross-talk between impaired microglia function and neurobiological factors such as inflammatory cytokines, serotonin metabolism, and neuroplasticity may lead to depression. At present, a large number of studies have proved that traditional Chinese medicine(TCM) plays an anti-depressive role by inhibiting microglia activation, which may be potential treatment strategies for depressive disorder. This paper reviewed the research progress of stress-induced microglia activation in depression and summarized the mechanism of TCM against depression with regard to microglia, hoping to provide experimental evidence and consideration for TCM against depression through microglia.

Background With the increasing pressures of modern life and work, combined with a growing older population, the incidence of comorbid anxiety and myocardial infarction (MI) is increasing. Anxiety increases the risk of adverse cardiovascular events in patients with MI and significantly affects their quality of life. However, there is an ongoing controversy regarding the pharmacological treatment of anxiety in patients with MI. The concomitant use of commonly prescribed selective serotonin reuptake inhibitors (SSRIs) and antiplatelet medications such as aspirin and clopidogrel may increase the risk of bleeding. Conventional exercise-based rehabilitation therapies have shown limited success in alleviating anxiety symptoms. Fortunately, non-pharmacological therapies based on traditional Chinese medicine (TCM) theory, such as acupuncture, massage, and qigong, have demonstrated promising efficacy in treating MI and comorbid anxiety. These therapies have been widely used in community and tertiary hospital settings in China to provide new treatment options for patients with anxiety and MI. However, current studies on non-pharmacological TCM-based therapies have predominantly featured small sample sizes. This study aims to comprehensively analyze and explore the effectiveness and safety of these therapies in treating anxiety in patients with MI. Method We will systematically search six English and four Chinese databases by employing a pre-defined search strategy and adhering to the unique rules and regulations of each database to identify studies that fulfilled our inclusion criteria, to qualify for inclusion, patients must be diagnosed with both MI and anxiety, and they must have undergone non-pharmacological TCM therapies, such as acupuncture, massage, or qigong, whereas the control group received standard treatments. The primary outcome measure will be alterations in anxiety scores, as assessed using anxiety scales, with secondary outcomes encompassing the evaluations of cardiopulmonary function and quality of life. We will utilize RevMan 5.3 to conduct a meta-analysis of the collected data, and subgroup analyses will be executed based on distinct types of non-pharmacological TCM therapies and outcome measures Results A narrative summary and quantitative analysis of the existing evidence on the treatment of anxiety patients with MI using non-pharmacological therapies guided by Traditional Chinese Medicine theory. Conclusion This systematic review will investigate whether non-pharmacological interventions guided by TCM theory are effective and safe for anxiety in patients with MI, and provide evidence-based support for their clinical application. Systematic review registration PROSPERO CRD42022378391

目的:系统评价中药联合常规降血压药物治疗高血压合并焦虑的临床疗效及安全性.方法:检索从建库至2020年12月Pubmed、the Cochrane Library、中国知网、维普、万方和中国生物医学文献数据库,收集中药联合常规降血压药物治疗高血压合并焦虑的临床随机对照试验,运用风险评估工具(rise of bias,ROB)评价文献质量,通过RevMan5.4软件进行数据分析.结果:本研究纳入18篇文献,共1 287例患者.Meta分析显示:与对照组比较,中药联合常规降血压药物能够提高高血压合并焦虑患者的降血压疗效[RR:1.29,95％CI(1.20,1.39)],降低患者的收缩压[MD:-10.15,95％CI(-13.03,-7.28)]和舒张压[MD:-7.18,95％CI(-8.14,-6.22)],降低汉密尔顿焦虑量表(hamilton anxiety scale,HAMA)评分[MD:-6.09,95％CI(-8.35,-3.84)],提高中医证候疗效[RR:1.56,95％CI(1.20,2.03)].结论:中药联合常规降血压药物治疗高血压合并焦虑患者的疗效确切,可以降低患者的收缩压和舒张压,改善患者的焦虑情绪,并且安全性较好.

目的 基于中国中医科学院西苑医院经皮冠状动脉介入(PCI)术后病人的住院及门诊处方,挖掘中医药在真实世界中治疗PCI术后病人的用药规律.方法 采集2016年—2019年在中国中医科学院西苑医院行PCI术病人的术后处方,并使用频次统计、复杂网络分析、关联规则分析、聚类分析及因子分析对处方进行分析.结果 共纳入4536首研究方剂,涉及534味中药,这些中药多为补虚药、活血化瘀药、清热药;以甘、苦、温为主,入脾经及肝经.拓扑学分析得到生黄芪、丹参、当归、川芎、茯苓、陈皮6味核心药物.二项、三项关联中高关联度药物组合分别为3组、22组,系统聚类分析归为9大类,因子分析获得13个公因子.结论 现代中医药治疗PCI术后病人的整体原则以益气活血、化痰理气为主.

