Volume 88  ·   Issue 28  ·  2008

Pancreatic cancer is the tumor with the highest malignancy degree and the worst prognosis among abdominal tumors. Because of the anatomical position of pancreas and the unique biological characteristics of pancreatic cancer, it is difficult to diagnose it in early stage. More than 80% of patients are in middle and late stage when they go to the doctor, and they lose the opportunity of radical surgery. Even the patients who obtain surgical resection, the 5-year survival rate after surgery is only about 5%. Although the development of modern surgical technology has reduced the perioperative mortality rate of pancreaticoduodenectomy to below 5%, the long-term survival rate of pancreatic cancer has not changed significantly in the past 30 years. How to further improve the early diagnosis rate and long-term survival rate of pancreatic cancer is a realistic problem that all basic and clinical researchers of pancreatic cancer must face for a long time.

objective To evaluate the effects of -1290A>G,-1195G>A and-765G>Csingle nucleotide polymorphisms(SNPs)in the promoter of cyelooxygenase(COX)-2 gene on the risk of pathogenesis of pancreatic cancer.Methods Peripheral blood samples were collected from 283 patients with pancreatic cancer and 566 nomud controls. Questionnaire survey was conducted to understand the demographic data and status of smoking and smoking cessation of the subjects.Polymerase chain reaction based restriction fragment length polymorphism(PCR-RFIP)was used to detect the genotypes of the gene fragments containing the 3 SNP sites in the promoter regions of the COX-2 gene.Statistical tests were performed to analyze the relations among different factors and the risk of pancreatic cancer.Results Three SNPs,-1290A>G,-1195G>A,and-765G>C were identified.A case-control analysis revealed 1.75-fold(95%CI=1.16-2.64)and 2.53－fold (95%CI=1.43-4.47)excesses of risks of developing pancreatic cancer for the -1195AA and -765CG genotype carlqerg respectively compared with the non-carriers.Compared with A-1290-G-1195-G-765 containing haplotype.greater risks of developing pancreatic cancer were observed for A-1290-A-1195-G-765(OR=1.26,95%,CI=1.02-1.56)and G-1290 A-1195-C-765(OR=5.54,95%CI=1.79-17.16)containing haplotypes.There were interactions between the-765CG or-1195AA genotype and smoking in the risk of developing pancreatic cancer.Conclusion The SNP of -1195A>G and -765G>C in the COX-2 promoter may play an important role in mediating hereditary susceptibility to developing pancreatic cancer.

Objective To investigate whether dendritic cells(DCs)pulsed with mutant K-ras peptide(12-Val)can induce efficiently specific anti-tumor immune response aganist pancreatic cancer.Methods Immature DCs were isolated from the pefipheral blood of a volunteer and were pulsed with synthesized mutant K-ras peptide(YKLVVVGAV).When the DCs were matured the expression rate of Kras antigen epitope on the DC's surface was detected by monoantibody(K-ras-12-Val).Autogeneic and homologous T cells were mixed with the mutant K-ras peptide-pulsed DCs.Human pancreatic cancer cells of the line Patu8988 were mixed with cytotoxic T lymphocytes(CTLs)cultured for 5 days.and the killing eriects of the CTLs on the ceils was assessed by MTY method.Patu8988 cells were iniected subcutaneously into nude mice.cancer cells were obtained from the tumor masses and injected subcutaneously into other nude mice to establish mice models of pancreatic cancer.Then 32 mice with pancreatic cancer were randomly divided into 4 equal groups:control group.K-ras specific CTL intra-tumor injection group,CTL caudal vein injection group,and IL-2 activated non-specific CTL intra-tumor injection group.The tumor size was measure regularly.Immunohistochemistry was used to detect the pathological analysis of the transplanted tumors.Results The mutational epitope(K-ras-12-Val)induced by mutant peptide could be foand on the DCs' suIface efficiently.After co-incubation with the mature DCs pulsed with tumor antigen the autogeneic T cells were activated.the CD8+T cells accounted for(44.8±2.1)%.Without damage the normaI tissue cells,the killing rate of activated K-ras specific CTLs to the tumor cell when Lhe ratios of CTL:Patu8988 cells were 10:1,20:1,and 50:1 were(21.2±1.9)%,(32.4±2.1)%,and(45.7±5.3)% respectively.alJ while the killing efficiency significantly superior to those of the non-specific activated Tlymphocyte(all P<0.05).Eight days after CTL iniection into the nude mice the tumor size of the intratumor injection group was(68±13)mm3,significantly smaller than those of the control group and IL-2 activated non-specific CTL intra-tumor injection group[(87±14)mm3 and(79±19)mm3,both P<0.05].The survival rates of the nude mice of the K-ras specific CTL intra-tumor injection group,CTL caudal vein injection group.and IL-2 activated non-specific CTL intra-tumor injection group were all significantly higher than that of the contml group(all P<0.05),and the survival rate ofthe K-ras specific CTL intra-tumor injection group was significantly higher than that of the IL-2 activated non-specific CTL intra.tumor injection group(P<0.05).Immunohistochemieal staining confirmed that K-ras specific CTL had the ability to move toward tumor.Conclusion DCs pulsed with mutant K-ras peptide(12-Val)induces specific anti-tumor immune response in pancreatic cancer efficiently.

