More interestingly, we also found that the absence of the two animal products in Yiqihuoxue formula, Tuyuan and Agkistrodon piscivorus, had no effects on decreasing SBE activity and Smad3 phosphorylation in the TGF-β1-treated NIH/3T3 fibroblasts (Additional file 1: Figure S1), indicating that these two animal components were not the necessary parts of the treatment formulation for systemic sclerosis, which meant that Yiqihuoxue formula had some redundancies. Here, SMAD3 is linked to systemic sclerosis.