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.

BACKGROUND: Thrombus formation and neointimal hyperplasia limit its use for revascularization of small-caliber vessels (<6mm diameter) in the coronary or peripheral circulation.OBJECTIVE: To improve hemocompatibility, the luminal surface of a small diameter expanded polytetrafluoroethylene (Eptfe) vascular prosthesis was modified with alginate and recombinant hirudin.DESIGN: Observational experiment.SETTING: This study was performed in Nanomedicine and Biosensor Laboratory, Bio-X Center, Harbin Institute of Technology from Marcy 2006 to June 2007.MATERIALS: The GORE-TEX Epife vascular grafts (W. L Gore & Associates, Inc., Flagstaff, AZ) used in this study were 4mm in internal diameter. rHir was obtained from Calbiochem, Germany. Sodium alginate (also called alginic acid sodium salt; medium viscosity) was purchased from Sigma.METHODS: A p-diazonium diphenyl amine polymer (PA) was used as an interlayer between alginate and recombinant hirudin (rHir). The diazonium moieties were capable of covalently coupling with electron-rich aromatic systems such as histidine and tyrosine residues of hirudin. No need for chemical pretreatment took all advantage by preserving the bulk properties with almost no effect on stability and elasticity of the Eptfe vascular graft. rHir amount on Epife surface Was determined by the Micro BCA (Bicinchoninic acid) Protein Assay kit.MAIN OUTCOME MEASURES: ① Determination rHir amount on Eptfe surface; ② Static water contact angles; ③ Attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR) was employed to confirm the change taking place in the Eptfe graft surface modification process; ④ Characterization of the surface morphology and platelet adhesion by SEM; ⑤ APTT and PT; ⑥ Percent hemolysis.RESULTS: ① The amount of rHir adsorbed onto the Eptfe vascular was deduced to be 16.35 μg/cm2. ② Surface analysis ATR-FTTR revealed the presence of new functional groups on the modified graft surfaces. ③ The water contact angle of the modified graft surface decreased. ④ The longer APTT and PT value lower than 5% hemolysis level and dramatically decrease of platelet adhesion assay showed that rHir modified graft had great improved blood compatibility.CONCLUS10N: Cross-linked Alg/rHir onto Eptfe can improve luminal surface and hemocompatibility.

BACKGROUND: The expanded polytetrafluoroethylene (ePTFE) vascular grafts hold promise for enhanced healing,extended suture retention, kink reduction and compression resistance. But thrombus formation still limits its use for revascularization of small-caliber vessels. It is the surface of ePTFE vascular graft that contacts with the blood. The current study focused on surface modification of ePTFE materials to improve its blood compatibility.OBJECTIVE: To characterize the heparin/alginate (H/A) gel modified ePTFE vascular graft and investigate the hemocompatibility and histocompatibility of the graft.DESIGN: Observation experiment.SETTING: Laboratory for Nanomedicine and Biosensor, Biomedicine Engineering Center, Harbin Institute of Technology.MATERIALS: The GORE-TEX ePTFE vascular grafts were 4 mm in internal diameter. Sodium alginate and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) were purchased from Sigma. Heparin sodium salt was obtained from Calbiochem. Nation and chitosan were purchased from Aldrich company. Human α-thrombin and AT Ⅲ were purchased from Haematologic Technologies, Inc. S-2238 was purchased from Chromogenix.METHODS: This study was performed at the Laboratory for Nanomedicine and Biosensor, Biomedicine Engineering Center, Harbin Institute of Technology between May 2006 and June 2007. The graft was first modified with Nation and then Chitosan/Nafion/Chitosan multilayer. Following the impregnation of heparin and alginate, covalent crosslinking was performed using ethylenediamine and EDC. Some characterization methods were employed: stastic water contact angle for the hydrophilicity; SEM for the surface morphology; ATR-FTIR for the surface chemical characteristics; APTT and PT,percent hemolysis and Chromogenic assay for the hemocompatibility of the ePTFE vascular graft after modification.MAIN OUTCOME MEASURES: ①Static water contact angles. ②Charactedzation of the surface morphology and platelet adhesion by SEM. ③ATR-FTIR ④APTT and PT. ⑤Percent hemolysis ⑥Chromogenic assay for heparin activity.RESULTS: ①ATR-FTIR revealed the presence of -CO-NH- at 1626 cm-1. ②The water contact angle was greatly decreased from (125±1)° to (84±2)° .③The prolonged APTT and PT, low percent hemolysis(0.065%) and low amount of platelet adhesion assay showed the H/A gel impregnated graft had good blood compatibility. ④Chromogenic assay showed the modified graft was less thrombogenic than the bare one, and the H/A coating had good stability in. PBS buffer.CONCLUSION: The H/A modified ePTFE vascular graft has great potential in applications utilizing small-diameter vascular grafts.