Objective To investigate the expression of radio-inducible herpes simplex virus thymidine kinase(TK)suicide gene controlled by early growth response-1(Egr-1)promoter in pancreatic cancer cells.Methods Adenoviral vector pAdEgr-1-TK containing green fluorescent protein(GFP)was,constructed.Human pancreatic cancer cells of the line PC-3 were cultured,transfected with pAdEgr-1-TK.and then exposed to 60Co source γ-radiation at the doses of 0,5,7.5,10,15,and 20 Gy respectively for 24 hours.RT-PCR and Westem blotting were used to detect the TK mRNA and protein expression in the PC3 cells.Results The TK mRNA expression levels of the PC3 cells exposed to γ-radiation at the doses of 0,5,7.5,10,15,and 20 Gy respectively were(67.3±2.1)%,(89.3±1.0)%,(114.7±5.7)%,(140.5±3.1)%,(134.5±4.0)%,and(117.4±3.4)%respectively.The TK mRNA expression Jevel was markedly increased after exposure to γ-radiation,especially that t the dose of 10 Gy(all P<0.01).The TK protein expression levels of the PC3 cells exposed to γ-radiation at the doses of 0,5,7.5,10,15,and 20 Gy were(5.4±0.7)%,(7.6±0.9)%,(21.5±1.5)%,(35.7±1.4)%,(32.1±1.2)%,and(28.8±1.5)%respectively.C:onclusion The Egr-1 promoter causes high expression of TK suicide gene in cancer ceils after exposure to 60Co-γ-radiation.These data provide an experimental basis for gene therapy.

Objective To observe the effect of MBD1-siRNA on the expressions of multiple tumor suppressor genes in pancreatic cancer cells,and to explore the role of MBD1 in carcinogenesis of pancreatic carcinoma.Methods Two siRNA sequences targeting MBD1 were designed by software and cloned into the expression plasmid pGCsi-U6/Nen/GFP.DNA sequencing was used to confirm if the recombinant plasmid was constructed correctly.The constructed plasmid and the blank plasmid pGCsi-U6/Neo/GFP were stably transfeeted into human pancreatic cancer cells of the line BxPC-3.Nude mice underwent subcutaneous injection of the BxPC-3 cells transfected with the plasmid pGCsi-U6/Neo/GFP containing MBDl or the blank plasmid pGCsi-U6/Neo/GFP to establish tumor models and were observed for 8 weeks.Mice without inoculation were used as controls.EiAt weeks later the mice were killed with the tumors taken out.RT-PCR wag used to detect the mRNA expression of MBD1 and the tumor suppressor genes related with DNA methylation.including CDH1.RASSF1A,TIMP3.P14ARF and Rb in transplanted tumors.Results MBD1-siRNA recombinant plasmids were constructed SUCCesSfUlly and stably transfected into the BxPC-3 cells.MBD1 was not detected in the tumors of the MBD1-siRNA group and could be found in the other 2 groups.However.the mRNA expression levels of CDH1,RASSF1A.TIMP3,P14ARF,and Rb of the MBD1-siRNA group(179.7±8.1,155.6±10.0,256.7±15.7,199.0±7.9,210.1±9.4)were all significantly higher than those of the other 2 groups(21.0±6.8,22.0±2.7,99.4±10.3,86.0±5.4,15.0±4.9,11.4±6.0,15.3±1.9.110.7±14.1.74.3±4.8.17.4±7.8,all P<0.05).Conclusion RNA interference decreases the expression of MBD1 in pancreatic cancer and up-regulate the transcription of tumor suppressor genes.MBD1 mediated transcriptional repression may play an important role in the development of pancreatic cancer.

