Complications of diabetes mellitus (DM) are related not only to elevated plasma glucose, but also plasma glucose fluctuations. However, the specific mechanism underlying the role of plasma glucose fluctuation in the pathogenesis of DM complications remains poorly understood. In the present study, the influence of acute fluctuant hyperglycemia and persistent hyperglycemia on vascular endothelial cell apoptosis, function, oxidative stress and inflammation was examined in vivo. Rats were assigned to three different groups (n = 10/group) that received 48-h infusions of saline (SAL group), continuous 50 % glucose (constant high glucose group [CHG]), or intermittent 50 % glucose (acute blood glucose fluctuation group [AFG]). Plasma 8-isoprostaglandin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were quantified by using enzyme-linked immunosorbent assay (ELISA) commercial kits. Plasma insulin levels were measured by radioimmunoassays (RIAs) using kits. The aortic segment was collected. The levels of malondialdehyde (MDA) and activity of glutathione peroxidase (GSH-PX) were measured in endothelial homogenates prepared from endothelial cells harvested from the aorta using colorimetric kits. Apoptosis of vascular endothelial cells was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Endothelial dysfunction was assessed by isometric tension recording to evaluate the endothelial function. The expression of B cell lymphoma-2 (Bcl-2), Bcl-2 Associated X protein (Bax), pro caspase-3, caspase-3 p17, 3-nitrotyrosine (3-NT) and p47phox protein in rat aortic endothelial cells were tested with Western blot analysis. Endothelial cells reactive oxygen species (ROS) formation was determined using dihydroethidium-dependent fluorescence microtopography in aortic cryo-sections. Expression of IL-6, TNF-α and ICAM-1 mRNAs in vascular endothelial cells were determined by real-time quantitative PCR. Endothelial cells apoptosis and dysfunction were observed significantly in the aortas of the AFG group (P < 0.05). The AFG had reduced Bcl-2 and pro caspase-3 levels and enhanced Bax mitochondrial translocation and caspase-3 p17 protein levels in comparison with the CHG group (P < 0.05). Both AFG and CHG induced β-cell dysfunction and insulin resistance (P < 0.05). AFG increased MDA and 8-isoprostaglandin levels in plasma, oxidative stress in vascular endothelial cells, and inflammatory cytokines in plasma and vascular endothelial cells (P < 0.05). Acute glucose fluctuation may cause significant oxidative stress and inflammation in endothelial cells, increase the adhesion of monocytes to endothelial cells, and elevate endothelial cell apoptosis, resulting in severe cardiovascular injury.

AIM: To investigate the candidate microRNA (miRNA), miR-221 as a novel biomarker for diabetic retinopathy (DR) in patients associated with type 2 diabetes (T2D). METHODS: The subjects involved were divided into four groups: healthy control (HC), no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) group. Serum miR-221 was validated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Also, serum angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) were examined by enzyme-linked immunosorbent assay. In addition, receiver operating characteristic (ROC) curve was performed to explore the diagnostic accuracy of miR-221, Ang II and VEGF for DR in patients with T2D. Spearman's rank correlation coefficient was executed to estimate the correlations of serum miR-221 with metabolic parameters and serum markers in patients with T2D. RESULTS: Primarily, serum miR-221, Ang II and VEGF were increased significantly in T2D patients compared to HC participant respectively, and progressive up-regulated in NDR, NPDR and PDR groups (P<0.001). Additionally, miR-221 in serum was remarkably positively correlated with metabolic parameters such as glycated hemoglobin (r=0.310, P=0.002) and homeostasis model assessment for insulin resistance (r=0.413, P<0.001), as well as serum markers for instance Ang II (r=0.667, P<0.001) and VEGF (r=0.499, P<0.001). Furthermore, serum miR-221 (AUC, 0.894; 95%CI, 0.833-0.955; P<0.001), Ang II (AUC, 0.888; 95%CI, 0.828-0.949; P<0.001) and VEGF (AUC, 0.785; 95%CI, 0.695-0.875; P<0.001) had evidently diagnostic efficiency in DR, and miR-221 is the most effective among them. CONCLUSION: Serum miR-221 as a potential biomarker could be related to not only occurrence but also progression for DR in patients with T2D. However, a prospective clinical trial is warranted.

Background: To evaluate the anatomic and functional outcomes in eyes of patients with macular edema (ME) caused by central retinal vein occlusion (CRVO) who were lost to follow-up (LTFU) for more than 6 months following treatment with anti-vascular endothelial growth factor (VEGF) therapy and to determine the predictive factors of visual prognosis in these patients. Methods: This study was conducted as a retrospective, case series investigation. Patients whose eyes were receiving intravitreal anti-VEGF treatment for CRVO-ME, with the next follow-up visit occurring more than 6 months following treatment were identified. Baseline disease characteristics (at the last visit before being LTFU), cause and duration of treatment interruption, and the resulting disease progression, complications, and outcomes were assessed. Baseline characteristics predictive of visual outcome were also analyzed. Results: This study included a total of 17 eyes of 17 patients. The mean duration of being LTFU was 7.8 ± 2.1 months. On the return visit after being LTFU, 7 of 17 eyes (41.2%) developed neovascular complications. Despite treatment, 12 eyes (70.1%) lost ≥ 3 best-corrected visual acuity (BCVA) lines, with 2 eyes (11.8%) developing a final BCVA of hand motion or more severe. At the final visit, the mean logarithm of minimal angle of resolution (logMAR) BCVA deteriorated significantly compared to before being LTFU (P < 0.001). The increasing duration of being LTFU is associated with a deterioration of visual acuity prognosis. Conclusion: In CRVO-ME patients who are receiving anti-VEGF therapy, unintentional treatment interruptions can cause visually disastrous consequences, including irreversible blindness. Patients who were LTFU for a long period should be strongly warned about their poor visual prognosis.

To evaluate the efficacy and tolerability of one-site versus two-site phacotrabeculectomy in the treatment of patients with coexisting cataract and glaucoma.A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify controlled clinical trials comparing one-site with two-site phacotrabeculectomy. The studies meeting the predefined criteria were reviewed systematically by meta-analysis. Efficacy estimates were measured by standardised mean difference (SMD) for the percentage intraocular pressure (IOP) reduction from baseline to end point, odds ratio (OR) for the percentage having a best-corrected visual acuity (BCVA) of 0.5 or better after surgery and relative risk (RR) for complete success rates. Tolerability estimates were measured by RR for adverse events. All of outcomes were reported with 95% confidence interval (CI). Data were synthesised by Stata 10.1 for Windows.Two-site phacotrabeculectomy was associated with numerically greater, and significant efficacy than one-site in lowering IOP (SMD, -0.19; 95% CI, -0.33 to -0.04; P=0.01). Numerically greater, but nonsignificant proportions of two-site patients than one-site patients had a BCVA of 0.5 or better (OR, 0.65; 95% CI, 0.30 to 1.39; P=0.26).Numerically greater, but nonsignificant proportions of two-site patients than one-site patients achieved the target IOP without anti-glaucoma medication at the end point (RR, 0.94; 95% CI, 0.84 to 1.04; P=0.22). Furthermore, there was nonsignificant difference in adverse events between two surgical procedures.The efficacy of two-site phacotrabeculectomy appears to be superior to one-site phacotrabeculectomy. One-site and two-site phacotrabeculectomy are similarly tolerable in postoperative adverse events.