| Study 1:Research on the Course of Treatment and Influencing Factors of Modified Jingxinzhidong Decoction in Treating Tic DisorderObjective:To explore the differences in the course of treatment of TD children of different ages and different stages in the process of drug reduction,and analyze the influencing factors of the course of treatment of TD with the modified Jingxinzhidong Decoction through retrospective analysis of TD(Tic Disorder)scientific research medical records established by Director Han Fei's outpatient department.Methods:The TD research medical records established by director Han Fei from January 2011 to December 2019 were collected,and the data of the medical records meeting the inclusion and exclusion criteria were collected,including the demographic characteristics,disease characteristics,first symptoms,risk factors,TCM syndrome types,treatment methods and treatment courses of the children.The differences of treatment course in different age groups and different stages in the course of drug reduction were analyzed.The factors that may affect the treatment course were analyzed by univariate analysis,and the significant factors in univariate analysis were analyzed by multivariate linear regression analysis.Results:1.General situation of TD cases:Among the TD cases in this study,there were 548 boys(77.29%)and 161 girls(22.71%).The average age of seeing a doctor was 8.34±2.41 years old.More than half of the children came from North China(355 cases,50.07%).The average onset age was 6.55 ± 2.10 years old,and the average course of disease was 21.20 ± 19.94 months.Most of the children showed motor-vocal combined tic(401 cases,56.56%)when they went to see a doctor.The severity of the disease was mostly mild(334 cases,47.11%)or moderate(348 cases,49.08%),the average YGTSS score was 35.67±14.56 points,581 cases(81.95%)had normal EEG,and 637 cases(89.84%)had no comorbidity.Ocular twitch was the most common first symptom(419 cases,59.10%).Emotional changes(391 times,23.63%),infection/inflammation(356 times,21.51%)and study stress(282 times,17.04%)were the most common disease risk factors.Liver hyperactivity wind movement syndrome(184 cases,25.95%)and yin deficiency wind movement syndrome(128 cases,18.05%)are the most common TCM syndrome types.538 cases(75.88%)did not use western medicine,and 562 cases(79.27%)took medicine regularly.2.The course of treatment of TD with modified Jingxinzhidong Decoction:The average course of treatment was 32.84±14.41 months.The course of treatment required by TD children of different ages was different(P=0.048).It was 28.09 ± 12.61 months for 5 and below 5 years old,31.70± 13.02 months for 5.1-10 years old,33.72± 14.45 months for 10.1-15 years old,and 38.32± 13.37 months for over 15 years old.The course of treatment at different stages in the process of drug reduction was different(P=0.000).One dose every day was 6.39 ± 2.86 months,two doses every three day were 9.30 ± 4.41 months,one dose every two day was 8.15 ± 3.73 months,one dose every three day was 5.15 ± 2.51 months,and one dose every four day was 3.92± 1.88 months.3.Influencing factors of the course of treatment of TD with modified Jingxinzhidong Decoction:Univariate analysis found that the course of treatment was positively correlated with the length of the course of disease(r=0.136),EEG(r=0.160),YGTSS score(r=0.559),was negatively correlated with combined Western medicine(r=-0.085),regular medication(r=-0.168),was positively correlated with disease severity(rs=0.452),and was related to the type of tic.Multivariate analysis showed that YGTSS score,regular medication or not,severity of disease,normal or abnormal EEG and combined with western medicine or not would affect the course of treatment.The regression equation can be expressed as course of treatment=0.496*YGTSS score-5.373*regular medication+10.371*severity+4.465*EEG-2.261*combined with western medicine+18.833(F=82.325,P=0.000<0.01,R2=0.365).Conclusion:1.The course of treatment of children with tic disorder by modified Jingxinzhidong Decoction in different age stages is different,and the required course of treatment is positively correlated with the age of children.2.The course of treatment of modified Jingxinzhidong Decoction in treating tic disorder is different at different stages in the process of drug reduction,and the course of treatment required by 2 doses every three day and 1 dose every two day are longer.3.The course of treatment of tic disorder with modified Jingxinzhidong Decoction is affected by YGTSS score,disease severity,regular medication or not,normal or abnormal EEG and use western medicine at the same time or not.Study 2:Research on the dynamic changes of the medication rules of Modified Jingxinzhidong Decoction in the treatment of tic disorder by professor Han FeiObjective:To analyze