Traditional Chinese Medicine Syndrome Identification Modes Of Unstable Angina Pector Is Caused By Coronary Heart Disease Based On Data Mining

Objective1. To establish networks of symptoms from four diagnostic methods that TCM syndromes/syndrome elements corresponding from unstable angina pectoris (UAP) patients, form the visualization graphs of symptoms from four diagnostic methods complex networks, and to explore the characteristics and significance of the distribution modes of symptoms from four diagnostic methods in complex network.2. To find the relationships between the traditional Chinese medicine (TCM) syndromes/syndrome elements from UAP patients and the biological parameters, establish the corresponding data platform, explore the roles that biological parameters or their combination modes have played in TCM syndromes identification of UAP patients.3. To establish the distinguished modes between UAP patients and healthy control group based on plasma metabonomics, screen the characteristic metabolites related to the syndromes, establish TCM syndromes identification modes in the metabolic level.Methods1. Literature reviewBy the methods of database retrieval and Shannon entropy mutual information, we screened the symptoms from four diagnostic methods and biological parameters that are both closely related to TCM syndromes/syndrome elements and to the pathophysiological mechanisms from UAP patients.2. Clinical epidemiological investi'gation and researchCombinations of literatures review and experts investigation were used to develop the UAP symptoms from four diagnostic methods questionnaires. We collected the clinical data of1576UAP patients.3. Testing of physicochemical indexWe collected149clinical testing indexes from411UAP patients and tested the levels of plasma TNF-α, MMP-9, ET, NO, APN, sICAM-1, Hcy, Ps, TAFI and HO-1of130UAP patients and30healthy people by ELISA method. Professionals were responsible for the inspections and the quality controls were executed strictly.4. Metabolomics experimental studyWe detected the plasma samples of45UAP patients and15healthy people with hydrogen nuclear magnetic resonance (1H-NMR) detection, and identified the plasma endogenous metabolites from micro-molecules to macro-molecules.5. Establishment of identification modes of TCM syndromes(1) We identified useful relationships among107symptoms from four diagnostic methods by means of Distance-based Mutual Information Model (DMIM). Pajek software2.0was used to analyze the node degrees, the node core values, the connected component and the clustering coefficients of the symptoms from four diagnostic methods network. Then we drew the K-core network graphs, classified graphs according to different colors and different degrees and the abstract graphs.(2) By Chi-Square Automatic Interaction Detection (CHAID) decision tree and ADTree, we established identification modes to explain the relationships between TCM syndromes/syndrome elements of UAP patients and the biological parameters. Folds cross validations were used in this research to minimize the bias produced by random sampling of the training and test data samples. The modes were successfully formed if the sensitivity, specificity and the accuracy were all higher than70%.(3) We analyzed the metabolomics data by OPLS/O2PLS-DA method in SIMCA-P12.0software. Characteristic metabolites related to blood stasis syndrome and qi deficiency syndrome were screened based on the combination of load matrix, VIP graphs and/tests/non parametric test results. Statistica6.0software was used for further clustering analysis to validate the identification effects of the characteristic metabolites.Results1. Symptoms from four diagnostic methods complex networks to identify the syndromes Calculation results of the network attribute indexes showed that:in the networks of UAP, coronary heart disease (CHD) combined with hypertension (HT) and CHD combined with diabetes mellitus (DM) patients, the degree values of107nodes were from0to6. There were3to5connective networks respectively in the three complex networks. and the networks with connected component No.1were the most complex ones. The abstract graphs displayed that: the network of UAP patients were made up of chest pain, tinnitus, chest distress, cough, short breath and burning sensation