| Objective:.Metabolic syndrome(MS)is a combination of multiple cardiovascular risk factors,with high incidence and great harm,especially in the elderly.Cardiopulmonary function is related to cardiovascular risk and plays an increasingly important role in the disease management of elderly patients with metabolic syndrome.Exercise therapy is an important modality of the primary prevention of cardiovascular disease,and it is also an important embodiment of the principle of "prevention before disease,prevention before disease changes" in traditional Chinese Medicine.At present,there is a lack of targeted research on the cardiopulmonary function,TCM syndrome characteristics,and the efficacy and mechanism of traditional Chinese exercises in elderly patients with metabolic syndrome.To investigate the cardiopulmonary function and related cardiovascular risk factors in elderly patients with metabolic syndrome.To study the syndrome characteristics of elderly patients with metabolic syndrome,and the differences of serum metabolomics in different syndromes,so as to provide reference for clinical diagnosis and treatment.To explore the evidence-based medical evidence of the efficacy of traditional Chinese medicine exercises on metabolomics intervention.To evaluate the efficacy and safety of traditional Chinese medicine(TCM)exercise"Wutipingheng exercise" on cardiopulmonary function and related cardiovascular risk factors in elderly patients with metabolic syndrome.To explore the mechanism of"Wutipingheng exercise" in improving cardiopulmonary function and related cardiovascular risk factors in elderly patients with metabolic syndromeMethods:1.Meta-analysis.The databases of China National Knowledge Infrastructure(CNKI),Wanfang,VIP,SinoMed,PubMed,EMbase and Cochrane Library were systematically searched from the establishment of the database to September 2022.The Cochrane risk assessment tool ROB was used to evaluate the methodological quality of the included studies,and RevMan 5.4 software was used for statistical analysis.2.Cross-sectional survey.The case data were collected and sorted out to establish a database.The cardiopulmonary function parameters and other clinical data of the samples were extracted,and the cardiopulmonary function and related cardiovascular risk factors of elderly patients with metabolic syndrome were obtained through comparative analysis.The information of the four TCM diagnoses of the samples was extracted,and the syndrome variables were extracted by exploring factor analysis,and then the distribution of TCM syndromes in elderly patients with metabolic syndrome was obtained by systematic cluster analysis.3.Randomized controlled trial(RCT).Elderly patients with metabolic syndrome admitted to the Department of Cardiology,General Medicine,Endocrinology and Respiratory Medicine of Guang ’anmen Hospital of China Academy of Chinese Medical Sciences from March 2021 to September 2022 were enrolled.The patients who met the inclusion criteria were randomly divided into the TCM exercise group and the control group.TCM Exercise group:Wutipingheng exercise was taught by professional rehabilitation trainers,and participants were required to practice 2-4 times per week for 45 minutes per time for 12 weeks according to the training requirements of the study.The control group received routine rehabilitation training under the guidance of professional rehabilitation trainers,and the training content was mainly moderate to low intensity aerobic exercise,2-4 times a week,45 minutes each time,and lasted for 12 weeks.Both groups were given reasonable drug treatment according to their conditions.The main outcome measures were cardiopulmonary exercise test and 6minute walk test.Triglyceride,low density lipoprotein,total cholesterol,high density lipoprotein,homocysteine,blood glucose,uric acid,fasting blood glucose,glycosylated hemoglobin;TCM symptom analysis.4.Serum metabolomics experimental study.To investigate the differences of serum metabolites in elderly patients with metabolic syndrome with different TCM syndromes by ultra-high pressure liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS),and to analyze the differential