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Star-shaped block polymers have recently attracted considerable attention owing to their unique properties and applicability in nanomedicine development.Compare to linear polymer and hyper-branched polymers,star-shaped block polymers have more advantages due to the unique structure.Star-shaped block polymer has become a desirable molecular biomaterial for delivery therapeutics and diagnostic agent to the diseased cells.This paper reviews the research about star-shaped block polymers and nanomedicine development in using them as drug and gene delivery carriers.
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Background Retinal vascular recanalization is key to the treatment of retinal vascular occlusive disease.Studies confirmed that urokinase by intravitreal injection inhibits the expression of occludin protein at tight junction complexes among retinal capillary endothelial cells.Objective This study was to observe the effects of urokinase via eye local injection on the outward permeability of blood-retinal barrier by detecting the concentration of intravitreal Evans blue (EB).Methods Sixty healthy Sprague-Dawley (SD) rats were randomly assigned to four groups,and the right eyes of the rats were used as experimental eyes.Urokinase of 4 μl (350 U) and the equal volume of PBS (0.01 mol/L) was intravitreally injected separately in the intravitreal urokinase group and the intravitreal PBS group,and 10 μl urokinase (1000U) and the equal volume of PBS was injected via retrobulbar tissue respectively as the retrobulbar urokinase group and the retrobulbar PBS group.Twenty-four hours after injection of drugs,0.5％ EB 4 μl was intravitreally injected.Four hours later,the rats were sacrificed and the right eyeballs were excised for the extraction and drying.EB was extracted from dried vitreous by formamide.Then,the concentration of EB in formamide was determined by a formamide extraction-ultraviolet spectrophotometry method to calculate the concentration of EB in vitreous.The use and care of experimental animals followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission (2011 version).Results The rat vitreous body showed the light blue color in intravitreal urokinase group and the retinal vessels were visible under the microscope,and that in the retrobulbar urokinase group presented blue color.However,in the intravitreal and retrobulbar PBS group,rat vitreous exhibited the deeper blue color and retinas were invisible.Absorbance of EB in formamide was 0.181 ±0.008,0.450±0.017,0.330±0.009 and 0.436±0.012 in the intravitreal urokinase group,intravitreal PBS group,retrobulbar urokinase group and retrobulbar PBS group,respectively.The intravitreal EB concentrations in the intravitreal urokinase group were (0.266±0.014)g/L,which was lower than (0.667±0.026) g/L,(0.496±0.015) g/L and (0.657±0.017) g/L of the intravitreal PBS group,retrobulbar urokinase group and retrobulbar PBS group,showing significant different among the four groups (F =100.406,P＜0.01),and the intravitreal urokinase group showed the lowest value in comparison with other three groups (all at P＜0.01).Conclusions Local application of urokinase around eye can augment the outward permeability of blood-retinal barrier in rats.Intravitreal assay of EB after intravitreal injection is a feasible approach to the determination of outward permeability of blood-retinal barrier.
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Objective To observe the occurrence and evolution of persistent submacular fluid (SMF) after scleral buckling surgery (SB) in rhegmatogenous retinal detachment,and then to study the related factors of persistent SMF and the effect of persistent SMF on visual outcome.Methods Ninety eyes of 89 patients with rhegmatogenous retinal detachment which had been performed SB were included in this study.Best corrected visual acuity (BCVA),intraocular pressure,slit-lamp microscopy,three mirror contact lens,indirect ophthalmoscopy and B-scan ultrasonography were measured for all patients.There were 21 eyes with atrophic holes while 42 eyes with horse-shoe tears,22 eyes with old retinal detachment while 68 new suffered eyes.Thirty-two eyes underwent scleral encircling surgery (SE) and 58 eyes underwent segmental scleral buckling surgery (SSB).The patients were divided into SMF group and non-SMF (NSMF) group according to the results of optical coherence tomography (OCT) at 1 month postoperatively.Thorough ophthalmologic examinations were performd at 1,3,6 and 12 months after surgery to the patients,further observations were continued to carry out unless the abnormality had resolved for at least 6 months.Results Patients who underwent SE (20 eyes,62.5 ％) had a higher incidence of persistent SMF at 1 month after surgery than those who underwent SSB (23 eyes,39.7 ％),the difference was significant (x2 =5.024,P＜ 0.05).Persistent SMF was more frequent in eyes with atrophic holes (66.7％) than that with horseshoe tears (38.1％),the difference was significant (x2 =4.582,P＜0.05).Persistent SMF was found in 72.7％ old retinal detachment eyes and in 39.7％ new suffered eyes,showed a striking differences (x2=7.264,P＜0.01).There was no significant difference in BCVA among SE and SSB groups at every time point (t=0.659,0.699,1.108,1.037,1.902; P＞0.05).The SMF group have a similar BCVA with NSMF group 1 and 3 months after surgery (t=1.812,1.957; P＞0.05),whereas the SMF group showed worse BCVA than NSMF group from since 6 months after surgery (t=2.324,2.147,2.184; P＜0.05).Conclusions Persistent SMF is more frequent after SE than SSB,the type of retinal breaks and old retinal detachment may be the potential influencing factors.Persistent SMF after SB may affect the final visual outcome.
