| Objective: To explore the role of the mechanism of "internal harboring of ambient evils and the formation of carbuncles by embedded toxins" in the development of acute coronary syndromes,and to further explore the therapeutic effects of the "method of detoxification and elimination of carbuncles",as well as the related metabolic substances and metabolic pathways.Methods:1.Apply epidemiological investigation methods to investigate the symptoms of acute coronary syndrome,establish a database of Chinese medicine symptoms,and apply statistical methods such as logistic regression analysis,multiple linear regression analysis,factor analysis,and indicator clustering to clarify the characteristics of the main Chinese medicine symptoms and symptoms elements of acute coronary syndrome and to qualitatively evaluate the symptoms.2.The study analyzed the database established by the prospective cross-sectional research survey,and randomly divided the patients with the highest rate of occurrence in the TCM evidence profile of acute coronary syndromes into experimental group T(western medicine + standardized traditional Chinese medicine + detoxification and elimination of carbuncle formula),control group A(western medicine + standardized traditional Chinese medicine),and control group B(Western medicine + standardized traditional Chinese medicine 10%)for a randomized,double-blind,controlled trial of the three groups,to analyze The specific application efficacy of " method of detoxification and elimination of carbuncles " in acute coronary syndromes,and study the effect of this treatment formula on biochemical indexes and inflammatory substances.3.To analyze the changes in specific metabolites and differential metabolic pathways before and after the treatment of ACS by metabolomics,including the "Detoxification and elimination of carbuncles method".Results:1 Epidemiologic findings(1)the nature of the main syndromic elements of acute coronary syndrome and the representative symptomsThe results of the study suggest that the evidence elements of acute coronary syndrome are mainly phlegm and blood stasis in the case of solid evidence,and qi,yin and yang deficiency in the case of deficiency.The main manifestations of phlegm evidence are:chest tightness,white phlegm,sticky mouth,greasy,thick moss,slippery pulse and stringy pulse.The main manifestations of Blood stasis are: tightness in the chest,dark complexion,chest pain,dark lips,rough skin,dark tongue,exposed veins in the neck,and symptoms of tortuous bruising of the veins at the base of the tongue.Yin deficiency is characterized by palpitations,red tongue,emaciation,dry mouth,heat in the hands and feet,and thin pulse.The main manifestations of yang deficiency are: lack of warmth in the hands and feet,fear of cold,white moss,and pallor.Qi deficiency is mainly characterized by shortness of breath,tiredness,laziness,mental fatigue,and teeth marks on the tongue.(2)The clinical symptom of phlegm and stasis is an important component of acute coronary syndrome.After factor analysis of all clinical symptoms of patients with acute coronary syndrome,33 symptoms with the highest contribution rate,which could reflect the distribution of syndromes to the greatest extent,were extracted.33 symptoms extracted from 14 factors were subjected to cluster analysis,so that each cluster represented the pathogenic characteristics of a certain aspect of the whole pathogenesis of acute coronary syndrome.The cluster analysis revealed that the syndromes could be summarized into five major categories of syndromic elements.Meanwhile,the clustering diagram showed that the symptoms of phlegm and blood stasis were mixed and clustered with each other,and finally clustered into one big category,which converged with the other deficiency syndromes.This suggests that phlegm and blood stasis is a combination of disease and evil that coexists with other deficiency syndromes and interacts with them in acute coronary syndromes.(3)Basic symptom types of acute coronary syndromesBy clustering the samples of clinical patients and analyzing the information of the four consultations,acute coronary syndrome can be summarized into the following four main symptom types:Category Ⅰ: a total of 42 cases,accounting for 12.24% of the total number of patients,with the disease locus evidence element of heart;the disease locus evidence element of heart;and the disease nature evidence element of qi deficiency + yin deficiency + blood stasis.Category Ⅱ: 178 cases,accounting for 51.90% of the total number of patients,with the disease locus symptomatic elements of heart and spleen;the pathognomonic symptomatic elements of phlegm + blood stasis.Category Ⅲ: 86 cases,accounting for 25.07% of the total number of patients;the disease locus elements were heart and spleen;the disease symptom elements were qi deficiency + blood stasis.Category Ⅳ: 37 cases,accounting for 10.79% of the total number of patients,with the disease locus syndrome elements of heart,spleen and kidney;the pathognomonic syndrome elements of yang deficiency + phlegm + blood stasis.