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...     

针刺配合肠炎散保留灌肠治疗肛窦炎临床研究

目的观察肛窦炎应用针刺配合肠炎散保留灌肠治疗的效果。方法选取2017年10月-2018年10月就诊的72例肛窦炎患者,采用随机数字表法分为观察组(n=36)与对照组(n=36)。对照组给予肠炎散保留灌肠治疗,观察组为针刺配合肠炎散保留灌肠治疗,比较2组症状、疗效及安全性。结果观察组症状(放射痛、指诊症状及镜检症状)少于对照组,总有效率高于对照组,差异有统计学意义(P<0.05);2组安全性相比,差异无统计学意义(P>0.05)。结论针对肛窦炎患者,予以针刺配合肠炎散保留灌肠治疗效果确切,可减少临床症状,加快疾病转归,且治疗安全性较好。     

充气温控毯用于神经外科手术患者的控温效果

目的评价充气温控毯用于神经外科手术患者的控温效果。方法40例择期行平卧位脑肿瘤切除术患者,年龄16—65岁,体重41-72 kg,ASAⅠ-Ⅲ级,随机分为2组(n=20):A组,术中充气温控毯24℃风档进行降温,肿瘤切除完毕前30 min进行复温;B组,术中充气温控毯维持中心温度正常(35．2—36．60℃)。均采用气管内静吸复合麻醉,静脉注射异丙酚1．5～2 mg／kg、芬太尼4-6μg／kg、维库溴铵0．1～0．2 mg／kg诱导,吸入0．6％-1．2％异氟醚维持;吸入氧浓度40％;异丙酚1．5～2 mg·kg-1·h-1持续输注;维库溴铵1～2 mg间断静脉注射。每5分钟记录1次中心温度(鼻咽温),观察围术期不良反应及并发症。结果A组2例患者因手术时间超过24 h剔除,共38例进行统计。A组患者降温速率(1．11±0．05)℃／h,复温速率(0．74±0．09)℃／h。A组患者89％(16/18)在硬脑膜打开前达到目标温度34℃,平台期平均中心温度(34．3±0．5)℃,距34℃最大升幅0．52℃,最大降幅为0．23℃。A组患者67％(12／18)手术结束时中心温度恢复正常。返回ICU后A组患者中心温度(返回ICU时实测温度的均值)(35．8±0．6)℃低于B组(36．6±0．4)℃(P<0．05)。A组患者4例术后出现寒颤、3例发热、1例死亡。结论神经外科手术中应用充气温控毯可较理想地降低体温,相对于降温效率其复温效率偏低。     

综合性医院抑郁症的特点及疗效分析

目的:了解综合性医院神经内科门诊抑郁症的临床特点及抗抑郁治疗的临床疗效.方法:对46例抑郁症患者的临床特点进行研究分析,同时对其中24例患者给予帕罗西汀治疗,对汉密尔顿抑郁评定表(HAMD)的平均总分数、汉密尔顿4因子及临床总体印象量表(CGI)评分在治疗前后进行比较.结果:46例抑郁症患者均以不同程度的躯体症状为主诉,临床表现多种多样,可涉及全身各系统;其中24例抑郁症患者给予帕罗西汀治疗后,汉密尔顿抑郁评定表的平均总分数、汉密尔顿4因子及临床总体印象量表评分分数在治疗后较治疗前显著减少(P＜0.01).结论:了解抑郁症患者躯体症状的临床特点,对于抑郁症的诊断和治疗至关重要.帕罗西汀对抑郁症患者具有明显的抗焦虑作用及早期改善睡眠的作用且整体抗抑郁疗效好.     

