ObjectiveTo investigate the clinical efficiency of oral warfarin after cardiac valve replacement and the influence of vitamin K epoxide reductase complex subunit 1(VKORC1) gene polymorphisms on warfarin maintenance dose.MethodsOne hundred and fifty-nine patients who got cardiac valve replacement surgery were chosen and received anticoagulation therapy by oral warfarin.The prothrombin time (PT),international normalized ratio (INR) of patients were recorded and the safety ranges of PT and INR were calculated statistically.VKORC1 gene polymorphism of patients weredetected by PCR-PFLP technology by adjusting the dose of warfarin,and the results were compared.ResultsThe safety monitoring range of PT of oral warfarin after cardiac valve replacement surgery was 15.36 -24.82 s,safety monitoring range of INR was 1.33 - 2.62.The occurrence rate of bleeding during anticoagulation was 13.21％(21/159).The weekly dose of warfarin of VKORC1 gene type AA [(24.28 ± 10.79) mg] was significantly higher than that of VKORC1 gene type GA[ ( 16.64 ± 7.43 ) mg] and type GG[ ( 12.12 ± 7.17 ) mg](P＜ 0.05or ＜0.01 ).ConclusionsThe polymorphism of VKORC1 gene is the dominant factor of the differences of warfarin maintenance dose.The warfarin dose in patients with different gene type is different.The clinical safety monitoring ranges of PT and INR in patients with oral warfarin after cardiac valve replacement are lower than the recommended ranges of European and American countries.Therefore,the index of patients after surgery should be detected regularly.

Objective:To explore the imaging manifestation of elastofibroma dorsi in18F-FDG PET-CT.Methods: The back soft tissue mass of abnormal metabolism was found by18F-FDG PET-CT scan, and then delayed imaging for the mass was performed.Results: Surgical pathology confirmed it was elastofibroma. The tumor showed clear boundary, there was no damage to adjacent ribs, and this method was mild radioactivity uptake, besides, metabolism was decreased at delayed imaging in18F-FDG PET-CT; the patient had no correlated clinical symptomatic and apparent positive physical signs.Conclusion: Tumor detection rate of18F-FDG PET-CT for elastofibroma dorsi is higher than normal CT detection. And the delayed manifestation for metabolism were decrease. Therefore, these situation accordance to benign tumor metabolism changes.

Objective To explore the clinical effect of small cell lung cancer(SCLC) treatment with recombinant human endostatin injection and cis-platinum complexes.Methods 100 patients with SCLC were divided into 2groups.The experiment group used cis-platinum complexes while the control group used recombinant human endostatin injection.Results The effective rate of experiment group was obviously higher than the control group ( 74.0％ vs60.0％,x2=2.16,P ＜ 0.05 ).The median survival time of experiment group was better than control group( t=2.02,P ＜ 0.05 ).The diverse of untoward effect of two groups had no difference ( P ＞ 0.05).Conclusion Recombinant human endostatin injection and cis-platinum complexes were better therapy for SCLC,which had stable effect,no severe untoward effect and overcome the drug-fast of cis-platinum complexes.

BACKGROUND: For decades, liposome drug carrier has been used to enhance drug stability and efficacy, reduce drug toxicity and adverse effects. However, they fail to provide long-term delivery due to insufficient stability. Studies have demonstrated that silica is not toxic, with chemically inert and biological compatibility, and can be used as modified material. OBJECTIVE: To characterize the silica coated liposome and investigate the controlled release property. DESIGN, TIME AND SETTING: In vitro observation. The study was performed at the Nanomedicine and Biosensor Laboratory, Biomedical Engineering Center, Harbin Institute of Technology from May 2007 to June 2008. MATERIALS: Dipalmitoylphosphatidylcholine (DPPC) was purchased from Nanjing Kangsente Chemical Engineering Company; tetraethylorthosilicate (TEOS) was purchased from Aldrich, USA. Doxorubicin (DOX) was purchased from Beijing Huafeng United Technology Company; Sephadex G-50 was purchased from Amersham Biosciences, Sweden. All other chemical agents were of analytical purity. METHODS: Liposome was formed from DPPC following the precipitation of silica by sol-gel method. MAIN OUTCOME MEASURES: Zeta-potential and dynamic light scanning were used for zeta-potential measurement and particle size distribution; transmission electron microscopy was used to collect the image of particle morphology; Fourier transform infrared spectroscopy (FTIR) was used to display chemical characteristics of Si-O-Si structure; Spectrophotofluorimetry was used to determine DOX regression equation and was further used for calculation in drug encapsulation efficiency and in vitro release.　RESULTS: ①Silica coated liposome was successfully prepared. ②FTIR proofed the presence of Si-O-Si at 1 166, 1 080, 859 and 526 cm-1. ③The DOX encapsulated silica coated liposome had encapsulation efficiency of 72.4%. ④Drug release profiles showed that sustained release of DOX was achieved after modification of silica on liposome. CONCLUSION: With Si-O-Si as protective layer, the liposome has increased stability and prolonged drug release.

