Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

BACKGROUND Chronic heart failure is a complex clinical syndrome.The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not clear.AIM To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure.METHODS The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target genes of chronic heart failure were searched in the Genecards database.The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 software.The protein-protein interaction network was constructed using the String database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database.Finally,our previously published relevant articles were searched to verify the results obtained via network pharmacology.RESULTS A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MAPK3,AKT1,JUN,MAPK1,TP53,TNF,HSP90AA1,p65,MAPK8,MAPK14,IL6,EGFR,EDN1,FOS,and other proteins.The pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-kappaB signaling pathway,AMPK signaling pathway,etc.Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MAPK,cAMP,and AMPK pathways to affect the mitochondrial structure of myocardial cells,oxidative stress,and energy metabolism,thus achieving the therapeutic effects on chronic heart failure.CONCLUSION The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes,oxidative stress,energy metabolism,and other processes.Future studies are warranted to investigate the role of the IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Efficacy and safety of Guipi Decoction combined with conventional Western medicine in the treatment of insomnia with deficiency of heart and spleen:a meta-analysis

Objective:To systematically evaluate the efficacy and safety of Guipi Decoction combined with Western medicine in the treatment of insomnia with deficiency of heart and spleen.Methods:English databases(PubMed,Web of Science,The Cochrane Library,EMBASE)and Chinese databases(CNKI,Wanfang database,China Biomedical Literature Service System,VIP database)were searched by computer.Randomized controlled trials of Guipi Decoction on insomnia with deficiency of heart and spleen were searched from the database construction to November 2021.After the first and second authors independently screened the literature,extracted the data and evaluated the risk of bias in the included studies,meta-analysis was performed using RevMan5.3 software.Results:A total of 9 RCTS were included after screening,including 914 patients.Meta-analysis results showed that:Total effective rate[RR=1.22,95%CI(1.16,1.30),P<0.00001],total PSQI score[MD=-3.05,95%CI(-3.96,-2.14),P=0.008],number of night awakening times[[MD=-1.18,95%CI(-1.42,-0.94),P<0.00001],adverse reaction rate[RR=0.32,95%CI(0.21,0.51),P<0.00001]were better than the control group,and the differences were statistically significant.Conclusion:The current evidence shows that,compared with pure using conventional western medicine,belongs to the spleen decoction combined western medicine therapy,cases both deficiency type of insomnia in the total effective rate,reducing the total PSQI score(improve sleep quality,sleep efficiency,sleep disorder,daytime function,etc.),reducing frequency of nighttime awakening,security,have more advantages.However,due to the limitation of the quality and quantity of articles included in the study,more randomized,double-blind,large-sample clinical studies are needed to confirm the above conclusions.

Clinical Observation on the Treatment of Insomnia in Germany with Deficiency of Heart and Spleen by the Ear Bean Therapy

Objective: To observe the effect of insomnia patients with deficiency of heart and spleen in Germany by the therapy of ear points pressing with bean. Methods: A total of 80 cases of insomnia with deficiency of heart and spleen in Germany were divided into the observation group and the control group, with 40 cases in each group. The patients in the control group were treated with oral modified Guipi Decoction(归脾汤), while the patients in the observation group were treated with oral traditional Chinese medicine(TCM) and the therapy of ear points pressing with bean. The efficacy, sleep quality, the TCM syndromes score and the incidence of adverse reactions were compared between the two groups. Results: The effective rate in the observation group was higher than that in the control group, and there was statistical difference between the two group(P<0.05). After treatment, the Pittsburgh sleep quality index scale(PSQI) score, insomnia severity index(ISI) score and the TCM syndromes score in the two groups were decreased sharply(P<0.01), and those scores in the observation group were lower than that in the control group(P<0.05). There was no adverse reaction between the two groups. Conclusion: The therapy of ear points pressing with bean is effective on insomnia in Germany, which is worth further study and promotion.

