Comparing the mechanism of four classic Gualou-Xiebai prescriptions for cardiovascular diseases with phlegm and blood stasis syndrome based on molecular network modeling

Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.

Effect of Gualou Xiebai Banxia decoction combined with Danshen Decoction on clinical efficacy of unstable angina with phlegm and blood stasis syndrome

Objective:To observe the clinical efficacy and safety of Gualou Xiebai Banxia decoction combined with Danshen decoction on unstable angina(UA)with phlegm and blood stasis syndrome.Method:Eighty patients with UA were randomly divided into treatment group(40 cases)and control group(40 cases)by random number table.The control group was given conventional western medicine treatment,and the experimental group was given Gualou Xiebai Banxia decoction and Danshen decoction on the basis of the control group.Both groups were treated for 4 weeks.Before and after treatment,the angina attacks,dosage of nitroglycerin,traditional Chinese medicine syndrome score,quality of life score,blood lipid,coagulation index and clinical total efficacy were observed and recorded.Results:After 4 weeks of treatment,the attack times and duration of angina in the two groups were both decreased compared with those before treatment.And the treatment group was more significantly reduced than the control group,the difference was statistically significant(p<0.05);the consumption of nitroglycerin of the treatment group was 90.0%,which was better than 67.5%of the control group,the difference was statistically significant(p<0.05);the total effective rate of the treatment group was 90%,which was better than 65%of the control group,the difference was statistically significant(p<0.05);the traditional Chinese medicine(TCM)syndrome score of the experimental group was lower than that of the control group,the differences was significant(p<0.05).The improvement of low density lipoprotein(LDL-C),total cholesterol(TC)and prothrombin time(PT)in the experimental group was better than that in the control group(p<0.05).During the study,there were no obvious adverse reactions in both groups.Conclusion:Gualou Xiebai Banxia decoction combined with Danshen decoction can effectively relieve the attack of angina and the consumption of nitroglycerin,improve clinical symptoms,regulate blood lipid and blood flow state,and improve the quality of life of patients with UA,with good clinical efficacy and safety.

Efficacy of Danlou Tablet in the Treatment of Coronary Heart Disease with Phlegm and Blood Stasis Syndrome and Its Effects on Serum Inflammatory Factors

[Objectives] To explore the efficacy of Danlou Tablet( DLT) in the treatment of coronary heart disease( CHD) with phlegm and blood stasis syndrome and its effects on serum inflammatory factors. [Methods]One hundred and ninety-seven patients with CHD and phlegm and blood stasis syndrome in our hospital from January 2016 to January 2018 were selected and randomly divided into two groups: control group( n =98) treated with aspirin plus atorvastatin,and research group( n =99) treated with DLT and aspirin plus atorvastatin for one month. The clinical efficacy and incidence of adverse reactions were observed. Serum secretory phospholipase A2( s PLA2),lipoprotein-associated phospholipase A2( LP-PLA2),oxidized low-density lipoprotein( ox-LDL),monocyte chemoattractant protein-1( MCP-1) and World Health Organization Quality of Life( WHOQOL-100) scores were compared before and after one month of treatment. [Results] The total effective rate was93. 94% in the research group,which was higher than that in the control group( 79. 59%,P < 0. 05);the levels of serum s PLA2,LP-PLA2,ox-LDL and MCP-1 in the research group were lower than those in the control group after one month of treatment( P < 0. 05). There was no statistical significance of the difference in the total incidence of adverse reactions between the research group and the control group( P > 0. 05).After one month of treatment,WHOQOL-100 scores were higher in two groups,which were higher in the research group than that in the control group( P < 0. 05). [Conclusions]DLT can significantly reduce the level of serum inflammatory factors,improve the quality of life in patients with CHD and phlegm and blood stasis syndrome.

