Objective To investigate the mechanism of Sut melanocytes growth inhibition in response to xCT -deficiency. Methods TTotal proteins were extracted from xCT-deficient Sut melanocytes and wild melanocytes, respectively, and were separated by 2-dimensional electrophoresis. Altered expression profile of proteins of Sut melanocytes was analyzed by PDQuest software and compared with that of wild melanocytes.Proteins with significant change were chosen to be identified by mass spectrometry and database query.Results Twenty proteins in Sut melanocytes altered significantly compared with wild melanocytes. Ten of the proteins were up-regulated, while the other tens were down-regulated. Four proteins from both up-regulated and down-regulated were identified respectively: up-regulated proteins were Tubulin alpha-1b, S100-A6,Nucleoside, S-formylglutathione, and down-regulated proteins were Calumenin,NDRG1 ,DPYSL2, 14kDa unknown protein. Conclusion The identification of the xCT-deficiency related proteins may provide supporting evidence for the mechanism research of Sut melanocytes' growth inhibition caused by xCT-deficiency.

Objective To investigate the effects of rosiglitazone,an agonist of proliferators activated receptor?(PPAR?),on expression of nuclear factor-kappa B(NF-?B)in peripheral blood mononuclear cells(PBMC)of multiple organ dysfunction syndrome(MODS) rats.Methods Forty male SD rats were randomly divided into four groups(n = 6 per group): vehicle control group,endotoxin(LPS) group,rosiglitazone(ROSI) pretreatment group,and PPAR-?antagonist GW9662 pretreatment group.Blood was taken 4 hours after operation,and mononuclear cells were separated.The expression of NF-?B p65in PBMC was detected by immunocytochemical method and image analysis was carried out.Results The expression of NF-?B p65 was low in vehicle control group.In LPS group,the expression of NF-?B p65 was significantly higher than that in vehicle control group(P0.05).Conclusion Rosiglitazone protected the MODS rats by inhibiting NF-?B activation.

Objective To investigate the protective effect of hydrogen-rich saline on lung injury associated with severe acute pancreatitis and its impact on P38MAPK and NF-κB expressions.Methods Fifty-four male Wistar rats were randomly (random number) divided into three groups:(1) hydrogen-rich saline treatment group (HRS group,n =18),in which the rats were treated with hydrogen-rich saline (6 mL/kg) administered intravenously via tail vein and HRS (20 mL/kg) administered subcutaneously at 5 min after successful modeling.(2) Severe acute pancreatitis model group (SAP group,n =18),in which rats received equivalent volume of normal saline instead of hydrogen-rich saline both intravenously and subcutaneously as in HRS group.(3) Sham operation group (SO group,n =18),in which rats were treated with sham surgery,and received equivalent volume of normal saline as in SAP group.The model of severe acute pancreatitis (SAP) was made by retrograde injection of 5％ sodium taurocholate (1 mL/kg) into cholepancreatic duct.All rats were sacrificed at 3 h,12 h,and 24 h separately after the operation (n =6 at a time).The levels of serum amylase,lipase were measured.The ratio of wet and dry lung tissues was measured.The histopathological changes of lung tissues were observed under optic microscope.The expressions of P38MAPK,p-P38MAPK and NF-κB were measured by using immunohistochemistry method.Results Compared with SAP group,there were no significant differences in levels of serum amylase [12 h (5306.7±909) vs.(5435.0 ±441.2)] and lipase [12 h (1897.8 ±149.4) vs.(1917.9± 106.8)] in HRS group (P ＞0.05),but there were significant differences in the ratio of wet and dry lung tissues [12 h (3.12 ± 0.58) vs.(1.87 ± 0.25)] and histopathology scores [12 h (2.14 ± 0.38) vs.(3.58 ±0.32)] (P ＜0.05).There was no significant difference in expression of P38MAPK in lung tissues among three groups at 12 h.Compared with SO group,the expressions of p-P38MAPK and NF-κB were significant increased in SAP group at 12 h,however,they were lower significantly in HRS group than those in SAP group.Conclusions Hydrogen-rich saline has a protective effect on lung injury associated with severe acute pancreatitis,and its mechanism may be likely related to the antioxidant effect and inhibiting the activation of P38MAPK and NF-κB.

