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Objective: To investigate the effect of erianin on uveal melanoma cells and its underlying mechanism. Erianin is a broad-spectrum antitumor compound, and whether it is effective in uveal melanoma cells is unclear. Methods: B16F10 cells (murine melanoma cells) were divided into 4 experimental groups and 1 control group. The control group was not treated with drugs, and the experimental groups were treated with 3.125 μmol·L-1, 6.25 μmol·L-1, 12.5 μmol·L-1, and 25 μmol·L-1 erianin. A real-time cell electronic analysis system (RT-CES) and CCK-8 assay were used to investigate the effects of different doses of erianin on the growth of uveal melanoma cells. The VEGF-A mRNA expression in uveal melanoma cells was detected by RT‒PCR. ELISAs were used to study the effect of erianin on VEGF-A secretion in uveal melanoma cells. Flow cytometry was used to investigate the effect of erianin on the cell cycle and apoptosis of uveal melanoma cells and its possible mechanism. Results: Uveal melanoma cells in the experimental group (3.125 μmol·L-1, 6.25 μmol·L-1, 12.5 μmol·L-1, and 25 μmol·L-1) were treated with erianin for 24 h, and the cell survival rate decreased to 93.93 ± 0.26%, 89.46 ± 2.50%, 64.30 ± 2.45% and 35.06 ± 1.40%, respectively. Erianin downregulated VEGF-A mRNA expression in cells and inhibited the level of VEGF-A in uveal melanoma cells, and the experimental group (25 μmol·L-1) had the most obvious inhibitory effect. In addition, compared with those of the control group, the apoptosis rates of the experimental groups (3.125 μmol·L-1, 6.25 μmol·L-1, 12.5 μmol·L-1, and 25 μmol·L-1) increased from 0% to 7.29%, 8.25%, 10.04%, and 35.67%, respectively, after 24 h of erianin intervention. The proportion of cells in G1 phase increased from 38.31% to 39.40%, 41.45%, 49.03%, and 59.24%, and the differences were statistically significant (PConclusions: Erianin has a significant inhibitory effect on uveal melanoma cells, and its mechanism is to inhibit the level of VEGF and induce apoptosis and S-phase arrest of cells in a concentration-dependent manner.

VEGFR-2 is an attractive therapeutic target for antitumor drug research by blocking tumor angiogenesis and PROTAC provides a new technology for targeted protein knockout. Herein, a library of novel VEGFR-2-PROTAC degraders were rationally designed and synthesized based on the Lys residue region on the surface of VEGFR-2 protein using protein structure-based drug design strategy. Among them, P7 exhibited preferable antitumor activity against HGC-27 cells and less toxic to human normal HUVEC, HEK293T and GES-1 cells in vitro, as well as the potent degradation activity of VEGFR-2 protein in HGC-27 cells (DC

Calcium is an important messenger in the mammalian nerve cells which mediates a variety of intracellular signal transduction pathways and plays critical roles in regulating the neuronal functions. Calcium signaling exerts its highly specific function in a defined sub-region of the cell, especially in the visual cortex of the brain. Detection of calcium signals in neurons is particularly important for the studying of neuronal function. The two-photon microscope has a unique advantage in the detection of calcium signal in the superficial cortex. In this paper, the application of two-photon in the in vivo detection of the visual cortical Ⅱ/Ⅲ layer of model animals are reviewed.

Myopia is one of the most common eye diseases in the world. MicroRNAs(miRNAs)are small, non-protein-coded single-stranded RNAs with a length of about 20-25 nucleotides,which are widely involved in the process of post-transcriptional regulation of many physiological and pathological processes of organisms. It has attracted extensive attention for the regulation role of miRNAs in the process of induction and development of myopia in recent years. This article reviews the regulatory role and related signal pathways of miRNAs in the development of myopia. It will provide highlights for the understanding of molecular mechanism of myopia and benefit for potential molecular diagnosis of myopia in the future.

A series of conjugates of podophyllotoxin and coumarin were prepared using the click reaction, and their cytotoxicities against A549, HepG2, HeLa, and LoVo cells were evaluated. Among them, compound 14e exhibited the strongest cytotoxicities against these cancer cells with IC50 values of 4.9–17.5 μM. Furthermore, 14e disrupted microtubules and induced cell cycle arrest at G1 phase by regulating P21 and Cyclin D1 in LoVo cells. In addition, 14e bond CT DNA and selectively inhibited Topo IIβ over Topo IIα. Molecular docking model showed that 14e appeared to form stable hydrogen bonds with several DNA bases and residue Gln778. Taken together, these conjugates have the potential to be developed as anti-tumor drugs.

A new series of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine derivatives as tubulin polymerization inhibitors were synthesized, and evaluated for the anti-proliferative activities. A structure–activity relationship study revealed that the free amino moiety of 1H-pyrazolo[3,4-b]pyridin-3-amine played an essential role in the anti-proliferative activities. Especially, compound 15c displayed the strongest anti-proliferation against MCF-7 cells with IC50 value of 0.067 ± 0.003 μM, and high selectivity over the normal human embryonic lung WI-38 cells with IC50 value of 23.41 ± 1.53 μM. Further mechanistic studies revealed that 15c showed strong anti-tubulin polymerization activity, changed the morphology of tubulin, and arrested the cell cycle at the G2/M transition in MCF-7 cells. Molecular docking analysis suggested that 15c well occupied the colchicine-binding pocket of tubulin. Additionally, 15c demonstrated anti-angiogenic activities with blocking the migration, invasion and tube formation, disrupting the newly formed tube, and regulating both MMP-9 and TIMP-1 in HUVEC cells. In summary, our results highlight that compound 15c is a potential antitumor compound that are worthy of further development.