The research idea of Xuebijing injection in influencing severe pneumonia-pulmonary fibrosis with blood stasis syndrome evolution by inhibiting inflammation, endotoxin and dispersing blood stasis

Severe pneumonia is one of the most serious infectious diseases.Delayed intervention may lead to pulmonary fibrosis,which greatly threatens people’s life and health.Blood stasis syndrome is an important underlying syndrome throughout the evolution of severe pneumonia-pulmonary fibrosis.Xuebijing injection(XBJ)was developed under the theoretical system of“Three syndromes and three methods”,demonstrating a good efficacy in treating severe pneumonia and pulmonary fibrosis due to its effect of removing blood stasis and dispersing toxins.Previous studies have shown that XBJ can protect vascular endothelial function,improve coagulation function and regulate immunity by inhibiting inflammatory.Hence,the research hypothesis is put forward that XBJ treats blood stasis syndrome by removing blood stasis and dredging blood vessels,to inhibit the disease progress of severe pneumonia to pulmonary fibrosis.Further researches are need to confirm the function and explore the mechanism of XBJ.

淋巴瘤证型及其“痰瘀”证素与趋化因子及凝血指标的相关性研究

目的分析淋巴瘤证型和主要病性证素“痰瘀”与常见趋化因子及其受体、凝血指标的相关性,初步探讨淋巴瘤“痰瘀”证素的现代科学本质。方法选择198例淋巴瘤患者,统计并分析不同证型患者趋化因子及受体(CXCL2、CXCR2、CXCL8、CXCL12、CXCR4)和凝血指标(PT、APTT、FIB、FDP、D-D)水平差异;并采用二元Logistic回归分析探讨“痰”、“瘀”与上述各指标的相关性。结果CXCL2、CXCR2、CXCR4、CXCL8、PT、APTT、FIB、FDP、D-D在不同证型中均有差异(P<0.05),在痰瘀互结证型的表达水平高于其他证型(P<0.05);CXCL12在不同证型之间的水平差异无统计学意义(P>0.05)。痰、瘀是淋巴瘤最主要的病性证素,其中CXCR2、CXCR4、D-D、FIB对“痰”有影响,D-D与“瘀”有密切相关性。结论淋巴瘤证型、“痰瘀”证素与常见趋化因子及其受体、凝血指标具有明确相关性,趋化因子和凝血功能异常可能是淋巴瘤“痰瘀”证素相关的生物标志物。

身痛逐瘀汤加味联合盐酸普拉克索片治疗痰瘀痹阻型不宁腿综合征的临床观察

目的观察身痛逐瘀汤加味联合盐酸普拉克索片治疗痰瘀痹阻型不宁腿综合征(RLS)患者的临床疗效。方法将50名痰瘀痹阻型RLS患者按照随机数字表法分为2组,对照组25例予盐酸普拉克索片治疗,治疗组25例在对照组基础上联合身痛逐瘀汤加味治疗。2组均治疗1周为1个疗程,治疗2个疗程后统计疗效,比较2组治疗前后国际RLS严重程度评分量表(IRLS)评分、匹兹堡睡眠质量指数量表(PSQI)评分及中医症状评分变化情况。结果治疗组总有效率92.00%(23/25),对照组总有效率60.00%(15/25),治疗组总有效率高于对照组(P<0.05)。与本组治疗前比较,2组治疗后IRLS评分、PSQI评分及中医症状评分均降低(P<0.05),且治疗组治疗后IRLS评分、PSQI评分及中医症状评分均低于对照组(P<0.05)。结论身痛逐瘀汤加味联合盐酸普拉克索片治疗痰瘀痹阻型RLS疗效确切,可有效改善患者临床症状及中医症状,改善患者睡眠质量,操作简便,临床疗效显著,安全性良好。

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

Diagnostic Accuracy of Chinese Medicine Diagnosis Scale of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease: A Study Protocol

Background Phlegm and blood stasis syndrome(PBSS) is one of the main syndromes in coronary heart disease(CHD). Syndromes of Chinese medicine(CM) are lack of quantitative and easyimplementation diagnosis standards. To quantify and standardize the diagnosis of PBSS, scales are usually applied. Objective: To evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. Methods: Six hundred patients with stable angina pectoris of CHD, 300 in case group and 300 in control group, will be recruited from 5 hospitals across China. Diagnosis from 2 experts will be considered as the "gold standard". The study design consists of 2 phases: pilot test is used to evaluate the reliability and validity, and diagnostic test is used to assess the diagnostic accuracy of the scale, including sensitivity, specificity, likelihood ratio and area under the receiver operator characteristic(ROC) curve. Discussion: This study will evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. The consensus of 2 experts may not be ideal as a "gold standard", and itself still requires further study.(No. ChiCTR-OOC-15006599).

