| The first part Influencing Factors on Long-Term Prognosis of Membranous Nephropathy Treated by Invigorating Spleen and Qi,Activating Blood and DetoxicationObjective To explore the factors on the long-term prognosis of membranous nephropathy treated by invigorating spleen and qi,activating blood and detoxication.To Comparing the differences in response to invigorating spleen and qi,activating blood and detoxication with or without the previous use of glucocorticoid and immunosuppressive agents to assess the influence of the previous treatment plan on the efficacy of Chinese medicine.Methods A single-center cohort study was conducted and the different baseline clinical indicators were analyzed by stratification.Kaplan-Meier method was used to compare the differences in renal cumulative survival rate between different groups.Univariate and multivariate Cox regression were used to analyze the correlation between clinical indicators and treatment prognosis and the independent factors affecting treatment prognosis.According to whether the patients use of glucocorticoid and immunosuppressive agents in the past,the propensity score matching method was applied for 1:1 matching of the baseline indicators of the patients.Comparing the two groups of patients on the response to traditional Chinese medicine treatment over time,further evaluate the influence of the previous use of glucocorticoid and immunosuppressive agents on the efficacy of invigorating spleen and qi,activating blood and detoxication.Result(1)A total of 386 patients were included in the study,including 223 males and 163 females.The median follow-up time was 45.0 months.By the end of follow-up,a total of 18 patients had achieved hard end point events and 40 patients had achieved composite endpoint events.(2)Kaplan-Meier method showed that there was no statistically significant difference in renal cumulative survival rate between different genders for hard end point events(P=0.136),but there was statistically significant difference in renal cumulative survival rate for composite endpoint events.The renal cumulative survival rate of women was higher than that of men(P=0.027).There was no significant difference in renal cumulative survival rate between different level of 24 hpro before treatment for hard end point event and composite endpoint event(P > 0.05).The stage of CKD showed statistically significant difference in renal cumulative survival rate of both hard endpoint events and composite endpoint events.The higher the CKD stage,the lower the renal cumulative survival rate(P < 0.05).There were statistically significant differences in renal cumulative survival rate between whether remission for hard end point events and composite end point events.The renal cumulative survival rate in complete remission(CR)group or partial remission(PR)group was significantly higher than that in no remission(NR)group(P<0.05).There was no statistical significance in renal cumulative survival rate between whether recurrence for hard end point events and composite endpoint events(P > 0.05).Whether use of glucocorticoid and immunosuppressive agents had no statistical significance in renal cumulative survival rate for the hard endpoint event(P=0.099).For the composite endpoint event,the renal cumulative survival rate in the previous use of immunosuppressive agents group was significantly lower than that in the non-immunosuppressive agents group,and the difference was statistically significant(P=0.009).(3)Univariate Cox regression showed that gender,the stage of pathology,the lever of albumin,hemoglobin,urea nitrogen,CKD stage,whether use of glucocorticoid and immunosuppressive agents and remission during treatment were the factors that affected the endpoint events.Multivariate Cox regression analysis showed that hemoglobin,CKD stage,whether use of glucocorticoid and immunosuppressive agents and remission during treatment were independent influencing factors for the prognosis of patients with membranous nephropathy treated with invigorating spleen and qi,activating blood and detoxication.(4)The method of invigorating spleen and qi,activating blood and detoxication in the treatment of MN can significantly reduce the proteinuria,increase albumin,protect renal function and improve blood lipid levels with the extension of treatment time,and the response to the initial TCM treatment is better in the non-immunosuppressive agents group.The incidence of composite end points was lower during the entire follow-up period in the non-glucocorticoid and immunosuppressive agents group(P <0.05).Conclusion(1)Hemoglobin,CKD stage and whether use of glucocorticoid and immunosuppressive agents and remission during treatment are independent factors affecting the prognosis of membranous nephropathy treated by invigorating spleen and qi,activating blood and detoxication(2)The method of invigorating spleen and qi,activating blood and detoxication for MN has a good clinical effect.With the extension of treatment time,it can significantly reduce proteinuria,increase albumin,stabilize renal function and regulate the levels of blood lipids.(3)Compared with patients who had previously used glucocorticoid and immunosuppressive agents,patients had better response to initial TCM treatment,higher effective rate,lower recurrence rate and incidence of end point events in the nonimmunosuppressive agents group.The second part Based on High Coverage Targeted Lipidomics to Explore the Factors of Difference in Therapeutic Effect of Traditional Chinese Medicine for Treatment of Membranous NephropathyObjective To investigate the difference of lipid metabolism before and after the treatment of membranous nephropathy with the method of invigorating spleen and qi,activating blood and detoxication.To further explore the lipid markers related to the efficacy of the method in the treatment of membranous nephropathy and find a new monitoring target for the treatment of membranous nephropathy with TCM.Methods Primary membranous nephropathy confirmed by renal biopsy were included in this study.They received TCM treatment of invigorating spleen and qi,activating blood and detoxication for one year in our department,and plasma samples were collected before and after treatment.High coverage targeting lipidomics was used to quantitatively analyze lipids in the samples before and after treatment.According to the treatment effect,the patients were divided into effective group and ineffective group,we explored the difference of lipid metabolism profile before and after TCM treatment and to research the lipid markers that affect the therapeutic effect.Result(1)A total of 675 lipids were identified by high performance liquid chromatography mass spectrometry(LC-MS),and 368 lipids with coefficient of variation(CV)less than 30% and missing value less than 10% were included for statistical analysis.(2)After adjusting for other clinical influencing factors,a cross-sectional analysis found that 16 lipids were positively correlated with 24-hour proteinuria;28 lipids including 5 types(Cer ds、LPCs、PCs、SMs、TG-FAs)were associated with albumin.(3)There were 105 lipids with statistical difference after the treatment of invigorating spleen and qi,activating blood and detoxication,including 43 sphingolipids(Cer d/SM),33 glycerides(DG/TG),18 glycerophosholipids(PC/LPC),8 fatty acyls and 3 sterol lipids.Among them,sphingolipids,glycerides and fatty acyls were significantly down-regulated,while LPC was significantly up-regulated and PC was significantly down-regulated.(4)Seven modules were identified by WGCNA network analysis of lipids with differences before and after treatment.After adjusting different clinical indicators,the results showed that the yellow module was correlated with the therapeutic efficacy of TCM.However,the correlation trend was no longer statistically significant when the relative concentration of lipids was divided into quartile groups.In the green module,compared with the low quartile,the high quartile significantly reduced the probability of effectiveness of TCM treatment.The yellow and green modules were mainly focus on TGs lipid molecules.(5)According to therapeutic efficacy,TGs molecules were grouped.11 TG molecules were significantly down-regulated in the effective group.Logistic regression was used to adjust different clinical indicators,and only four lipid molecules,TG56:2-FA20:0,TG56:2-FA20:1,TG56:3-FA20:0,and TG56:5-FA20:2,were found to be most closely related to the therapeutic effect of TCM.ROC curve analysis showed that these four lipids could further improve the predictive efficacy of treatment based on the combined clinical indicators.Conclusion(1)This study shows that the therapeutic effect of invigorating spleen and qi,activating blood and detoxication in the treatment of membranous nephropathy may be achieved by regulating lipid metabolism(2)The lipid type of TGs molecules are most closely related to the therapeutic effect of TCM.Four lipid molecules,TG56:2-FA20:0,TG56:2-FA20:1,TG56:3-FA20:0 and TG56:5-FA20:2,can further improve the prediction efficiency of the therapeutic efficacy of TCM on the basis of combining with other clinical indicators... |
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