Regulating and tonifying spleen and kidney traditional Chinese medicine in the treatment of chronic uric acid nephropathy: A systematic review

Objective:To systematically evaluate the efficacy and safety of traditional Chinese medicine for regulating spleen and kidney.Methods:We developed a search strategy and then retrieved the database including CNKI,Wanfang data knowledge service platform,VIP journals resource integration service platform,PubMed,Embasefor randomized controlled trial of regulating spleen and kidney traditional Chinese medicine compared with conventional western medicine in the treatment of chronic uric acid nephropathy.The search deadline was set to June 30,2020.For the included literature,we applied the cochrane collaboration network risk bias assessment tool to evaluate the methodological quality,and evaluated the level of evidence according to GRADE standards.Quantitative data was analyzed by RevMan5.3 software,and trial sequential analysis method was used to analyze its efficiency.Results:A total of 709 cases in 10 articles were included.Compared with the control group,the related traditional Chinese medicine group improved the effective rate[RR=1.45,95%CI(1.32,1.58)],reduced the level of UA[MD=-36.24,95%CI(-41.03,-31.45)],BUN[SMD=-1.27,95%CI(-1.47,-1.07)]and SCR[MD=-36.33,95%CI(-55.79,-16.87),P=0.0003],the difference between the two groups was statistically significant(P<0.05).There was no evidence that a significant adverse reaction occurred.The results of TSA analysis showed that the Chinese medicine group had definite evidence for improving the efficiency.According to the GRADE evaluation criteria,the efficiency,UA,BUN and SCR outcome indicators were extremely low-quality evidence.Conclusions:Traditional Chinese medicine for regulating spleen and kidney in the treatment of chronic uric acid nephropathy improved efficiency,reduced the level of UA,BUN,SCR.Meanwhile,the therapy was proved to be safe.Nevertheless,the conclusions need further high-quality evidence to support.

ACUPUNCTURE TREATMENT FOR 100 CASES WITH INSOMNIA OF THE TYPE OF THE HEART AND SPLEEN DEFICIENCY

cases of insomnia of the type of heart and spleen deficiency were treated by acupuncture.Results indicated that 95 cases were cured,accounting for 95%;3 cases were markedly effective,accounting for 3% and the 2 cases were ineffective,accounting for 2%,the total effective rate was 98%.

Optimized new Shengmai powder(优化新生脉散方) inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder(优化新生脉散方, ONSMP) on myocardial fibrosis in heart failure(HF) based on rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham(n = 10) and operation(n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low(L), medium(M), and high(H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen(COL) Ⅰ and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the m RNA levels of COL Ⅰ, COL Ⅲ, α-smooth muscle actin(α-SMA), and c-Fos proto-oncogene(c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor(p-ELK1), p-c-Fos, α-SMA, COL Ⅰ, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL Ⅰ/Ⅲ content, down-regulate the m RNA of COL Ⅰ/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

Preoperative application of combination of portal venous injection of donor spleen cells and intraperitoneal injection of rapamycin prolongs the survival of cardiac allografts in mice

Objective:To investigate the effects of preoperative portal venous injection of donor spleen cells(PVIDSC) and intraperitoneal injection of rapamycin in the acute rejection of cardiac allograft in mice and the underlying mechanisms. Methods:Homogenous female B6 mice and BALB/c mice were used as recipients and donors of heart transplantation. These mice were randomly divided into different groups and received PVIDSC alone,rapamycin alone,or PVIDSC and rapamycin combined therapy. In addition,the underlying mechanism was studied by measuring a number of cytokines. Results:Preoperative combination of PVIDSC and intraperitoneal injection of rapamycin significantly prolonged the survival of heterotopic cardiac allograft in mice,but had no effects on the survival time of cardiac allografts in mice pre-sensitized by skin grafting. Preoperative combination of PVIDSC and intraperitoneal injection of rapamycin increased the expression of IL-10 and Foxp3 and reduced the expression of INF-γ. Short-term preoperative administration of rapamycin promotes the expression of CD4^+CD25^+Foxp3^+ regulator T cells. However,preoperative using alone of rapamycin,or combination of PVIDSC and rapamycin had no effects on the inhibition of proliferation of memory T cells. Conclusions:Preoperative application of combination of PVIDSC and rapamycin significantly prolonged the survival time of cardiac allografts in mice but not in mice pre-sensitized by skin grafting. This may be explained by the fact that combination of PVIDSC and rapamycin inhibited the cellular immune response and induced the expression of IL-10 from Tr1 cells and CD4^+CD25^+FoxP3^+ regulatory T cells.

