Clinical Observation And Mechanism Research Of Yiqi Tongyang Prescription In The Treatment Of Chronic Immune Thrombocytopenia

BackgroundImmune thrombocytopenia(ITP)is an acquired autoimmune disease characterized by isolated thrombocytopenia.The initial onset of the disease(especially in children)is mostly self-limited,and when the disease persists for no more than 12 months,it is transformed into Chronic Immune thrombocytopenia(CITP),The disease of CITP is easy to repeat,delayed and not cured,and the long-term treatment effect is not good.Western medicine often has many problems such as drug dependence,drug resistance and side effects,which is the hotspot and difficulty in the current medical field of hemorrhagic diseases.Traditional Chinese medicine has its own unique advantages in improving clinical symptoms,promoting the reduction of hormone drugs,reducing the toxic and side effects of western drugs and promoting platelets.ITP is an autoimmune disease mainly characterized by pechymosis and pechymosis of skin and mucosa and bleeding of viscera.ITP can be classified into the categories of "blood syndrome","spots" and "epistaxis" in TRADITIONAL Chinese medicine.Due to its frequent fatigue symptoms,ITP can also be classified into the category of"exhaustion",which has been explicitly named as "purpura disease".Based on the "fu yang thought" and "warming Yang nourishing Qi" and "tong yang"as the entry point,Professor Ma Rou,Xiyuan Hospital,Chinese Academy of Traditional Chinese Medicine obtained long-term experience in the treatment of chronic and refractory recurrent ITP.Professor Ma Rou believes that the pathogenesis of ITP is mainly "fire" and "air injury".The acute stage is mainly "fire",and the treatment is to harmonize camp wei,cool blood and stop bleeding.Chronic stage is mainly "qi injury",qi deficiency day long injury Yang can be seen Yang deficiency symptoms,so the increase and decrease of qi tongyang prescription.Clinical observation shows that it has obvious advantages in improving TCM syndromes,increasing PLT count,alleviating bleeding and fatigue symptoms.TCM follows the principle of syndrome differentiation and treatment and emphasizes individualized treatment,which can significantly reduce the clinical symptoms of patients and improve their quality of life.Embodies its overall concept,syndrome differentiation and treatment characteristics.Objective1.Through clinical trial observation,to explore the effect of Yi qi Tong yang prescription on improving clinical symptoms and improving platelet level in patients with CITP.2.To analyze the change characteristics of T lymphocyte,cytokines and platelet activating molecule expression of patients with CITP before and after treatment and its relationship with clinical efficacy,to explore the possible mechanism of action from the perspective of "nourishing air temperature Yang" to treat air-resistant blood group CITP,and to provide a new idea and method for clinical treatment of CITP.MethodsRandomized controlled clinical trials were used in this study.A total of 60 CITP patients who were admitted to the Hematology Department of Xiyuan Hospital,Chinese Academy of Traditional Chinese Medicine from February 2021 to December 2021 were selected and randomly divided into two groups by random number table method.The Yi qi Tong yang group was given Yi qi Tong yang formula(components:Radix pseudostellariae,fried Atractylodes with bran,Poria cocos,licorice,cassia twig,white peony root,Cynomorium,medicinal Indianmulberry root,sichuan Bi Xie,yam,ginger,jujube),the control group given to spleen decoction(components:Codonopsis,Astragalus,fried Atractylodes,Angelica,Poria with Hostwood,Polygala,longan meat,Radix Aucklandiae,licorice,ginger,jujube),a dose of daily,morning and evening points,4 weeks for a course of treatment,3 courses.The investigators visit the patients once every 4 weeks,and record platelet count,TCM syndrome score,bleeding score,chronic disease function assessment-fatigue scale score.The clinical efficacy was evaluated by comparison before and after treatment,comparison between groups and statistical analysis.At the beginning and end of the experiment,detected immune cells,cytokines and platelet activating factors and analyze the changes of immune function before and after the treatment of CITP with Yi qi Tong yang formula.15 healthy control group cases were randomly selected to detect the above indicators and compare,and explore the possible mechanism of its action in the treatment of CITP.ResultsA total of 60 cases were included in the clinical efficacy observation part of this study,1 case was lost to follow-up,and 59 cases were statistically analyzed finally,29 cases in the Yi qi tong yang group,30 cases in the control group and 15 healthy control group.The baseline data of the three groups before treatment were balanced and comparable.1 Western medicine curative effect and platelet count analysis1.1 Curative effect analysis of Western medicineThere were 6 cases(20.69%)of complete response,7 cases(24.14%)of effective response,13 cases(44.83%)of ineffective response and 3 cases(6.9%)of recurrence in 29 cases of Yi qi tong yang group.The total effective rate was 44.83%.In the control group,there were 30 cases,including 4 cases of complete response(13.33%),7 cases of effective response(23.33%),16 cases of ineffective response(53.33%)and 3 cases of recurrence(6.67%).The total effective rate was 36.66%.There was no significant difference between the two groups in clinical efficacy(P>0.05).1.2 Platelet count analysisBefore treatment,there was no significant difference in PLT count between Yi qi tong yang group and control group(35.17±19.62 vs 36.80±20.42,P>0.05).The PLT count of the first,second and third courses of Yi qi tong yang group was 43.55±26.92,48.55±26.88 and 57.38±34.68,respectively,and the PLT count increased significantly with the course of treatment(P<0.05).The PLT count of the control group was 47.30±33.75,51.27±37.66 and 55.43±34.04 in the first,second and third courses,respectively.The PLT count of the first course was significantly increased(P<0.05),and gradually increased in the second and third courses,but the trend slowed down,and there was no significant difference(P>0.05).There