BACKGROUND:Thrombus formation and neointimal hyperplasia still limit the use of small-caliber expanded poly(tetrafluoroethylene) (ePTFE) vascular prosthesis with a diameter less than 6 mm for revascularization in the coronary or peripheral circulation. Bioactive surface heparin coating is one conceivable path for above-mentioned problems.OBJECTIVE: To elevate the anticoagulant property of ePTFE, this study promoted the patency of a novel small-caliber ePTFE vascular graft by modifying its luminal surface with covalently crosslinked poly(vinyl alcohol)/ p-diazonium diphenyl amine polymer/heparin gel (PVA/PA/Hep gel) and examined the hemocompatibility of the graft.DESIGN, TIME AND SETTING: Observational experiments were performed at the Nanomedicine and Biosensor Lab,Biomedical Engineering Center, Harbin Institute of Technology from May 2006 to June 2007.MATERIALS: The ePTFE vascular grafts (diameter of 4 mm), Nafion (Naf) and Poly(vinyl alcohol) (Aldrich, USA), heparin (Mw 12 000- 14 000) (Calbiochem, USA), p-diazonium diphenyl amine polymer (PA) (this lab, China) were used in this study.METHODS: ①The vascular graft surface was firstly modified with Nafion. ②Following the impregnation of the mixture of PVA/PA/Hep, covalent crosslinking between polyvinyl alcohol and heparin was performed using crosslinker PA under ultraviolet radiation.MAIN OUTCOME MEASURES: ①Contact angles, ②Attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR), ③Activated partial thromboplastin time (APTT) and prothromhin time (PT), ④hemolysis test, ⑤platelet adhesion test and ⑥thrombosin inactivation test.RESULTS: ①The water contact angle of the vascular graft surface was greatly decreased after modifying. ATR-FTIR revealed the disappearance of diazonium groups at 2 172 cm-1 and 2 224 cm-1. Vascular prosthesis after modifying had prolonged APTT and PT, low percent hemolysis and low amount of platelet adhesion. Modified vascular prosthesis had inhibitory effect on thrombosin activity and good coating stability.CONCLUSION: Converage of PVA/PA/Hep has good antithrombotic function and low percent hemolysis, resulting in improving hemocompatibility of vascular prosthesis.