Correlation of Platelet and Coagulation Function with Blood Stasis Syndrome in Coronary Heart Disease: A Systematic Review and Meta-Analysis

Objective To investigate the correlation of platelet and coagulation function with blood stasis syndrome(BSS)in coronary heart disease(CHD).Methods The protocol for this meta-analysis was registered on PROSPERO(CRD42019129452).PubMed,Excerpta Medica Database(Embase),the Cochrane Library,and China National Knowledge Infrastructure(CNKI)were searched from inception to 1st June,2020.Trials were considered eligible if they enrolled BSS and non-BSS(NBSS)patients with CHD and provided information on platelet and coagulation function.The platelet function,coagulation function,and fibrinolytic activity were compared between the BSS and NBSS groups.Forest plots were generated to show the SMDs or ESs with corresponding 95%CIs for each study.Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity.Results The systematic search identified 1,583 articles.Thirty trials involving 10,323 patients were included in the meta-analysis.The results showed that mean platelet volume,platelet distribution width,platelet aggregation rate,platelet P selectin,fibrinogen,plasminogen activator inhibitor-1(PAI-1),thromboxane B2(TXB2),6-keto-prostaglandin F1alpha(6-keto-PGF1α),and TXB2/6-keto-PGF1αwere higher in the BSS group than in the NBSS group(P<0.05 or P<0.01).Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD(P<0.01).The R and K values in thromboelastography and tissue plasminogen activator(t-PA)and t-PA/PAI-1 were lower in the BSS group than in the NBSS group(all P<0.01).No difference was found in the results of platelet count,plateletcrit,maximum amplitude,von Willebrand factor,prothrombin time,thrombin time,international normalized ratio,etc.between groups.Conclusions Increased platelet function,hypercoagulability,and decreased fibrinolytic activity were found among CHD patients with BSS.

稳定型心绞痛证候特点及其痰瘀互结型的影响因素

目的:探讨稳定型心绞痛证候特点及其痰瘀互结型与理化指标的相关性分析。方法:选取2018年1月—2020年12月就诊于北京中医药大学东直门医院的稳定型心绞痛病人194例,统计受试者基线资料及相关实验室检查指标,并根据中医四诊信息归纳病人证候信息。结果:194例受试者中,痰瘀互结型86例(44.3%),气虚血瘀型52例(26.8%),气阴两虚型29例(14.9%),气滞血瘀型27例(13.9%)。单因素分析结果提示稳定型心绞痛的中医证候影响因素包括体质指数(BMI)、血红蛋白(Hb)及天门冬氨酸氨基转移酶(AST)。Logistic回归分析提示痰瘀互结型独立影响因素为BMI、Hb、AST。结论:稳定型心绞痛证候分布中痰瘀互结型占比最高;BMI、Hb、AST是稳定型心绞痛中医辨证为痰瘀互结型的独立影响因素。

不同系统疾病痰瘀互结证主要症状及特点探讨

目的 通过整理痰瘀相关证诊断标准的四诊信息,挖掘不同系统不同疾病痰瘀互结证的主要症状和相应特点,为构建普适性痰瘀互结证临床诊断标准提供基础。方法 系统检索中国期刊全文数据库(CNKI)、中文科技期刊数据库(CCD)、中国学术期刊数据库(CSPD)与中国生物医学文献数据库(CBM)、《中医病证诊断疗效标准》等收录的痰瘀相关证的标准、指南、共识,开展痰瘀相关证四诊信息的整理和条目筛选。检索日期为建库以来2021年10月1日。结果 最终纳入包含痰瘀相关证诊断标准的文献208篇。其中,病证结合类诊断标准文献共174篇,包含呼吸、循环、神经等九大系统,共计68种疾病。将其按照不同系统疾病进行分类,结果提示虽同为痰瘀互结证,但不同系统痰瘀互结证的临床症状与所涉疾病的病变特点差异较大,而局部肿块、疼痛、麻木在多系统疾病痰瘀互结证的临床表现上具有一致性,且舌脉一致性高。结论 痰瘀互结证是许多重大疾病尤其是慢性非传染性疾病的常见证候。其中,痰瘀互结证在不同系统疾病中,局部肿块、疼痛、麻木、舌脉等临床症状和体征一致性高,可以作为构建普适性痰瘀互结证诊断标准的基础。

