Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition

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糖尿病足感染患者病原菌分布 和C-肽及视黄醇结合蛋白-4水平分析

摘要：目的 探讨糖尿病足感染患者病原菌分布、C-肽和视黄醇结合蛋白-4（RBP4）的水平以及感染相关危险因素。方法 收集乌鲁木齐市友谊医院和新疆生产建设兵团医院2016年2月至2017年6月住院的201例糖尿病足患者临床资料，依据是否发生感染分为感染组（n=63）和未感染组（n=138）。采用ELISA法检测两组患者血清中hs-CRP、PCT、D-二聚体、纤维蛋白原（FIB）、C-肽和RBP4水平并分析感染组患者病原菌分布情况。感染相关危险因素采用Logistic回归分析。结果 感染组患者血清hs-CRP、PCT、D-二聚体、FIB、RBP4、餐后2 h C-肽水平均显著高于未感染组（均P<0.05）。63例糖尿病足感染患者足部分泌物共分离培养出83株病原菌，其中革兰阴性菌46株（55.42%），以铜绿假单胞菌（24.10%）、大肠埃希菌（13.25%）居多；革兰阳性菌37株（44.58%），以金黄色葡萄球菌（37.34%）为主。单因素分析显示，两组患者在病程、使用抗菌药物、使用三代头孢、患糖尿病肾病、合并骨髓炎和神经缺损性伤口方面差异有统计学意义（均P<0.05）。多因素分析显示，患者病程、既往使用抗菌药物、使用三代头孢、合并骨髓炎和神经缺损性伤口均是感染发生的独立危险因素。结论 需依据病原菌分布及耐药性情况合理应用抗生素，并针对病程长、既往使用抗菌药物、使用三代头孢、合并骨髓炎和神经缺损性伤口等独立危险因素做好相应预防措施。     

Cross-domain retinopathy classification with optical coherence tomography images via a novel deep domain adaptation method

Deep learning based retinopathy classification with optical coherence tomography (OCT) images has recently attracted great attention. However, existing deep learning methods fail to work well when training and testing datasets are different due to the general issue of domain shift between datasets caused by different collection devices, subjects, imaging parameters, etc. To address this practical and challenging issue, we propose a novel deep domain adaptation (DDA) method to train a model on a labeled dataset and adapt it to an unlabelled dataset (collected under different conditions). It consists of two modules for domain alignment, that is, adversarial learning and entropy minimization. We conduct extensive experiments on three public datasets to evaluate the performance of the proposed method. The results indicate that there are large domain shifts between datasets, resulting a poor performance for conventional deep learning methods. The proposed DDA method can significantly outperform existing methods for retinopathy classification with OCT images. It achieves retinopathy classification accuracies of 0.915, 0.959 and 0.990 under three cross-domain (cross-dataset) scenarios. Moreover, it obtains a comparable performance with human experts on a dataset where no labeled data in this dataset have been used to train the proposed DDA method. We have also visualized the learnt features by using the t-distributed stochastic neighbor embedding (t-SNE) technique. The results demonstrate that the proposed method can learn discriminative features for retinopathy classification.     

Feasibility of neonatal haemoglobin A1C as a biomarker for retinopathy of prematurity

Abstract

Introduction

Retinopathy of prematurity (ROP) is a potentially serious eye disorder affecting very preterm infants. Non-proliferative ROP (NP-ROP), also known as Early Stage ROP, is characterized by deficient retinal angiogenesis. Proliferative ROP (P-ROP), also known as Late Stage ROP, is characterized by pathologic angiogenesis. The use of neonatal haemoglobin A1C as a biomarker for ROP has not yet been evaluated.     

Taurine: A therapeutic agent in experimental kidney disease

Summary Taurine is an abundant free amino acid in the plasma and cytosol. The kidney plays a pivotal role in maintaining taurine balance. Immunohistochemical studies reveal a unique localization pattern of the amino acid along the nephron. Taurine acts as an antioxidant in a variety ofin vitro andin vivo systems. It prevents lipid peroxidation of glomerular mesangial cells and renal tubular epithelial cells exposed to high glucose or hypoxic culture conditions. Dietary taurine supplementation ameliorates experimental renal disease including models of refractory nephrotic syndrome and diabetic nephropathy. The beneficial effects of taurine are mediated by its antioxidant action. It does not attenuate ischemic or nephrotoxic acute renal failure or chronic renal failure due to sub-total ablation of kidney mass. Additional work is required to fully explain the scope and mechanism of action of taurine as a renoprotective agent in experimental kidney disease. Clinical trials are warranted to determine the usefulness of this amino acid as an adjunctive treatment of progressive glomerular disease and diabetic nephropathy.     

Targeting epigenetic modifications as a potential therapeutic option for diabetic retinopathy

Diabetic retinopathy (DR) is the leading cause of visual impairment in adults of working age (20–65 years) in developed countries. The metabolic memory phenomena (persistent effect of a glycemic insult even after retrieved) associated with it has increased the risk of developing the complication even after the termination of the glycemic insult. Hence, the need for finding early diagnosis and treatment options has been of great concern. Epigenetic modifications which generally occur during the beginning stages of the disease are responsible for the metabolic memory effect. Therefore, the therapy based on the reversal of the associated epigenetic mechanism can bring new insight in the area of early diagnosis and treatment mechanism. This review discusses the diabetic retinopathy, its pathogenesis, current treatment options, need of finding novel treatment options, and different epigenetic alterations associated with DR. However, the main focus is emphasized on various epigenetic modifications particularly DNA methylation which are responsible for the initiation and progression of diabetic retinopathy and the use of different epigenetic inhibitors as a novel therapeutic option for DR.     

Phorbol Ester-Mediated Stimulation of Phospholipase D Activity in Sciatic Nerve from Normal and Diabetic Rats

Evidence for the presence of phospholipase D activity in sciatic nerve was obtained by incubation of 32P-prelabeled nerve segments in the presence of ethanol and measurement of [32P]phosphatidylethanol (PEth) formation expressed as a fraction of total phospholipid radioactivity. PEth synthesis was enhanced with increasing concentrations of ethanol (100 mM-2 M). 4-beta-Phorbol dibutyrate (100 nM-1 microM) stimulated PEth formation up to twofold in a time- and dose-dependent manner. The stimulatory effect evoked by 100 nM phorbol ester was completely abolished by Ro 31-8220 (compound 3), a selective protein kinase C inhibitor. Efforts to identify the phospholipid precursor of PEth were unsuccessful, suggesting this product arises from a small discrete precursor pool. On subcellular fractionation of nerve, the ratio of basal and 4-beta-phorbol dibutyrate-stimulated phospholipase D activity recovered in a myelin-enriched fraction, compared with a nonmyelin fraction, was 0.5 when results are expressed as a percentage of total phospholipid radioactivity. This ratio rises to 1.2 if the results are calculated assuming only phosphatidylcholine and phosphatidylethanolamine are potential precursors. The results suggest that myelin is a major locus of phospholipase D activity. Nerve from streptozotocin-induced diabetic and control animals displayed the same basal phospholipase D activity, but the enzyme in diabetic nerve was stimulated to a greater extent by a suboptimal concentration of 4-beta-phorbol dibutyrate. These results support the conclusion that protein kinase C modulates phospholipase D activity in nerve and suggest that in diabetic nerve the enzyme activation mechanism may possess increased sensitivity.