Multidrug resistance-associated protein 1 (MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily.It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs,heavy metal anions,toxicants,and conjugates of glutathione,glucuronide and sulfate.With the advance of sequence technology,many MRP1/ABCC1 polymorphisms have been identified.Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility.In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms.In this review,we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance,toxicity,disease susceptibility and severity,prognosis prediction,and methods to select and predict functional polymorphisms.

Objective To investigate the expression of folate receptor(FR) in primary hepatocellular carci noma and to explore its correlation with clinical and pathological features.Methods Immunohistochemistry was used to detect the expression of FR alpha and beta in primary hepatocellular carcinoma (45 cases),cirrhosis (32 cases) and normal liver tissue (20 cases).And then the relationship between the expression of FR alpha and clinic0pathological features was analyzed.Results The positive expression of FR alpha was detected in 88.9％ (40/45) primary hepatocellular carcinoma,18.8％ (6/32) cirrhosis,and there was no positive expression of FR alpha in normal liver tissue.There was no FR beta expression in primary hepatocellular carcinoma and cirrhosis,only 15％ (3/20) normal liver tissue expressed FR beta.The expression of FR alpha did not correlate with gender and age,but the positive expression of early-mid-term patients was higher than that of the advanced patients.Conclusion FR alpha is presented in most liver tissues of primary hepatocellular carcinoma,which provide basis of early diagnosis and molecular drug target.

Objective To approach the role of Kupffer cell (KC) in regulation of liver regeneration after partial hepatectomy (PH). Methods Condition medium of kupffer cells (KCCM) was prepared and the role of KCCM in promoting rat primary hepatocytes proliferation was observed by MTT method. The PH animal model was reproduced in mice and the rate of liver regeneration was measured and the expression features of TNF-?, TGF-? and TGF-?_1 were determined by immunohistochemical methods after PH with KC depletion. Results KCCM could promote primary hepatocyte proliferation significantly (A=0.746?0.06) compared with control (A=0.536?0.06, P

Objective To investigate the application of structured triglyceride (STG) in malignant obstructive jaundice (MOJ) patients after pancreaticoduodenectomy.Methods The records of 21 MOJ patients received pancreaticoduodenectomy in our hospital were retrospectively analyzed.The patients received parenteral nutrition on the first postoperative day, of whom 7 were given STG (STG group) and 14 were given medium and long chain triglyceride (MCT/LCT group).The changes of liver function, lipid profile, albumin, and postoperative complications were compared between the two groups.Results The triglyceride levels in the STG group on the 3rd and 7th postoperative days were significantly lower than those in the MCT/LCT group [3rd day:(1.85 ±0.90) mmol/L vs.(2.18 ±1.41) mmol/L;7th day: (1.62 ±0.78) mmol/L vs.(2.46± 1.62) mmol/L;both P =0.042];the level of high-density lipoprotein on the 7th postoperative day was significantly higher than that in the MCT/LCT group [(0.67 ±0.64) mmol/L vs.(0.45 ±0.15) mmol/L, P =0.046].The albumin in the STG group returned to normal on the 3rd postoperative day, which was significantly higher than that in the MCT/LCT group [(35.50 ±2.91) g/L vs.(30.66 ±5.08) g/L, P =0.048].There were no significant differences in terms of liver function, length of hospital stay, wound healing, systemic inflammatory response syndrome, and infection between the two groups.Conclusions Parenteral nutrition with structured triglyceride after pancreaticoduodenectomy in MOJ patients is tolerable and safe.STG has less influence on lipid metabolism than MCT/LCT does, and can increase albumin level rapidly.

