Objective To discuss the effect of 5-Aza-CdR on pancreatic carcinoma Capan-2 cell proliferation and PCDH8 gene expression.Methods Pancreatic carcinoma Capan-2 cells were treated with different doses of 5-Aza-CdR with or without gemcitabine,negative control group without drug,0.08μmol/L group with 0.08μmol/L 5-Aza-CdR,0.40 μmol/L group with 0.40 μmol/L 5-Aza-CdR,2.00 μmol/L group with 2.00 μmol/L 5-Aza-CdR,10 μmol/L group with 10 μmol/L 5-Aza-CdR,50 μmol/L group with 50 μmol/L 5-Aza-CdR. The inhibition ratio of Capan-2 cell proliferation were observed by MTT assay and PCDH8 gene and protein expression were detected by RT-PCR and Western blot. Results The inhibition ratio was increased with 5-Aza-CdR dose increasing(P<0.01),but decreased apparently with times extending(P<0.01). Inhibition ratio in 5-Aza-CdR and gemcitabine group was higher than those with only 5-Aza-CdR or gemcitabine groups(P<0.05 or P<0.01).The levels of PCDH8 gene and protein expression were increased significantly in 5-Aza-CdR treatment groups,with dose dependent (P <0.01 ).Conclusion 5-Aza-CdR can inhibit the proliferation of pancreatic carcinoma Capan-2 cell proliferation,and increase PCDH8 gene expression. The inhibition effect is strong when combined with gemcitabine.

Objective To develop an intermittent type treatment instrument for cervical vertebra.Methods Biomechanics,human body engineering and electronics technique were used.It could heat and lead in the intermittent type.The control electric circuit was composed by 555 IC.Results The product had a good therapeutic effect for cervical vertebra disease.It could alleviate some bad symptoms.Conclusion The intermittent type treatment instrument for cervical vertebra has better treatment effect.It is more desirable to add the function of heating except for pulling.

Objective To investigate the effects of 17?-estradiol (E2) on the gene expression of typeⅠA bone morphogenetic protein receptor (BMPR-ⅠA) and core-binding factor alpha 1 (Cbf?1) in rat bone marrow stromal cells exposed to the differentiation medium and to elucidate the effects of E2 on osteoblastogenesis. Methods Adherent bone marrow stromal cells were cultured in differentiation medium containing DEX (10 -7 mol/L), 1,25-(OH)2D3 (10 -9 mol/L) and different concentrations of E2. Effects of different concentrations of E2 on the gene expression of BMPR-ⅠA and Cbf?1 was quantified by RT-PCR based on the comparison with an internal reference, ?-actin expression, and identified by Northern blotting. Alkaline phosphatase (ALP) activity of cells was detected. Contents of type Ⅰ collagen were determined by Van Gieson staining. Results E2 could evidently inhibit the expression of BMPR-ⅠA and Cbf?1 mRNA during the differentiation process of bone marrow stromal cells into osteoblasts in a dose-dependent manner. These were confirmed by Northern blotting. The ALP activity increased in a concentration-dependent manner, but the amount of type Ⅰ collagen decreased in a concentration-dependent manner. Conclusion E2 can significantly inhibit the gene expression of BMPR-ⅠA and Cbf?1 in bone marrow stromal cells and inhibit osteoblastogenesis in vitro.

Objective To assess the effect of PRISMA statement on intervention-related systematic reviews and meta-analyses published in Evidence-based medicine .Methods Intervention-related systematic reviews and meta-analyses published in Evidence-based medicine from 2001 to 2011 were assessed according to the PRISMA scale and analyzed by Meta Analysist software.Results Seventy intervention-related systematic reviews and meta-analyses involving 14-disease spectra were included in this study.PRISMA statement and systematic reviews and meta-analysespublished by au-thors in colleges and universities could improve their academic level (P<0.05), fund support and the number of authors showed no significant effect on their academic level.Conclusion Literature retrieval methods,literature screening methods,bias assessment methods, and other analyzing methods used systematic reviews and meta-analyses published in Evidence-based medicine and their academic level can be improved by PRISMA statement.

Chimeric antigen receptor T-cell (CAR-T) immunotherapy has made a breakthrough in the clinical treatment of a variety of hematological tumors.However, the CAR-T cell products listed at China and abroad are all autologous CAR-T.Compared with autologous CAR-T treatment, universal CAR-T exhibits significant advantages, which could fulfill the treatment demand of more patients, but also displays high technical barriers.This paper reviews the universal CAR-T, clearly points out the two major challenges faced by the development of universal CAR-T, and then summarizes and analyzes the feasible solutions according to the mechanism causing the two major problems.This paper also summarizes domestic and foreign companies producing universal CAR-T and the latest clinical progress of their superior products, and then discusses the feasibility of the development strategy from another aspect, in order to provide ideas for developing a new generation of universal CAR-T cell therapy products.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.