HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.     

2016至2018年某医院真菌血流感染者流行病学特征及耐药性分析

目的分析真菌性血流感染的病原菌分布以及耐药特征，为真菌血流感染的早期合理用药提供理论依据。 方法回顾性分析武汉大学人民医院2016年1月至2018年12月收治的真菌性血流感染者的菌群、科室分布以及耐药性。 结果入组192例真菌血流感染者的血培养样本中共分离192株真菌，其中白色念珠菌检出率为31.77%（61/192），其次热带念珠菌检出率为18.75%（36/192）；重症医学科检出率最高为33.85%（65/192）。所有菌株均对两性霉素B敏感，对其他抗菌药物耐药率分别为5-氟胞嘧啶4.49%（9/192）、伊曲康唑5.73%（11/192）、氟康唑10.94%（21/192）和伏立康唑11.46%（22/192）；除两性霉素B外，2016至2018年真菌对其他抗菌药物的耐药率均逐年上升，其中2018年所分离192株光滑念珠菌对伊曲康唑耐药菌率达46.7%。 结论真菌血流感染病原菌以念珠菌属为主，对目前抗真菌药物具有较高敏感性，但耐药率逐年上升，加强监测血培养病原菌变化及耐药趋势对指导临床用药至关重要。     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Confidentiality Discussions and Private Time With a Health-Care Provider for Youth,United States, 2016

Purpose

The objective of the study was to define factors associated with adolescent and young adult (AYA) experiences with private time and having discussed confidentiality and the impact of these experiences on improving delivery of clinical preventive services.

甲状腺乳头状癌伴发桥本甲状腺炎的临床研究

背景与目的：甲状腺乳头状癌（papillary thyroid carcinoma，PTC）和桥本甲状腺炎（Hashimoto’s thyroiditis，HT）的发病率均呈上升趋势，两者之间的关系已成为目前研究的热点。探讨PTC和HT之间的关系。方法：回顾性分析2014—2015年期间在中国科学院大学附属肿瘤医院头颈肿瘤外科行甲状腺癌手术治疗的首诊患者306例，术后病理学检查均明确诊断为PTC，其中术后病理学确诊伴发HT者42例，比较伴发HT与未伴发HT患者的临床病理学特征。结果：PTC患者女性发病年龄高于男性（46.2岁 vs 41.9岁）。相较于与未伴发HT的PTC患者，伴发HT的患者中女性比例更高（93% vs77%），中央区淋巴结数目较多［（5.0±3.4）枚 vs （2.5±2.7）枚］，术前促甲状腺激素（thyroid-stimulating hormone，TSH）水平较高［（3.28±1.91）μU/mL vs （2.12±1.29）μU/mL］，术前抗甲状腺过氧化物酶抗体（thyroid peroxidaseantibody，TPOAb）阳性率较高（55% vs 14%），术前甲状腺球蛋白抗体（thyroglobulin antibodies，TgAb）阳性率较高（69% vs 13%）。发生中央区淋巴结转移的患者中，中央区淋巴结转移数目与中央区淋巴结总数显著相关（Pearson相关系数=0.582）。多因素logistic回归分析发现，男性、低龄、被膜侵犯是PTC患者中央区淋巴结转移的独立危险因素。结论：伴发HT对PTC患者的预后无显著影响。伴发HT的PTC患者TSH水平显著偏高，提示HT可能是PTC发病风险因素之一。中央区淋巴结转移数目与中央区淋巴结总数相关，推测PTC淋巴结转移可能与淋巴结炎症反应相关。     

以胜任力为导向的医学研究生综合素质课程体系构建及探索

通过比较中美研究生教育，总结现有教学经验，以学生需求和社会需求为中心，探索构建以胜任力为导向的医学研究生综合素质课程体系，加强理想信念与品德教育、创新创业教育、学术道德与诚信教育、心理健康教育等，发挥综合素质课程的积极价值引领作用，促进医学生从个性化发展成长为具备社会适应能力的合格医者的转变。