Objective To Investigate the mechanism of augmenter of liver regeneration (ALR) in promoting proliferation of damaged hepatocyte. Methods The inhibitory effects of ALR on the expression of TGF-?_1 in hepatic stellate cell and Kupffer cell were studied by immunohistochemistry and Western blot. The effects of hepatic stellate cell (Ito cell) conditioned medium (ICCM+) and Kupffer cell conditioned medium (KCCM+) prepared by treatment of using augmenter of liver regeneration (ALR) on damaged hepatocytes proliferation were studied by MTT. The antagonistical role of ALR on TGF-?_1, which inhibited damaged hepatocyte proliferation was investigated by MTT determination. Results Immunoreactive positive signal of TGF-?_1 in hepatic stellate cell and Kupffer cell stimulated by ALR were decreased. Immunolabeling of TGF-?_1 in hepatic stellate cell stimulated by ALR was weakened. The proliferation of damaged hepatocytes was increased significantly by administration of ICCM and KCCM. ALR could reverse the inhibitory role of TGF-?_1 on the proliferation of damaged hepatocyte. Conclusion ALR can promote proliferation of injured hepatocyte indirectly by inhibiting expression of TGF-?_1 in hepatic stellate cell and Kupffer cell.

Objective To investigate therapeutic ways a nd effects of using prosthetic materials to repair incisional hernia of the abdo minal wall.Methods Marlex mesh was used in 32 cases and Com posix mesh in 5 cases. Positions of mesh implanted: Retromuscular placement in 1 5 cases, premuscular placement in 12 cases and inlaying mesh into abdominal wall defeat in 10 cases.Results 33 patients were followed for 3 months to 28 months postoperatively, 32 patients were cured without reccurrence. One reccurented at 6 months postoperatively.Conclusion App lication of prosthetic materials to repair incisional hernia of abdominal wall i s safe, and has a low reccurrent rate.

Objective To investigate the pile protein (paxillin) and carbonic anhydrases Ⅸ (CA Ⅸ)expression and its significance in duodenal papilla carcinoma patients.Methods Eighty-seven cases of duodenal papilla carcinoma were enrolled as our subject.Immunohistochemical staining was used to detect the expressions of paxillin and CAⅨ in site of tumor,adjacent tissue and duodenal papillitis tissue.Results Sixtyfive cases (74.7％ (65/87)) were showed a higher expression of paxillin in cancer site than that of adjacent tissue (41％ (16/39),P ＜ 0.05) and duodenal papillitis tissue (41.3％ (19/46),P ＜ 0.05),and the difference was statisically significant (x2 =19.869,P ＜0.05).While a higher expression of CA Ⅸ in 62 cases (71.3％) in cancer site was seen,higher than that of adjacent tissue (33.3％ (13/39),P ＜ 0.05) and duodenal papillitis tissue (30.4％ (14/46),P ＜ 0.05),and the difference was statisically significant (x2 =26.936,P ＜ 0.05).As the increase of the cancer tissue malignant degree and the surrounding tissue invasion or distant metastasis degree,paxillin and CA Ⅸ expression increased.Conclusion The paxillin and CAⅨ might served as the early indicators for diagnosis and judgment of prognosis of duodenal papilla cancer.

Objective To investigate the expression and clinical value of miRNA -22 in esophageal and gastric cancer tissues and cell lines.Methods Realtime -PCR was performed to detect the expression of miRNA -22 in human esophageal cancer cell lines ECA109,TE -1,TE -8,TE -13 and normal esophageal epithelial cells HEEC,48 cases of esophageal cancer tissues and matched adjacent normal tissues,human gastric cancer cell lines SGC -7901,MKN -45,NCI -N87,AGS,NUGC -3,SUN -1,normal human gastric mucosa cell line GES -1 and normal stomach fibroblastic cell NSFC,88 cases of gastric cancer tissues and matched adjacent normal tissues.Results The expression of miRNA -22 was much less in four esophageal cancer cell lines than that of immortalized normal esophageal epithelial cells HEEC,and the expression of miRNA -22 was much less in six gastric cancer cell lines than that of gastric mucosal epithelial cell line GES -1 and normal stomach fibroblastic cell line NSFC.The esophageal cancer tissues showed aberrant down regulation of miRNA -22 compared with the adjacent non -tumor tissues [(3.51 ±1.05)vs.(11.23 ±2.95),t =18.13,P <0.05].The gastric cancer tissues showed aberrant down regula-tion of miRNA -22 compared with the adjacent non -tumor tissues [(2.15 ±1.23)vs.(9.14 ±2.86),t =22.93, P <0.05].Conclusion The expression of miRNA -22 was much lower in esophageal and gastric cancer tissues and cell lines,which provided basement to nosogenesis,early diagnosis and create drug treatment of the cancers.