Vascular endothelial growth factor-2 (VEGFR-2) plays a pivotal role in tumor angiogenesis. Herein, a library of novel 2-(4-(1H-indazol-6-yl)-1H-pyrazol -1-yl)acetamide derivatives were designed and synthesized as VEGFR-2 inhibitors based on scaffold hopping strategy. These compounds exhibited the excellent inhibitory in both VEGFR-2 and tumor cells proliferation. Especially, compound W13 possessed potent VEGFR-2 inhibition with IC50 = 1.6 nM and anti-proliferation against HGC-27 tumor cells with IC50 = 0.36 ± 0.11 μM, as well as less toxicity against normal GES-1 cells with IC50 = 187.46 ± 10.13 μM. Moreover, W13 obviously inhibited colony formation, migration and invasion of HGC-27 cells by adjusting the expression of MMP-9 and E-cadherin, and induced HGC-27 cells apoptosis by increasing ROS production and regulating the expression of apoptotic proteins. Furthermore, W13 blocked the PI3K-Akt-mTOR signaling pathway in HGC-27 cells. In addition, anti-angiogenesis of W13 was proved by inhibiting tube formation and the expression of p-VEGFR-2 in HUVEC cells. All the results demonstrated that W13 could be developing as a promising anticancer agent for gastric cancer therapy.

Bromodomain protein 4 (BRD4) plays a crucial role in transcriptional regulation and is considered to be a viable drug target for cancer treatment. Herein, we designed and synthesized a series of indole-2-one derivatives through scaffold hopping drug design. Most of the compounds showed potent BRD4 inhibitory activities and anti-proliferation activities in cancer cell lines. Especially, compound 12j exhibited excellent BRD4 inhibitory activities (BD1 IC50 = 19 nM, BD2 IC50 = 28 nM) and anti-proliferation potency with IC50 values of 4.75 μM and 1.35 μM in HT-29 and HL-60 cells, respectively. Additionally, docking studies showed that the hydrophobic pocket next to KAc region and WPF shelf were critical to the activity of the compound. Compound 12j could arrest the cell-cycle progression of HT-29 cells into the G1 phase and reduce the expression of c-Myc. Moreover, compound 12j exhibited favorable oral pharmacokinetic properties. All the results demonstrated that compound 12j was a potent BRD4 inhibitor and had merely potential for colon cancer treatment.

Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis, and a number of Aurora kinase inhibitors have been evaluated in the clinic. Herein we report the synthesis and their antiproliferation of 3,5-disubstituted-2-aminopyrazines as kinases inhibitors. Amongst, 4-((3-amino-6- (3,5-dimethylisoxazol-4-yl)pyrazin-2-yl)oxy)-N-(3-chlorophenyl) benzamide (12Aj) exhibited the strongest antiproliferative activities against U38, HeLa, HepG2 and LoVo cells with IC50 values were 11.5 ± 3.2, 1.34 ± 0.23, 7.30 ± 1.56 and 1.64 ± 0.48 μM, as well as inhibited Aurora A and B with the IC50 values were 90 and 152 nM, respectively. Molecular docking studies indicated that 12Aj appeared to form stable hydrogen bonds with either Aurora A or Aurora B. Furthermore, 12Aj arrested HeLa cell cycle in G2/M phase by regulating protein levels of cyclinB1 and cdc2. In addition, the bioinformatics prediction further revealed that 12Aj possessed good drug likeness using SwissADME. These results suggested that 12Aj was worthy of future development of potent anticancer agents as pan-Aurora kinases.

AIM: To observe the efficacy and safety of a new posterior chamber intraocular lens(ICMO V4c)implantation in patients with high myopia and low astigmatism and to provide reference for the clinical diagnosis and treatment of these patients. METHODS: The study was to analyze the clinical data of patients with high myopia who underwent ICMO V4c implantation with low degree of astigmatism in our hospital from January 2015 to December 2016. The patients were followed up for 1, 3 and 6mo after operation. The items we analyzed including preoperative and postoperative uncorrected visual acuity(UCVA)and best corrected visual acuity(BCVA), diopter, spherical and cylinder equivalent, and manifest refraction spherical equivalent(MRSE), intraocular pressure(IOP), endothelial cell counting, anterior chamber depth(ACD), arch height and postoperative complications. RESULTS: Postoperative UCVA and BCVA improved compared with preoperative, and the difference between preoperative and postoperative was statistically significant(Pt=38.510, 20.100, 34.300; Pt=3.998, 2.837, all Pt=0.383, P>0.05). The corneal endothelium counts in the patients at 3mo and 6mo after surgery were lower than those before surgery(t=2.119, 2.411; all Pt=5.850, 5.260, 2.556; all PCONCLUSION: The new posterior chamber intraocular lens implantation in the treatment of high myopia with low astigmatism reaches satisfaction with less complications, is a good supplement to corneal refractive surgery.

Fundus diseases can seriously damage the visual acuity of patients, including age-related macular degeneration (ARMD), retinal choroidal neovascularization (CNV), retinal vein occlusion (RVO), central serous chorioretinopathy (CSC), diabetic retinopathy (DR), etc. At the same time, fundus disease generally has a long course, high severity, long-term delay, high recurrence rate, and as long as the patients do not receive timely treatment or do not receive the correct treatment, there will be a variety of complications, causing serious damage to the structure of the patient’s eyes and the patient’s visual function. Clinical trial simulation (CTS) is a newly emerging interdisciplinary subject in recent years. With the increasing cost in the process of new drug development, computer simulation technology has attracted extensive attention of pharmaceutical enterprises. Clinical treatment of fundus diseases includes hormone therapy, etiological treatment, vitrectomy, laser treatment, etc, But the effect is different. This study mainly analyzes the effect of intravitreal injection of conbercept in the treatment of fundus diseases. Based on the analysis and research of CTS research at home and abroad, aiming at the relationship between dosage, blood concentration and efficacy, the change of blood concentration under different dosage was analyzed, and the influence on drug effect under different administration scheme was predicted. Main work: establishment of simulation model (including proportional advantage model, pharmacokinetics / pharmacodynamics model), simulation calculation, model simulation and result analysis.