Objective:To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxici-ties related to high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis (DGGE), and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:We identified three SNPs of GSTP1, including rs1695 (A313G), rs1138272 (G439T), and rs4891 (T555C). The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases (62.7%), 16 cases (31.4%), and 3 cases (5.9%), respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin (OR=0.25, 95%CI=0.06-1.00, P=0.049). The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity (OR=0.125, 95%CI=0.02-0.78, P=0.026). Conclusion:GSTP1 rs1695 (A313G)/rs4891 (T555C) gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.

Objective To investigate the changes of CA125 between primary cytoreductive surgery and interval debulking surgery for prediction the rate of optimal interval cytoreductive surgery and prediction the recurrence and the prognosis in patients with epithelial ovarian cancer.Methods A total of 39 cases with suboptimal primary cytoreductive surgery admitted from Jan.1996 to Jan.2009 were retrospectively analyzed.The median age of patients was 56 years( range:41 -68 years).Based on the changes in CA125level between primary cytoreductive surgery and interval debulking surgery,all cases were divided into four groups,group A (CA125 reduced to normal after primary cytoreductive surgery,n=6),group B (CA125reduced to normal after 1 - 2 cycles of chemotherapy,n =11 ),group C ( CA125 reduced to normal after 3 -4 cycles of chemotherapy,n =14),and group D ( CA125 did not reduced to normal after the chemotherapy,n =8 ), and all received platinum-based chemotherapy.The response to chemotherapy evaluated by pathological examination versus CA125 level,and recurrence and prognoses were also analyzed.Results ( 1 )The rate of optimal interval cytoreductive surgery in group A,B,C and D were 6/6,8/11,9/14 and 2/8respectively,in which there were statistically different between group A or B and group D (P ＜0.05).(2)The clinical benefit rates evaluated by the pathological examination in group A,B,C and D were 4/6,4/11,5/14 and 0,respectively and there were statistically different between group A and group D (P =0.030).( 3 ) There was significant difference in the recurrence rate between group A and group D (3/6 vs.8/8,P =0.024),while there were not significant differences between group B or C and group D ( all P ＞ 0.05 ).The rate of drug-resistant recurrence in group A,B,C and D were 1/6,3/11,5/14 and 7/8,respectively,in which there were significant differences between group A,B or C and group D ( all P ＜ 0.05 ). ( 4 ) The median progression-free survival (PFS) for patients in group A,B,C and D were 32,10,18 and 3 months,respectively,in which there were significant differences in the PFS between group A,B or C and group D (P =0.012,P =0.003,P =0.032 ).The median overall survival (OS) were 44,45,44 and 16 months,respectively.There were significant differences in the OS between group A,B or C and group D ( P =0.022,P =0.004,P =0.000 ).Conclusion The change of CA125 between primary cytoreductive surgery and interval debulking surgery may be predict the recurrence type and the prognosis in patients with epithelial ovarian cancer.

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 investigate the diagnostic values of imaging techniques and endoscopy in detection the causes of post-hepatic obstructive jaundice.Methods The clinical data of 57 patients with post-hepatic obstructive jaundice were retrospectively studied.The causes of the obstruction and the findings of uhrasonography(US),computerized tomography(CT),magnetic resonance imaging(MRI)or MRIcholangiopancreatography(MRCP),endoscopic retrograde cholangiopancreatography(ERCP)and endoscopic ultrasonography(EUS)were compared.Results The causes of 57 patients with post-hepatic obstruetive jaundice were benign obstruction in 42(including stones in common bile duct in 38,ascariasis of CBD in 1,postoperative stricture in 2 and chronic pancreatitis in 1),and malignant lesions in 15(including pancreatic head carcinoma in 11 and ampullary carcinoma in 4).The diagnostic accuracy in terms of lesion location of US,CT,MRI+MRCP,ERCP and EUS were 71.93%(41/57),88.00%(22/25),94.59% (35/37),100.00%(47/47)and 96.77%(30/31),respectively;the diagnostic accuracy of cause of obstruction were 63.16%(36/57),80.00%(20/25),83.78%(31/37),100%(47/47)and 96.77% (30/31),respectively.Conclusion Benign diseases are the main causes of post-hepatic obstructive jaundice,but malignant ones are not rare.It is important to combine miscellaneous imaging techniques and endoscopy in diagnosis.

