| Objeictive:To summarize the characteristics of TCM syndromes of Parkinson’s disease(PD)constipation;to observe the clinical efficacy of Shengqing Jiangzhuo Recipe in the treatment of PD constipation;to analyze the characteristics of intestinal flora in PD and its correlation with TCM syndrome,hope provide reference for Chinese medicine treatment of PD constipation.Methods:Study 1 used a cross-sectional study to collect 239 subjects from Dongzhimen Hospital,Beijing Hospital and Peking University Third Hospital,including 120 patients with PD constipation,49 patients with PD non-constipation,and 70 patients with normal control(NC)group.The TCM syndrome scales were evaluated in three groups,and the differences in TCM syndrome scores of the three groups and the frequency difference of TCM syndromes in the three groups were compared,and the TCM syndrome characteristics of PD constipation were summarized.Unified Parkinson’s Disease Rating Scale(UPDRS),Constipation Severity Assessment(CSI)and H-Y Classification for PD constipation group,analysis of the correlation between TCM syndromes of PD constipation and various observation scales.In the second study,a randomized,double-blind,placebo-controlled multi-center clinical trial was conducted to observe the clinical efficacy of 63 patients with PD constipation treated with Shengqing Jiangzhuo Recipe,including 43 in the experimental group and 20 in the control group.The observation group was treated with Shengqing Jiangzhuo Chinese medicine granules on the basis of conventional treatment.The control group was given placebo granules on the basis of conventional treatment,treatment for 12 weeks.According to the intention-to-treat(ITT-LOCF)analysis and the per-protocol set analysis,the improvement of CSI scores of the main efficacy indicators before and after treatment was compared.The secondary efficacy indicators UPDRS,Parkinson’s Fatigue Scale-16(PFS-16)and TCM syndrome before and after treatment were compared.Study 3 used a cross-sectional study method to collect 53 subjects from Dongzhimen Hospital,Beijing Hospital and Peking University Third Hospital,including 38 PD group,and NC group 15 people.The fecal samples of the subjects were collected,and DNA extraction,PCR amplification and 16S rDNA high-throughput sequencing technology were used to compare the intestinal flora differences between the two groups,and to summarize the intestinal flora characteristics of PD patients.UPDRS,CSI,H-Y classification,TCM Syndrome Scale was performed for the PD group,analyze the correlation between the intestinal flora of PD and the observation scales.Results:1.The most common TCM syndromes in PD constipation group were Liver wind(98.33%),Marrow deficiency(90.00%),Yin deficiency(76.67%),and Qi deficiency(74.17%).The PD constipation group had the highest scores of Liver wind(20.35±6.523),Marrow deficiency(13.27±5.302),Qi deficiency(9.25±5.030),and Yin deficiency(7.86±3.347).After correlation analysis,the results showed that patients with PD constipation had H-Y grade and Kidney deficiency(r=0.479,p=0.000),Spleen deficiency(r=0.248,p＝0.006),Qi deficiency(r=0.183,p=0.045),and Blood deficiency(r=0.264,p=0.004),Yang hyperactivity(r=0.519,p=0.000),Endogenous heat(p=0.194,p=0.034)showed positive correlation;UPDRS integral and Yang deficiency(r-0.183,p=0.045),Marrow deficiency(i=0.264,p=0.004),Yang hyperactivity(r=0.189,p=0.039),and Blood stasis(r=0.220,p=0.016)were positively correlated.Based on this,a model of H-Y grading and UPDRS for PD constipation patients was established using TCM syndrome scores.The model equation for evaluating H-Y grading of PD constipation patients using TCM syndrome scores was yH-Y grade=-2.070+9.017xKidney deficiency+0.824xYang hyperactvity;using the TCM syndrome score to evaluate the model equation of UPDRS in patients with PD constipation is yUPDRS=18.163+0.685xMarrow deficiency+0.359xYang hyperactivity.2.The results of Shengqing Jiangzhuo Recipe in the treatment of PD constipation showed that the improvement of CSI score in the experimental group was better than that in the control group at 12 weeks(p=0.021).After treatment,the CSI score decreased by 6.72 ± 8.850 compared with that before treatment.Comparison of the two groups of symptoms in CSI showed that the improvement of the score of the test group III(normal bowel movements)was better than that of the control group at 8 weeks(p=0.007);the