the dynamic changes of the medication rules of Professor Han Fei's treatment of TD with the modified Jingxinzhidong Decoction in different stages.compare the medication characteristics and prescription rules of each stage,and then excavate potential new prescription combinations based on the research method of data mining.Methods:The TD scientific research medical records established by Director Han Fei's outpatient clinic from January 2011 to December 2019 were collected.screened according to the inclusion and exclusion criteria.and the first diagnosis prescriptions meeting the criteria were entered into the prescription management module of TCM inheritance assistance system(V2.5)according to the different initial diagnosis time,and four prescription databases were established.Using data mining methods such as frequency analysis,association rules,complex system entropy clustering,the high-frequency drugs,efficacy classification,nature and taste tropism and prescription rules of the first diagnosis prescriptions in each stage are analyzed and compared,and the core drug combinations and potential new prescription combinations of the first diagnosis prescriptions from 2016 to 2018 are mined.Results:1.High-frequency drug analysis:Mother of pearl,Fructus Aurantii,Angelica dahurica and Radix Paeoniae Alba are commonly used in the first diagnosis prescription from 2007 to 2009.Mother-of-pearl,Fructus Aurantii,Angelica dahurica and Rhizoma Phragmitis are commonly used in the first diagnosis prescription from 2010 to 2012.Schizonepeta,Dendrobium.Magnolia and Cicada Slough are commonly used in the first diagnosis prescriptions from 2013 to 2015.Angelica dahurica,Magnolia.Polygonum multiflorum and Cicada Slough are commonly used in the first diagnosis prescriptions from 2016 to 2018.In addition,keel,oyster,jujube seed,platycladi seed.Bupleurum root and Bombyx Batryticatus are commonly used in the first diagnosis prescriptions at each stage.2.Classification of drug efficacy and analysis of nature,taste and meridian tropism:The drugs used in each stage are mainly tranquilizing drugs,exterior-relieving drugs,liver-calming and wind-relieving drugs,heat-clearing drugs and deficiency-tonifying drugs,and the proportion of tranquilizing drugs and deficiency-tonifying drugs is generally increasing,while the proportion of heat-clearing drugs is gradually decreasing.The four qi of drugs used in each stage are mainly cold,warm and flat,and the proportion of cold drugs is generally decreasing,while the proportion of flat drugs is gradually increasing.The five flavors of drugs used in each stage are bitter,pungent and sweet,and the proportion of sweet drugs gradually increases,while the proportion of bitter and pungent drugs gradually decreases.The tropism of drugs used in each stage is mainly heart,liver and lung,and the proportion of drugs used in heart meridian and lung meridian is generally increasing.3.Analysis of association rules:Bupleurum with Fructus Aurantii and Acorus gramineus with Polygala tenuifolia are often used as the first diagnosis prescriptions from 2007 to 2009;From 2010 to 2012,the first diagnosis prescription is usually Bupleurum with Phragmites reeds and Bombyx batryticatus with Paeonia alba;The prescription for the first diagnosis from 2013 to 2015 is usually Dendrobium,Bombyx Batryticatus with Bupleurum,Bupleurum with Bombyx Batryticatus and Cicada;The prescription for the first diagnosis from 2016 to 2018 is usually to use Caulis Polygoni Multiflori with Semen Ziziphi Spinosae,Semen Platycladi,Os Draconis and Concha Ostreae with Semen Ziziphi Spinosae and Semen Platycladi.In addition,keel with oyster,spinosaur jujube seed with platycladi seed,Bupleurum root with Batryticatus silkworm,Angelica dahurica with Magnolia flower are often used in the first diagnosis prescriptions at each stage.4.New prescription analysis of the first diagnosis prescription from 2016 to 2018:The first diagnosis prescription from 2016 to 2018 was analyzed based on complex system entropy clustering,and 16 core drug combinations were obtained.On this basis,8 new prescription combinations were obtained by further mining.Conclusion:1.Professor Han Fei's treatment of TD is based on the heart,liver and lung.The basic treatment methods are tranquilizing the mind,calming the wind and relieving exterior syndrome,with special emphasis on the use of tranquilizing the mind.Draconis,Oyster,Semen Ziziphi Spinosae,Semen Platycladi,Bupleurum Radix and Bombyx Batryticatus are the core drug groups of Jingxinzhizhong Decoction.2.Professor Han Fei pays more and more attention to the pathogenesis of deficiency of yin and blood in heart and liver and external wind triggering internal wind when treating TD.On the basis of tranquilizing method,he focuses on nourishing yin and blood in heart and liver,dispersing