Objective To analyze the reasons of cardiac permanent pacemaker replacement and the strategies to prevent relevant complicationsMethods The clinical data of 57 patients.38 males and 19 females,aged 74±8(56-94),31 with sick sinus syndrome,26 with Ⅱ or Ⅲ degree atrioventricular block,who underwent 63 times of cardiac permanent pacemaker replacement,including 13 times of lead replacement.were analyzed.Results The reason of replacement included battery normal exhaustion for 57 case-times.battery exhaustion before the defined schedule for 2 cuge-times.lead electrodes incompletely fractured for 2 case-times.and infection of pacemaker pocket for 2 case-times.There were 9 cases of placement-related complications:pacemaker pocket hematoma(n=4),lead dislocation(n=3),and abandoned lcads falling into the right ventricle(n=2).The average lifetime of old pacemakers was 9.25 years(2-15 years).The pacing threshold of ventricular leads after pacemaker replacement was(0.77±O.40)V,significantly higher than the initial pacing threshold[(O.60±0.21)V,P<0.01].There were no significant differences in the lead impedance and R wave amplitude between the pacemaker replacement and initial implantation[(854±136)Ω vs(828±176)Ω,and(12±4)mV VS(12±4)mV,both P>0.05].Conclusion The main reason of pacemaker replacement is battery exhaustion.Most implanted ventricular leads still can be used.A rare serious complication of cardiac pacemaker replacement operation iS abandoned lead falling into the right ventricle,and correct disposing of initial leads help avoid this complication.

Objective To explore the effect of use of lens culinaris agglutinin(LCA)-coupled spin column(ACSC)in detection of α-fetoprotein(AFP)isoform AFP-L3 and to evaluate the value of AFP-L3 as a biomarker in diagnosis of hepatoeellular-carcinoma(HCC).Methods The serum samples of 132 patients with elevated AFP level(20-1000μg/L),79 diagnosed as with HCC and 53 with benign liver diseases(35 with liver cirrhosis and 18 with chronic hepatitis)underwent ACSC to isolate the fraction of AFP-L3.The contents of AFP and AFP-L3 were detected oy micro-particle immunoassay.The ratio of AFPL3 to toml AFP.AFP-L3%.was calculated.Correlation between the abnormMly elevated AFP-L3% and HCC was analyzed.Results Detection of AFP-L3%using ACSC method Was operating friendly.The average valUC of AFP-L3%in the patients with HCC was 36.4%.significantly higher than those of the patients with benign liver diseases(5.3%respectively,P<0.01).The area under the receiver operating characteristic(ROC)curve of AFP-L3%was 0.807.Taking AFP-L3%≥10%as diagnostic criteria,the sensitivity of AFP-L3%in HCC diagnosis Was 84.8%(67/79)and the specificity Was 92.5%(49/53),with a total conformity rate of 87.9%compared to the confirmed clinical diagnosis.Conclusion ACSC is of clinical value in detecting AFP-L3.AFP-L3% is a valuable biomarker in diagnosis and prediction of prognosis of HCC.

Objective To investigate the mutations of the mismatch repair genes hMLH1 and hMSH2 in hereditary nonpolyposis colorectal cancer(HNPCC).Methods The DNA samples of 76 probands of HNPCC families underwent PCR amplification and sequencing on 35 exons in hMLH1 and hMSH2 genes.Results (1)The overall mutation rate of the hMLH1 and hMSH2 genes was 33%(25/76).(2)22 mutations were found,16 in the hMLH1 gene and 6 in the hMsH2 gene.(3)The spectrum of mutation type included franle shift,nonsense,splice site,and misserlse mutations.Missense mutation was the most coinnlon mutation type.Condusion The hMLH1 and hMSH2 mutations in Chinese HNPCC families show a wide spectrum.It seems that hMLH1 gene iS involved more frequently than hMSH2 gene.A certain number of HNPCC families Can be benefited from the genetic screening for mutation of the mismatch repair genes.

