The human immunodeficiency virus type 1(HIV-1)can interact with and exploit the host cellular machinery to replicate and propagate itself.Numerous studies have shown that the Mitogen-activated protein kinase(MAPK)signal pathway can positively regulate the replication of HIV-1,but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood.In this study,we used the Extracellular signal-regulated kinase(ERK)pathway inhibitor,PD98059,the Jun N-terminal kinase(JNK)pathway inhibitor,SP600125,and the p38 pathway inhibitor,SB203580,to investigate the roles of these pathways in HIV-1replication.We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity.In addition,SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity.We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059when cells were treated with all three MAPK pathway inhibitors in combination.Finally,we show that HIV-1virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.

Objective To explore protein expression and significance of MAGE genes in colorectal carcinoma(CRC)tissues.Methods The expression of MAGE genes were studied by using tissue chip and immunochemistry methods in primary CRC tissue and paired adjacent tissue samples in 97 cases.Data were analyzed with x2-test by SPSS 16.0 software.Results The protein expression of MAGE-A3,MAGE-A4 and MAGE-A10 genes were 57％(56/97),63％(61/97)and 28％(27/97)respectively in 97 cases of primary adenocarcinoma.The protein expression frequency of MAGE-A3 in poor colorectal adenocarcinomas was significantly higher than in well-and moderately disfferentiated adenocarcinomas(x2 =9.133,P =0.010).MAGE-A10 in poor colorectal primary adenocarcinomas was significantly higher than in well and moderately adenocarcinomas(x2 =15.280,P =0.000); MAGE-A10 protein expression was significantly higher in stage TNM Ⅲ + Ⅳ than in stage TNM Ⅰ + Ⅱ(x2 =4.227,P=0.040); MAGE-A10 gene expression was higher in metastasis lymphoid node than in no metastasis lymphoid node(x2 =5.557,P =0.018),and the expression level was higher in primary lesion with the increasing of the numbers of lymphoid node metastasis(x2 =7.296,P =0.026).Conclusions The protein expression of MAGE genes is associated with the tumor differentiation,TNM stage and lymphoid node metastasis.MAGE-A3 and MAGE-A10 genes are the possible prognosis marker and potential target of immunotherapy of CRC.

Objective:To establish a pristine-induced rheumatoid arthritis model in mice,and to evaluate its histological and immunological distinction.Methods:Thirty female BALB/c mice,6-8 weeks old,were randomly divided into 2 groups,a control group and pristine group.The mice in pristine group were injected intraperitoneally with 0.5 ml pristine three times at 0,9,and 18 weeks, while mice in the control group receiving saline at the same time.Arthritis score and paw thickness were measured and histopathological assessment of joint sections was performed.The expression of phagocytes,dendritic,neutrophils,T and B cells markers in spleen were determined by flow cytometry.Results:In model-marking group,11 mice were presented with macroscopic evidence of arthritis such as erythema or swelling.The paw thickness in pristine-induced mice was significant higher than that in the control groups[(2.90±0.51) mm vs(1.29±0.47 mm),P<0.05].In addition,arthritis score in pristine-induced mice was 9.55±2.80 at 21 weeks after first injection with 0.5 ml pristine.H&E staining revealed a significant increase of synovial inflammation, cartilage and bone destruction after stimulated with pristine.Meanwhile,the expression levels of CD11b,CD11c,GR1,CD4,CD8 and CD154 were obviously increased in model-marking group when compared with that in control group.Conclusion: The pristine-induced model presents the similar histological and immunological distinctions with human rheumatism arthritis,which can mimic the pathogenesis of rheumatism arthritis.

s:The partical coding sequence of E2 gene of 13 Hog Cholera Virus(HCV) field isolates, Shimen strain, Chinese vaccine strain(C strain) and Thiverval strain attenuated by low temperature in France,were obtained by reverse trancriptase -polymerse chain reation (RT-PCR) and sequenced.All size were 251bp.The obtained 224bp sequences were analysed by DNA star and compared with the previously published sequences of Alfort strain ,Brescia strain and other references strains.The results showed that those sequencing fragments of 13 HCV field strains were the sequence of E2 gene of HCV.Compared with Shimen strain,the base substitute of all stains were randomly distributed in the entire sequence,and had not base insert and base gap.The variation most occurred at 3' end. The identity of nucleotide sequence and amino acid sequenceof 22 HCV strains were 78.1%～100%?78.4%～100%. The identity of nucleotide sequence and amino acid sequence of 13 HCV field strains were 78.1%～100%?78.4%～100%.The identity of nucleotide sequence and amino acid sequence of 4 HCV field strains isolated in the 1970s～1980s were 79.0%～88.3%?81.1%～87.8%.The identity of nucleotide sequence and amino acid sequence of 9 HCV field strains isolated in the 1990s were 80.8%～100%?83.8%～100% respectively. This paper showed that the genetic variation of HCV was diversity.

