| Research Purposes:Clinical research:Based on grounded theory,we explored the clinical experience of Professor Wang Sumei in the treatment of tic disorders and her understanding of stress sensitivity.Through retrospective study and cross-sectional study,the relationship between stress sensitivity of tic disorders,constitution and temperament was explored,and a theoretical model of emotional pathogenism of "constitution-temperament-stress" was constructed,and the prevention and treatment of tic disorder was discussed from the perspective of "preventive treatment of disease".Basic research:This study aims to establish a rat model of tic disorder induced by chronic constraint stress.By investigating the regulatory effect of Jian-pi Zhi-dong decoction(JPZDD)on polarization of hippocampal microglia cells in the rat model,preliminary to explore the possible biological mechanism of stress pathogenesis and the regulating effect of JPZDD on stress.Research methods:Clinical research:Study 1,based on the grounded theory,we first conducted semi-structured interviews with Professor Wang Sumei,4 of her disciples and graduate students,and 6 parents of children with tic disorders.Secondly,we collected Professor Wang Sumei’s academic papers and works on the treatment of tic disorders.The two parts of information were taken together as the original data,three-level coding was carried out to generate categories,and the relationship between various categories was further analyzed.Combined with my own experience of learning from teachers,listening to her words,observing her actions and digging her theories,the core categories were formed.To construct the theoretical model of Professor Wang Sumei in the treatment of tic disorders and her understanding of the stress sensitivity of the disease.Study 2,a retrospective study was conducted to collect and screen temperament types of 80 children with tic disorder who were treated in the pediatric outpatient department of the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 2021 to December 2022.Compared with the normal model group,the distribution characteristics of temperament types and temperament dimensions of children with tic disorders were explored.Study 3,through a cross-sectional study,common stressors and stress intensity were detected by the Adolescent self-rating life events Scale,and the severity of tic disorders was detected by Yale score,so as further explore the relationship between stress and tic disorder.Study 4,the theoretical model of"constitution-temperament-stress" was initially constructed,and the prevention and treatment of tic disorder was discussed from the perspective of "preventive treatment of disease",so as to provide useful reference for the clinical diagnosis and treatment of tic disorders.Basic research:Build a rat model of chronic restrain stress tic disorder induced by chronic restraint stress with intraperitoneal injecting IDPN.The behavioral changes of each group were detected by stereotyped behavior score,open-field test,elevated plus-maze test and suger-water preference test.The activation of microglia in the hippocampus was detected by immunohistochemistry,and the co-localization of M1(Iba-1+/CD86+)and M2(Iba-1+/CD206+)of hippocampal microglia cells were detected by immunohistochemical double staining.Enzyme-linked immunosorbent assay was used to detect the cytokines IL-6,IL-1β,IL-4,and IL-10 in hippocampal tissue.Preliminary explore the regulatory effect of JPZDD on M1/M2 polarization and stress of microglia.Study results:Clinical research:Study 1:In this study,a total of 11 interview data were collected,referred to 10 papers and 1 monograph.After conducting a three-level coding analysis and summary,six categories were summarized:theory,method,formula,medicine,doctor-patient collaboration,and curative effect elements.A core category of "curative effect factors" was formed.Professor Wang Sumei believed that the pathogenesis of tic disorder was spleen deficiency and hyperactivity of liver,and internal disturbance of wind and phlegm.The disease was located in the liver and spleen,related to the five viscera.She put forward the treatment method of reinforcing the earth and inhibiting the wood,by adding or subtracting Liu-jun-zi decoction and Xie-qing pill was adopted to establish JPZDD.In the acute attack period,the method of inhibiting wood,calming the liver and extinguishing the wind were used to treat tic disorder.In the remission phase,she used the method of supporting soil to strengthen the spleen and reduce phlegm to suppress wood,which provided ideas for clinical diagnosis and treatment.Under the guidance of traditional Chinese medicine thinking of"absorbing symbols" and "taking numbers",with "spleen deficiency and liver hyperactivity"as the main line,"preventive treatment of disease" and "syndrome differetiation",the treatment is supported by reinforcing earth and inhibiting wood,with pharyngeal four needles,massage and patching,so as to achieve the combination of Chinese and Western,internal and external treatment,prevention and treatment.Study 2:①General information:A total of 80 case information of children with tic disorder were collected,including 56 male children,accounting for 70%.There were 24 female children,accounting for 30%.The male to female ratio is about 2.34:1.In terms of age,the youngest age included in this study is 4 years old,and the oldest age is 12 years old.There were 39 children aged 4 to 7 years old in the early school age,accounting for 48.75%;There were 41 school-age children aged 8 to 12,accounting for 51.25%.②Distribution of temperament types:There were 4 troublemakers,accounting for 5%;32 easy-going patients,accounting for 40%;5 slow-reacting patients,accounting for 6.25%;There were 39 people with intermediate annoyance type and intermediate easy type,accounting for about 48.75%.