3.Small interfering RNA delivery mediated by mPEG-PCL-g-PEI polymer nanoparticles.
Wei HUANG ; Ming Lü ; Zhonggao GAO ; Mingji JIN ; Changqing YANG
Acta Pharmaceutica Sinica 2011;46(3):344-9
The aim of this paper is to report the synthesis of the mPEG-PCL-g-PEI copolymers as small interfering RNA (siRNA) delivery vector, and exploration of the siRNA delivery potential of mPEG-PCL-g-PEI in vitro. The diblock copolymers mPEG-PCL-OH was prepared through the ring-opening polymerization. Then, the hydroxyl terminal (-OH) of mPEG-PCL-OH was chemically converted into the carboxy (-COOH) and N-hydroxysuccinimide (NHS) in turn to prepare mPEG-PCL-NHS. The branched PEI was reacted with mPEG-PCL-NHS to synthesize the ternary copolymers mPEG-PCL-g-PEI. The structure of mPEG-PCL-g-PEI copolymers was characterized with Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The mPEG-PCL-g-PEI/siRNA nanoparticles were prepared by complex coacervation, and the nanoparticles size and zeta potential were determined, separately. The cytotoxicities of mPEG-PCL-g-PEI/siRNA nanoparticles and PEI/siRNA nanoparticles were compared through cells MTT assays in vitro. The inhibition efficiencies of firefly luciferase gene expression by mPEG-PCL-g-PEI/ siRNA nanoparticle at various N/P ratios were investigated through cell transfection in vitro. The experimental results suggested that the ternary (mPEG5k-PCL(1.2k))1.4-g-PEI(10k) copolymers were successfully synthesized. (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k) could condense siRNA into nanoparticles (50-200 nm) with positive zeta potential. MTT assay results showed that the cytotoxicity of (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k)/siRNA nanoparticles was significantly lower than that of PEI(10k)/siRNA nanoparticles (P < 0.05). The expression of firefly luciferase gene could be significantly down-regulated at a range of N/P ratio from 50 to 150 (P < 0.01), and maximally inhibited at the N/P ratio of 125. The mPEG-PCL-g-PEI polymers could delivery siRNA into cells to inhibit the expression of target gene with very low cytotoxicity, which suggested that mPEG-PCL-g-PEI could serve as a new type of siRNA delivery vector.
5.Experimental study of cryoablation on rabbit's VX2 brain tumor under MRI guidance and real-time monitoring
Chengli LI ; Chuanchen ZHANG ; Guohua XIE ; Wei WANG ; Ming LIU ; Yubo Lü ; Jiqing SONG
Chinese Journal of Radiology 2008;42(6):650-654
Objective To verify the feasibility of eryoablation on rabbit brain tumor under interventional MRI guidance.Methods The procedures were performed under general anaesthesia.Twenty-two New Zealand white rabbit'S brains were inoculated with VX,tumor tissue through cranial holes. MR-guided cryoablation were conducted as preliminary experiment when diameter of brain tumor grew up to 0.8 cm in size.Cryoablation lasted two cycles of 5 minutes freezing, in 2 rabbits.and of 10 minutes freezing in another 2 rabbits.After procedure and MR scanning.rabbits were executed.Specimens of rabbit'S brain showed complete necrosis pathologically after cryoablation of cycles of 10 minutes freezing.The optimal parameters of eryoablation were defined.Except for the two rabbits that died of infection,the other 16 rabbits were divided into control group and therapeutic group.According to the optimal parameters of cryoablation,cryoablation of 10 minutes freezing were performed for rabbit brain tumors in therapeutic group.Venous injeetion of 20%mannitol and subcutaneous injection of dexamethasone were used for dehydration.None of rabbit brain tumors in the control group were treated.After cryoablation,MRI scanning Was performed immediately,7 days later,14 days later and 60 days later,to observe the ablative area and the pathologic changes.The survival time wag recorded.Resuits Brain tumors could be found in all New Zealand white rabbits after inoculation except two died of inflammation.The maximum diameter of brain tumors Was from 0.7 to 1.0 elEL The tumors showed slight low signal on T1WI and slight high signal on T2WI as well as comrast enhancement after injection of Gd-DTPA.Pathologically coagulative necrosis were observed after cryoablation immediately,7 days and 14 days later,and liquefactive necrosis was found 60 days later.The correlation between MRI and pathologic appearance of tmnors are consistent.The therapeutic area ranged from 1.0 to 1.5 em.,The maximium diameter of ice ball ranged from 1.5 to 2.0 cm Conclusion CiToablation for brain tumor iS a safe and feasible therapy.
6.Effects of ear point needle embedding therapy on memory disorder and expression of beta-amyloid protein in the rat of vascular dementia.
Chinese Acupuncture & Moxibustion 2006;26(11):804-808
OBJECTIVETo study the mechanism of auricular acupuncture for improvement of learning and memory disorders in the rat of vascular dementia (VD).
METHODSThe vascular dementia rat model was made by 4-vessel occlusion method. Four groups, a sham operation group, a normal control group, a model group and an auricular acupuncture group were set up. After acupuncture was given at auricular points, Brain and Kidney. Immunohistochemical analysis, behavioural observation and computer image analysis were made.