Background To assess the corneal diameter and its associations in children. Design Cross-sectional school-based study. Participants The Shandong Children Eye Study included 6026 children aged 4-18 years. Methods Horizontal corneal diameter was measured by laser interferometry based ocular biometry. Main Outcome Measures Horizontal corneal diameter. Results Corneal diameter measurements were available for 5970 (99.1%) children. In multivariate analysis, larger horizontal corneal diameter (mean:12.02 ± 0.38 mm;median:10.0 mm;range:10.1-15.0 mm) was associated (regression coefficient r:0.41) with longer corneal curvature radius (P

The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors.

Room temperature ionic liquids (RTILs) played an important role in the electrochemistry because of the advantageous properties. Due to the different electrochemical behavior from the dilute solution, it was still remained a significant challenge to obtain the insight into the interfacial structure. Although the spectroelectrochemistry offered the rich spectroscopic information for obtaining the interfacial structure at molecular level, the lack of the spatial information of those techniques at nano/subnanometer scale led the difficulties in the determination of the spatial structure of double layer. Here, the surface enhanced Raman spectroscopy (SERS) Stark tuning rates of CN stretching frequency were employed to determine the electric double layer structure on Au electrode, and probes with different lengths, involving cyanide ion (CN − ), thiocyanate (SCN − ), 3-aminopropanenitrile (3-APN) and 6-aminohexanenitrile (6-AHN), were used as rulers to measure the spatial structure of double layer. In this approach, SERS combined with electrochemical control was performed to distinguish the orientation of surface species and detect the vibrational frequency of the nitrile stretching mode. For shorter probes (such as CN − and SCN − ), the nitrile group were located in the electric double layer region, resulting in measureable Stark tuning rates (d ν CN /d E ), while for longer probe molecules (such as 3-APN and 6-AHN), the interfacial potential completely decayed before reaching the nitrile group location, resulting in the negligible Stark tuning rates. The vibrational Stark tuning rates suggested that the potential drop occurred over a range of 5–6 A from the metal surface into the bulk phase of ionic liquids. The results demonstrated that the overall potential mostly dropped across the first layer and only a small fraction across the second layer. The preliminary results allowed us to obtain an insight into the physical picture of the interfacial structure of RTILs/metal system.

Purpose To investigate the prevalence of macular abnormalities in Chinese patients affected by uveitis. Methods A retrospective study was performed by reviewing the medical records and high-definition spectral domain optical coherence tomography (SD-OCT) scans in a cohort of 413 uveitis eyes to assess the presence of macular abnormalities. Results Macular abnormalities were observed in 242 (58.6%) of the 413 examined eyes with uveitis. The observed macular abnormalities include diffuse macular edema, cystoid macular edema (CME), and serous retinal detachment. In addition, vitreoretinal abnormalities in the patients with uveitis were evaluated through SD-OCT. The evaluated vitreoretinal abnormalities include epiretinal membrane, tractional CME, macular adhesions, macular hole, and choroidal neovascularization. The most frequent abnormality in the uveitis patients was CME, observed in 105 eyes (25.4%), and followed by epiretinal membrane, observed in 52 eyes (12.6%). Moreover, the percentage of uveitis patients with vitreoretinal abnormalities (23.1%) was significantly high. Conclusions Macular abnormalities were more frequently observed in uveitis compared with those in the general population. Multiple patterns of macular abnormalities indicate lesions of multilayer of cells. Therefore, when following up uveitis patients, it is highly recommended to screen with SD-OCT to evaluate the macular alterations of those patients. Careful observation of the macular abnormalities using SD-OCT may help to identify patients who are at risk for visual loss secondary to foveal changes and provide preventive treatment.

The surface plasmon resonance (SPR) catalyzed reaction has attracted considerable attention due to its promising application in heterogeneous catalysis. The acquirements on mechanism of the conversion reaction are still in challenge. It was found that the cyclic conversion of para-aminothiophenol (PATP) and 4,4′-dimercaptoazobenzene (DMAB) was critically dependent on the interfacial environments, such as hydrogen, oxygen and water, which were of the fundamental issues in electrochemistry. Here, the in situ surface enhanced Raman spectroscopy (SERS) combined with electrochemical control was developed to investigate the cyclic conversion of PATP and DMAB at the interface of [BMIm]BF4/Ag electrode and to probe the interfacial structure of water. The surface-catalyzed coupling reaction of PATP commonly occurred to produce DMAB in a fast rate with the illumination of laser. The results revealed that water played the vital role in the reduction of DMAB. The expected reduction of DMAB was absent in the extremely negative potential due to the lack of the free water at the interface in the “dried” [BMIm]BF4. The similar experiments were performed in the [BMIm]BF4/H2O mixtures with the water molar fraction of 0.01, 0.1, 0.3, 0.5, 0.7 and 0.9 respectively. The trace water in the [BMIm]BF4/H2O mixture (xw < 0.1) was mainly mixed with RTILs through the hydrogen bonding between water and RTILs. It hindered the diffusion of trace water to interface which resulted in the absence of the reduction of DMAB. With the increase of water content, the formation of clusters network water allowed the diffusion of water to the interface to facilitate the reduction. The surface reaction behavior was similar to that in the aqueous solution as the interface was completely surrounded by larger water clusters in solutions with high water content (xw = 0.7–0.9). By this strategy, the electrochemical reduction of DMAB could be served as the probe to monitor the water structure in the [BMIm]BF4/H2O mixtures, and it was believed that SERS could be developed as the powerful tool for monitoring the interfacial reaction and to resolve the interfacial structure in RTILs, particularly for the water structure.

To conduct a meta-analysis on the effects of orthokeratology in slowing myopia progression.A literature search was performed in PubMed, Embase, and the Cochrane Library. Methodological quality of the literature was evaluated according to the Jadad score. The statistical analysis was carried out using RevMan 5.2.6 software.The present meta-analysis included seven studies (two randomized controlled trials and five nonrandomized controlled trials) with 435 subjects (orthokeratology group, 218; control group, 217) aged 6 to 16 years. The follow-up time was 2 years for the seven studies. The weighted mean difference was -0.26 mm (95% confidence interval, -0.31 to -0.21; p0.001) for axial length elongation based on data from seven studies and -0.18 mm (95% confidence interval, -0.33 to -0.03; p = 0.02) for vitreous chamber depth elongation based on data from two studies.Our results suggest that orthokeratology may slow myopia progression in children. Further large-scale studies are needed to substantiate the current result and to investigate the long-term effects of orthokeratology in myopia control.

