| Research BackgroundIdiopathic Membranous Nephropathy?shorted for "IMN"?is regarded as one of the common primary glomerular diseases,accounting for nearly 45%of primary nephrotic syndrome.Although current western medicine treatment got a certain achievement,the side effects are significant.The Chinese medicine treatment has some advantages with less side effects.IMN's Chinese comprehensive treatment can reduce patients' urine protein quantitation level and increase the plasma-albumin,showing its advantages in improving and protecting the renal function with more safety.Guided by Li Dongyuan's Yin-Fire hypothesis and Zhang Zhongjing's water retention theory,Professor Yu Renhuan created the therapy and tonifying spleen,damp clearing and collaterals regulating prescriptions,which can invigorate spleen and supplement qi,clear heat and expel damp,reinforce the kidney and regulate the collaterals.It was used for treating the IMN,showing a sound clinic curative effect.The intestinal flora plays an important role in the aspects of digestion and metabolism,immunity and defense,inflammation and cell proliferation,which can not only communicate with the intestinal epithelial cells,but also interact with the remote organs and bodily systems.There is the possibility between chronic kidney disease-colonic axis and the occurrence,development and prognosis of IMN.The patients of chronic kidney diseases?shorted for "CKD"?has changes in intestinal microecology and the imbalance of intestinal microecology also further accelerates the development of nephropathy.Based on the abnormal pathology,the immunologic derangement controlled by the intestinal flora may be considered as the initial factors of autoimmune disease,including the IMN.Study One Research on Cohort of Adopting Jianpi Qushi Heluo Fang to Cure IMNObjectives:The Chinese medicine treatment group mainly uses the Jianpi Qushi Heluo Fang and there is also a comparison group combined conventional treatment of traditional chinese medicine and western medicine.According to a cohort study to evaluate the effectiveness and safety of the Chinese medicine treatment with Jianpi Qushi Heluo Fang and combined conventional treatment of traditional chinese medicine and western medicine,providing the new ideas for curing the membranous nephropathy by Chinese medicine.Methods:Adopting the single-center cohort study,147 patients from the department of nephrology,Xiyuan Hospital,China Academy of Traditional Chinese Medicine,are qualified based on the observation of the IMN patients who were diagnosed precisely by their clinic and pathology from July,2016 to December,2018.The Chinese medicine treatment group mainly uses the Jianpi Qushi Heluo Fang and the comparison group takes the treatment combined conventional treatment of traditional chinese medicine and western medicine.The western medicine treatment mainly choose the immunosuppressive therapy and the Chinese medicine treatment uses the treatment based on syndrome differentiation,offering the other Chinese herbal decoction?except Jianpi Qushi Heluo Fang?.The duration of follow-up was more than 6 months.The main curative effect indexs include patients' 24h urine protein quantitation level and the plasma-albumin,the therapeutic evaluation criterion was evaluated by the IMN's evaluation criterion mentioned in KIDGO guidebook issued in 2012,and the safety was assessed by the incidence of complications.It also evaluated the difference of the curative effect and safety of the Chinese medicine treatment with Jianpi Qushi Heluo Fang and combined conventional treatment of traditional chinese medicine and western medicine.Results:1.Analysis on Patients' Baseline Characteristics147 patients aging from 18 to 80 years'old were recruited,including 84 male patients and 56 female patients,and 7 cases fell off during the treatment.The patients for Chinese treatment group were 75,with the average age of 52.80 ± 13.75 years' old,including 42 male patients and 33 female patients.The patients for comparison group were 65,with the average age of 50.02 ± 15.74 years' old,including 42 male patients and 23 female patients.Both groups had no statistically significant differences in the aspects of age,gender,height,weight,heart rate,blood pressure,course of disease,pathological grading,CKD staging,complicating disease and basic therapy,24h urine protein quantitation,plasma-albumin,urea nitrogen,serum creatinine,eGFR,cholesterol,triglyceride and other physicochemical indexes before the treatment,and P>0.05.2.Therapeutic Evaluation Through Chinese medicine treatment,the 24h urine protein quantitation was reduced obviously in 3 months,6 months and 12 months than pre-treatment levels and P<0.05 and the plasma-albumin was increased greatly in 6 months and 12 months and P<0.05.The urea nitrogen,serum creatinine and eGFR in 3 months,6 months and 12 months had no statistically significant differences and P>0.05.The cholesterol and triglyceride were significantly lower than pre-treatment levels after 12 months and P<0.05.Due to the treatment of comparison group,the 24h urine protein quantitation was greatly reduced in 6 months and 12 months and P<0.05 and the