was no significant difference in PLT count at each time point between groups(P>0.05).2 Integral analysis of TCM curative effect and TCM syndrome2.1 Analysis of TCM efficacyIn the Yi qi tong yang group of 29 cases,0 cases(0%)were clinically cured,10 cases(34.48%)were significantly effective,18 cases(62.07%)were effective and 1 case(3.45%)was ineffective.The total effective rate was 28 cases(96.55%).In the control group of 30 cases,0 cases(0%)were clinically cured and 3 cases(10.00%)were significantly effective.22 cases(73.33%)were effective,5 cases(16.67%)were ineffective,and the total effective rate was 26 cases(83.33%).X 2 test showed significant difference in therapeutic effect between groups(P<0.05).2.2 Integral analysis of TCM syndromesBefore treatment,there was no significant difference in TCM syndrome score between Yi qi tong yang group and control group(25.97±6.00 vs 26.83±8.00,P>0.05).The TCM syndrome score of the first,second and third courses of Yi qi tong yang group was 18.41 ±5.129,14.24±4.30 and 9.93±4.22,respectively,and the TCM syndrome score decreased significantly with the progress of the course(P<0.01).In the control group,the TCM syndrome score of the first,second and third courses was 20.77±5.48,16.03±5.519 and 12.93±6.00,respectively,and the TCM syndrome score decreased significantly with the progress of the course(P<0.01).After the third course of treatment,there was significant difference in TCM syndrome score between the two groups(P<0.05).3 Bleeding score analysisBefore treatment,there was no significant difference in bleeding degree between Yi qi tong yang group and control group(P>0.05).After treatment,the bleeding degree of Yiqi tong yang group was significantly decreased(P<0.05),while the bleeding degree of control group was not significantly decreased(P>0.05).4 Evaluation of chronic disease treatment function-fatigue scale(FACIT-F score)analysis.Before treatment,there was no significant difference in FACIT-F score between Yi qi tong yang group and control group(42.07±07.62 vs 42.50±7.47,P>0.05).The FACIT-F score of Yi qi tong yang group was 47.00±4.55,48.69±4.09 and 50.83±2.22 respectively in the first,second and third course of treatment,and the FACIT-F score increased significantly with the progress of treatment(P<0.01).The FACIT-F score of the control group was 45.40±7.20,47.07±7.02 and 48.17±6.18 in the first,second and third course of treatment,respectively,and the FACIT-F score increased significantly with the course of treatment(P<0.05).After the third course of treatment,there was significant difference in FACIT-F score between the two groups(P<0.05).5 Analysis of security indicatorsIn the course of medication,1 patient with mildly abnormal liver function was found in the Yi qi tong yang group.The patient was treated with 2 gluconolactone tablets orally twice a day,and the liver function returned to normal after treatment.Other patients liver and kidney all functions fluctuated within the normal range,and no other serious adverse reactions or events or complications were observed.6 T lymphocyte balance in peripheral blood is unstableCompared with healthy control group,Th1 cells in ITP patients’ peripheral blood were significantly increased(P<0.05),Th2 cells were significantly decreased(P<0.05),and Th1/Th2 cells were significantly increased(P<0.05).Treg cells were significantly decreased(P<0.05),and Th17/Treg was significantly increased(P<0.05).After treatment,Treg cells were significantly increased(P<0.05),Th1 cells,Th2 cells,Thl/Th2,and Th17/Treg,the differences were not statistically significant(P>0.05).The Yi qi tong yang group was divided into the effective group and the invalid group according to whether the treatment was effective.Compared with the invalid group,Treg cells in the effective group were significantly increased(P<0.05),Th1 decreased,Th2 increased,Th1/Th2 decreased,and Th17/Treg decreased,but the differences were not statistically significant.There were no significant differences in the above indexes between the effective group and the healthy control group(P>0.05),and there were significant differences in the above indexes between the ineffective group and the healthy control group(P<0.05)(paired sample T test was used for the pre and post comparison,and independent sample T test was used for inter-group comparison).7 Peripheral blood cytokinesCompared with healthy control group,before treatment,INF-y,TNF-β and IL-1βin Yi qi tong yang group were significantly increased(P<0.05),IL-4 was significantly decreased(P<0.05),and IL-10 was decreased compared with healthy control group,but there was no significant difference(P>0.05).After treatment,il-1β in Yi qi tong yang group was significantly lower than before(P<0.05),INF-γ and TNF-β were lower than before,IL-4 and IL-10 were higher than before,but the difference was not statistically significant(P>0.05).The Yi qi tong yang group was divided into effective group and ineffective group according to whether the treatment was effective.The INF-γ of effective group and ineffective group was all significantly different compared with healthy controls.There was no significant difference between effective group and ineffective group(P>0.05).Platelet activating factorThe results showed that compared with healthy control group,the expression of CD62p was significantly increased(P<0.01)in yi qi tong yang group before treatment.After treatment,the expression of CD62p was lower than before,and there was no significant difference before and after treatment(P>0.05).After treatment,the expression of CD62p was still significantly different from that of healthy control group(P<0.05).Conclusion1 Yi qi Tong yang Prescription has significant effects in improving TCM syndrome,increasing PLT count,alleviating bleeding and fatigue symptoms,etc.,with safety and fewer side effects,it has a prospect of clinical application.2 Immune dysfunction exists in CITP patients.Yi qi Tong yang can regulate the imbalance of related cytokines by inhibiting Th1 expression and promoting Th2 and Treg expression,improve the immune state of patients,reduce the destruction of platelets,and increase the number of platelets.3 Abnormal activation of platelets was found in CITP patients.