The Relationship Between TCM Syndromes Of Parkinson's Disease And Clinical Stages, Substantia Nigra Changes And Intestinal Flora

Objective:Analyzed the characteristics of TCM patterns of patients with different clinical stages and subtypes of Parkinson’s disease(PD),analyzed the correlation between different TCM patterns of PD and substantia nigra pathologic change and intestinal flora,and explored the key TCM patterns of PDMethods:Study 1:a review of the screening of Parkinson’s disease cases in the study of TCM syndrome characteristics and TCM intervention in Parkinson’s disease was conducted,and 424 consecutive cases with no repeat were included with TCM syndrome diagnosis scale(PD-PES-13)and the Unified Parkinson’s Disease Assessment Scale(UPDRS)completely recorded.The disease stages were defined and grouped according to the H-Y classification,with 147 cases in the early group,250 cases in the middle group,and 27 cases in the late group.The differences of single TCM pattern and compound TCM patterns in three groups were compared.According to the accompanying symptoms in prodromal stage,424 cases were divided into two different groups,281 cases with constipation in prodromal stage and 143 cases without constipation in prodromal stage.Propensity score matching method were applicated in 1:1 matching according to duration,gender and age.135 cases with constipation in prodromal stage and 135 cases without constipation in prodromal stage were successful matched.UPDRS scores and TCM patterns between the two groups were compared.According to anosmia in prodromal stage or not,424 subjects were divided into 219 cases with anosmia in prodromal stage and and 205 cases without anosmia in prodromal stage,and the differences of UPDRS scores,TCM patterns were compared.Study 2:The design used was cross-sectional survey research.141 patients with Parkinson’s disease and 85 normal control cases from Dongzhimen Hospital of Beijing University of Chinese Medicine were included.The SIEMENS ultrasound diagnostic apparatus was used to measure the area of strong echo of substantia nigra,and the clinical characteristics and TCM syndrome characteristics were evaluated using different scales.Based on the UK Brain Bank Parkinson’s disease diagnostic standard as the gold standard,the ROC curve analysis was used to establish the PD subsigma strong echogenic cutoff value.The correlation between visual hallucination and strong echogenic area of substantia nigra in PD was analyzed in PD group.The correlation between TCM patterns and strong echo of substantia nigra in PD group was analyzedStudy 3:The design used was cross-sectional survey research.25 PD subjects and 25 healthy control subjects from Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine were included.Fecal samples were collected and analyzed for intestinal flora abundance using 16Sr RNA high-throughput sequencing.The clinical features and TCM patterns were evaluated using different scales.The differences in intestinal flora between the two groups were compared;the correlation between the relative abundance of intestinal flora in the PD group and clinical features and TCM patterns distribution were analyzed.Results:1.Research on the relationship between PD stage and TCM syndromes showed that the frequency of Sui reduction,Qi deficiency,Yin deficiency and internal heat all show a trend of gradual increase with the disease duration.The frequency of liver wind increased gradually in the early and middle stages and decreased in the late stage.Te occurrence frequency of Sui reduction,Qi deficiency,Yin deficiency,liver wind and kidney deficiency in the middle stage was significantly higher than that in the early stage(Sui reduction P<0.01,and the rest P<0.05).The frequency of Sui reduction in late stage was significantly higher than that in early stage(P<0.01).The compound pattern analysis showed that the frequency of Yin deficiency and Sui reduction,Qi and Yin deficiency,Yin deficiency and internal heat,Qi deficiency and internal heat all presented a gradually increasing trend.The frequency of Yin deficiency and Sui reduction,dynamic wind Yin deficiency,Qi and Yin deficiency in middle stage were significantly higher than that in early stage(P<0.01).The frequency of Yin deficiency and Sui reduction in late stage was significantly higher than that in early stage(P<0.01).The frequency of Yin deficiency and internal heat in late stage was significantly higher than that in early stage(P<0.05)The analysis of PD clinical subtyping showed that there was no significant difference between group with constipation in prodromal stage and without in gender,age,age of onset and course of disease after the propensity score matching(P>0.05).UPDRS,UPDRS-II,UPDRS-Ⅲ,UPDRS-Ⅳ scores of group with constipation in prodromal stage were significantly higher than the group without(P<0.05).There was no difference in the total score of UPDRS and subtotal score between group with hyposmia in prodromal stage and group without(P>0.05).The analysis of the relationship between the clinical subtyping and TCM patterns showed that the frequency of spleen deficiency,Qi deficiency,blood deficiency,Yin