Objective To identify uropathogens responsible for urinary tract infection in children less than 5 years of age and determine the antibiograms.Methods The data of 523 children(2 months to 5 years old) admitted at the Shengjing Hospital of China Medical University from January 2008 to December 2013 were studied retrospectively.Results Out of 523 children suffering from urinary tract infection,54 (10.3％) were complicated urinary tract infection,including 24 vesicoureteral reflux,8 ureter-pelvic junction stenosis,5 hydronephrosis,4 double kidneys,2 renal dysplasia,2 bladder diverticula,2 bladder ear,2 neurogenic bladder,1 urethral vaginal fistula,1 congenital megaureter,1 horseshoe kidney,and 1 Ureteral cyst and stone.A total of 487 cases underwent urine culture,207 (42.5 ％) had positive bacterial growth,the gramnegative bacteria accounted for 94.69％,gram-positive bacteria 5.31％.E coli was the most common uropathogens in gram-negative bacteria (79.23 ％),the second was Klebsiella (5.31％),the third was Proteus mirabilis(2.90％).Gram-positive bacteria was almost Enterococcus (4.35％).Twenty one strains were extended-spectrum beta-lactamase enzyme positive(ESBLs +),and they were sensitive to imipenem,amikacin and piperacillin/tazobactam.Conclusion The clinical features were atypical in children with urinary tract infection,we should investigate the underlying causes such as urinary anomalies or stones.E coli was still the most common uropathogens in children with urinary tract infection,the empirical therapy should according to the patient's conditions while awaiting the culture and sensitivity results.

Objective To compare the treatment response of plasma exchange and immunoadsorption for children suffering from severe systemic lupus erythematosus (SLE),and then find the more advantageous treatment method.Methods Between March 2007 and March 2013,27 children with severe SLE were collected from the Department of Pediatric Nephrology and Rheumatology of Shengjing Hospital of China Medical University.Part of them about 11 children accepted plasma exchange treatment (plasma exchang group) and the others accepted immunoadsorption(immunoadsorption group).The clinical features,ANA,IgG,serum ions,the cost of treatment and the hospitalization time were reviewed,and the comparative analysis were performed in two groups.Results There were comparabilities between plasma exchange group and immunoadsorption group in age,gender,couse of disease and systemic lupus erythematosus disease activity index(SLEDAI) score before treatment.(1)In plasma exchang group,11 children were conducted 26 times treatment.The SLEDAI score significantly decreased after plasma exchange (19.00 ± 3.77 vs 5.34 ± 4.35,P ＜0.05),and the ANA and IgG significantly decreased as well[2 439.58 ± 1 430.56 vs 303.54 ± 169.32; (8.35 ± 5.67) g/L vs (4.04 ± 2.23) g/L,P ＜ 0.05].(2) There were 16 children in immunoadsorption group,they accepted immunoadsorption treatment about 44 times.The SLEDAI score after immunoadsorption significantly decreased (18.25 ± 4.62 vs 4.25 ± 2.23,P ＜ 0.05),and the ANA and IgG significantly decreased as well [2 560.39 ± 1 563.78 vs 289.62 ± 137.62 ; (9.98 ± 6.03) g/L vs (3.23 ± 1.37) g/L,P ＜0.05].(3) There were no statistical differences in the value of SLEDAI score,ANA and IgG after the treatment between two groups.(4) The concentrations of serum potassium,sodium and chlorine and calcium in the children treated by plasma exchange or immunoadsorption were consistent with the original.(5) The hospitalization expense in plasma exchange group was distinctly higher than that of immunoadsorption group (P ＜ 0.05).(6) There was no significant difference in the length of hospitalization between two groups [(33.6 ± 8.60) d vs (31.9 ± 14.6) d,P ＞ 0.05].Conclusion The treatment both plasma exchange and immunoadsorption were effective methods for the children with severe SLE.However,the cost of plasma exchange was much higher and had a great influence on the concentration of antihypertensive drugs.