metabolic pathways among different syndromes.To detect and analyze the changes of serum ceramide metabolic profile before and after "Wutipingheng exercise" intervention in elderly patients with metabolic syndrome.Results:1.A total of 8 randomized controlled trials with 654 patients were included in the Meta-analysis,and the overall methodological quality of the included studies was not high.The results of Meta-analysis showed that traditional Chinese exercises could improve body mass index,fasting blood glucose,triglyceride,high low-density lipoprotein cholesterol and total cholesterol levels in patients with metabolic syndrome compared with conventional exercise.One of the studies with high methodological quality showed that Tai Chi exercise could improve systolic blood pressure,diastolic blood pressure,and triglyceride levels in patients with metabolic syndrome.Yijinjing exercise can improve the quality of life and satisfaction of patients.No significant adverse events were reported.2.A total of 337 patients were included in the cross-sectional study,and all of them were enrolled in the MS group.Among them,176 cases(43.7%)were female,the oldest was 82 years old,the youngest was 60 years old,the shortest disease duration was 3 months,and the longest disease duration was more than 30 years.The average age was(69.45±8.87)years.There were 75 cases in the control group(HC group),including 37 females,the oldest was 81 years old,the youngest was 60 years old,and the average age was(68.86±9.24)years old.A total of 337 TCM clinical syndrome survey scales were collected.After collation and analysis,low-frequency items with occurrence frequency less than 10%were deleted,54 main symptoms and signs items were obtained,and 11 common factors were obtained after exploratory factor analysis.With the method of systematic cluster linkage between groups,Pearson correlation was used as the interval measurement standard,and the trend of factor contribution rate in the gravel map was referred to,the syndrome analysis results were obtained after comprehensive analysis:syndrome of qi and Yin deficiency:F2:fatigue and lazy speech,spontaneous sweating,night sweat,dry mouth and thirst,shortness of breath and fatigue,weak pulse,tongue crack and less moss;Yin deficiency of liver and kidney syndrome:F1:depression,hot heart of hands and feet,irritability,belching acid regurgitation,red tongue,tongue crack,number of pulses,bitter mouth,less fur,yellow urine,fullness and tightness of the two sides,blurred vision,fine pulse,good restlessness;Phlegm-dampness internal obstruction syndrome:F5:obesity,cough,spit,slippery pulse,greasy moss,abdominal distension;Syndrome of phlegm and blood stasis:F3+F6:fat tongue,greasy mouth,loss of appetite,abdominal distension,tongue teeth,loose stool,thick coating,tongue ecchymosis,limb numbness,tortuous and cyanosis of sublingual vein,dark purple tongue,greasy coating,pulse string,chest tightness,smooth pulse,and difficult defecation;Spleen and kidney deficiency syndrome:F4:amnesia,cold limbs,heavy pulse,waist and knee soreness/heavy,tinnitus and deafness,weak pulse,facial and limb edema,dark face.Regression method was used to calculate the score of each sample in each factor,and the highest score was used to determine the syndrome.The distribution of syndrome in elderly MS patients was obtained:97 cases of Yin deficiency of liver and kidney,accounting for 28.78%;There were 78 cases of qi and Yin deficiency syndrome,accounting for 23.15%;64 cases had phlegm and blood stasis syndrome,accounting for 18.99%;55 cases had phlegm dampness and internal obstruction,accounting for 16.32%;There were 43 cases of spleen and kidney deficiency,accounting for 12.76%.A total of 131 elderly patients with metabolic syndrome completed cardiopulmonary exercise testing(CPET),6minute walk test(6MWT)and static pulmonary function test(PFT),and were enrolled in the MS-C group.Compared with the control group(HC group),the cardiopulmonary exercise test parameters AT,HRpeak,VO2peak(L/min),VO2peak(L/min·kg),VO2/HRpeak,VEpeak,METS,HRR,OUES and 6MWT in MS-C group were significantly lower than those in the control group.The difference was