A Preliminary Bionetwork Research Of Qi Deficiency And Qi Stagnation In The Context Of Coronary Heart Disease Angina Pectoris

Objective:By combining literature and data mining methods, we want to study coronary heart disease via collecting clinical coronary heart disease Qi deficiency blood stasis pattern and Qi stagnation blood stasis pattern cases. We also want to distinguish two common Chinese medicine patterns Qi deficiency blood stasis pattern and Qi stagnation blood stasis pattern, drawing a diagram of molecular biological networks, getting the relevant type of biological activity and verifying each other clinical parameters detected by the method and the results obtained by literature mining, preliminary inquiry to get the molecular basis of the TCM argument. In conclusion, we aim to create a systematic and convenient intuitive method to distinguish the biological indicators, to contribute for establishing a systematic and objective evaluation system of TCM research.Methods:1、In this study, we establish a data dictionary related NEI genes and HPO of Qi deficiency blood stasis pattern, Qi stagnation blood stasis pattern, to get Qi deficiency blood stasis pattern and Qi stagnation blood stasis pattern characterization term keywords from HPO database. For example, the keyword of Qi deficiency blood stasis pattern is " palpitations which is corresponded the HPO characterization term "Palpitations". We input all of these characterizations of terms keywords entered in PubMed database and retrieve the literature in this summary or title containing these words, and download the summary of these documents, save in Xml format, download Xml file and cleaning and sorting data, then constructed relevant literature archive of Qi deficiency blood stasis pattern and Qi stagnation blood stasis pattern, find characteristically NEI genes by two different literature mining method of Pubminer and Genclip, also find syndromes characterized keywords characteristic NEI genes, then get the two syndromes of key genes and functional annotation clustering by the DAVID Bioinformatics Resources 6.7 software analysis. Finally we get the pattern biological enrichment analysis results through biological pathways and KEGG pathway analysis, In order to explore the different bioactive substances between two patterns, such as hormones, receptors, cytokines, neurotransmitters, etc.2、With coronary heart disease as the starting point, collect coronary heart disease Qi deficiency blood stasis pattern and Qi stagnation blood stasis pattern clinical data, we validate the results of previous literature and data mining, discuss the law of NEI network changes in patients with unstable angina, exploratory find the differences between the two patterns bioactive substances, we also confirmed the literature and data mining can become an effective means of clinical application in the study of TCM pattern.Result:1, Annotation of gene function cluster test results:Use DAVID Bioinformatics Resources 6.7,NIAID/NIH (http://david.abcc.ncifcrf.gov/) software to analyze the above nodes, convert Qi deficiency blood stasis pattern and Qi stagnation blood stasis pattern key gene names. Qi deficiency blood stasis pattern has 17 key genes into three functional annotation clustering, and the abundance score greater than 5.0.Qi stagnation blood stasis pattern has 34 key genes into 15 functional annotation clustering, the abundance score greater than 7.0.The result turns out that Qi deficiency blood stasis pattern clusters related complement, signal transduction, inflammation-related and also associated with myasthenia gravis, immune deficiency diseases, such as glycoprotein’s neuro-endocrine-immune system. Qi stagnation blood stasis pattern clusters include a large number of related neuropathies, late cleavage inactive protein or C segment produced bioactive peptides after amidation, glycoprotein’s, proteins containing disulfide bonds; secretion of hormones and hormone cells biological effects of neuroendocrine response, signal transduction, extracellular region, the phosphorylation reaction, phosphorus metabolism, cellular energy metabolism have regulatory role. In addition, besides Qi stagnation blood stasis pattern related genes also associated with cardiovascular and digestive systems have some relevance.2, GO (Gene Ontology) analytic results:Qi deficiency blood stasis pattern key genes participate in 143 different biological processes (BP),20 different cell components (CC),16 different biological functions (MF); Qi stagnation blood stasis pattern key gene involved in 495 different biological processes,19 different cellular components,20 kinds of different biological functions. The number of genes involved in these common Gene Ontology results from 2-20.Qi deficiency blood stasis pattern related genes participate in major biological processes are involved:the classical pathway of complement, proteins mature peptide bond cleavage, affect circulating immunoglobulin autoimmune diseases, acute inflammation, the adaptive immune response. Qi stagnation blood stasis pattern related genes is mainly produced in biological processes are:intercellular signaling, regulating secretion, regulating system functions such as blood pressure, heart rate, respiration, etc., regulate cellular localization, neural signal transduction, cell surface receptor-mediated signal transduction of organic compounds react positively regulated molecular function, conduction of nerve impulses and so on.3、KEGG pathway analysis results:Qi deficiency blood stasis pattern genes related with complement system pathways and regulating autophagy pathway, Qi stagnation blood stasis pattern genes related with nervous excitement legend-receptor pathway, Jak-STAT signal pathway, cytokine pathway intrinsic link, fat cells and hematopoietic cell lineages factor pathway associated.4、Clinical Data Analysis Results:we select 3 male Qi deficiency blood stasis pattern patients from 87 cases hospitalized patients who has angina pectoris, age between 60-70 years, duration of more than 10 years, and no family history,4 patients who has Qi stagnation blood stasis pattern and 3 same age male normal detecting them related indicators, and the results shown below:the patiens who has Qi deficiency blood stasis pattern patient C3, C4 level are significant difference compared with the normal; Qi stagnation blood stasis pattern CORT T3, T4, T, E2 levels are significant differences compared to the normal.Conclusion:1、Compared with two methods excavated and analysis genetic data, the result display that Qi deficiency blood stasis pattern clusters related endocrine, signal transduction, hematopoietic cells, and inflammatory reactions; Qi stagnation blood stasis pattern clusters related glycoprotein’s containing disulfide bonds protein, G protein-coupled receptor signaling system, catecholamine neurotransmitter activity related to the regulation, which related to the sympathetic regulation. Literature and data mining description that intrinsic biological characteristics of TCM syndrome can effectively identify the NEI level. The literature mining as a province that, effort, and simple mining methods syndromes biological indicators, are also being increasingly adopted by researchers.2、By detecting clinical indicators, biological indicators of early NEI verified through literature and data mining tools to find the network, and to verify the biological active ingredients with different TCM syndrome vary among patients with different syndromes in hormone levels may signal have different performance and distinction on the intrinsic conduction system to adjust the level of the body, which offers the possibility and theoretical support for the objective of the standardization of TCM diagnostic syndromes.