| Research ObjectiveThis study uses data mining methods to study the effective prescriptions of TCM Niu Tianfu for clinical treatment of coronary heart disease,and analyzes the medicinal properties of the drugs in the prescription,the frequency of use and association rules,and the core drug combination to discover the mentor treatment.The rules of medication for coronary heart disease,combined with the experience of learning from teachers,make a preliminary summary of the experience of the instructor in treating coronary heart disease.At the same time,according to the results obtained through data mining above,combined with the actual situation of the clinical instructor's medication,a representative high-frequency drug combination was selected,and further research was conducted using the method of Chinese medicine network pharmacology to explore its mechanism of action.In clarifying the law,we hope to provide more objective data support and reference for clinical guidance of coronary heart disease prescription and drug development.Research methodBased on the "Traditional Chinese Medicine Assistance Platform(V2.5)" software,collect and organize the prescriptions of Director Niu Tianfu for clinical treatment of coronary heart disease,use association rules Apriori algorithm and complex system entropy clustering,etc.,using the software's "data analysis system" And "statistical report system" under the "prescription analysis system" for data analysis.Then use Cytoscape 3.7.2software(http://www.cytoscape.org/)to study the network pharmacological mechanism of the drug combination mined.1 Collect the prescription of coronary heart disease of Director Niu Tianfu,and use this as a source for prescription analysis,and conduct in-depth analysis and research on the sexual classics,frequency of use,association rules between drugs,prescription rules,etc.High-frequency drug combination,found the core combination,and based on this,the previous five flavors of high-frequency drugs "Salviae Miltiorrhizae Radix","ChuanxiongRhizoma","Paeoniae Radix Rubra","Fructus Aurantii" and "Poria" are the research objects.Further research is done on the law of high-frequency drug prescriptions,and the frequency of drugs and common combinations are analyzed.2 Network pharmacological analysisThe high-frequency drug combination "Paeoniae Radix Rubra-Chuanxiong Rhizoma-Bupleuri radix-Fructus Aurantii" obtained by the association rule Apriori algorithm and the complex system entropy clustering method was used as the research object.Relying on the Traditional Chinese Medicine System Pharmacology Analysis Platform(TCMSP)to retrieve the chemical constituents and action targets of "Paeoniae Radix Rubra,Chuanxiong Rhizoma,Bupleuri radix,Fructus Aurantii",and then build the active ingredient-predicted target,and build a protein interaction network for coronary heart disease.We also performed gene ontology(GO)function enrichment analysis and Kyoto gene and gene encyclopedia(KEGG)pathway enrichment analysis to explore the mechanism of the drug combination in the treatment of coronary heart disease.Research result1 Data Mining-based Director Niu Tianfu's Medication Rule for Coronary Heart Disease(1)Study on the prescription of the overall prescription: A total of 912 effective prescriptions for the treatment of coronary heart disease by Director Niu Tianfu were collected.Cold and warm drugs were used in the trials,followed by flat,cold and hot drugs.The five flavors of traditional Chinese medicine are involved in the prescription,the bitter medicine is the most,followed by the sweet and spicy.The meridian of the traditional Chinese medicine involved in the prescription is ranked according to their respective proportions from high to low.The first five are liver meridian,heart meridian,lung meridian,spleen meridian,and kidney meridian.In the statistical results of the drug frequency,the five drugs with the highest frequency of use were"Salviae Miltiorrhizae Radix"(567),"Chuanxiong Rhizoma"(495),"Paeoniae Radix Rubra"(406),"Fructus Aurantii"(387),and “Poria "(363).The three drug combinations with the highest frequency were "Paeoniae Radix Rubra,Chuanxiong Rhizoma"(377),"Chuanxiong Rhizoma,Fructus Aurantii"(340),and "Chuanxiong Rhizoma,Bupleuri radix"(326).Analysis of the"association rules" drug combination with frequency ? 10 resulted in 99 rules.Based on the improved mutual information method,cluster analysis was performed to obtain the correlation between two drugs.There were 42 drug pairs with a correlation coefficient of?0.04.Based on the above correlation degree results,based on the entropy clustering of complex systems,four core combinations were evolved.Based on the extraction of theabove core combinations,an unsupervised complex system entropy clustering algorithm was used to obtain 4 new prescriptions.