| [Objective]The basic theories of traditional Chinese medicine(TCM),the exploration and research of modern Chinese medicine on lung cancer are summarized in this paper,especially the basic viewpoints and theories of contemporary "cancerous toxin" pathogenesis theory on the etiology,pathogenesis,treatment principle and prescription of lung cancer.On this basis,The clinical efficacy of Fufei Jiedu prescription in the treatment of stage ⅢB/Ⅳ non-small cell lung cancer(NSCLC)based on the pathogenesis theory of " cancerous toxin" was objectively evaluated,which founded on the pathogenesis theory of " cancerous toxin",and the mechanism of action was explored by metabolomics methods.So as to improve the clinical efficacy of lung cancer,and lays a foundation for the improvement and development of the basic theoretical system of Chinese medicine on lung cancer,of the pathogenesis theory of " Cancerous toxin ",clinical application,popularization and further research of Fufei Jiedu prescription.[Methods]1.Theoretical researchBy referring to domestic and foreign literature on lung cancer research,including ancient literature,and then sorted and summarized,to discuss the basic theories of TCM on the disease name,etiology,pathogenesis,diagnosis,syndrome differentiation,treatment principles,treatment methods,prevention and care of lung cancer.To review the research results of modern Chinese medicine on the clinical treatment and mechanism exploration of lung cancer.To explore the etiology,pathogenesis,treatment and prescription of lung cancer based on the important innovative theoretical achievements of modern Chinese medicine--the pathogenesis theory of "cancerous toxin".2.Clinical researchAccording to the unified inclusion and exclusion criteria,a total of 108 stage Ⅲ B/ⅣNSCLC patients were included and randomly divided into treatment group and control group,54 patients in each group.Based on the standard Western medicine treatment,the treatment group was treated with Fufei Jiedu prescription orally at the same time,while the control group was not treated with Chinese medicine or proprietary Chinese medicine with similar efficacy.The main efficacy indicator,general health of quality of life(EORTC QLQ-LC43)and other efficacy indicators were evaluated at the 12th weekend.All efficacy indicators and safety indicators were evaluated at the 24th weekend,including short-term efficacy,quality of life(EORTC QLQ-LC43),TCM symptom score and efficacy,physical status(KPS)score and efficacy,lung tumor markers,high coagulation state indicators,and adverse reactions.3.Metabolomics researchAccording to the inclusion and exclusion criteria of clinical study,10 patients with stage ⅢB/Ⅳ non-small cell lung cancer were included.On the basis of standard Western medicine treatment,patients take Fufei Jiedu prescription plus or minus,5ml peripheral blood was collected from each patient before treatment and 2 weeks after treatment,the plasma was centrifuged and separated,according to the standard process,untargeted metabolomics assays were performed by liquid mass spectrometry(LC-MS),the original detection files(.RAW)were imported into Compound Discoverer 3.1(CD3.1)software for Spectrogram processed and database searched,the qualitative and quantitative results of metabolites were obtained,and then multivariate statistical analysis was carried out.The Differential Metabolites were screened according to the screening criteria of differential metabolites.The biological significance of metabolites was revealed through the enrichment analysis of metabolites.[Results]1.Theoretical Research:The names of lung cancer related diseases in TCM mainly include:Xiji,Xiben,Lung cough,Zhiyin,Feiji,Pulmonary gangrene,Laosou,Pulmonary flower sore,etc.Etiology includes invasion of external evil,diet injury,emotional disorders,deficiency of vital qi.The pathogenesis includes stagnation of qi,mutual knot of phlegm and blood stasis,internal accumulation of poison and toxin,weakness of qi and yin,and visceral dysfunction.The diagnosis emphasizes the combination of look,listen,question and feel the pulse--four ways of diagnosis,pay more attention to pulse diagnosis,and also needs to combine with modern examination.There is no unified standard for syndrome differentiation,but there are"Initial stage,middle stage,final stage"and "three steps" can be followed.Treatment principles and methods include support healthy energy,taking care of both tip and root,regulating qi-flowing for eliminating phlegm,resolving hard lump,improve blood circulation and disperse stasis,detoxification and eliminating cancer,attacking poison and anti-cancer,combining to treat,each has its appropriate.Prevention and care focus on preventive treatment,regulating emotions,and concerning the balance.Modern TCM plays a role of "reducing toxicity and increasing efficiency" in syndrome differentiation and treatment combined with various treatments of Western medicine.TCM plays an anticancer role in regulating tumor microenvironment,inducing apoptosis,promoting autophagy and blocking cell cycle.The