deficiency,YangKang and internal heat in group with constipation in prodromal stage was significantly higher than that in the group without(P<0.01).The occurrence frequency of Qi deficiency and internal heat,Yin deficiency and internal heat,dynamic wind and Yin deficiency,Yin deficiency Sui reduction and Qi and Yin deficiency in group with constipation in prodromal stage was significantly higher than that of the group without(P<0.01).Spleen deficient,Qi deficiency,blood deficiency,Yin deficiency,Sui reduce,YangKang frequency were significantly higher in group with hyposmia in prodromal stage than that of group without(P<0.05),Yin deficiency and Sui reduce,Qi and Yin deficiency frequency were significantly higher in group with hyposmia in prodromal stage than that of group without(P<0.01),and Qi deficiency and internal heat frequency was significantly higher in group with hyposmia in prodromal stage than that of group without(P<0.05).2.In the PD group,111 of the 141 subjects completed the acquisition of substantia nigra ultrasound signals(72 males and 39 women),and 61 of the 85 normal control subjects completed the substantia nigra ultrasound information acquisition.The results of the ROC curve between the PD group and the control group showed that when the cutoff value of SNL was 0.235 cm2,the performance of diagnosing PD was the best.The sensitivity is 70.3%,the specificity is 77.0%,and the area under the curve is 0.775(95%CI:0.699-0.851,P<0.001).Based on this cutoff value,78 subjects(70.27%)in the PD group met SNL≥0.235 cm2;14 subjects in the control group(22.95%)met SNL≥0.235 cm2.The area of SNL in PD with visual hallucination group was significantly higher than that in PD without visual hallucination group(P=0.01 8).The scores of NMSS and UPDRS-Ⅱ in PD with visual illusion were higher than those in PD without visual illusion(P=0.027,NMSS;P=0.036,UPDRS-Ⅱ).Binary logistic regression analysis showed that SNL(OR=4.227,P=0.012)and NMSS(OR=0.027,P=0.042)were related to PD with visual hallucinations.Correlation analysis between TCM patterns and the area of strong echo of substantia nigra showed that the ratio of SN+(75.5%)in the group with Sui reduced pattern was significantly higher than that in the group without(41.2%),(P<0.01).The area of SNL in the Sui reduced group was larger than that in the group without(P<0.05).The distribution of Sui reduced was positively correlated with SNL(P<0.05);the partial correlation analysis between the area of the substantia nigra echo and TCM patterns scores using age and sex as control variables showed that the scores of Sui reduced were positively correlated with SNL(P<0.05)3.The comparison of intestinal flora between PD group and the normal control group showed that the observed species index,chao index and ACE index of PD group were significantly higher than that of the control group(P<0.01).LefSe analysis showed that Methanobacteria,Euryarchaeota,Archaea,Oscilillospira,Lactobacillaceae were species with significant effect in PD groupThe correlation analysis between relative abundance of intestinal flora and clinical characteristics in PD group showed that the relative abundance of Actinobacteria were positively correlated with the course of disease(Pearson’s R=0.448,P=0.003),and were positively correlated the scores of constipation severity assessment(Pearson’s R=0.448,P=0.015),and were negatively correlated with bilateral olfactory test scores(Pearson’s R=-0.517,P=0.040).Correlation analysis between the relative abundance of intestinal flora and TCM patterns in PD group showed that there was a significant correlation between the relative abundance of Bacteroides and liver wind pattern(Spearman’s R=0.432,P=0.031).Conclusions:1.TCM patterns of Yin deficiency and Sui reduction,Qi and Yin deficiency,and Yin deficiency and dynamic wind throughout the whole course of PD,and gradually increased with disease progression.The proportion of Yin deficiency and internal heat increased significantly in the late stage of PD.2.PD patients with constipation in prodromal stage have more severe exercise symptoms than those without.It is suggested that potential mechanisms of constipation in the prodromal stage may be a factor to accelerate disease progression.3.The frequency of Yin deficiency Sui reduction,Qi and Yin deficiency,dynamic wind Yin deficiency,Qi deficiency and internal heat,internal heat Yin deficiency in group with constipation in prodromal stage were significantly higher than those without.4.The best diagnostic performance was obtained when the cut off value of strong echo area of substantia nigra was 23.5mm2.There was a significant correlation between Sui reduction and the echo area of substantia nigra.PD with visual hallucinations have a larger area of strong echo in the substantia nigra5.The increased relative abundance of methanobacteria in the archaea in the fecal flora maybe have correlation with PD.The relative abundance of actinomycetes in fecal flora was correlated with the course of disease,the severity of constipation and the severity of anosmia.The relative abundance of bacteroidetes in fecal flora is correlated with the liver wind pattern.