Objective To investigate the best models of esophageal cancer surgical approaches,lymphadenectomy ranges and postoperative comprehensive treatment.Methods From January 1998 to December 2007 in 10 years,1 162 cases of different parts with esophageal cancer were analysized which were treated with surgically adopting sequential abdomen,chest,neck three-incision approaches.Taking three-step screening way of preoperative imaging,preoperative ultrasound localigation fineneedle aspiration biopsy cytology and intraoperative rapid fieezing pathological examination were applied to make the selectivity of the first-times cervico-thoraco-abdominal three-field lymph node dissection (3FLND),first-times standard thoracoabdominal two-field lymph node dissection (2FLND) and second-times third-field cervical lymphadenectomy.Meanwhile,we implemented actively postoperative comprehensive treatment and observed the overall clinical efficacy and long-term survival.Results In the group of 1 162 cases with esophageal cancer surgery.The operating resection rate was 100 ％,Radical resection of 97.6 ％ (1 134/1 162).Perioperative overall complication rate was 16.4 ％ (191/1 162).Anastigmatic fistula was 0.6 ％ (7/1 162).Five cases dead in 30 days after surgery.The whole group of lymph node metastasis rate was 52.6 ％ (611/1 162),lymph node metastasis degree in 12.1％ (3 092/25 564).Full group of the first-times 3FLND was 348 cases.The positive rate was 94.8 ％ (330/348),Implementing the first-times 2FLND was in 814 cases and the second-times thirdfield cervical lymph node dissection was performed in 89 cases.The postoperative complications of the 3FLND was significantly higher than that of 2FLND (23.6 ％ vs 13.4 ％).The difference was statistically significant (x2 =18.37,P ＜ 0.001).However,The difference was not statistically significant between 3FLND and 2FLND (P ＞ 0.05).There is no significant difference between the first-times 3FLND with the second-times 3FLND accumulating survival (P ＞ 0.05).But different degree of lymph node metastasis determined prognosis.The difference was significant (x2 =35.57,P ＜ 0.001).In our group the postoperative comprehensive treatment application rate was 87.2 ％.Surgery combined with comprehensive treatment overall 1,3,5 years survival rates were 92.1％,69.2 ％,49.6 ％ respectively.Conclusions The sequential three-incision approaches and selectivity of lymph node dissection have the radical nature thoroughly,fewer complications,high quality of life and the long-term survival advantages.It should be a widely used method in the clinical surgery of the esophageal cancer.Implementing the three-step screening way to selecting the first-times 3FLND,the firsttimes 2FLND and the second-times third-field cervical lymphadenectomy that have targeted strongly and high accuracy,a definite object in view and avoiding patient excessive trauma.Applying the comprehensive treatment after surgery and the re-treated of patients with recurrence that can further more improve the longterm survival of patients.The comprehensive treatment should be the target direction of the future development of esophageal cancer.

ObjectiveTo identify the factors influencing the transfer of porcine endogenous retroviruses across the membrane of a new bioartificial liver (BAL),which is a necessary caution to consider for BALs carrying porcine hepatocytes.MethodsA novel porcine BAL composed of two circuits was constructed using a plasma filter with membrane pore size of 500 nm and a plasma component separator with membrane pore sizes 10 nm,20 nm,30 nm,and 35 nm.Co-cultured cells of porcine hepatocytes and mesenchymal stem cells or single porcine hepatocytes were incubated in the bioreactors.The BAL was continuously worked for 72 hours during which the supernatant was collected from the internal and external circuits every 12 hours.PERV RNA,reverse transcriptase (RT) activity,and in vitro infectivity from the supernatant were detected.ResultsIn the plasma filter group,the PERV RNAlevels were the same in both circuits,suggesting little to no effect of the plasma filter on the PERV RNA's crossing.With plasma component separators,PERV RNA was found in the external circuits at different times without positive RT activity and HEK293 cell infection,but its level was reduced significantly.The larger the membrane pore size was,the earlier and the more RNA was detected.ConclusionsThe membrane pore size,the treatment time and the viral level in the internal circuit are contributing factors influencing the transfer of PERV RNA across the membrane in a BAL.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.