Combined Intravitreal Anti-VEGF and Photodynamic Therapy versus Photodynamic Monotherapy for Polypoidal Choroidal Vasculopathy: A Systematic Review and Meta-Analysis of Comparative Studies

Purpose

The aim of this study was to evaluate the efficacy and safety of photodynamic therapy (PDT) combined with intravitreal vascular endothelial growth factor (VEGF) inhibitors compared to those of PDT alone in the treatment of polypoidal choroidal vasculopathy (PCV).

Methods

A systematic search of Pubmed, Embase, and the Cochrane Library was performed to identify all comparative studies that compared the outcomes of the two approaches. Outcomes of interest included visual outcomes, anatomic variables, and adverse events.

Results

Two randomised controlled trials and nine retrospective studies including a total of 543 cases were identified. At three and six months post-injection, no significant difference in visual acuity was found in the combined therapy group compared with the PDT monotherapy group, with pooled weighted mean differences (WMDs) of 0.074 (−0.021, 0.17) at three months and 0.082 (−0.013, 0.18) at six months. However, the mean changes in visual acuity at month 12 in the combined therapy group were significantly better than those in the PDT monotherapy group, with pooled WMDs of 0.11 (0.012, 0.21). Similar efficacy was found at 24 months (WMD: 0.21; 95%CI: 0.054, 0.36; P = 0.008). Patients in the combined therapy group also might benefit from reduced retinal haemorrhage (OR: 0.32; 95% CI: 0.14, 0.74; P = 0.008). Polyp regression, recurrence of PCV, central retinal thickness reduction, and pigment epithelial detachment resolution did not differ significantly between the two treatments.

Conclusions

Combined treatment appeared to result in better visual acuity and lower retinal haemorrhage. However, combined treatment did not affect the resolution and recurrence of lesions. Given the inherent limitations of the included studies, future well-designed RCTs are awaited to confirm and update the findings of this analysis.     

Effects of BmK AS on Nav1.2 expressed in <Emphasis Type="Italic">Xenopus laevis</Emphasis> oocytes

In the present study, the pharmacological effects of BmK AS, a β-like scorpion toxin on rNav1.2 α-subunit expressed in Xenopus laevis oocytes were investigated using a two-electrode voltage-clamp recording. It was found that the voltage dependence of rNav1.2 inactivation was significantly shifted towards positive membrane potential by 500 nM BmK AS, whereas the activation curves of rNav1.2 were unruffled at the same dosage. The inactivation curves of both slow and fast inactivation currents were positively moved about 12.8 and 9.7 mV, respectively. In addition, the persistent currents of rNav1.2 were invariable. The effects of BmK AS on the rNav1.2 inactivation were opposite to the previous results found in the peripheral sensory neurons. The results suggested that Nav1.2 might be the target of BmK AS in the central nervous system, and BmK AS might have an excitatory effect on the central neuron through enhancing Nav1.2.     

Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a member of the family of acyl-CoA dehydrogenases (ACADs). Unlike the other ACADs, which are soluble homotetramers, VLCAD is a homodimer associated with the mitochondrial membrane. VLCAD also possesses an additional 180 residues in the C terminus that are not present in the other ACADs. We have determined the crystal structure of VLCAD complexed with myristoyl-CoA, obtained by co-crystallization, to 1.91-A resolution. The overall fold of the N-terminal approximately 400 residues of VLCAD is similar to that of the soluble ACADs including medium-chain acyl-CoA dehydrogenase (MCAD). The novel C-terminal domain forms an alpha-helical bundle that is positioned perpendicular to the two N-terminal helical domains. The fatty acyl moiety of the bound substrate/product is deeply imbedded inside the protein; however, the adenosine pyrophosphate portion of the C14-CoA ligand is disordered because of partial hydrolysis of the thioester bond and high mobility of the CoA moiety. The location of Glu-422 with respect to the C2-C3 of the bound ligand and FAD confirms Glu-422 to be the catalytic base. In MCAD, Gln-95 and Glu-99 form the base of the substrate binding cavity. In VLCAD, these residues are glycines (Gly-175 and Gly-178), allowing the binding channel to extend for an additional 12A and permitting substrate acyl chain lengths as long as 24 carbons to bind. VLCAD deficiency is among the more common defects of mitochondrial beta-oxidation and, if left undiagnosed, can be fatal. This structure allows us to gain insight into how a variant VLCAD genotype results in a clinical phenotype.     