Objective To investigate the expression of p53,bcl-2,and bax,apoptosis regulating genes,in adenoid cystic carcinoma of larcrimal gland and the roles thereof in elinical prognosis.Methods 56 patients of adenoid cystic carcinoma of larerimal gland were divided into two groups according to the prognosis:poor prognosis group with recurrence or metastasis within 5 years(n=32)and better prognosis group(n=24)surviving tumor free within 5 years.The protein expression levels of p53,tumor suppressor gene,bax,apoptosis promoting gene,and bel-2,anti-apoptosis gene,were analyzed by strepavidin peroxidase method.8 cases of normal lacrimal gland tissues were used as controls.Results(1)The overall positive rate of p53 of the patients with adenoid cystic carcinoma of larcrimal gland was 73.2%.significantly higher than that of the normal controls(0,P<0.05).The p53 positive rate of better prognosis group waft 62.5%,significantly higher than that of the poor prognosis group(81.3%,P<0.05).The protein expression of p53 in adenoid cystic carcinoma of larerimal gland was negatively correlated with clinical prognosis.(2)The overall expression rate of bcl-2 of the patients with adenoid cystic carcinoma of larcrimal gland was 69.6%,significantly lower than that ofthe control group(P<0.05).The expression bel-2 protein was correlated with better clinical prognosis.(3)The bax positive rate of the patients with adenoid cystic carcinoma of larcrimal gland group was 60.7%.not significantly lower than the control group.The bax positive rate of the better prognosis group was 91.7%.significantly higher than that of the poor prognosis group(65.6%,P<0.05).Conclusion Some apoptosis regulating genes,such as mutation-type(mt)p53 play an important role in the gene ration and development of adenoid cystic carcinoma of larcrimal gland.p53,bax,and bel-2 proteins may act as valuable signals for clinical prognosis.The patients with over expression of bcl-2 and bax and low expression of p53 may have better prognosis than the contrary ones.

Objective To investigate the effect of allogeneic hemopoietic stem cell transplantation (HSCT)in patients with acute lymphocytic leukemia(ALL)or chronic myelocytic leukemia(CML)resistant to imatinib mesylate(IM).Methods Fourteen patients ALL[n=4,au with Ph(+)chromosome] or CML(n=10.1 in acceleration phase and 4 in blastic crisis)resistant to IM received allogeneic HSCT.The hematopoietie stem cells transplanted to 7 cases were from identical sibling donors.and hematopoietic stem ceHs transplanted to the other 7 were from mimatched related donom.Eight Cash received recombinant human granulocyte-colony stimulating factor(rhG-CSF)mobilized bone marrow transplantation plus peripheral blood stem cell transplantation(PBSCT),and 6 only received PBSCT.Ten case8 were given rhG-CSF mobilized donor lymphocyte infusion(DLI)to prevent or treat relapsing.Results All patients achieved complete allogeneic engraftment and the median times of neutrophil recovery and platelet recovery were 16 and 13 days respectively.There was no treatment related death.Nine of the 14 patients developed acute graft versus host disease(GVHD),7 being in the grade Ⅱ and 2 being in grade Ⅲ;and 6 of the 13 evaluable patients developed extensive chronic GVHD.The hematological relapse Was 9.Conclusion Allo-HSCT can be an important salvage option for patients with Ph(+)chromosome with leukemia resistant to IM.

Objective To investigate the epidemiologieal characteristics of invasive n080cornjal eandidiasis in teaching hospitals in Beijing.Methotis The clinical data of consecutive cases diagnosed as with nosecomial candidiasis hospitalized in Beijing Chaoyang Hospital(CYH)(n=43)and Peking Union Medical College Hospital(PUMCH)(n=34)from January 2004 to September 2006 were retrospectively analyzed to evaluate the incidence and mortality,and the relationship between antifungal therapy and outcomes.The minimum inhibitory concentrations(MICs)for Gandida spp were determined by microdilution method.Results The incidence rates of nosocomial candidiasis of CYH and PUMCH were 0.053% and 0.025%respectively in 2004.and increased to 0.cr74%and 0.049%respectively in 2006.Candidemia accounted for 55.8%(43/77)of the Candida infection,followed by intra-abdominal infection(26.0%,n=20),intra-thoracic infection(9.1%,n=7),and biliary tract infection(7.8%,n=6).The species mostly frequently isolated were Candida albicans(57.1%),followed by C. tropicalis(19.5%),C.glabrata(14.3%),and C. parasilosis(2.6%).The susceptibility rotes of C. albicans,C. tropicalis,C.glabrata.and C. parusilosis to fluconazole were 97.7%.86.7%,63.6%.and 100%respectively.No isolates were resistant to amphotericin B.The crude mortality rate of Candida infection was 37.7%.The mortality rate of the candidemia patients who did not receive systemic antifurlgal therapy was 72.7%,significantly higher than those who received antifungal therapy(37.5%,P=0.043).Most patients received fluconazole as the first choice(91.7%in PUMCH and 79.2%in CYH)with the survival rotes of 63.6% and 52.6%reslmctively.Conclusion With high morbidity and mortality,invasive nosocomial candidiasis is a big problem in teaching hospitals.Further investigation is necessary to evaluate the incidence and to idantify which antifungal agents are most protective for candidiasis.

