| NSCLC patients undergoing surgery often presented a series of complex symptoms,such as fatigue,cough,shortness of breath and pain,and experienced a heavy symptom burden,which seriously affected the quality of life and subsequent treatments.Due to the complex and different pathogenesis of symptoms,there are no unified clinical protocol for the management of NSCLC postoperative symptoms at present.Therefore,most patients with NSCLC did not take treatment measures after surgery,or only accepted a simple symptomatic treatment for a single symptom,for example,use non-steroidal anti-inflammatory drugs and paracetamol to treat pain,use bronchodilators to treat cough.While there were adverse drug reactions and the curative effects need to be improved.Improving the complex symptoms is the unique advantage of Traditional Chinese Medicine(TCM)in treating diseases.Qidongbufei(QDBF)decoction is a prescription created by Dr.Houwei,it is established according to the pathogenesis of "qi and yin deficiency,phlegm and blood stasis" in NSCLC postoperative patients.It has been applied clinically for many years and has achieved certain efficacy in improving postoperative symptoms of NSCLC.In this study,QDBF decoction was used as an intervention.First,a small sample size pilot study was conducted to explore the feasibility,evaluation methods and sample size estimation,and second,a randomized,double-blind,placebo-controlled study was further carried out to confirm the efficacy and safety of QDBF decoction in improving postoperative symptoms of NSCLC.At the same time,the serum cytokines of patients before and after treatment were detected,and the possible mechanism of QDBF decoction was preliminarily discussed.Ultra performance liquid chromatography mass spectrometry(UPLC-MS)was also used to analyze the active components of QDBF decoction to provide references to explain the material basis of efficacy and drug quality control.1 Research ObjectivesTo evaluate the efficacy and safety of QDBF decoction in the treatment of patients with NSCLC undergoing surgery,explore the possible mechanisms and main active ingredients of QDBF decoction.2 Research MethodsClinical trials included two parts:pilot study(n=36)and the formal study(n=120),adopting prospective,randomized,double-blind,placebo-controlled trial design,NSCLC patients were enrolled according to inclusion and exclusion criteria and divided into treatment group and control group in the ratio of 1:1,treatment group was given QDBF decoction and the control group was given placebo,100 ml each time.twice a day,for 4 weeks in total.Curative effect evaluation included mean symptom severity,symptom threshold events.lung function,and six-minute walking distance(6MWD).Safety indicators included blood routine,biochemistry,urine routine,electrocardiogram and adverse events.Mixed effect model.T test and other statistical methods were used to analyze the efficacy and safety evaluation indexes of the two groups,and the cross-sectional analysis of postoperative symptoms and qualitative analysis of efficacy evaluation indexes were conducted.Meanwhile,serum cytokines levels were detected before and after treatments by ELISA,and the changes of related cytokines were compared.UPLC-MS was used to detect QDBF decoction,so as to identify the main active ingredients.3 Research ResultsA total of 36 subjects were included in the pilot study,of which 2 subjects were detached.After 4 weeks’ intervention,compared with the control group,the symptom threshold events’reduction rate was significantly increased in the experimental group by 14.8%per week on average(treatment group VS control group:23.4%VS 8.6%,P=0.0145<0.05).In the improvement of 6 MWD,the treatment group increased(99.64±60.05)meters,and the control group increased(47.47±57.05)meters,and the treatment group was better than the control group(P<0.05).In FEV1%improvement,the treatment group increased by(12.47±11.34)%,the control group increased by(6.56±12.02)%,the treatment group was better than the control group(P<0.05);In terms of the improvement of FVC%and FEV1/FVC,the values of treatment group increased significantly(P<0.05),but the control group did not change(P>0.05).There were no significant differences in the improvement of mean symptom severity between the two groups(P>0.05).A total of 120 subjects were included in the formal trial,of which 12 subjects were detached.Cross-sectional analysis showed that each postoperative NSCLC patient had an average of 10.03 symptoms with relatively mild degrees.Shortness of breath(94.1 2%),fatigue(92.31%),pain(88.89%),and cough(88.03%)ranked the top 4 symptoms with high incidence.There was no statistical signifiance in demographic data,medical history,surgical methods and other clinical basic information between two groups.After 4 weeks’ intervention,it showed that the average symptom severity of treatment group was decreased by 0.273 points per week,while that of control group was deereased by 0.18 points per week,and the treatment group was better than the control group(P<0.05).In terms of the number of symptom threshold events reduced,the treatment group reduced 0.7 symptom threshold events per week on average,and the control group reduced 0.44 symptom threshold events per week on average,and the treatment group was better than the control group(P<0.05).In the subgroup of baseline pain score≥ 4,the pain score of the treatment group decreased(0.94±1.44)points,and that of the control group decreased(0.43±1.75)points,and the treatment group was better than the control group(P<0.05).In the subgroup of age≥ 60,the drymouth score of the treatment group decreased(2.80±2.30)points,and that of the control group decreased(0.70±1.70)points,and the treatment group was better than the control group(P<0.05).In terms of fatigue score,the treatment group decreased by(1.98±2.19)points and the control group decreased by(0.97±1.74)points,and the treatment group was better than the control group(P<0.05).In terms of drowsy score,the treatment group decreased by(0.98±1.80)points and the control group decreased by(0.14±1.70)points,and the treatment group was better than the control group(P<0.05).In terms of the improvement of nausea,numbness and disturbed sleep,the scores of treatment group decreased significantly(P<0.05),but the control group did not change(P>0.05).In FEV1%improvement,the treatment group increased by(17.65±14.39)%,and the control group increased by(9.74±13.39)%,the treatment group was better than the control group(P<0.05);The 6 MWD of treatment group was increased by(79.66±61.56)meters and that of control group was increased by(51.61±53.98)meters,and the treatment group was better than the control group(P<0.05).Neutrophil was decreased(2.70±1.91)×109/L in treatment group and(1.73±1.25)×109/L in control group,the difference had statistical significance(P<0.05).in shortness of breath,cough,FVC%,FEV1/FVC improvement,there were no statistical differences between the two groups(P>0.05).Experimental researches shows that IL-17 and IgE were decreased in treatment group and increased in control group significantly(P<0.05).IFN-γ increased in treatment group and decreased in control group,and there was significant difference between the two groups(P<0.05).There were no significant differences in IL-6,IL-4,COX-2 and PGE2 between the two groups(P>0.05).In UPLC-MS,by contrast with single drug chromatogram,A total of 33 active ingredients were identified,including baicalin,chrysin,luteolin,han baicalin,baicalein,baicalein isomer,skullcapflavone-Ⅱ,wogonin,Radix Ophiopogonis flavanone E,mulleinisoflavone glucoside,formononetin,rosmarinic acid,lithospermic acid,salvianolic acid A,etc.4 Research Conclusions①QDBF decoction could relieve the overall postoperative symptoms of early NSCLC,relieve fatigue,nausea,numbness,disturbed sleep,drowsy,moderate and severe pain,and elderly patients’ dry mouth,reduce white blood cells and neutrophils and increase lung function and 6MWD,and has good safety.②the efficacy evaluation indexes "average symptom severity" and "symptom threshold events" tend to objectify the symptom evaluation in TCM field,which needs to be further verified and popularized.③ QDBF decoction regulated IL-17,IgE and IFN-y to exert drug effects.④33 active components were identified by UPLC-MS,which proved that multiple components and multiple targets might be the characteristics of TCM in treating diseases,and indicated the material basis of drugs’ efficacy. |
PDF Full Text Request