Based On The Theory Of “Qi Collateral-Blood Collateral” And The Composition Of Immune Cells To Investigate The Network Pharmacology Of "XinJiaJianDingChuan Decoction" And The Clinical Study On The Intervention Of Children With Acute Asthma Attack

This study mainly consists of four parts: theoretical study of traditional Chinese medicine,network pharmacology study,bioinformation study,clinical experiment study and literature review study.The progress theory of "Qi collateral-blood collaterals" was applied to the clinical treatment of children's asthma.By using network pharmacology,the author analyzed Xin Jia Jian Dingchuan Decoction,the clinical experience prescription of the tutor in the treatment of children's asthma,and inferred the pharmacology and molecular biological mechanism of Xin Jia Jian Dingchuan Decoction in the treatment of children's asthma.The characteristics of immune inflammatory infiltration and prognosis of asthma in children were predicted by means of bioinformatics research.Combined with clinical case observation,data collection and specimen analysis,the efficacy evaluation of the difference between Xin Jia Jian Dingchuan Decoction combined with Western medicine therapy and the simple Western medicine treatment.Part ?: Theoretical study of traditional Chinese medicine--based on the progress theory of "Qi collateral-blood collaterals" to explore the syndrome treatment of children asthma" Qi collateral-blood collateral " theory is based on the theory of the the collaterals disease,The diseases of zang-fu organs are closely related to Qi,blood and body fluid,and ultimately attributed to collaterals and veins.Lung to breathe with primary air breathing,as well as Lungs regulating hundreds of blood vessels,consistent to "Qi network" and "blood Collateral"(context),all belong to "bullishness of circulation system" and "heart vein blood circulation system".And the ends of their as with the bullishness of circulation system of traditional Chinese medicine network branch "Qi network" for the end of the disease,blood circulation system network branch the "context",as the qi-blood disease,also for nerve immunity and microvascular obstructive diseases,so this article from the theory of progress of " Qi collateral-blood collaterals " to discuss the childhood asthma,with Xin-Tong-Tong-luo and Luo-Xu-Tong-Bu method in order to guide clinical practice.Part ?: Network pharmacological research--the mechanism of Xin Jia Jian Dingchuan Decoction in the treatment of asthma attacks in children based on network pharmacologyObjective: To investigate the Xin Jia Jian Ding Chuan Decoction in the treatment of acute asthma attack in children by network pharmacology.Methods: With the help of the Traditional Chinese Medicine Systems Pharmacology(TCMSP)platform to screen the active components of the Xin Jia Jian Ding Chuan Decoction,combined with the results of the analytical components identification of the Xin Jia Jian Ding Chuan Decoction,the potential target genes of the active ingredients were screened through the Drug Bank database.Four databases,CTD Platform,Uniprot Platform,TTD Platform and Gene Cards,were used to obtain the target genes strongly related to childhood asthma,and the intersection target genes were obtained through Venn online tool,and the PPI network diagram of the intersection target genes was constructed by combining with String database.Using Cytoscape3.8.0 in Network analyzer plug-in to build "drug ingredients targets-disease targets" Network,will be the main active composition of screening and validation key targets for molecular docking,with the help of DAVID online tools for intersection target function of the gene ontology(GO)and Kyoto encyclopedia(KEGG)gene and genome pathway enrichment analysis,get a new add and subtract soup treating children asthma important signaling pathways regulating target genes and enrichment.Results: 1.There were 40 active components in Xin Jia Jian Ding Chuan Decoction;2.2.There were 134 effective targets for the 12 herbal drugs in Xin Jia Jian Ding Chuan Decoction,which intersected 30,247 molecules strongly related to asthma,129 key targets were obtained(130 genes with corresponding names were found in this recipe),and52 core genes were screened out by degree value greater than average;3.The molecular docking results showed that the components played the most important role in ephedra,followed by convoluta convoluta,mulberry bark and Perilla seed,followed by white peony,scutellaria,ginger pinellia,cassia twine,radix radish,radish seed and schizandrae chinensis.4.GO enrichment and KEGG pathway enrichment results showed Xin Jia Jian Ding Chuan Decoction for independent tyrosine phosphorylation,protein kinase B signal is regulation,transmembrane receptor protein kinase signaling pathways,positive regulating angiogenesis,serine phosphorylation,positive negative regulation of cell apoptosis,cell migration,positive regulating cell proliferation,positive transcriptional regulation of RNA polymerase II promoter and pathway enrichment is obvious for VEGF signaling pathways,HIF-1 signal pathway,protein,polysaccharide,Fox O signal pathways in cancer,sticky spot,Rap1 signal pathways,cancer pathways,Ras signaling pathways,9 signaling pathways such as PI3K-Akt signal pathway had strong correlation.Conclusions: This study provides proteomics,genomics and metabolomics basis for the study of the mechanism of Xin Jia Jian Ding Chuan Decoction in the treatment of children with asthma,and provides scientific basis for the development of clinical combined efficacy of Xin Jia Jian Ding Chuan Decoction in multi-effect sites,multi-target sites,multi-pathway and multi-component.Part ?: Bioinformatics-Bioinformatics analysis of diagnostic biomarkers related to immune cell infiltration in childhood asthmaBackground: Asthma is the most common chronic disease in children,and immune cell infiltration plays a key role in the progression of childhood asthma(CA).Therefore,the purpose of this study was to explore potential biomarkers for diagnostic CA and to analyze the role of immune cell infiltration in CA progression.Methods: The gene expression profile of CA(GSE40732)was downloaded from GEO database,and the relative abundance of 29 immune-related items in each sample was calculated by single-sample gene-set enrichment analysis(SSGSEA).We used an estimation algorithm to calculate the immune and stromal scores in patients with CA.We then examined differences in immune cells,human leukocyte antigen(HLA)genes,immune checkpoint molecules,T-Helper 1(Th1)/ interferon-?