| Objective:Based on the theory of treating cough with phlegm,this study conducted a meta-analysis of randomized controlled trials using Er Chen Tang as the basic formula to treat asthma in children during the non-acute attack period,in order to provide evidence-based medicine evidence for the treatment of asthma in children and clinical efficacy.The study also explored the characteristics of TCM syndrome elements in the non-acute attack period of asthma and their correlation with clinical biochemical indicators,in order to provide ideas and methods for the clinical treatment of asthma in children.Finally,animal experiments were conducted to investigate whether Huan Xiao Liu An Decoction can regulate the IL-13/STAT6 signaling pathway and reduce airway mucus secretion by regulating inflammatory factors,providing experimental evidence for the clinical application of Huan Xiao Liu An Decoction in asthma in children treatment.Methods:1.A search was conducted for clinical randomized controlled trials of Er Chen Tang as the basic formula for treating asthma worldwide.After literature screening and data extraction,the Cochrane systematic evaluation method was used to conduct a meta-analysis of the total effective rate,TCM syndrome score,pulmonary function and laboratory tests,asthma control,respiratory infection frequency,post-treatment wheezing frequency,and recurrence rate.2.A retrospective study was conducted to develop a syndrome differentiation scale and collect cases of children with non-acute attack period asthma who met the inclusion criteria.The relevant data was entered into an Excel database,and the weight values corresponding to each symptom and sign were calculated for each patient.SPSS 26.0 was used for statistical analysis,and the distribution of syndrome elements was explored.Based on the results of cluster analysis and clinical discussion of the relationships between the syndrome elements,correlation analyses were conducted between the syndrome elements and general information,as well as physical and chemical indicators.3.Forty 4-week-old male Wistar rats were randomly divided into a blank control group(n=10)and an asthma model group(n=30).The asthma model group was sensitized by intraperitoneal injection of a 10%OVA and AL(OH)3 mixed solution(1 ml)on days 1 and 8.Starting from day 15,the rats were stimulated with a 1%OVA solution by inhalation for 30 minutes per day for 7 consecutive days.The asthma model group was further randomly divided into a simple model group,a Huan Xiao Liu An Decoction group,and a dexamethasone group(each n=10)for drug intervention for 6 weeks.All groups except the blank control group were given medication 30 minutes before inhalation stimulation,and the concentration of the OVA solution used for inhalation stimulation increased weekly.HE and PAS staining were used to observe the pathological changes in lung tissue of rats in each group.The lung function machine was used to detect the Area-Rrs value,Area-Rn value,and Area-Ers value of rats in each group.ELISA was used to detect the content of IL-13 and TNF-α in serum and BALF of rats in each group.WB and PCR were used to detect the expression of IL-13,Muc5ac,and Stat6 protein and gene in lung tissue of rats in each group.Immunohistochemistry was used to detect the expression of IL-13 and Muc5ac protein in lung tissue of rats in each group.Results:1.A total of 45 literatures were included in this study,and the study showed that the modified Er Chen Tang formula is used alone or combined with western medicine was found to be more effective than western medicine alone in treating non-acute pediatric asthma in terms of overall efficacy and improvement in traditional Chinese medicine syndrome,especially in improving wheezing,cough,fatigue,spontaneous sweating,poor appetite,and abnormal bowel movements.In terms of lung function,the improvement in FEV1,FEV1/FVC,FVC,PEFv,PEF,FEF25%,and FEF75%was better than western medicine alone,but the improvement in FEF50%was similar to western medicine alone.In terms of laboratory tests,the decrease in serum TNF-α content in children treated was better than western medicine alone,but the decrease in IgE and EOS content was similar to western medicine alone.The improvement in asthma control level,C-ACT score,symptom dimension score,emotional dimension score,and activity limitation dimension score of the PAQLQ questionnaire were better than western medicine alone,In terms of