Objectives To study the expression patterns of steroid receptor coactivators (SRC) and steroid-induced stromal cell-derived factor-1 (SDF-1) in endometriosis,and to explore the roles of SRC in the steroid-induced SDF-1 expression endometriosis.Methods From May 2010 to October 2012,16 endometriosis cases at stages Ⅲ or Ⅳ according to the revised American Society for Reproductive Medicine classification undergoing surgery in the First Affiliated Hospital to Nanjing Medical University were enrolled in this study.Their ectopic endometrium were from ovarian endometriomata which were identified pathologically with 9 cases at proliferative phase and 7 cases at secretory phase.The normal endometrium were acquired from the healthy women with normal menstrual cycle (n =10,proliferative phase =5,secretory phase =5).The mnRNA levels of SRC and SDF-1α during the menstrual cycle were detected by quantitative real-time polymerase chain reaction.Ectopic endometrium stromal cells were purified and cultured in medium containing 17β-estradiol (10-8mol/L) or 17β-estradiol (10-8 mol/L) + progesterone (10-6 mol/L).At 24,48,72 and 96 hours,the supernatants were collected to measure SDF-1α expression by ELISA.Ectopic endometrium stromal cells were transfected respectively with siRNA of SRC-1 and SRC-2 using lipofectamine.Two days after transfection,17β-estradiol (10-8 moL/L) or 17β-estradiol (10-8 mol/L) + progesterone (10-6 mol/L) were added into the media.On the third day after the steroid hormones treatment,the media were collected to quantify SDF-1α expression with ELISA.Results (1) Cyclical changes: the SRC-1,SRC-2 and SDF-1 α showed marked cyclic differences in normal endometrium (P ＜ 0.05).In proliferative phase and secretory phase,the SRC-1,SRC-2 and SDF-1 α were 5.6 ± 1.2,3.8 ± 1.1,2.7 ± 0.5 and 2.6 ± 1.0,2.1 ± 1.0,1.6-± 0.5,respectively.There was no periodic variation in the expression of SRC-1,SRC-2 and SDF-1α in ectopic endometrium throughout the menstrual cycle.(2) Steroid-induced SDF-1α expression in ectopic endometrium stromal cells: the 17β-estradiol-induced SDF-1α expression was (1 803 ± 196),(2 272 ± 261) and (2 162 ± 258) ng/L at 48,72 and 96 hours.At the same time points,the SDF-1α expression induced by 17β-estradiol and progesterone was (1 307 ± 150),(1 518 ± 301) and (1 550 ± 144) ng/L,respectively.There was significant difference between two groups (P ＜0.05).(3) The effects of SRC silencing on steroid hormones-induced SDF-1 α expression in ectopic endometrium stromal cells: the expression of 17β-estradiol-induced SDF-1α at 72 hours was significantly decreased from (2 313 ± 357) ng/L to (1 155 ± 244) ng/L after the silencing of SRC-1 (P ＜ 0.05).After the silencing of SRC-2,the 17β-estradiol-induced SDF-1 α at 72 hours was (1 958 ±324) ng/L.There was no significant difference compared with the before the silencing (P ＞ 0.05).The expression of SDF-1 α at 72 hours induced by 17β-estradiol + progesterone was (1 534 ± 449) ng/L and (2 051 ± 380) ng/L respectively before and after the silencing of SRC-2 and showed the significant difference (P ＜ 0.05).Conclusion During the expression of SDF-1 α regulated by steroids in ectopic endometrium cells,SRC-1 is the major coactivator of 17β-estradiol and SRC-2 is the major coactivator of progesterone.

Objective To study the effect of rimonabant, cannabinoid receptor 1(CB1) antagonist, on the expressions of CB1 andα-smooth muscle actin (α-SMA) in C57 mice with experimental hepatic fibrosis, and their mechanisms in liver fibrosis progression thereof. Methods Thirty C57 mice were randomly divided into three groups, normal control group, mod-el control group and model+rimonabant group, 10 mice for each group. The mouse model of experimental hepatic fibrosis was induced by intraperitoneal injection with 10%CCl4 for two weeks. The normal saline was delivered by gavage daily in normal control group and model control group. Rimonabant was given to mice in model+rimonabant group. Mice were sacri-ficed at the end of eight weeks. Samples of liver tissue were collected. The expressions of CB1 andα-SMA in liver tissue of mice were observed by immunohistochemical staining. The score of fibrosis stage (S) in liver tissue was also analyzed. Re-sults The positive expressions of CB1 andα-SMA and the score S were significantly higher in model control group and model+rimonabant group than those in normal control group (P<0.05). The positive expressions of CB1 andα-SMA and the score S were significantly lower in rimonabant group than those in model control group (P<0.05). There were positive corre-lations in CB1,α-SMA and S scores between normal control group, model control group and model+rimonabant group (P<0.05). Conclusion The activation of CB1 can promote the formation of liver fibrosis. The anti-fibrotic effect of rimonabant, CB1 antagonist, related with the inhibiting of the proliferation and activation of hepatic stellate cells (HSC), and the inhibit-ing of the expression of CB1.

Objective To study the inhibitory effect of fluorouracil combined with DDP on the growth of human osteosarcoma cell line MG-63,and to explore its influence on the expressions of transient receptor potential vanilloid 5 (TRPV5 )and transient receptor potential vanilloid 6 (TRPV6 )proteins.Methods The MG-63 cells were cultured by the density of 5 × 104 mL-1 .Fluorouracil group,DDP group,fluorouracil+ DDP group and control group containing 10% FBS were set up.The inhibitory rates of growth of MG-63 cells at different time were detected by CCK-8 assay.The apoptosis of MG-63 cells after treated with different drugs was determined by Hoechst staining Kit.The immunocytochemical staining was used to treatent to detect the expressions of TRPV5 and TRPV6 before and after treatment.Results Fluorouracil and DDP both inhibited the growth of MG-63 cells in a time-and dose- dependent manner.There were a lot of black particles in the MG-63 cells and the cells were smaller,aging or death when they were exposed to fluorouracil or DDP.Compared with 24 h group,the inhibitory rates of proliferation of MG-63 cells after treated with the sigle drug of fluorouracil or DDP for 48 and 72 h were increased significantly (P <0.05).Compared with control group,the apoptotic rates of MG-63 cells in fluorouracil group and DDP group 24,48,and 72 h after treatment were increased (P < 0.01)in a time-dependent manner. The expression levels of TRPV5 and TRPV6 in MG-63 cells 72 h after treatment of fluorouracil and DDP were decreased significantly compared with before treatment (P < 0.05 ). Conclusion Fluorouracil, DDP and fluorouracil combined with DDP could significantly inhibit the proliferation of MG-63 cells,induce the apoptosis, and decrease the expression levels of TRPV5 and TRPV6.

