Aim To investigate the regulatory effect of p38MAPK signal pathway on the apoptosis of human esophageal cancer cells induced by valdecoxib.Methods The tumor cells were inoculated in the dose of 1?107?L-1.After 6 h,the cells were divided into control group,solution group,400,200,100,50,25 ?mol?L-1 valdecoxib group and various concentration valdecoxib+SB203580 group,cultured for 72 h.FCM and DNA Ladder were used to detect the apoptosis of Eca109 cells.p38 mRNA expression was detected by RT-PCR.The expression of p-p38MAPK protein was detected by immunohistochemical staining and FCM.Results ① Valdecoxib could increased the apoptosis rate of Eca109 cell in concentration-dependent fashion.Apoptosis rate was increased to 48.46% in 400 ?mol?L-1 valdecoxib group at the incubation time of 72 h.DNA ladder was the most recognized marker of apoptosis,and there was obvious DNA ladder in valdecoxib treated group,especially in 400 ?mol?L-1 group.② Valdecoxib could increase the expression of p38MAPK,while SB203580 could inhibit the over-expression induced by valdecoxib,at the same time,the apoptosis rate was been decreased.③ The expression of p38MAPK protein was positively correlated with the apoptotic rate(r=0.822,P=0.000).Conclusions Valdecoxib could activate p38MAPK pathway,thus induce the apoptosis of Eca109 cells,which may be one of the mechanisms for the inhibition of cell growth by valdecoxib.

Aim To investigate the effects and possible mechanism of valdecoxib on apoptosis of cancer in nude mice.Methods The tumor model was established by inoculating 2?106 cell both in the left and right armpit respectively.The mice were divided randomly into control group and valdecoxib group(20 mg?kg-1?day-1).Valdecoxib was dissolved in carboxymethylcellulose sodium and administered from the second day after inoculation.The mice were killed after 4 weeks.The volumn and inhibitory rate were calculated according to the length and width of xenograft tumor.H.E staining was used to observe the cell structure of the stomach and colon.The apoptotic rate was detected by FCM.The expression of COX-2,c-jun and c-fos protein was detected by FCM and immunohistochemical staining.Total RNA was extracted with Trizol method and the expression of COX-2 mRNA was detected by RT-PCR.Results(1) The body weight of nude mice was higher in valdecoxib treated group in a time-dependent manner.(2) Valdecoxib inhibited the growth of tumor.The weight of tumor was decreased from(1.43?0.52)g in control group to(0.93?0.53)g in valdecoxib treated group.The ratio of inhibition on the growth of tumor was 45.80%.(3) Valdecoxib increased the apoptosis rate from(14.15?0.48)% in control group to(29.80?6.35)% in treated group.(4) The expression of COX-2 mRNA and protein decreased in treated group compared with that in control group.FCM and immunohistochemical staining showed that the expressions of c-jun and c-fos were increased in valdecoxib treated group.There was statistical significance compared with control group.(5) There was significantly negative correlation between the ratio of apoptosis and the expression of COX-2(r=-0.726,P=0.008);there was significantly positive correlation between the ratio of apoptosis and the expressions of c-jun and c-fos protein respectively(r=0.603,0.813;P=0.038,0.001);(6) Valdecoxib did not affect cell structure of stomach and colon.Conclusions valdecoxib inhibits the growth of the xenograft tumor in nude mice and induces the apoptosis.Decreasing expression of COX-2 and up-regulating the expressions of c-jun and c-fos may be one of the mechanisms for the apoptosis.

Thirty patients with malignant obstructive jaundice were treated with biliary stent implantation+brachytherapy+conformal radiotherapy (study group; n=15) or biliary stent implantation alone (control group; n=15). Total bilirubin (TBIL) levels significantly declined within 1 month in both groups. However, at 6 months, TBIL values began to increase in the control group and continuously declined in the study group. Maximum tumor diameter increased in the control group, while decreased in the study group (remission rate, 13/15 ). As for the study group, the survival rate at 0. 5, 1, and 2 years was 15/15,14/15, and 10/15, respectively, higher than the control group (15/15,5/15,and 1/15) . Combining biliary stent implantation with brachytherapy and conformal radiotherapy might be a safe and effective treatment of choice for patients with malignant obstructive jaundice.