大肠癌血瘀证与非血瘀证患者中性粒细胞、凝血功能与肿瘤指标的差异性分析

目的通过检测大肠癌血瘀证与非血瘀证患者血液中的中性粒细胞、凝血功能相关指标及肿瘤标志物,分析大肠癌血瘀证与非血瘀证患者中性粒细胞、凝血功能与肿瘤指标的差异性表达。方法回顾性分析300例大肠癌患者,分为血瘀证组与非血瘀证组,统计各组中性粒细胞数目、凝血功能相关指标(D-二聚体、纤维蛋白原、血小板、凝血酶原时间)和肿瘤标志物(CEA和CA19-9),对比分析各指标的差异表达。结果所入组大肠癌患者血瘀证与非血瘀证的比例约为1∶3。中性粒细胞计数值比较,血瘀证组明显高于非血瘀证组(P<0.0001)。血瘀证组D-二聚体(D-dimer)、纤维蛋白原(fibrinoger,FIB)、血小板(platelets,PLT)的表达均明显高于非血瘀证组(P<0.0001),血瘀证组凝血酶原时间(prothrombin time,TT)明显短于非血瘀证组(P=0.0122)。血瘀证组CEA、CA19-9的表达均明显高于非血瘀证组(分别为P=0.0002和P=0.002)。结论大肠癌血瘀证患者呈现血液高凝状态,大肠癌血瘀证患者的中性粒细胞计数和肿瘤标志物的表达均显著高于非血瘀证患者。

肺苏颗粒治疗慢性阻塞性肺疾病急性加重期痰热瘀肺证临床研究

目的观察肺苏颗粒治疗慢性阻塞性肺疾病急性加重期(AECOPD)痰热瘀肺证的临床疗效及对患者生活质量、凝血功能和免疫功能的影响。方法采用随机数字表法将120例患者分为观察组和对照组各60例。对照组予常规西医治疗,观察组在对照组基础上予肺苏颗粒口服,每次1袋,每日3次,连续7 d。观察2组临床疗效,比较2组治疗前后中医症状评分、圣乔治呼吸问卷(SGRQ)评分、凝血功能指标(纤维蛋白原、D-二聚体)、免疫功能指标(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)),并观察不良反应。结果观察组总有效率为93.10%(54/58),对照组为79.66%(47/59),2组比较差异有统计学意义(P<0.05)。与本组治疗前比较,2组治疗后中医症状积分及咳嗽、喘息、脉络瘀血评分,SGRQ评分均下降(P<0.05);2组治疗后比较,观察组上述评分均低于对照组(P<0.05)。与本组治疗前比较,2组治疗后血浆纤维蛋白原和D-二聚体含量均下降(P<0.05);2组治疗后比较,观察组血浆纤维蛋白原和D-二聚体含量均低于对照组(P<0.05)。与本组治疗前比较,2组治疗后外周血CD4^(+)和CD4^(+)/CD8^(+)均显著升高,CD8^(+)显著降低(P<0.05);2组治疗后比较,观察组外周血CD4^(+)和CD4^(+)/CD8^(+)高于对照组,CD8^(+)低于对照组(P<0.05)。2组均未出现药物相关的不良反应。结论在常规西医治疗基础上联合肺苏颗粒治疗AECOPD痰热瘀肺证可显著提高临床疗效,改善患者生活质量,利于凝血功能恢复,并增强细胞免疫功能。

基于病证结合的冠心病动物模型制备研究进展与思考

冠心病的临床研究和动物实验研究一直是心血管领域的常见病。病证结合动物模型体现了中西医结合的理念,不仅有西医的疾病特点,而且借助中医思维用不同实验方法来表现独特的中医证候特点,是中医药研究冠心病预防和治疗的有效工具。文章对常用冠心病中医证候的动物模型建立方法进行总结,并以冠心病痰瘀互结证动物模型为例提出思考。

