| Objective:Non-small cell lung cancer(NSCLC)is the most common pathological type of lung cancer.High mortality make survival and prognosis of patients be the focus of attention.With the continuous progress of anti-tumor therapy area,it is of great significance to explore the long-term efficacy and mechanism of drugs.Therefore,the starting point of this study is to understand the prognostic factors of NSCLC and to clarify the long-term efficacy and mechanism of Traditional Chinese medicine for patients.Based on the theory of astringent and strengthening,Chinese herbs has been used in the clinical treatment of NSCLC for many years.It is reported that the representative prescriptions of Qi Jia Fu zheng Prescription and Qi Jia Fuz heng Capsule can improve cancer-induced fatigue and enhance immune function.Through clinical observation,there are many long-term survivors of NSCLC patients who have received TCM compound syndrome differentiation therapy,but its specific long-term efficacy is not clear,and the molecular mechanism of action also needs to be further explored.Methods:1 The results of clinical studies on adjuvant treatment of NSCLC by Chinese medicine were searched,including Randomized controlled trials(RCT),cohort studies and casecontrol studies.The effects of TCM on overall survival and survival rate of NSCLC patients were investigated through Meta analysis,which will provide evidence for the clinical research of this study.2 Retrospective analysis was conducted through collection of clinical data and follow-up of survival information of NSCLC patients.By SPSS 25.0 software,overall survival analysis of the included patients and stratified analysis were conducted.Then,according to the results of survival analysis,the medication rule of patients with survival benefit was analyzed,and the core prescription(HXF)of the astringent and strengthening method was summarized.3 According to the prescription of HXF,the drug components and functional targets were searched in the bioinformation database,and the genes related to the prognosis of NSCLC were retrieved.After the pairing of TCM targets and disease targets,the possible target gene set of HXF affecting the prognosis of NSCLC was obtained.PPI network(Protein Protein interaction,PPI)and enrichment analysis were performed to predict the possible target genes and pathways of NSCLC patients affected by fixation and rehabilitation.4 The experimental animals were divided into groups,and each group was randomly divided into cage A and cage B.①General state and body weight of the mice were observed,the tumor inhibition rate was calculated,and the morphological changes of tissue cells were observed by staining the tumor tissue sections.Moreover,the survival time of the mice was recorded,and the survival data were analyzed and the survival curve was drawn.②Immunohistochemical method was used to compare the expression of CCND1 and Ki67 proteins in tumor tissues of each group of mice.Western blot was used to detect the relative expression levels of C-MyC,p53 and Bax proteins to verify the possible mechanism of HXF action on NSCLC.Results:1 Systematic evaluation and Meta-analysis were performed on 2318 patients with stageⅢ～Ⅳ NSCLC in 22 clinical studies.The control group was treated with Western medicine(platinum-containing chemotherapy/EGFR-TKIs),and the observation group was additionally treated with oral Traditional Chinese medicine compound.The 22 studies included 20 RCTS,1 cohort study,and 1 case-control study.There were 15 studies on TCM combined with chemotherapy,7 studies on TCM combined with EGFR-TKIs,and 20 studies on fuzheng TCM compound.Meta-analysis results showed that compared with the western medicine group,TCM compound combined with western medicine treatment had a positive impact on OS and 1,2 and 3-year survival rate.Patients receiving TCM compound combined chemotherapy showed a better survival benefit in OS and 1,2,and 3-year survival rate.Combined EGFRTKIs had positive impact on influencing OS and 1,2 survival rate,but had no obvious influence on 3-year survival rate.Fuzheng compound combined with Western medicine show better survival benefit compared with non-fuzheng compound for OS and 1,2 and 3-year survival rate of NSCLC patients.2 The average survival time of 424 