| At present,chemotherapy is an important treatment method for malignant tumors,which can prolong the survival of patients.However,as the chemotherapy cycle accumulation,it is accompanied by a higher incidence of adverse reactions and a declining quality of life.The overall physical state of the patient declines,and most patients cannot complete the corresponding cycle chemotherapy or maintenance therapy.There is increasing evidence that Chinese medicine can significantly reduce the incidence of chemotherapy-related adverse reactions,improve the physical state of patients,and enhance chemotherapy tolerance.The Yiqiwenyang decoction is an experience decoction of Professor Li Peiwen's with effect in preventing and treating chemotherapy related bone marrow suppression.The prescription is based on the principle of 'enhanced Qi and Yang,improved spleen and kidney function',and its clinical application has been nearly 20 years.Pre-basic animal experiment and clinical trials have shown that Yiqiwenyang decoction could effectively reduce the occurrence of chemotherapy-induced myelosuppression,reduce the rate of neutrophils decline,and could increase the secretion of related stimulating immune factors,reduce the expression of inhibitory immune factors such as VEGF.Based on the previous research,this study further explored the efficacy of Yiqiwenyang decoction in the prevention and treatment of chemotherapy-induced myelosuppression and the effect on regulating of inflammatory factors.The heart rate variability index was used to evaluate the efficacy of TCM reducing the toxicity of chemotherapy and improving the physical state.Purpose:1.To observe the effect of Yiyangyangfang on the improvement of quality of life and TCM symptoms,and to prevent and treat chemotherapy-related myelosuppression.2.To clarify the effect of Yiqiyangyang on physical fitness before and after chemotherapy and its influence on heart rate variability3.To observe the effect of Yiqiwenyang decoction on peripheral blood inflammatory factors,revealing the synergistic effect of Yiqiwenyan decoction on peri-chemotherapy.4.To explore the predictive accuracy of changes in heart rate variability index on bone marrow suppression after chemotherapy.Method:1.By a prospective,randomized,controlled trial.The primary outcome was HRV changes,while the secondary outcomes were chemotherapy-related side-effects and alterations in immune function.Then,set up the Yiqiwenyang group and the chemotherapy alone group(control group),and applied a 12-channel 24-hour dynamic electrocardiograph to perform heart rate variability testing before the intervention of the patients.After 7 days of Chinese medicine intervention,Yiqiwenyang group received chemotherapy,and the control group did not interfere with chemotherapy directly.On the 7th day after chemotherapy,the heart rate variability of the two groups was continuously monitored.Before and after chemotherapy,the 7th and 14th day after chemotherapy,hematology routine test value and symptoms of traditional Chinese medicine were collected.Symptom indicators,quality of life scores,incidence of chemotherapy-related adverse reactions,and systemic inflammation index(NLR,PLR,MLR)after 2 cycles of treatment were statistically processed.2.Before chemotherapy(before Chinese medicine intervention)and on the 7th day after chemotherapy,the two groups of patients collected peripheral venous blood in the morning,and the supernatant was taken after centrifugation.The serum IL-4,IL-10 sPD-1,sPD-L1,VEGF and TGF-? were detected by ELISA.Statistical analysis was performed on the values obtained by ELISA.3.Using the receiver operating characteristic curve(ROC curve)to evaluate the occurrence of myelosuppression and WBC counts after chemotherapy.The cutoff value was defined as the Youden's index,the maximum value approximation.Correlation of HRV prediction of myelosuppression.Result:A total of 56 patients with advanced cancer were enrolled in the study,of which 52 patients were completed the study.Three patients were lost to follow-up in experimental group,24 patients in the YQWY group were completed the study,and one patients in control group was decommissioned due to immunetherapy.1.By recording the heart rate variability index of 12-channel 24-hour dynamic electrocardiogram detection and TCM symptoms,quality of life scores,and hematology indicators before and after chemotherapy,the results suggest that:(1)There was no significant difference in QLQ-C30 score between two group(P>0.05),but Yiqiwenyang decoction had certain curative effect in improving the symptoms of TCM during chemotherapy in patients with advanced cancer.The score of TCM symptoms decreased by more than 1/3,but less than 2/3.The curative effect was partially effective.Among them,the improvement of TCM symptoms such as fatigue,anorexia,weak waist and knees during chemotherapy were more obvious.Yiqiwenyang decoction could improve the patient's tolerance to chemotherapeutic drugs,and is a better clinical drug regimen for accompany chemotherapy in advanced malignant tumors.(2)Yiqiwenyang decoction could significantly improve the incidence of chemotherapy-related myelosuppression in patients with advanced cancer than control group(P<0.05),and reduce the use of granulocyte colony-stimulating factor drugs.At the 14th day,the ratio of leukopenia in Yiqiwenyang group was significantly lower than the control group(P<0.05).This could reflect that Yiqiwenyang decoction could alleviate bone marrow suppression in patients with advanced tumor.The incidence of fatigue at grade ? and above was significantly lower than that of the control group(P=0.030).