theory and practice of syndrome differentiation and treatment of lung cancer represented by the pathogenesis theory of "cancerous toxin" is an excellent achievement of the development of modern Chinese medicine,which pointed out that "cancerous toxin" is the root cause of the occurrence and development of malignant tumors caused by internal and external pathogenic factors,elimination of cancer and detoxification,strengthening the body resistance to eliminate pathogenic factors are the fundamental treatment of lung cancer,Fufei Jiedu prescription is an important formula for the treatment of lung cancer based on the achievement.2.Clinical Research:The disease control rate of Fufei Jidu prescription in the treatment of stage ⅢB/Ⅳ NSCLC was 84.6%,compared with 64.7%in the control group,and the difference was statistically significant(P<0.05).The scores of somatic function,role function,emotion function,social function and general health of the treatment group at the 12th and 24th weekend,were improved compared with that of the control group,the differences were statistically significant(P<0.05),The scores of symptoms,include shortness of breath,insomnia,pain,fatigue,nausea and vomiting,constipation and 24th weekend of anorexia were alleviated compared with the control group,and the differences were statistically significant(P<0.05).In the lung cancer specific module,the scores of shortness of breath,cough,peripheral neuropathy,pain in other parts at the 12th and 24th weekend,hemoptysis,arm and shoulder pain at 24th weekend in the treatment group were reduced compared with that of the control group at the same period,the differences were statistically significant(P<0.05).Most of the TCM symptoms and total symptom scores of the treatment group at the 12th and 24th weekend,were lower than those of the control group,the differences were statistically significant(P<0.05).The TCM symptom efficiency of the treatment group at the 12th and 24th weekend was higher than that of the control group,the differences were statistically significant(P<0.05).The KPS score of the treatment group was higher than that of the control group at the 12th and 24th weekend,and the score stability rate was also higher than that of the control group,the differences were statistically significant(P<0.05).CEA,SCC and CYFRA21-1 in the treatment group were all lower than those in the control group at the same period of 12th and 24th weekends,the differences were statistically significant(P<0.05).The D-D and FDP of the treatment group at 12th and 24th weekends were lower than those of the control group at the same period,the D-D at 12th weekend,D-D and FDP at 12th and 24th weekends were statistically significant(P<0.05).There were 12 kinds of adverse reactions with the incidence of more than 10%in the two groups.All the adverse reactions in the treatment group were reduced compared with the control group except ALT,oral ulcer and proteinuria,differences with statistical significance(P<0.05).The incidence of adverse reactions greater than grade I hemoglobin,neutrophils,oral ulcer,nausea and vomiting,diarrhea,alopecia,peripheral neuropathy and constipation in the treatment group were lower than those in the control group,and the incidence of adverse reactions greater than grade Ⅱ leukocytes,neutrophils,nausea and vomiting,alopecia,peripheral neuropathy and constipation in the treatment group were also lower than those in the control group,the difference was statistically significant(P<0.05).3.Metabolomics Research:A total of 9644 untargeted peaks were detected and 592 metabolites(positive mode)were observed.The metabolites were significantly separated before and after treatment of fufei Jiudu prescription by OPLS-DA model showed.R2Y and Q2Y were 0.923 and 0.374 respectively in the model,a total of 21 kinds of DMs were screened out,of which 9 belonged to lipids and 12 belonged to other classes.Compared with before treatment,the levels of 8 kinds of DMs were up-regulated and 13 kinds of DMs were down-regulated after treatment.Enrichment analysis showed that the DMs with the most significant influence after treatment were lipids,mainly including the metabolism of Fatty alcohols,Fatty esters,Quinones,Aromatic polyketones,Steroids and Glycerides.[Conclusion]Fufei Jiedu prescription based on the pathogenesis theory of "cancerous toxin" has a positive effect on the treatment of stage ⅢB/Ⅳ NSCLC,Compared with simple western medicine treatment,this prescription can control disease progression,improve quality of life,reduce clinical symptoms and improve the symptom response rate,stabilize or improve patients’physical state and improve the stability rate of performance status score,reduce the sensitive tumor markers of NSCLC,improve hypercoagulable state and reduce adverse reactions.Its mechanism may be related to regulating metabolism,changing metabolic spectrum and internal environment,regulating DMs,and significantly affecting lipid metabolism,mainly including the metabolism of Fatty alcohols,Fatty esters,Quinones,Aromatic polyketones,Steroids and Glycerides. |