Background: Alzheimer’s disease (AD) as an age-related, irreversible neurodegenerative disease, characterized by cognitive dysfunction, has become progressively serious with a global rise in life expectancy. As the failure of drug elaboration, considerable research effort has been devoted to developing therapeutic strategies for treating AD. TCM is gaining attention as a potential treatment for AD. Gastrodia elata Blume, Polygala tenuifolia Willd., Cistanche deserticola Ma, Rehmannia lutinosa (Gaertn.)DC., Acorus gramineus Aiton, and Curcuma longa L. (GPCRAC) are all well-known Chinese herbs with neuroprotective benefits and are widely used in traditional Chinese decoction for AD therapy. However, the efficacy and further mechanisms of GPCRAC extracts in AD experimental models are still unclear. The purpose of this study was to investigate the synergistic protective efficacy of GPCRAC extracts (composed of extracts from these six Chinese medicines), and the protein targets mediated by GPCRAC extracts in treating AD. Methods: Scopolamine-induced cognitive impairment mouse model was established to determine the neuroprotective effects of GPCRAC extracts in vivo, as shown by behavioral tests and cerebral cholinergic function assays. To identify the potential molecular mechanism of GPCRAC extracts against AD, label-free quantitative proteomics coupled with tandem mass spectrometry (LC-MS/MS) were performed. The integrated bioinformatics analysis was applied to screen the core differentially expressed proteins in vital canonical pathways. Critical altered proteins were validated by qPCR and Western blotting. Results: Administration of GPCRAC extracts significantly recovered scopolamine-induced cognitive impairment, as evidenced by the improved learning and memory ability, increased Ach content and ChAT activity, as well as decreased AchE activity in the hippocampus of mice. In total, 390 proteins with fold-change>1.2 or <0.83 and p < 0.05 were identified as significant differentially expressed proteins, of which 110 were significantly up-regulated and 25 were significantly down-regulated between control and model group. By mapping the significantly regulated proteins, we identified five hub proteins: PPP2CA, Gsk3β, PP3CC, PRKACA, and BCL-2 that were associated with dopaminergic synapse and apoptosis signaling pathway, respectively. Western blotting and QPCR demonstrate that the expression levels of these core proteins could be significantly improved by the administration of GPCRAC extracts. These pathways and some of the identified proteins are implicated in AD pathogenesis. Conclusion: Administration of GPCRAC extracts was effective on alleviating scopolamine-induced cognitive impairment, which might be through modulation of dopaminergic synapse and apoptosis signaling pathway. Consequently, our quantitative proteome data obtained from scopolamine-treated model mice successfully characterized AD-related biological alterations and proposed novel protein biomarkers for AD.

现代医学将出现心血管疾病或症状的同时伴发焦虑、抑郁等心理障碍的疾病称为双心病.目前,诊治双心病颇为棘手且尚无定论.赵海滨教授基于阴阳平衡理论,从肝脏着手,认为二脏皆存在虚弱和偏亢的病机,故治疗以补虚泻实为法,使其恢复"阴平阳秘"之态,则双心病自愈.本研究旨在结合病案总结赵海滨教授辨治双心病的经验,为临床认识双心病开拓新思路.

双心疾病是心内科常见病,临床以冠心病伴焦虑抑郁多见.针对双心疾病,基于中医"心主血脉""心主神明"的生理功能,结合心身医学"形神同调"思想,我们提出中医学"双心学说",血脉之心与神明之心生理相依,病理互损,双心为病.结合临床认为"瘀热虚滞"是双心疾病中冠心病伴焦虑抑郁的重要病机,其中瘀为基,热为渐,虚为枢,滞为扰.梳理相关机制研究,发现"瘀热"与炎症通路激活、"虚滞"与"线粒体能量代谢障碍"存在相关性,且炎症通路与线粒体能量代谢障碍存在交叉对话现象.由此从"瘀热虚滞"的病机角度,结合炎症机制和线粒体能量代谢过程,探索性阐释"瘀""热""虚""滞"导致冠心病伴焦虑抑郁的发病内涵,可以为中医药治疗该病提供一定的思路.

