This study had several limitations: (1) These Nlrp3 and other components could also have been included in the macrophage-released EVs, which caused activation of NLRP3 inflammasome; (2) We did not explore whether the HMGB1+ EVs level could be used as a prognostic marker for sepsis; (3) The released EVs might contain LPS itself which cause a similar effect on hepatocyte, which need further investigation. Here, HMGB1 is linked to Sepsis.