Aim To investigate the effects of suppressor of cytokine signaling-1(SOCS-1)on advanced glycation end products(AGEs)induced-renal tubular epithelial-myofibroblast transdifferentiation and activation of JAK/STAT in cultured human renal tubular epithelial cells(HKC).Methods Stable transfections of HKC with pCR3.1 vector and pCR3.1/SOCS-1 were performed with Lipofectamine 2000,and cells were selected with geneticin.Cells were stimulated with BSA and AGEs. The protein expressions of SOCS-1,α-SMA,E-cadherin,Col I,signal transducer and activatior of transcription 1,3(STAT1,STAT3),p-STAT1 and p-STAT3 were observed by Western blot.The protein synthesis of TGF-β_1 in the supernatants of the HKC was detected by enzyme-linked immunoadsorbent assay(ELISA).α-SMA and E-cadherin mRNA were measured by reverse transcription and polymerase chain reaction(RT-PCR).Results Compared with control group,the expression levels of α-SMA protein and mRNA and Col I were significantly increased in HKC with AGEs stimulation and there was a higher concentrations of TGF-β_1 in the supernatants.However,the expression of E-cadherin protein and mRNA were decreased with AGEs stimulation.Overexpression of SOCS-1 inhibited AGEs-induced activation of STAT1 and STAT3 and high expression of α-SMA protein and mRNA and Col I,and reversed the expression of E-cadherin protein and mRNA induced by AGEs.Meanwhile,overexpression of SOCS-1 reduced the concentration of TGF-β_1 in the supernatants of HKC with AGEs stimulation.Conclusion Overexpression of SOCS-1 inhibits AGEs-induced renal tubular epithelial-myofibroblast transdifferentiation maybe partly through blocking activation of JAK/STAT.

Objective To observe the change of coagulation function in chronic stress depression model rats and the effects of elec-troacupuncture (EA) on it. Methods A total of 32 Sprague-Dawley rats were randomly divided in control group (n=8), model group (n=8), EA group (n=8) and fluoxetine group (n=8) after a week of acclimation. The 21-day unpredictable mild stress combined with solitarily feed-ing was used to make the depression model in the latter three groups, meanwhile EA group and the fluoxetine group accepted EA and fluox-etine. They were measured the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). Serum levels of 6-keto-prostaglandin F1α(6-keto-PGF1α), P-selectin, thromboxane B2 (TXB2) were determined with enzyme-linked im-munoabsorbent assay. Results The cross and rear scores were significantly lower in the model group than in the control group (P<0.01). The scores increased in EA group and the fluoxetine group (P<0.01) compared with the model group. Compared with the control group, PT, APTT and TT decreased (P<0.01), FIB increased (P<0.05), the level of 6-keto-PGF1αdecreased, the level of P-selectin and TXB2 increased (P<0.01) in the model group. Compared with the model group, PT, APTT and TT increased (P<0.05), the level of 6-keto-PGF1αincreased (P<0.01), and the level of P-selectin and TXB2 decreased (P<0.05) in EA group and the fluoxetine group, and FIB decreased in EA group (P<0.05). Conclusion The chronic stress depression rats are impaired in the coagulation function and platelet activation, and can be allayed with electroacupuncture and fluoxetine.

Objective To explore the clinical application and safety of treatment of percutaneous radioactive 125I seed implantation treatment in lung metastases under CT guidance.Methods Twenty-seven lung metastatic malignancy cases (67 nodules) were studied.Eighteen cases (46 nodules) were hepatic cancer,4 cases (9 nodules) were prostate cancer,and 5 cases (12 nodules) were breast carcinoma.Diameters of lung nodules ranged from 0.5 cm to 4.0 cm with an average diameter of 2.1 cm.125I seeds were embedded under CT guidance,using 2 to 33 particles/nodule with an activity of 18.5 to 29.6 MBq/grain for each particle.Tumor matched peripheral dose was 90-120 Gy.Postoperative validation and quality evaluation followed.Results Four months later,24 nodules showed CR,30 showed PR,5 showed NC and 8 showed PD.The total effective rate was 80.6％ (54/67).In the course of treatment,11 patients had pneumothorax,3 had heavy lung compression and 4 had hemoptysis.All conditions were improved by pleural puncture or under close follow-up observation.Conclusion 125I seed implantation is an effective and safe technique in treatment of metastatic lung tumors under CT guidance.

Objective To study the effect of Kanglaite combined with comprehensive therapy on advanced non-small cell lung cancer.Methods Sixty-one patients with advanced non-small cell lung cancer were randomly divided into treatment group ( n=31 ) and control group ( n=30 ).Both groups were given comprehensive therapy.Treatment group were additionally treated with intravenous injection of 200 ml Kanglaite.Clinical efficacy,quality of life,pain relief and adverse reactions of the two groups were observed.Results ( 1 ) Quality of life was improved in 20 cases (64.5％ ),stabled in 8 cases (25.8％),declined in 3 cases ( 9.7％ ) of treatment group,and in the control group there were 9 cases ( 30.0％ ) improved,9 cases ( 30.0％ ) stabilized,12 cases (40.0％ ) declined respectively.Quality of life in treatment group was higher than in control group ( U=2.91,P＜0.01 ).( 2 ) Pain relief:the number of patients with complete remission,partial remission,no change,and progression were 5 cases ( 16.1％ ),16 cases ( 51.6 ％ ),16 cases (51.6％ ),6 cases (19.4％) and 4 cases (12.9％ ) in treatment group,and in control group they were 2 cases(6.7％ ),9 cases (30.0％ ),11 cases(36.7％ ) and 8 cases(26.7％ ) respectively.The effect of treatment on pain relief in treatment group was better than that in control group ( U=2.32,P＜0.05 ).(3) Clinical efficacy:in the treatment group there were 12 cases (38.7％) with partial remission,14 cases (45.2％) stabilized,and 5 cases (16.1％ ) progressed,and in control group the numbers were 8 cases (26.7％ ),8 cases (26.7％ ) and 14 cases (46.7％ ) respectively.The clinical efficacy in treatment group was better than that in the control group( U=2.04,P＜0.05).(4) There were significant difference on the change of white blood cell count and gastrointestinal reactions Ⅲ and Ⅳ degrees between treatment group and contrl group [22.6％ (7/31) vs.53.3％(16/30),x2=6.139 P＜0.05;19.4％ (6/31) vs.46.7％ (14/30),x2=5.161,P＜0.05].Conclusion Kanglaite injection combined with comprehensive therapy can improve clinical efficacy of therapy for advanced non-small cell lung cancer,reduce the toxic adverse reaction,protect immunity system and improve the quality of life of patients.

