| This paper consists of 3 parts:a literature review section,a clinical research section and a metabolomics research section.The literature review firstly introduces a comprehensive study on the application of metabolomics in bronchial asthma,including pathogenesis,diagnosis and differential diagnosis,typing and treatment,etc.Secondly,it introduces the TCM syndrome classification and objectification study of TCM syndrome in asthma under different stages of asthma.We found that there were significant differences in the expression and distribution of methylation genes and metabolites molecules between patients with cold and hot syndrome.In the clinical study section,asthma patients were randomly divided into the experimental and the control group to observe the clinical efficacy of Xiao-Qinglong decoction in treating the chronic persistent duration of asthma.In the metabolomics study part,the serum of asthma patients before and after treatment was subjected to metabolomics testing to explore the mechanism of Xiao-Qinglong decoction granules in patients with cold syndrome of asthma.Objective:1.The study intends to conduct a randomized controlled study of Xiao-Qinglong decoction granules in the treatment of patients with cold symptoms of asthma to evaluate the clinical efficacy of Xiao-Qinglong decoction granules in the treatment of patients with cold symptoms of asthma and to evaluate the safety of Xiao-Qinglong decoction granules in the treatment of patients with cold symptoms of asthma.2.The mechanism of Xiao-Qinglong decoction granules in the treatment of patients with cold symptoms of asthma will also be explored through metabolomic assays and analysis of small molecule metabolites in the serum of subjects before and after treatment.Methods:1.Clinical study:A total of 60 patients with cold syndrome of chronic persistent asthma were included according to the uniform inclusion and exclusion criteria.The control group was given conventional treatment plus placebo,while the experimental group was given conventional treatment plus Xiao-Qinglong decoction granules.The main efficacy and safety indicators were evaluated until the end of 2 weeks.The efficacy indicators included the TCM symptom score,symptom score and Mini-Asthma Quality of Life Questionnaire(Mini-AQLQ)score,and all efficacy and lung function were evaluated until the end of 4 weeks,including the TCM symptom score,symptom score,Asthma Control Test(ACT)score and lung function(FEV1,FEV1/FVC,VCmax,FVC,PEF).2.Metabolomics study:5 ml of morning fasting peripheral blood was collected from patients with chronic persistent asthma before and 2 weeks after treatment,and the plasma was centrifuged and separated,and the serum samples were subjected to non-targeted metabolomic assays using liquid-liquid mass spectrometry(LC-MS)according to standard procedures.)and other methods were used to analyze and identify metabolic markers,screen for differential biomarkers within and between the two groups,and perform metabolic pathway analysis on the biomarkers.To investigate the mechanism of action of Xiao-Qinglong decoction in the treatment of patients with cold symptoms in the chronic persistent phase of asthma.Results:1.Xiao-Qinglong decoction was able to improve the TCM syndrome score,improve clinical symptoms,enhance quality of life and improve FEV1 and FEV1/FVC levels in patients with chronic persistent cold symptoms of asthma.The results of the study showed that there was no significant improvement in the efficacy of the TCM symptoms in the test group before and after treatment(P>0.05),and there was no significant difference between the treatment group and the control group(P>0.05).In the aspect of the total TCM symptom score,primary symptom score and secondary symptom score,the test group improved at 2 weeks and 4 weeks after treatment(P<0.05),and there was no significant difference between the test group and the control group after treatment(P>0.05).In terms of ACT and Mini-AQLQ scores,the ACT and Mini-AQLQ scores improved significantly before and after treatment in the test group(P<0.05),and there was no significant difference in ACT scores and Mini-AQLQ scores between the test and control groups after treatment(P>0.05).In the aspect of pulmonary function indexes,In terms of pulmonary function indicators,the levels of FEV1 and FEV1/FVC increased in the test group(P<0.05),but there was no significant improvement in FVC,VCmax,and PEF(P>0.05),and there was no significant difference in pulmonary function indicators between the test group and the control group(P>0.05).In terms of FeNO,comparing the FeNO level before and after treatment in the test group,the results showed that the FeNO level improved before treatment compared with that after treatment in the test group(P<0.05),and there was no difference between the test group and the control group comparing the FeNO level after treatment(P>0.05).2.Potential differential metabolites were screened by LC-MS technique with P<0.05,Fold Change>1 and VIP>1.There were 75 differential metabolites between the test group before and after treatment,and 295 differential metabolites between the control group and the test group after treatment.Before and after treatment,the test group mainly involved phosphonate and hypophosphonate metabolism,citric acid cycle(TCA cycle),nitrogen metabolism,glutamatergic synapse,and proximal tubular bicarbonate recovery pathway.The differences between the treatment group and the control group involved caffeine metabolism,biosynthesis of ubiquitin and other terpenoid quinones,folate biosynthesis,steroid biosynthesis,cutin,soft alkali and wax.Between the differential metabolites before and after treatment and the different metabolites between the control group and the test group,it was found that the histidine metabolism pathway,phosphonate and phosphate metabolism pathways could be mainly concentrated.The related metabolites involved 2-aminoethylphosphonate,thimalic acid.Conclusion1,Xiao-Qinglong decoction can improve the TCM symptoms,clinical outcomes,living standards and lung function in patients with cold symptoms in the chronic persistent phase of asthma,and can increase FEV1 and FEV1/FVC levels and effectively reduce FeNO in patients.2.Through metabolomic studies,it can be found that Xiao-Qinglong decoction can affect the levels of 2-aminoethylphosphonate and thiomalonic acid,and perturb the histidine metabolic pathway with phosphonate and phosphate metabolic pathways.It is hypothesized that Xiao-Qinglong decoction may play a role in asthma treatment by regulating the histidine metabolic pathway through thiomalonic acid. |
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