of five centres. The network of CHD combined with HT included cardiopalmus, nausea and vomiting, dizziness, chest pain, chest distress, cold abdomen and waist. Nodes of CHD combined with DM network were chest pain, chest distress, burning sensation of five centres, cough, hypodynamia and short breath. Results of k-core networks:in the networks of UAP and CHD combined with HT, there were5nodes with the k core value4, which made4-core networks. In the networks of CHD combined with DM, there were17nodes with the k core value3, which formed a3-core network. Classification figures according to different colors showed that:the central nodes suggested the qi deficiency, yang deficiency and qi stagnation syndrome in the three networks. Around the central arranged combinations of symptoms from four diagnostic methods reflected qi deficiency, yin deficiency, blood stasis, phlegm, yang deficiency, heat deposition, qi stagnation and spleen deficiency syndromes.2. Clinical routine test indexes to identify the syndromesIdentification modes of13syndromes/syndrome elements of UAP patients were formed by CHAID method. The identification mode of blood stasis contained TSH, Left ventricular diameter, MPV, DBIL, PTA, Q-T interval, QRS and ALB. The identification mode of qi deficiency contained X TAL, RDW-CV, K, TSH, MONO, hs-CRP, LDL and A peak. The identification mode of yang deficiency contained D-Ⅱ dimer, PDW, FT4, LP(a), CI and PT. The identification mode of cold coagulation contained CRP, RDW-CV, AST, PT and HDL. The identification mode of phlegm contained D-Ⅱ dimer, QTc, MCHC, CK and urine RBC. The identification mode of qi stagnation contained P-LCR, INR, PTA, E peak, Na, TP and MCHC. The identification mode of phlegm-blood stasis contained hs-CRP, TBIL, GGT, PLT, FBG and P-R interval. The identification mode of qi stagnation-blood stasis contained LVPWT, PLT, NE%and BSA%. The identification mode of blood-heat stasis contained hs-CRP, LP(a), MONO, FIB, RDW-CV and MCV. The identification mode of qi-yin deficiency contained MCH, P, MCV, EC and QRS. The identification mode of qi-yang deficiency contained D-Ⅱ dimer, MPV, E peak, P and PT. The identification mode of yin-yang deficiency contained FT3, ALT and MONO%. The identification mode of phlegm-heat stasis contained CI, FS, RDW-CV, RBC, D-Ⅱ dimer, CK-MB, PTA and BUN.3. Biological parameters to identify the syndromesNodes of blood stasis ADTree mode were Ps. MMP-9, NO, sICAM-1, TAFI, Hcy and HO-1. Nodes of qi deficiency ADTree mode were TNF-α, NO. TAFI, sICAM-1, Hcy, APN, Ps and HO-1. Nodes of yin deficiency ADTree mode were MMP-9, APN, sICAM-1, ET and HO-1. Nodes of yang deficiency ADTree mode were TAFI, Ps, sICAM-1, HO-1and MMP-9. Nodes of cold coagulation ADTree mode were sICAM-1, NO, APN, MMP-9, Ps, ET and HO-1. Nodes of phlegm ADTree mode were TNF-α, Ps, NO, HO-1, sICAM-1and TAFI. Nodes of qi stagnation ADTree mode were HO-1, ET, TAFI, Hcy, sICAM-1and NO. Nodes of heat deposition ADTree mode were TAFI, TNF-α, MMP-9, Hcy, Ps, HO-1and APN. 4. Characteristic metabolites to identify the syndromes39endogenous metabolites had been detected, of which34were micro-molecules and5were macro-molecules. OPLS/O2PLS-DA integral matrix graphs of CPMG and LED showed that: distribution region of UAP patients and healthy people, blood stasis and non-blood stasis patients, qi deficiency and non-qi deficiency patients could be completely separated along the t(1) axis direction. The separated modes had a high fitting degree. Characteristic metabolites screening results showed that:characteristic metabolites of blood stasis were valine and acetone. Characteristic metabolites of qi deficiency were acetyl glutamic acid, Lysine, valine and carnitine.Conclusion1. Complex network analysis has contributed a lot to the study on distribution modes of symptoms from four diagnostic methods. With it, we can find the symptoms from four diagnostic methods or their groups that can identify TCM syndromes, analyze the core syndromes of disease, summarize the relationships between various syndromes and the correlation degrees.2. Main biological mechanism of TCM syndrome/syndrome elements for UAP patients(1) Main biological mechanisms of blood stasis syndrome contained thyroid function abnormalities with lower TSH; abnormal MPV and coagulation state; bleeding