基于动态尿液代谢组学探讨当归——桂枝干预寒凝血瘀证的作用机制

目的:基于1H NMR动态尿液代谢组学技术研究当归—桂枝干预寒凝血瘀证(CCBSS)的动态调控机制。方法:将15只SD雌性大鼠随机分成正常组、模型组及当桂3∶1组。通过体重变化、血液流变学和纤维蛋白原(FIB)指标评价模型构建成功与否,同时收集各组大鼠不同时间点(第0、第5、第10、第14天)的尿液样本进行1H NMR代谢组学分析,从代谢层面上阐明CCBSS的发病机制和当归—桂枝干预CCBSS的动态调控机制。结果:与模型组相比,当桂3∶1组大鼠在给予药物干预后其体重降低减缓,FIB指标回调(均P>0.05),同时血液流变学显著回调(P<0.01);动态尿液代谢组学结果显示,模型组的代谢轮廓在第5、第10、第14天与正常组明显区分,而当桂3∶1组的代谢轮廓也随着时间的推移逐渐与模型组区分并趋于正常组,基于多元统计分析共筛选出了18种与CCBSS相关的生物标志物,扰动了牛磺酸和低牛磺酸代谢等代谢通路,而当桂3∶1可显著回调这9种生物标志物(乳酸、吡哆醇、琥珀酸、牛磺酸、磷酸肌酸、马尿酸、4-羟基苯乙酸、2-氧戊二酸、柠檬酸)(均P<0.05),主要干预牛磺酸和低牛磺酸代谢、TCA循环等途径的紊乱。结论:CCBSS的发生发展是一个动态而缓慢的过程,当桂3∶1可通过回调不同时间点的不同代谢物而改善CCBSS。

肝豆灵汤治疗肝豆状核变性早期肾损害临床观察

目的:观察肝豆灵汤治疗痰瘀互结型肝豆状核变性患者早期肾损害的临床疗效。方法:选取安徽中医药大学第一附属医院符合肝豆状核变性早期肾损害诊断的住院患者70例,随机分为两组各35例。两组均予二巯基丙磺酸钠常规治疗,对照组另予百令胶囊,治疗组予肝豆灵汤口服,6天为1个疗程,共治疗4个疗程。观察两组患者临床疗效,比较治疗前后两组患者24小时尿铜、肾功能指标[肌酐(CREA)、尿素氮(BUN)、胱抑素C(CysC)]、尿系列蛋白指标[尿视黄醇结合蛋白(URBP)、尿β2微球蛋白(Uβ2-MG)、尿转铁蛋白(UTRF)、尿免疫球蛋白G(UIgG)、尿微量白蛋白(mALB)、尿α1微球蛋白(Uα1-MG)、尿N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)]、24 h尿总蛋白定量(24 hUPQ)、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)]及不良反应发生情况等。结果:治疗后,治疗组总有效率为91.43%,优于对照组的68.57%(P﹤0.05);两组24小时尿铜在治疗后均升高(P﹤0.05),治疗组升高幅度优于对照组(P﹤0.05);治疗组CREA、CysC、BUN水平降低,降低幅度优于对照组(P﹤0.05);治疗组URBP、Uβ2-MG、UTRF、UIgG、mALB、Uα1-MG、UNAG、24 hUPQ、UTP值均有所下降,且治疗组下降幅度优于对照组(P﹤0.05);两组患者的SOD、GSH-PX、CAT水平均明显上升,MDA水平明显下降(P﹤0.05),且治疗组改善程度优于对照组(P﹤0.05)。结论:肝豆灵汤能有效改善痰瘀互结型肝豆状核变性早期肾损害患者的症状,促进体内排铜,保护肾功能,改善早期肾损害,临床疗效较好。