Objective To manufacture magnetic microbubbles with dual-response to ultrasound and magnetic fields.Methods Microbubbles of ultrasound contrast agent (ST68) based on a surfactant were prepared by the acoustic cavitation method.Fe3O4 magnetic nanoparticles with negative charge were synthesized using the polyol procedure.Magnetic microbubbles were generated by depositing polyethylenimine and Fe3O4 magnetic nanoparticles alternately onto the microbubbles using the layer-by-layer self-assembly.In vitro ultrasonography was performed on a silicone tube with/without magnetic microbubbles (3 × 108/ml) by a self-made device to observe the movement of magnetic microbubbles under the effects of magnetic field.In vivo imaging was performed on the kidney of New Zealand rabbits before and after the injection of magnetic microbubbles.Results The Fe3O4 nanoparticles carried a stable negative charge of (-24.6 ± 6.7) mV and more than 98％ of the particles were less than 8 μm in diameter,meeting the size requirement of an ultrasound contrast agent for intravenous administration.There was no echoic signal in the silicone tube before injection of magnetic microbubbles,but there were strong echoic signals after injection.After applying a magnetic field,the magnetic microbubbles moved along the direction of the magnetic flux.In vivo ultrasound imaging could not visualize the kidney before injection of magnetic microbubbles,but could remarkably visualize the kidney after injection.Conclusions The magnetic microbubbles exhibit favorable magnetic targeting and ultrasound contrast enhancement characteristics.Such properties may serve as the foundation to study their potential for simultaneous diagnosis and treatment in the future.

Objective To fabricate an ultrasound/fluorescence bi-modal contrast agent by encapsulating fluorescent quantum dots into polymeric ultrasound contrast agent microbubbles.Methods Polylactic acid (PLA,500 mg),(1R)-(+)-camphor (50 mg) and CdSe/ZnS quantum dots (0.5 ml,2.3 μmol/L)were dissolved or dispersed in dichloromethane (10 ml) to form in an organic phase.Ammonium carbonate solution and poly (vinyl alcohol) solution were employed as the internal and external water phase,respectively.The fluorescent microbubbles were generated using double emulsion solvent evaporation and lyophilization methods.The morphology and illumination were characterized by scanning electron microscopy (SEM) and fluorescence spectrophotometry.Synchronized contrast-enhanced ultrasound and fluorescence imaging was acquired by injecting fluorescent microbubbles into the silicone tube coupled to a self-made ultrasound/fluorescence imaging device.Ultrasound/fluorescence bi-modal in vivo imaging was acquired on the kidney of New Zealand rabbits and suckling mice.Results The fluorescent microbubbles were hollow spheres with an averaged diameter of (1.62 ± 1.47) μm.More than 99％ of these microbubbles were less than 8 μm in diameter,which meeted the size criteria for ultrasound contrast agents.The fluorescence emission peak of the microbubbles appeared at 632 nm,indicating that good luminescence properties of quantum dots were maintained.In vitro ultrasound/fluorescence imaging showed no echoic signal when the silicone tube was filled with saline,but there was a strong echo when filled with fluorescent microbubbles.The liquid column with fluorescent microbubbles emitted red luminescence under ultraviolet irradiation.The kidney of the rabbit was remarkably enhanced after the administration of fluorescent microbubbles.Bright fluorescence could be observed at the injection site of the suckling mice via subcutaneous injection.Conclusions A bi-modal but single contrast agent based on polymeric microbubbles has been successfully fabricated for the use of ultrasound and fluorescence imaging.It retains the good characteristics of both echogenicity and fluorescence,which complement each other in case of limitations imposed by uni-modal,single agents.