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Objective Mannitol-poly(D,L-lactide-co-glycolide) (M-PLGA),a star-shaped biodegradable polymer,was synthesized with the intent in this research,to provide novel nanoformulation for cervical cancer chemotherapy.Methods The novel star-shaped copolymer was prepared by ring-opening polymerization,and characterized by NMR.The docetaxel-loaded M-PLGA nanoparticles,prepared by modified nano-precipitation method,were observed to be near-spherical shape with narrow size distribution.Results The CLSM results showed the uptake level of M-PLGA NPs was higher than PLGA NPs in Hela cells.A significantly higher level of cytotoxicity was achieved by docetaxel-loaded M-PLGA NPs than that of commercial Taxotere and docetaxel-loaded PLGA NPs,indicating that the star-shaped biodegradable polymer M-PLGA could be superior to the linear polymer PLGA as a drug carrier.The study on drug loading and encapsulation efficiency also proved that star-shaped M-PLGA could carry higher level of drug than linear polymer,therefore could be more efficient for cancer treatment.Conclusions In conclusion,the star-shaped M-PLGA copolymer may be used as a potential and promising drug-loaded biomaterial applied in developing novel nanoformulations for cervical cancer therapy.
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Objective To investigate the main causes and risk factors of recurrent retinal detachment (RRD) after silicone oil removal (SOR) in eyes with complex retinal detachment.Methods It was a retrospective case series study.A total of 458 eyes of 455 consecutive patients who underwent pars plana vitrectomy with silicone oil tamponade were recruited in this study.All patients underwent vitrectomy operation.Additionally,they were given heavy water,membrane peeling,retinotomy or partial cutting,intraocular laser photocoagulation or frozen,gas-liquid exchange or direct oil exchange operation accordingly.Ninety-eight eyes with multiple holes,old retinal detachment,hyperplasia and serious traction lesions underwent scleral buckling surgery simultaneously.Intravitreal silicone oil was padded at the end of operation.Cutting,stripping or resection and 360° preventive laser photocoagulation were applied while the epiretinal membrane was found and need treatment during SOR.Holes or suspicious hiatus underwent intraocular laser photocoagulation or cryotherapy during the operation.One week after SOR and during follow-up,the visual acuity,intraocular pressure (IOP),slit lamp microscope,and ophthalmoscope examination were examined with the same technique and methods as preoperation.The eyes were divide into two groups based on the attachment status of retina after SOR,which were reattached group (419 eyes) and redetached group (39 eyes) respectively.The following data were recorded.,the age of patients,ocular axial length,logarithm of minimum angle of resolution (logMAR) best corrected visual acuity (BCVA) and IOP before vitrectomy operation and before and after SOR,the number of retinal breaks,the duration of silicone oil filling,the duration of follow-up,and the related factors during vitrectomy operation and SOR.The relation of age,sex,high myopia,the size and location of holes,aphakic eye,proliferative vitreoretinopathy (PVR) C3 level and above,previous history of failed retinal detachment operation,360° preventive laser photocoagulation,assistant scleral buckling surgery,SOR via corneal puncture to RRD after SOR were analyzed.Odds ratio (OR) and its 95％ confidence interval (CI) were calculated for the age ＜40 years old and gender.High myopia,assistant scleral buckling surgery and SOR via corneal puncture were further analyzed by multiple regression equation.Results After SOR operation,the total average logMAR BCVA was 0.86 ± 0.63.The average