Objective To investigate the significance of use of modification of diet in renal disease (MDRD)equation in calculating glomemlar filtration rate(GFR)so as to estimate the prevalence of"renal insufficiency"in type 2 diabetes patients.Methods Serum creatinine(Scr)and 24h-urinary albumin excretion(24 h-UAE)were measured in 1576 hospitalized type 2 diabetes patients.MDRD equation was used to calculate the GFR(GFRMDRD).GFRMDRD<60 ml/min per 1.73m2 was defined as"renal insufficiency"RemlIs(1)Of the 1576 subjects,908(57.6%),503(31.9%),and 165(10.5%)had GFRMDRD≥90,90-60,and<60 ml/min per 1.73 m2 respectively.The prevalence of"renal insufficiency"was increased with aging(P<0.01).(2)The prevalence rates of"renal insufficiency"of the normo-,micro-,and macroalbuminuric groups were 4.8%,14.4%,and 43.4%respectively,with significant differences among them(all P<0.01).(3)Of the 165 subjects with"renal insufficiency",21(12.7%)had neither abnormal Scr nor abnormoalbuminuria.Conclusion Able to discover renal insufficiency early.MDRD equation has important clinical significance in evaluating the progression of renal dysfunction in type 2diabetes patients.

Objective To investigate the effect of intermittent hiigh shcese(IHG)on the pancreatic islet β-cell function and mechanism thereof.Methods Rat pancreatic islet β-cells of the line INS-1 were cultured and randomly divided into 3 groups:IHG group exposed to fluctuating concentrations of glucose,stable high glucose(SHG)group exposed to 16.7 mmoL/L glucose,and control group exposed to normal concentration(5.5 mmoL/L)glucose. 24,48,and 72 hours later radioimmunoassay wag used to detect the insulin secretion index(ISI).72 h later,the concentration of insulin in the cells wag detected with mdioimmunoassay.The contents of oxidative stress markers,nitrotyrosine(NT)and 8-hydroxy-2-deoxyguanosine(8-OHdG)were detected.Real-time PCR wag used to detect the mRNA expression of pemxiredoxin 1(PDX-1),ATF-4,one of the transcription factors of the family bZIP,and insulin.Western blotting wag used to detect the protein expression of ATF-4.Results The ISI of the IHG and SHG groups decreased time-dependently.The ISI of IHG and SHG groups were 0.64±0.1l and 1.31±0.04 respectively,both significantly lower than that of the control group(1.67±0.23,both P<0.05).The intracellularinsulin contents of the IHG and SHG groupswere(10.91±0.14)and(11.08±O.03)μU/μg respectively,both significantly lower than that of the control group[(12.37±0.37)μU/μg,both P<O.05].The intracellular concentrations of 8-OHdG and NT of the SHG and IHG groups,were significandy higher than those of the control group(all P<0.01),and those of the IHG group were significantly higher than tIlose of the SHG group(both P<0.05).The mRNA and protein expression levels of ATF-4 of the IHG group were all significantly higher than those of the control group(all P<O.05)and those of the IHG group were significantly higher than those of the SHG group(both P<0.05).Condusion IHG and SHG induce severe impairment in pancreatic islet β cell functions,especially IHG,which is closely associated with the aggravation of oxidative stress and endoplasmic reticulum stress triggered by intermittent high glucose.