tendency with lower PTA level; prolongation of QT interval and being prone to cardiac arrhythmia; protein metabolic disorder with lower ALB; protection function with increased DBIL; platelet activation function abnormalities with the change of Ps; disorder in extracellular matrix metabolism with higher MMP-9; disorder in lipid metabolism, amino acid metabolism and vascular endothelium injury;(2) Main biological mechanisms of qi deficiency syndrome contained electrolyte disturbances with lower K ion; inflammatory response with higher hs-CRP and abnormal level of RDW-CV, MONO and TNF-α; ventricular early diastolic dysfunction; compensatory increase in TSH; impaired endothelial function with reducing NO; disorder in glucose, lipid and amino acid metabolism;(3) Main biological mechanisms of yin deficiency syndrome contained disorder in extracellular matrix metabolism with abnormal MMP-9; disorder in lipid metabolism with reducing APN:(4) Main biological mechanisms of yang deficiency syndrome contained coagulation state with higher D-Ⅱ dimmer; platelet activation and thrombosis tendency with abnormal PDW and reducing Ps; coagulation and fibrinolysis disorders with abnormal TAFI; disorder in lipid metabolism with higher LP(a); electrolyte disorders with Cl ion;(5) Main biological mechanisms of cold coagulation syndrome contained inflammatory responses with abnormal CRP; exogenous coagulation abnormalities with elevated PT; disorder in lipid metabolism with lower HDL; abnormal intercellular adhesion state with abnormal sICAM-1; endothelial function injury with elevated ET;(6) Main biological mechanisms of phlegm syndrome contained coagulation and fibrinolytic function change with abnormal D-II dimmer; prolongation of QTc interval and being prone to cardiac arrhythmia; anaemic tendency with rising of MCHC; myocardial injury with increased CK; inflammatory response with significant rising of TNF-a; hyper-function in platelet activation with elevated Ps;(7) Main biological mechanisms of qi stagnation syndrome contained bleeding and coagulation abnormalities with increased P-LCR, decreased INR and PTA; left ventricular diastolic dysfunction; disorder in protein metabolism and liver damage tendency with decrease of TP; anaemic tendency with elevated levels of MCHC; disability in antioxidant with significantly reduced HO-1; disorder in endothelial function with abnormal ET;(8) Main biological mechanisms of heat deposition syndrome contained coagulation and fibrinolysis disorders with abnormal TAF1; inflammatory response with rising of TNF-a and Hcy; hyper-function in platelet activation with elevated Ps;(9) Main biological mechanisms of phlegm-blood stasis syndrome contained inflammatory response with abnormal hs-CRP; oxidative stress reaction with rising of GGT; coagulation condition with higher PLT; disorder in glucose metabolism;(10) Main biological mechanisms of qi stagnation-blood stasis syndrome contained ventricular remodeling with change of left ventricular posterior wall thickness; coagulation and thrombosis tendency with elevated PLT; inflammatory state with higher NE%;(11) Main biological mechanisms of blood-heat stasis syndrome contained inflammatory state with rising of hs-CRP and RDW and abnormal level of MONO; coagulation tendency with higher FIB;(12) Main biological mechanisms of qi-yin deficiency syndrome contained anaemic tendency with abnormality of MCH; electrolyte disturbances with reduced P ion; possible inflammatory state with rising of MCV; ventricular systolic dysfunction with prolongation of QRS;(13) Main biological mechanisms of qi-yang deficiency syndrome contained coagulation and fibrinolytic function change with higher D-H dimmer; thrombotic tendency with decrease in PT and MPV; left ventricular diastolic function;(14) Main biological mechanisms of yin-yang deficiency syndrome contained abnormal thyroid function and inhibition state with significantly reduced FT3; possible inflammatory state with MONO%anomalies; rising risk of CHD with higher ALT;(15) Main biological mechanisms of phlegm-heat stasis syndrome contained severe electrolyte disturbances with reduced Clion; inflammatory reaction with higher RDW; abnormal blood rheological function with increased RBC; myocardial damage with CK-MB abnormalities; clotting tendency with increased PTA.