| Coronary heart disease(CHD),also called ischemic heart disease,refers to clinical syndrome resulting from myocardial ischemia and anoxia caused by coronary insufficiency when coronary atherosclerosis leads to vascular luminal stenosis,excessive strength or mental stress.Its main clinical symptom is paroxysmal crushing retrosternal pain,within the scope of “chest stuffiness and pain” of TCM.CHD induced by vascular lesions such as vascular endothelial injury and atherosclerosis caused by hypertension,dyslipidemia,overweight/obesity,hyperglycemia/diabetes,unhealthy lifestyle(smoking,unreasonable diet,lack of physical activity),social psychological factor or genetic factor has become one of major killers to human health.Traditional Chinese medicine has accumulated rich experiences in syndrome differentiation and treatment of this type of diseases.Traditional Chinese medical records act as a carrier of famous and veteran TCM doctors' academic thoughts and clinical experiences.Medical record research is an important “think tank” resource for deeply excavating famous doctors' clinical experiences as well as practically enhancing clinical effects on CHD.Along with development of information science and technology and in face of mass data in famous doctors' medical records,it has important significance to rationally use such data to dig out tacit knowledge,academic thoughts and syndrome-differentiation-based medicine application rules hidden behind explicit experiences.Data mining(DM)techniques such as bayesian algorithm,cluster analysis and support vector machine have been widely used in medical field,and gradually become indispensable method for obtaining valuable medical record information.It is necessary to integrate with correlation thinking of “principle-method-recipe-medicines” of TCM,choose famous doctors' primary clinical medical record data on CHD treatment under guidance of basic TCM theory,as well as adopt modern data mining technology to reveal syndrome differentiation treatment laws of disease,sign,symptom,method,recipe and medicine.Such way helps improve level of clinical syndrome-treatment of CHD,and provides beneficial example for clinically based innovative drug R&D and famous veteran TCM doctors' experience inheritance.With extensive and deep application of data mining technology into TCM field,medical and computer professionals begin to utilize data mining results in comprehensive analysis,input them into computer network system,and think about how to combine advanced computer technology with traditional TCM treatment,so as to better hand down and carry forward this precious medical heritage of our country.Establishment of TCM clinical diagnosis system,expert diagnosis & treatment system,and etc sets an excellent example for research of intelligentized TCM diagnosis & treatment,but these systems all have certain defects and are not well applied practice.The tutor,Professor Wu Yiling,is the first one to systematically construct “syndrome differentiation based treatment of collateral disease”,“collateral doctrine” and “qi collateral doctrine” in China,to form complete theoretical system of collateral disease.For collateral doctrine,a systematic theory for guiding vascular disease prevention and treatment,its core theory-ying wei theory-is proposed as a major theoretical innovation.Chest stuffiness and pain is located in collaterals of the heart,and belongs to collateral lesion research.The tutor investigates etiology,pathogenesis and effective therapeutic prescription of this disease under guidance of collateral doctrine and on the basis of ying-wei theory.“Nutrients are inside the collaterals.Defense occurs outside collaterals.”(The Internal Canon of Medicine)“If ying and wei are obstructed,blood flow is suspected to stop.”(Treatise on Febrile Diseases)ying-wei uses qi and blood for circulation.Blockage of ying,wei,qi and blood results in qi stagnation and blood stasis.“Transferring happens through blood vessels but vessels are obstructed”(Synopsis of Golden Chamber).Accumulation leads to stasis and finally obstruction.Based on these ideas,he puts forward that underlying pathogenesis of this disease is a pathological process of collateral stasis resulting from collateral blockage caused by collateral qi deficiency/stasis.In case of injury of heart,ying and wei will be regulated(Classics on Medical Problems).The tutor indicates regulating ying,wei,qi and blood and keeping patent collateral is an important therapeutic principle of chest stuffiness and pain.He firstly puts forward a medicine application law for CHD-“removing the wind,eliminating collateral stasis and dredging