The suprachoroidal space (SCS) is the potential space between the sclera and choroid.Drugs delivered through SCS can bypass the sclera,avoiding clearance by conjunctival and scleral blood vessels and lymphatic circulation,so that more drugs can reach the disease tissues such as choroid and retina.SCS drug delivery does not disrupt the ocular integrity,is safer than the intravitreal drug injection and more effective than trans-scleral drug delivery.In addition,SCS delivery only needs a very small volume of drug,which makes it possible to be carried out in multiple parts of the sclera,and the specific disease area can be more precisely targeted.SCS drug delivery is suitable for the treatment of choroidal and retinal diseases.However,currently SCS drug delivery is still a novel field and many aspects need to be more in-depth studied,including its safety,delivery methods,drug formulation and effectiveness.

The human sclera accounts for 95％ of the surface of the eyeball,providing ample contact area which is suitable for targeted trans-scleral ocular drug delivery.Currently there are several tans-scleral sustained-release strategies,including intra-scleral delivery,episcleral delivery,as well as tans-scleral iontophoresis.Different devices and methods have their own advantages and disadvantages,for example,intrascleral delivery is somehow invasive,and episcleral delivery device needs to be made thin to prevent erosion of conjunctiva,iontophoresis needs to be frequently repeated as of its short-term effect.With the development of bio-material engineering technology,episcleral microfilm could become an ideal drug delivery route for posterior segment ocular diseases.

Transgenic animals are those in which recombinant DNA technology is used to remove a gene or a specific part of DNA with exogenous DNA, which is hereditable and can be expressed stably. Transgenic rodent technology, first demonstrated by Gordon in 1980,opened the door to the next step in biotechnology and gene regulation, which has been used to reproduce or mimic a part of a human disease in a complex cellular environment by creating in vivo models with germ line transmission of the introduced genetic regulatory elements. Animal models for drug discovery are developing increasingly, which is promoting the research and development new drugs greatly. The use and development of transgenic animals in pharmacological research is reviewed in this article.

Nephrotic syndrome(NS)is the most frequent cause of glomerular disease in children,it can deve-lop many complications,including infection,thrombosis and acute kidney injury,while acute adrenocortical suppression is a complication of some drugs administration. This review focuses on the pathophysiology and management of common complications in patients with NS.

· Heterochromia was observed in a six-month-old Dutch pigmented rabbit and the rabbit was examined for general and eye anomalies. The rabbit showed a blue eye with fundus hypochromia on the right and a brown eye with partial fundus hypochromia on the left. White fur (white forelock) was present, but deafness was not apparent although no objective audiologic examination was performed. Histology studies of both eyes revealed that significantly fewer pigment cells in iris stroma and less pigmentation in retinal pigment epithelium and choroid in the right eye than in the left eye.

Objective To construct the eukaryotic expression vector for human hypoxia inducible factor-1? gene (pSNAV-HIF-1?), and to investigate the apoptosis and intracellular calcium concentration of the transfected A?25-35 induced hippocampal neurons of primary culture. Methods Human hypoxia inducible factor-1? gene from pBSKhHIF1?T7 was inserted into pSNAV2.0 by the method of gene recombination, then the constructed vector was transfected into hippocampal neurons of primary culture and followed by A?25-35 for treatment. Empty pSNAV2.0 vector was treated the same way as pSNAV-HIF-1? as a control. The expression level of HIF-1? protein was assayed by Western blotting. Apoptosis was detected by flow cytometry. Intracellular calcium concentration was determined by laser scanning confocal microscopy with Fluo-3/AM as the fluorescent dye. Results It was shown that pSNAV-HIF-1? was successfully constructed by restriction enzyme digestion, PCR and DNA sequencing. The expression level of HIF-1? protein was significantly increased in transfected hippocampal neurons of primary culture (P

