Objective:To establish multidrug resistant human hepatoma cell subline(HepG2/DOX) and study its biological features.Methods:Doxorubincin-resistant human hepatoma cell subline (HepG2/DOX) was induced by doxorubincin-gradually increasing concentration.To observe cells by light microscope and analyze number and structure of chromosomes of these tumor cells.Sensitivity of anticancer drugs was screened in HepG2,HepG2/DOX cells by MTT method.The immunohistochemistry method was used to measure MDR-1 gene product Pgp expression.Results:HepG2/DOX and HepG2 were different in shape,growth speed.The number and structure of their chromosomes were also different.The value of 50% inhibitory concentration(IC50,?g/ml) for DOX,CDDP,MMC,5-FU,and MTX in HepG2,HepG2/DOX cells was (0.070 and 1.161),(0.214 and 1.317),(0.162 and 0.498),(0.313 and 1.683),(0,007 and 0.217) respectively.MDR-l gene product Pgp170 expression was found either in HepG2/DOX or HepG2 cells.Pgp170 exprssion in HepG2/DOX was higher than in HepG2.Once HepG2/DOX had been cultured in DOX free RPMl1640 medium for 5 weeks,the IC50(?g/ml)for DOX in HepG2/DOX reduced to 0.684.Conclusion:HepG2/DOX has the characteristics of MDR.The drug-resistance was correlated with over expression of MDR-1 gene product Pgp 170 and slow growth.

Neuroendocrine carcinoma of the pancreas is uncommon in clinic,which has a low malignancy,maintains indolent patterns of growth,and has a good long-term prognosis.However,because of its atypical clinical manifestation,its delayed presentation often results in distant metastasis,in which the liver is the most common site.Currently,the treatment of pancreatic neuroendocrine liver metastasis is limited and requires a diverse and multidisciplinary combination of therapy.This manuscript will discuss the current status of treating pancreatic neuroendocrine carcinoma liver metastasis.

Teacher's career development in British medical school has experienced a very long process from establish to gradually mature.So far,it has already set up its system and its own characters in strategy and teacher's self-development.By analyzing characters of teacher's career development in British medical school including teacher development center,teacher's self-development and assessment for medical educators,we aimed to raise enlightenments on teacher's career development in China.

Objective To evaluate the role of emergency and staged hepatectomy in peritoneal metastasis associated with ruptured hemorrhage of resectable hepatocellular carcinoma (HCC) patients,and investigate the impact of surgery timing-selecting on peritoneal metastasis of postoperative HCC patients.Methods A retrospective analysis was conduct on the pooled data from 38 HCC patients with spontaneously ruptured hemorrhage treated in our hospital from August 2011 to January 2016.These patients were divided into emergency group who underwent hepatectomy within 24 hours at admission,and staged group who underwent the procedure one week after admission.Perioperative events,overall survival (OS) and disease-freesurvival (DFS) rates,incidence of recurrent and metastatic disease were compared between the two groups.Results The perioperative blood loss and transfusion were much more in emergency group than staged group (both P ＜ 0.05).Nevertheless,the incidence of postoperative mortality was not significantly different (6.0％ vs 0％,P ＞ 0.05).The median survival was 22.5 months in emergency group versus 14.2 months in staged group.The 6-month,1-year,3-year OS rates in emergency group were 88.2％,82.4％ and 30.3％ respectively,and 6-month,1-year,3-year DFS rates were 81.3％,54.7％ and 27.3％.The 1-year OS and 6-month DFS rates were higher than those of staged group (both P ＜ 0.05).The incidence of peritoneal metastasis in staged group was higher than that in emergency group,but it was not significantly different (38.1％ vs 29.4％,P ＞ 0.05).Univariate and multivariate analysis indicated that tumor diameter ≥ 10 cm and AFP ＞ 10 000 μg/L were the risk factors for peritoneal metastasis after hepatectomy for HCC patients with spontaneously ruptured hemorrhage.Conclusions Emergency hepatectomy would warrant a better short-term prognosis compared with staged hepatectomy for the HCC patients with spontaneously ruptured hemorrhage.Staged hepatectomy would not raise the possibility of postoperative peritoneal metastasis.The predictors of tumor diameter ≥ 10 cm and AFP ＞ 10 000 μg/L were risk factors for peritoneal metastasis after hepatectomy for spontaneously ruptured HCC patients.