logMAR BCVA was 0.82 ± 0.59 and 0.99 ± 0.70 respectively for the reattached and redetached groups,which was not statistically different (F=1.559,P＞0.05).The number of high myopia eyes in the reattached and redetached groups were 116 and 22 eyes,respectively,accounted for 27.7 ％ and 56.4 ％,and the difference was statistically significant (x2=13.984,P＜0.01).Three eyes underwent vitrectomy with scleral buckling occured RRD,accounting for 3.1％; while 36 eyes underwent vitrectomy without scleral buckling occured RRD,accounting for 10.0％.The incidence of RRD between them was statistically significant (x2 =4.761,P＜0.05).The incidence of RRD was not retated to the PVR levels before the operation,previous history of failed retinal detachment operation,aphakic eye and preventive laser photocoagulation (OR=1.626,1.699,1.986,0.709; 95％ CI:0.836-3.162,0.832-3.658,0.921-4.279,0.268-1.875; P＞0.05).RRD had a close relation with high myopia and assistant scleral buckling surgery (OR=3.380,0.284; 95％CI:1.733-6.595,0.086-0.944; P＜0.05).The raise of risk derived from SOR via corneal puncture had no statistical significance (OR=2.119; 95％CI:1.043-4.306; P＞0.05).The incidence of RRD after SOR was 8.5％; of which,35.9％ originated from new breaks and 69.2％ were related to new breaks,in contrast,only 5.1％ originated from PVR but 51.3％ were related to PVR.Conclusions High myopia is an independent prognostic risk factor of RRD after SOR.Combined scleral buckling surgery is a protective factor of RRD after SOR.To the well reattached eyes before SOR,the new breaks seems to be the main cause of RRD,wheras PVR was probably a secondary phenomenon.
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Objective To investigate the change of levels of related cytokines,including transforming growth factor-β2 (TGF-β2),basic fibroblast growth factor (bFGF),platelet-derived growth factor (PDGF),interleukin-6 (IL-6),interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) and behavior in streptozotocin-induced diabetic rats between the before and after fracture,at the same time,to analyse the relativity of them.Methods The rat models of diabetic were induced by intraperitoneal injection of streptozotocin,which were divided into different diabetes mellitus group (DM group) randomly.The right tibiofibula of all the rats of diabetes mellitus group and normal control group(NC group) were broken,and then treated with external fixation.The bone callus formation was evaluated by X-ray.When all the operation above was completed,the rats were domesticated in different cages.The concentration of related cytokines of the DM groups and NC group was detected at different time.Results The behavior changes of diabetes fracture rats were distinct and appeared a series symptoms such as bradykinesia,dull,polydipsia,polyphage,polyuria,emaciated obviously.The concentration of related cytokines (TGFβ2,BFGF,PDGF,IL-6,IL-8 and TNF-α) of the two groups was detected at 1,2 and 4 weeks.The difference between them was significantly(TNF-α:the concentration of NC group were (9.87 ± 1.06) ng/ml,(14.07 ± 1.43)ng/ml and(12.02 ± 1.02) ng/ml; the concentration of DM group were (11.65 ± 1.18) ng/ml,(16.29 ± 1.24)ng/ml and(13.87 ± 1.25)ng/ml ; P ＜ 0.05).X-ray films showed that the fracture healing of NC group was more superior than that of DM group.Conclusion The reduction of TGF-β2,BFGF,PDGF and the increase of IL-6,IL-8,TNF-α in early fracture are one of important reasons for delayed union and nonunion in diabetic rats.At the same time,there is a cooperative action between them.Dynamic observation of the concentration of related cytokines will provide eliable experimental data to estimate fracture healing,delayed union and nonunion.It is favourable to acquaint the regulatory mechanism of fracture healing at molecular level.