Visual Acuity and Size of Choroidal Neovascularization in Highly Myopic Eyes with a Dome-Shaped Macula.

INTRODUCTION: A dome-shaped macula (DSM) is an inward convexity or anterior deviation of the macular area. DSM is believed as a protective factor in maintaining visual acuity in highly myopic eyes. OBJECTIVE: To investigate the correlation between best-corrected visual acuity (BCVA), choroidal neovascularization (CNV), and a dome-shaped macula (DSM) in highly myopic eyes. METHODS: In this retrospective and observational case series study, BCVA tests and optical coherence tomography (OCT) were performed in a total of 472 highly myopic eyes (refractive error ≥6.5 diopters or axial length ≥26.5 mm). CNV was detected by fundus fluorescein angiography (FFA), and the CNV area was measured by ImageJ software. BCVA, central retinal thickness (CRT), and the CNV area were compared between highly myopic eyes with and without DSM. RESULTS: The data revealed 13 eyes with DSM complicated by CNV, for an estimated prevalence of 25%. The eyes with CNV in the DSM group showed worse BCVA than those in the non-DSM group (1.59 ± 0.69 and 0.63 ± 0.64, respectively, p < 0.05), and the CNV area in the DSM group was larger than that in the non-DSM group (2793.91 ± 2181.24 and 1250.71 ± 1210.36 pixels, respectively, p < 0.05). After excluding the eyes with CNV, the DSM group had better BCVA than the non-DSM group (0.33 ± 0.17 and 0.44 ± 0.48, respectively, p < 0.05); however, no significant difference was observed in the CRT of eyes with CNV between the DSM group and the non-DSM group. CONCLUSION: These results show that DSM might be a protective mechanism for visual acuity, but its protective capability is limited. DSM eyes have better visual acuity within the protective capability. If a more powerful pathogenic factor exceeding the protective capability is present, then the eye will have more severe CNV and worse visual acuity.

Effect of forsythin in inhibiting renal cell carcinoma via PI3K/Akt signaling pathway / 中草药

Objective: To investigate the mechanism of forsythin in inhibiting the growth, migration and invasion of human renal cancer cells (786-0). Methods Human renal cancer cells (786-0) were cultured in vitro, and different concentrations of forsythin were added. Cell viability was detected by MTT assay, cell apoptosis was detected by AO/EB assay, cell migration and invasion abilities were respectively investigated by wound healing and transwell migration assays. The expression levels of PI3K, p-PI3K, Akt, p-Akt, FOXO3a, p-FOXO3a, p21, p27, Fasl, Bim, MMP-2, and MMP-9 were detected by Western bloting. Results:In 786-0 cells, forsythin effectively inhibited the growth of renal cancer cells, promoted apoptosis, interfered with cell cycle, and upregulated expression levels of p21, p27, Fasl, and Bim, when compared with control group (P < 0.05, 0.01); Compared with the control group, different concentrations of forsythin can significantly inhibit the migration and invasion of renal cancer cells, and reduce the synthesis of MMP-2 and MMP-9 (P < 0.05, 0.01). Meanwhile, forsythin can significantly inhibit the phosphorylation of PI3K, Akt and FOXO3a in a concentration-dependent manner (P < 0.05, 0.01). Conclusion: Forsythin can regulate apoptosis and cell cycle, and inhibit the growth of renal cancer cells by down-regulating the PI3K/Akt signaling pathway. At the same time, forsythin can effectively inhibit the ability of renal cell migration and invasion through the PI3K/Akt pathway.

Comparison of 0.025% FK-506, 0.05% Cyclosporin A, and 0.3% Sodium Hyaluronate Eye Drops for the Treatment of Botulinum Toxin B-Induced Mouse Dry Eye.

