Objective To systemically review the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis. Methods Such databases as MEDLINE, EMbase, The Cochrane Library, VIP, CNKI and CBM were electronically searched for comprehensively collecting randomized controlled trials (RCTs) on the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis from inception to July 2012. References of included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results Totally, five RCTs involving 6 307 patients were included. The results of meta-analysis showed that, no significant difference was found in 28-day mortality (RR=1.00, 95%CI 0.84 to 1.19, P=1.00) and 90-day mortality (RR=1.00, 95%CI 0.87 to 1.14, P=0.96) between the rhAPC group and the placebo group. The results of subgroup analysis showed that, the two groups were similar in the 28-day mortality of patients with different Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (APACHE II scorelt;25: RR=1.06, 95%CI 0.93 to 1.21, P=0.37; APACHE II score≥25: RR=0.93, 95%CI 0.69 to 1.24, P=0.60), and in the 28-day mortality by protein C deficiency class (APC deficiencylt;80%: RR=0.96, 95%CI 0.56 to 1.65, P=0.89; APC deficiencygt;80%: RR=0.61, 95%CI 0.34 to 1.08, P=0.09). Besides, bleeding risk in the rhAPC group was 1.62 fold more than that in the placebo group (RR=1.62, 95%CI 1.17 to 2.23, P=0.004). No significant difference was found in the incidence of adverse reaction (RR=1.04, 95%CI 0.92 to 1.18, P=0.53). Conclusion Current evidence suggests that, rhAPC could not improve the prognosis of patients with severe sepsis, but it significantly increases bleeding risk.
Objective To investigate the protective mechanism of ulinastatin（UTI） in pulmonary microvascular endothelial cells （PMVECs） attacked by serum from the patients with severe sepsis. Methods PMVECs were cultured in vitro and randomly divided into 4 groups，ie. a normal group （culture medium with 10% fetal bovine serum，group N），a health group （culture medium with 10% healthy human serum，group H），a patient group （culture medium with 10% human septic shock serum，group S），and a ulinastatin group （culture medium with 1000 U/mL UTI and 10% human septic shock serum，group U）. The proliferation activity of PMVECs was measured by MTT expressed by optical density （OD）. The concentration of TNF-α in supernatant of culture medium was examined by ELISA at 0，1，2，4，6 hours. The expression of NF-κB was examined by immunohistochemistry at 1 hour. Results Compared with group N，the cell proliferation activity of group S decreased significantly，and the cell proliferation activity of group U decreased slightly at each time poi nt. Compared with group N，the cell proliferation activity of group S and group U at 1，4，6 hours were significant different （Plt;0.05 ）. Compared with group S，the cell proliferation activity of group U at 1，2，6 hours increased significantly （Plt;0.05）. Obviously positive expression of NF-κB in PMVECs could be seen in group S，a little positive expression in group S，and no expression in group N and group H. Compared with group N，the TNF-α levels of group S and group U increased significantly at each time point with significant differences （Plt;0.01）. Compared with group S，the TNF-α levels were significantly reduced at each time point in group U （Plt;0.01）. Conclusions UTI can reduce the release of TNF-α by inhibiting NF-κB activation，thus reduce PMVECs injury attacked by serum from severe sepsis patients.