NSCLC patients included was 95.43 months,and the median survival time was 82.03 months.The 6-month survival rates were 100%,1-year survival rates were 98.64%and 96.72%,2-year survival rates were 64.63%and 60.66%,3-year survival rates were 52.38%and 44.26%,and 5-year survival rates were 27.89%and 22.95%.The 6month survival rates of stage Ⅲ and Ⅳ were 98.39%and 61.11%,and the 1-year survival rates were 56.45%and 27.78%.The 2-year,3-year and 5-year survival rates of stage ⅲ were 41.39%,26.88%and 11.29%,and the 2-year,3-year and 5-year survival rates of stage iv were 0.00%.A Cox multivariate proportional risk regression model was established for 424 NSCLC patients.The results showed that≥ 12 months of TCM exposure was an independent prognostic protective factor.TCM exposure≥ 6m in stage Ⅰ～Ⅱ patients and≥ 12m in stage Ⅲ～Ⅳpatients showed survival benefit.Meanwhile,disease stage and whether stage Ⅲ～Ⅳ patients received chemotherapy were independent prognostic factors of NSCLC patients.3 Data analysis of TCM prescriptions of patients with survival benefit of TCM exposure duration≥ 12 months’ showed that in 215 prescriptions,the cumulative frequency of TCM was 8751 times,including 194 Chinese medicines.By comprehensive analysis,the core formulae were Astragalus,Turtle shell,Fritillaria thunbergii,Herba nobilis,Codonopsis pilosula,Black plum,Paeonia lactiflora,cooked rehmannia,Angelica sinensis and liquorice.4 According to the composition of core prescriptions,a total of 188 components and 324 target genes were retrieved in the database,and 1412 target genes related to NSCLC prognosis were retrieved.A network set of 96 gene targets was obtained,in which the core genes were TP53,AKT1,CASP3,ESR1,JUN,EGFR,TNF,MYC,IL6,HIF1A,STAT3,MAPK3,CCND1.Combined with enrichment analysis results,it can be predicted that the main mechanism of HXF affecting the prognosis of NSCLC may be the regulation of apoptosis and cell cycle and other biological processes.5 The results of observation and detection in tumor-bearing mice showed that:①HXF has a certain effect on improving the general state and correcting anemia of mice;② The results of survival analysis showed that the median survival time of mice in the Sino-Western combination group was statistically significant compared with that in the tumor-bearing model group(30.83±1.74)(P<0.05),the survival time of mice in the chemotherapy group(29.00±0.89)was not significantly better than that in the tumor-bearing model group,and there was a significant difference between the sino-western combination group and the chemotherapy group(P<0.05).③The blood results showed that compared with the tumorbearing model,the high,medium and low dose groups of HXF had obvious efficacy in improving inflammatory response and correcting anemia(P<0.01).④ In terms of tumor inhibition,the median value of tumor mass of mice in the combination group of HXF and Western medicine,chemotherapy group and high-dose HXF group was significantly lower than that in the tumor-bearing model group,and the Ki67 expression in the combination group was significantly lower than that in the chemotherapy group.⑤ In terms of the effect on apoptosis,TUNEL test results showed that the apoptosis rate of the high dose group was significantly different from that of the tumor-bearing model group(P<0.05).Compared with the tumorbearing model group,the expression of Cyclin D1 protein in the integrated Chinese and Western medicine group was significantly different(P<0.05),while the high-dose HXF group showed a decreasing trend,and the result was not statistically significant(P>0.05).The relative expression levels of p53 and Bax protein in the combination group were significantly higher than those in the chemotherapy group(P<0.01).Conclusions:1 The core prescription(HXF)has a positive impact on the survival and prognosis of NSCLC patients.2.HXF can prolong the survival time of Lewis tumor-bearing mice;By improving the degree of weight loss and anemia,promote the expression of p53 and Bax,and reduce the expression of Cyclin D1 in combination with cisplatin,HXF can promote the apoptosis of tumor cells and inhibit cell proliferation,so as to play a comprehensive role in influencing the prognosis of NSCLC patients. |
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