statistically significant(P<0.05).The VE/VCO2 slope value increased,and the difference was statistically significant(P<0.05).In terms of static pulmonary function parameters,the MS-C group had significantly lower FVC,FEV1 and MVV parameters than the HC group(P<0.05).There was no significant difference in FEV1/FVC(%)between the two groups(P=0.575).Compared with the HC group,the MS-C group had significantly lower VO2peak(L/min·kg),METS,SBPR and HRR parameters(P<0.05),and the HCY value was higher in the MS-C group than in the HC group(P<0.05).There was no significant difference in SBPR and hs-CRP between the two groups(P>0.05).3.A total of 174 patients who met the inclusion criteria were enrolled in this randomized controlled study.During the study,37 cases were dropped out of the sample(15 cases in the Wutipingheng group and 22 cases in the control group),and 137 cases completed the study,including 72 cases in the exercise group and 65 cases in the control group.The two groups of patients were balanced and comparable in gender,weight and other general data,as well as the baseline levels of cardiopulmonary function,clinical biochemical indicators and cardiovascular risk factor related indicators.After the intervention,the systolic blood pressure and diastolic blood pressure of the two groups were significantly improved(P<0.05).Body weight,waist circumference,hip circumference,and body mass index seemed to decrease,but there was no significant difference between the two groups(p>0.05).There was no significant difference in the above parameters between the two groups after intervention(p>0.05).The core indicators of the main cardiopulmonary exercise test VO2peak,VO2peak(L/min·kg),HRpeak,VO2/HRpeak(ml/beat),METS,and 6MWT in the two groups were significantly improved compared with those before treatment(p<0.05).There was no significant difference between the two groups(p>0.05).The AT index in the Qigong group showed a significant improvement trend compared with that before treatment(p=0.037),while the control group also showed an improvement trend,but the change was not significant(p=0.06).The other indicators SBPR,OUES and VD/VTpeak in the two groups had no significant changes before and after rehabilitation intervention(p>0.05).In terms of static pulmonary function,FVC and FEV1 of the two groups showed a certain improvement trend after 12 weeks of rehabilitation training,but the difference was not statistically significant(p>0.05).FEV1/FVC had no significant change before and after rehabilitation intervention in the two groups(p>0.05).In terms of MVV,the exercise group was significantly improved after rehabilitation intervention(p=0.037),while the improvement trend in the control group was not statistically significant(p=0.122).There was no significant difference in static pulmonary function indexes between the two groups(p>0.05).The main biochemical indexes of the two groups were improved to varying degrees.In terms of blood lipids,the levels of TG(p=0.018,p=0.028)and HDL-C(p=0.020,p=0.042)in the exercises group and the control group were significantly improved.CHO and LDL-C levels were not statistically different(p>0.05).In terms of blood glucose,the fasting blood glucose(P=0.029,P=0.042)and glycosylated hemoglobin(p=0.017,p=0.028)of the exercise group and the control group were significantly improved,and the difference was statistically significant.In terms of other metabolic indicators,the blood and urine levels of the two groups were significantly improved after rehabilitation intervention(p=0.029 in the exercise group and p=0.027 in the control group).There was no significant difference in biochemical indicators between the two groups(p>0.05).For cardiovascular disease risk factors VO2peak(L/min·kg),METS,SBPR,HRR,OUES,hs-CRP and HCY,after rehabilitation intervention,the control group had significant improvement in VO2peak(L/min·kg),HRR and HCY,and the differences were statistically significant(p<0.05).In addition to the significant improvement of the above indicators(p<0.05),the improvement trend of METS in the exercise group was also statistically significant(p=0.037).After comparing the absolute value of the