collateral qi”.He is the first one to use worm-type wind-removing and antispasmodic drug in treatment of CHD,and develop Tongxinluo Capsules.Experimental researches demonstrate this drug has triple protective effect on blood,vessel and cardiac muscle tissue.Clinical studies show it has significant effect on CHD.The tutor's serial researches on CHD reflect integrated disciplinary development law and feature of TCM-“theory + clinics + new drug”,inherit innovation,and integrate new knowledge.With clinical medical records of 346 CHD patients who were treated by the tutor at Outpatient Department of Collateral Disease from 2009 to 2016 as original data,this article adopts DM techniques such as bayesian algorithm and cluster analysis to deeply analyze syndrome type classification,syndrome-symptom relevance and core prescription of these cases,establishes auxiliary CHD diagnosis and treatment system using above-described medical record data and combining with the tutor's experiences and collateral doctrine,as well as utilizes network pharmacological method to investigate representative Chinese patent medicine for CHD treatment-Tongxinluo Capsules and dig out its target point and pathway of treating disease,in order to carry forward the tutor's academic thoughts.Part I Collateral doctrine guided investigation into theories aboutprevention and treatment of CHD angina pectorisObjective: Investigate theories about prevention and treatment of CHD angina pectoris under guidance of collateral doctrineMethods: Investigate disease name evolution,etiology,pathogenesis,treatment method,treatment principle and representative prescription of chest stiffness and pain through literature search and data summarization as well as on the basis of deeply mining TCM literatures.Then,analyze and sketch out the tutor's collateral doctrine guided research of theory,method,recipe and medicine of CHD angina pectoris treatment as well as action mechanism of Tongxinluo Capsules.Results:1.Systematically summarize ancient people's knowledge about disease name,etiology,pathogenesis,treatment method,treatment principle and medicine application of chest stiffness and pain,thus to lay foundation for systematic summarization of the tutor's theories about prevention and treatment of CHD angina pectoris.2.As guided by collateral doctrine,sketch out pathogenesis of CHD “collateral qi deficiency/stasis,stagnation and blockage as well as its treatment principle of “dredging collaterals”.Analyze the drug application features of “regulating ying,wei,qi and blood”,“characteristics of the five internal organs” and “removing the wind,eliminating collateral stasis and dredging collateral qi”.This article also summarizes progresses in fundamental experiments and clinical evidence-based researches of Tongxinluo Capsules,a representative drug of CHD treatment,in order to provide theoretical support for subsequent data mining in combination with clinical medical cases,and subsequent establishment of auxiliary CHD diagnosis and treatment system.Summary:Focused on a typical collateral lesion-CHD angina pectoris,this part traces origins and systematically summarizes ancient doctors' knowledge about disease name,etiology,pathogenesis,treatment method,treatment principle and medicine application of this disease.It also extracts tutor Wu's collateral doctrine guided academic thoughts about etiology,pathogenesis,treatment method,treatment principle and medicine application law of this disease,in hope of providing theoretical support for subsequent data mining in combination with clinical medical cases.Part II DM technology based research and analysis of 346 clinical CHDangina pectoris cases treated by Professor Wu YilingObjective: Use bayesian algorithm,cluster analysis and frequency analysis to systematically analyze clinical CHD angina pectoris cases treated by the tutor,as well as dig out syndrome type,syndrome-symptom relevance,frequently-used drugs,and core prescription of each syndrome of this disease.Methods: Medical records were from 381 CHD angina pectoris patients who were treated by the tutor at Outpatient Department of Collateral Disease of Hebei Yiling Hospital Affiliated to Hebei Medical University from January 2009 to December 2016.According to TCM and western medicine CHD diagnosis criteria,case inclusion criteria and exclusion criteria,346 medical cases were included in total.Original data of these cases were summarized systematically: electronic type-in,error correction,supplement,symptom standardization,and etc.Bayesian algorithm was used to analyze syndrome classification and syndrome-symptom relevance.Probability quantification was used