In this paper, a novel combined leakage CMA and direct decision (DD) adaptive algorithm using automatic iteration step adaptive blind equalizer is presented. In contrast to known CMA algorithm, the novel algorithm can approach the performance of mean-square error and fast convergent rate. For adaption of filters, efficient automatic iteration step and DD algorithm is present. The novel algorithm is lower computational complexity withO(N) and N is the filter order. Furthermore, the relation of novel algorithm to CMA algorithm is investigated. Finally, it is shown that proposed combined LCMA-DD algorithm is robust against amplitude and phase offset with fast convergence and mean-square error.

To assess the corneal diameter and its associations in children.Cross-sectional school-based study.Six thousand twenty-six children aged 4-18 years were included in the Shandong Children Eye Study.Horizontal corneal diameter was measured by laser interferometry-based ocular biometry.Horizontal corneal diameter.Corneal diameter measurements were available for 5970 (99.1%) children. In multivariate analysis, larger horizontal corneal diameter (mean: 12.02 ± 0.38 mm; range: 10.1-15.0 mm) was associated with longer corneal curvature radius longer axial length, male gender, younger maternal age, rural region of habitation and lower intraocular pressure measurements. Higher prevalence of abnormally large corneas (macrocorneas; horizontal diameter ≥ 12.76 mm; mean value +2 × standard deviations; mean: 2.6%; 95% CI: 2.2, 3.0) was associated with longer corneal curvature radius, longer axial length, younger maternal age and male gender. Higher prevalence of abnormally small corneas (horizontal diameter ≤ 11.24mm; mean value -2 × standard deviations; mean: 2.4%; 95% CI: 2.0, 2.8) was correlated with shorter corneal curvature radius, shorter axial length and urban region of habitation. Neither abnormally large nor small corneas were correlated with time spent indoors/outdoors.In 4 to 18-year-old children, larger corneal diameter was associated most strongly with flatter corneal curvature, followed by longer axial length and male gender. Corneal diameter was independent of age beyond an age of 4 years. Abnormally large and abnormally small corneas may be defined as being ≥12.76 and ≤11.24 mm in diameter, respectively. Corneal diameter was not correlated with time spent indoors/outdoors.

Purpose: To investigate ocular axial length (AL) in Chinese children. Methods: The Shandong Children Eye Study included 6,364 children aged 4-18 years. Results: Longer AL (mean 23.45 ± 1.20 mm, range 18.80-28.59 mm) was associated (multivariate analysis; correlation coefficient r2: 0.61) with older age (p < 0.001, standardized correlation coefficient β = 0.35, unstandardized regression coefficient B = 0.13, 95% confidence interval [CI] 0.12, 0.15), male gender (p < 0.001, β = -0.24, B = -0.10, 95% CI -0.29, -0.19), urban region (p < 0.001, β = 0.10, B = 0.25, 95% CI 0.20, 0.31), body height (p < 0.001, β = 0.22, B = 0.02, 95% CI 0.01, 0.02), maternal education (p < 0.001, β = 0.07, B = 0.07, 95% CI 0.05, 0.10), paternal myopia (p < 0.001, β = 0.09, B = 0.26, 95% CI 0.20, 0.33), maternal myopia (p < 0.001, β = 0.08, B = 0.23, 95% CI 0.17, 0.30), more time spent indoors reading/writing (p < 0.001, β = 0.05, B = 0.03, 95% CI 0.02, 0.04), less time spent outdoors (p = 0.005, β = -0.03, B = -0.01, 95% CI -0.02, -0.003), longer corneal curvature radius (p < 0.001, β = 0.36, B = 1.63, 95% CI 1.53, 1.74) and higher intraocular pressure (p = 0.008, β = 0.03, B = 0.01, 95% CI 0.004, 0.02). High axial myopia (AL ≥26.0 mm) present in 202 children (3.4 ± 0.2%, 95% CI 2.92, 3.84) was associated with less time spent outdoors (p = 0.002, odds ratio 0.92, 95% CI 0.87, 0.97) in multivariate analysis. Conclusions: In children in the less developed Eastern Chinese province of Shandong, the prevalence of high axial myopia was >10% among 16-year-olds. A modifiable factor associated with higher prevalence of high axial myopia was less time spent outdoors.

The plasmon catalyzed surface reaction has been attracted considerable attention due to its promising application in heterogeneous catalysis. This kind of plasmon catalysis played bilateral roles in driving the unconventional reactions or destructing the surface molecule layer. The acceleration or inhibition on this catalysis is still remained significant challenge. In this paper, monolayer film of Au nanoparticles was fabricated at air/water interface as substrates both for surface enhanced Raman spectroscopy (SERS) and plasmon catalyzed surface reaction. The influence from several issues, involving surfactants, coadsorption species, the solvent and water, were systemically investigated to probe the acceleration and inhibition on the plasmon catalysis reaction. The concentration and molecular weight of surfactant polyvinylpyrrolidone (PVP) exhibited significant influence in the reactive activity for the plasmon catalyzed dimerization of para-nitrothiophenol (PNTP) to p,p'-dimercaptoazobenzene (DMAB). A suitable molecular weight of 10,000 and concentration of 10mg/mL were beneficial for improving the conversion efficiency of PNTP to DMAB. The higher molar ratio of coadsorbed 1-octanethiol and the aprotic solvents resulted in the inhibition of dimerization because 1-octanethiol occupied the surface sites to isolate the adsorbed PNTP molecules with a larger distance and lack of proton source. The plasmon catalysis occurred in ionic liquids suggested that water was essential for the dimerization of PNTP, in which it was used to accelerate the reaction rate and severed as the hydrogen source.