difference of the above cardiovascular disease risk factors with statistical differences in each group,it was found that the improvement of Δ VO2peak(L/min·kg)in the exercise group was more significant than that in the control group(p=0.030).In the comparison of the difference value of homocysteine ΔHCY,the improvement of the exercise group tended to be greater than that of the control group,but the difference was not statistically significant(p=0.061).There was no significant difference in the difference values of other items(p>0.05).The 10 symptoms with the highest positive rate of TCM syndromes in elderly patients with metabolic syndrome obtained in the previous part of the study were selected.They were fatigue,dry mouth and thirst,impatience and irritability,insomnia and dreams,constipation,waist and knee soreness,dizziness,palpitations,chest tightness,limb numbness,cold and cold limbs,limb drowsiness,abdominal distension,nocturia,spontaneous sweating,night sweats,tinnitus/deafness,five upset and hot,eating more easily hungry,good rest.The TCM symptoms of the two groups before the rehabilitation intervention were balanced and comparable(p>0.05).The symptoms of the patients before and after the rehabilitation intervention were analyzed and compared.The results showed that the patients in the exercise group had additional improvement in impatience,irritability,insomnia and dreams,and spontaneous sweating(p=0.044,p=0.045,p=0.046,respectively).There was no significant difference in other symptoms between the two groups(p>0.05).In terms of safety evaluation,none of the participating patients reported obvious discomfort during exercise rehabilitation.4.Metabolomics differential metabolites and pathway analysis:With VIP>2,p<0.001;0.001 as the screening condition,the VIP scores of metabolites were ranked and statistically analyzed,and the following 15 target metabolites were found to be significantly different:16 ceramide(D18:1/20:0),No.15 ceramide(D18:1/22:0),No.63 ceramide(D18:0/18:0),No.61 ceramide(T18:0/16:0),No.74 ceramide(D18:0/16:0),No.10 glycerate(18:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)),No.68(S)actinidine,No.65 glycerate TG(14:0/14:0/14:1(9Z)),No.78 acetyl-β-alanine,No.81 pyroglutamine,No.75 octadecamide,No.76 dihydroxydocosatrienoic acid(22:3),No.79 p-cresyl sulfate,No.80 Phenylacetyl glutamine,hydroxyleucine No.77.Metabolic pathway analysis showed that these metabolites mainly affected glycerophospholipid metabolism,linoleic acid metabolism,α-linolenic acid metabolism,arachidonic acid metabolism,fatty acid metabolism,etc.In addition to common differential metabolites in elderly MS,differential metabolites in each syndrome group of elderly MS:There were 12 kinds of differential metabolites in the liver-kidney Yin deficiency syndrome group.Eight were up-regulated,PC(18:0/20:3(5Z,8Z,1 1Z))、Leucyl-Hydroxyproline、Nervonoylacetone、Palmitic amide、TG(18:1(9Z)/16:0/18:3(9Z,12Z,15Z))、PC(18:0/P-18:1(11Z))、PC(18:0/P-16:0)、13’-Hydroxy-alpha-tocopherol;Four downregulated metabolites were armillaripin、PE-NMe2(20:1(11Z)/15:0)、PENMe2(20:1(11Z)/15:0)、Phenylacetylglutamine.There were 12 differential metabolites in the qi and Yin deficiency syndrome group,and TG(18:1(9Z)/16:0/18:3(9Z,12Z,15Z))、PC(18:0/20:3(5Z,8Z,1 1Z))、S-MethylmalonylCoA、Palmitic amide、Leucyl-Hydroxyproline、13’-Hydroxy-alpha-tocopherol、1Butylamine、Nervonoylacetone、PC(18:0/P-18:1(11Z));Three were down-regulated:Pivaloylcarnitine;PA(18:4(6Z,9Z,12Z,15Z)/24:1(15Z));PE(0:0/20:0);PENMe2(20:1(11Z)/15:0)、PE-NMe(24:1(15Z)/24:1(15Z)).There were 13 differential metabolites in the phlegm-dampness internal obstruction syndrome group,of which 8 were up-regulated:PC(18:0/20:3(5Z,8Z,11Z))、PE-NMe2(20:1(11Z)/15:0)、TG(18:1(9Z)/16:0/18:3(9Z,12Z,15Z))、PC(18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z))、Leucyl-Hydroxyproline、Nervonoylacetone、Palmitic amide、PC(18:0/P-18:1(11Z))、PC(18:0/P-16:0);Three metabolites were down-regulated:PE-NMe2(20:1(11Z)/15:0)、PE-NMe(24:1(15Z)/24:1(15Z))、Phenylacetylglutamine、Phenylacetylglutamine.There were 15 kinds of differential metabolites in the phlegm and blood stasis syndrome group.Among them,up-regulated