Theoretical Discussion on Treatment of Cubital Tunnel Syndrome Based on Theory of Liver,Spleen and Kidney

Cubital tunnel syndrome is a disease in which ulnar nerve is compressed by its surrounding tissues,and its main clinical manifestations are pain,sensory disturbance and dyskinesia.Its incidence rate is the second highest among peripheral nerve entrapment diseases,and it is one of the common clinical diseases.The theory of liver,spleen and kidney can guide the treatment of cubital tunnel syndrome with traditional Chinese medicine and acupuncture.By discussing the traditional Chinese medicine(TCM)pathogenesis and treatment principles of cubital tunnel syndrome,it provides modern medical theoretical support for TCM treatment of cubital tunnel syndrome.

三七总皂苷对肺心病兔肺纤维化组织Cathepsin B表达的影响

目的从病理学角度研究三七总皂苷对肺心病兔肺纤维化Cathepsin B表达的调控.方法健康日本大耳兔40只,随机分为五组,每组8只,分别为正常对照组、肺心病模型组、三七总皂苷预防组、治疗组及西药治疗组.观察光镜下五组动物CB蛋白的表达及肺组织的病理结构变化.结果与模型组相比,三七总皂苷预防组能明显减轻肺泡水肿,减轻肺间质、肺细小动脉及肺泡壁纤维化,明显减少肺泡水肿液及炎细胞渗出,降低CB蛋白在肺组织中的表达;三七总皂苷治疗组及西药治疗组也有上述作用,但不及三七总皂苷预防组明显.结论三七总皂苷能明显改善肺心病兔肺纤维化的程度,显降低CB蛋白在支气管上皮细胞和肺泡上皮细胞的表达,减轻致纤维化因素对肺间质、肺部细小动脉及肺泡壁的病理损伤,对肺心病肺脏损伤具有保护作用.

THE OUTLINES OF THE PROFICIENCY EXAMINATION FOR INTERNATIONAL ACUPUNCTURE & MOXIBUSTION PROFESSIONALS

I International Professional Acupuncturists Proficiency Examination (On Probation) The Test Outline for Basic Theory of Traditional Chinese Medicine Basic Characteristics of Traditional Chinese Medicine1.1 The meaning and basic content of the integrated concept.1.2 The implications of treatment according to differentiation of syndromes; differentiating syn- dromes and diseases.2. Yin-Yang and Five

基于“肝脾同调”阐析慢性肝病的中医治疗

慢性肝病是临床常见疾病,“郁、虚、湿、毒、瘀”是其核心病机,在疾病的不同阶段各有侧重,其中,以“郁、虚”为核心的肝脾失调是慢性肝病发生发展的关键。“肝脾同调”是治疗慢性肝病的基本治法,在慢性肝病不同阶段,其“肝脾同调”内涵同中有异。根据肝、脾生理病理特性,治脾明辨虚实,厘清轻重,活用运脾、健脾、温脾、醒脾、补脾等法;调肝体用并重,精准辨证,活用疏肝、缓肝、散肝、柔肝等法。临床上,治脾与调肝相辅相成,治调并举,常获良效。

李延从脾胃论治冠心病的临床经验

冠心病为临床中常见的心血管疾病,可归属中医学的“胸痹”“心痛”等疾病范畴。李延教授认为本病之病性总属本虚标实之证,以脾虚、脾胃健运失常为本,标实在于痰浊、血瘀、气滞、寒凝等有形实邪痹阻心脉。治疗时重视调理脾胃,重用黄芪、白术、党参、五味子等健脾养心以治本,结合通阳化浊、活血化瘀、疏肝理气、温阳散寒等治法,标本兼治,通补兼顾,使脾气健旺,心气充沛,瘀去痰消,胸阳得以舒展,则心之血脉恢复畅通,胸痹心痛诸症得到缓解。李延教授从脾胃论治冠心病的经验可为中医临床诊治冠心病提供参考。

