Urinary Metabolite Profiling Offers Potential for Differentiation of Liver-Kidney Yin Deficiency and Dampness-Heat Internal Smoldering Syndromes in Posthepatitis B Cirrhosis Patients

Zheng is the basic theory and essence of traditional Chinese medicine (TCM) in diagnosing diseases. However, there are no biological evidences to support TCM Zheng differentiation. In this study we elucidated the biological alteration of cirrhosis with TCM “Liver-Kidney Yin Deficiency (YX)” or “Dampness-Heat Internal Smoldering (SR)” Zheng and the potential of urine metabonomics in TCM Zheng differentiation. Differential metabolites contributing to the intergroup variation between healthy controls and liver cirrhosis patients were investigated, respectively, and mainly participated in energy metabolism, gut microbiota metabolism, oxidative stress, and bile acid metabolism. Three metabolites, aconitate, citrate, and 2-pentendioate, altered significantly in YX Zheng only, representing the abnormal energy metabolism. Contrarily, hippurate and 4-pyridinecarboxylate altered significantly in SR Zheng only, representing the abnormalities of gut microbiota metabolism. Moreover, there were significant differences between two TCM Zhengs in three metabolites, glycoursodeoxycholate, cortolone-3-glucuronide, and L-aspartyl-4-phosphate, among all differential metabolites. Metabonomic profiling, as a powerful approach, provides support to the understanding of biological mechanisms of TCM Zheng stratification. The altered urinary metabolites constitute a panel of reliable biological evidence for TCM Zheng differentiation in patients with posthepatitis B cirrhosis and may be used for the potential biomarkers of TCM Zheng stratification.

Analysis and Recognition of Traditional Chinese Medicine Pulse Based on the Hilbert-Huang Transform and Random Forest in Patients with Coronary Heart Disease

Objective. This research provides objective and quantitative parameters of the traditional Chinese medicine (TCM) pulse conditions for distinguishing between patients with the coronary heart disease (CHD) and normal people by using the proposed classification approach based on Hilbert-Huang transform (HHT) and random forest.Methods. The energy and the sample entropy features were extracted by applying the HHT to TCM pulse by treating these pulse signals as time series. By using the random forest classifier, the extracted two types of features and their combination were, respectively, used as input data to establish classification model.Results. Statistical results showed that there were significant differences in the pulse energy and sample entropy between the CHD group and the normal group. Moreover, the energy features, sample entropy features, and their combination were inputted as pulse feature vectors; the corresponding average recognition rates were 84%, 76.35%, and 90.21%, respectively.Conclusion. The proposed approach could be appropriately used to analyze pulses of patients with CHD, which can lay a foundation for research on objective and quantitative criteria on disease diagnosis or Zheng differentiation.

The Comparative Study on Two Models of Syndrome Differentiation of the Hand, Foot and Mouth Disease: An Investigation Analysis of the Signs and Symptoms on 2 325 Cases

Objective To realize the characteristics of “zheng” differentiation-treatment for hand, foot and mouth disease (HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explored. Methods Total of 2 325 cases with HFMD were recorded by distributing them into exterior syndrome stage, interior syndrome stage, severe syndrome stage and recovered syndrome stage, respectively, and the main symptoms and subsidiary symptoms of different stages of HFMD have been observed. The major and minor pathogenesis of HFMD in different stages were obtained, and compared with the “2010 Guideline for the Diagnosis and Treatment of HFMD”. Results It was found that the major pathogenesis of exterior stage was defined as “the invation of the wenevil to the defender of the body with the collaterals got involved”, and the minor as “qi deficiency”; in interior stage, “the fury of Gan-Yang” was the main pathogenesis, and “qi in chaos and qi deficiency” was the minor; in severe syndrome stage, “the damage of heart, liver and lung” was the main pathogenesis, and “qi in chaos” was the minor; and the pathogenesis of recovered stage was “qi-yin deficiency”. Compared with the “2010 Guideline for the Diagnosis and Treatment of HFMD”, it showed that “the obstruction of the fei-pi qi by the mixture of shi-re evil” and “the mixture of shi-re” in vivo was quite difficult to be explained in completely different context in the general situation; in the severe stage, the TCM clinical characteristics of syndrome differentiation might lose; in the early acute severe cases, the phenomenon that xin-yang and fei-qi almost ran out was difficult to be observed, then, the line between the severe and the acute severe became vague. Conclusions The theory of syndrome differentiation by stages of HFMD was reasonable in the actual situation of clinical description on HFMD which was expected to be further tested and widely applied in the “zheng” differentiation-treatment of HFMD in the future.

Circulating miR-583 and miR-663 Refer to ZHENG Differentiation in Chronic Hepatitis B

Traditional Chinese medicine (TCM) ZHENG as the key pathological principle is to understand the human homeostasis and guide TCM treatment. Here, circulating microRNAs (miRNAs) were utilized to differentiate between ZHENGs including liver-gallbladder dampness-heat syndrome (LGDHS) and liver-kidney yin deficiency syndrome (LKYDS) in chronic hepatitis B (CHB). Sera samples of CHB patients with LGDHS (n=35), LKYDS (n=24), and healthy controls (Ctrls,n=21) were analyzed by microarray and real-time RT-PCR. Receiver-operator characteristic (ROC) curves were established to evaluate the levels of serum miRNA for discriminating LGDHS and LKYDS. The target genes of miRNAs were predicted by TargetScan. Gene Ontology (GO) and pathways were analyzed using DAVID tool. The results showed that 22 miRNAs were differentially expressed between LGDHS and LKYDS (fold change>2.0 andP<0.01). Circulating miR-583 and miR-663 were significantly higher (P<0.001) in CHB patients with LGDHS than those with LKYDS and Ctrls. ROC curve analysis revealed that miR-583 and miR-663 were sensitive and specific enough to distinguish LGDHS from LKYDS. Pathway enrichment analysis indicated that 354 putative targets for miR-583 and 68 putative targets for miR-663 were mainly involved in Axon guidance, Neurotrophin, and MAPK signaling pathway. miR-583 and miR-663 may be potential markers for ZHENG differentiation in CHB.

Clinical Applications of Omics Technologies on ZHENG Differentiation Research in Traditional Chinese Medicine

Traditional Chinese medicine (TCM) ZHENG is the basic concept of TCM theory. The effectiveness of TCM treatment depends on the accuracy of ZHENG differentiation. ZHENG differentiation, using the “four diagnostic methods,” has the drawbacks of subjectivity and variability. Following development of omics technologies, which study the functional activities of human body from a system-wide perspective, it has been more and more applied in study of objectivity differentiating TCM ZHENG and understanding its biological mechanisms. This paper reviewed the literatures of clinical TCM ZHENG differentiation researches, underlying omics technologies, and indicated the increased trends of related articles with four kinds of omics technologies, including genomics, transcriptomics, proteomics and metabolomics, and the correlations between ZHENG differentiation and findings in omics studies. Moreover, the paper summarized the typical omics application in common studied diseases and TCM ZHENGs and discussed the main problems and countermeasure of ZHENG differentiation researches. The work here may provide a reference for further research of TCM ZHENG differentiation using omics technologies.