(Th1/IFN-?)pathways,and N6-methyladenosine(M6A)in the two subtypes.Marker genes were extracted from high immunity,low immunity and control.Go and KEGG pathway enrichment analysis was performed.Meanwhile,the protein-protein interaction(PPI)network was constructed and visualized,and the central genes were identified.Finally,we performed transcription factor enrichment analysis on marker genes.Type 2 immune responses are characteristic of upper respiratory allergic rhinitis and lower respiratory asthma,and the details of these responses are well understood.Ig E-triggered hypersensitivity to airborne allergens,activation of airway epithelial cells,chemotherapy attraction of effector cells(mast cells,eosinophils,and basophils),and remodeling of epithelial cells and subepithelial stroma.Results:According to the immunogenomic maps of 29 immune characteristics,CA subtype was identified.We named two CA subtypes: high immunity and low immunity.Immune hypertype was characterized by immune activation,increased immune score and the highest CD4+ T cell infiltration.The expression of HLA gene,immune checkpoint molecule and IFN-? gene was activated in patients with high immune subtype.In addition,immune-related M6 a RNA methylation was increased in immunohigh subtypes.Functional and signal pathway enrichment analysis further indicated that the genes differentially expressed between the high immune subtypes and other subtypes were mainly involved in olfactory transduction and chemical stimulation of olfactory sensory perception.PPI network analysis showed that 7 central genes were found in the high immune subtype and 14 central genes were found in the low immune subtype.IRF1,IRF4 and PAX5 are important transcriptional regulators in CA immune response.Conclusion: A comprehensive description of CA subtypes based on immune characteristics is helpful to provide potential therapeutic strategies for CA.Part ?: Clinical experimental study--clinical study on the intervention of "Xin Jia Jian Ding Chuan Decoction" in asthma attack(wind and phlegm beating syndrome)Objective: Observation of terbutaline sulfate + budesonide atomization joint new add and subtract anti-asthma soup(Xin Jia Jian Ding Chuan Decoction,XJJDCD)and terbutaline sulfate +budesonide atomization joint singulair(meng Ruth Turner)treating children asthma(wind phlegm muscle certificate)of clinical observation and research.The study shows that the incidence of acute asthma in children is 51.0%,and this type of asthma is the main syndrome of children's acute asthma attacks.Therefore,it is an important purpose to seek effective Chinese medicine therapy for the treatment of this type of asthma.Methods: Selection the Department of pediatrics of The First Affiliated Hospital of Henan University of Chinese Medicine and The First Affiliated Hospital of Zhengzhou University in December 2019 to January 2021 through the randomized,controlled trial design,were randomly divided into treatment group(treatment group)which combines traditional Chinese medicine with western medicine and western medicine control group(control group),according to the discharge standard,combine traditional Chinese and western medicine group original cases 62 cases,excluding cases in 2 cases,the western medicine control group in the original case 61 cases,excluding cases in 1 case,and finally into a total of 120 children with asthma(wind phlegm muscle certificate),60 cases in each group,the western medicine control group given terbutaline sulfate + budesonide atomization joint singulair(meng Ruth Turner),the integrated treatment of traditional Chinese and western medicine treatment group on the basis of the western medicine control group the atomization treatment +XJJDCD,To observe the clinical efficacy of terbutaline sulfate + budesonide atomization combined with XJJDCD in the treatment of acute mild to moderate asthma attack(wind-sputum beating syndrome),and to provide a scientific clinical experimental basis for the prognosis of acute asthma attack(wind-sputum beating syndrome).Effectiveness evaluation indicators: Fe NO,lung function test,blood routine and immunization,peripheral blood indicators:(1)Serum markers of asthma: ICAM-1,IL-33;(2)Macrophage polarization: M1 type(TNF-?);M2 type(TGF-? and VEGF).(3)Indicators of Hypoxia,vascular remodeling and matrix deposition: HIF-1?,MPO,NOS2,ANG-1,TIE-2,MMP12,MMP9.Results: The clinical experimental results and discussion found that,on the basis of the baseline data is consistent,in the two groups of Fe NO,FEV1 / FVC,Ig E and CD4 / CD8 T cells before and after treatment with statistical significance(P < 0.05),but no difference between the two groups after treatment(P > 0.05),and prove that combine traditional Chinese and western medicine treatment compared with western medicine can produce the same effect,so the treatment can be combine traditional Chinese and western medicine program,can also relieve asthma acute onset of mild-to-moderate,and relieve allergic reaction,reduce the attack opportunity.Eosinophils,NOS2,IL-33,TNF-?,TGF-?1,Tie-2,ANGI,ICAM-1,VEGF,MPO,HIF-1?,MMP9 and MMP12 were different between the two groups before and after treatment and also the after treatment between two groups(P < 0.05).Clinical trials show that the integrated treatment of traditional Chinese and western medicine group has better advantages,which can inhibit the allergy,improve asthma inflammation,regulating immune regulation(M1,M2,immune response),antioxidant to improve oxidative stress,repair the airway epithelium,inhibition of epithelial cells and relieve matrix deposition,to improve the airway inflammation,airway hyperresponsiveness than western medicine.