Purpose Spectral-domain optical coherence tomography (SD-OCT) is a noninvasive technique that can provide high-resolution images of macular morphology. The purpose of this study was to examine the pathological mechanism of uveitis and compare the changes in the macula of uveitis patients and the histopathological features of experimentally induced uveitis in mice. Methods Macular OCT was performed on 78 eyes of 51 patients of the Eye Hospital of Shandong University of Traditional Chinese Medicine, China, with apparent uveitis changes. C57BL/6 mice were injected with interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from naive mice immunized with complete Freund adjuvant IRBP(1-20) to induce uveitis. The disease was monitored by indirect fundoscopy. The eyes of the mice with experimental autoimmune uveitis (EAU) were enucleated 18 days after injection and classified according to pathological characteristics. Results The characteristics of uveitis were classified into six categories. Macular edema was detected in 48 eyes (61.5%); macular epiretinal membrane in 22 eyes (28.2%); choroidal neovascularization and macular lamellar holes in 4 eyes (5.1%), respectively; macular atrophy in 10 eyes (12.8%); and serous neuroepithelium detachment in 22 eyes (28.2%). As in human patients, pathological examinations of mouse EAU showed inflammation, folds, and atrophy of the outer part of the neuroretina, choroidal neovascularization with hemorrhagic retinal detachment, serous neuroepithelium detachment, and epiretinal membrane formation. Conclusions Macular OCT of uveitis patients can display different morphological characteristics. Mouse EAU can simulate human uveitis. The comparative analysis of macular OCT in human uveitis and transfer EAU histopathology changes could provide important information on the pathogenesis of human uveitis.

Purpose To compare primary intra-ocular lens (IOL) implantation with use of press-on spherical lens for aphakia correction following unilateral infantile cataract removal. Methods Sixty infants with a unilateral cataract underwent cataract surgery and were randomly assigned to the IOL (A group) or no IOL group (B group). Residual refractive error was corrected with spectacles in the A group and a press-on spherical lens was used to treat aphakia in the B group. Grating visual acuity (VA) was measured and patients were followed for up to 1 year. Results LogMAR VA in the operated eyes of both groups was significantly better 1 year than 1 month after surgery. Mean logMAR VA difference between 1 year and 1 month after surgery was higher in the A group (0.457 ± 0.110) than in the B group (0.323 ± 0.114, p

PURPOSE: To examine the prevalence of refractive errors and prevalence and causes of vision loss among preschool and school children in East China. METHODS: Using a random cluster sampling in a cross-sectional school-based study design, children with an age of 4-18 years were selected from kindergartens, primary schools, and junior and senior high schools in the rural Guanxian County and the city of Weihai. All children underwent a complete ocular examination including measurement of uncorrected (UCVA) and best corrected visual acuity (BCVA) and auto-refractometry under cycloplegia. Myopia was defined as refractive error of ≤-0.5 diopters (D), high myopia as ≤ -6.0D, and amblyopia as BCVA ≤ 20/32 without any obvious reason for vision reduction and with strabismus or refractive errors as potential reasons. RESULTS: Out of 6364 eligible children, 6026 (94.7%) children participated. Prevalence of myopia (overall: 36.9 ± 0.6%;95% confidence interval (CI):36.0,38.0) increased (P

AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy (PDT) vs ranibizumab monotherapy in the treatment of age-related macular degeneration (AMD).METHODS:The Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Pubmed, and Embase were searched. There were no language or data restrictions in the search for trials. Only randomized controlled trials (RCTs) were included. Methodological quality of the literatures was evaluated according to the Jadad Score. RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review, among which four of them were included in quantitative analysis. The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity (BCVA) change vs baseline at month 12 compared with that of the combination treatment group, and the statistical difference was significant (WMD, -2.61; 95% CI, -5.08 to -0.13; P=0.04). However, after the removal of one study, the difference between the two groups showed no significant difference (WMD, -2.29; 95% CI, -4.81 to 0.23; P=0.07). Meanwhile, no significant central retinal thickness (CRT) reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up. Nevertheless, the combination group tended to have a greater reduction in CRT (WMD, -4.13μm; 95%CI, -25.88 to 17.63, P=0.71). The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference (RR, 0.72; 95% CI, 0.54 to 0.95; P=0.02). Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month 12 between the two groups (RR, 0.93; 95% CI, 0.76 to 1.15; P=0.52). The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab monotherapy group. As major adverse events, the differences in the number of eye pain, endophthalmitis, hypertension and arterial thromboembolic events were not significant between the two groups, and the incidence of serious adverse events in the two groups was very low.CONCLUSION:For the maintenance of vision, the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference. Compared with the combination of ranibizumab and PDT, patients treated with ranibizumab monothearpy may gain more visual acuity (VA) improvement. The combination treatment group had a tendency to reduce the number of ranibizumab retreatment. Both the two treatment strategies were well tolerated.

The identification of the biomarkers of patients with acute anterior uveitis (AAU) may allow for a less invasive and more accurate diagnosis, as well as serving as a predictor in AAU progression and treatment response. The aim of this study was to identify the potential biomarkers and the metabolic pathways from plasma in patients with AAU. Both plasma metabolic biomarkers and metabolic pathways in the AAU patients versus healthy volunteers were investigated using ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) and a metabonomics approach. The principal component analysis (PCA) was used to separate AAU patients from healthy volunteers as well as to identify the different biomarkers between the two groups. Metabolic compounds were matched to the KEGG, METLIN, and HMDB databases, and metabolic pathways associated with AAU were identified. The PCA for UPLC–MS data shows that the metabolites in AAU patients were significantly different from those of healthy volunteers. Of the 4,396 total features detected by UPLC–MS, 102 features were significantly different between AAU patients and healthy volunteers according to the variable importance plot (VIP) values (greater than two) of partial least squares discriminate analysis (PLS-DA). Thirty-three metabolic compounds were identified and were considered as potential biomarkers. Meanwhile, ten metabolic pathways were found that were related to the AAU according to the identified biomarkers. These data suggest that metabolomics study can identify potential metabolites that differ between AAU patients and healthy volunteers. Based on the PCA, PLS-DA, several potential metabolic biomarkers and pathways in AAU patients were found and identified. In addition, the UPLC–MS technique combined with metabonomics could be a suitable systematic biology tool in research in clinical problems in ophthalmology, and can provide further insight into the pathophysiology of AAU.