long-term efficacy,the improvement in respiratory tract infection frequency,wheezing episode frequency,and wheezing recurrence rate was also better than western medicine alone.The meta-regression model results showed that the experimental group was a protective factor compared to the control group for overall efficacy,and female patients had a lower effective rate than male patients after treatment.2.A study of TCM syndrome elements found that the main disease location for non-acute attack period asthma in children was in the lungs and surface,involving the spleen and kidneys,and the disease location of the lungs ran through the entire disease.The main diseases were phlegm,wind,heat,and qi deficiency,which is consistent with the characteristics of the "real deficiency and virtual excess,and deficiency-excess mixed" pathogenesis of this period.Fifteen effective binary association rules("syndrome element pairs")were obtained through association analysis.The top three rules in terms of support were phlegm-lungs,wind-lungs,and windsurface,and the top three rules in terms of lift were {cold}=>{surface},{wind}=>{surface},and {cold}=>{phlegm}.Regression analysis results showed that phlegm syndrome was more likely to be diagnosed in the pre-school period,and disease course and gender had no significant impact on the diagnosis of phlegm syndrome.The correlation between syndrome elements and auxiliary examination showed that IgE was positively correlated with lung syndrome elements(P<0.05,r>0);FEV1/FVC was negatively correlated with yang deficiency(P<0.05,r<0),and MEF25%was negatively correlated with cold and yang deficiency(P<0.05,r<0);FeNO50 was positively correlated with yang deficiency(P<0.05,r>0),and CaNO was positively correlated with spleen,yin deficiency,and drinking(P<0.05,r>0).Cluster analysis results showed that the non-acute attack period of asthma is often a mixture of deficiency and excess,with the lungs,spleen,and kidneys being the most common disease locations,and the cause of the disease is a combination of external pathogenic factors and internal hidden factors.3.Animal Experiment:① Airway hyperresponsiveness in rats of each groupCompared with the blank control group,the single modeling group were significant differences in Area-Rrs values in physiological saline,Mech6.25,12.5,25,and 50 mg/mL,and the differences were statistically significant(P<0.05).Compared with the single modeling group,the dexamethasone group showed significant differences in Area-Rrs values in physiological saline,Mech6.25,12.5,and 25 mg/mL,and the differences were statistically significant(P<0.05);the Huan Xiao Liu An Decoction group showed significant differences in Area-Rrs values in physiological saline,Mech25,and 50 mg/mL,and the differences were statistically significant(P<0.05).The Area-Rrs values of the single modeling group and dexamethasone group gradually increased with the concentration of stimulation,while the blank control group and Huan Xiao Liu An Decoction group both peaked at the dose of MeCh25 mg/mL.Compared with the blank control group,there were significant differences in Area-Rn values of the single modeling group in physiological saline,Mech6.25,and 50 mg/mL,and the differences were statistically significant(P<0.05).Compared with the single modeling group,the dexamethasone group showed significant differences in Area-Rn values in Mech50 mg/mL,and the differences were statistically significant(P<0.05);the Huan Xiao Liu An Decoction group showed significant differences in Area-Rn values in Mech6.25 and 50 mg/mL,and the differences were statistically significant(P<0.05).The Area-Rn values of all groups gradually increased with the concentration of stimulation,and all peaked at the dose of MeCh50 mg/mL.Compared with the blank control group,there were significant differences in Area-Ers values of the single modeling group in Mech12.5,25,and 50 mg/mL,and the differences were statistically significant(P<0.05);the dexamethasone group showed significant differences in Area-Ers values in Mech50 mg/mL,and the differences were statistically significant(P<0.05);compared with thesingle modeling group,there were significant differences in Area-Ers values of the dexamethasone group in Mech25mg/mL,and the differences were statistically significant(P<0.05);compared with the single modeling group;the Huan Xiao Liu An Decoction group showed significant differences in Area-Ers values in Mech50 mg/mL,and the differences were statistically significant(P<0.05).The Area-Ers values of all groups gradually increased with the concentration of stimulation,and all peaked at the dose of MeCh50 mg/mL.