ObjectiveTo study the expression of p27 and its relationship with CpG island methylation phenotype (CIMP) in insulinoma.MethodsExpression of p27 was tested in 27 insulinoma tissues and 11 paired control tissues by immunohistochemistry staining.CpG island methylation of p16,MLH1,RAR-β,MGMT,THBS1 (CIMP) was detected in 27 insulinoma tissues and 11 paired cantrol tissues by methylation specific PCR (MSP).The data of p27 and CIMP expression were correlated with the clinicopathological characteristics.ResultsThe positive expression rate of p27 in insulinoma tissues was significantly lower than that in paired control tissues (48％ vs 91％,P =0.008).High rate of CIMP occurrence in insulinoma tissues was 33％ (9/27),while it was 18％ (2/11) in paired control tissues,and difference between the two groups was not statistically significant ( P =0.350 ).The methylation of MGMT was reversely associated with p16 methylation ( P =0.004).p27 expression in insulinoma tissues was reversely associated high rate of CIMP occurrence but it was not statistically significant ( P =0.420).Neither the expression of p27 nor the occurrence of CIMP was associated with the clinicopathological features.ConclusionsDown-regulation of p27 and high rate of CIMP occurred in insulinomas,suggesting that the inactivation of p27 and epigenetic alterations of several genes might contribute to the carcinogenesis of insulinoma.

ObjectiveTo investigate whether neuronal intermediate filament protein(NF-66) could be used as a molecular marker for the determination of malignancy of insulinoma.MethodsThe expression of NF-66 protein was detected in insulinoma and pana - cancerous tissues and 3 insulinoma cell lines by immunohistochemistry staining. The relationship between the expression of NF-66 protein and the clinicopathological characteristics,survival was analyzed by univariate and multivariate statistical analysis.ResultsExpression of NF-66 was found in 102(77％ ) out of 132 insulinomas and none of 98 paired control (P =4.86 × 10-31 ).NF-66 was highly expressed in 3 insulinoma cell lines.The expression of NF-66 was found in 96 (81％) out of 118 benign tumors (P =0.003),while out of 14 malignant insulinomas,6(43％ ) were found to express NF-66 ( P =0.003 ).The expression of NF-66 was significantly associated with tumor size (3 cm as the cut-off point),distant metastasis (38％ vs 81％,P =0.013) and distant plus lymph node metastasis (46％ vs 81％,P =0.009),respectively.The expression of NF-66 was not correlated with age,gender,recurrence and overall survival.ConclusionsDown-regulation of NF-66 was significantly associated with tumor malignancy,suggesting that NF-66 could be a potentially novel molecular bionarker to distinguish malignancy from benign insulinoma.

Objective To analyze the incidence,mortality and survival rates of pancreatic cancer in Pudong New Area of Shanghai from 2002 to 2010.Methods The residents in Pudong New Area of Shanghai were recruited in this study during the period 2002 ～ 2010,the incidence,mortality were calculated according to different age groups and genders.The standardized morbidity and mortality of pancreatic cancer were calculated by world standard population.Logarithmic linear regression was used to calculate the annual percentage change (APC) of incidence and mortality.The 1 ～ 5 year survival of pancreatic cancer patients was analyzed by Kaplan-Meier method and COX regression analysis,and the survival of patients with different TNM staging,with or without operation was determined.Results Among 3089 newly occurred pancreatic cancer cases during 2002 ～ 2010,1707 and 1382 cases were males and females,respectively,with an average age of (69 ± 12) and (73 ± 12) years old,the crude incidence for both genders was 13.32/100 000,and it was 14.71/100 000 for males,which was higher than that in females (11.93/100 000).The ratio of male and female for incidence of age standardize was 1.57:1.There were 2963 death in total,including 1627 males and 1336 females,with a crude mortality rate of 12.78/100 000.The crude mortality rate for males was 14.02/100 000,which was higher than that in females (11.53/100 000).The ratio of male and female ASR for mortality was 1.55:1.Both incidence and mortality significantly increased for males aged over 35 and females aged over 40.The peak of morbidity and mortality appeared in male over 80 years old,and in female over 85 years old.The 1 ～ 5 year survival rates of pancreatic cancer patients were 16.59％,7.31％,5.23％,4.33％ and 3.87％,respectively.The differences in 1 ～5 year survival rates between surgical and non-surgical management groups were statistically significant (P ＜ 0.05).The median survival time of TNM 0 ～ Ⅱ,Ⅲ and Ⅳ staging was (250.00 ± 33.37),(224.00 ± 15.82),(86.00 ± 4.52) d.There was a statistically significant difference among the survival of TNM-Ⅳ and TNM 0 ～ Ⅰ,TNM Ⅲ (P ＜ 0.001).Conclusions The incidence and mortality of pancreatic cancer in males are higher than those in females in Pudong New Area of Shanghai.The survival is associated with TNM staging at diagnosis and whether surgical operation is performed.