to represent strength of relevance.SPSS19.0 statistic software was used to classify efficacy of 122 drugs used for these 346 cases.Frequency analysis was used for statistical analysis of drug application frequency,four properties and five tastes,and channel tropism.This software was also utilized for cluster analysis to extract core prescription of each syndrome type.Results:1.Study of syndrome type and syndrome-symptom relevance of CHDThrough using Bayesian DM method and combining with the tutor's clinical experiences,8 types of syndrome were extracted,which were ranked as below from high to low in terms of occurrence frequency: deficiency of both qi and yin(54),collateral qi deficiency and stagnation(51),obstruction of the lung by phlegm and stasis of heart collateral(49),kidney deficiency,collateral stasis and heart collateral stasis(47),collateral qi stasis(45),heart collateral contracture(35),stagnancy of liver-qi and stasis of heart collateral(33),obstruction of spleen,adverse rising of stomach-qi and stasis of heart collateral(32).The tutor's laws in syndrome-differentiation based treatment of CHD angina pectoris were revealed.On such basis,“man-machine integrated” analysis of relevance between each syndrome and symptom of CHD angina pectoris was done.Results show:(1)Syndrome of collateral qi deficiency and stagnation: primary symptoms: pull pain in heart and chest(0.75);fatigue and weakness(0.50);deep and thin pulse(0.51);secondary symptoms: palpitation and laziness to speak(0.48);teeth print in tongue(0.39);accompanied symptoms:(1)cool hands and feet(0.27);worsening of heart pain in case of coldness(0.17);(2)dry mouth(0.28);red tongue(0.21);(2)Syndrome of collateral qi stasis: primary symptoms: paroxysmal chest pain(0.74);secondary symptoms: emotional depression(0.49);thready and slippery pulse(0.43);accompanied symptoms:(1)ecchymosis in tongue(0.29);(2)agitation and irritability(0.21);yellowish fur(0.24);(3)Syndrome of heart collateral contracture: primary symptoms: sudden oppressive pain in chest(0.79);secondary symptoms: chill and cold limbs(0.46);pain relief in case of warmness(0.37);agitation and irritability(0.44);thready pulse(0.46);accompanied symptoms:(1)frequent sighing(0.29);flank discomfort bilaterally(0.22);(4)Syndrome of deficiency of both qi and yin: primary symptoms: depression and pain in heart and chest(0.68);pain in shoulder,back and inner arm(0.65);spontaneous perspiration(0.52);secondary symptoms: tiredness and laziness to speak(0.43);dizziness(0.31);thready and weak pulse(0.39);accompanied symptoms:(1)palpitation and sleeplessness(0.18);(5)Syndrome of stagnancy of liver-qi and stasis of heart collateral: primary symptoms: distress,swelling and pain in chest and hypochondrium(0.79);pain in back and both arms(0.49);thready pulse(0.54);secondary symptoms: gastric cavity swelling(0.37);tongue darkness(0.39);accompanied symptoms:(1)bitter taste(0.22);vexation(0.15);(6)Syndrome of obstruction of spleen,adverse rising of stomach-qi and stasis of heart collateral: primary symptoms: chest distress and pain after meal(0.62);loss of appetite(0.75);floating and soft pulse(0.65);secondary symptoms: nausea and vomit(0.45);sticky and uncomfortable mouth(0.34);accompanied symptoms:(1)adverse rising of stomach-qi(0.27);white,thick and greasy fur(0.22);(7)Syndrome of obstruction of the lung by phlegm and stasis of heart collateral: primary symptoms: asphyxia-like oppressive pain in chest(0.64);cough and turbid saliva and phlegm(0.72);slippery pulse(0.61);secondary symptoms: asthma and shortness of breath(0.46);obesity(0.39);accompanied symptoms:(1)massive wet phlegm(0.23);yellow and thick expectorated phlegm(0.16);slippery and rapid pulse(0.20);(8)Syndrome of kidney deficiency,collateral stasis and heart collateral stasis: primary symptoms: chest distress and pain(0.50);soreness and weakness of waist and knees(0.84);upper excess and lower deficiency of pulse(0.89);secondary symptoms: deafness(0.32);palpitation and night sweat(0.32);dysphoria in chestpalms-soles(0.48);accompanied symptoms:(1)swelling pain of head(0.18);(2)tiredness and weakness(0.20);(3)edema of lower limbs(0.27).2.Study of drugs frequently used for treatment of CHDFrequency analysis was used to study the tutor's features of medicine application in treatment of CHD angina pectoris.Results showed the first 30 most frequently used drugs were: the root of red-rooted salvia,lignum dalbergiae odoriferae,scorpio,leech,raw astragali radix,cassia twig,ligusticum wallichii,allium macrostemon,root of common peony,pinellia ternate,the root of kudzu vine,American ginseng,corydalis tuber,trichosanthes kirilowii Maxim,immature