To explore the effects of exogenous interleukin (IL)-2 and IL-23 on differentiation of IRBP 1-20-specific T cells originated from C57BL/6 mouse with experimental autoimmune uveitis (EAU) and to investigate the difference in pathogenicity.Experimental study. Thirty C57BL/6 mice were immunized subcutaneously with 200 µl emulsion containing 200 µg interphotoreceptor retinoid-binding protein (IRBP) 1-20 and 0.8 mg mycobacterium tuberculosis in complete Freund's adjuvant, distributed over six spots at the tail base and on the flank. On postimmunization Day 13, spleens and draining lymph nodes were removed from mice, and a part of spleens, as the control group, was reserved for examining the expression of IFN-γ mRNA and IL-17 mRNA by RT-PCR. T cells were isolated from the rest of spleens and lymph nodes by passage through a nylon wool column, and then T cells were stimulated for 48 hours with IRBP 1-20 in the presence of antigen-presenting cell and mouse recombinant cytokine IL-2 or IL-23. The IRBP 1-20-specific T cells were separated by Ficoll gradient centrifugation, the expressions of IFN-γ mRNA and IL-17 mRNA were assessed by RT-PCR, and IFN-γ and IL-17 in T cells supernatant were detected using a commercial ELISA kit. The T cells were cultured for another 48 hours, and then the proportions of IL-17(+)γδ(+)T cells were analyzed by flow cytometry. EAU models were built in 30 C57BL/6 mice, T cells from which were randomly divided into two groups according to the methods mentioned above: IL-2 group and IL-23 group. Transfer EAU models were built in other 6 mice and divided into two groups, IL-2 group and IL-23 group, by intraperitoneal injection of 3.5×10(6) IRBP-special-T cells from IL-2 group or IL-23 group respectively. Clinical changes were observed by indirect ophthalmoscopy on postimmunization day 3, 7, 14. For histopathological evaluation, whole eyes were collected on postimmunization day 21. Rank sum test, one-way ANOVA and paired t test were used to analyze the results. A comparison of pathogenicity was made between Th1 and Th17 through clinical observation and histopathological evaluation of B6 mouse.Rosette formation was found among T cells on poststimulation day 2. There was a statistical difference in the expression of IFN-γ mRNA between the IL-2 group and normal group or IL-23 group (0.26 ± 0.02 vs. 0.12 ± 0.05 or 0.10 ± 0.00) (F = 80.51, P = 0.003); however, the expression of IFN-γ in the IL-2 group [(13 124.67 ± 107.73) µg/L] was higher than that of the IL-23 group [(3953.67 ± 117.34) µg/L] (t = 169.61, P = 0.000); and the expression of IL-17 mRNA in the IL-2 group [(588.67 ± 77.43) µg/L] was lower than that of the IL-23 group [(5038.33 ± 88.00) µg/L] (t = -361.71, P = 0.000). Flow cytometer showed that the concentration of IL-17 in the IL-2 group [(3.23 ± 0.28)%] was significantly lower than that in the IL-23 group [(9.93 ± 0.55)%] (t = -33.18, P = 0.001). There was a significant difference in the proportion of IL-17(+)γδ(+)T cells between the IL-23 group and IL-2 group (9.93 ± 0.55 vs. 3.23 ± 0.28) (t = -33.18, P = 0.001). Inflammatory response could not be detected in either group three days after injection of IRBP 1-20-specific T cells. Both groups of mice had the most severe inflammatory response on the 14 th day, of which that of the IL-23 group was significantly more severe.IL-23 facilitates IRBP 1-20-specific T cells to differentiate into Th17, whereas IL-2 inhibits this process and induces these cells to differentiate towards Th1. Further studies showed that the pathogenicity of Th17 cells was significantly higher than that of Th1 cells.

PURPOSE To describe prevalence and associations of anisometropia in children. METHODS The cross-sectional school-based study included children aged 4 to 18 years. RESULTS The study included 6025 (94.7%) of 6364 eligible children. Mean refractive anisometropia was 0.37 ± 0.57 diopters (median: 0.25 diopters; range: 0-7.88 diopters; prevalence [≥1 diopter]: 7.0% ± 0.3%). In multivariate analysis (regression coefficient r: 0.66), higher refractive anisometropia was associated with older age (P < 0.001; β: 0.07; B: 0.01; 95% CI: 0.01-0.02), higher maternal education level (P < 0.001; β: 0.04; B: 0.02; 95% CI: 0.01-0.03), more total time spent indoors reading or writing (P = 0.001; β: 0.04; B: 0.01; 95% CI: 0.01-0.02), larger intereye difference in axial length (P < 0.001; β: 0.57; B: 1.20; 95% CI: 1.15-1.24), shorter mean axial length of both eyes (P = 0.03; β: -0.03; B: -0.02; 95% CI: -0.03 to -0.001), larger intereye difference in best corrected visual acuity (BCVA) (P < 0.001; β: 0.14; B: 1.83; 95% CI: 1.54-2.12), and lower stereoacuity (P < 0.001; β: 0.08; B: 0.31; 95% CI: 0.22-0.39). Refractive anisometropia showed a U-shaped correlation with refractive error. Higher anisomyopia was associated (r: 0.57) with older age (P = 0.001; β: 0.05; B: 0.006; 95% CI: 0.002-0.009), higher level of paternal education (P = 0.001; β: 0.01; B: 0.01; 95% CI: 0.01-0.02), more total time spent indoors reading or writing (P = 0.01; β: 0.03; B: 0.01; 95% CI: 0.00-0.01), larger intereye difference in axial length (P < 0.001; β: 0.22; B: 0.26; 95% CI: 0.23-0.29), greater myopic refractive error (P < 0.001; β: -0.46; B: -0.07; 95% CI: -0.08 to -0.07), and lower corneal astigmatism (P < 0.001; β: -0.10; B: -0.06; 95% CI: -0.08 to -0.05). In the same multivariate model, hyperopic anisometropia was not significantly associated with time spent indoors with reading (P = 0.18). Cylindrical anisometropia (mean: 0.30 ± 0.32 diopters; prevalence [≥1 diopter]: 3.7% ± 0.2%) increased with higher refractive anisometropia (P < 0.001; β: 0.16; B: 0.09; 95% CI: 0.08-0.11), greater myopic refractive error (P < 0.001; β: -0.06; B: -0.01; 95% CI: -0.01 to -0.01), higher corneal astigmatism (P < 0.001; β: -0.22; B: -0.15; 95% CI: -0.17 to -0.13), and lower mean BCVA (P < 0.001; β: 0.11; B: 0.90; 95% CI: 0.68-1.17). CONCLUSIONS In 4- to 18-year-old children, refractive anisometropia and anisomyopia increased with systemic parameters such as age, parental education level, and lifestyle of the children, for example, more time spent indoors reading or writing. In contrast, hyperopic anisometropia and cylindrical anisometropia were not related with lifestyle parameters.

