Hirudin, an acidic polypeptide secreted by the salivary glands of Hirudo medicinalis, inhibits HIF1α/VEGF and p38 MAPK/NF-κB pathways and activates NRF-2/HO-1 pathways to prevent DN and other vascular complications [226]. The gene discussed is NFKB1; the disease is liver dysplastic nodule.