[Biological connotation of four traditional Chinese medicine syndromes of rheumatoid arthritis based on "disease-syndrome-symptom" association network].

The present study explored the biological connotation of traditional Chinese medicine(TCM) syndromes of rheumatoid arthritis(RA) from the "disease-syndrome-symptom" association network. RA patients with four TCM syndromes(dampness-heat obstruction, phlegm-stasis obstruction, Qi-blood deficiency, and liver and kidney deficiency), three for each type, were assigned as the RA TCM syndrome group, and three healthy volunteers as the normal control group. The differential gene sets of four syndromes were screened out through transcriptome expression profiling and bioinformatics mining. The relevant gene sets of syndrome-related clinical symptoms were collected from TCMIP v2.0(http://www.tcmip.cn/). The "disease-syndrome-symptom" association networks of four RA syndromes were established by using the intersection genes of syndrome-related differential genes and symptom-related genes, and the key network target genes of each syndrome were screened out and the corresponding biological functions were mined through topological feature calculation and enrichment analysis. The genes associated with clinical symptoms such as vasculitis, joint pain, and fever in the damp-heat obstruction syndrome ranked the top, and the key network target genes of this syndrome were most significantly enriched in the pathways related to material and energy metabolism and thermal reaction biological processes. The clinical symptom-related genes of the phlegm-stasis obstruction syndrome were most significantly enriched in the pathways related to "immunity-inflammation", nervous system regulation, and sensory response. The clinical symptoms such as hypoglycemia, hypotension, weight loss, palpitation, and arrhythmia in Qi-blood deficiency syndrome were predominant, and its key network target genes were most significantly enriched in the pathways related to the nervous system and "immunity-inflammation" response. The abnormal symptoms in the liver and kidney in the liver and kidney deficiency syndrome were commonly seen, and its key network target genes were most significantly enriched in the "immunity-inflammation" regulatory pathways, and liver and kidney development and metabolic response. In conclusion, the differences and connections of the biological basis between different TCM syndromes of RA are in line with the theoretical interpretation of TCM on the etiology and pathogenesis of RA. This study summarized the objective essence of syndromes to a certain extent from the "disease-syndrome-symptom" association network and is expected to provide a theoretical basis for the discovery of serum biomarkers of RA syndromes.