③Characteristics of temperament dimensions:Compared with the normal group of children,there was no significant difference in the nine dimensions of temperament in the 4～7 year-old group(P>0.05).The score of mood in temperament dimension of 8～12 years old group was significantly increased,the difference was statistically significant(P<0.05).The scores of attention and reaction were significantly decreased,the difference was statistically significant(P<0.05),while the comparison of other temperament dimensions had no significant difference.Study 3:In general,a total of 42 children with TD were collected in this study,among which 31 were male,accounting for 73.81%;There were 11 cases of female children,accounting for 26.19%,and the ratio of male to female was about 2.82:1.In terms of age,the youngest child was 6 years old,the oldest was 13 years old,and the most children were 7 and 8 years old.Negative life events have a certain positive correlation with the Yale score.Being scolded by parents,criticized or punished,family pressure on learning,and obvious changes in living habits are common negative life events.Study Four:①A theoretical model of emotional pathogenicity with the trinity of"constitution-temperament-stress" was constructed:Based on the susceptibility of"constitution-temperament," emotional and other stress factors act together,leading to the imbalance of qi activity and liver wind internal movement,causing the disease.causing this disease.It is advocated to first soothe the liver and regulate qi,focus on tonifying the spleen and regulating the liver,prioritize adjusting the mind and calming the spirit,assist the lung and reduce the qi,and guide the regulation of qi.②Under the guidance of the "preventive treatment of disease" theory,we propose to "preventing disease before it occurring" by regulating stress and preventing the disease;"early treatment of pre-existing diseases," by early identification and treatment to prevent the disease from forming;"preventing change from existing disease" by actively controlling the comorbidity to prevent transmission,and"prevent recurrence after recovery," by reducing medication rationally to prevent the disease from recurring.Basic research:Behavioral results:① Results of stereotyped behavior score:Before treatment,compared with blank group,the stereotyped behavior score of rats in TD group was significantly increased,the difference was statistically significant(P<0.01).After treatment,compared with blank group,stereotype score of model group was significantly increased,the difference was statistically significant(P<0.01);Compared with the model group,the stereotype score of the western medicine group had a downward trend,and the difference was not statistically significant(P>0.05),while the stereotype score of the traditional Chinese medicine group was significantly decreased,and the difference was statistically significant(P<0.05).②The results of open-field experiment:Before treatment,compared with the blank group,the total movement distance,average speed,the times and distance of entering the central area of the model group were significantly increased,and the differences were statistically significant(P<0.05).After treatment,compared with model group,the total distance,average speed of exercise and the times of entering the central area in western medicine group and Chinese medicine group had a trend of shortening,but the difference was not statistically significant(P>0.05),while the distance of entering the central area were significantly shortened,and the difference was statistically significant(P<0.05).Results of elevated plus-maze test:Before treatment,compared with the blank group,the OE%of rats in the TD group had a decreasing trend,and the difference was statistically significant(P<0.05);After treatment,compared with model group,OE%in Chinese medicine group had a increasing trend,but the difference was not statistically significant(P>0.05).④Results of suger-water preference test:Before treatment,compared with blank group,the sugar water preference coefficient of model group and Chinese medicine group was significantly decreased,and the difference was statistically significant(P<0.05).After treatment,compared with the model group,the sugar water preference coefficient of the western medicine group and the Chinese medicine group had an increasing trend,but the difference was not statistically significant(P>0.05).Molecular results:Immunohistochemical test results:①Morphologically,the MG cells in the hippocampus of rats in the blank group were small and differentiated into a large number of multistage processes,which were elongated and unactivated in a branched state.In the model group,the hippocampal MG cells body were enlarged,the processes were short,the branches were reduced,and most of the MG cells were activated like "amoeba".The MG of the western medicine group and the traditional Chinese medicine group were recovered,and the shape was close to that of the blank group.The improvement effect of the traditional Chinese medicine JPZDD group was more obvious.② Results of immunofluorescence experiment:Compared with the blank group,the(Iba-1+/CD86+)co-localization expression of MG in the model group was increased,and the(Iba-1+/CD206+)co-localization expression was correspondingly increased.Compared with the model group,the co-localization expression of MG(Iba-1+/CD86+)was decreased in the western medicine group and the Chinese medicine group,while the co-localization expression of(Iba-1+/CD206+)was increased,which was significantly improved by JPZDD.③ Results of ELISA experiment:Compared with blank group,the expression level of IL-1β in hippocampus of rats in model group was significantly increased(P<0.01).The expression level of IL-6 had a increasing trend,but the difference was not statistically significant(P>0.05).The expression levels of IL-4 and IL-10 were significantly decreased,and the differences were statistically significant(P<0.05,P<0.01).Compared with model group,the expression level of IL-1β in hippocampus of western medicine group and Chinese medicine group was significantly decreased,the difference was statistically significant(P<0.05,P<0.01).The expression levels of IL-4 and IL-10 were significantly increased,and the differences were statistically significant(P<0.05,P<0.01).Research conclusions:Clinical research:Based on grounded theory,the theoretical model of Wang Sumei’s treatment of tic disorder was constructed.Through retrospective study and cross-sectional study,the relationship between stress sensitivity of tic disorder and constitution and temperament was explored,and a theoretical model of emotional pathogenicity with the trinity of "constitution,temperament and stress" was constructed,and the prevention and treatment of tic disorder was discussed from the perspective of "preventive treatment of disease".Basic research:Chronic restraint Stress of TD rats have anxiety and depression-like behavior,which may be related to the abnormal activation of MG.By reinforcing earth and inhibiting wood,JPZDD can reduce the stereotypical exercise score of TD rats with chronic restraint stress,improve the sugar and water preference coefficient,and regulate the open field test and elevated cross maze scores to regulate stress,which may be related to the MG polarization balance in hippocampus. |
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