| Background:One of the essence of traditional Chinese medicine is syndrome differentiation and treatment,and the essence of syndrome differentiation and treatment lies in the grasp of syndromes.As long as the syndromes are the same,even different diseases can also adopt the same treatment,that is,the so-called ’ same treatment for different diseases ’.Qi stagnation and blood stasis syndrome is a common clinical syndrome,which can appear in many clinical systems and diseases.With the development of high-throughput sequencing,various omics technologies and bioinformatics,people ’s understanding of traditional Chinese medicine has gradually shifted from macro to micro.How to integrate information at all levels is still a major problem in the modernization of traditional Chinese medicine.Phenotypic group is the sum of the overall phenotypic characteristics expressed by genotypes under the influence of specific environment,which has the overall characteristics.Phenotypic group is a quantitative study of the complex relationship between various levels of phenotypic group.Syndrome phenotypic group was first proposed by Wang Zhong et al.in 2015,which can explain the scientific connotation of syndromes under the guidance of the holistic concept of TCM theory and the concept of syndrome differentiation and treatment.It has important value in the modernization of TCM and individualized medical research.However,in recent years,no research papers on phenomics have been published at home and abroad.Based on this,this paper defines the phenotype group of qi stagnation and blood stasis syndrome as qi stagnation and blood stasis syndrome related disease group,symptom group,traditional Chinese medicine group and genome.Among them,the disease group and symptom group are the macro phenotype group of qi stagnation and blood stasis syndrome.The genes corresponding to qi stagnation and blood stasis syndrome,disease and symptom are the micro phenotype group of qi stagnation and blood stasis syndrome.The genes of traditional Chinese medicine and traditional Chinese medicine are the phenotype group of qi stagnation and blood stasis syndrome.According to the principle of ’prescription syndrome corresponding ’,traditional Chinese medicine can be classified into macro phenotype group,and the genes corresponding to traditional Chinese medicine can be classified into micro phenotype group.Objective:The phenotypic group network of qi stagnation and blood stasis syndrome was constructed,and the characteristics of qi stagnation and blood stasis syndrome network were found.The multi-level phenotypic information of qi stagnation and blood stasis syndrome,symptoms(signs),traditional Chinese medicine and genes were integrated to carry out the phenotypic group study of qi stagnation and blood stasis syndrome,and to explore the common mechanism of qi stagnation and blood stasis syndrome for the same treatment of different diseases,so as to provide clues for the clinical diagnosis and treatment of qi stagnation and blood stasis syndrome and the development of new drugs for syndromes.Material and Method:The clinical research papers related to qi stagnation and blood stasis syndrome published in China National Knowledge Infrastructure(CNKI),Chinese Science and Technology Journal Database(VIP),Wanfang Data Knowledge Service Platform,Pubmed,Cochrane Library and Web of Science from the establishment of the database to May 20,2022.In the Chinese patent medicine value evaluation information database,the Chinese patent medicine information with the main function of promoting qi and activating blood was retrieved.The above two parts of data were combined,and the data were screened according to the inclusion and exclusion criteria.The related diseases,symptoms and traditional Chinese medicine of qi stagnation and blood stasis syndrome were extracted and standardized.The diseases were classified and summarized according to ICD-11,and the diseases with the highest frequency in the three categories with the highest frequency were selected as the research objects of qi stagnation and blood stasis syndrome.Association rules were used to construct the network of qi stagnation and blood stasis syndrome related symptoms(signs)group and traditional Chinese medicine group.The complex network analysis method was used to select the top 15 symptoms(signs)of degree centrality,intermediary centrality and adjacent centrality,traditional Chinese medicine as important symptoms(signs)of qi stagnation and blood stasis syndrome and important traditional Chinese medicine.The important symptoms(signs)of qi stagnation and blood stasis syndrome and the related targets of important traditional Chinese medicine were retrieved in the current public bioinformatics database.The link relationship between the targets was constructed based on the PPI network with more than 240,000 undirected links collected by the Barabasi team.The related targets were weighted by the support between qi stagnation and blood stasis syndrome,symptoms(signs)and traditional Chinese medicine in association rules.The weighted scores were added as the final score of the target.The nodes were scored by random walk algorithm,and the nodes with the final score≥10 were taken as the important targets of qi stagnation and blood stasis syndrome.Finally,the default of the three-layer network of the microphenotypic group of qi stagnation and blood stasis syndrome is a fully connected network.Starting from the qi stagnation and blood stasis syndrome,the nodes directly connected to any node in the target layer of qi stagnation and blood stasis syndrome in the important symptom(sign)layer and the important Chinese medicine layer are found as the final core sub-network.GO and KEGG enrichment analysis was performed on the core sub-network of qi stagnation and blood stasis syndrome,and the intersection of GO/KEGG between qi stagnation and blood stasis syndrome and disease was taken as the common mechanism of qi stagnation and blood stasis syndrome.Results:Finally,1761 articles related to qi stagnation and blood stasis syndrome and Chinese patent medicine data were included.The three categories with the highest frequency of disease were urogenital