Establishment Of Macro-level Quantitative Diagnostic Criteria And Metabolism Studies In High-normal Blood Pressure With Liver Fire Hyperactivity Syndrome

Objective:This study aims to establish quantitative diagnostic criteria of high-normal blood pressure with liver fire hyperactivity syndrome.The diagnostic criteria provides theoretical and practical basis for the normalization and standardization of liver fire hyperactivity syndrome.Byexploring potential metabolic biomarkers of this syndrome,a discriminant model of metabonomics is constructed to interprets the scientific connotation of high-normal blood pressure with liver fire hyperactivity syndrome from the view of metabonomics.Methods:1.This study established macroscopic quantitative diagnostic criteria for liver fire hyperactivity syndrome of high-normal blood pressure.The syndrome diagnosis scale was established by using statistical methods such as literature collation,expert consultation,factor analysis and cluster analysis.And then the diagnosis scale was evaluated from three aspects:reliability,validity and responsiveness.Moreover,weight coefficient of entries was also calculated by using both subjective and objective methods.After establishing a syndrome diagnosis model by the normalization method,the threshold value was established by drawing ROC curve and the syndrome degree was classified through method of percentiles.Finally,both retrospective and prospective testing were on scheduled.2.This study carried on a metabolic model of liver fire hyperactivity syndrome of high-normal blood pressure.By using the method of plasma metabolomics based on ultra performance liquid chromatography-mass spectrometry,we analyzed plasma samples from three sources:healthy volunteers,patients with liver fire hyperactivity syndrome of high-normal blood pressure and patients with liver fire hyperactivity syndrome of hypertension.Carried on multivariate statistical and metabolic pathway analysis,we filtered different metabolic markers and metabolic pathways,which revealed the characteristics of metabolic patterns in the syndrome.Then,we integrated the data and regard as the independent variables.The partial least squares method was used to establish a metabolomics discriminant model of liver fire hyperactivity syndrome of high-normal blood pressure.Results:1.This study established macroscopic quantitative diagnostic criteria for liver fire hyperactivity syndrome of high-normal blood pressure.We established a diagnostic scale on liver fire hyperactivity syndrome of high-normal blood pressure.Our results showed that reliability,validity and responsiveness of the scale were good.Based on the diagnostic scale,a diagnostic model was established:Y=20*Irritability+ 15*Head swelling+ 11*Dry mouth+ 23*Mouth bitter+ 3*Constipation+4*Dry eye+ 8*Dark color urine+ 9*Rapid pulse+ 7*Tongue red(Y stands for syndrome points).The threshold of diagnostic scale was 122,with the sensitivity of 94.7%and the specificity of 92.0%.Then,we formulated a diagnostic grading standard with mild degree of 122-150 integral,moderate of 150-214 integral,and severe of greater than 214 integral.Therefore,clinical retrospective and prospective tests showed that there were a good specificity,sensitivity and accuracy in the diagnostic criteria.2.This study carried on a metabolic model on liver fire hyperactivity syndrome of high-normal blood pressure.Firstly,the patients with liver fire hyperactivity syndrome of high-normal blood pressure were transversely compared with both healthy volunteers and liver fire hyperactivity syndrome of hypertension patients respectively.After that,19 differential metabolites was filtered as characteristic metabolic biomarkers of internal pathological process from original healthy status to high-normal blood pressure to finally hypertension with liver fire hyperactivity syndrome.Moreover,we also filtered 33 biomarkers represented liver fire hyperactivity syndrome of high-normal blood pressure and 12 biomarkers represented the process from high-normal blood pressure to hypertension with the same syndrome.Based on the results above,we established a discriminant model of metabonomics:Y=-0.152*X1+ 0.131*X10+ 0.036*X11+ 0.132*X20+ 0.081*X19-0.101*X31+ 0.082*X15-0.038*X9+ 0.079*X24+ 0.043*X23+ 0.076*X16-0.070*X13-0.006*X8+ 0.040*X5.Model interpretation ability was 88.4%and model predicted value was 88.1%.The results identified that the model had accurate prediction ability.Conclusions:1.We established a diagnostic scale of liver fire hyperactivity syndrome of high-normal blood pressure,which had high accuracy and good sensitivity.On this basis,the quantitative diagnosis criteria was feasible,and the clinical practicability was high valued.2.We screened out characteristic metabolic markers which reflected the occurrence of high-normal blood pressure with liver fire hyperactivity syndrome and the process of high-normal blood pressure progressing into hypertension.Then,we preliminary constructed a metabolomics discriminant model of liver fire hyperactivity syndrome of high-normal blood pressure.