β-胡萝卜素立体异构体对环磷酰胺处理小鼠免疫功能的比较研究

就β-胡萝卜素立体异构体对环磷酰胺处理小鼠的免疫功能影响进行了比较研究。结果显示β-胡萝卜素立体异构体对外磷酰胺造成的免疫功能低下具有不同程度的改善作用，提高胸腺和脾脏指数，增强脾脏细胞对刀豆素A（ConA）的反应性和NK活性，血清溶菌酶含量也有所增加。综合各项指标，9-顺式和全反式混合物的作用最明显，提示一定浓度的9-顺式对于提高β-胡萝卜素对机体的总体作用是有一定意义的。     

家兔静注水杨醛-N'-(2-呋喃硫羰基)腙铜配合物的药物动力学

目的：研究水杨醛－Ｎ′－（２－呋喃硫羰基）腙铜配合物（ＣＳＦＣ）在兔体内的药物动力学。方法：１０只家兔静脉注射ＣＳＦＣ５ｍｇ·ｋｇ－１，用反相ＨＰＬＣ法测定血清药物浓度。结果：ＣＳＦＣ的血药浓度－时间曲线符合二室开放模型，主要药动学参数为：Ｔ１２α＝３．４±１．７ｍｉｎ，Ｔ１２β＝６５．５±１４．６ｍｉｎ，Ｋ１２＝０．１１８３±０．０６６９ｍｉｎ－１，Ｋ２１＝０．０２２８±０．００６５ｍｉｎ－１，Ｋ１０＝０．１２０２±０．０４０７ｍｉｎ－１，Ｖ０＝０．３０５±０．１８４Ｌ·ｋｇ－１，ＣＬ＝１．８９６±０．４７０Ｌ·ｋｇ－１·ｈ－１，ＡＵＣ＝１７０．１±５７．０ｍｇ·ｍｉｎ－１·Ｌ－１。结论：ＣＳＦＣ在兔体内分布迅速而广泛，消除也较快。家兔静注５ｍｇ·ｋｇ－１，可维持抗结核杆菌有效血浓度６ｈ。     

中老年男性下尿路症状的流行病学调查

为了了解下尿路症状在中、老年男性中的流行情况，用附加了二个症状问题的ＳＬ问卷对８７１名５２～７４岁的男子作回顾性调查，对调查结果作了年龄分组分析。结果发现：平均ＩＰＳＳ总分为４．９３分，无症状者为１２．２％，轻症者为６４．７％，中度症状者为１９．６％，重症者为３．５％。夜尿者占７２．３％，尿终滴沥占５４．４％，而症状中分值＞３分者尿终滴沥占２５．６％，夜尿占１４．６％，平均ＱＯＬ为１．７４，ＱＯＬ为０～２、３、４～６的比例分别为５２．７％、４６．０％、１．３％。ＱＯＬ与ＩＰＳＳ的相关性较好（ｒ＝０．６２），与梗阻症状群的相关性（ｒ＝０．５７）优于与刺激症状的相关性（ｒ＝０．４４）。中重度症状者中有７２．０％的人未进行治疗。     

胃癌组织p16基因蛋白表达的意义

目的　检测 p1 6基因蛋白在胃癌组织、癌旁组织中的表达及其分布特点 ,分析其与胃癌临床病理学特征及预后的关系 .方法　采用 S- P免疫组织化学法对 53例胃癌组织及 35例癌旁组织进行 p1 6蛋白的定位观察 .结果　各病理类型胃癌组织、癌旁组织均有 p1 6基因蛋白表达 .阳性率分别为 62 .3% (33/53)和 88.6% (31 /35) ,阳性细胞的棕黄色颗粒主要位于细胞核 .胃癌 p1 6基因蛋白表达与性别、年龄、肿瘤部位在统计学上无差异 (P>0 .0 5) ;而与组织学类型、病理分级、淋巴结转移、临床病理分期在统计学上有差异 (P<0 .0 5) .p1 6蛋白阳性者 5年生存率 51 .0 %高于 p1 6蛋白阴性者 2 0 .0 % (P<0 .0 5) .结论　 p1 6基因缺失和表达水平的改变与胃癌发生、发展密切相关 ,检测 p1 6基因蛋白表达可作为辅助临床判断胃癌的生物学行为及推测预后的指标