Objective:On the basis of the use of chemical methods to establish mouse model of lupus nephritis and its biological identification , we investigate the reverse effect of pathological lesions of B 7-1 human-mouse chimeric antibody blockade against B7/D28 signaling pathway in mice with lupus nephritis model.Methods:Pristane was injected intraperitoneally to 6-week-old female C57BL/6J mice at dose of 0.5 ml per mouse in one go,and urine protein,ANA and renal pathological changes were detected on a monthly basis.Mice whose urine protein content reached ++and ANA fluorescence intensity reached ++were randomly devided into three groups ,five each.Antibody intervention group was sequentially injected with B 7-1-mouse chimeric antibody by orbital venous , positive control group was injected with immunosuppressant CTX , negative control group was injected with isotype control IgG.Urine protein and ANA were also detected on a monthly basis.Mice were sacrificed three months after intervention was executed.Kidney was used for H&E dying , IC detection and electric microscope observation.Results: After four-month Pristane induction , urine protein content of 80%mice reached +-+++,meanwhile,serum ANA fluorescence intensity reached ++-+++.Glomerulonephritis infiltrating cells were observed Mice with urine protein and ANA , glomerular inflammatory cell infiltration , tubular epithelial cell degeneration visible edema ,vascular congestion significantly ,fibrosis.After antibody intervention ,urine protein content in antibody intervention group gradually reduced from ++-+++to ±-+++,ANA ++-+++to +-++,and were significantly different from that in the negative control group ( P<0.01 ).Analysis of kidney H&E dying showed that antibody glomerular infiltration of inflammatory cells in the intervention group and tubular congestion and other symptoms were improved significantly.Immunofluorescence staining indicated that fluorescence intensity of IC was significantly reduced in the antibody intervention group.Electron dense deposits reduction and glomerular basement membrane uniformity were observed in antibody intervention group by electric microscope when compared with the negative control group.Conclusion:B7-1 antibodies could downregulate immune response through inhibiting B 7-1/CD28 signaling pathway , reducing the production of autoantibodies and reversing pathological damage caused by autoimmune response .

Objective To estimate the cancer incidence and mortality in Chongqing in 2014.Methods On basis of the methods and criteria of data quality control made by NCCR,authors compiled and summarized the 2014 tumor registration data reported by 11 registries in Chongqing.The datas which were stratified by area (urban/rural),gender,age and cancer type,incidence and mortality were calculated combined with national population.Results All 11 cancer registries reported 24 506 new cancer cases (14 610 were male and 9 896 were female)in 2014.The crude incidence in Chongqing was 244.66/105 (male was 289.01/105,female was 199.47/105).Sex ratio was 1.45:1.00,male was significantly higher than female.The incidence of lung cancer,colorectum,liver,esophagus,breast,stomach were the top six tumor.The incidence rate of all age groups in 2014 increased with age,the incidence rate increased from 40-44 years old group,and reached the highest incidence rate in the 80-84 years old group.Conclusion The data quality and representativeness in Chongqing tumor registration are gradually improved.Cancer registration as the basis of cancer prevention and control work,play an irreplaceable role.

OBJECTIVETo evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery for treating gastric gastrointestinal stromal tumors(GIST).

METHODSRetrospective analysis was performed on the clinical data of 46 patients with gastric GIST undergoing laparoscopic and endoscopic cooperative surgery between June 2009 and June 2011 at the Renji Hospital of Shanghai Jiaotong University School of Medicine.

RESULTSThere were 27 males and 19 females with the mean age of 58.5 years. Thirty-three patients received endoscopy-assisted wedge resection, and 13 cases received laparoscopy-assisted endoscopic resection. All the operations were successful. The mean operative time was (85.5±29.3) min, the mean blood loss was (31.4±12.2) ml, the mean post-operative gastrointestinal functional recovery time was (31.6±14.9) h, and the mean post-operative hospital stay was (5.1±2.9) d. No post-operative complication occurred. NIH risk assessment showed that 34 cases were very low risk and 12 low risk. No recurrence or metastasis was found during the follow-up ranging from 2 to 26 months(median, 12.6 months).