小麦根系特征对干旱胁迫的响应

干旱胁迫时, 小麦(Triticum aestivum)根系率先产生应激响应, 同时向地上部发出信号, 诱导地上部发生生理反应, 从而提高植株抗旱能力。根系构型包括平面几何性状和立体几何结构(即拓扑构型), 具有遗传稳定性和可塑性。干旱胁迫影响根系理化特性, 如根源化学信号、根系细胞酶类和根系渗透作用的响应。根系通过调整其解剖学结构和水分吸收动力等来适应干旱胁迫。该文从根系构型、理化特性和解剖学结构3个方面, 系统阐述了小麦根系特征对干旱胁迫的响应, 并探讨了其与干旱胁迫的关系和当前研究中存在的问题, 以期为相关研究提供参考。     

The Expression Pattern of Classical MHC Class I Molecules in the Development of Mouse Central Nervous System

Classical major histocompatibility complex (MHC) class I, first identified in the immune system, is also expressed in the developing and adult central nervous system (CNS). Although the MHC class I molecules have been found to be expressed in the CNS of different species, a necessary step to elucidate the temporal and spatial expression patterns of MHC class I molecules in the brain development has never been taken. Frozen sections were made from the brains of embryonic and postnatal C57BL/6 J mice, and the expression of H-2D^b mRNA was examined by in situ hybridization. Immunofluorescence was also performed to define the cell types that express H2-D^b in P15 mice. At E10.5, the earliest stage we examined, H2-D^b was expressed in neuroepithelium of the brain vesicles. From E12.5 to P0, H2-D^b expression was mainly located at cerebral cortex, neuroepithelium of the lateral ventricle, neuroepithelium of aquaeductus and developing cerebellum. From P4 to adult, H2-D^b mRNA was detected at olfactory bulb, hippocampus, cerebellum and some nerve nuclei. The major cell types expressing H-2D^b in P15 hippocampus, cerebral cortex and olfactory bulb were neuron. H2-K^b signal paralleled that of H2-D^b and the expression levels of the two molecules were comparable throughout the brain. The investigation of the expression pattern of H-2D^b at both embryonic and postnatal stages is important for further understanding the physiological and pathological roles of H2-D^b in the developing CNS.     

Decrease in Formalin-Inactivated Respiratory Syncytial Virus (FI-RSV) Enhanced Disease with RSV G Glycoprotein Peptide Immunization in BALB/c Mice

Respiratory syncytial virus (RSV) is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV) vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study.     

Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases

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Highlights? Crystal structure of CCM3-MST4 heterodimeric complex ? Structural mechanism driving CCM3-GCKIII heterodimerization ? Conformational changes required for CCM3-GCKIII heterodimerization ? Synergistic effects of CCM3-MST4 complex on cell proliferation and migration     

Developmental Potential of Prepubertal Mouse Oocytes Is Compromised Due Mainly to Their Impaired Synthesis of Glutathione

Although oocytes from prepubertal animals are found less competent than oocytes from adults, the underlying mechanisms are poorly understood. Using the mouse oocyte model, this paper has tested the hypothesis that the developmental potential of prepubertal oocytes is compromised due mainly to their impaired potential for glutathione synthesis. Oocytes from prepubertal and adult mice, primed with or without eCG, were matured in vitro and assessed for glutathione synthesis potential, oxidative stress, Ca²⁺ reserves, fertilization and in vitro development potential. In unprimed mice, abilities for glutathione synthesis, activation, male pronuclear formation, blastocyst formation, cortical granule migration and polyspermic block were all compromised significantly in prepubertal compared to adult oocytes. Cysteamine and cystine supplementation to maturation medium significantly promoted oocyte glutathione synthesis and blastocyst development but difference due to maternal age remained. Whereas reactive oxygen species (ROS) levels increased, Ca²⁺ storage decreased significantly in prepubertal oocytes. Levels of both catalytic and modifier subunits of the γ-glutamylcysteine ligase were significantly lower in prepubertal than in adult oocytes. Maternal eCG priming improved all the parameters and eliminated the age difference. Together, the results have confirmed our hypothesis by showing that prepubertal oocytes have a decreased ability to synthesize glutathione leading to an impaired potential to reduce ROS and to form male pronuclei and blastocysts. The resulting oxidative stress decreases the intracellular Ca²⁺ store resulting in impaired activation at fertilization, and damages the microfilament network, which affects cortical granule redistribution leading to polyspermy.