基于转录组学分析降尿酸方对痰浊瘀阻型尿酸性肾病患者NLRP3/IL-1β信号通路的影响

目的:探讨降尿酸方对痰浊瘀阻型尿酸性肾病患者PBMCs中NLRP3/IL-1β的影响。方法:从一项单中心随机对照试验中随机选取6例受试者,其中试验组(降尿酸方联合非布司他治疗)和对照组(降尿酸方安慰剂联合非布司他治疗)各3例受试者。对试验组和对照组治疗前后与3例正常人群共15例样本的外周血白细胞进行mRNA-seq分析;提取试验组和对照组患者治疗前后的外周血单个核细胞,Western blot检测PBMCs中NLRP3、IL-1β蛋白水平差异,RT-qPCR检测PBMCs中NLRP3、Caspase-1、IL-18基因表达水平。结果:KEGG分析降尿酸方治疗后涉及到的通路有NOD样受体信号通路、NF-κB信号通路、Toll样受体信号通路等。试验组干预12周后PBMCs中NLRP3、IL-1β蛋白水平降低,NLRP3、Caspase-1、IL-18基因水平明显低于对照组(P<0.05)。结论:降尿酸方可以抑制痰浊瘀阻型尿酸性肾病患者NLRP3/IL-1β信号通路,减轻对肾脏的炎性损伤。

基于六维辨证观拆解慢性阻塞性肺疾病辨治体系

六维辨证观是综合多种辨证思维所提出的辨证观念,旨在从病因、病位、病期、病性、病势、病理等6个维度对疾病证态进行系统辨析,有利于临床把握整体,抓住机要。慢性阻塞性肺疾病(COPD)是一种以进行性气流受限和持续的呼吸道症状为特征的呼吸系统疾病,发病多责之于肺气本虚,内外感召或他脏及肺,常有慢性肺系疾病迁延日久或先天不足因素。病位主要在肺,最常波及脾肾,病久可牵连心肝及六腑,是典型的多系统复杂疾病。基本病机是本虚标实,即肺脾肾虚损,痰瘀互结成积,除见气虚气滞、阴阳虚损等病理状态外,还最常见痰饮瘀及微型癥瘕等病理产物。本病分期明确,卫气同病、气分期和气营同病阶段病情寒热之性及邪正之势多变,可因病邪性质、季节地域、体质等因素表现不一,需要谨慎判断和用药;气血同病阶段寒热错杂、虚实并见,治疗棘手,恰是中医药发挥优势的大好时机。

自拟消腺方配合外治法治疗小儿腺样体肥大痰凝血瘀证的临床观察

目的 探讨自拟消腺方配合中医外治法治疗小儿腺样体肥大痰凝血瘀证的临床疗效,旨在为中医内治外治结合治疗腺样体肥大提供可靠的依据。方法 选取2019年4月至2023年4月在福建中医药大学附属第二人民医院儿科接受治疗的80例腺样体肥大患儿进行研究,随机抽取40例作为对照组,予口服自拟消腺方治疗,40例作为观察组,在口服自拟消腺方治疗的基础上予穴位按摩治疗。观察和分析两组患儿的中医证候评分、体征、生活质量评分等疗效指标。结果 治疗前两组患儿的各项指标无显著性差异(均P> 0.05),具有可比性。治疗后,两组患儿主要证候积分、生活质量调查表(OSA-18)评分都有所改善,观察组患儿的改善程度更明显。观察组患儿的治疗总有效率高于对照组(P <0.05)。结论 自拟消腺方配合中医外治法治疗小儿腺样体肥大痰凝血瘀证的效果明确,能显著改善患儿生活质量。