system diseases,circulatory system diseases,musculoskeletal system or connective tissue diseases.The diseases with the highest frequency in these three categories were dysmenorrhea(155 times),stable coronary heart disease(268 times)and lumbar disc herniation(48 times).The important symptoms(signs)of qi stagnation and blood stasis syndrome are chest distension,chest pain,hypochondriac pain,fixed pain,tingling,purple tongue,purple tongue,purple tongue,petechia,astringent pulse,string pulse,thin pulse and deep pulse.The important traditional Chinese medicine is bupleurum,radix paeoniae rubra,rhizoma ligustici wallichii,angelica sinensis,,safflower and peach kernel.The important symptoms(signs)of stable coronary heart disease are chest distension,chest pain,tingling,fixed pain,hypochondriac distension,shortness of breath,palpitation,upset,dizziness,purple tongue,purple tongue,string pulse,string pulse,astringent pulse and thin pulse.The important traditional Chinese medicine is salvia miltiorrhiza,rhizoma ligustici wallichii,bupleurum,angelica,safflower,notoginseng,astragalus and peach kernel.The important symptoms(signs)of dysmenorrhea are less abdominal pain,less abdominal distension,premenstrual abdominal pain,menstrual abdominal pain,pain rejection,chest distension,breast distension,menstrual blood clip block,dark purple menstruation,less menstrual flow,purple tongue,purple tongue spot,wiry pulse and deep pulse.The important traditional Chinese medicines are Angelica sinensis,Cyperus rotundus,Corydalis yanhusuo,Ligusticum chuanxiong,Paeonia lactiflora,Safflower,Paeonia lactiflora,Persicae semen,Curcuma zedoaria,Bupleuri Radix and Salvia miltiorrhiza.The important symptoms(signs)of lumbar disc herniation are unfavorable rotation of the waist,unfavorable elevation of the waist,stiffness of the waist,low back pain,leg pain,ting pain,fixed pain,night pain,purple tongue spot,purple tongue,purple tongue,thin white coating,wiry pulse,astring pulse.The important traditional Chinese medicines are Angelica sinensis,Chuanxiong,Achyranthes bidentata,peach kernel,safflower,earthworm,Eucommia ulmoides,Corydalis yanhusuo,Dipsacus asper,Astragalus membranaceus,Cyperus rotundus,Angelicae Pubescentis Radix,Spatholobi Caulis.A total of 602 targets were obtained from qi stagnation and blood stasis syndrome,193 targets were obtained from important symptoms(signs),994 targets were obtained from important traditional Chinese medicine,310 targets were obtained from stable coronary heart disease,563 targets were obtained from important symptoms(signs),1018 targets were obtained from important traditional Chinese medicine,154 targets were obtained from dysmenorrhea,661 targets were obtained from important symptoms(signs),1047 targets were obtained from important traditional Chinese medicine,58 targets were obtained from lumbar disc herniation,53 targets were obtained from important symptoms(signs),and 1002 targets were obtained from important traditional Chinese medicine.There were 55 important targets and 10 core targets in qi stagnation and blood stasis syndrome,46 important targets and 24 core targets in stable coronary heart disease,154 important targets and 129 core targets in dysmenorrhea,75 important targets and 42 core targets in lumbar disc herniation.A total of 35 CC,571 BP,39 MF,and 24 KEGG pathways were obtained for qi stagnation and blood stasis syndrome.A total of 27 CC,817 BP,46 MF,and 43 KEGG pathways were obtained for stable coronary heart disease.A total of 49 CC,1932 BP,92 MF,and 131 KEGG pathways were obtained for dysmenorrhea.A total of 19 CC,714 BP,37 MF,and 71 KEGG pathways were obtained for lumbar disc herniation.There were two intersections of CC between qi stagnation and blood stasis syndrome and three representative diseases,which were membrane rafts and membrane microdomains.There were 19 intersections of BP,including positive regulation of epithelial mesenchymal transformation,cartilage development,connective tissue development,and regulation of epithelial to mesenchymal transformation.There was one intersection of MF,which was cytokine receptor binding.There were three intersections of KEGG,which were AGE-RAGE signaling pathway,Th17 cell differentiation and human T cell leukemia virus 1 infection in diabetic complications.Conclusion:The biological mechanism of qi stagnation and blood stasis syndrome can be divided into two categories.One is closely related to atherosclerosis.The main mechanism may be that under the stimulation of a series of physical and chemical factors,through the membrane raft and membrane micro area of the cell membrane,on the one hand,it affects the binding of various cytokines and receptors in the body.On the other hand,the abnormal expression of vascular endothelial molecules,a variety of inflammatory mediators invade vascular endothelial cells,making vascular endothelial cells transform into mesenchymal cells.At the same time,oxidative stress is initiated,vascular homeostasis is destroyed,and extracellular matrix is remodeled.With the infiltration and migration of inflammatory cells,intravascular damage is increasing,plaque area is expanding and instability is increasing.In this process,due to the feedback regulation mechanism of the body and the addition of human intervention such as lifestyle and drugs,plaques may dissolve and wounds may be repaired.However,the long-term recurrence of this process will cause vascular calcification and fibrous lesions,destroy vascular smooth muscle and vascular endothelial function,make blood vessels unable to contract and relax normally,and fail to exert normal secretory function,thus triggering a series of vascular events and becoming an important pathological process of many diseases.The other category includes gastrulation embryo formation,myeloid cell differentiation,etc.,which are mostly derived from embryonic tissue,may be more inclined to genetic factors,and may be closely related to qi stagnation and blood stasis syndrome.However,there are not many studies in this area.At the same time,it is not clear whether genetic factors are closely related to atherosclerosis.These may become future research directions. |
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