plasma-albumin had no statistically significant differences between 3 months,6 months and 12 months and P>0.05.The urea nitrogen had no statistically significant differences between 3 months,6 months and 12 months and P>0.05 and the treatment of serum creatinine was obviously decreased in 3 months and P<0.05.The eGFR was increased and P<0.05 and the serum creatinine and eGFR had no statistically significant differences between 6 months and 12 months and P>0.05.The cholesterol and triglyceride were reduced in 6 months and 12 months and P<0.05.Comparing with both groups,the treatment of 24h urine protein quantitation and plasma-albumin had no statistically significant differences between 3 months and 6 months and P>0.05 and the 24h urine protein quantitation in 12 months were less than the comparison group and P<0.05 and the plasma-albumin was more than the comparison group and P<0.05.The urea nitrogen in 12 months were less than the comparison group and P<0.05 and the serum creatinine and eGFR in 3 months,6 months and 12 months had no statistically significant differences and P>0.05.The cholesterol and triglyceride in 3 months,6 months and 12 months had no statistically significant differences and P>0.05.The curative effect of both groups in 3 months and 6 months had no statistically significant differences and P>0.05 and in the treatment of 12 months,the curative effect of Chinese medicine treatment group was higher than the comparison group and P<0.05.The syndrome integral of Chinese medicine treatment group in 3 months,6 months and 12 months were less than the pre-treatment and P<0.05,but there were no statistically significant differences between the pre-treatment and after-treatment in 3 months,6 months and 12 months of the comparison group and P>0.05.The syndrome integral of Chinese medicine treatment group were greatly less than the comparison group in 6 months and 12 months and P<0.01 and its effectiveness were higher in the treatment of 6 months and 12 months and P<0.01.Comparing to the major clinical endpoint events,the 3 patients'serum creatinine in the Chinese medicine treatment group got doubled,5 patient's serum creatinine in the comparison group got doubled and 2 patients came to the end-stage renal failure.The SCr doubling and end-stage renal failure had no statistically significant differences and P>0.05.During the treatment,the occurrence rate of diabetes and abnormal liver function in the comparison group were significantly higher than those of the Chinese medicine treatment group and P<0.05.Conclusion:The therapeutic schedule mainly using the Jianpi Qushi Heluo Fang to cure the IMN can decrease the 24h urine protein quantitation,increase the plasma-albumin and improve the clinical effects of the clinical symptoms.Comparing to the integration of conventional Chinese medicine and western medicine treatments,it shows a better long-term clinical effect in reducing urinary protein,increasing the patients'plasma-albumin and improving the life quality in the treatment of 12 months.Considering of the safety,the adverse reaction ratio of diabetes and abnormal liver function was lower.Study Two Research on Exploring the Mechanism of Curing IMN Based on the Intestinal Flora's Jianpi Qushi Heluo FangObjectives:1.Apply the 16S rRNA gene sequencing and Preliminary discussion of the difference of intestinal flora between the IMN patients and healthy people.2.Observe the influence of the intestinal flora of the IMN patients by Jianpi Qushi Heluo Fang and western medicine immunosuppressive therapy through the randomized controlled trial,trying to find the functional mechanism of IMN in the Chinese medicine treatment.Methods:1.Selected 30 MN patients from the department of nephrology,Xiyuan Hospital,China Academy of Traditional Chinese Medicine for outpatient and inpatient service,who didn't use hormone and immunosuppressive therapy from July,2016 to December,2018 and selected 10 persons with physical fitness from physical examination center,Xiyuan Hospital,China Academy of Traditional Chinese Medicine from July,2016 to August,2017.Apply the 16S rRNA gene sequencing and compare the intestinal flora's difference between IMN group and healthy group.2.Among 30 IMN patients who didn't use hormone and immunosuppressive therapy,select 15 IMN patients to join the IMN Chinese treatment group and offer the Jianpi Qushi Heluo Fang.Select 15 patients of them to create the IMN western medicine group,offering the treatment of hormone and immunosuppressor.The duration of treatment is 6 months.Apply the 16S rRNA gene sequencing and compare the intestinal flora's difference between different IMN treatment group pre-and-after the treatment.Results:1.In GeneralThis research chose 30 IMN patients from Xiyuan Hospital,China Academy of Traditional Chinese Medicine for outpatient and inpatient service,aging from 26 to 69 years' old with the average age of 48.83±11.31 years' old,including 17 male patients and 13 female patients.The healthy group had 10 cases,aging from 31 to 56 years' old,with the average age of 44.10±9.23 years' old,including 5 male patients and 5 female patients.The differences were not statistically significant