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Objective To explore the clinical treatment strategies of laparoscopic hepatocellular carcinoma ablation for patients with severe cirrhosis background.Methods We analyzed the clinical data of 430 patients and analyzed the indications,key techniques,efficacy and safety of laparoscopic hepatocellular carcinoma ablation for patients with severe cirrhosis background,and summarized the related experiences.Results The first complete ablation rate for the entire cohort was 94％,the 2-year local recurrence rate was 2.8％.No significant complications were found postoperatively.Conclusions Laparoscopic hepatocellular carcinoma ablation is a minimally invasive,safe and effective treatment strategy for patients with small cancer under severe cirrhosis background.Especially when the tumor is located in the " high-risk parts" for ablation,it could be a preferred method for pre-transplant treatment of these patients.
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Objective To screen the formulation of self-microemulsifying drug delivery system (SMEDDS) for sirolimus (SRL) and prepare the SRL-SMEDDS pellets.Methods Co-emulsifier,oil phase and emulsifier were chosen by solubility test and ternary phase diagrams,central composite design and response surface method were adopted to screen and optimize the preparation and formulation of liquid SRL-SMEDDS.The selected liquid SRL-SMEDDS formulations were prepared into pellets by extrusion-spheronization method.Results The final pellets from liquid SRL-SMEDDS formulation :SRL 0.4%,Labrafil M1944CS 9.3%,Cremophor EL 15.9%,Transcutol P 8.0%,MCC 49.8%,lactose 13.3%,CMS-Na 3.3%.Dissolution test showed superphosphate (SSP) in the dissolution water is much greater than the commercially available sirolimus tablets ;while in 0.4% SDS solution,the two formulations showed similar dissolution.Conclusion SMEDDS can improve the dissolution of SRL in v itro.
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Objective To investigate the molecular mechanism how edaravone reduces cytotoxicity caused by hypoxia/reoxygenation-induced injury.Methods Ischemia model-hypoxia/ reoxygenation model which also called oxygen and glucose deprivation/reoxygenation model (OGD-R) was established.Cells were divided into control group,OGD-R group,OGD-R with edaravone of different concentration groups Cells of OGD-R model were pretreated with the appropriate concentration of edaravone or combine with the specific channel blockers LY294002 and MK2206 individually,the expression levels of ERK,AKT and Bcl-2 were detected with Western-blot,while the expression levels of BDNF and Bcl-2 mRNA detected with RT-PCR,the expression levels of BDNF protein detected with ELISIA,the levels of LDH releasing and Hoechst33258 staining used with homologue assay kit or regents.Results The pretreatment of cultured neurons with edaravone alleviated hypoxia/reoxygenation induced neuronal injury in a dose-dependent manner (LDH releasing reduced,Caspase-3 activity and ratio of nuclear pyknosis declined).The edaravone pretreatment did not increase significantly the p-ERK expression levels,but the amount of p AKT expression was significantly increased(P＜0.01).Pretreatment of edaravone(10 μmol/L) remarkably reduced the LDH release and declined the ratio of nuclear pyknosis after reoxygenation (P＜0.01),which was inhibited by MK2206.Compared to OGD-R,edaravone pretreatment markedly promoted BDNF and Bcl-2 mRNA expression at each time point,and the most pronounced effects occured at 8 h after OGDR.ELISIA analysis showed that BDNF protein level was significantly elevated after edaravone pretreatment at the same point.Western blot analysis indicted that edaravone pretreatment significantly enhanced Bcl-2 protein expression at 8 h after OGD-R,which was blocked by MK2206.Conclusions Edaravone may alleviate hypoxia/reoxygenation induced neuronal injury by enhancing BDNF and Bcl-2 expression and inhibiting Caspase-3 activity through activation of the PI3K/Akt pathway.