Objective To investigate the inhibitory effect of X-linked inhibitor of apoptosis associated factor-1(XAF1) on xenograft growth in nude mice with hepatocellular carcinoma. Methods The models of xenografted nude mice with human hepatocellular carcinoma cell line SMMC7721 were established. Intratumor injection was performed on three tumor sites in each group of mice (n=5) with recombinant adenovirus Ad5/F35-XAF1, control virus Ad5/F35-Null at the same infective titre or PBS of the same volume every two days for two weeks. The volumes of xenografts in all nude mice were measured every three days, and the differences between Ad5/F35-XAF1 group and the other two groups were compared. The apoptosis of tumor cells was determined by in situ end-labeling TUNEL method, the expression of XAF1 protein and microvessel density (MVD) were detected by immunohistochemistry. Results Intratumoral injection of Ad5/F35-XAF1 significantly inhibited the growth of tumor xenografts with smaller tumor size, less tumor weight and lower MVD compared with those injected with control virus Ad5/F35-Null and PBS (P<0.05 or P<0.01). However, the apoptosis index and expression of XAF1 protein in Ad5/F35-XAF1 group were significantly increased compared with the other two groups (P<0.01). Conclusion Ad5/F35-XAF1 significantly inhibits xenograft growth in nude mice with hepatocellular carcinoma, which is probably associated with the effects of XAF1 inducing hepatocellular carcinoma cell apoptosis and suppressing tumor angiogenesis.

Objective To investigate the prevalence and risk factors of metabolic syndrome (MS) in residents in Pudong New District of Shanghai. MethodsA total of 5 584 residents aged 20-80 years were randomly selected from Pudong New District of Shanghai through multistage sampling and interviewed from April to July of 2008. Metabolic syndrome was defined according to three diagnostic criteria for MS, issued by the modified National Cholesterol Education Program Adult Treatment Panel Ⅲ criteria ( NCEP-ATP Ⅲ ), International Diabetes Federation (IDF), and Chinese Diabetes Society (CDS). ResultsThe crude prevalences of MS in the adult population in Pudong New District were 18.2％ and 13.1％ standardized ( male 19. 1％, female 17.4％, the age-standardized 15.6％ and 13.2％ ) with CDS criterion, 31.8％ and 24.4％ standardized ( male 28.4％ ,female 35.1％ ,the agestandardized 22. 7％ and 25.0％ ) with NCEP-ATP Ⅲ criterion, and 21.7％ and 17.0％ standardized ( male 15.9％ ,female 26.7％, the age-standardized 13.8％ and 19.2％ ) with IDF criterion. The age-specific prevalence of MS increased according to three diagnostic criteria, and the age-adjusted prevalence was higher in males than females in junior age groups and higher in females than males in senior ones. Significant differences were present among region, education, marriage status, smoking, work intensity, recreation, and physical activity according to some diagnostic criteria. ConclusionsSubstantial proportions of adults in Pudong New District of Shanghai suffer from metabolic syndrome, and there exists a tendency for young people involved. MS has become a noteworthy public health problem. It suggests that community-integrated control strategy of MS should be made a priority.

OBJECTIVE Dynamics of serum and urine metabolites in hepatic injury rats induced by ethanolic extract from Rhizoma Dioscoreae Bulbiferae(RDB)was investigated by 1H-NMR-based metabo?nomic methods in order to discover early biomarkers of liver toxicity induced by RDB. METHODS Rats were ig adminisetred with RDB at a dose of 5 g·kg-1 for 28 d. Rats were sacrificed 3,7,14 and 28 d af?ter RDB administration,as well as after a recovery period,respectively. Blood was taken for routine bio?chemical analysis by an automatic biochemical analyzer. Liver/body mass indexes were calculated ,and liver pathological changes were observed with hematoxylin-eosin staining. Urine samples were collected before and 3,7,14 and 28 d after RDB administration,respectively,as well as after withdrawal. Metabo?nomic analysis was carried out for serum and urine samples. Principal component analysis and orthogonal partial least squares-discriminant analysis were used for screening and identifiying early biomarkers. RESULTS Compared with the control group,total bilirubin (TB) and total cholesterol (TC) values were increased in 3-28 d in RDB group(P<0.05,P<0.01). Total bile acid(TBA)was elevated in 7-28 d (P<0.05,P<0.01). TB,TC and TBA became normal after discontinuation with RDB. There was no significant difference between RBD-treated group and control group in the activity of glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase,and the content of glucose also was not different between the two groups. The ratio of liver/body mass was elevated at 3-28 d(P<0.01)but returned to normal after withdraval of RDB. The enlargement and necrosis of hepatocytes were observed 7 d after RDB administration,and lesion degree was aggravated with the extension of RDB delivery time. Meta?bonomic analysis showed that the serum lipids (low density lipoprotein/very low density lipoprotein (LDL/VLDL),glutamic acid,choline phosphate and glycerolphosphatecholine were increased in the early stage. Pyruvate and N-acetylglutamate were decreased in urine. These metabolites became normal 7 d after discontinuation with RDB. CONCLUSION The serum lipids (LDL/VLDL),glutamic acid,glycerol phosphate choline,as well as urine pyruvic acid salt and N-acetyl glutamate may be used as the early biomarkers for liver toxicity induced by RDB.