皮内针联合子午流注五音疗法用于心脾两虚型不寐临床观察

目的探讨皮内针联合子午流注五音疗法对心脾两虚不寐症患者的临床效果。方法选择天水市中医医院脾胃病科2021年5月—2021年10月入住的心脾两虚型不寐患者100例,根据随机数字表法分为对照组、观察组,各50例。对照组给予皮内针干预,观察组在对照组基础上加用子午流注五音疗法干预,2周后比较两组总有效率、匹兹堡睡眠质量指数(PSQI)得分。结果观察组总有效率为94.00%(47/50),高于对照组的74.00%(37/50),差异有统计学意义(P<0.05);干预后,两组PSQI得分较干预前均下降,且观察组低于对照组,差异有统计学意义(P<0.01)。结论皮内针联合子午流注五音疗法能有效改善心脾两虚型不寐患者的睡眠质量,值得临床推广应用。

基于“心受气于脾”论治类风湿关节炎累及心脏病变

类风湿关节炎累及心脏病变属于复合病证,根据其发病过程与临床表现,可归属于中医学“脏痹-心痹”。心痹为痹证日久缠绵不愈,复感风、寒、湿邪,向内传入于心所致。该文基于“心受气于脾”理论探讨其病因、病机与治疗。通过梳理古代文献,发现类风湿关节炎累及心脏病变的病因为脾气不足,卫阳不固,外感风、寒、湿邪气侵入机体,瘀血顽痰阻滞发为心痹。其病机为脾气不足,营卫虚弱;脾阳不足,痰浊内生;脾失健运,痰瘀互结。现代研究表明,细胞免疫失调、血脂异常以及血凝与类风湿关节炎合并心脏病变关系密切,这与中医病机一致。在治疗时选用补益卫阳,和营通痹;温阳散寒,化痰逐饮;益气活血,健脾祛痰之法,代表方剂分别为黄芪桂枝五物汤、苓桂术甘汤、赤茯苓汤。该文提出“心受气于脾”理论,为临床治疗类风湿关节炎累及心脏病变提供思路与指导。

象性合参论远志效用特色与优势

采用药性与法象理论合参方法,融合现代药理与临床认识,阐释远志双调心神的作用机制,为远志治疗难治性病证提供药学与临床依据。研究发现,远志的特殊药象是其宁心安神功效的药材学基础,结合其“辛烈开窍”的性能特点,采用象性合参的方法,不仅有助于理解远志双调心神的特殊功效及其“安神不闭窍,开窍不动神”的药效特点,而且对认识用其治心神疾患、睡眠紊乱以及惊风、中风、癫痫等病证的作用优势,也提供了“象思维”的路径。象性合参还可揭示远志交通心肾的作用机制,并与其双调心神作用结合,拓展治疗心神失常之应用范围。因此,运用象性合参阐释远志的多重药理效用,是探析其治疗疑难杂病机制的重要方法。

果蝇心脏发育研究三十年进展

果蝇(Drosophila melanogaster)作为最早用于研究心脏发育基因调控的模式生物,已经走过三十年的历程。果蝇心脏发育过程经历了胚胎期、幼虫期和成虫期三大阶段。在胚胎早期,Tinman、Dorsocross和Pannier等基因是关键的调控因子。Tinman参与最早的心脏前体细胞分化和心脏细胞形成,而Dorsocross和Pannier则影响心脏前体细胞的定向分化和心脏管腔的形成。进入胚胎晚期和幼虫期,果蝇的心管经历进一步的发展和重塑,该过程主要受到转录因子Hand、Mef2以及Hox基因家族的调控。在成虫期,Hox基因家族和Tinman依旧发挥重要作用。虽然果蝇心脏与脊椎动物成熟心脏存在形态上的差异,但两者心脏的早期发育过程以及调控基因和信号通路都有保守性。本文综述了果蝇心脏发育基因调控研究的三十年进展以及利用果蝇模型研究人类心脏相关疾病的潜在希望。

