| ObjectivesIn order to obtain more scientific and effective results to guide clinical treatment,by observing the clinical efficacy of intrapleural injection of cinobufotalin in the treatment of malignant pleural effusion.To explore the molecular mechanism of cinobufotalin injection in the treatment of malignant pleural effusion,by detecting the concentration of vascular endothelial growth factor in malignant pleural effusion and studying the correlation between the concentration and clinical efficacy.MethodsA single-center,prospective,randomized,controlled method was conducted in this study.The patients were randomly divided into treatment group(cinobufagin group)and control group(interleukin-2 group)by random number table method.After one course of thoracic perfusion therapy,the clinical efficacy was evaluated.The main outcome indicator was clinical efficiency and the secondary outcome indicators were erythrocyte in pleural effusion,lactate dehydrogenase in pleural effusion,tumor markers in pleural effusion,KPS score,clinical symptoms and adverse reactions.Through the above results,we compare the efficacy of intrapleural infusion of cinobufotalin and interleukin-2 in the treatment of malignant pleural effusion.Then we detected the concentration of vascular endothelial growth factor in malignant pleural effusion and studied the correlation between the concentration and clinical efficacy,expecting to explore the molecular mechanism of cinobufotalin injection in the treatment of malignant pleural effusion.ResultsA total of 33 patients with malignant pleural effusion who met the inclusion criteria were enrolled in the study.There were 17 cases in the treatment group(cinobufagin group)and 16 cases in the control group(interleukin group).Remove shedding cases,each group remaining 15 patients.1.Evaluation of the effect of pleural effusion volume:In the treatment group,0 cases were cured,2cases were markedly effective,7cases were effective,6cases were ineffective,and the effective rate was 60%.In the control group,0 cases were cured,1 cases were markedly effective,5cases were effective,9cases were ineffective,and the effective rate was 40%.The effective rate of the control group was lower than that of the treatment group,but there was no significant difference between the two groups(P=0.269>0.05).2.Evaluation of the effect of pleural effusion volume quality:The erythrocyte level in pleural effusion of patients in cinobufotalin group was significantly lower than that before treatment.73.33%of patients in cinobufotalin group had erythrocyte decrease of more than 25%,which was significantly higher than that of 33.33%of patients in interleukin-2 group.The difference between the two groups was significant(P?0.016<0.05).The level of lactate dehydrogenase in pleural effusion of cinobufotalin group was lower than that before treatment.40%of patients in cinobufotalin group had lactate dehydrogenase decrease of more than 25%,which was significantly higher than that of 33.33%of patients in interleukin-2 group.There was no significant difference between the two groups(P=0.527>0.05).The level of tumor markers in pleural effusion of cinobufotalin group was significantly lower than that before treatment.73.33%of patients in cinobufotalin group had tumor markers decrease of more than 25%,which was significantly higher than that of 33.33%of patients in interleukin-2 group.The difference between the two groups was statistically significant(P?0.031<0.05).3.Therapeutic evaluation of TCM symptom score:There was no significant difference in TCM symptom score between the treatment group before treatment and the treatment group on the 8th day(P?0.239>0.05);there was significant difference in the treatment group on the 14th day(P= 0.034<0.05);There was no significant difference in the scores of TCM symptoms between the interleukin-2 group on the 8th day and the 14th day of treatment compared with the scores of TCM symptoms before treatment.The P values were 0.288 and 0.071,respectively,which were>0.05.There was no significant difference in TCM symptom score between two groups on the 8th day of treatment(P?0.688>0.05),also on the 14th day of treatment(P=0.395>0.05).4.Evaluation of KPS score:There was no significant difference in KPS score between the 8 th day and 14th day in cinobufotalin group and that before treatment,P values were 0.855 and 0.706,respectively,all>0.05.There was no significant difference in KPS score between the interleukin-2 group on the 8th and 14th day of treatment and that before treatment.The P values were 0.847 and 0.692,respectively,which were>0.05.There was no significant difference in KPS score between the two groups on the 8th day of treatment(P?0.711>0.05)and on the 14th day of treatment(P=0.695>0.05).5.Evaluation of the expression of vascular endothelial growth factor in pleural effusion:?After treatment,the concentration of vascular endothelial growth factor in cinobufotalin group was significantly lower than that before treatment(P?0.038<0.05).There was no significant difference in the concentration of vascular endothelial growth factor between before and after treatment in IL-2 group(P = 0.132>0.05).There was no significant difference in the decrease of vascular endothelial growth factor between two groups(P =0.066>0.05).?46.67%of patients in cinobufotalin group had VEGF decrease of more than 25%,which was significantly higher than that of 13.33%of patients in interleukin-2 group.The difference between the two groups was significant(P=0.016<0.05).?In cinobufotalin group,the decrease of vascular endothelial growth factor in pleural effusion of 9 effective patients and 6 ineffective patients were 937.04±1056.98 pg/ml and-10.00±214.12 pg/ml,respectively.The decrease of vascular endothelial growth factor concentration in effective patients was significantly greater than that in ineffective patients(P=0.028<0.05).6.Safety evaluation:There were no serious adverse events such as bone marrow depression,liver and kidney damage,arrhythmia and so on.Pain and fever were the main adverse reactions in cinobufotalin group,with the incidence of 13.33%and 6.67%respectively.The main adverse reaction of IL-2 group was transient fever,the incidence was 13.33%.Conclusions1.Intrapleural infusion of cinobufotalin injection in the treatment of malignant pleural effusion can control the growth of pleural effusion to a certain extent,and significantly reduce the content of erythrocyte and tumor markers in pleural effusion,which is worthy of further research and application.2.Intrapleural infusion of cinobufotalin injection can reduce the score of TCM symptoms,but has little effect on KPS score.3.Cinobufotalin injection can significantly reduce the concentration of vascular endothelial growth factor in pleural effusion,and the decrease of vascular endothelial growth factor may be related to the efficacy of controlling the volume of pleural effusion.4.Intrapleural infusion of cinobufotalin injection has less adverse reactions and higher acceptance. |
PDF Full Text Request