(4)The top two syndromes with the highest rate of occurrence in acute coronary syndromes were phlegm + blood stasis and qi deficiency + blood stasis,which were related to the five viscera,with the heart,spleen,and kidneys being the most closely related,but the distribution of pathogenic syndromes among syndromes with different pathogenic syndromes also varied.The results of clustering showed that phlegm and stasis were the most common syndromes in acute coronary syndromes,and that phlegm and stasis were one of the key pathogenic mechanisms of acute coronary syndromes.(5)Study on the correlation between symptomatic elements of acute coronary syndromes and the degree of coronary artery lesionsRegression analysis of the correlation between symptomatic elements and the extent of coronary artery disease showed that blood stasis,phlegm,qi deficiency and yin deficiency were related to the Gensini score,and that the above symptomatic elements were important factors aggravating the extent of coronary artery stenosis and the scope of lesions.(6)The distribution of syndromes in the angina class of acute coronary syndromes has a certain pattern.From the distribution table of the main symptoms of acute coronary syndrome in different angina levels,it can be seen that the symptoms of yang deficiency tend to increase in distribution as angina progresses from one level to another.Symptoms representing yin deficiency are less frequently distributed in angina class II and class III,and more frequently distributed in cardiac function class IV.Symptoms representing qi deficiency gradually increased in distribution with increasing angina.Symptoms representing phlegm and stasis interconnections had high and consistent weights during the gradual aggravation of acute coronary syndrome,suggesting that phlegm and stasis interconnections existed in the main aspects of acute coronary syndrome,and that because of the gradual deepening of disease evils and the emergence of evil realities and positive deficiencies,the related deficiency factors of yang,yin,and qi deficiencies were more prominent in the manifestations in the angina pectoris grades Ⅲ and Ⅳ.2 The results of the randomized controlled trial study(1)After treatment,the overall efficacy of the three groups of patients differed significantly(P<0.01).Both two comparisons are statistically different(P<0.05).The efficacy of test group T was better than that of control group B and control group A,and control group A was better than control group B.(2)After treatment,the frequency and duration of angina attacks were significantly reduced in the three groups,and the difference was statistically significant(P < 0.01).Both two comparisons were statistically different(P < 0.05).Test group T was superior to control group B and control group A in these two aspects,and control group A was superior to control group B.(3)Comparison of TCM symptom scores showed significant differences among the three groups after treatment(P < 0.01).Both two comparisons were statistically different(P< 0.05).Test group T was superior to the other two groups in improving symptom scores,and control group A was superior to control group B.(4)In the comparison of ECG efficacy,there is a statistical difference between the three groups after treatment(P<0.05),and the difference between two and two comparisons is statistically significant(P < 0.05).The efficacy of test group T was better than the other two groups,and the efficacy of control group A was better than control group B.(5)After treatment,the indicators of TNF-α,IL-1,MMP-9,and SCD40 L were significantly improved,and the difference was statistically significant(P<0.01).In the two-by-two comparison,the test group T was statistically different from the other two groups in the comparison of the indicators(P<0.05),and the test group T improved the indicators better than the other two groups.(6)There was a statistical difference in the incidence of MACE among the three groups of therapies(all P values <0.05).There is a significant difference between the experimental group T and the other two groups(P < 0.01),and the experimental group T is better than the control group A and control group B.(7)The results of the study indicate that "internal carbuncle" may be a "hidden symptom" in acute coronary syndrome from the perspective of measuring evidence by prescription."Phlegm and stagnation of evils are stored inside and become poisonous to become carbuncle" may be one of the important internal lesion mechanisms of acute coronary syndromes in Chinese medicine.3 Metabolomics findings(1)By PCA analysis,the samples before and after treatment showed an overall trend in metabolite levels.The Chinese and western medicine treatment groups gradually converged to the normal population after treatment,indicating that they can regulate metabolites in the body and produce a therapeutic effect on acute coronary syndromes.