“肝脾同调-血水同治”对增殖性糖尿病性视网膜病变PPV围手术期的影响

目的探究“肝脾同调-血水同治”对增殖性糖尿病性视网膜病变(proliferative diabetic retinopathy,PDR)玻璃体切除术(pars plana vitrectomy,PPV)患者围手术期的影响。方法选取2021年6月—2023年6月本院收治的63例PDR患者,按照简单随机法分为常规组(n=31)和同调组(n=32),常规组给予常规围术期治疗(术前3~5 d至术后7 d),同调组在常规组基础上实施“肝脾同调-血水同治”治法,比较2组临床指标、并发症(高眼压、玻璃体积血、视力下降)、眼压、炎症反应分级(前房闪辉、前房炎症细胞、纤维蛋白渗出),干预前后炎症因子水平[前房液白细胞介素-6(Interleukin-6,IL-6)、血清C反应蛋白(C-reactive protein,CRP)]。结果同调组手术时间、住院时间低于常规组(P<0.05);2组并发症总发生率比较无统计学意义(P>0.05);术后1 d、3 d,2组眼压均随时间延长而下降(P<0.05),且术后1 d同调组低于常规组(P<0.05);术后1 d、1周,2组前房闪辉、前房炎症细胞和纤维蛋白渗出评级随时间延长明显减轻(P<0.05),且术后1 d同调组前房闪辉评级明显低于常规组(P<0.05);术后1 d、1周,2组前房液IL-6、血清CRP均随时间延长而降低(P<0.05),且同调组均低于常规组(P<0.05)。结论“肝脾同调-血水同治”应用于PPV治疗的PDR患者,可减少患者围术期并发症,有效控制炎症反应,缩短手术时间和住院时长,具有临床应用价值。

从“虚瘀劫肝”论原发性肝癌中医药防治思路

理论创新是中医药发展的源泉,在新理论指导下形成的新方药或新诊治方案是中医药临床防治重大疑难疾病的新突破口。正邪交争,正不胜邪是慢性疾病持续进展的内在驱力和一般特性,慢性肝病持续恶性进展囊括了:肝纤维、肝硬化、肝癌等逐步恶化的病理进程。其在遵循中医“正不胜邪”基本病机的基础也必须有其特殊性和指向性,也可理解为在慢性肝病持续进展的病理状态下将一般性的病机进行指向性和特征性的阐发。肝正虚主要是指维持正常肝再生修复的相关机制和途径异常或紊乱,肝邪胜则是指肝损伤因素持续存在及其下游触发的恶性肝再生状态进行性亢进;而“瘀”作为正邪交争过程中产生的最主要病理产物也在不断推动疾病的恶性发展。在此基础上,从“虚瘀劫肝”论肝癌的病理新认识及补虚(补肾生髓、健脾)祛瘀(疏肝、柔肝、化肝)阻断慢性肝病持续恶性进展以防治肝癌的基本思路,期望有益于疑难肝脏病症的临床防治。

加裁调脾护心方治疗高血压心脾两虚证的临床研究

目的:观察加裁调脾护心方治疗高血压心脾两虚证的临床疗效。方法:选取2022年10月—2023年11月就诊于安徽中医药大学第一附属医院心内科的高血压病人60例,采用随机数字表法分为治疗组与对照组,每组30例。对照组予以常规西药规范治疗,治疗组在对照组基础上加用加裁调脾护心方。观察两组中医证候积分、中医证候疗效、匹兹堡睡眠质量指数(PSQI)评分、生活质量评价量表(SF-36)评分。结果:治疗4周后,两组中医证候积分较治疗前下降(P<0.05),且治疗组低于对照组(P<0.05);治疗组中医证候疗效总有效率高于对照组,差异有统计学意义(P<0.05)。两组治疗后PSQI评分、SF-36评分均较治疗前改善(P<0.05),且治疗组改善程度优于对照组(P<0.05)。结论:加裁调脾护心方可减轻病人临床症状,提高睡眠质量,改善生活质量。