血管内皮生长因子在发绀型先天性心脏病中的变化

目的观察血管内皮生长因子(VEGF)在发绀型先天性心脏病(CCHD)中变化及其与病情严重程度关系。方法采用ELISA方法检测和比较20例CCHD和18例健康儿童的血清VEGF,并探讨CCHD患儿血清VEGF与血红蛋白及动脉血氧饱和度间的关系。结果CCHD患儿组VEGF明显高于正常对照组,差异有显著性[(164.65±55.73)ng/Lvs(25.56±10.67)ng/L,t=10.41 P<0.01];VEGF水平与动脉血氧饱和度呈明显负相关(r=0.602 P<0.01);VEGF水平与血红蛋白浓度呈明显正相关(r=0.795 P<0.01)。结论CCHD患儿血清VEGF浓度升高,并与病情严重程度相关,提示VEGF在CCHD病理生理中可能起重要作用。     

糖尿病自主神经病变临床分析

目的探讨糖尿病自主神经病变与脑血管病变、血糖、糖尿病肾病病变关系。方法测定65例糖尿病患者的心率变异性,据此将患者分为自主神经病变组20例和无自主神经病变组45例,2组患者均接受经颅多谱勒检查,并检验糖化血红蛋白、高敏CRP和尿微量白蛋白。结果自主神经病变组脑血管顺应性下降,脑血流减慢,血糖、尿微量白蛋白及高敏CRP升高。结论糖尿病自主神经病变与血糖控制有关,与炎症和糖尿病肾病相关,可能是促进糖尿病脑血管病变的危险因素之一。     

Attention,response inhibition and brain event-related potential alterations in adults with beta-thalassaemia major

We investigated neural correlates of cognitive function in adults with beta thalassaemia major (β-TM) compared to healthy controls using scalp-recorded event-related potentials (ERPs). Event-related potential studies in the field of β-TM are scarce and mostly limited to children. A stop-signal task was used to evaluate indices of attention and response inhibition function, considered to be the hallmark of executive control. Correlations between task performance, ERPs and haemoglobin were also examined. Results showed impaired cognitive performance in β-TM patients, as indicated by longer response times than controls. Haemoglobin was negatively correlated with response times to Go stimuli. Electrophysiological results indicated significant β-TM-related alterations in neuronal activity, reflected in greater peak amplitudes of several task-related ERP components. A possible interpretation of these ERP results is that β-TM patients need to recruit additional brain resources when dealing with cognitive challenge. Significant correlations were found between levels of haemoglobin and amplitude of all ERP components; the lower the haemoglobin, the more pronounced the ERPs amplitude. The present study represents a novel investigation of cognitive function and related brain dynamics in β-TM in adult. Integrating neuropsychological assessment and interventions into traditional disease management, may be imperative in achieving a better quality of life for these patients.     

基于血红蛋白F的镰状细胞病基因治疗的研究进展

镰状细胞病(SCD)是一种单基因遗传病,严重威胁患者寿命和生活质量。本文从SCD的发病机制及基于胎儿血红蛋白F(Hb F)的替代治疗入手,回顾了近年对BCL11A、ZBTB7A、KLF-1、c-MYB和SOX6等参与Hb F基因表达调控的转录因子的研究进展,以及CRISPR/Cas9、TALEN、锌指核酸酶等基因编辑技术在该领域的应用,为SCD及β-地中海贫血等β-样血红蛋白病的新治疗方案的探索提供坚实的理论基础。     

Discovery of DS79932728: A Potent,Orally Available G9a/GLP Inhibitor for Treating β-Thalassemia and Sickle Cell Disease

Therapeutic reactivation of the γ-globin genes for fetal hemoglobin (HbF) production is an attractive strategy for treating β-thalassemia and sickle cell disease. It was reported that genetic knockdown of the histone lysine methyltransferase EHMT2/1 (G9a/GLP) is sufficient to induce HbF production. The aim of the present work was to acquire a G9a/GLP inhibitor that induces HbF production sufficiently. It was revealed that tetrahydroazepine has versatility as a side chain in various skeletons. We ultimately obtained a promising aminoindole derivative (DS79932728), a potent and orally bioavailable G9a/GLP inhibitor that was found to induce γ-globin production in a phlebotomized cynomolgus monkey model. This work could facilitate the development of effective new approaches for treating β-thalassemia and sickle cell disease.     

Scoring System to Predict Hospital Outcome After Subarachnoid Hemorrhage–Incorporating Systemic Response: The CRIG Score

ObjectivesLocal and systemic proinflammatory and prothrombotic processes after aneurysmal subarachnoid hemorrhage (aSAH) precipitate delayed cerebral ischemia (DCI) and determine clinical outcome. Recent studies using admission and temporal trends of mean platelet volume to platelet count ratio (MPV:PLT) and neutrophil to lymphocyte ratio (NLR) have identified patients developing DCI. We examine if MPV:PLT and NLR along with admission clinical or radiological features can be used to develop a scoring system to predict DCI and in-hospital clinical outcome.Materials and methodsA 7-year retrospective cohort of aSAH patients admitted to a tertiary care medical center was used to study and identify clinical, radiological and laboratory parameters to predict DCI and clinical outcome (good: discharge to home or rehabilitation facility; poor: all other discharge destinations). Using regression analyses a scoring system (Clinical, Radiological, Inflammatory, dysGlycemia, CRIG) was developed.ResultsOf 271 patients, admission clinical grade (World Federation of Neurological Surgeons’ scale), radiological grade (modified Fisher score), NLR and glycated hemoglobin were identified as contributors for CRIG score. CRIG_DCI score threshold of 112 and CRIG_discharge 109, respectively predicted DCI and adverse clinical outcome in score development cohort. The same threshold predicted DCI and adverse clinical outcome with 78.1 and 100% sensitivity, 44.0 and 52.2% specificity, and 63.2 and 61.4% accuracy, respectively in the score validation cohort.ConclusionsCRIG is an easily calculable scoring system that incorporates systemic response of aSAH – thus, alluding to its multisystem nature. It can be used at the time of admission to predict DCI and clinical outcome.     

Molecular and geographical heterogeneity of hemoglobinopathy mutations in Azerbaijanian populations

With the carrier rate of 4%–8.6%, β-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. Α- and β-globin genes were evaluated in the carriers of mutations identified via hematological indices and hemoglobin fractions (n = 1,757). Genotyping of β-thalassemia carriers identified through population screening revealed 32 mutations, with codon 8 [–AA]–34.96%, IVS-II-1 [G > A]–16.35%, and IVS-I-110 [G > A]–10.12% leading the spectrum. Analysis of associations of β-thalassemia mutations with geographical regions of the country identified the strongest association between codon 8 [–AA] and Shaki-Zaqatala, and codon 5 [–CT] in Mountainous Shirvan regions (ri > 6.00; p < 0.05). HbS, HbD-Punjab, and HbE were the most prevalent among our variant hemoglobin cohort, commonly inherited in compounds with β-thalassemia than in the homozygous state. We identified nine α-thalassemia mutations, 20.5 kb and 3.7 kb deletions together accounting for 74% of the spectrum. Point mutations of α-thalassemia were less common among our observations and were mainly inherited in compounds with deletions. Our results allow a better understanding of the wide spectrum of mutations in Azerbaijan and highlights the high heterogeneity of hemoglobinopathies in the local population.