Aim To investigate the effects of high glu-cose on cholesterol metabolism in renal tubular cells and the intervention of the anthocyanins. Methods HK-2 cells were grown in the DMEM medium supple-mented with 10% FBS and were divided into 5 groups:normal glucose group, high glucose group, mannitol group, C3G group and Cy group. Effect of anthocya-nins on cell viability was detected with MTT, and cho-lesterol accumulation was detected with Amplex Red Cholesterol Assay kit and Filipin staining. Expression of ABCA1 was detected with RT-qPCR and Western Blot. Results In compared with control groups, HG significantly promoted cholesterol mass inside the cell and decreased the cholesterol concentration in the me-dium after treatment for 24 h or 48 h. The levels of mRNA and protein of ABCA1 were detected with RT-qPCR and Western blot, and both were decreased in the presence of HG. Whereas treatment with C3G and Cy markedly attenuated HG-induced cholesterol mass inside the cell by up-regulating the expression of AB-CA1. Conclusions High glucose can reduce the ex-pressions of the ABCA1, and then decrease cholesterol efflux and increase the cholesterol accumulation in HK-2 cells. Anthocyanins can decrease cholesterol accu-mulation by up-regulating the expression of ABCA1.

Objective:To investigate the expression and mechanism of NF-κB signal pathway in murine lupus nephritis.Methods:The BXSB mice as well as C57BL/6 of 16 weeks were used.Transmission electron microscope and PAS were used to detect the pathological change of renal tissue.RT-PCR and ELISA were used to detect the expression of HMGB1 mRNA and protein.The expression of HMGB1,p- NF-κB,RAGE,IκB and PCNA protein was detected by immunohistochemical stain,FCM and Western blot.Results:The level of BUN in serum and Micro-albumin in urine of BXSB mice was higher than that in C57BL/6 mice.The expression of HMGB1 mRNA and HMGB1 protein level in peripheral blood increased significantly in BXSB group.Compared with those in control group,electron microscopy and PAS revealed the thickness of glomerular basement membrane(GBM),fusion of foot processes partly of epithelial dell and subepithelial electron-dense deposits in the renal tissue of BXSBA mice.Compared with that of control group,expression of PCNA was higher in glomeruli of BXSB mouse.HMGB1 protein over-expression localized in cytoplasm and extracellular milieu,especially in proliferative glomeruli in BXSB group,while the HMGB1 protein primarily confined to the nuclear of tubule in control group.In BXSB group,the expression of p-NF-κB and RAGE increased,while the expression of IκB decreased.There were positive correlation between the expression of HMGB1,RAGE and p-NF-κB protein (r=0.833,0.621,0.848,P＜0.01),while the expression of p-NF-κB protein negatively correlated with that of IκB.Conclusion:HMGB1 could activate NF-κB through combining with its receptor-RAGE,induce the form of proliferative glomerulonephritis by promoting the proliferation of inherent cell of glomeruli,which may play an important role in the murine lupus nephritis.

Objective To investigate the risky sexual behaviors,associated factors and characteristics of sexual network among clients receiving methadone maintenance treatment (MMT) at the clinics in Taizhou prefecture of Zhejiang province.Methods A cross-sectional survey was conducted.Data was collected through questionnaire and from the national unified MMT system.Urine was collected to test heroin,methamphetamine,3,4-methylenedioxymethamphetamine (MDMA) and ketamine.Blood was collected to test infections on HIV,hepatitis C vims(HCV) and syphilis.Results Totally,362 clients were recruited.Most of the clients were male (88.7％),31--40 year-olds (54.5％),married (61.6％) and having received junior high school education (56.6％).85.1％ of them received urine test with 82(26.6％) positive for heroin,21 (6.8％) positive for methamphetamine,19 (6.2％) positive for MDMA and none for ketamine.77.1％ of them received blood test,and prevalence rates for HIV,HCV and syphilis were 1.1％,36.7％ and 3.6％.19.5％ of the clients who had sex in the past 6 months.Factors as having multiple sexual partners and positive for club drugs were under higher risk.Sexual networking seemed to be loose,linear and acyclic among this population but overlapping with the drug-using network.Conclusion Effective and targeted interventions should be taken among the MMT clients since continuing drug use and HIV/STD related sexual behavior were found common in them,suggesting there was a risk of HIV/STD transmission in this ppulation.