bitter orange,fried jujube kernel,pericarpium citri reticulatae,white peony root,dogwood,rhizoma alismatis,schisandra chinensis,rhizoma acori graminei,inula flower,radix ophiopogonis,poria cocos,periostracum cicada,albizia flower,loranthus parasiticus,thunberg fritillary bulb and gastrodia elata.According to “collateral doctrine”,common collateral-dredging drugs are classified in terms of function into qi-&collateral-dredging,blood-stasis-dispersing& collateral-dredging,phlegm-eliminating & collateral-dredging,wind-removing &collateral-dredging,collateral-nourishing,and antidotal & collateral-dredging.3.Frequency analysis of representative syndromes and symptoms of CHDFrequency analysis and descriptive analysis were used for statistics of high-frequency symptoms of each syndrome.Top five symptoms of each syndrome were selected.Results were as below:(1)Deficiency and stagnation of collateral qi: pull pain in heart and chest,with aggravation in case of motion;chest distress and shortness of breath;fatigue and weakness;light red tongue;thin and white fur;(2)Collateral qi stasis: chest pain;chest tightness;emotional depression;red tongue;yellow fur;(3)Heart collateral contracture: sudden chest distress or pain;flank discomfort bilaterally;thready pulse;frequent sighing;aversion to cold;(4)Deficiency of qi and yin: depression and pain in heart and chest;palpitation and shortness of breath;pain in shoulder,chest pain spreaded to shoulder,back and inner arm;thready and weak pulse;weakness of four limbs;(5)Stagnancy of liver-qi and stasis of heart collateral: chest distress and pain;thready pulse;distress,swelling and pain in chest and hypochondrium;rage;pain in back and both arms;(6)Obstruction of spleen,adverse rising of stomach-qi and stasis of heart collateral: worsening chest distress and pain after satiation;loss of appetite;abdominal fullness and distention,with worsening after meal;sense of vomit;floating and soft pulse;(7)Obstruction of the lung by phlegm and stasis of heart collateral: asphyxia-like oppressive pain in chest;cough and turbid saliva and phlegm;thick and greasy fur;asthma and shortness of breath;slippery pulse;(8)Kidney deficiency,collateral stasis and heart collateral stasis: chest distress and pain;upper excess and lower deficiency of pulse;soreness and weakness of waist and knees;dizziness and tinnitus;dysphoria in chestpalms-soles.4.Analysis of core prescription of representative CHD syndromeCore prescriptions of each syndrome extracted by cluster analysis are:(1)Collateral qi deficiency and stagnation: American ginseng,raw astragali radix,cassia twig,root of common peony,trichosanthes kirilowii Maxim,allium macrostemon,the root of red-rooted salvia,lignum dalbergiae odoriferae,leech,scorpio,ligusticum wallichii,rhizoma corydalis;(2)Collateral qi stasis: immature bitter orange,allium macrostemon,cassia twig,root of common peony,trichosanthes kirilowii Maxim,rhizoma pinelliae preparata,the root of red-rooted salvia,lignum dalbergiae odoriferae,leech,scorpio;(3)Heart collateral contracture: cassia twig,white peony root,the root of red-rooted salvia,lignum dalbergiae odoriferae,scorpio,centipede,periostracum cicada,ligusticum wallichii,corydalis tuber,honey-fried licorice root;(4)Deficiency of both qi and yin: American ginseng,raw astragali radix,radix ophiopogonis,schisandra chinensis,dogwood,fried jujube kernel,the root of red-rooted salvia,lignum dalbergiae odoriferae,leech,scorpio;(5)Stagnancy of liver-qi and stasis of heart collateral: radix bupleuri,immature bitter orange,white peony root,cassia twig,the root of red-rooted salvia,lignum dalbergiae odoriferae,leech,scorpio,inula flower,fructus citri,fingered citron;(6)Obstruction of spleen,adverse rising of stomach-qi and stasis of heart collateral: rhizoma atractylodis,Mangnolia officinalis,pericarpium citri reticulatae,rhizoma pinelliae preparata,inula flower,the root of red-rooted salvia,lignum dalbergiae odoriferae,leech,scorpio,ligusticum wallichii,rhizoma acori graminei;(7)Obstruction of the lung by phlegm and stasis of heart collateral: trichosanthes kirilowii Maxim,allium macrostemon,pinellia ternate,citrus reticulata blanco,pericarpium citri reticulatae,poria cocos,immature bitter orange,thunberg fritillary bulb,the root of red-rooted salvia,lignum dalbergiae odoriferae,leech,periostracum cicada,rhizoma acori graminei;(8)Kidney deficiency,collateral stasis and heart collateral stasis:loranthus parasiticus,root of common peony,white peony root,dogwood,fried jujube kernel,the root of kudzu vine,rhizoma alismatis,the root ofred-rooted salvia,lignum dalbergiae odoriferae,leech,scorpio,gastrodiaelata,fossil