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.     

Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

大鼠骶髂关节传入神经通路的实验研究

目的:通过逆行神经追踪法研究大鼠骶髂关节的传入神经通路。方法:30只雄性Sprague-Dawley大鼠随机分成非交感神经切除组(A组)和交感神经切除组(B组),每组15只,交感神经切除组切除左侧L1以下椎旁交感干。两组左侧骶髂关节注入30%的辣根过氧化物酶(HRP)20μl,72h后取出双侧的L1-S1背根神经节(DRG),TMB法染色后在光学显微镜下观察HRP阳性神经元细胞并计数。结果:两组左侧L1、L2背根神经节内HRP阳性神经元差异有显著性意义(P<0·05),B组HRP阳性神经元明显减少;左侧L3-S1背根神经节内HRP阳性神经元差异无显著性意义(P>0·05)。结论:L1-S1神经节含有支配同侧骶髂关节的传入神经元,同侧椎旁交感干可能是骶髂关节到L1-L2神经节重要的传入神经旁路,而不是到L3-L5神经节的传入旁路或重要的传入旁路。     

胸腺内注射异基因抗原诱导鼠神经移植免疫耐受的实验研究

目的探讨小鼠胸腺内注射异基因抗原在同种异体异基因坐骨神经移植免疫耐受中的作用。方法自供体小鼠C57BL／6的脾细胞中提取MHC抗原注人受体鼠Balb／c小鼠胸腺内，于2周后移植供体鼠坐骨神经。48只Balb／c小鼠随机分为4组，A组（胸腺内注射组）、B组（自体神经移植组）、C组（冷冻异体神经移植组）、D组（异体神经移植加用免疫抑制剂组）。于3周后进行电生理学、组织学、免疫学检测。结果A组运动神经传导速度（38．23m／s）与D组（36．39m／s）相比无显著性差异（P〉0．05），组织学、电镜、免疫学（混合淋巴细胞培养及迟发性超敏反应）检测结果均证实B组分别优于A组、D组和C组。结论胸腺内注射异基因MHC抗原可诱导大鼠对异体坐骨神经移植的特异性免疫耐受。     

根管预备程度对无髓牙根管壁应力影响的分析

目的 分析不同根管腔的直径对根管壁应力的影响。方法 在已建立的下颌第一磨牙模拟常规法根管预备修改的实验模型基础上，再修改根管腔直径，使根管直径扩大到牙根直径的1／3和1／2，并在修改模型上加载，计算在不同加载条件下牙齿各部及管壁的最大应力。结果 根管腔直径增大会引起根管壁应力的升高，该变化主要出现在根管口和根上1／3段，侧向加载时产生的应力差异大于垂直加载时产生的应力差异。结论 根管预备应以去除根管壁的感染物质，获得良好的根管成形为原则，过度的预备不仅没有必要，甚至有害。     

超顺磁氧化铁标记骨髓基质干细胞移植治疗帕金森病鼠的实验研究

目的:研究应用超顺磁氧化铁(SPIO)标记骨髓基质干细胞(MSCs)移植治疗帕金森病(PD)大鼠后的在体MRI观察。方法:分离、获取大鼠骨髓基质细胞,脂质体转染法将SPIO标记MSCs;制作PD模型,SPIO标记的MSCs移植到PD大鼠右侧纹状体区,应用MRI在体观察脑内移植的骨髓基质细胞的存活和迁徙情况。结果:体外SPIO标记的骨髓基质细胞普鲁蓝染色阳性;脑内移植SPIO标记MSCs的PD大鼠磁共振T2和T2GRE扫描检查显示在移植区呈低信号改变。随时间的延长,移植区信号向周围扩大。脑纹状体区的铁染色也可见SPIO标记MSCs从移植部位向四周迁移。结论:SPIO可用于体外标记MSCs,通过MRI技术可以对标记细胞脑内移植后进行初步的活体示踪,有利于MSCs移植治疗PD后的疗效观察。     

磷酸化信号传导与转录激活因子3在前列腺癌早期诊断中的应用

目的 探讨前列腺穿刺标本中磷酸化信号传导与转录激活因子3(P-STAT3)表达在前列腺癌(PCa)早期诊断中的应用价值.方法采用免疫组织化学方法检测接受重复穿刺的PCa患者初次穿刺未检出癌的标本(29例)、重复穿刺确诊PCa时的癌灶标本(29例)、重复穿刺确诊PCa时的非癌灶标本(29例)以及良性前列腺增生(BPH)患者初次穿刺标本(29例)中P-STAT3的表达.统计学分析其与临床诊断的相关性及对PCa发生的预测作用.结果 P-STAT3在PCa患者癌灶标本、非癌灶标本及初次穿刺标本中阳性表达率分别为93.1%(27/29)、82.8%(24/29)和86.2%(25/29),在BPH标本中阳性表达率为10.3%(3/29),前三者的阳性率明显高于后者(X2=60.123,P=0.000);如以初次穿刺标本中P-STAT3表达阳性作为PCa的诊断标准,该方法的敏感性为86.2%,特异性为89.7%.结论 检测穿刺标本P-STAT3表达可以作为前列腺穿刺活检的辅助诊断方法,用于PCa的早期诊断,预测PCa的发生.     

国外经皮冠状动脉腔内成形术后留置动脉鞘管的护理进展

经皮冠状动脉腔内成形术（PTCA）是近30年来治疗冠心病的主要技术之一，其相应的护理技术在过去近10年里有着明显的改进。本文以穿刺股动脉途径为重点综述国外PTCA术后留置动脉鞘管的护理进展：动脉外鞘管拔除责任者、拔除时间、拔管后局部压迫方法等内容，旨在提升PTCA术后的护理质量。