Paxillin promotes the migration and angiogenesis of HUVECs and affects angiogenesis in the mouse cornea.

Neonatal vascular ophthalmopathy is a refractory ophthalmologic disease, and is a major cause of blindness. Occurrence of neonatal vascular ophthalmopathy may be associated with Paxillin, a cellular adhesion molecule which promotes the migration of endothelial cells and angiogenesis. To explore the role of PXN in corneal angiogenesis, human umbilical vein endothelial cells were divided into five groups: i) Control group; ii) Empty vector-transfected control group; iii) PXN knockdown group (shPXN group); iv) PXN-negative control (NC) group; and v) PXN over-expressed group (overExp group). PXN protein levels, migration and tube formation were assessed in the different experimental groups. Mice were divided into four groups: i) Control; ii) Model; iii) shPXN; and iv) overExp groups. Tube formation was significantly increased in the overExp group compared with the empty vector-transfected control group (P<0.01). Tube formation was significantly decreased in the shPXN group compared with the PXN-NC group (P<0.01). In mice, blood corpuscles were significantly decreased in the shPXN group. PXN promoted the migration of endothelial cells and corneal angiogenesis. The results of the present study suggest a role for PXN in corneal angiogenesis and provide a theoretical basis and potential target for the treatment of corneal angiogenesis.

The role of radiotherapy in pulmonary large cell neuroendocrine carcinoma: propensity score matching analysis.

The aim of the study was to investigate the survival advantage of radiotherapy (RT) in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC). Patients with pulmonary LCNEC were extracted from the Surveillance, Epidemiology, and End Results (SEER) dataset between January 2004 and December 2013. Propensity score matching (PSM) analysis with 1:1 was used to ensure well-balanced characteristics of all comparison groups. A total of 1480 eligible cases were identified, with a median follow-up time of 11 months (0-131 months). After PSM, 980 patients were classified in no radiotherapy (No RT) and radiotherapy (RT) groups (n = 490 each). Patients in the RT group harbored significantly higher 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates compared to those in the No RT group (both P < 0.05). Furthermore, RT was an independent favorable prognostic factor of OS as well as CSS in multivariate analysis, both before [OS: hazard ratio (HR) 0.840, 95% confidence interval (CI) 0.739-0.954, P = 0.007; CSS: HR 0.847, 95% CI 0.741-0.967, P = 0.014] and after (OS: HR 0.854, 95% CI 0.736-0.970, P = 0.016; CSS: HR 0.848, 95% CI 0.735-0.978, P = 0.023) PSM. In subgroup analysis, American Joint Committee on Cancer (AJCC) stage II and III, tumor size 5-10 cm, patients who underwent no surgery, or patients who received chemotherapy could significantly benefit from RT (all P < 0.05). To sum up, our findings suggested that RT could prolong the survival of patients with pulmonary LCNEC, especially those with stage II and III, tumor size 5-10 cm, those with no surgery, or those who received chemotherapy.

Inhibition of EZH2 alleviates angiogenesis in a model of corneal neovascularization by blocking FoxO3a-mediated oxidative stress.

Enhancer of zeste homolog 2 (EZH2), a well-known methyltransferase, mediates histone H3 lysine 27 trimethylation (H3K27me3) and plays a vital role in ophthalmological disease. However, its role in corneal neovascularization (CoNV) remains unclear. In vitro and in vivo models were assessed in hypoxia-stimulated angiogenesis and in a mouse model of alkali burn-induced CoNV. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions and different reoxygenation times to identify the molecular mechanisms involved in this process. In this study, we found that EZH2 was positively related to corneal alkali burn-induced injury. Inhibition of EZH2 with 3-Deazaneplanocin A (DZNeP) alleviated corneal injury, including oxidative stress and neovascularization in vivo. Similarly, inhibition of EZH2 with either DZNeP or small interfering RNA (siRNA) exerted an inhibitory effect on hypoxia/reoxygenation (H/R)-induced oxidative stress and angiogenesis in HUVECs. Moreover, our study revealed that ablation of reactive oxygen species (ROS) with N-acetyl-cysteine suppressed angiogenesis in HUVECs exposed to H/R stimulation. Furthermore, Forkhead-box protein O3a (FoxO3a), which was positively associated with ROS production and angiogenesis, was elevated during H/R. This effect could be reversed through the suppression of the transcription activity of EZH2 with DZNeP or siRNA. In addition, the PI3K/Akt pathway, which is the upstream of FoxO3a, was activated in both DZNeP-treated mice and EZH2-inhibited HUVECs. Collectively, our results demonstrated that the inhibition of EZH2 alleviated corneal angiogenesis by inhibiting FoxO3a-dependent ROS production through the PI3K/Akt signaling pathway. These findings indicate that EZH2 may be a valuable therapeutic target for CoNV.

The Application of Artificial Neural Networks and Logistic Regression in the Evaluation of Risk for Dry Eye after Vitrectomy.

Supervised machine-learning (ML) models were employed to predict the occurrence of dry eye disease (DED) after vitrectomy in this study. The clinical data of 217 patients receiving vitrectomy from April 2017 to July 2018 were used as training dataset; the clinical data of 33 patients receiving vitrectomy from August 2018 to September 2018 were collected as validating dataset. The input features for ML training were selected based on the Delphi method and univariate logistic regression (LR). LR and artificial neural network (ANN) models were trained and subsequently used to predict the occurrence of DED in patients who underwent vitrectomy for the first time during the period. The area under the receiver operating characteristic curve (AUC-ROC) was used to evaluate the predictive accuracy of the ML models. The AUCs with use of the LR and ANN models were 0.741 and 0.786, respectively, suggesting satisfactory performance in predicting the occurrence of DED. When the two models were compared in terms of predictive power, the fitting effect of the ANN model was slightly superior to that of the LR model. In conclusion, both LR and ANN models may be used to accurately predict the occurrence of DED after vitrectomy.

Anomalous retinal artery associated with branch retinal artery occlusion and neovascular glaucoma: A case report.

BACKGROUND: Congenital anomalous retinal artery is rare and does not typically affect visual acuity. However, an abnormal artery that passes through and supplies blood to the macular area complicated with branch retinal artery occlusion may negatively impact visual acuity. This study reports an unusual case of anomalous retinal artery combined with retinal artery occlusion. CASE SUMMARY: A 52-year-old male presented with severely reduced vision in the right eye. The fundus examination revealed an anomalous artery, extending from the superior temporal arcade and crossing the macula into the inferior temporal quadrant. The anomalous artery was partially occluded, with a narrowed lumen. A cherry-red spot was observed with whitening of the macular area, suggesting macular edema. Fundus fluorescein angiography revealed disc leakage and a delayed filling time. Optical coherence tomography revealed increased thickness of the neuroretina and underlying layers. The patient was treated with vessel dilation, hyperbaric oxygen, ocular massage, and thrombolytics. Visual acuity of the right eye subsequently improved to 20/200 from hand motion at 4 cm. This improvement in visual acuity persisted when the patient was examined at the 1-mo follow-up visit. The patient was subsequently followed via telephone interview. The information provided via interview indicated that visual acuity in the affected eye was stable up to 6 years from the time of the initial presentation. However, after 3 additional years, the patient was diagnosed with neovascular glaucoma in the right eye, which was subsequently enucleated. CONCLUSION: Although congenital retinal vascular anomaly, including anomalous retinal artery, rarely affects vision, when complicated with branch retinal artery occlusion, the abnormal artery that supplies the macula may severely reduce visual acuity.

Orbital neuroblastoma metastasis: A case report and literature review.

RATIONALE: Neuroblastoma is one of the most common tumors found in children, and mostly arises in the adrenal gland and paravertebral regions. Orbital neuroblastoma metastasis is relatively rare, and is associated with poor prognosis. Since the symptoms and signs of orbital neuroblastoma are not specific, its diagnosis remains challenging. PATIENT CONCERNS: A 3-year-old girl presented with periorbital ecchymoses (raccoon eyes) and proptosis for 40 days. DIAGNOSES: Abdominal magnetic resonance imaging (MRI) and sonography analysis revealed a large mass in the left adrenal gland (primary tumor). The computed tomography and MRI further revealed multiple soft tissue masses in the skull and both orbits with erosion of the adjacent bones (the metastasis). The histological analysis of the tumor removed from the right orbit confirmed the diagnosis of neuroblastoma. INTERVENTIONS: The mass on the right face was surgically removed. OUTCOMES: The patient exhibited no deteriorative signs at the 6-month follow-up. LESSONS: Clinical manifestations, such as periorbital ecchymoses and proptosis, in combination with radiological analysis and histological findings, are important for the diagnosis of orbital neuroblastoma metastasis.

Torsional and burst mode phacoemulsification for patients with hard nuclear cataract: A randomized control study.

This article aims to evaluate the outcomes of torsional and burst mode phacoemulsification in hard nuclear cataracts.Eighty eyes with grade IV or V nuclear opalescence were treated with phacoemulsification and intraocular lens implantation using conventional mode (Group A, n = 40) or torsional and burst mode phacoemulsification (Group B, n = 40). For good visualization of anterior capsule, trypan blue was injected to the anterior chamber before continuous circular capsulorhexis. The mean cumulative dissipated energy and ultrasound time were recorded. The best-corrected visual acuity, endothelial cell density, and central corneal thickness were measured before and at 1 month after surgery.The cumulative dissipated energy and ultrasound time of Group B were significantly less than that of Group A. The postoperative best-corrected visual acuities of the 2 groups were comparable. At 1 month after surgery, the changes in the endothelial cell density were significantly greater in Group A than in Group B, and the changes in the central corneal thickness were not significantly different between the 2 groups.Torsional and burst mode is a safe and effective surgical method for treating hard cataracts.

Risk Factors for Dry Eye Syndrome: A Retrospective Case-Control Study.

PURPOSE: To investigate the independent risk factors of dry eye syndrome (DES) in Chinese. METHODS: A hospital-based age- and sex-matched population was enrolled with a case-control ratio of 1:2, with 789 DES case patients and 1119 healthy family members. Both groups underwent standard ophthalmologic examinations, including slit-lamp evaluation of the anterior segment, measurement of tear film breakup time, Schirmer test, and corneal fluorescein staining. Data on demographic characteristics and lifestyle habits were collected using a questionnaire. Dry eye syndrome risk factors were identified by univariate and multivariate logistic regression analyses. RESULTS: The following independent risk factors showed significant association with DES: diabetes (odds ratio [OR], 1.408; 95% confidence interval [CI], 1.031 to 1.924), hepatitis C (OR, 3.326; 95% CI, 1.632 to 6.776); connective tissue disease (OR, 2.157; 95% CI, 1.679 to 2.771), benign prostatic hyperplasia (OR, 3.892; 95% CI, 2.476 to 6.116), rosacea (OR, 3.747; 95% CI, 1.972 to 7.120), posttraumatic stress disorder (OR, 1.449; 95% CI, 1.043 to 2.013), hematopoietic stem cell transplantation (OR, 7.269; 95% CI, 2.312 to 22.849), head and neck radiotherapy (OR, 8.776; 95% CI, 3.096 to 24.873), postmenopausal estrogen therapy (OR, 1.912; 95% CI, 1.160 to 3.151), antihistamines (OR, 2.040; 95% CI, 1.516 to 2.746), antidepressants (OR, 1.982; 95% CI, 1.077 to 3.647), contact lenses (OR, 2.366; 95% CI, 1.266 to 4.423), and video display terminal exposure for more than 6 h/d (OR, 2.275; 95% CI, 1.451 to 3.568). Potentially protective factors against DES were vitamin supplements (OR, 0.716; 95% CI, 0.528 to 0.972) and Ω-3 fatty acid-rich diet (OR, 0.514; 95% CI, 0.332 to 0.796). CONCLUSION: Several known risk factors of DES are applicable to Chinese, and some distinctive dietary factors may be protective in this population.

Paxillin regulates vascular endothelial growth factor A-induced in vitro angiogenesis of human umbilical vein endothelial cells.

The purpose of the present study was to investigate the role of paxillin in the vascular endothelial growth factor A (VEGF­A)­induced adhesion, proliferation, migration and capillary formation of endothelial cells (ECs) in vitro. Human umbilical vein ECs (HUVECs) were used to evaluate these four processes in vitro. The HUVECs were either mock­transfected (control), transfected with scramble small interference RNA (siRNA) or transfected with siRNA specifically targeting paxillin. VEGF­A (20 ng/ml) was used to stimulate angiogenesis. The VEGF­A treatment significantly increased the adhesion, proliferation, migration and tube formation of the HUVECs in the control and scramble siRNA groups, whereas the siRNA­-mediated knockdown of paxillin inhibited these VEGF­A­induced effects. Paxillin is essential for VEGF­A­mediated angiogenesis in ECs and its inhibition may be a potential target for antiangiogenic therapies.

Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative process that leads to a selective loss of dopaminergic neurons, mainly in the basal ganglia of the brain. Numerous studies have analyzed the ability of optical coherence tomography (OCT) to detect retinal nerve fiber layer (RNFL) thickness abnormalities and changes in PD, but the results have not always been consistent. Therefore, we carried out a meta-analysis to evaluate the RNFL thickness measured with OCT in PD. METHODS AND FINDINGS: Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PUBMED and EMBASE. For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence interval (CI). The statistical analysis was performed by RevMan 5.0 software. Thirteen case-control studies were included in the present meta-analysis, containing a total of 644 eyes in PD patients and 604 eyes in healthy controls. The results of our study showed that there was a significant reduction in average RNFL thickness in patients with PD compared to healthy controls (WMD = -5.76, 95% CI: -8.99 to -2.53, P = 0.0005). Additionally, differences of RNFL thickness in superior quadrant (WMD = -4.44, 95% CI: -6.93 to -1.94, P = 0.0005), inferior quadrant (WMD = -7.56, 95% CI: -11.33 to -3.78, P<0.0001), nasal quadrant (WMD = -3.12, 95% CI: -5.63 to -0.61, P = 0.01) and temporal quadrant (WMD = -4.63, 95% CI: -7.20 to -2.06, P = 0.0004) were all significant between the two groups. CONCLUSION: In view of these results and the noninvasive nature of OCT technology, we surmise that OCT could be a useful tool for evaluating the progression of the Parkinson disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01928212.

[Effects of focal adhesional kinase signaling on TNF-α induced gelatinases activity in cornea epithelium].

OBJECTIVE: To investigate the effect of focal adhesional kinase (FAK) on tumor necrosis factor α (TNF-α)-induced MMP-2 and -9 activities in cornea epithelium. METHODS: Experimental research. The human corneal epithelial cells (HCE) were cultured in vitro. HCEs were incubated with different concentrations of TNF-α for 24 h, including 1 µg/L (group B), 10 µg/L (group C) and 100 µg/L (group D). The control group (group A) was incubated with phosphate buffer solution. The activities of MMPs were examined by gelatin zymography and the phosphorylation of FAK was examined by western blot analysis. FAK was down regulated by FAK siRNA following lipofectamine-mediated transfection in corneal epithelial cells. Down-regulation was confirmed using western blot analysis. Cells cultured with different concentrations of TNF-α (Groups B to D) and the control group (group A) was at similar volumes of media. Then the activities of MMP-2 and -9 were examined by gelatin zymography and the phosphorylation of FAK by western blot analysis. Statistical methods adopted one-way ANOVA and Tukey's honestly significant test between each group. RESULTS: Gelatin zymography: Activities of MMP-2 and -9 in TNF-α treated groups were greater than those of the control group. The activity of MMP-2 in A, B, C and D groups was 124.06 ± 4.06, 146.72 ± 5.51, 241.18 ± 5.65 and 389.95 ± 4.44, respectively with F = 2960.91, P = 0.000. The activity of MMP-9 in A, B, C and D groups was 122.78 ± 5.86, 165.70 ± 7.90, 479.49 ± 6.22 and 495.88 ± 5.03 (F = 4937.46, P = 0.000). Significant differences were found in each two groups (P = 0.000). Western blot analysis:the phosphorylation of FAK (p-FAK) in test groups (10-100 ng/ml) were significantly greater than that in control group (p-FAK of group C and D was 0.52 ± 0.03 and 0.61 ± 0.06, F = 431.03, P = 0.000). p-FAK levels in 100 ng/ml group were greater than that in 10 ng/ml group (P = 0.005). After down-regulating the protein FAK, TNF-α had no effect on the activity of MMP-2 (The data of MMP-2 were 55.13 ± 0.66, 55.67 ± 0.43, 55.49 ± 0.20 and 55.91 ± 0.37 in groups A, B, C and D, F = 2.73, P = 0.079). We detected the increasing activity of MMP-9 in group C, D and p-FAK in group D (The data of MMP-9's activity were 80.48 ± 0.39, 81.26 ± 0.62, 84.43 ± 0.47, 85.56 ± 0.61 in groups A, B, C and D, F = 105.80, P = 0.000). The activity of MMP-9 in group D was stronger than that from the group C (P = 0.019). We just only detected a small quantity of p-FAK in group D (0.47 ± 0.05), which was weaker than that before down regulating the protein FAK (t = 5.03, P = 0.001). CONCLUSION: Our results demonstrate the critical role of FAK in TNF-α induced activity of MMP-2 and -9 in human corneal epithelium cells. Blocking the FAK signaling pathway can reduce the activity of MMP-2 and -9 which may play an important role in prevention and treatment of corneal diseases.