fragment and oyster.Summary: This part selected 346 patients,performed bayesian syndrome type analysis of 92 symptoms occurring in these cases,studied relevance between each syndrome-symptom,and chose symptoms with strong relevance as typical symptoms of the syndrome.Results showed:(1)The tutor's CHD syndrome classification integrates characteristics of ying wei theory,excess syndrome,deficiency syndrome,qi movement and qi transformation as well as properties of the five internal organs.There were eight types of syndrome: collateral qi stasis,collateral qi deficiency and stagnation,heart collateral contracture,deficiency of both qi and yin,stagnancy of liver-qi and stasis of heart collateral,obstruction of the lung by phlegm and stasis of heart collateral,kidney deficiency,collateral stasis and heart collateral stasis,and obstruction of spleen,adverse rising of stomach-qi and stasis of heart collateral.(2)Analyzing principal,secondary and accompanied symptoms in combination with strength of relevance between each syndrome-symptom has important value for identification of syndrome type.(3)Frequency analysis is utilized to find out drugs frequently used in CHD cases treated by Professor Wu.According to “collateral doctrine”,frequently-used common collateral-dredging drugs are classified in terms of function into qi-& collateral-dredging,blood-stasis-dispersing&collateral-dredging,phlegm-elimi nating&collateral-dredging,wind-removing&collateral-dredging,collateral-nou rishing,and antidotal&collateral-dredging.(4)Frequency analysis is used to calculate high-frequency symptoms of these eight syndromes,which confirm above bayesian algorithm extracted statistical results about symptoms with strong relevance between each syndrome.(5)Cluster analysis is applied to extract core prescription of each syndrome,which reflect correlation between disease,syndrome,symptom,method,recipe and medicine in the tutor's treatment of each syndrome of CHD as well as provide objective data support for syndrome-differentiation based treatment of CHD.The extracted core prescriptions become one of important sources of collateral doctrine guided innovative traditional Chinese medicines R&D for treating CHD.In-depth investigation into the tutor's features in drug application of CHD treatment plays a positive role in handing down collateral doctrine and Professor Wu's clinical experiences.Part III Establishment and verification of auxiliary diagnosis andtreatment system based on Professor Wu Yiling's treatment ofCHD angina pectorisObjective: Combine medical record data summarization and analysismethods with Professor Wu Yiling's clinical experiences,in order toconstruct “disease-syndrome-symptom-prescription” model and establishsystem software that can embody Professor Wu's clinical practice featuresand be used in intelligent diagnosis and treatment.In addition,verifysyndrome identification accuracy and prescribing similarity of the system.Methods: Network-based auxiliary CHD diagnosis and treatment system of browser/server model was developed through utilizing the collected medical records of 346 CHD patients treated by the tutor and adopting computer network engineering related technology.“Disease-syndrome-symptom-prescription” model was constructed through calculating syndrome model and case model.For establishment of syndrome model,expert's experiences were used to summarize principal and secondary symptoms of certain disease syndrome;the model was set up according to information content of symptom.For establishment of case model,bayesian network was used to calculate relevance between syndrome and symptom,and obtain syndrome and symptom model;then,empirical model of disease-syndrome-symptom was combined through integrating syndrome model without medical record and syndrome model with medical record.40 CHD patients were enrolled using randomized controlled method.These patients were subject to diagnosis and treatment by the tutor and auxiliary CHD diagnosis and treatment system respectively to verify syndrome identification accuracy of the system.Related correlation analysis method of SPSS19.0 was used to calculate similarity in prescribing.Results:1.Based on medical record contents and expert experiences,auxiliary CHD diagnosis and treatment system was developed successfully.Intelligent auxiliary diagnosis & treatment module,intelligent diagnosis & treatment management module,clinical data module interface,data statistical analysis module,basic data management module,registered user review module,subordinate body management module,comprehensive information management module interface and personal information management