(3)Yiqiwenyang decoction can improve the heart rate variability of patients with advanced cancer before and after chemotherapy.The difference(?)of the SDNN,SDANNi,SDNN,RMSSD,VLF between baseline and the 7th day after chemotherapy was significant improvement in Yiqiwenyang group than the control group(P<0.05).While the changes of TP,LF,HF were smaller in both group without significant improvement.Yiqiwenyang could regulate the autonomic nerve function(performance status)to let patients better tolerate chemotherapy.(4)There was no significant difference in baseline NLR between the two groups.The MLR and PLR in the Yiqiwenyang group were higher than those in the control group(P<0.05).After 2 cycles of chemotherapy,the NLR,PLR,and MLR decreased from baseline in the Yiqiwenyang group compared with the control group,which was 4.48±2.42 before NLR intervention,which decreased to 3.37±2.30,which was significantly lower than before,but the difference did not reach statistical significance(P=0.70),but NLR<4 had positive effects on prognosis.While in control group,NLR of after 2cycles chemotherapy was higher(4.43±2.30)than baseline(3.44±2.61)2.The detection of sPD-1,sPD-L1,VEGF,IL-10,IL-4 and TGF-? in serum samples before and after chemotherapy in the enrolled patients indicated that the serum VEGF of Chinese medicine Yiqiwenyang group was interfered by traditional Chinese medicine.The concentration of IL-4 was significantly lower than that of the control group and had a certain inhibitory effect(P=0.007;P=0.032).There were no significant differences between the two groups before and after TGF-? and sPD-L1 chemotherapy.There were significant differences of sPD-1 between the two groups before and after chemotherapy.The Yiqiwenyang group was lower than the control group,but there was no statistical difference between the Yiqiwenyang group and the control group(P=0.09;P=0.680).The IL-10 concentrations in the two groups were statistically different before chemotherapy,but there was no significant difference in IL-10 concentrations between the Yiqiwenyang group and the control group after chemotherapy(P=0.356;P=0.476).3.The detection of sPD-1,sPD-L1,VEGF,IL-10,IL-4 and TGF-? in serum samples before and after chemotherapy in the enrolled patients indicated that the serum VEGF of Chinese medicine Yiqiwenyang group was interfered by traditional Chinese medicine.The concentration of IL-4 was significantly lower than that of the control group and had a certain inhibitory effect(P=0.007;P=0.032).There were no significant differences between the two groups before and after TGF-? and sPD-Ll chemotherapy.There were significant differences between the two groups before and after sPD-1 chemotherapy.Although the sPD-1 of Yiqiwenyang group was lower than the control group,but there was no statistical difference between before and after in both group(P=0.09;P=0.680).The IL-10 concentrations in the two groups were statistically different before chemotherapy,but there was no significant difference after chemotherapy(P=0.356;P=0.476)4.The change of heart rate variability(?)in the Yiqiwenyang group was consistent with the occurrence of myelosuppression and the improvement of TCM symptoms.In this study,the ROC curve was used to find the correlation between HRV change(categorical variable)and WBC count on the 14th day after chemotherapy(variables).When the ? of heart rate variability was positive or negative(variation>0 and<0)as the categorical variable,the white blood cell count as the variable on the 14th day after chemotherapy,the results show that the SDNN? and the WBC count on the 14th day after chemotherapy were related to the truncation.When the SDNN? was positive as the categorical variable,the cutoff value WBC?4.18,which is a good match for the occurrence of myelosuppression.In conclusion:1.Yiqiwenyang decoction could improve the change of heart rate variability before and after chemotherapy,reduces the influence of chemotherapy drugs on overall heart rate variability,and improved patients' physical status and had better tolerance to chemotherapy.2.Yiqiwenyang decoction could effectively prevent and treat chemotherapy-related myelosuppression,and reduce the degree of leukocyte and neutrophil decline after chemotherapy,as well as reduce the incidence of chemotherapy-related fatigue,and have certain curative effect in improving TCM symptoms.3.Yiqiwenyang decoction could further reduce the concentration of immunosuppressive factors such as VEGF and IL-4.The improvement of immunosuppression and its synergistic mechanism in patients with advanced tumors by Yiqiyang should be further elaborated.4.The change of HRV index and the incidence of myelosuppression had a good predictive value and could be used as a reliable indicator for predicting chemotherapy-related myelosuppression.5.Heart rate variability can accurately reflect the overall state of the body,reflecting the clinical efficacy of Yiqiwenyang decoction,which can be used as an evaluation index for the clinical efficacy of traditional Chinese medicine. |
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