RESULTSAuricular acupuncture could decrease significantly the beta-amyloid protein (A beta) immunoreactivive neurons and increase its average optical density in the parietal cortex of the VD rats (P < 0.05).
CONCLUSIONAuricular acupuncture can reduce or inhibit the over-production of Abeta in the brain, so as to improve the learning and memory capacity of the VD model rat.
Acupuncture Points ; Acupuncture, Ear ; methods ; Amyloid beta-Peptides ; analysis ; Animals ; Dementia, Vascular ; therapy ; Immunohistochemistry ; Male ; Memory Disorders ; therapy ; Rats ; Rats, Wistar
7.Endoscopic sphincterotomy plus balloon dilation for difficult bile duct stones
Ming JI ; Yongjun WANG ; Li YU ; Yinglin NIU ; Peng LI ; Fujing Lü ; Wei LI ; Shutian ZHANG
Chinese Journal of Digestive Endoscopy 2010;27(11):568-571
Objectiye To evaluate the therapeutic efficacy and safety of (endoscopic sphincterotomy, EST) plus balloon dilation for difficult bile duct stones. Methods Patients with difficult common bile duct stones on endoscopic retrograde cholangiopancreatography (ERCP) from March 2008 to December 2009 were randomly divided into 2 groups to receive EST or EST plus balloon dilation ( EST + EPBD), respectively. The success rate of complete stone removal, number of endoscopic sessions, the rate of using mechanical lithotripsy and the complication rate related to the procedure were compared between the 2 groups. Results Compared with EST alone, EST plus balloon dilation resulted in similar outcomes in terms of overall successful stone removal rate (2/62 vs. 2/61 ) and early complication rate (4/62 vs. 6/61, P >0. 05). However,EST group needed more sessions ( EST 15/46 vs. EST + EPBD 5/57, P <0. 05) and use of mechanical lithotripsy to achieve complete removal of stones ( EST 12/61 vs. EST + EPBD 4/61, P <0. 05 ). Conclusion EST plus balloon dilation is as safe and effective as, but more convenient than EST, for endoscopic removal of common bile duct stones.
8.Temporary placement of fully covered metal stent for benign biliary strictures
Ming JL ; Yongjun WANG ; Peng LI ; Fujing Lü ; Wei LI ; Shutian ZHANG
Chinese Journal of Digestive Endoscopy 2011;28(12):668-670
ObjectiveTo explore the efficacy and safety of temporary placement of fully covered metal stent in the treatment of benign biliary strictures.MethodsFully covered metal stents were placed in 36 patients with benign biliary strictures.All patients were followed up every 1-2 months and the stents were removed when adequate biliary drainage was achieved.ResultsResolution of the benign biliary strictures was achieved in 28 of 36 patients (77.8% ).All fully covered metal stents were removed successfully.Complications were observed in 3 patients (8.3%) after stent placement and in 1 (2.8% ) after stent removal.ConclusionTemporary placement of fully covered metal stents for benign biliary strictures is safe and efficacious.Further investigation is required to longer follow-up.
9.Fluoroscopy guided laser lithotripsy for difficult bile duct stones
Yongjun WANG ; Ming JI ; Li YU ; Yinglin NIU ; Peng LI ; Fujing Lü ; Wei LI ; Shutian ZHANG
Chinese Journal of Digestive Endoscopy 2011;28(4):185-188
Objective To evaluate the efficacy and safety of fluoroscopy guided frequency-doubled double-pulsed laser lithotripsy for removing difficult bile duct stones. Methods From March 2008 to December 2009, patients with difficult bile duct stones were divided into cholangioscopy guided group ( n = 21 )and fluoroscopy guided group ( n = 19) to receive corresponding treatments. The success rate of complete stone removal and the complication rate related to the procedure were compared between the two groups.Results There are no significant differences between 2 groups in regarding of either success rate of complete stone removal ( 19/21, 90. 5% in cholangioscopy guided group vs. 17/19, 89. 5% in fluoroscopy guided group, P >0. 05 ) or rate of procedure related complication (4/21, 19. 0% in cholangioscopy guided group vs. 3/19, 15. 8% in fluoroscopic guided group, P = 0. 559 ). Conclusion Frequency-doubled doublepulsed laser lithotripsy guided by cholangioscopy or fluoroscopy are both safe and effective.
10.Covered versus uncovered self-expandable metal stents for malignant biliary obstruction: a randomized, controlled study
Ming JI ; Yongjun WANG ; Peng LI ; Fujing Lü ; Wei LI ; Shutian ZHANG
Chinese Journal of Digestive Endoscopy 2012;(12):673-675
Objective To compare therapeutic efficacy and safety of covered and uncovered self-expandable metal stents for malignant biliary obstruction.Methods From October 2010 to August 2012,patients with unresectable malignant biliary obstruction were recruited and divided into 2 groups to receive covered metal stents (group A) or uncovered metal stents (group B).Efficacy and complication of the procedure were compared.Results A total of 81 patients were recruited,with 41 in group A and 40 in group B.Stents were placed successfully in all patients.The median patency time of stent in group A was 182.5 d,which was not significantly different from that of group B (195.0 d,P =0.616).Complications occurred in 3 patients of group A (7.3%) and 4 of group B (10%).Conclusion Covered and uncovered metal stents are both safe and effective for treatment of malignant biliary obstruction with same patency time.