(2)Study on the regularity of prescriptions containing salvia miltiorrhiza: the top five medicines used frequently are "Salviae Miltiorrhizae Radix"(567),"Chuanxiong Rhizoma"(318),"Cortex Moutan"(262 times),and "Paeoniae Radix Rubra"(255)"Carthami Flos"(223).The three drug combinations with the highest frequency were "Chuanxiong Rhizoma,Salviae Miltiorrhizae Radix"(318),"Cortex Moutan,Salviae Miltiorrhizae Radix"(262times),and "Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix"(255).Analyze the drug combinations with frequency of ?10 obtained from "association rules" to obtain 100 rules.Based on the improved mutual information method,cluster analysis was performed to obtain the degree of correlation between two drugs,and a total of 50 drug pairs with a correlation coefficient ? 0.04 were obtained.According to the above correlation degree results,based on the entropy clustering of complex systems,five core combinations were evolved.Based on the extraction of the above core combinations,an unsupervised unitary hierarchical clustering algorithm was used to obtain 5 new prescriptions.(3)Study on the prescription law of Chuanxiong prescriptions: The top five medicines used frequently are Chuanxiong Rhizoma(495),Paeoniae Radix Rubra(377),Fructus Aurantii(340),and Bupleuri radix(326)),"Salviae Miltiorrhizae Radix"(318).The three drug combinations with the highest frequency were "Paeoniae Radix Rubra,Chuanxiong Rhizoma"(377),"Chuanxiong Rhizoma,Fructus Aurantii"(340),and "Chuanxiong Rhizoma,Bupleuri radix"(326).Analysis of the "association rules" drug combination with frequency ? 10 resulted in 58 rules.Based on the improved mutual information method,cluster analysis was performed to obtain the correlation between two drugs,and 40 drug pairs with a correlation coefficient ? 0.04 were obtained.Based on the above correlation degree results,based on the entropy clustering of complex systems,three core combinations were evolved.Based on the extraction of the above core combinations,an unsupervised unitary hierarchical clustering algorithm was used to obtain 5 new prescriptions.(4)Study on the prescription rule of prescriptions containing red peony: The top five medicines with frequent use are "Paeoniae Radix Rubra"(406),"Chuanxiong Rhizoma"(377),"Fructus Aurantii"(317),and "Bupleuri radix"(312),"Carthami Flos"(293).The three drug combinations with the highest frequency were "Paeoniae Radix Rubra,Chuanxiong Rhizoma"(377),"Paeoniae Radix Rubra,Fructus Aurantii"(317),and "Chuanxiong Rhizoma,Fructus Aurantii"(316).Analysis of the "association rules" drug combination with frequency ? 10 resulted in 68 rules.Based on the improved mutual information method,cluster analysis was performed to obtain the correlation between twodrugs,and 22 drug pairs with a correlation coefficient ? 0.04 were obtained.Based on the above correlation degree results,based on the entropy clustering of complex systems,three core combinations were evolved.Based on the extraction of the above core combinations,an unsupervised unitary hierarchical clustering algorithm was used to obtain 5 new prescriptions.(5)Study on the prescription rules of prescriptions containing pupa shell: The top five drugs used frequently are "Fructus Aurantii"(387),"Chuanxiong Rhizoma"(340),"Bupleuri radix"(321),and "Paeoniae Radix Rubra"(317),"Carthami Flos"(257).The three drug combinations with the highest frequency were: Chuanxiong Rhizoma,Fructus Aurantii(340),Bupleuri radix,Fructus Aurantii(321),and Paeoniae Radix Rubra,Fructus Aurantii(317).Analyze the drug combinations with frequency of ?10 obtained from "association rules" to obtain 104 rules.Based on the improved mutual information method,cluster analysis was performed to obtain the correlation between two drugs,and 21 drug pairs with a correlation coefficient ? 0.04 were obtained.Based on the above correlation degree results,based on the entropy clustering of complex systems,three core combinations were evolved.(6)Study on the prescription rule of prescriptions containing Poria: the top five drugs used frequently are "Poria"(363),"Atractylodes Macrocephalae Rhizoma"(288),"Salviae Miltiorrhizae Radix"(207),"Chuanxiong Rhizoma"(170)," Fructus Aurantii(161).The three drug combinations with the highest frequency of occurrence were "Atractylodes Macrocephalae Rhizoma,Poria"(288),"Salviae Miltiorrhizae Radix,Poria"(207),and"Chuanxiong Rhizoma,Poria"(170).Analysis of "association rules" for drug combinations with frequency ? 