Clinical And Mechanism Study Of Xihuang Capsule Combined With Radiotherapy In The Treatment Of Radiation Injury Of Lung Squamous Cell Carcinoma Based On Network Pharmacology

Objectives:Objective to explore the potential mechanism of Xihuang capsule in the treatment of radiation injury of lung squamous cell carcinoma through network pharmacology;The clinical efficacy of Xi Huang capsule combined with stereotactic radiotherapy in the treatment of lung squamous cell carcinoma was evaluated in the near future,the incidence and grading of RP in February,the efficacy of RP,the score of TCM syndrome,KPS score,QOL score,pulmonary function classification,D-Dimer level,tumor marker level,immune function,incidence rate of adverse reactions and safety index.Objective to provide dialectical thinking and methods for the clinical treatment of lung squamous cell carcinoma with the theory of "coexistence of toxin and blood stasis" combined with radiotherapy,so as to improve the curative effect of traditional Chinese medicine in lung cancer combined with radiation injury.Methods:1.Network pharmacology: the main components and targets of Xihuang capsule were obtained through tcmsp database,and screened according to its oral utilization and drug like properties,supplemented by published literature reports;The potential targets of lung squamous cell carcinoma and radiation injury were found by genecards,OMIM,digenet database and TTD database,and the duplicate values were deleted;The "drug component target" network of Xihuang capsule was constructed by using Cytoscape 3.8.2 software;The three targets were selected to draw the Wayne diagram,and the PPI labeled in the Wayne diagram was constructed by string11.0 database.The topological analysis of the PPI was carried out by Cytoscape 3.8.2 software;Finally,the enrichment analysis was carried out by Cytoscape 3.8.2 and systems dock web site.2.Clinical part: 64 patients were randomly divided into control group and Xihuang capsule group according to the standard of radiotherapy.A total of 61 cases were collected according to the exclusion criteria.The control group(30 cases)received stereotactic gamma ray radiotherapy and symptomatic treatment after radiotherapy.The Xihuang capsule group(31 cases)received oral Xihuang Capsule on the basis of the control group.2 months later.The short-term curative effect,the RP classification and incidence rate,RP efficacy,TCM syndrome score,KPS score,QOL score,pulmonary function classification,D-Dimer,tumor markers,immune function,incidence of adverse reactions and safety index between two groups were observed and analyzed by SPSS26 statistical software after February.Results:1.Network pharmacology: in this study,69 kinds of active ingredients and 309 targets were obtained by mining tcmsp database and literature reports;By mining genecards,OMIM,digenet,TTD and other disease databases,1841 disease targets of lung squamous cell carcinoma and 1601 disease targets of radiation injury were obtained.The Wayne map was drawn to obtain 119 intersection targets.PPI was constructed by string11.0 database and optimized by Cytoscape 3.8.2 software.The analysis showed that the average degree centrality was 10.04 and the average dielectric centrality was 1.50 × The degree centrality and medium centrality,which are both greater than the mean,can screen 21 key targets,accounting for 18.91% of the total nodes.The key targets were analyzed by go biological process enrichment analysis and KEGG pathway enrichment analysis through metascape database.The analysis of the first 20 enrichment analysis pathways showed that the prevention and treatment of radiation injury of lung squamous cell carcinoma by Xihuang capsule might be related to the following pathways;(1)biological process mainly involved in oxidative stress,gland development,radiation resistance,growth stimulating factor,regulatory protein serine / threonine kinase Cell migration and movement,apoptosis and other metabolic pathways are regulated;(2)Cell composition involves cell membrane,nucleus,matrix and so on;(3)Molecular functions mainly involve binding transcription factors,protein kinases,ubiquitin protein ligases,cytokine receptors and regulating the activities of MAP kinases,Phosphotransferases and other enzymes;(4)KEGG pathway analysis,Xihuang capsule treatment of lung squamous cell carcinoma radiation injury may be related to TNF signaling pathway,MAPK signaling pathway;(5)The analysis of active component disease target pathway network showed that the main active components of Xihuang capsule in the treatment of radiation injury of lung squamous cell carcinoma were ellagic acid β-Sitosterol,Petunia,quercetin,etc.2.Clinical observation:(1)there was no significant difference in the short-term efficacy between the two groups;(2)The incidence of RP and grade Xihuang capsule group were better than that of the control group after radiotherapy and 2 months after operation,and the difference was statistically significant;(3)In terms of TCM clinical syndrome improvement between the two groups,Xihuang capsule group was better than the control group,and the difference was statistically significant;(4)KPS score and QOL score between the two groups,Xihuang capsule group were better than the control group,and the difference was statistically significant;(5)The improvement of lung function in Xihuang capsule group was better than that in control group,with statistical difference;(6)The level of D-dimer in Xihuang capsule group was significantly lower than that in the control group;(7)Comparison of tumor markers between the two groups: Xihuang capsule group was better than the control group in reducing the levels of SCC and CYFRA21-1,with statistical difference,but there was no statistical difference in reducing the level of CEA between the two groups;(8)Comparison of immune function between the two groups: the improvement of immune function index in Xihuang capsule group was better than that in the control group,with statistical difference;(9)Two groups of adverse reactions and safety comparison: Xihuang capsule group in reducing the incidence of bone marrow suppression is better than the control group,there is a statistical difference between the two groups during the observation period did not appear obvious abnormalities,allergic reactions and other serious adverse events.Conclusions:1.Network pharmacology: Xihuang capsule can prevent radiation-induced lung injury of lung squamous cell carcinoma,and its biological process mainly involves oxidation stress,glandular development,radiation resistance,stimulating growth factor,regulatory protein serine / threonine kinase,cell migration and movement,apoptosis and other metabolic pathways;Cell composition involves cell membrane,nucleus,matrix and so on;Molecular functions mainly involve binding transcription factors,protein kinases,ubiquitin protein ligases,cytokine receptors and regulating the activities of MAP kinases,Phosphotransferases and other enzymes;According to KEGG analysis,Xihuang capsule in the treatment of radiation injury of lung squamous cell carcinoma may be related to TNF signaling pathway and MAPK signaling pathway.The main active components of Xihuang capsule are quercetin,Petunia,ellagic acid β-Sitosterol,etc.2.Clinical observation: Xihuang capsule can reduce the RP grade and incidence of patients with lung squamous cell carcinoma after stereotactic gamma ray radiotherapy and 2 months after radiotherapy,improve the clinical symptoms of traditional Chinese medicine,improve the KPS score and QOL score of patients,enhance lung function,and reduce the level of D-dimer and tumor markers,Improving immune function and reducing the incidence of adverse events can play a therapeutic effect,and good safety,it is worthy of wide clinical use.