Objective To construct double expression retroviral vectors targeting chronic myeloid leukemia (CML) b3a2-type mRNA and investigate its effect on the phenotype of K562 cells. Methods The eGFP coding sequence was inserted into the retroviral vector pMSCV-neo to construct pMSCV/GFP, then H1-RNA pol III-based transcription cassettes was subcloned into it to form pMSCV/GFP-H1-BCR/ABL40AS. Two control vectors pMSCV/GFP-H1-BCR/ABL40S & pMSCV/GFP-H1-BCR/ABL80AS were constructed in addition. All these constructions were identified by restriction enzyme analysis and DNA sequencing. After that, the recombinant vectors were transferred into retrovirus packaging cell line PT67 by using lipofectamine2000, and G418 were used to select stable virus-producing cell lines. Viral titer was determined by infection of NIH3T3 cells sequentially. The cell-growth curve was assayed, cell apoptosis was checked with Annexin V-PE/7AAD double staining and flow cytometry analysis after 24-hour infection, the PKR phosphorylation was assayed by Western blotting. Results The plasmids were successfully constructed. Four cell lines, named as PT67-MSCV/GFP, PT67-40as, PT67-40s and PT67-80as were gained by G418 selection, and virus titers were 6.2?10~ 5 , 5.6?10~ 5 , 4.6?10~ 5 and 6.0?10~ 5 CFU/ml respectively. PT67-40as suspensions could induce K562 cell apoptosis by (22.54?3.19)%, significantly different from PT67-MSCV/GFP or PT67-40s (P

Malignant biliary obstruction is often in an advanced stage at the time of diagnosis, and palliative relief of obstruction has become the main treatment option. Biliary stent implantation is currently the most widely used treatment for the relief of biliary obstruction, but stent reobstruction has become a common problem in clinical practice. Endoscopic retrograde cholangiopancreatography (ERCP) combined with intraductal radiofrequency ablation can solve the problem of direct obstruction in malignant biliary obstruction and improve stent patency rate, survival time, and survival rate, with few complications and a low surgery-related mortality rate, and therefore, it can be used as a safe and feasible palliative treatment method for malignant biliary obstruction.

Objective To systematically evaluate the clinical efficacy of ABO-incompatible living donor liver transplantation (ABO-I LDLT) and compare with ABO-compatible LDLT (ABO-C LDLT). Methods A systematic search of multiple databases at home and abroad was conducted to retrieve the literatures related to the statistical comparison of clinical efficacy between ABO-I LDLT and ABO-C LDLT. The literature screening was conducted, the quality of literatures was evaluated and data extraction was performed. Using Rev Man 5.3 software, a Meta-analysis was performed by random effect model or fixed effect model. Results A total of 432 articles were searched, and 6 articles published in English were eventually included according to the inclusion criteria. The Meta-analysis demonstrated that there was no significant difference in the postoperative 1-, 3- and 5-year survival rate of the recipients and grafts and the incidence of rejection responses between the ABO-I LDLT and ABO-C LDLT groups (all P≥0.05). The incidence of postoperative biliary complications and hepatic artery embolization in the ABO-I LDLT group was significantly higher than that in the ABO-C LDLT group [odds ratio (OR)=2.08, 95% confidence interval (CI) 1.25-3.45, P=0.005; OR=2.24, 95%CI 1.03-4.89, P=0.04]. Conclusions Compared with the ABO-C LDLT, ABO-I LDLT yields lower clinical efficacy, whereas it is still an effective method for the treatment of end-stage liver disease.