(2)An in-depth comparison of urine samples from patients with acute coronary syndrome(ACS)before and after treatment was conducted by orthogonal partial least squares discriminant analysis(OPLS-DA).The results showed that the urine metabolic profiles changed significantly before and after the standardized Western medicine treatment and the comprehensive treatment with Chinese and Western medicines,reflecting the effectiveness of the treatment.The replacement test further validated the robustness and predictive performance of the model.(3)Through the OPLS-DA model and variable weight value(VIP)analysis,the treatment of ACS in the Chinese and western medicine groups significantly affected 63 metabolites,of which 47 were up-regulated and 16 were down-regulated.Compared with the western medicine group,21 metabolites were up-regulated and 8 were down-regulated in the Chinese and western medicine group,highlighting the specific difference of Chinese medicine.Comparing with the healthy people group,a total of 123 ACS characteristic metabolites were screened,of which 82 were up-regulated and 41 were down-regulated,representing ACS characteristic regulatory metabolites.Finally,20 characteristic metabolic differentiators of ACS in the Chinese and western medicine group were screened,including dopamine and isocitric acid,revealing the metabolic regulation mechanism of the combination of Chinese and western medicine.(4)Through KEGG pathway enrichment analysis,in the treatment of acute coronary syndromes,Chinese and western drug therapies showed significant performance in the antioxidant pathway,inflammatory mediator regulation of TRP channels,nicotinic acid and nicotinamide metabolism,uracil metabolism and other pathways.Compared with the western drug therapy group,the Chinese and western drug therapy group showed higher enrichment in inflammatory mediators on TRP channel regulation,antioxidant pathway and nitric oxide synthesis pathway.(5)Chinese medicine treatment demonstrated comprehensive regulation of the cardiovascular system through multi-pathway and multi-level metabolic regulation,including multifaceted metabolic regulation,cardiovascular system regulation,antioxidant and anti-inflammatory effects,lipid metabolism regulation,immune system regulation,and specific differential therapeutic effects.Conclusion:1 The results of this study suggest that the pathognomonic syndromes of acute coronary syndrome are characterized by phlegm and blood stasis as the main solid syndromes,and by qi,yin,and yang deficiencies as the main deficiency syndromes.2 Phlegm and stasis are the most common syndromes in acute coronary syndromes.Phlegm-stasis interconnection is one of the important core mechanisms and influencing factors in the TCM syndromes of acute coronary syndromes,and it is more likely to aggravate the degree and scope of coronary artery lesions than other syndromes.The evolution of symptoms of acute coronary syndrome is the result of the progression of phlegm-stasis inter-conjunction and the aggravation of Zhengqi weakening.3 From the perspective of "phlegm and stasis inter-conjugate to form carbuncle",the treatment of acute coronary syndrome with the formula of detoxification and elimination of carbuncle is better than the control group in terms of improving the overall clinical efficacy,angina pectoris duration and seizure frequency,Chinese medicine symptom scores,electrocardiogram changes,and serum indexes(TNF-alpha,IL-1,MMP-9,SCD40L),and the treatment is safe and effective.The therapy is safe and effective.4 The phlegm and stagnant stasis syndrome of ACS will cause “internal carbuncle”lesions,and the mechanism of “internal carbuncle” is one of the key lesions in the development of ACS.5 The Chinese medicine therapy targeting the pathogenesis of " Phlegm and stasis are intertwined,harboring toxins to form carbuncles." mainly regulates the inflammatory mediators on TRP channels,antioxidant pathway and nitric oxide synthesis pathway,which can reduce the inflammatory response,improve the vascular function,improve the coronary artery blood flow,and play a therapeutic role in the treatment of ACS.6 Herbal therapy produces regulation of phenols,carboxylic acids,amino acids,nucleotides,lipids,bioactive molecules,organic acids,biogenic amines,vitamin derivatives,nucleosides,alkaloids,and other metabolites through antioxidant pathways,inflammatory mediators regulation of TRP channels,nicotinic acid and nicotinamide metabolism,and uracil metabolism multiple pathways,and the therapy can have a positive impact on antioxidant and anti-inflammatory,lipid metabolism regulation,immune system regulation,Neurotransmitters,energy metabolism and other aspects. |
PDF Full Text Request