To assess the safety, efficacy, predictability, stability, and changes in cylindrical degree and axis after iris recognize-guided LASIK with the Zyoptix 4.01 System for the correction of myopic astigmatism.The present study was a prospective, nonrandomized, self-controlled trial. Iris recognize-guided LASIK with the Zyoptix 4.01 System (BauschLomb) was performed in 97 patients (183 eyes) with myopic astigmatism in a 6-month trial. Patients were divided into 3 group according to the pre-operative cylindrical degree: Group 1, -0.50 to -1.00D, 79 eyes; Group 2, -1.25 to -2.00D, 70 eyes; Group 3, 2.00 to 4.00D, 34 eyes. They were also grouped by preoperative astigmatism axis: Group A, with the rule (WTR) astigmatism, 126 eyes; Group B, against the rule (ATR), 34 eyes; Group C, oblique axis astigmatism, 23 eyes. After a Hansatome microkeratome cut, iris recognized wavefront-based excimer ablation (Zyoptix 100) was performed. The degree and axis of astigmatism pre-operative and at various times post-operatively (1 day, 1 month, 3 month and 6 months) were analyzed and compared.At 6 month post-operatively, uncorrected visual acuity (VA) was 1.0 or better in 92.3% of the eyes, and 0.5 or better in all eyes. No eye lostor = 1 lines of best spectacle-corrected VA (BSCVA) at 6 month post-operatively; 60 eyes gained 1 line of BSCVA, and 22 eyes gained 2 lines. The cylindrical degree of astigmatism decreased from (-1.54 +/- 0.65) D of pre-operation to (-0.26 +/- 0.25) D (6 month, post-operatively), the difference between these two groups was statistically significant. The uncorrected VA (UCVA) and the degree of astigmatism returned to normal in the first week and tended to be stable after 1 month. Six months after the operation, WTR astigmatism decreased from106 eyes (per-operation) to 45 eyes (post-operation). ATR astigmatism decreased from 43 eyes (per-operation) to 31 eyes (post-operation). Oblique astigmatism increased from 34 to 38 eyes. Sixty-nine eyes became non-astigmatism 6 months after the operation.Iris recognize-guided LASIK using Zyoptix is an effective and safe procedure for the treatment of myopic astigmatism.

PURPOSE To examine the thickness of the macular choroid and its associations in school children aged 6 to 18 years. METHODS The school-based cross-sectional Shandong Children Eye Study included 6026 (94.7%) of 6364 eligible children fulfilling the inclusion criterion of an age from 4 to 18 years. Spectral-domain optical coherence tomography (SD-OCT) was performed for a subgroup of 972 school children aged 6+ years. All participants underwent ocular examinations, including measurement of visual acuity, cycloplegic refractometry, biometry, and SD-OCT (enhanced depth imaging mode) for measurement of choroidal thickness. RESULTS The study included 972 children (501 girls) with a mean age of 11.3 ± 3.3 years (range, 6-18 years) and mean axial length of 24.10 ± 1.56 mm (range, 16.57-28.82 mm). Mean choroidal thickness was thicker (P < 0.001) at 500 μm temporal to the foveola (290 ± 67 μm) than in the subfoveal region (283 ± 67 μm; range, 113-507 μm) and the region 500 μm superior to the fovea (283 ± 66 μm), where it was thicker (P < 0.001) than at 500 μm inferior of the foveola (281 ± 66 μm), and it was thinnest (P < 0.001) at 500 μm nasal of the foveola (268 ± 67 μm). In multivariate analysis, thicker SFCT was (overall correlation coefficient r: 0.51) associated with shorter axial length (P < 0.001; standardized correlation coefficient β: -0.48; B: -23.7; 95% confidence interval [CI]: -27.2 to -20.3), male sex (P = 0.006; β: -0.08; B: -10.7; 95% CI: -18.3 to -3.11), and younger age (P = 0.04; β: -0.07; B: -1.46; 95% CI: -2.85 to -0.07). CONCLUSIONS As in adults, thicker SFCT in children and teenagers was markedly associated with shorter axial length, and to a lesser degree with male sex and older age. As in adults, increasing axial myopia in teenagers is associated with choroidal thinning and development of a leptochoroid.