lung,relieving exterior syndrome and dredging orifices.The use of warm,invigorating and peaceful drugs gradually increased,while the use of bitter,pungent and dry drugs gradually decreased,indicating that the tutor's use of drugs for TD was more light,clear and peaceful.3.Through complex system entropy cluster analysis of the first diagnosis prescriptions from 2016 to 2018,8 combinations of new prescriptions were obtained.The efficacy of the new prescriptions was mostly biased towards relieving exterior syndrome and nourishing yin,which was consistent with the characteristics of the above changes in medication rules.Study 3:Research on the effect of Jingxinzhizhong Decoction on the expression of PD-1/PD-L1 pathway on the surface of T lymphocytes in children with tic disorderObjective:To analyze the correlation between PD-1/PD-Ll and YGTSS score in TD group,observe the changes of PD-1/PD-L1 pathway before and after treatment with Jingxinzhizhong Decoction,and explore the correlation between PD-1/PD-L1 pathway and TD,and the effect of Jingxinzhizhong Decoction on its expression.Methods:From October 2020 to December 2020,TD children who saw a doctor in Guang'anmen hospital and met the inclusion and exclusion criteria and non-TD children who were examined in our hospital at the same time were collected.The expression of PD-1 and PD-L1 on the surface of CD4+T and CD8+T cells in the two groups of children were detected,and YGTSS scores were performed on TD children.The expression of PD-1/PD-L1 in the two groups of children were compared and the correlation with YGTSS scores was analyzed.The expression of PD-1 and PD-L1 on the surface of CD4+T and CD8+T cells were detected again after 12 weeks of treatment with Jingxinzhidong Decoction in children with TD,and the efficacy and safety were evaluated to analyze the effect of Jingxinzhidong Decoction on the expression of PD-1/PD-L1 in children with TD.Results:1.There is no significant difference in gender and age composition between the two groups,and the baseline data are consistent and comparable.2.The expression of PD-1 on the surface of CD4+T and CD8+T cells in peripheral blood of children in TD group was higher than that in non-TD group,and the difference was statistically significant.The expression of PD-L1 on CD4+T and CD8+T cells in peripheral blood of children with TD was higher than that of non-TD group,but the difference was not statistically significant.3.The expression of PD-1 on the surface of CD4+T cells in peripheral blood of children in TD group before treatament was positively correlated with YGTSS score,and the regression equation was Y=39.600X+13.341;The expression of PD-1 on the surface of CD8+T cells in peripheral blood of children in TD group before treatment was positively correlated with YGTSS score,and the regression equation was Y=50.724X+8.042.4.After 12 weeks of treatment,1 case(4.17%)was clinically controlled,11 cases(45.83%)were markedly effective,9 cases(37.50%)were effective,and 3 cases(12.50%)were ineffective.The total effective rate is 87.50%.After treatment,the YGTSS score was significantly lower than that before treatment,and the difference was statistically significant.No obvious adverse reactions occurred during the treatment,and there was no abnormal change in urine routine and liver and kidney function indexes of children before and after treatment.5.After 12 weeks of treatment with Jingxinzhidong Decoction,the expression of PD-1 and PD-L1 on the surface of CD4+T and CD8+T cells in the peripheral blood of children in TD group decreased significantly,and the difference was statistically significant.Conclusion:1.The expression of PD-1 on the surface of CD4+T and CD8+T cells in peripheral blood of children with TD is significantly higher than that of healthy children,and it is related to YGTSS score.It is speculated that the disorder of T lymphocyte subsets and cellular immune dysfunction caused by the increase of PD-1 are closely related to TD.2.The expression of PD-1 and PD-L1 on the surface of CD4+T and CD8+T cells in the peripheral blood of children with TD after treatment with Jingxinzhidong Decoction decreased significantly,indicating that Jingxinzhidong Decoction can regulate the immune function of children and enhance the immunity of children by down-regulating the expression of PD-1/PD-L1.3.In this study,the total effective rate of Jingxinzhidong Decoction in treating TD was 87.50%.After treatment,the children's tic symptoms were significantly improved,the YGTSS score was significantly reduced,there was no abnormal change in safety indicators before and after treatment,and there was no obvious adverse reaction during the treatment.It once again confirmed the effectiveness and safety of treating TD from the heart. |
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