Self-assembled carbon monoxide nanogenerators managing sepsis through scavenging multiple inflammatory mediators

Sepsis,a life-threatening syndrome of organ damage resulting from dysregulated inflammatory response,is distinguished by overexpression of inflammatory cytokines,excessive generation of reactive oxygen/nitrogen species(RONS),heightened activation of pyroptosis,and suppression of autophagy.However,current clinical symptomatic supportive treatment has failed to reduce the high mortality.Herein,we developed self-assembled multifunctional carbon monoxide nanogenerators(Nano CO),as sepsis drug candidates,which can release CO in response to ROS,resulting in clearing bacteria and activating the heme oxygenase-1/CO system.This activation strengthened endogenous protection and scavenged multiple inflammatory mediators to alleviate the cytokine storm,including scavenging RONS and cfDNA,inhibiting macrophage activation,blocking pyroptosis and activating autophagy.Animal experiments show that Nano CO has a good therapeutic effect on mice with LPSinduced sepsis,which is manifested in hypothermia recovery,organ damage repair,and a 50%decrease in mortality rates.Taken together,these results illustrated the efficacy of multifunctional Nano CO to target clearance of multiple mediators in sepsis treatment and act against other refractory inflammation-related diseases.

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results

Purpose:To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization(PETACE)for patients with unresectable hepatocellular carcinoma(HCC).Materials and methods:We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1,2015 and August 30,2016.The complication rate,tumor response rate,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Adverse events were generally mild and included abdominal pain and fever,although a major complication was reported in 1 patient(1.8%).During a median follow-up of 10.0 months(range,3.0-24.0 months),14 patients(25.5%)achieved a complete tumor response,25(45.5%)had a partial response,9(16.4%)showed stable disease,and 7(12.7%)had disease progression.The 1-month overall response rate was 70.9%,and the local tumor response rate was 89.0%.The 1-month tumor response rate was 100%for Barcelona Clinic Liver Cancer(BCLC)stage A or B disease and 62.8%for BCLC stage C disease.The median PFS was 6.1 months(95%confidence interval[95%CI],3.4-8.8 months;range,1.0-24.0 months).The median OS was 11.0 months(95%CI,7.1-14.9 months;range,2.0-24.0 months).Kaplan-Meier analysis(log-rank test)found significant differences in OS between patients grouped by tumor number(P=0.006),tumor size(P=0.035),and Eastern Cooperative Oncology Group(ECOG)score(P=0.005).The tumor number(1 vs.>2)was the only factor independently associated with OS(hazard ratio[HR],2.867;95%CI,1.330-6.181;P=0.007).Conclusions:PE-TACE for unresectable HCC may be safe,with favorable tumor response rates and survival time,especially in patients with a single large tumor.Longer follow-up using a larger series is necessary to confirm these preliminary results.

Characterization of Natural Killer Cells in the Liver of Young Mice

OBJECTIVE To determine the quantity and quality of liver NK cells from young and adult mice and compare their characteristics. METHODS C57BL/6 mice were used at 2 weeks （young） and 8 weeks （adult） of age. The percentage and absolute number of NK cells in the liver and spleen were analyzed. The cytotoxicity of NK cells in the liver and spleen against various targets were detected by a 4 h ^51Cr-release method. FACScan was used to analyze the expression of CD69, Mac-l1 Ly49C/I and CD94 on the NK cells. Perforin mRNA levels were analyzed by the reverse transcription polymerase chain reaction （RT-PCR）. RESUTLS The percentages of NK cells in the liver of young and adult mice were similar （11.9%＋1.7% vs. 9.9%＋1.6%, P〉0.05）, but the absolute number per liver weight was higher in the young animals （11.6＋2.5×10^5/g vs. 3.4＋0.8×10^5/g, P〈0.05）. The level of NK cytotoxicity was extremely high in the liver of young compared to adult mice （71.0%＋5.5% vs. 23.8%＋4.4%, P〈0.05）, but this difference was not observed in the spleen. Phenotypes of the liver NK cells from young and adult mice were completely different from each other. The liver NK cells from young mice were CD69^high Mac-1^low Ly49C/ I^low, whereas NK cells from older mice displayed inverse antigen levels （CD- 69^low Mac-1^high Ly49C/I^high）. The expression levels of other NK cell-related markers were similar in both groups.The perforin mRNA level in the liver lymphocytes from young mice was consistently greater compared to adult mice. CONCLUSION From 2 to 8 weeks C57BU6 mice liver NK cells undergo age-associated changes. At 2 weeks of age the liver NK cells showed a high level of NK cytotoxicity and a unique phenotype which was not apparent at 8 weeks of age.