Background Dimethyl sulfoxide(DMSO) is a commonly used adjuvant to promote testing drug solubility to prepare multi-levels testing drug concentrations.DMSO is cell type-dependent cytotoxic and its toxicity can interfere the testing drug evaluation.Determining its safe concentration on commonly used cell types is important for ocular drug development.Objective This study was to determine the minimal toxic concentration of DMSO for in vitro ocular cell lines in a simulated drug screening setting.Methods Retinal pigment epithelial (RPE) cells were isolated from one pigmented rabbit and primarily cultured.Human RPE cell strain (ARPE19),scleral fibroblasts line (S75-Fron),human Müller cell line (MIO-M1),human lens epithelial cell line (HLEC),human choroidal melanoma cell line (OCM-1),human umbilical endothelial cell (HUVEC) and human HeLa cell line (HELA) were cultured.Different concentrations of DMSO (1.6％,1.0％,0.8％,0.4％,0.2％ and 0.1％) were prepared with 160 μl DMSO solution and 9.84 ml RPMI1640 (or DMEM/F12 or DMEM) containing 2％ fetal bovine serum.Different concentrations of DMSO were added in medium for 96 hours,and the and viability (absorbance) of the cells was detected using MTS to evaluate the cytotoxicity of DMSO.Results Rabbit primary RPE cells showed the yellow-green fluorescence for cytokeratin(CK) and HMB45 red fluorescence for S100.The viability of the cells was gradually declined as the increase of DMSO dose,showing significant differences in ARPE19,S75-Fron,HLEC,OCM-1,HUVEC and primary RPE cells (all at P＜0.05),and when DMSO concentrations were ≥ 0.8％,the cell viabilities were significantly lower.But no significant difference was found in MIO-M1 cells among different doses of DMSO (F=0.830,P=0.547).The minimal toxic concentration of DMSO for ARPE19,HUVEC,HELA,HLEC,MIO-M1,OCM-1,primary RPE cells and S75-Fron was 0.8％,0.1％,0.8％,＞1.6％,＞1.6％,0.2％,0.2％,0.2％,respectively,and HUVEC was more sensitive to the cytotoxicity of DMSO (P=0.02),and MIO-M1 was the least sensitive to DMSO (P =0.39).The viability of HUVEC and primary RPE cells went down with the increase of DMSO dose,and S75-Fron viability started to decline in 0.1％ DMSO and then stabilize with the higher concentrations until 1.6％ DMSO at which the viability showed further decline.Conclusions The tolerability of ocular cells in vitro to DMSO varies depending on the cell types.The minimal toxic concentration ranged from 0.1％ to 1.6％.The result suggests that a concurrent DMSO control should be set up along with the testing compound.

Objective To explore the value of echocardiography in the diagnosis of the parachute mitral valve(PMV).Methods The echocardiographic characteristics of 12 patients with PMV between 2005 and 2012 were reviewed retrospectively,including the morphology,movement and blood flow of mitral valve apparatus,and other associated cardiac abnormalities.Results Of the mitral valve leaflets in these 12 cases,all were thickened and opened restricted in diastole.Axial view showed that in all cases mitral valves opened eccentrically and in 2 cases they didn't close tightly.Each patient only had single papillary muscle in left ventricle,which received all chords of mitral valves.Of papillary muscles in these patients,4 were located at posteromedial wall,3 at anterolateral wall,2 at middle posterior wall,2 at apical wall,and 1 at posterolateral wall.Of the 12 patients,only one were simple PMV,11 had associated cardiovascular anomalies,2 had mild regurgitation in systolic period and 11 had increased trans-valve peak flow velocity.Conclusions Echocardiography is reliable in the diagnosis of PMV,which could provide a comprehensive evaluation of valvular lesions and other associated cardiovascular anomalies.