Objective To explore the effects of xemderma pigmentosum group D(XPD)/P44 subcomplex on the cell cycle of the hepatoma cells.Methods Human hematoma cells of the line SMMC7721 were cultured and transfected with human XPD gene by LipofectAMINE and 2 strains with stably transfected plasmid pEGFG-N2 and stably transfected recombinant plasmid pEGFG-N2/XPD were selected.After stably transfection,the antisense oligonucleotides of P44 were added to treat the stably transfected cells.The cells were divided into 6 groups:Group①(control group),Group②transfected with the blank plasmid pEGFP-N2,Group③transfected with the recombinant plasmid pEGFP-N2/XPD,Group④transfected with ASODN complementary to the translation initiation site of pEGFP-N2/XPD,Group⑤transfected with antisense oligodeoxynucleotides(ASODN)complementary to the translation terminal site of pEGFP-N2/XPD.and Group⑥transfected with ASODN complementary to the translation exon5 site of pEGFP-N2/XPD.The expression Ievels of wild-type P44,XPD,cdk7,cdk2,c-myc,and cdc25A were detected by RT-PCR and Westem blotting.The cell growth and the cell cycle were examined by MTT and flow cytometry(FCM)Results The P44 and XPD mRNA expression levels of Group③were significantly higher than those of Groups①and②(both P<0.01).Western blotting indicated that the changes of P44 and XPD protein expression levels were consistent with those of their mRNAs respectively:while the tuRNA and protein expression levels of cdk7,cdk2,c-myc,and cdc25A were all decreased.MTT method showed that the hepatoma cells grew slowly,FCM showed that the number of the cells arrested at the G1 stage of Group③were higher than those of Groups①and②.After the blockage of P44 gene expression,the expression levels of XPD mRNA and protein were decreased.The XPD mRNA and protein expression levels of Groups④,⑤,and⑥were significantly higher than those of Group③(all P<0.01).The mRNA and protein expression levels of cdk7,cdk2.c-myc,and cdc25A were upregulated.MTY method indicated that ceils grew fast.FCM showed that the nulnbers of the cells arrested at the G1 stage of Group④,⑤,and⑥were all lower than that of Group③.The expression levels of cell cycle regulatory genes including cdk7,cdk,c-myc,and cdc25A were markedly decreased,the hepatoma cells grew slowly;after the blockage of P44 gene expression the expression levels of XPD mRNA and protein were decreased.whereas the expression levels of the cell cycle regulatory genes mentioned above were enhanced.and the hepatoma cells grew faster.Conclusion XPD gene inhibits the proliferation and promotes the apoptosis of hepatoma ceils.The expression of XPD may be regulated by its molecular partner P44.XPD/P44 subcomplex iB involvod in the regulation of DNA damage checkpoint.

Objective To investigate the regulation of receptor activator of nuclear factor κB ligand (RANKL)and osteoprotegerin(OPG)mRNA expression by prostaglandin E2(PGE2)in osteoblastic-like cells and involved signaling pathways.Methods Rat UMR106 osteoblast-like cells were cultured and treated with various dose of PGE2 or regulators of difierent signaling pathways such as protein kinase A,protein kinase C,ERK-MAPK and calcium/calmodulin pathways for difierent period of time,the cells were then harvested at indicated time points.total RNA were isolated and RANKL/OPG mRNA expression were studied by real-time PcR.Results PGE2,Forskolin and db-cAMP increased RANKL mRNA by 2.8 times (P=0.002),2.2 times(P=0.006)and 2.1 times(P=0.005)respectively.and inhibited OPG mRNA expression by12%(P<0.01),85%(P=0.005)and 70%(P=0.013)respectively.while RANKL and OPG mRNA expression were down.regulated by A23187 bv 58%(P=0.002)and 53%(P=0.017)respectively.As for inhibitory experiments.the stimulatory eriects of PGE2 on RANKL mRNA expression could be inhibited only by KT-5720 by 53%(P<0.01).while the other inhibitors did not have any effect at all.The inhibitory effects of PGE2 on OPG mRNA expression were partially blocked by KT-5720 by 47%(P=0.01),verapamil by 38%(P=0.029)and W7 bv 43%(P<0.01)respectively,while KN-62.ehelerythrine and PD98059 had no effects.Conclusion PGE,can up-regulate the expression of RANKL but down-regulate the expression of OPG.The up-regulation of RANKL mRNA expression by PGE2 was mediated through the activation of PKA signaling pathway while PGE2 induced down-regulation of OPG mRNA expression was predominantly mediated via PKA as well as the Ca2+/Calmodulin signaling pathways.