between both groups' gender,age?age stratification?,height,weight,heart rate and blood pressure and P>0.05.Among 30 IMN patients,15 patients were from IMN Chinese medicine treatment group and 15 patients were from the IMN western medicine treatment group.There were 5 cases fell off from IMN western medicine treatment group and 10 patients completed the follow-up.Differences were not statistically significant between both groups'gender,age?age stratification?,height,weight,heart rate,blood pressure,pathological grading,24h urine protein quantitation before treatment,plasma-albumin,urea nitrogen,serum creatinine,eGFR and TCM score and P>0.05.2.Therapeutic EvaluationIMN Chinese medicine treatment group reduced the 24h urine protein quantitation after treatment and P<0.05,increased the plasma-albumin and P<0.05.Before and after the treatment,urea nitrogen,serum creatinine and eGFR showed no statistically significant differences and P>0.05.After the treatment of IMN western medicine treatment group,the 24h urine protein quantitation was reduced and P<0.05.Before and after the treatment,plasma-albumin,urea nitrogen,serum creatinine and eGFR showed no statistically significant differences and P>0.05.After both treatment,24h urine protein quantitation,plasma-albumin,urea nitrogen,serum creatinine and eGFR showed no statistically significant differences and P>0.05.The effective rate of IMN Chinese medicine treatment group was 60%,while the other group was 60%.There was no statistically significant differences between two groups and P>0.05.After the treatment of IMN Chinese medicine treatment group,the syndrome integral was reduced greatly and P<0.05.The syndrome integral of IMN western medicine treatment group had no statistically significant differences before and after the treatment and P>0.05.After the treatment,the syndrome integral of IMN Chinese medicine treatment group and western medicine treatment group showed no statistically significant differences and P>0.05.The syndrome curative effect of both groups had no statistically significant differences and P>0.05.In the aspect of safety evaluation,there occurred complications in the treatment process of IMN western medicine treatment group,such as respiratory infection,abnormal liver function and diabetes,and no complications occurred in the treatment process of IMN Chinese medicine treatment group.3.Analysis on Intestinal FloraConsidering of the euryarchaeota level,the Firmicutes and Bacteroidetes of great relatively abundance got statistically significant differences between IMN group and healthy group and P<0.01.Both of IMN Chinese medicine treatment group and IMN western medicine treatment group had statistically significant differences before and after the treatment and P<0.01.Proteobacteria of relatively abundance had statistically significant differences between different IMN treatment group pre-and-after the treatment and P<0.05.For the genera level,IMN group's Prevotella9 and Megamonas got a higher relatively abundance than that of the healthy group and P<0.05.After the treatment of Chinese medicine,the Bacteroides and Alistipes got a higher relatively abundance and P<0.05,while the Faecalibacterium and Lachnospiraceaeunclassified was reduced and P<0.05.After the treatment of western medicine,Megamonas's relatively abundance was higher and P<0.05,and the relatively abundance of Faecalibacterium and Lachnospiraceaeunclassified was reduced and P<0.05.As Metastat analyzed,due to the comparison of IMN group and the healthy group,the differentiated bacteria were mainly including Bifidobacterium?77?,Dorea,Christens-enellaceaeR-7group,Parabacteroides,Bifidobacterium,Coprococcus3,Escherichia-Shigella and Coprococcus3.Before and after the treatment of Chinese medicine,the differentiated bacteria were mainly including Butyricimonas,Bacteroides,Alistipes and Lachnospira.Before and after the treatment of western medicine,the differentiated bacteria were mainly including Ruminococcus2,Lachnospira,LachnospiraceaeND3007group,Bifidobacterium,[Eubacterium]ventriosumgroup and Alistipes.Conclusion:1.There was a certain difference of intestinal flora between IMN patients and healthy people and the intestinal flora of those IMN patients was disordered.2.There existed difference of intestinal flora before and after the immunosuppression treatment using western medicine,which can be regarded as the treatment can change the intestinal flora.3.There was difference of intestinal flora occurred before and after the treatment of Jianpi Qushi Heluo Fang,which can be regarded as the adjustment of the intestinal flora.4.The relatively abundance changes of Faecalibacterium and the differences between Alistipes and Lachnospira may be the common influence factor in the process of the immune-suppression treatment using western medicine and Jianpi Qushi Heluo Fang.5.Both the treatment of Jianpi Qushi Heluo Fang and immunosuppression have certain curative effects,but to some extent,the changes of intestinal flora between the two groups are different,which may be related to the different mechanism of action of the two groups. |
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