To evaluate the efficacy of 5-fluorouracil polyactic acid microsphere in prevention of proliferative vitreoretinopathy (PVR).5-fluorouracil polyactic acid microsphere or 5-fluorouracil were used to implant into rabbits vitreous cavity. 48 healthy rabbits were divided into 3 groups: rabbits in Group 1 received implantation of 5-fluorouracil polyactic acid microsphere; rabbits Group 2 served as polyactic acid microsphere control; rabbits in Group 3 received only 5-fluorouracil powder. Macrophages were injected into vitreous cavity of rabbit to induce PVR. 0.2 ml BSS containing 25 mg microsphere with 2.6 mg 5-fluorouracil was injected into vitreous cavity of two eyes in Group 1. 0.2 ml BSS containing 25 mg microsphere without medicine and 0.2 ml BSS containing 2.6 mg 5-fluorouracil were injected into rabbits vitreous cavity in Group 2 and 3 respectively, Drug content in aqueous humor was measured regularly. Release feature of 5-fluorouracil polyactic acid microsphere in vivo was observed. The efficacy of the inhibition of PVR was evaluated according to Ryan's grade of proliferative vitreoretinopathy.The releasing time of 5-fluorouracil polyactic acid microsphere was much longer than 5-fluorouracil powder. Its half life T(1/2) was 379.05 h with low clearance rate. The attack rate of retinal detachment in Group 2 was 62.5% and 71.9% on the 21st and 28th day respectively. The attack rate of retinal detachment in Group 3 was 64.3% and 78.6% whereas that of Group 1 was 13.3% and 13.3% on the 21st and 28th day. There was statistical difference in retinal detachment rate in Group 1 and 2 or 3 (P0.01). No differences was found in retinal detachment ration in Group 2 and 3 (P0.05).Implantation of 5-fluorouracil polyactic acid microsphere into vitreous cavity can effectively prevent proliferative vitreoretinopathy induced by macrophages in rabbit model.

To study the results of using multifocal intraocular lens (MIOL) for the treatment of cataract.After the small incision phacoemulsification, MIOL was inserted into the eye in 30 cases (36 eyes, test group); single-focal intraocular lens (SIOL) was inserted in 32 cases (40 eyes, control group). Visual acuity, focal depth, corneal astigmatism, contrast sensitivity, glare sensitivity, operative complications and untoward visual symptoms were observed. The follow-up period was 6.0 approximately 18.0 months.Percentage of patients with uncorrected near visual acuity 0.5 or better accounted was 80.6% (29/36) in the test group and 25.0% (10/40) in the control group, there was a significantly statistical difference between these two groups 6 months postoperatively (P0.05). There was no significantly statistical difference between the corrected near and far visual acuity and uncorrected far visual acuity of these two groups (P0.05). In patients with +1.00 - -1.00 D accommodation power, the percentage of patients with visual acuity 0.5 or better was 97.2% (35/36) in the test group and 97.5% (39/40) in the control group, there was no significantly difference between these two groups (P0.05). In patients with -1.50 D and -2.50 - -3.50 D accommodation power, the percentage of patients with visual acuity 0.5 or better was 97.2% (35/36) and 88.9% (32/36) in the test group, respectively; which was significantly greater than those in the control group [0.0% (0/40) and 0.0% (0/40), respectively] (P0.05). In patients with visual acuity 0.5 or better, the depth of focus was 4.50 D in 86.11% cases of the test group and was 2.00 D in 97.5% cases of the control group. There was no statistically significant difference between the preoperative corneal stigmatism and corneal astigmatism 1 week, 1 month, 3 months and 6 months after the operation in both groups (P0.05). Low frequency contrast sensitivity and glare sensitivity (28.49 +/- 6.45 and 16.97 +/- 4.40, respectively) in the test group were significantly lower than those of the control group (36.20 +/- 7.45 and 24.05 +/- 6.08, respectively) (P0.05). There was no significantly statistical difference in medium and high frequency contrast sensitivity and glare sensitivity between these two groups (P0.05). Two eyes needed Nd:YAG laser posterior capsulotomy in both groups. Two patients (5.6%) with unilateral MIOL complained glare at night.MIOL implantation is a safe and effective method for the treatment of cataract. MIOL has a distinct advantage in providing a full-distance visual acuity.

PURPOSE We examined the distribution of intraocular pressure (IOP) and its associated factors in children. METHODS Using a random cluster sampling from kindergartens, primary schools, and junior and senior high schools from rural Guanxian County and the city of Weihai, the school-based cross-sectional Shandong Children Eye Study included children aged 4 to 18 years. All participants underwent an ocular examination, including ocular biometry, cycloplegic refractometry, and noncontact tonometry. RESULTS Mean IOP was 17.6 ± 2.7 mm Hg (range, 10-28 mm Hg). The IOP increased up to an age of 10 years and subsequently decreased with older age. In multivariate regression analysis, higher IOP was associated with female sex (P < 0.001; standardized correlation coefficient β, 0.06; regression coefficient β, 0.34; 95% confidence interval [CI], 0.18, 0.50), higher body mass index (P < 0.001; correlation coefficient β, 0.09; regression coefficient β, 0.07; 95% CI, 0.04,0.09), younger age (P < 0.001; correlation coefficient β, -0.15; regression coefficient β, -0.13; 95% CI, -0.17,-0.10), maternal myopia (P < 0.001; correlation coefficient β, 0.05; regression coefficient β, 0.34; 95% CI, 0.15,0.53), and more time spent indoors with reading/writing (P = 0.002; correlation coefficient β, 0.05; regression coefficient β, 0.07; 95% CI, 0.03,0.11), and with the ocular parameters of longer axial length (P < 0.001; correlation coefficient β, 0.14; regression coefficient β, 0.29; 95% CI, 0.21,0.37) and smaller corneal horizontal diameter (P < 0.001; correlation coefficient β, -0.06; regression coefficient β, -0.31; 95% CI, -0.46,-0.15). CONCLUSIONS In children aged 4 to 18 years, IOP showed an M-shaped association with age. Higher IOP was associated with the nonocular parameters of female sex (P < 0.001), higher body mass index (P < 0.001), younger age (P < 0.001), maternal myopia (P < 0.001), and more time spent indoors with reading/writing (P = 0.002), and with the ocular parameters of longer axial length (P < 0.001) and smaller corneal horizontal diameter (P < 0.001).