The seed proteins and subnetworks associated with the gene ontology evaluation re sults have been matched with all the KEGG pathways, the gene onto logy, and also the functional evaluation final results employing DAVID and GeneSpring dependant on the dierently expressed genes in the cold and heat pattern comparisons. 3. six. The Intersection Network between the Cold Pattern and the Heat Pattern. Figure 4 exhibits the intersection network among the cold pattern and also the heat pattern, which in cludes the vast majority of dierently expressed genes in the cold and heat pattern comparisons.
All subnetworks are proven in Figures three and 4. According to the gene ontology examination outcomes and also the other benefits, Figure five was drawn to outline the net functions on the cold and heat patterns and also to reveal the rela Bosutinib clinical trial tionships concerning the two patterns while in the practical and biological processes in the network. In these networks, protein ubiquitination and RNA splic ing have been the frequent biological processes during the TCM cold and heat patterns of RA. The dierent biomarkers for the TCM cold and heat patterns of RA are clear: the cold pattern was related to the regulation of translation as well as the Jak STAT cascade, although the heat pattern was associated with fatty acidmetabolismandtheI ?Bkinase/NF ?Bcascade. Inaddi tion, protein ubiquitination, proliferation, and apoptosis re lated towards the cell cycle will be the biological approach connections involving the cold pattern plus the heat pattern.
CTLA4 and PSMD8 have been the signicant biomarkers in the two the cold and heat patterns. The signicant biomarkers from the cold pattern had been EIF4A2, CCNT1, and IL7R, when XL147 the signicant bio markers of your heat pattern have been PRKAA1, HSPA8, and LSM6. Within this research, we utilized software package to recognize network primarily based gene expression biomarkers and biomarkers that had been orga nized by sets of dierentially expressed genes that have been mem bers of established functional networks. Our leading ndings werethenetwork that had been equivalent and dierent among the TCM cold pattern RA individuals along with the TCM heat pattern RA patients. The CAMs, T cell receptor signaling pathway, and pro teasome may be linked to each the TCM cold and heat pat terns in RA patients.
Specically, CTLA4, which was a seed gene in these pathways and was up regulated in each patterns, participates inside the pathways of CAMs and T cell receptor

signaling. The CTLA4 molecule is expressed on activated T lymphocytes and has lately been identied as a significant unfavorable regulator in autoimmune disorders. Quantitative alterations of CTLA4 contribute to autoimmune tissue destruction, as well as expression of CTLA4 plays a downregulatory part in rheuma toid articular inammation.