BackgroundAlzheimer's Disease (AD) as an age-related, irreversible neurodegenerative disease, characterized by cognitive dysfunction, has become progressively serious as a result of a global increase in life expectancy. As more mechanism of AD were discovered, therapeutic strategies using traditional Chinese medicine are under investigation for AD treatment, with efforts to improve efficacy and clarify the mechanism. Gastrodia, elata Blume, Polygala tenuifolia Willd . , Cistanche deserticola Ma , Rehmannia lutinosa (Gaertn.)DC. ,Acorus gramineus Aiton , and Curcuma longa L. are well-known chinese herbs with neuroprotective effects and widely used as a combination in traditional Chinese decoction for AD treatment. The purpose of this study was to investigate the synergistic protective efficacy of the combination (composed of extracts from these six Chinese medicines, CuraUltra), and the protein targets on scopolamine-induced cognitive impairment, using the proteomics analysis.MethodsScopolamine-induced cognitive impairment mouse model was established. Behavioral tests, Nissl Staining, cerebral cholinergic system alterations and neuronal apoptosis characteristics were examined to evaluate the ameliorating effects of CuraUltra on cognitive impairment induced by scopolamine. To identify the potential molecular mechanism responsible for the effect on CuraUltra treatment, label-free quantitative proteomics by tandem mass spectrometry (LC-MS/MS) were performed. Critical altered proteins were validated by qPCR and Western blotting. Molecular docking was finally performed to evaluate the binding potential of chemical components with the target proteins.Results Administration of CuraUltra significantly recovered scopolamine-induced cognitive impairment, as evidenced by the improved learning and memory ability, reduced pathological damage of hippocampus, increased content of Ach, decreased activity of AchE, and ameliorated expression levels of the neuronal apoptosis-related protein in the hippocampus of mice. Using quantitative proteomics technology, we observed 252 differentially expressed proteins. Compared with the model group, after CuraUltra treatments, a remarkedly alteration in PPP3CC , PKA , P38MAPK , RASA4 , DNAJB1 , SNAPIN was also observed. Notably, several significant proteins are in the glutamatergic synapse signaling pathway. Moreover, we confirmed that the PPP3CC appears to decreased as the AD pathological development, and may be positively correlated with the phosphorylation level of PKA , thereby inhibiting the activation of P38MAPK phosphorylation.ConclusionsAdministration of CuraUltra was effective on alleviating scopolamine-induced cognitive impairment, which might be through modulation of glutamatergic synapse. Consequently, our quantitative proteome data obtained from scopolamine-treated model mice successfully characterized AD-related biological alterations and proposed novel protein biomarkers for AD.

一、花椒 说到花椒,大家的第一反应就是麻辣的川菜,它不仅可以除去各种鱼类、肉类的腥膻臭气,也可增进食欲.不过,除了此用途之外,花椒还是一味流传千年、历史悠久的中药. 花椒:味辛、性温,归脾、胃、肾经,具有温中止痛、除湿止泻、杀虫止痒、解鱼腥毒的功效,可以用来治疗脾胃虚寒湿胜所致的腹痛腹泻,亦可治疗虫积腹痛、湿疹、阴痒等症.

目的:以某中医药大学中医药文化进校园志愿服务活动为中心,调研该活动的实施现状和存在问题,探索进一步完善该活动的策略和路径,以更好推动中医药文化进校园活动的深入开展.方法:对参与该志愿活动的某中医药大学大学生志愿者及三所合作学校的中小学生进行问卷调查,并对调研数据进行统计分析.结果:95.84％的小学生、91.30％的初中生、96.29％的高中生对志愿者的授课内容表示"比较理解"和"完全理解".83.33％的小学生、69.57％的初中生、77.78％的高中生表示以后只要"开设相关课程就会参加".94.83％的志愿者参与活动的目的是"为中医药文化传播贡献力量".结论:该志愿服务活动得到了中小学生和大学生志愿者的普遍认可和欢迎,但仍存在较大提升空间,大学生志愿者自身素质是影响该志愿服务活动效果的主要因素,充分发挥该志愿服务活动各参与方的作用,着力提升大学生志愿者综合素质,是提升该志愿服务活动效果的最佳路径.

新型冠状病毒肺炎(COVID-19)属广义温病的范畴,遵循温病卫气营血传变规律,除了典型的呼吸系统症状外,还可出现心脏并发症.本文从逆传心包角度分析了肺炎相关心脏并发症的可能原因,并根据目前的诊疗指南总结其证候及治疗.原因可能与体质因素、疫毒致病力、失治误治相关,根据疫毒扰神、邪闲心包、心阳虚脱、气虚络阻证等不同的证候采取相应的针药治疗,并针对心脏轻症提出了治疗建议.中医药应发挥在救治传染病和危重症方面的优势,尽早干预,全程参与.

本文介绍运用升降散治疗顽固性嗳气验案1则.