module are important components of this system.This lays a foundation for big data collection and research of clinical evidences of CHD.2.40 CHD patients were selected using randomized controlled method to verify syndrome identification accuracy and prescribing similarity.Results showed the accuracy was 75%.Correlation coefficients of prescribing were 0.554,0.324,0.232,0.065,0.495,0.335,0.551,0.102,0.941,0.093,0.001,0.366,0.325,0.519,0.889,0.747,0.924,0.465,0.192,0.253,0.944,0.161,0.212,0.881,0.506,0.087,0.243,0.875,0.348,0.486,0.017,0.235,0.428,0.344,0.098,0.278,0.340,0.103,0.263 and 0.178 respectively.There were 6 cases of high correlation,5 cases of moderate correlation,11 cases of low correlation and 18 cases of weak correlation.Summary:A software-hardware-integrated CHD diagnosis and treatment system was developed successfully.A platform was set up to convert medical records into CHD clinical evidences,apply these evidences into clinics,collect clinical evidences and further transform them to serve the clinics.Along with data accumulation,such system will definitely promote CHD diagnosis & treatment model development,enhance CHD clinical service level,and provide support for subsequent upgrade,research and development.It has important significance for handing down and carrying forward famous veteran TCM doctors' experiences.Part IV Study of action mechanism of Tongxinluo Capsules based onnetwork pharmacologyObjective: Construct “traditional Chinese medicine chemical compound ingredients(traditional Chinese medicine ingredients)-drug target” network using network pharmacology method with Tongxinluo Capsules as research carrier,conduct enrichment analysis of target and pathway,and discuss action mechanism of Tongxinluo Capsules.Method: Literature search and TCMSP,TCM Database@Taiwan,Chemspider,and Chemical book search was used to retrieve Tongxinluo Capsule component MOL structure.“traditional Chinese medicine chemical ompound ingredients-drug target” network was constructed.Cytoscape(3.4.0)software was utilized to further analyze correlation network between molecules and target proteins.Enrichment analysis of pathway was performed based on R language to clarify molecular mechanism of Tongxinluo Capsules.Results:1.Information about compounds screened from Tongxinluo CapsulesAmong 12 drugs contained in Tongxinluo Capsules,241 Chinese herbal medicinal ingredients were searched from ginseng;74 Chinese herbal medicinal ingredients were searched from leech;12 Chinese herbal medicinal ingredients were searched from scorpio;123 Chinese herbal medicinal ingredients were searched from root of common peony;10 Chinese herbal medicinal ingredients were searched from periostracum cicada;81 Chinese herbal medicinal ingredients were searched from ground beetle;23 Chinese herbal medicinal ingredients were searched from centipede;149 Chinese herbal medicinal ingredients were searched from sandalwood;127 Chinese herbal medicinal ingredients were searched from lignum dalbergiae odoriferae;132 Chinese herbal medicinal ingredients were searched from frankincense;47 Chinese herbal medicinal ingredients were searched from jujube kernel;46 Chinese herbal medicinal ingredients were searched from borneol.2.Target genes related to compounds of Tongxinluo CapsulesUsing above-described method,it is predicted that 12 herbal medicine ingredients of Tongxinluo Capsules involve 3025 action targets including ADORA3,SFTPA1,IRGM,RNASEL,XRCC1,ALPI,SFTPA2,NR0B2,SERPINE1,CYP2A13 and etc.3.Demonstration and network feature analysis of the constructed traditional Chinese medicine ingredients-drug target networkAmong the constructed traditional Chinese medicine ingredients-drug target network,the top 20 compounds in terms of node degree are resveratrol,Arbutin,Ethanol,Hydroquinone,daidzein,Eugenol,Toluene,Palmitic Acid,Kaempferol,Phenol,Apigenin,Adenosine Triphosphate,Ellagic Acid,Luteolin,Cholesterol,Sodium Dodecyl Sulfate,Histamine,Taurine,Dibutyl Phthalate,and selenomethylselenocysteine.Further analysis of correlation network between molecules and target proteins using Cytoscape(3.4.0)software found,this network had worldlet characteristics(correlation: 0.907,R-squared: 0.688),suggesting good stability of the relationship network constituted by molecules and targets.It is indicated that active ingredients of Tongxinluo Capsules can correct body balance network in state of disease,contribute to formation of new body balance,and thus exert therapeutic effect of regulating body.4.Enrichment analysis of pathway related to target geneEnrichment analysis of pathway was done based on R language(R3.3.1).Analysis results showed: pathways