PC(18:0/20:3(5Z,8Z,11Z))、Nervonoylacetone、Leucyl-Hydroxyproline、Palmitic amide、PC(18:0/P-18:1(11Z))、TG(18:1(9Z)/16:0/18:3(9Z,12Z,15Z))、PC(18:0/P-16:0)、TG(8:0/8:0/i-12:0)、13’Hydroxy-alpha-tocopherol、Dihydroxydocosatrienoic acid(22:3);Five were downregulated:PE-NMe(24:1(15Z)/24:1(15Z))、PE-NMe2(20:1(11Z)/15:0)、PENMe(24:1(15Z)/24:1(15Z))、p-cresol sulfate、Pivaloylcarnitine.There were 17 differential metabolites in elderly MS patients with Spleen and kidney deficiency,and 12 were up-regulated:PE-NMe2(20:1(11Z)/15:0)、TG(18:1(9Z)/16:0/18:3(9Z,12Z,15Z))、Leucyl-Hydroxyproline、TG(8:0/8:0/i-12:0)、PC(18:0/20:3(5Z,8Z,11Z))、PE-NMe(24:1(15Z)/24:1(15Z))、Palmitic amide、Armillaripin、LysoPE(0:0/20:0)、S-Methylmalonyl-CoA、PC(18:0/P-18:1(11Z))、PC(18:0/P-16:0)、13’-Hydroxy-alpha-tocopherol;Five were down-regulated:E-10Hydroxynortriptyline、S-Methylmalonyl-Co A、L-Palmitoylcarnitine、Pivaloylcarnitine.The specific metabolic difference ceramides in elderly patients with metabolic syndrome were ceramide(D18:1/20:0),ceramide(D18:1/22:0),ceramide(D18:0/18:0),ceramide(T18:0/16:0),and No.74 ceramide(D18:0/16:0).Before and after the intervention of "Wutipingheng exercise",the above-mentioned Ceramide showed a downward trend,and the Ceramide Ceramide(D18:0/16:0)in the liver and kidney Yin deficiency group decreased significantly before and after the intervention.The Ceramide Ceramide(D18:1/20:0),Ceramide(D18:0/18:0)and Ceramide(T18:0/16:0)decreased significantly before and after qi and Yin deficiency intervention.The Ceramide(T18:0/16:0)and Ceramide(D18:0/16:0)decreased significantly before and after the intervention of phum-dampness internal resistance.The Ceramide(D18:1/20:0),Ceramide(T 18:0/16:0)and Ceramide(D 18:0/16:0)decreased significantly before and after the intervention of phlegm and blood stasis mutual accumulation.Ceramide Ceramide(T18:0/16:0)and Ceramide(D 18:0/16:0)decreased significantly before and after intervention of spleen and kidney deficiencyConclusion:1.The Meta analysis results show that the traditional Chinese medicine exercise therapy in patients with the metabolic syndrome to improve obesity,blood pressure,blood sugar,blood fat index has potential advantages,and is safe,but in the number of poor methodological quality as a whole,the research study is less,the conclusion obtained reliability is low,the higher quality of clinical trials to verify the curative effect was warranted.2.The overall cardiopulmonary function of elderly patients with metabolic syndrome is significantly lower than that of the normal group,and the risk of cardiovascular disease is higher.Through sorting out the TCM clinical data of elderly MS,the syndrome classification and distribution of elderly MS patients were obtained after exploratory factor analysis and systematic cluster analysis,which provides a reference for clinicians to better grasp the TCM syndrome rules of elderly MS.3.Compared with conventional aerobic exercise,wutipingheng exercise may improve the cardiopulmonary function and related cardiovascular disease risk factors in patients with MS more significantly and objectively,with good safety.4.The significantly different metabolites in the positive and negative ion mode between the elderly MS group and the healthy group mainly included amino acids,sugars,fatty acids,glycerates,phospholipids,organic acids,nucleosides,alkaloids,etc.The categories of differential metabolites between the sub-groups of each syndrome group and the healthy group were roughly the same,and there were some differences in specific metabolites.Through further analysis and literature review,it was found that these metabolites mainly affected glycerophospholipid metabolism,linoleic acid metabolism,α-linolenic acid metabolism,arachidonic acid metabolism,fatty acid metabolism,etc.5.After Wutipingheng exercise intervention,the above five ceramides in elderly MS patients have significantly decreased compared with those before treatment.Wutipingheng exercise may improve the cardiopulmonary function,cardiometabolic status and reduce cardiovascular risk in elderly patients with MS by improving the mechanism of ceramide metabolic profile. |
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