目的 研究急性脑出血大鼠应激性肝损害细胞因子信号转导抑制因子1(SOCS1)与白细胞介素-1受体相关激酶(IRAKs)的交叉对话及涤痰通瘀方对其的调控作用.方法 将SD大鼠随机分成脑出血组、涤痰通瘀组、正常组.建立大鼠急性脑出血模型,采用免疫共沉淀法检测SOCS1与I RAK-1、2、4、M之间的相互作用,并观察造模后不同时相点各组大鼠肝组织病理染色结果.结果 SOCS1与IRAK-1、2、4、M可以相互作用,对急性脑出血大鼠肝损害起到一定的保护作用,同时涤痰通瘀方对SOCS1/IRAKs交叉对话有一定的调控作用.结论 SOCS1/I RAK-1、2、4、M相互作用,对LPS细胞内信号转导炎性级联反应起到抑制效应,在肝损害保护效应中发挥关键作用.经涤痰通瘀方干预后,可以有效改善肝组织病理学结构,是防治脑出血应激性肝损害的重要途径.

Objective To investigate the influence of Chaihu Longgu Muli Tang(Chinese Thorowax Root, Bone Fossil of Big Mammals and Oyster Shell Decoction, CLMT) on the mobilization of bone marrow c-kit+stem cells in rats after myocardial infarction(MI). Methods Male SD rats were randomly divided into sham-operation group,model group and CLMT group,and each group was divided again into 3-d sub group,7-d subgroup and 14-d subgroup. The CLMT group was intragastrically given CLMT, and other groups were orally given distilled water. The heart function was reviewed by using echocardiogram, changes of myocardial pathology were reviewed after HE staining,and severity of myocardial fibrosis was observed by after Masson staining. The number of c-kit+positive cells in bone marrow and peripheral blood was detected by using flow cytometry (FCM), and number of c-kit+positive cells in MI border zone was detected by using immunohistochemistry technique. Results The heart function declined gradually along with MI time extension in model group, and difference in heart function had statistical significance compared with sham-operation group at all time points (P <0.05). The heart function trended to stable in CLMT group and was better than that in model group, and difference in LVEF and LVFS had statistical significance compared with model group at time points of 7 d and 14 d(P<0.05). Pathological staining showed that myocardial cells were in alignment without collagen fibers in sham-operation group,necrosis and fibrosis of myocardial cells in model group that aggravated gradually along with MI time extension. The severity of myocardial necrosis and fibrosis was milder in CLMT group than that in model group. The number of c-kit+positive cells in bone marrow and peripheral blood reached peak in model group and CLMT group 7 d after MI, and difference number of c-kit+positive cells had statistical significance compared with sham-operation group,and was higher in CLMT group than that in model group. The difference in number of c-kit+positive cells had statistical significance between 7-d subgroup and 14-d subgroup (P <0.05). The number of c-kit+positive cells in MI border zone was higher in model group than that in sham-operation group,and difference in number of c-kit+positive cells had statistical significance between 7-d subgroup and 14-d subgroup (P<0.05). The number of c-kit+positive cells in MI border zone was higher in CLMT group than that in model group, and difference in number of c-kit+positive cells MI border zone had statistical significance between 7-d subgroup and 14-d subgroup (P<0.05). Conclusion CLMT can improve the mobilization of bone marrow c-kit+stem cells after MI and heart function.

Ischemic myocardium initiates the mobilization and homing of bone marrow mesenchymal stem cells (BM-MSCs) to promote myocardial regeneration after acute myocardial infarction (AMI). Inflammation caused by necrotic cardiomyocytes induce major pathological changes (cardiac remodeling and myocardial apoptosis) as well as anxiety disorder. This process may be inhibited by the differentiation and paracrine effects of BM-MSCs. However, the spontaneous mobilization of BMSCs is insufficient to prevent this effect. Given the anti-inflammatory effects of BM-MSCs, ventricular remodeling and anxiety following AMI, methods focused on enhancing BMSCs mobilization are promising. BFG is a classical traditional Chinese prescription medicine and has been proved effective in treating AMI and reducing anxiety, but the potential mechanism of its function remains unknown. In the present study, we explored the effects of Chaihulonggumulitang (BFG) on AMI and anxiety in vivo and in vitro . We also tested its effects in promoting BMSCs mobilization and alleviating inflammation. Our data showed that the classical Chinese prescription BFG promoted BM-MSCs mobilization, inhibited inflammatory response, and improved heart damage and anxiety developed from AMI. Thus, we provided an underlying mechanism of BFG function in psycho-cardiology conditions such as AMI.