related to target gene of Tongxinluo Capsules focus on metabolism,genetic information process,environmental information process,cell metabolism process,biological process and human disease.The involved metabolism includes Retinol metabolism?Metabolism of xenobiotics by cytochrome P450?Steroid hormone biosynthesis?Ascorbate and aldarate metabolism,and etc.The involved genetic information process includes Ribosome?RNA transport?m RNA surveillance pathway?DNA replication and etc.The involved environmental information process includes TNF,VEGF,AMPK,PI3K-Akt,Sphingolipid,NF-kappa B,HIF-1,Erb B,MAPK and other signal pathways.The involved Cellular Processes includes Focal adhesion,Apoptosis-multiple species,Apoptosis,Cell cycle and p53 signal pathway.The involved biological process includes Progesterone-mediated oocyte maturation,Osteoclast differentiation,Longevity regulating pathway-multiple species,Adipocytokine,Thyroid hormone,Toll-like receptor,NOD-like receptor,RIG-I-like receptor,PPAR signal pathway,and etc.The involved human disease includes cancer,amyotrophic lateral sclerosis(ALS),prion disease,bacillary dysentery,salmonella infection,pertussis,legionnaires' disease,leishmaniasis,Chagas(American trypanosomiasis),malaria,toxoplasmosis,tuberculosis,hepatitis C,hepatitis B,measles,influenza A,HTLV infected herpes simplex virus infection,Epstein-Barr virus infection,virus caused cancer,chemical caused cancer,micro RNA cancer,colorectal cancer,renal cell carcinoma,pancreatic cancer,endometrial cancer,glioma,prostate cancer,thyroid cancer,melanoma,urinary bladder cancer,chronic granulocytic leukemia,acute myelogenous leukemia,small cell lung cancer,non small cell lung cancer,breast cancer,diabetes complications,non-alcoholic fatty liver disease(NAFLD),insulin resistance,type-II diabetes,platinum resistance,endocrine disease,and etc.Summary:This part collected more than a thousand medicinal ingredients of Tongxinluo Capsules,constructed traditional Chinese medicine ingredients-drug target network through network pharmacology method,established traditional Chinese medicine ingredients-drug target network,used Cytoscape(3.4.0)software to further analyze correlation network between molecules and target proteins,as well as conducted R-language-based enrichment analysis of pathway to clarify molecular mechanism of Tongxinluo Capsules.Network analysis of Tongxinluo Capsule ingredients with high intermediate number and network degree found these ingredients had anti-inflammation,anti-platelet-aggregation,antipyretic,analgesic,anti-neoplastic and immunity-regulating effects.Studies found targets of main active ingredients of Tongxinluo Capsules mainly involved energy metabolism,oxidative stress,as well as molecular reactions of signal transduction at cell nucleus,cytoplasm and cytomembrane like protein binding,ion binding and enzyme reaction.Further enrichment analysis of pathway found biological pathways where these target proteins located involved lipid metabolism,inflammatory reaction,vasodilatation,vascular endothelial cell protection,myocardial cell protection,and etc.This might be main mechanism of Tongxinluo Capsules in the treatment of cardiovascular and cerebrovascular diseases.Conclusions:1.Guided by the theory of collateral,around the representative collateral disease of angina pectoris of coronary heart disease,the rule of treatment and the rule of drug use were abstracted,etc.,and put forward that the disease is in collateral of the heart,and the main pathological mechanism is “Collateral Qi stasis/deficiency stagnation,collateral stasis resistance and collateral spasm”.In order to provide theoretical support for the follow-up of data mining and analysis of clinical medical cases,the rules and characteristics-“adjust Ying Wei Qi and blood”,follow the characteristics of “five zang organs” and “removing the wind,eliminating collateral stasis and dredging collateral qi” in the treatment of angina pectoris of coronary heart disease were summarized.2.This study is the first one to systematically summarize clinical medical records of CHD angina pectoris patients treated by Professor Wu Yiling.With collateral doctrine as the guidance,eight syndromes of CHD were proposed through using Bayesian analysis and combining with expert experiences.Principal,secondary and accompanied symptoms were analyzed in combination with syndrome-symptom relevance.Frequency analysis was used to summarize drugs frequently used in treatment of this disease,and cluster analysis was used to extract the core prescriptions of each syndrome type.It has important value for collateral-doctrine-gui... |
PDF Full Text Request