Objective To optimize the condition of converting murine naive CD4+ CD25-T cells ( effector T cells,Teffs) to CD4-CD8-double negative regulatory T cells ( DN Tregs) in vitro.Methods Naive Teffs from C57BL/6 mouse were isolated with magnetic activated cell sorting( MACS)and co-cultured with DBA/2 mature dendritic cells (mDCs) with different doses of recombinant murine interleukin-2 (IL-2).The percentage of converted DN Tregs was examined by flow cytometry after 6 days.Purified DN Tregs were co-cultured with CFSE labeled Teffs.The proliferation rate of Teffs were evaluated by flow cytometry.Results Without IL-2,the percentage of CD4-CD8-T cells was 6.21％ ± 2.03％.With IL-2,the percentage was 14.77％ ± 2.15％ ( 25 ng/ml),21.29％ ± 2.68％ (50 ng/ml),43.45％ ±4.45％ (75 ng/ml),and 28.59％ ±3.05％ ( 100 ng/ml) respectively.The IL-2 concentration of 75 ng/ml signilicantly enhanced the conversion of Teffs to DN Tregs ( separately t =10.700,8.288,6.158,3.932,all P ＜ 0.05).Highly purified DN Trega significantly suppress the proliferation of Teffs in vitro.Conclusions Teffs are converted to DN Trega in vitro with the LPS-activated allogeneic mDCs and that 75 ng/ml of IL-2 is the optimal concentration for the conversion of Teffs to DN Trogs in vitro.

Objective To evaluate the feasibility of OX40L gene silence in dentritic cells by RNAi through lentiviral vector, so that to explore the influence of CD4 + CD25 + T regulatory cells by blocking OX40/OX40L costimulation signals. Methods Serial plasmids were constructed, consisting of lentiviral vector framework, containing different OX40L siRNA sequences. The most effective packaged one by 293T cells to be the operating siRNA vector named OX4OL-RNAi-LV was chosen. The negative comparing vector was NC-GFP-LV. DCs isolated from C57BL/6 mice by magnetic selecting system were cultured in vitro and divided into 3 groups. Experimental group and negative control group were transfected with OX40L-RNAi-LV and NC-GFP-LV, respectively, and the blank control group was given the same volume culture solution. The MOI was 25. The status of transfection and GFP expression was monitored by GFP fluorescence. 6 days later, CD86 positive DCs were isolated and were co-cultured with CD4 + CD25 + T regulatory cells isolated from na(y)ve BALB/C. 6 days later, the proliferation and apoptosis of Tregs were evaluated by flow cytometry.Results The most effective siRNA sequence targeted the C,CTCATACAAGAATGAGTA episode of OX40L gene. The suppressive ratio of the OX40L protein expression was 73.1%. While the MOI was 25, the DCs transfected ratio by lentiviral vectors was at the level of 86. 4%. After co-cultured for 6 days, the CD4+CD25 +T regulatory cells of experimental group have a higher proliferation index (respectively, 38.3% vs.24.5 % ,22. 9%, F = 95.40, P = 0. 000) and lower apoptosis percentage ( respectively, 8.7 % vs. 20. 1%,19.8%, F=244.22,P=0. 000) than negative group and blank group. Conclusions The OX40L siRNA lentiviral vetor was constructed. This vector could effectively transfect DCs and block OX40/OX40L pathway, so to promote CD4 + CD25 + T regulatory cells proliferation in vitro.