Fig. 3

Network diagram to explain the upstream and downstream relationship of the Pathway-risk model. The red pathways meant hazarded pathways (HR > 1) and the blue pathways meant protective pathways (HR < 1). The pathways included in this model can be classified as two types, hypoxia and immune dysregulation. The pathway related to hypoxia was HIF-1 pathway. 1. Hypoxia further induced cellular injury and metabolic disorder. The pathways related to metabolic disorder included steroid biosynthesis pathway, Nitrogen metabolism pathway and energy dependent of regulation of mTOR by LKB1-AMPK. The pathways related to cellular injury included TEL pathway and ATF2 pathway. The cell repair was the negative feedback of cellular injury, and the pathways related to cellular injury included GAB1 signalosome and TGF-beta receptor signaling activates SMADs. 2. Immune dysregulation can be classified as anti-immunity, promoting-immunity and bipolar immune regulation. The pathways related to anti-immunity were TGF-beta receptor signaling activates SMADs pathway and IL22 soluble receptor pathway; the pathways related to promoting-immunity were NKT pathway, NF-kappaB pathway and PKA-mediated phosphorylation of CREB; the pathways related to bipolar immune regulation were IL-4 pathway and negative regulation of RIG-I/MDA5 pathway