Clinical And Network Pharmacology Study Of Qijia Fuzheng Recipe In The Treatment Of Advanced Non-small Cell Lung Cancer With Deficiency Of Spleen And Kidney

1 OBJECTIVE AND SIGNIFICANCETo observe the improvement of TCM syndrome scores and quality of life in the treatment of advanced NSCLC with Qijiafuzheng Formula combined with chemotherapy;explore the molecular mechanism of Qijiafuzheng Formula in the treatment of NSCLC based on network pharmacology,and treat the NSCLC subsequent studies of small cell lung cancer establish the basis.2 METHODS2.1 clinical studyThe clinical study is an open-label clinical controlled trials that included patients with advanced NSCLC who met the criteria.The patients were divided into experimental group and control group.The experimental group was treated with Qijiafuzheng Formula combined with chemotherapy,and the control group was given the same regimen with chemotherapy alone.The patients were interviewed before medication,at week 2,at week 4,at week 6 and at week 8,and the clinical data were collected and recorded on the case report form.The main observation indexes includes TCM symptom score,single symptom score,while the secondary observation indexes includes blood routine and liver and kidney function indexes,KPS score and weight changes.To evaluate the improvement of TCM symptom score,single symptom score,quality of life and safety of Qijiafuzheng Formula in patients with advanced NSCLC by analyzing data.To evaluate the detoxification effect of Qijiafuzheng Formula on side effects of chemotherapy by analyzing the changes of blood test,liver and kidney function and the occurrence of adverse reactions.2.2 network pharmacology researchThe network pharmacology research part is based on the network pharmacology research method,through the retrieval public database carries on the screening and the target prediction to the active ingredient of Qijiafuzheng Formula.NSCLC related targets were screened,and the intersection of drug active ingredient targets and disease targets was selected to obtain common potential targets.Build networks with STRING and Cytoscape software to screen key targets.KEGG pathway analysis and GO analysis were conducted based on key targets,and the "drug component-key target-pathway" action network was constructed to speculate the molecular mechanism of Qijiafuzheng Formula in the treatment of NSCLC.3 RESULTS3.1 clinical study62 patients with advanced NSCLC who met the criteria were included in the clinical study,including 30 patients in the treatment group and 32 patients in the control group.There were no statistically significant differences between the two groups in age distribution,gender distribution,baseline weight,KPS score,clinical stage and pathological type(p<0.05).At the baseline,there were no significant differences in TCM symptom score,quality of life score,blood picture,liver and kidney function between the two groups(p<0.05).(1)Main observation indicators:? TCM syndrome scores:intra-group comparison:TCM syndrome scores before and after treatment(18.07±8.51 points before treatment,13.47±5.72 points after treatment,4.6±4.17 points before and after treatment)were statistically significant(p<0.05).There was no significant difference in the scores of the syndrome before and after treatment(18.81±7.53 before treatment,18.69±7.56 after treatment,and the difference between before and after-0.56±2.66)(p>0.05).Comparison between groups:The difference between the groups after treatment was statistically significant(p<0.05).?Single symptom score:intra-group comparison:There was statistical difference between the treatment group in fatigue,shortness of breath,insomnia,spontaneous sweating/night sweat treatment,p<0.05,and the other symptoms were not statistically different,p>0.05.There was no statistical difference between the symptom groups in the control group before and after treatment,p>0.05.Comparison between groups:fatigue,shortness of breath,insomnia,spontaneous sweating/night sweat symptoms improved after treatment,the difference between the groups was statistically significant(p<0.05),the treatment group effective rate was 57.1%,52%,43.5%and 37.5%;There was no significant difference in the improvement of chest tightness,chest pain,palpitations,cough,cough,nausea/vomiting,diarrhea and constipation symptoms after treatment(p>0.05).(2)Secondary observation indicators:?There was no significant difference in white blood cell and neutrophil count between the treatment group before and after treatment(p>0.05).The difference of white blood cell and neutrophil count before and after treatment was statistically significant(p<0.05),and showed a downward trend.The difference of leukocyte and neutrophil reduction before and after treatment was statistically significant(p<0.05).?There was no significant difference in red blood cell,platelet count and hemoglobin level between the two groups(p>0.05).There was no significant difference in red blood cell,platelet count and hemoglobin level before and after treatment in the control group(p>0.05).?The change rate of KPS scores before and after treatment was statistically significant(p<0.05).?The difference in body weight change rate before and after treatment was statistically significant.(3)Safety indicators:Before and after treatment,there were no obvious abnormalities in liver and kidney function,urine routine and ECG.3.2 network pharmacology researchIt is predicted that Bianjia Fuzhengfang will treat 106 NSCLC targets and scre en 20 key targets,including SRC,EGFR,KDR,MMP9,ERBB2,MMP2,PLG,PTGS2,ESR1,FLT1,TIMP 1,PGR,MMP 1,HSP90AA1.,CDK2,CDK4,CDK1,TOP2A,HSP90AB 1,TOP2B.(2)The KEGG pathway analysis classifies the pathways enriched by the target accord ing to their functions,and is divided into seven functional groups including cancer-re lated functional groups and hormone-related functional groups.Most of these genes(a bout 60.71%)are enriched in cancer-related functional groups,including prostate cance r-related pathways,signaling pathways such as the PI3K-Akt signaling pathway.?GO analysis of key targets showed that the biological functions of Qijiafuzheng include participation in extracellular matrix disassembly,cyclin-dependent protein serine/threo nine kinase activity in Gl/S transition of mitotic cell cycle,transmembrane receptor Body protein tyrosine kinase activity,ErbB2 signaling pathway,cyclin binding,regulatio n of telomerase activity,etc.?To construct a"pharmaceutical component-key target-pat hway"network to screen out 32 major components of NSCLC,as well as p53 signali ng pathway,VEGF signaling pathway,NSCLC pathway,IL-17 signal transduction path way,Prostate cancer pathway,HIF-1 signaling pathway,adhesion junction pathway,pancr eatic cancer pathway,bladder tumor pathway,progesterone-mediated oocyte maturation pathway,estrogen signal transduction pathway,fluid shear stress and atherosclerosis 12 main active pathways.4 CONCLUSION4.1 clinical studyQijiafuzheng Formula can improve the clinical symptoms of patients with advanced NSCLC with spleen and kidney deficiency,improve quality of life,and reduce chemotherapy-related myelosuppression.It can be used as a reference for clinical application of Qijiafuzheng Formula.4.2 network pharmacology researchQijiafuzheng Formula may interfere with non-small cell lung cancer through multi-channel and multi-target.The pharmacological mechanism may be through intervention of SRC,EGFR,KDR,MMP9 and other key targets to interfere with iN-OS activity,extracellular matrix degradation and cells cyclin binding protein and other molecular functions and processes affect estrogen signaling,HIF-1 signaling,VEGF signaling,etc.,thereby inhibiting angiogenesis and controlling tumor growth and invasion and metastasis.