基于TRAF2/AP-1信号通路探讨柴苓合剂对痰瘀互结MS-IR大鼠炎症因子影响

目的基于TRAF2/AP-1信号通路探讨柴苓合剂对痰瘀互结代谢综合征胰岛素抵抗(MS-IR)大鼠糖代谢、脂代谢、炎症因子的部分作用机制。方法48只SPF级SD雄性大鼠随机分为空白组和造模组。造模组大鼠采用高脂高糖饲料喂养,注射小剂量链脲佐菌素(STZ)(35 mg/kg),同时用物理刺激方法,建立痰瘀互结型MSIR大鼠模型。造模成功后将大鼠随机分为模型组,柴苓合剂低、中、高剂量组,西药组进行干预。给药各组分别进行柴苓合剂、吡格列酮干预治疗3周,空白组、模型组给予等体积的蒸馏水灌服。生化检测大鼠空腹血糖(FBG)、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR);ELISA法检测血清肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)水平;Western Blot检测肝组织TRAF2、JNK、AP-1蛋白表达;HE染色切片,光学显微镜观察用药前后肝细胞损伤、肝细胞坏死、脂质堆积、炎症细胞浸润等情况。结果(1)糖代谢指标水平。与空白组相比,模型组大鼠FBG、FINS、HOMA-IR水平均升高(P<0.01);与模型组相比,柴苓合剂低、中、高剂量组及西药组FBG、FINS、HOMA-IR水平均降低(P<0.01);与西药组比较,柴苓合剂高剂量组FBG、FINS、HOMA-IR水平差异无统计学意义(P>0.05);与柴苓合剂低剂量组比较,柴苓合剂高、中剂量组及西药组FBG、FINS、HOMA-IR水平均降低(P<0.01);与柴苓合剂中剂量组比较,柴苓合剂高剂量组及西药组FBG、FINS、HOMA-IR水平降低(P<0.01)。(2)脂代谢指标水平。与空白组相比,模型组大鼠甘油三酯(TG)、胆固醇(CHO)水平均升高(P<0.01);与模型组相比,柴苓合剂低、中、高剂量组及西药组TG、CHO水平均降低(P<0.01);与西药组相比,柴苓合剂中、高剂量组TG、CHO水平均降低(P<0.05,P<0.01),柴苓合剂低剂量组TG、CHO水平差异无统计学意义(P>0.05);与柴苓合剂低剂量组相比,柴苓合剂中、高剂量组TG、CHO水平均降低(P<0.01);与柴苓合剂中剂量组相比,柴苓合剂高剂量组TG、CHO水平均降低(P<0.01)。(3)TNF-α、IL-6水平。与空白组相比,模型组大鼠TNF-α、IL-6水平均升高(P<0.01);与模型组相比,柴苓合剂低、中、高剂量组及西药组TNF-α、IL-6水平均降低(P<0.01);与西药组相比,柴苓合剂低、中、高剂量组TNF-α、IL-6水平均降低(P<0.01);与柴苓合剂低剂量组相比,柴苓合剂中、高剂量组TNF-α、IL-6水平均降低(P<0.05,P<0.01);与柴苓合剂中剂量组相比,柴苓合剂高剂量组TNF-α、IL-6水平均降低(P<0.01)。(4)肝组织TRAF2/JNK/AP-1信号通路蛋白表达。与空白组相比,模型组大鼠肝组织TRAF2、JNK、AP-1蛋白表达均上调(P<0.01);与模型组比较,柴苓合剂低、中、高剂量组及西药组肝组织TRAF2、JNK、AP-1蛋白表达水平均降低(P<0.05,P<0.01);与西药组比较,柴苓合剂高剂量组肝组织TRAF2、JNK、AP-1蛋白表达水平均降低(P<0.01),柴苓合剂低、中剂量组肝组织TRAF2、JNK、AP-1蛋白表达水平差异无统计学意义(P>0.05);与柴苓合剂低剂量组比较,柴苓合剂高剂量组肝组织TRAF2、JNK、AP-1蛋白表达水平均降低(P<0.01),柴苓合剂中剂量组肝组织AP-1蛋白表达差异无统计学意义(P>0.05),TRAF2、JNK蛋白表达水平均降低(P<0.01);与柴苓合剂中剂量组比较,柴苓合剂高剂量组TRAF2、JNK、AP-1蛋白表达水平均降低(P<0.05,P<0.01)。结论柴苓合剂高剂量能显著改善痰瘀互结MS-IR大鼠糖代谢、脂代谢和炎症因子,其作用机制可能是柴苓合剂通过调控TRAF2蛋白作用于JNK蛋白,引起它的下游反应,又通过JNK的磷酸化作用于AP-1,释放炎症因子,从而TRAF2作用于JNK,然后磷酸化于AP-1使炎症因子降低有关。