test group Ⅳ(frequency of reduction)was 4 weeks,8 weeks,and12-week score improvement was better than the control group(P<0.05);the improvement of the 4-week score of the test group Ⅵ(pain and blood in the stool)was better than that of the control group(p=0.038).The internal comparison results of the CSI test group showed that the CSI scores at 4 weeks,8 weeks,and 12 weeks were lower than those at 0 weeks(p<0.05).The ITT-LOCF analysis of the experimental group PFS-16 showed that the improvement at 8 weeks and 12 weeks was better than that in the control group(p<0.05),PPS analysis of the experimental group PFS-16 showed that the improvement at 12 weeks was better than that in the control group(p=0.008).The PFS-16 scores of the experimental group after treatment in the ITT-LOCF analysis were improved compared with those before treatment(p<0.05),and the 12-week scores improved compared with the 4-week scores.(p=0.022),the PFS-16 scores at 8 weeks and 12 weeks after treatment in the PPS analysis were improved compared with those before treatment(p<0.01),and the 12-week scores improved compared with the 4-week scores(p=0.015).The improvement of yin deficiency in the experimental group at 8 weeks and 12 weeks was better than that in the control group(p<0.05).The scores of the pulp depletion at each follow-up point in the experimental group gradually decreased(p<0.05).There were no significant differences in adverse events between the two groups.3.The results of intestinal flora analysis of PD patients showed that there was no significant difference in the diversity index between PD group and NC group,PD constipation group and NC group(p<0.05).There were some overlaps in the gut microbiota types in the PD groupand the NC group at the classification levels of the phylum,the class,the order,the family,the genus,and the species.At the phylum level,the abundance of Tenericuets in the PD group was significantly higher than that in the NC group(p=0.005).At the class level,the abundance of Mollicutes in the PD group was significantly higher than that in the NC group(p=0.005).At the family level,the abundance of PD group Peptococcaceae,Lactobacillaceae was significantly higher than that of NC group(p=0.002,p=0.005);PD group Burkholderiaceae was significantly lower than that of the NC group(p=0.005).At the species level,the abundance of PD group Lautropia was significantly lower than that of NC group(p=0.005).Correlation analysis between intestinal flora diversity and clinical indicators in patients with PD shows that OTU number,chao index,ace index and shannon index were positively correlated with Phlegm muddiness(rOTu=0.364,pOTU=0.025;rchao=0.385,pchao=0.017;race=0.374,pace=0.021;rshannon=0.389,pshannon=0.016)and negatively correlated with UPDRS(rOTU=-0.364,pOUT=0.025;rcbao=-0.383,pchao=0.018;race=-0.350,pace=0.031;rshannon=-0.330,pshannon=0.043);shannon index was positively correlated with Kidney deficiency and Yang deficiency(rKidney deficiency=0.421,pKidney deficiency=0.008;rYang deficiency=0.391,pYang deficiency=0.015);simpson index was negatively correlated with kidney deficiency(r=-0.463,p=0.003).Correlation analysis between intestinal flora diversity and clinical indicators in patients with PD constipation shows that OTU number,chao index,ace index,shannon index were positively correlated with Phlegm muddiness(rOTU=0.379,pOTU=0.030;rchao=0.411,pcha=0.017;race=0.382,pace=0.028;rshanno=0.388,pshannon=0.026)and negatively correlated with UPDRS(rOTU=0.407,pOTU=0.019;rchao=-0.398,pchao=0.022;race:=-0.392,pace=0.024;rshannon=-0.366,pshannon=0.036);shannon index was positively correlated with kidney deficiency(r=0.357,p=0.042);simpson index was negatively correlated with kidney deficiency(r=-0.387,p=0.026).Conclusions:1.Tenericutes,Mollicutes,RF39,Peptococcaceae,Lactobacillaceae,Burkholderiaceae,02d06,and Lautropia microflora groups are significantly different from the NC group.These differences may be related to the occurrence of PD,For example,constipation;2.Kidney deficiency and Phlegm muddiness in PD and PD constipation patients may be related to intestinal flora diversity;3.The typical TCM syndrome of PD constipation is Liver wind,Marrow deficiency,Yin deficiency,Qi deficiency;4.Shengqing Jiangzhuo Recipe may have the effect of improving PD Yin deficiency constipation,and it is safer. |
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