Recent discoveries about the effects of drugs of abuse on the brain and the mechanisms of their addictions, and new actions of available medications are offering many opportunities for the discovery and development of novel medications to treat addictive disorders.This article reviews the current medications that have shown promising results for treating opioid, cocaine, methamphetamine, cannabis, alcohol and nicotine addictions.

Relapse is the reinstatement of drug-seeking and drug-taking behaviors following a period of abstinence.It is one of the main characteristics of drug addiction and is also the major problem requiring immediate action for the treatment of drug addiction.In this review,in order to offer new ideas to eventually treat drug addiction,efforts are made to describe the establishment of two animal models of relapse-the drug self-administration (SA) and extinctionreinstatement procedure,and the drug-conditioned place preference(CPP) and extinction-reactivation procedure.Then attention is given to assess the criterion validity of the animal models of relapse and to explore the neurobiological mechanisms involved in relapse.

Objective　To study the effect of glucagon-like peptide 2 (GLP-2) on mitogen-activated protein kinase (MAPK) activity in small intestinal epithelia in mice after radiation injury and its relation with the change of small intestinal epithelial proliferation. Methods　Mice were given a single dose of 8 Gy of total body 60Co gamma irradiation and then divided into GLP-2 and control groups. The activity of MAPK and proliferation rate in small intestinal epithelia were measured. Results　The activity of MAPK in small intestinal epithelia was higher in GLP-2-treated mice than in irradiated mice, and the proliferation rate in small intestinal epithelia significantly increased in GLP-2-treated mice. These two indices were of significantly positive correlated. Conclusion　GLP-2 can promote small intestinal epithelial proliferation in irradiated mice, and this may be related to activation of MAPK in small intestinal epithelia.

Objective　To investigate the effects of glucagon-like peptide 2 (GLP-2) on recovery of small intestinal epithelia from radiation injury in mice. Methods　Mice received a single 8 Gy dose of total body irradiation from 60Co gamma ray followed by treatment with GLP-2 or vehicle. DNA and protein content in small intestinal mucosa were measured, and small intestine was processed for histological examination with light microscope and scanning electron microscope. Results　Small intestinal mucosal DNA and protein content, villus height, and villus number significantly decreased in irradiated mice, partial villus tips were ulcerated. GLP-2 administration caused increase in DNA and protein content, villus height, and villus number as compared with irradiated control group. Meanwhile, the villus tips were lack of ulceration. Conclusion　GLP-2 can promote recovery of small intestinal epithelia from radiation injury in mice.

[Objective] To evaluate the efficacy and safety of drainage blood autotransfusion after total knee or hip arthroplasty.[Methods]Drainage blood in the first 6 hours postoperation was collected and reinfused using the ContavacTM CBCⅡ system in 30 patients taken total knee or hip arthroplasty.The efficacy was evaluated basing on the amount of the allogenic transfusion,the decreasing of the hemoglobin level and the morphology of the red blood cells in the drainage blood.The safety was evaluated basing on whether the patients had autotransfusion complications including fever,hemolytic reaction,coagulation disorders,pulmonary embolism and systemic infection.[Results]The volumes of total blood drainage,autotransfusion and allogenic transfusion were(946?433)ml,(622?313)ml and(233?348)ml,respectively.The average hemoglobin level of drainage blood was 99.67g/L and no apparente haemolysis happened.However,the hemoglobin level significantly decreased after operation in the peripheral blood.Only one rheumatoid arthritis patient had an abnormal fever during autotransfusion process,no other complication was observed.[Conclusion]Drainage blood in the first 6 hours postoperation is valid blood content.Drainage blood autotransfusion is an effective and safe way to slow down the hemoglobin reduction and reduce allogenic blood transfusion in patients being treated with total knee or hip arthroplasty.

Objective To elucidate whether down-regulation of homo sapiens eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) expression induces apoptosis in pancreatic cancer cells and its possible mechanisms. Methods Two siRNAs targeting human EEF1A2 were synthesized and the siRNA/liposome complexes were transfected into the pancreatic cancer cell line BxPC-3. RTPCR and Western blot were used to analyze the change of EEF1A2 expression and the apoptosis rate of BxPC-3 cells was studied using Annexin-V/PI assay. To identify the mechanisms involved, the apoptosis associated proteins such as caspase-3, caspase-8, caspase-9, PARP, cytochrome C and Bid were detected by Western blotting. Results Both EEF1A2-targeting siRNAs reduced the EEF1A2expression, and the No. 2 siRNA inhibited EEF1A2 expression to less than 25 % in mRNA and protein levels. Down-regulation of EEF1A2 expression in BxPC-3 cells enhanced cell apoptosis (15.28% ±3.65%) at a greater level than negative siRNA-expressing cells (10. 11% ± 3. 05%) or mock cells (9.41 % ±4.14 %). Furthermore, reduction of EEF1A2 activated the pro-caspase-8, pro-caspase-3,pro-caspase-9,PARP and Bid to their active forms, and increased the expression of cytochrome C.Conclusions These data suggest that EEF1A2 down-regulation could significantly induce apoptosis of pancreatic cancer cell line BxPC-3, which is likely mediated by the death receptor and mitochondrial apoptotic pathways.

