Although this study fully demonstrated the application of rhein on the pathophysiological changes of LPS-induced ALI/ARDS and its mechanism for the first time, several concerns need yet to be addressed: 1) Whether the administration pathways will affect the prognosis and outcome of ALI/ARDS when rhein is applied; 2) In the ALI/ARDS model, why does rhein affect the polarization of macrophages and the outcome of ALI/ARDS mainly by interfering with the upstream signal of Trem2 (NFATc1) rather than the downstream signal (NF-κB)? The gene discussed is NFATC1; the disease is acute respiratory distress syndrome.