In spite of shTLR4 application showing more negative effects in inflammatory factor release after CPB in our present study, current clinical experimental studies showed no statistical significance in alleviating the tissue damage and inflammatory factor expression by ethyl pyruvate (EP, the HMGB1 inhibitor) or TAK-242 (TLR4 antagonist) treatment in CPB [34] or sepsis-induced inflammation [35], so the clinical effects of the TLR4/HMGB1 pathway inhibition strategy need to be further evaluated in the future study. This evidence concerns the gene TLR4 and Sepsis.