Objective To explore the effect and the possible mechanisms of silent homo sapiens eukaryotic translation elongation factor 1 alpha 2(EEF1A2)gene on the growth of pancreatic cancer cell in vivo.Methods The pancreatic cancer xenograft models in mice were established.The mice were equally divided into control group,negative control group and EEF1A2 group,which were injected with PBS,negative control siRNA and EEF1A2 siRNA into xenograft tumors respectively.The size and weight of tumors in each group were measured.The expression of EEF1A2 and PCNA in tumor tissue of each group was detected by immunohistochemistry.The cell apoptosis rate in tumor tissue of each group was determined by TUNEL.Results In xenograft nude mice models,since the 17th day of injection,the growth of tumor size in EEF1A2 group was obviously slower than that of negative control group and control group(all P＜0.05).By the end of the treatment,the tumors were cut off and weighted.The weight of tumors in EEF1A2 group(0.27g± 0.06g)were significantly lower than those of control group and negative control group(0.39g± 0.08g and 0.43g± 0.07g,P＜0.05).EEF1A2 mostly expressed in cytoplasm of pancreatic cancer cell.In negative control group and control group,the positive cells distributed densely and the positive rate was(72.58 ± 25.47)％ and (76.75±23.19)％ respectively.The distribution of positive cells in EEF1A2 group was scattered and the positive rate was(34.78±21.36)％,the difference was statisically significant(P＜0.01).The expression of PCNA at protein level in EEF1A2 group was significantly lower those that of control group and negative control group(P＜ 0.01).The result of TUNEL test indicated that the cell apoptosis rate in EEF1A2 group was higher than those of control group and negative control group (P＜0.01).Conclusions The EEF1A2 gene can be effectively silented in vivo,which significantly inhibits the growth of pancreatic cancer cell.It may be related with inhibition of cell proliferation and promotion cell apoptosis.

Objective To investigate the effects of over-expression of homo sapiens eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) on in vitro invasion and lung metastasis of human pancreatic cancer SW1990 cells.Methods Letivirus-mediated delivery of EEF1A2 was used to enhance the expression of EEF1A2 gene in human pancreatic cancer SW1990 cells,the SW1990 cells stably over-expressing EEF1A2 protein (SW1990/EEF1A2 cells) were obtained,and the parent SW1990 cells and SW1990/GFP cells were used as the control,and the expressions of EEF1 A2 mRNA and protein were determined by Real-time PCR and Western blotting.The invasion ability of cells was determined by Transwell assay.The lung metastasis model was established by injection of SW1990 cells into the tail vein.Whole lung tissues were harvested,and visible nodules on tung surface were counted macroscopically 8 weeks later.Results The EEF1 A2 mRNA expression of SW1990/EEF1A2 was 3.252 ± 0.344,which was significantly higher than those in SW1990/GFP cells (1.000 ±0.060) and SW1990 cells (0.944 ±0.041,t =2.255,2.305,P＜0.01) ; the EEF1A2 protein expression was 0.833 ± 0.050,which was significantly higher than those in SW1990/GFP cells (0.247 ± 0.035) and SW1990 cells (0.273± 0.041,t=0.572,0.559,P＜0.01).The ability of invasion of SW1990/EEF1A2 cells was (60 ±4) cells,which was sigmificantly higher than (33 ±4) cells in SW1990/GFP group and (26 ± 3) cells in SW1990 group (t =31.33,34.78,P ＜ 0.01).Furthernore,SW1990/EEF1 A2 cells had a much higher incidence of lung metastasis in nude mice than SW1990/GFP cells and SW1990 cells in vivo (100％ vs.20％,20％,P ＜ 0.05).Conclusions EEF1 A2 over-expression can obviously increase the in vitro invasion and lung metastasis of pancreatic cancer SW1990 cells.

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain (PH) and native Han and Tibetan healthy volunteers living at high altitude (HNH and HNT). After healthy volunteers were administrated orally cotrimoxazole tablets, plasma concentration of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole was determined by RP-HPLC, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters t(1/2) of sulfamethoxazole in PH, HNH and HNT were, respectively, 9.30 +/- 1.11, 10.99 +/- 1.23 and 10.44 +/- 1.05 h; tmax were 1.4 +/- 0.3, 2.0 +/- 1.1 and 1.8 +/- 0.4 h; Cmax were 94.42 +/- 15.26, 89.33 +/- 7.67 and 87.43 +/- 11.61 micro x mL(-1); AUC(0-t) were 1202.5 +/- 238.3, 1 434.7 +/- 193.9 and 1302.8 +/- 103.0 microg x h x mL(-1); AUC(0-infinity) were 1240.7 +/- 255.3, 1511.5 +/- 211.9 and 1363.9 +/- 116.5 microg x h x mL(-1); CL were 1.01 +/- 0.22, 0.81 +/- 0.12 and 0.89 +/- 0.08 L x h(-1) x kg(-1); V were 13.27 +/- 1.73, 12.81 +/- 2.15 and 13.28 +/- 1.20 L x kg(-1). Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH. The t(1/2) was significantly higher and the CL was significantly lower in HNH and HNT than that in PH, and the AUC(0-infinity) was significantly lower in HNT compared with HNH. This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia. This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.