In this study,the effects of pirrolidine dithiocarbamate (PDTC) plus leflunomide (Lef) models were investigated.NIH mice and Wistar rats served as donors and recipients respectively.Mouse-to-rat cardiac xenotransplantation was performed.The recipients were divided into 5 groups:group A (the control group),group B (PDTC group),group C (PDTC plus CsA group),group D (PDTC plus Lef group) and group E (PDTC plus Lef and CsA group).The expressions of IKKα/β,by immunohistochemistry and Western blot as well as electrophoretic mobility shift assay (EMSA).The median survival time of cardiac xenografts in the control group,PDTC group,PDTC plus CsA group,PDTC plus Lef group and PDTC plus Lef and CsA group was (2.17±0.41),(2.33±0.52),(4.67±1.21),(7.00±1.79) and (9.00±1.41) days respectively.The survival time of xenografts in the PDTC plus Lef and CsA group was significantly longer than that in other four groups (P<0.05 for all),that in the PDTC plus Lef group longer than that in the control group,PDTC group and PDTC plus CsA group (P<0.05 for all),that in PDTC plus CsA group longer than the control group and PDTC binding activity were notably increased in mouse-to-rat cardiac xenografts.The expressions were decreased in the control group,PDTC group,PDTC plus CsA group,PDTC plus Lef and PDTC plus Lef and CsA group in turn.It was concluded that PDTC plus Lef and CsA can significantly suppress prolonging the survival of the cardiac xenografts.

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.Extensive het-erogeneity exists in the clinical course and prognosis of GISTs due to multiple genetic mutations.Since the advent of tyrosine kinase inhibit-ors(TKIs),such as imatinib,the survival of patients with GISTs has substsntially improved.However,progression or metastasis often occurs in these patients.For advanced and metastatic GISTs,drug selection and surgical indications have been studied and debated in recent years.With further research in etiology and TKI resistance,novel target agents such as ripretinib,avapritinib,and other pathway inhibitors have been introduced into clinical practice,enabling a more individualized and accurate treatment modality for advanced and metastatic GISTs.This review provides an update on the current therapeutic development landscape in advanced and metastatic GISTs.

Objective:To evaluate the prognostic value of tumor burden score(TBS)combined with serum tumor markers in patients with resectable colorectal liver metastasis(CRLM)after curative hepatectomy.Methods:We retrospectively retrieved and analyzed clinicalpatho-logical data of patients with CRLM who underwent curative hepatectomy between Jan 2012 to Dec 2023 in The First Affiliated Hospital of Chongqing Medical University.Serological tumor markers and TBS were utilized to generate prediction model,where the serological index was derived from the sum of carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels,and TBS was calculated from preoperative radiological images.The cutoff values were determined as the sum of CEA and CA19-9 levels and preoperative TBS.The pa-tients were then categorized based on prediction parameters into low-risk(lacking any high-level index),medium-risk(with one high-level in-dex)and high-risk(with two high-level indices)groups.Overall survival(OS)and disease-free survival(DFS)were compared using Kaplan-Meier curves,and multivariate Cox regression analysis was performed to determine possible prognostic risk factors.The receiver operating characteristic curve(ROC)and C-index were employed to assess the discriminatory power of the prediction model.Results:Median follow-up time was 43(4-112)months.Kaplan-Meier survival analysis suggested that the median OS time and 5-year OS of low-,median-,and high-risk groups were 64,54,and 30 months and 55%,38%,and 23%respectively(P=0.001 9).The median DFS time and 3-year DFS were 36,22,and 11 months,and 47%,35%,and 16%respectively(P<0.001).Multivariate Cox regression analysis revealed that in-dependent prognostic risk factors for postoperative OS were the sum of CEA and CA19-9 level(hazard rstio[HR]=1.81,95%confidence inter-val[CI]:1.09-3.01,P=0.021),TBS(HR=1.42,95%CI:1.02-2.84,P=0.032),bilobar metastasis(HR=1.99,95%CI:1.25-3.16,P=0.004),and primary tumor nodal invasion(HR=1.51,95%CI:1.37-3.34,P=0.028).Multivariate Logistic regression analysis showed that the sum of CEA and CA19-9 levels(odds ratio[OR]=2.44,95%CI 1.26-4.71,P=0.008)and TBS(OR=2.95,95%CI:1.50-5.78,P=0.002)associated significantly with postoper-ative recurrence.The ROC curve and C-index revealed that serum tumor markers combined with TBS(area under the curve=0.630,95%CI:0.552-0.707,P<0.05;C-index=0.627)were more effective in predicting the prognosis of patients with CRLM than either CEA or TBS alone.Conclusions:The prediction model based on serum tumor markers combined with TBS demonstrated better efficacy than any single serolo-gical or radiological index and may provide new insights aiding individualized and accurate clinical decision-making for patients with CRLM.