PURPOSE: To compare the effects of FK-506, cyclosporin A (CsA), and sodium hyaluronate (HA) eye drops for the treatment of botulinum toxin B (BTX-B)-induced mouse dry eye. METHODS: CBA/J mice were randomized into 5 groups. The groups received treatment with eye drops containing 0.025% FK-506 combined with 0.3% HA (FK-506+HA group), 0.025% FK-506 (FK-506 group), 0.05% CsA (CsA group), 0.3% HA (HA group), or 0.9% saline (saline group) 3 days after an intralacrimal gland injection with 20 mU of BTX-B. Tear production, corneal fluorescein staining, blink rate, and the mRNA and protein expression levels of inflammatory cytokines were measured. RESULTS: FK-506+HA eye drops increased tear production and reduced the corneal fluorescein staining scores at all time points after treatment compared with those in the saline group. Compared with those in the saline group, the tear production and severity of corneal epithelial defects in the FK-506 group were significantly improved at weeks 2 and 4. Compared with the saline eye drops, the CsA eye drops ameliorated only tear production and corneal fluorescein staining scores at week 4 after administration. The FK-506+HA, FK-506, and CsA eye drops downregulated the expression of inflammatory cytokines in both the keratoconjunctival tissues and lacrimal glands at week 4. CONCLUSIONS: The topical application of 0.025% FK-506 combined with 0.3% HA, 0.025% FK-506, or 0.05% CsA can suppress the expression of inflammatory cytokines and can alleviate the signs of dry eye. Topical application of 0.025% FK-506 combined with 0.3% HA showed the best therapeutic effect and may be a possible therapy for dry eye.

Effect of 0.025% FK-506 eyedrops on botulinum toxin B-induced mouse dry eye.

PURPOSES: To investigate the effect of FK-506 eye drops on Botulinum toxin B (BTX-B)-induced mouse dry eye. METHODS: Forty-five CBA/J mice were followed up for 4 weeks after treatment with 0.025% FK-506, vehicle or 0.9% saline eye drops 3 days after intralacrimal glands injection with 20 milliunits BTX-B. Tear production, corneal fluorescein staining, the mRNA, and protein expression of cytokines were measured. The activation of nuclear factor-κB (NF-κB) was detected by Western blotting. The infiltration of inflammatory cells was examined by immunohistochemistry. RESULTS: After treated with FK-506 eye drops, aqueous tear production in the mice began to recover at week 1, and then increased to the levels of pre-BTX-B injection at week 4 (2.21 ± 0.43 vs. 2.52 ± 0.71 mm, t = 0.84, P > 0.05). The severity of corneal epithelial defects was alleviated at week 2 and further improved at week 4 when compared with those in the vehicle- and saline-treated groups. The gene expression of IL-1ß and TNF-α in the FK-506 and vehicle-treated groups were 47.01% and 45.56%, 85.91% and 115.83% of that in the saline-treated group in the ocular surface, while in the lacrimal glands 49.16% and 67.60%, 94.91% and 95.77% of that in the saline-treated group, respectively. The ratio of phosphorylated IκB-α to total IκB-α in the keratoconjunctival tissues was lower in the FK-506-treated group than in the vehicle- and saline-treated groups (both P < 0.05). No inflammatory cells were detected in all groups. CONCLUSIONS: Topical application of FK-506 can inhibit NF-κB activation and related inflammatory response and alleviate the signs of dry eye.

Minocycline inhibits alkali burn-induced corneal neovascularization in mice.

The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV). A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS) or minocycline twice a day (60 mg/kg or 30 mg/kg) for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs). The mRNA expression levels of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMPs), interleukin-1α, 1ß, 6 (IL-1α, IL-1ß, IL-6) were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1ß and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1ß, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1ß, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d.) can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs.

Re-evaluation of marketed chemical drugs and biological products of therapeutic - a systematic review of literature / 中华流行病学杂志

<p><b>OBJECTIVE</b>To assess the current status on re-evaluation of marketed drug in China since the promulgation of drug law in 1985.</p><p><b>METHODS</b>Review of literature on Chinese pharmaceutical abstract and CBMdisc from 1985 to 2001 year was done.</p><p><b>RESULTS</b>4029 papers and 855 marketed drugs from 1985 to 2001 were included. Drugs on anti-infection agent, cardiovascular system and digestive system were the main drugs being re-evaluated, with the proportions of 27.1%, 20.1% and 11.1% respectively. The amounts of both marketed drugs and literature were increasing year by year. The method used for re-evaluation were random and non-random clinical trial. 41.4% of all the samples had a sample size of 50 - 100 research subjects. There were 13 papers with more than 5000 samples. The level on evidence based literature was assessed. 44 papers were graded as first class, and 182 papers the second, 2466 papers the third and 1337 papers the fourth. The quality of literature was improved year by year.</p><p><b>CONCLUSION</b>The amount, quality as well as the sample size of literature being re-evaluated on marketed drug were increased from 1985 to 2001. However, the design and evaluation of those trials were not standardized.</p>