The patient was a 72-year-old female with alternating distension and pain in both lower limbs for 2 months and sudden disturbance of consciousness for 2 h. She was admitted to the hospital on February 28, 2002. Skull CT showed "acute massive left cerebral infarction" (Figure 1). She was admitted to the neurology department. She had no similar medical history in the past, and had a history of hypertension, erysipelas of lower limbs and senile purpura for more than 10 years, and a history of drug-induced purpura for more than 2 months. Physical examination on admission: blood pressure 160/90 mm Hg (1 mm Hg =0.133 kPa), Glasgow score 9 points, soft neck, reduced muscle strength of right upper and lower limbs, purpura of both lower limbs, rough skin and red and swollen superficial veins of right lower limb.

Objective To prepare gemcitabine-loaded nanovesicles and to observe its morphology,structure,particle size,and drug-release performance in vitro.Methods Diemulsion technique was used to prepare nanovesicles as carrier from amphiphilic block copolymer of poly(ethylene glycol)-block-poly(D,L-lactide),and gemcitabine was used as the model drug.The morphology of vesicles was determined by scanning electron microscope(SEM)and transmission electron microscope(TEM),and its drug loading (DL),encapsulation ratio(ER),and drug-release curve in vitro were detected by UV-Vis-NIR Spectmphotometer.Results The Gemcitabine-loaded nanovesicles is a kind of hollow nanosphere with the mean size of 200.6 am.DL of 4.14%and ER of 20.54%.The nanovesicles showed its excellent controlled-release characteristic in the experiment of dmg release in vitro.Conclusion The nanovesieles prepared from PEG-PDLLA can be served as one of carriers for Gemcitabine with good performance of drug controlled-release.It will provide a reliable experimental base for the further researches in vivo.

Homocysteine is highly correlated with Cardiovascular events, and supplementation with folic Acid, vitamins B6 and B12 can reduce homocysteine levels. However, whether folic Acid and/or B vitamins can prevent the occurrence of Cardiovascular disease (CVD) has been controversial in academic circles. Existing data show that low homocysteine levels may benefit more significantly in Women than in men, but there is still a lack of large-scale randomized, double-blind, placebo-controlled trials in Women. Therefore, Birmingham Women's Hospital affiliated to Harvard Medical School conducted a Study on Women's Antioxidant and Folio Acid Cardiovascular Study (WAFACS), whose results were published in May 2008<In the Journal of the American Medical Association (JAMA, 2008, 299:2086-2087).

Condyloma acuminatum is a common sexually transmitted disease caused by human papillomavirus (HPV). Due to the lack of specific and highly effective anti-HPV drugs at present, the common clinical therapies such as laser, freezing, electrocautery, microwave and other physical therapies, local drug therapy and surgical therapy can only remove the warts visible by naked eye, but have no effect on the subclinical infection and latent state of. HPV. How to solve the subclinical infection and latent infection of HPV and reduce the recurrence rate of condyloma acuminatum is a problem that scholars pay attention to. In recent years, local 5-aminoketovaleric acid photodynamic therapy (ALA-PDT) has been used to treat condyloma acuminatum, which has attracted more and more attention.

In order to ensure the scientificity and validity of clinical trials, randomized, double-blind and placebo-controlled methods are usually adopted and regarded as standard methods. Because the subjects of clinical trials are humans rather than animals, and the essence of placebo effect is to achieve certain effects through substances without direct pharmacological action or changing the atmosphere in the course of treatment, how to realize the scientificity of the trials as much as possible on the premise of ensuring the rights and interests of subjects has been a widely concerned and controversial issue for a long time.

Department of General Surgery, General Hospital of the People's Liberation Army, Beijing, General Surgery Center of the Army, Institute of General Surgery, General Hospital of the People's Liberation Army, Chinese Medical Association<The 2008 Gastrointestinal Cancer Surgery Summit Forum, co-sponsored by the editorial committee of Chinese medical journal and Beijing Cancer Hospital of Peking University, was held in Beijing from April 25 to 27, 2008. Nearly 700 experts from all over the country attended the meeting. The meeting was chaired by Professor Li Rong of General Surgery of Beijing People's Liberation Army General Hospital and Professor Ji Jiafu of Beijing Cancer Hospital of Peking University.