This paper described the existing problems of transformation benefit from a target,two ideas,three questions,four reasons,and five measures.Through establishing clear objectives,combing the status of the achievement trasformation some problems were raised.Also,it Was analyzed for the reasons of deficient transformation benefit and suggested the taken measures.

OBJECTIVETo investigate the effects of arsenic trioxide (As(2)O(3)) on the apoptosis and p-glycoprotein (P-gp) expression of multidrug-resistant human leukemia cells.

METHODSHuman multidrug-resistant leukemia cell line K562/ADM overexpressing the MDR1 gene, was used as the target cells. The cell proliferating activity was assessed using the MTT colorimetric assay. Cytomorphology was investigated under light, confocal and electron microscopes. DNA fragmentation was examined using agarose gel electrophoresis, while p-gp expression, cell cycle status and sub-G1 cells were determined using flow cytometry.

RESULTSZero point five to 20 micromol/L As(2)O(3) inhibited the proliferation of K562/ADM cells, and K562/ADM cells were more sensitive to As(2)O(3) than the parental K562 cells. As(2)O(3)-induced apoptosis of K562/ADM cells was determined by the observance of typical morphological changes and the appearance of DNA ladder and sub-G1 cell populations. As(2)O(3) significantly inhibited the P-gp expression of K562/ADM cells, and synergistically enhanced the sensitivity of the drug-resistant cells to adriamycin.

CONCLUSIONSAs(2)O(3) induces growth-inhibition and apoptosis, down-regulates P-gp expression and exerts a synergistic effect in combination with adriamycin in multidrug-resistant leukemia cells.

ATP-Binding Cassette, Sub-Family B, Member 1 ; analysis ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Drug Resistance, Multiple ; Gene Expression ; Genes, MDR ; Humans ; Leukemia ; genetics ; metabolism ; Oxides ; pharmacology

Objective To fabricate an antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface,and to investigate its surface characteristics,swelling behavior,drug release behavior in vitro,antiinfection performance in vivo,and tissue biocompatibility.Methods Cross-linked starch (CSt) was synthesized first and then CSt was loaded with gentamicin (GEN) as a carrier (GEN@CSt),then 4-arm-polyethylene glycol (PEG) was added to it which was mixed by ultrasound.The surface of titanium (Ti) was covered with a layer of poly dopamine (PDA).The drug-loaded hydrogel was fixed to the titanium surface,subsequently capped by poly lactic-co-glycolic acid (PLGA) membranes,and then the Ti-PDA-PEG (GEN@CSt)-PLGA composite coating was fabricated finally.Surface morphology of the system was observed,while the swelling behavior was characterized;release behavior of the composite coating was detected;the bacteriostatic experiments were carried out with staphylococcus aureus (SAU),staphylococcus epidermidis (SEP) and escherichia coli (ECO) in vitro.The animal models of infected bone defect was established in 36 New Zealand white rabbits.These animals were randomly divided into three groups.Group 1 animals were implanted with drug-loaded composite coatings.Group 2 animals were implanted with drug-free composite coatings.Group 3 animals were implanted with bare titanium rods.The infection data were collected periodically to carry out antiinfection experiments in vivo.Another 12 rabbits were divided into the experimental group and the control group randomly.Biocompatibility of the materials was observed by histopathology after implantation of the corresponding materials into the femoral condyle.Results The composite coating adhered to the titanium surface firmly,presenting a smooth and translucent shape.The ratio of CSt/PEG affects swelling behavior varied,starch-free gels maintained an equilibrium swelling of 7.4,after the ratio reached 1 ∶ 1,the equilibrium swelling ratio remained at 3.0.In-vitro the release rate of the first 8 h was fast,and the cumulative release amount accounted for 83％ of the total in the first 7 days,lasting more than 13 d.In vitro antibacterial test,the average diameter of the inhibition ring was 3.6±0.13 cm (SAU),3.4±0.11 cm (SEP),3.7±0.10 cm (ECO).In-vivo anti-infection experiment,the infection situation of the group 1 was better than the control groups 2 and 3.The pathological results indicated that inflammatory reaction in the experimental group was basically the same as the control group.Conclusion The study successfully fabricated the antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface.The system has a reasonable drug release behavior,and effectively inhibited the growth of bacteria in vivo and in vitro.It also has good biocompatibility to stand a promising strategy to improve the orthopedics anti-infection.