Objective To investigate the protective effects and mechanisms of intraperitoneal administration of thymosin β4 on severe acute pancreatitis in rats.Methods Fifty-four male Sprague-Dawley rats were randomly (random number) divided into sham operation (SO) group,severe acute pancreatitis (SAP) group and thymosin β4 (Tβ4) pretreatment group (n =18 in each group).SAP rat model was prepared by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct.Rats in Tβ4 group were treated with thymosin β4 (6 mg/kg) by intraperitoneal administration prior to SAP modeling.Six rats in each group were sacrificed at 3,6,12 hours,respectively after modeling.The serum levels of amylase,tumor necrosis factor-α (TNF-α),interleukin-1 β (IL-1 β),and interleukin-6 (IL-6)were detected,and pathological scores of the tissue of pancreas head were evaluated under light microscope.Pancreatic nuclear factor-kappa 1B (NF-κB) p65 and IκB α levels were detected by the Western blot.All data were analyzed by using the analysis of variauce or t test.Results The levels of serum amylase of SAP 3,6 and 12 hours groups were (3221 ±394) U/L,(4509 ±474) U/L and (6280 ±728) U/L,which were significantly higher than (2598±416) U/L,(3639 ±373) U/L and (4782 ±466) U/L of the Tβ4 groups (t =-2.666,-3.530,-4.245,P ＜ 0.05).The levels of serum TNF-α of the SAP 3,6 and 12 hours groups were (247.7 ± 18.5) pg/mL,(313.5 ± 17.7) pg/mL and (359.3 ±22.6) pg/mL,which were higher than (182.3 ± 13.6) pg/mL,(258.9 ± 14.9) pg/mL and (278.1 ± 16.3) pg/mL of the Tβ4 groups (t =-6.964,-5.769,-7.152,P ＜ 0.05).The levels of serum IL-1 β of the SAP 3,6 and 12 hours groups were (258.2±10.5) pg/mL,(345.1 ±22.0) pg/mL and (430.9 ±25.4) pg/mL,which were higher than (170.3 ± 12.4) pg/mL,(263.5 ± 13.3) pg/mL and (303.7 ± 16.1) pg/mL of the Tβ4 groups (t =-13.258,-7.762,-10.355,P ＜ 0.05).The levels of serum IL-6 of SAP 3,6 and 12 hours groups were (266.3 ±11.5) pg/mL,(355.0 ±24.4) pg/mL and (429.2 ±33.7) pg/ mL,which were higher than (171.1 ± 13.0) pg/mL,(234.9 ± 19.2) pg/mL and (277.2 ± 19.2) pg/ mL of the Tβ4 groups (t =-13.401,-9.474,-9.582,P ＜ 0.05).The pancreatic pathological scores of the SAP3,6 and 12 hours groups were (6.25 ±0.94),(8.83 ±0.82) and (12.08 ±1.16),which were higher than (4.17 ± 0.93),(6.33 ± 0.82) and (7.33 ± 1.25) of the Tβ4 groups (t =-3.867,-5.303,-6.823,P ＜ 0.05).The relative expression of pancreatic NF-κB p65 in SO group was (0.95 ±0.11),which was significantly lower than (2.40 ±0.17) of the SAP 12 hours group (t =-17.368,P＜ 0.05).The relative expression of pancreatic NF-κB p65 in Tβ4 group was 1.50 ± 0.10,which was significantly lower than SAP 12 hours group (t =10.917,P ＜0.05).The relative expression of pancreatic IκB α in SO group was (1.93 ±0.11),which was significantly higher than (0.78 ±0.18) of the SAP 12 hours group (t =13.260,P ＜ 0.05).The relative expression of pancreatic IκB α in Tβ4 group was (1.12±0.10),which was significantly higher than SAP 12 hours group (t =-4.112,P ＜ 0.05).Conclusions Thymosin β4 has the protective effect on SAP rat model,and the mechanism may be associated with inhibition of NF-κB signaling pathway and decreased proinflammatory cytokines.