CONCLUSIONLaparoscopic and endoscopic cooperative surgery for gastric GIST is both feasible and safe with minimal invasiveness, fast recovery and satisfactory short-term outcomes.

Adult ; Aged ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; surgery ; Gastroscopy ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Treatment Outcome

OBJECTIVETo explore the role of phospholipase C-gamma1 (PLC-gamma1) signaling pathway in H(2)O(2)-induced apoptosis of PC12 cells.

METHODSPC12 cells were exposed to 50 micromol/L H(2)O(2) after pretreatment with 10 micromol/L U73122, a specific PLC-gamma1 inhibitor. Hoechst/PI double staining was performed to observe the morphological changes of the cells under light microscope. MTT assay was used to evaluate the cell viability, and the percentage of apoptotic cells was analyzed by flow cytometry. DNA fragmentation assay was carried out to characterize the cell apoptosis.

RESULTSAfter inhibition of the PLC-gamma1 signaling pathway with 10 micromol/L U73122, PC12 cells showed obvious apoptotic morphology, the viable cells decreased significantly, and the percentage of apoptotic cells rose to 35.7%. PC12 cells treated with U73122 presented with a distinct DNA ladder on electrophoresis resulting from DNA cleavage in the apoptotic cells.

CONCLUSIONPLC-gamma1 signaling pathway plays an important protective role in H(2)O(2)-induced PC12 cell apoptosis.

Animals ; Apoptosis ; drug effects ; Estrenes ; pharmacology ; Hydrogen Peroxide ; pharmacology ; PC12 Cells ; Phospholipase C gamma ; antagonists & inhibitors ; metabolism ; Pyrrolidinones ; pharmacology ; Rats ; Signal Transduction

OBJECTIVETo perform the genetic identification of cloche(172) mutant zebrafish.

METHODSThe chemical mutagen N-ethyl-N-nitrosourea (ENU) was used to treat the AB stain male fish. Large-scale forward genetic screening was carried out to search for lyC-deficient zebrafish mutant by WISH. The morphology changes of the embryos at 3 days postfertilization (3dpf) stage were observed and the cloche(172) gene was identified by mapping and complementation test.

RESULTSWe selected 4 lyC-deficient zebrafish by WISH. cloche(172) mutant showed morphological changes similar to cloche mutant in 3dpf stage. One fourth of the embryos showed cloche phenotype as found in complementation test, and the cloche(172) gene was mapped on the telomere of zebrafish 13 chromosome where cloche gene was located. Numerous red blood cells were observed in the cloche(172) mutant, while only a few cells were found in the cloche mutant in the tail region by o-dianisdine staining.

CONCLUSIONcloche(172) gene which is responsible for the phenotype of cloche mutant may be a novel point mutation allele of the cloche mutant.

Alleles ; Animals ; Chromosome Mapping ; Cloning, Molecular ; Embryo, Nonmammalian ; embryology ; metabolism ; Ethylnitrosourea ; toxicity ; Genetic Complementation Test ; Male ; Muramidase ; genetics ; Mutation ; Zebrafish ; embryology ; genetics ; Zebrafish Proteins ; genetics

OBJECTIVETo explore the clinicopathologic features, treatment and prognosis of gastrointestinal stromal tumor (GIST) complicated with synchronous other alimentary malignant tumors.

METHODSClinical data of 525 patients with GIST undergoing surgical treatment from August 2004 to November 2012 in Shanghai Renji Hospital were reviewed retrospectively, among whom 46 patients presented synchronous other alimentary malignancy.

RESULTSGIST and other alimentary malignancy coexisting cases were less likely to be screened out preoperatively (2.2%, 1/46) and associated with elder age (P=0.001), more likely arise from stomach (P=0.000), smaller tumor maximum diameter (P=0.000), and lower mitotic count (P=0.000). According to NIH postoperative risk classification, there were 36 at very low risk, 9 at low risk, and 1 at high risk. Although the risk of GIST recurrence was lower for GIST and other alimentary malignancy coexisting cases, their 5-year survival rate was lower than that of patients with GIST alone (36.1%VS. 82.2%, P=0.000).

CONCLUSIONSGIST patients complicated with synchronous alimentary malignant tumor are usually low or very low risk and has minimal impact on the prognosis. Survival depends primarily on the synchronous alimentary malignant tumors. Therefore, it is reasonable to lay emphasis on the treatment of the alimentary malignant tumor, and perform synchronous resection of GIST if possible.

Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms ; diagnosis ; pathology ; therapy ; Gastrointestinal Stromal Tumors ; diagnosis ; pathology ; therapy ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies