Potential Mechanism of Platelet GPIIb/IIIa and Fibrinogen on Retinal Vein Occlusion.

PURPOSE: To explore the role of coagulation and fibrinolytic factors, and the potential mechanism of platelet aggregation in the pathogenesis of retinal vein occlusion. METHODS: Coagulation and fibrinolytic parameters in patients with retinal vein occlusion were determined using hemagglutinin and HISCL-5000. Relationships between these elevated parameters and factors representing typical clinical manifestations of retinal vein occlusion were examined, and these parameters were analyzed using a STRING database to indicate the potential role of platelet aggregation. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) levels were evaluated by flow cytometry after antiplatelet treatment in patients and mouse models. Furthermore, the GPIIb/IIIa ligand fibrinogen in peripheral blood and retina of mouse models was assessed by the turbidimetric method and real-time PCR, respectively. RESULTS: In patients, significant increases in peripheral blood fibrinogen and GPIIb/IIIa levels were observed (p = 0.0040, p < 0.0001, respectively). A positive correlation was observed between macular thickness (MT) and both fibrinogen and GPIIb/IIIa (r = 0.4528, p = 0.0063; r = 0.3789, p = 0.0427, respectively). After intravitreal injections of anti-vascular endothelial growth factor drugs, a significant reduction in fibrinogen levels was observed (p = 0.0072). In addition, the use of antiplatelet drugs resulted in a significant decrease in GPIIb/IIIa (p < 0.0001). In a mouse model, antiplatelet therapy significantly reduced both peripheral blood and retina fibrinogen levels and the overall rate of vein occlusion 3 days after occlusion (p < 0.0005). In addition, the reduction in GPIIb/IIIa levels after antiplatelet therapy was remarkable. CONCLUSION: Fibrinogen and GPIIb/IIIa may be involved in retinal vein occlusion and blocking platelet aggregation may be a new therapeutic approach for retinal vein occlusion.

Burden of blindness and vision loss in China over the past 30 years: findings and predictions based on the Global Burden of Disease Study 2019.

AIMS: To investigate the burden of blindness and vision loss (BVL) in China over the past 30 years according to year, age and sex, and to estimate future predictions. METHODS: We analysed the years lived with disability (YLDs), number of cases, age-standardised YLD rates (ASYRs) and age-standardised prevalence rates (ASPRs) of BVL in China from 1990 to 2019. We focused on changes over time using estimated annual percentage changes (EAPCs). Additionally, we used the Bayesian age-period-cohort model to predict the BVL burden from 2020 to 2030. RESULTS: The number of YLDs and prevalent cases due to BVL increased from 2.57 (95% uncertainty interval (UI) 1.74 to 3.72) and 90.76 million (95% UI 72.21 to 111.92) in 1990 to 5.42 (95% UI 3.61 to 8.02) and 211.67 million (95% UI 168.21 to 259.66) in 2019, respectively. The BVL ASYRs and ASPRs showed a decreasing trend, with EAPCs of -0.13 (95% CI -0.28 to 0.02) and -0.11 (95% CI -0.19 to -0.04), respectively. The elderly and female populations had a higher BVL burden. The numbers of YLDs and cases due to BVL are projected to continue rising to 7.74 and 279.49 million in 2030, respectively. The ASYRs and ASPRs also showed increasing trends. CONCLUSION: While rates of BVL in China have decreased, there has been a notable increase in the number of YLDs and new cases over the past 30 years. Projections suggest that the burden of BVL will continue to rise over the next 11 years. To address this challenge, appropriate policies must be implemented.

SDF­1α/CXCR4 signaling promotes capillary tube formation of human retinal vascular endothelial cells by activating ERK1/2 and PI3K pathways in vitro.

The purpose of this study is to address the effect and mechanism of stromal cell­derived factor­1 (SDF­1)α/chemokine (C­X­C motif) receptor 4 (CXCR4) signaling on capillary tube formation of human retinal vascular endothelial cells (HRECs). The expression of CXCR4 in HRECs was quantified by reverse transcription (RT­PCR) and western blotting. The effects of SDF­1α/CXCR4 signaling in capillary tube formation and migration of HRECs was examined using three­dimensional Matrigel assay and wound scratching assay respectively in vitro. Cell proliferation of HRECs was examined using cell counting kit (CCK)­8 assay in the presence of different concentrations of SDF­1α protein. The effect of SDF­1α/CXCR4 signaling in HREC expression of VEGF, basic fibroblast growth factor (bFGF), IL­8 and intercellular cell adhesion molecule (ICAM)­1 was examined using RT­PCR and western blotting. RT­PCR and western blot analysis revealed CXCR4 was expressed in HRECs. The number of intact capillary tubes formed by HRECs in the presence of SDF­1α was markedly more compared with a PBS treated control group. However, it was reduced with treatment with an CXCR4 antagonist. Wound scratching assay showed a significant increase in the number of migrated HRECs under SDF­1α stimulation and the number was reduced with treatment with an CXCR4 antagonist. RT­PCR and western blotting showed that SDF­1α significantly promoted VEGF, bFGF, IL­8 and ICAM­1 expression in HRECs. The proliferation of HRECs in the presence of SDF­1α was promoted in a dosage­dependent manner. SDF­1α/CXCR4 signaling can increase HREC capillary tube formation through promoting HREC migration, proliferation and expression of VEGF, bFGF, IL­8 and ICAM­1.

MicroRNA-21 is a new marker of circulating tumor cells in gastric cancer patients.

The detection of circulating tumor cells (CTCs) has received great attention. MicroRNA-21 (miR-21) plays crucial roles in carcinogenesis and is considered as one of the most studied oncomiRNAs. We determined if miR-21 could be used a marker for the detection of CTCs in gastric cancer patients. Peripheral blood samples were collected from 53 preoperative patients with gastric cancer and 20 healthy volunteers. Real-time reverse transcription-polymerase chain reaction was used to detect the level of miR-21. Receiver operator characteristic curves (ROC) were constructed. Patients with gastric cancer display a significantly higher level of miR-21 in peripheral blood than those from controls. The miR-21 level was associated with the tumor node metastasis (TNM) stage, tumor size and tissue categories. The area under ROC curve was up to 0.853 ± 0.086. This study highlights the potential of the detection of miR-21 in peripheral blood as a novel tool for monitoring CTCs in gastric cancer patients.

Concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a treatment paradigm also applicable to patients in Southeast Asia.

The majority of nasopharyngeal carcinoma (NPC) patients present at locally advanced stage. The poor prognosis has led to increasing interests in exploring the use of chemotherapy (CT). Intergroup-0099 trial was the first randomized trial comparing concurrent chemoradiotherapy (CCRT) with radiotherapy (RT) alone. Its outcome established the treatment standard in the United States as standard of care for locally advanced NPC. However, criticism has been arisen, particularly about its reproducibility and applicability in Southeast Asia where NPC is an endemic disease. Subsequently, new evidence has been provided by a large number of publications from various centers. In this article, through comprehensively analyzing recent meta-analyses and randomized controlled trials performed in Asian centers, we conclude that CCRT as a treatment paradigm is also applicable to patients in Southeast Asia and should be standard of practice in locally advanced disease. However, the CT regimen varied markedly among those trials, and the optimal regimen and scheduling remains to be determined. Moreover, a number of patients experienced toxicities and the treatment compliance was generally poor. With the emergence of new RT techniques such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), the role of concurrent CT with these new techniques needs to be tested. New chemotherapeutics have been investigated in the recurrent or metastatic disease. However, their effectiveness in previously untreated NPC is unclear. Previous efforts have been made for immunotherapy and targeted therapy in palliative setting. Their role in newly diagnosed NPC should be evaluated, particularly when they are combined with CT or RT.