② Levels of IL-13 and TNF-α in serum and BALFCompared with the blank control group,the IL-13 and TNF-α levels in the serum and BALF of rats in the single modeling group were higher,and the differences were statistically significant(P<0.05);compared with the single modeling group,the IL-13 and TNF-α levels in the serum and BALF of rats in each drug intervention group were lower,and the differences were statistically significant(P<0.05),but there was no significant difference between the two treatment groups(P>0.05).③ IL-13,Muc5ac,and p-Stat6 expression in the lung tissue of each group of rats were detected by WB and PCR.Compared with the blank control group,the levels of IL-13 protein,Muc5ac protein,pStat6 protein,IL-13 mRNA,and Muc5ac mRNA in the lung tissue of the model group rats increased significantly(P<0.05).Compared with the model group,the levels of IL-13 protein,Muc5ac protein,p-Stat6 protein,IL-13 mRNA,and Muc5ac mRNA in the lung tissue of rats in each treatment group decreased significantly(P<0.05).However,the levels of Muc5ac protein,p-Stat6 protein and IL-13 mRNA,Muc5ac mRNA expression in the lung tissue of rats in the Huan Xiao Liu An Decoction group were lower than those in the dexamethasone group,and the difference was statistically significant(P<0.05).There was no statistically significant difference in the expression of Stat6 mRNA among the groups(P>0.05).④Immunohistochemistry was used to detect IL-13 and Muc5ac expression in the lung tissue of each group of rats.Compared with the blank control group,the levels of IL-13 and Muc5ac expression in the lung tissue of the model group rats increased significantly(P<0.05).Compared with the model group,the levels of IL-13 and Muc5ac expression in the lung tissue of rats in each treatment group decreased significantly,and the difference in IL-13 and Muc5ac expression between the Huan Xiao Liu An Decoction group and the model group was statistically significant(P<0.05).However,there was no significant difference among the treatment groups.Conclusion:1.The modified Er Chen Tang formula can improve the overall clinical efficacy and traditional Chinese medicine syndrome,especially for wheezing,coughing,fatigue,spontaneous sweating,poor appetite,and bowel movements in children with asthma during non-acute attacks.It can also improve lung function indicators such as FEV1,FEV1/FVC,FVC,PEFv,PEF,FEF25%,FEF75%,and reduce TNF-α levels,improve asthma control,reduce respiratory tract infections,wheezing attacks,and recurrence rate,and enhance long-term efficacy.The meta-regression model showed that the treatment group was a protective factor compared to the control group in terms of overall efficacy,and the effective rate of female patients after treatment was lower than that of male patients.2.The main affected areas in children with non-acute attack period asthma are the lungs and surface,involving the spleen and kidneys.The main pathogenic factors are phlegm,wind,heat,and qi deficiency,and phlegm is a latent pathological factor throughout the disease course,with a mixture of deficiency and excess.The correlation between syndrome elements and auxiliary examinations showed that immunoglobulin IgE was positively correlated with lung syndrome elements statistically,while lung function indicators FEV1/FVC,FeNO50 were negatively correlated with Yang deficiency statistically,and MEF25%was negatively correlated with Cold and Yang deficiency statistically.CaNO was positively correlated with spleen,Yin deficiency,and drinking statistically.Cluster analysis results showed that the disease was characterized by a mixture of deficiency and excess,with the lungs,spleen,and kidneys being the most commonly affected areas,and both external and internal factors contributing to the disease.3.The Huan Xiao Liu An Decoction may inhibit the proliferation of goblet cells in the airway epithelium,reduce mucous secretion in the lumen,decrease the Area-Rrs value,AreaRn value,and Area-Ers value in the airways of rats,regulate IL-13 and TNF-α levels in serum and BALF,and modulate the expression of IL-13,Muc5ac,p-Stat6 protein,and gene,thereby improving airway inflammation and hyperresponsiveness,and reducing airway mucous hypersecretion. |
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