Treatment of corneal dermoid with lenticules from small incision lenticule extraction surgery: a surgery assisted by fibrin glue.

AIM: To observe the clinical efficacy of the combined use of small incision lenticule extraction (SMILE)-derived lenticule patches in corneal dermoid excision, with fixation of the lenticule patches assisted by fibrin glue. METHODS: Seventeen eyes of 17 patients with corneal dermoid were treated with dermoid removal combined with SMILE-derived lenticule transplantation. All lenticule patches were fixed by fibrin glue. Ocular changes were assessed using slit lamp microscopy and anterior-segmental optical coherence tomography. The best-corrected visual acuity (BCVA) and ocular dioptric variations were examined preoperatively and postoperatively. Intraocular pressure (IOP) was also monitored in all visited time. RESULTS: Totally, 18 lenticule patches were used on 17 eyes of 17 cornea dermoid patients. The mean follow-up time was 11.47±5.28mo. All lenticule patches were successfully glued, kept on its location and maintained transparent during the follow-up time, with a consecutive epithelial cover for 1wk. Nine of the patients could coordinate visual and optometry exam well. Their preoperative BCVA is 0.60±0.35 in decimal, significantly improved to 0.80±0.26 in decimal at 6mo postoperatively (Z=-2.392, P=0.017), but the changes of their corneal astigmatism diopters showed no significance, with 2.22±1.91 D preoperatively, and 2.28±1.31 D at 6mo postoperatively (Z=-0.135, P=0.893). Limbal pannus formation occurred in 4 (23.52%) cases and decreased with the application of tacrolimus eyedrops. IOP increased in 2 (11.76%) cases, but well decreased by timolol maleate eyedrops. All the adult patients or guardians of minor patients were satisfied with the cosmetic improvement. CONCLUSION: Dermoid excision combined with transplantation of SMILE-derived lenticule patches using fibrin glue is a safe and effective novel tectonic keratoplasty procedure for corneal dermoid.

The effects of inorganic anions on degradation kinetics and isotope fractionation during the transformation of tris(2-chloroethyl) phosphate (TCEP) by UV/persulfate.

Tris(2-chloroethyl) phosphate (TCEP), as a typical chlorinated flame retardant, is attracting more attention as a carcinogen. Although persulfate-based oxidation exhibits good performance in removing refractory organic pollutants, the kinetics of persulfate-based remediation are affected by inorganic anions, which causes inaccurate remediation efficiency. This study combines steady-state radical concentration modelling with isotope fractionation to investigate the effects of inorganic anions on TCEP degradation by UV/persulfate (UV/PS). In the absence of anions during UV/PS system, the observed degradation rate was (9.7 ± 0.1) × 10-5 s-1, which was approximately 93 % attributed to sulfate radical (SO4-•) oxidation based on radical modelling. Carbon isotope fractionation, coupled with the identification of transformation products by mass spectrometry, suggests a carbon bond split during TCEP degradation with a carbon isotopic fractionation value (ε) of -1.6 ± 0.2 ‰ (± 95 % confidence intervals). With respect to co-existing anions in UV/PS system, the addition of chloride (Cl-) had a negligible effect on degradation rates, while the addition of hydrogencarbonate (HCO3-) caused them to decrease, and the addition of hydrogenphosphate (HPO42-) caused them to increase. Radical modelling suggested that SO4-• was transformed to chlorine radicals (Cl•/Cl2-•), phosphate radicals (HPO4-•), and carbonate radicals (CO3-•). Furthermore, the overlapping 95 % confidence intervals (C.I.) and the statistical tests (p > 0.05) both agree that Cl- and HPO42- gain identical ε values. Nevertheless, when HCO3- coexisted in the UV/PS system, the ε values were distinct. The addition of HCO3- would result in ε variation of TCEP in the UV activated PS process, which should receive more attention when applying remediation.

LncRNA NR024118 is downregulated in sepsis and inhibits LPS­induced apoptosis of cardiomyocytes.

It has been reported that lncRNA­NR024118 can suppress lipopolysaccharide (LPS)­induced inflammatory responses, which promote sepsis. The present study aimed to investigate the involvement of NR024118 in sepsis. Research subjects included 82 patients with sepsis without myocardial dysfunction (MD), 35 patients with sepsis with MD and 82 healthy controls. The expression levels of NR024118 in plasma collected from these participants and LPS­induced AC16 cells were measured by reverse transcription­quantitative PCR. The expression levels of IL­16 in these plasma samples and LPS­induced AC16 cells were measured by ELISA. The correlation between the expression levels of NR024118 and IL­6 across plasma samples were analyzed by Pearson's correlation coefficient. The action potential duration (APD) was measured at 50 and 90% repolarization. Cell apoptosis was determined by cell apoptosis assay. The expression levels of p­transcription factor p65 were detected by western blot analysis. NF­κB activity were analyzed by luciferase reporter assay. It was found that NR024118 was downregulated and IL­6 was upregulated in the plasma of patients with sepsis. Among patients with sepsis, the individuals with MD exhibited even lower expression levels of NR024118 and higher expression levels of IL­6. Among patients with sepsis with MD, the expression levels of NR024118 and IL­6 were inversely correlated. LPS could induce MD to construct the sepsis models based on the increased expression levels of TNF­α, IL­1ß, IL­6 and shortened APD by LPS­mediated induction. Overexpression of NR024118 significantly reduced the secretion of IL­6 and apoptosis of cardiomyocytes under LPS treatment. Functional studies demonstrated that NR024118 had negative regulation on p65 phosphorylation and NF­κB activation. NR024118 was suppressed in sepsis and inhibited LPS­induced apoptosis of cardiomyocytes.

Design of selective, ATP-competitive inhibitors of Akt.

This paper describes the design and synthesis of novel, ATP-competitive Akt inhibitors from an elaborated 3-aminopyrrolidine scaffold. Key findings include the discovery of an initial lead that was modestly selective and medicinal chemistry optimization of that lead to provide more selective analogues. Analysis of the data suggested that highly lipophilic analogues would likely suffer from poor overall properties. Central to the discussion is the concept of optimization of lipophilic efficiency and the ability to balance overall druglike propeties with the careful control of lipophilicity in the lead series. Discovery of the nonracemic amide series and subsequent modification produced an advanced analogue that performed well in advanced preclinical assays, including xenograft tumor growth inhibition studies, and this analogue was nominated for clinical development.

Synthesis and structure based optimization of novel Akt inhibitors.

Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).