Objective To explore the value of two-dimensional strain echocardiography for quantitative assessing the change of regional left ventricular myocardial function in rats following acute myocardial infarction. Methods Sixty Wistar rats were randomly divided into two groups. The study group consisted of 50 rats with occlusion of LAD for 30-45 minutes and the sham-operated group consisted of 10 rats without occlusion of LAD. Echocardiography were performed before operation, which was defined as baseline, and 1 week, 4 weeks and 8 weeks after operation. Left ventricular internal diameter at diastole ( LVIDd) and systole < LVIDs), fractional shortening( FS), ejection fraction (EF) and left ventricular mass(LVM) were measured by anatomical M-model echocardiography. High frame rate two-dimensional images were recorded in the left ventricular short-axis views at the papillary muscle level. Peak systolic radial strain(PRS) and circumferential strain(PCS) of each segment were measured using 2-dimensional strain software. The rats were sacrificed and the infarcted size of each segment was measured using triphenyl tetrazolium chloride (TTC) after echocardiography was performed. Fibrosis of left ventricular myocardium was displayed using Van Gieson stain in 1 weeks after infarction. Results Based on the TTC findings,the left ventricle of the study group was divided into three regions:infarcted,peri-infarct and remote myocardial regions. Van Gieson stain showed fibrosis existed in all the three regions. Compared with baseline and sham-operated group, PRS and PCS of infarcted, peri-infarct and remote myocardial regions of the study group significantly decreased within 1 week after operation ( P <0. 01) and persisted for 8 weeks. PCS and PRS of infarcted, peri-infarct and remote myocardial regions of the study group in 4 weeks and 8 weeks after operation showed no significant difference when compared with those in 1 week after operation ( P >0. 01). Compared with baseline and sham-operated group,LVIDd,LVIDs and LVM of study group all increased significantly ( P <0. 05) in 4 weeks and 8 weeks after operation,and FS and EF reduced significantly ( P <0. 05). Two-dimensional strain obtained in interobserver and intraobserver both showed high agreement. Conclusions Two-dimensional strain echocardiography can assess regional function of myocardium with different perfusion in rats following acute myocardial infarction, and provides a sensitive and reliable method to follow up the process of left ventricular remodeling after myocardial infarction.

Objective To explore the effects of umbilical cord-derived mesenchymal stem cells (UCMSCs) on fibroblast-like synoviocytes(FLSs) from patients with rheumatoid arthritis(RA). Methods collagen-induced arthritis(CIA) models were developed on Wistar rats and 1 ×106 UCMSCs were given by intravenous injection from tail vein on the 17th day. On day 42, rats were sacrificed and synovial tissues were obtained to detect matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13. Synovial tissues from patients with RA and osteoarthritis(OA) treated by knee arthroplasty were used to isolate FLSs. RNA of FLSs were extracted to compare MMP-1, MMP-3 and MMP-13 expression. FLSs and UCMSCs were cocultured through transwell for 72 hours. Then levels of MMPs were compared in the supernatants by Luminex. The MMPs expressed by FLSs and soluble factors expressed by MSCs were detected by real time-polymerase chain reaction(PCR). After adding antibodies to soluble factors, the MMPs expressions of RA FLSs were compared. Results MMP-1 (6.9±5.4, 1.3±1.4, P<0.05), MMP-3 (6.0±6.5, 1.4±1.0, P<0.05) and MMP-13 (21.8± 20.8, 1.5±1.6, P<0.05) expression were much higher in CIA rats compared with healthy controls. MMP-1 (1.3±1.4, 6.9±5.4,8.7±6.8, P<0.05), MMP-3(1.4±1.5, 6.0±6.5, 6.0±5.7, P<0.05) and MMP-13(3.0±3.2,
22±21, 22±26, P<0.05) expression were inhibited by UCMSCs in vivo. In vitro, MMP-1 (1.8±0.9, 0.9±0.7, t=2.44, P<0.05), MMP-3(2.6±1.7, 1.1±1.0, t=2.25, P<0.05) and MMP-13(2.4±2.3, 0.6±0.7, t=2.37, P<0.05) levels were higher in RA than OA FLSs. After coculture, MMP-13(1.3±1.2, 0.9±1.2, t=3.63, P<0.05) expressed by FLSs were down-regulated, however MMP-1 (1.5±1.4, 6.6±6.0, t=3.90, P<0.05) and MMP-3 (7±17, 22±35, t=2.86, P<0.05) were up-regulated when analyzed by paired t-test. Soluble factors such as I-DO, HGF and IL-10 were elevated. Anti-IL-10 antibody could decrease the function of UCMSCs by inhibiting MMP-13 expression in RA FLSs. Conclusion UCMSCs ameliorates RA by secreting soluble factor IL-10, which may inhibit MMPs expressed by FLSs.