The mechanisms of ventilator-induced diaphragmatic damage (VIDD) are not fully elucidated [80] . Previous studies have shown that high tidal volume ventilation leads to the activation of serine/threonine kinase/protein kinase B (Akt) and c-Jun NH2-terminal kinase (JNKs) [81] . Activation of the phosphoinositide 3-OH kinase (PI3-K)/Akt pathway also results in the phosphorylation of the class O of forkhead box transcription factor (Foxo) proteins [82] . Li et al. demonstrated that a high tidal volume ventilation-induced diaphragmatic damage model was associated with the activation of JNK and Foxo4, and this process was dependent on the Akt and JNK pathways. These data help us to understand the effects of mechanical forces on the diaphragmatic injury, as well as suggest whether inhibiting the Akt and JNK pathways offers possible treatment options [83] .