Triamcinolone as an adjunct to the combination of anti-VEGF for the management of diabetic macular edema

AIM:To assess the efficacy of intravitreal triamcinolone(IVTA)as an adjunct to the combination of anti-vascular endothelial growth factor(VEGF)for the management of diabetic macular edema(DME).METHODS:A total of 51 patients with visual disabilities causing by DME from two sites were retrospectively collected and assigned to two groups according to the therapeutic method:intravitreal conbercept(IVC)combined with focal laser(24 eyes)and IVC combined with focal laser and IVTA(27 eyes).Best-corrected visual acuity(BCVA),the required number of IVCs,central retinal thickness(CRT),the mean costs of treatment burden and safety were compared over 12 mo.RESULTS:From baseline to month 1 through month 12,IVC combined with focal laser and IVTA improved the mean average change in BCVA superior to IVC combined with focal laser(+5.20 vs+2.71 letters).At month 12,20.83%of the IVC combined with focal laser and 37.04%of IVC combined with focal laser and IVTA arms gained more than 10 BCVA letters.During the period,the mean CRT decreased significantly in the IVC combined with focal laser and IVTA arm(-245.9μm)compared to the IVC combined with focal laser arm(-98.45μm).The average of 6.45 and 1.25 conbercept injections performed in the IVC combined with focal laser and IVC combined with focal laser and IVTA arms,respectively.The mean cost of treatment burden for 12 mo was$6247.44±4069.18 in the IVC combined with focal laser arm and$1679.19±542.73 in the IVC combined with focal laser and IVTA arm,with a statistically significant difference.Apart from occasional minor subconjunctival hemorrhage,no other significant ocular adverse events(AEs)were observed in either group during the 12-month period.CONCLUSION:It is effective and cost-effective to treat DME by utilizing triamcinolone as an adjunct to the combination of anti-VEGF.

Ruthenium-106 plaque brachytherapy for the treatment of diffuse choroidal hemangioma in Sturge-Weber syndrome

AIM:To evaluate the efficacy of ruthenium-106 plaque brachytherapy for the treatment of diffuse choroidal hemangioma(DCH)in Sturge-Weber syndrome(SWS).METHODS:A total of 8 patients with DCH in SWS managed with plaque brachytherapy were retrospectively included.Patients were treated with ruthenium-106 plaque therapy(median apex dose:83 Gy)at the thickest tumor region.On follow-up,we recorded the tumor thickness,the best-corrected visual acuity(BCVA),subretinal fluid(SRF)status,and complications following treatment.RESULTS:At a median follow-up of 43 mo,tumor regression was observed in all cases,with a complete resolution of SRF and reduction in tumor-thickness.No radiation complications were recorded during the follow up time.CONCLUSION:Ruthenium-106 plaque therapy to the thickest portion of the tumor seems to be a useful treatment in patients with DCH in SWS.

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet,China

AIM: To evaluate the outcomes of intravitreal antivascular endothelial growth factor(anti-VEGF) agents for patients with retinal vein occlusion(RVO) related-macular edema(ME) in Tibetan.METHODS: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients(93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People’s Hospital from Jan 2018 to December 2019 were collected.RESULTS: The mean patient age was 56.8±10.6y, 45(50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity(BCVA) significantly increased(52.2±21.8 letters) in comparison with the baseline(38.2±24.1 letters, P<0.001);while the central retinal thickness(CRT) significantly reduced(245.5±147.6 μm) in comparison with the baseline(504.1±165.2 μm, P<0.001). The 43.0% of the eyes gained≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted.CONCLUSION: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.

Thermal-induced Unfolding of β-Crystallin and Disassembly of its Oligomers Revealed by Temperature-Jump Time-Resolved Infrared Spectroscopy

β-Crystallins are the major structural proteins existing in the vertebrate lens, and their conformational stability is critical in maintaining the life-long transparency and refraction index of the lens. Seven subunits of β-crystallins naturally assemble into various heteroge- neous oligomers with different sizes. Here, we systematically investigated the thermal sta- bility of the different secondary structures present in β-Crystallins and then the dynamic process for the thermal-induced unfolding of β-crystallins by Fourier transform infrared spectroscopy-monitored thermal titration and temperature-jump nanosecond time-resolved IR difference absorbance spectra. Our results show that the N-terminal anti-parallel β-sheets in β-crystallin are the most unstable with a transition midpoint temperature at 36.0-2.1℃, leading to the formation of an intermediate consisting vastly of random coil structures. This intermediate structure is temporally assigned to that of the monomer generated by the thermal-induced disassembly of β-crystallin oligomers with a transition midpoint tempera- ture of 40.4-0.7℃. The global unfolding of β-crystallins that leads to denaturation and aggregation indicated by the formation of intermolecular anti-parallel β-sheets has a transi- tion midpoint temperature determined as 72.4-0.2 ℃. Temperature-jump time-resolved IR absorbance difference spectroscopy analysis further reveals that thermal-induced unfolding of β-crystallins occurs firstly in the anti-parallel β-sheets in the N-terminal domains with a time constant of 50 ns.

Construction of a eukaryotic expression vector pEGFP-C1-BMP-2 and its effect on cell migration

Objective: Bone morphogenetic proteins (BMPs) are known to play an important role in bone and cartilage development. Recent research has shown that BMPs may induce tumorigenesis and promote tumor to spread, but the molecular mechanisms have not been elucidated. The aim of the present study was to investigate the regulatory function of BMP-2 in the migration of COS-7 cells and the underlying mechanisms. Methods: Human BMP-2 genetic fragment was amplified and introduced into the pEGFP-C1 vector. After being confirmed by XhoI and BamHI digestion analyses and DNA sequencing, the recombinant pEGFP-C1-BMP-2 plasmid was transfected into COS-7 cells. The influence of BMP-2 on cell migration and cofilin activity was detected by cell scratch assay and Western blotting. Results: The recombinant pEGFP-C1-BMP-2 was effectively expressed in COS-7 cells. An increased phosphorylation of both LIMK1 and cofilin and an enhancement of cell migration were observed in cells with overexpression of BMP-2. Conclusions: A recombinant pEGFP-C1-BMP-2 vector was successfully constructed and overexpression of BMP-2 regulated the activities of the downstream molecules of the Rho GTPase signaling pathway, which might contribute to the enhancement of cell migration.

Design,synthesis,and screen of cathepsin K inhibitors

We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e,9d,9p,9j and 9k （IC_（50）≤0.005μmol/L） were equal to or greater than that of the lead compound 9a.Less hydrophobic compounds showed weaker potency,which can be explained by the hydrophobic nature of the cathepsin K binding pockets.