10 resulted in 305 rules.Based on the improved mutual information method,cluster analysis was performed to obtain the correlation between two drugs,and 53 drug pairs with a correlation coefficient ? 0.04 were obtained.Based on the above correlation degree results,based on the entropy clustering of complex systems,three core combinations were evolved.Based on the above correlation degree results,based on the entropy clustering of complex systems,three core combinations were evolved.2 The combination of "Paeoniae Radix Rubra,Chuanxiong Rhizoma,Bupleuri radix,and Fructus Aurantii" was used to study the multi-component,multi-target complex network relationship in the treatment of coronary heart disease.The active ingredients of the drug combination "Paeoniae Radix Rubra-Chuanxiong Rhizoma-Bupleuri radix-Fructus Aurantii" were screened and combined with literature supplements to obtain 66 active active ingredients,346 drug targets were screened,and 6785 target targets were obtained.The first 1200(Relevance score ?12.10)were used as research targets,and 152drug-disease common targets were obtained.Draw a network diagram of the "drug-component-target-disease" interaction.Compounds with a Degree value ? 10 include quercetin,beta-sitosterol,kaempferol,Ferulic Acid,Stigmasterol,Albiflorin,nobiletin,naringenin,Benzoylpaeoniflorin,baicalein,Myricanone,isorhamnetin,Synephrine,saikosaponin a,and elagic acid can interact with 83,32,29,28,28,25,20,18,18,16,14,13,12,12,and 11 protein targets,respectively.It is speculated that these 15 ingredients are the main active ingredients in the combination of "Paeoniae Radix Rubra-Chuanxiong Rhizoma-Bupleuri radix-Fructus Aurantii" for the treatment of coronary heart disease;from the perspective of the target,there are three with a degree value greater than 10,PTGS2,PTGS1,SCN5 A,It can interact with 30,20,and 10 compounds,respectively,indicating that these targets may play an important role in the treatment of coronary heart disease.The PPI network of protein interactions was obtained by analysis.The interactions between proteins and proteins were relatively large,such as IL6,AKT1,VEGFA,EGF,CASP3,etc.It can be speculated that these targets are the core targets in the protein interaction network.It is of great significance for the combination of drugs to treat coronary heart disease.The GO results showed that the intersection gene set was enriched to 2,250 biological process pathways.Among them,the number of enriched genes> 10 was 594,which was mainly related to oxidative stress,the regulation of inflammatory response,coagulation,and angiogenesis.The intersection gene set was enriched to 107 cell component expression processes,of which the number of enriched genes> 10 was 30,mainly related to the endoplasmic reticulum,extracellular matrix,receptor complexes,etc.;intersection genes The collection is enriched to 171 processes related to molecular functions,of which the number of enriched genes> 10 is 33,which mainly binds to cytokine receptors,cytokine activity,growth factor receptors,and heme.And so on.KEGG results showed that it was mainly related to MAPK signal pathway,PI3K-Akt signal pathway,VEGF signal pathway,HIF-1 signal pathway,TNF signal pathway,and JAK-STAT signal pathway.Analysis conclusion1.Director Niu Tianfu has flexible medications and exquisite compatibility for treating coronary heart disease.He often uses drugs such as promoting blood circulation and removing blood stasis,replenishing qi and clearing collaterals,calming and calming the nerves,and relieving water and dampness,emphasizing the conditioning of yin and yang.The principle of heartfelt reasoning is based on syndrome differentiation and treatment;emphasizing the whole,the internal organs are related,which is in line with the principle of treating both the symptoms and the symptoms of traditional Chinese medicine,and has guiding significance for the clinic.The traditional Chinese medicine inheritance auxiliaryplatform system is also of great significance to the research inheritance and development of famous medical drugs.2.The "Paeoniae Radix Rubra-Chuanxiong Rhizoma-Bupleuri radix-Fructus Aurantii" drug combination contains a variety of chemical components with complex targets and a wide range of diseases.Its pharmacological mechanism may be the active chemical components of the drug combination quercetin,?-Sitosterol,kaempferol,and ferulic acid regulate key targets such as PTGS2,PTGS1,SCN5 A,CASP3,PPARG,AR,ADRB2,etc.,and pass MAPK,PI3K-Akt,VEGF,HIF-1,TNF,JAK-Signal pathways such as STAT are involved in the mechanisms of oxidative stress,inflammatory response,coagulation,and angiogenesis to treat coronary heart disease. |
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