IFI 30、PD-L1在人脑胶质瘤中的表达及与病人预后的关系

目的 探讨γ干扰素诱导蛋白30（IFI 30）、程序性死亡因子配体1（PD-L1）在人脑胶质瘤中的表达及与病人预后的关系。方法 选择2015年5月~2019年5月手术切除的103例人脑胶质瘤组织和瘤旁组织，采用免疫组织化学染色检测IFI 30、PD-L1表达情况。随访24个月，记录无进展生存期和总生存期。结果 胶质瘤组织IFI 30、PD-L1高表达率[分别为70.87%（73/103）、68.93%（71/103）]明显高于瘤旁组织[分别为19.42%（20/103）、21.36%（22/103）；P<0.001]。胶质瘤组织IFI 30表达水平与PD-L1表达水平呈明显正相关（r=0.583，P<0.05）。随访24个月，生存75例，死亡28例；多因素logistic回归分析显示，IFI 30高表达、PD-L1高表达是增加病人死亡风险的独立危险因素（P<0.05）。生存曲线分析显示，IFI 30高表达组2年累积生存率（64.52%）和2年累积无进展生存率（65.56%）均明显低于低表达组（分别为82.25%、89.45%；P<0.05）。PD-L1高表达组2年累积生存率（61.78%）和2年累积无进展生存率（60.14%）均明显低于低表达组（分别为88.52%、79.86%；P<0.05）。结论 人脑胶质瘤组织IFI 30、PD-L1呈高表达，与病人不良预后密切相关。     

运用六经辨证治疗子嗽探析

妊娠期间,咳嗽不已,称"妊娠咳嗽",亦称"子嗽",孕妇咳嗽日久未见好转,咳嗽胸痛甚则咳而呕吐,或咳嗽剧烈或久咳不愈,可损伤胎气,导致堕胎、小产。笔者运用六经辨证治疗外感型中表寒里热证子嗽,认为此类患者病在太阳阳明,属于寒热错杂之表寒里热,采用《伤寒论》中方证麻杏甘石汤合止嗽散,使热从外泄,宣发卫气,散寒不助热、解表不伤正,故辨证论治取得了显著的疗效。同时子嗽治疗还需注意健脾固肾安胎,应将顾护胎元贯穿治疗妊娠咳嗽的始终。     

双球囊与缩宫素用于促宫颈成熟以及引产的效果比较

目的比较双球囊与缩宫素用于促宫颈成熟并引产的临床效果。方法选取于2017年7月—2018年7月在本院分娩的足月妊娠孕妇100例为研究对象,随机平均分为观察组和对照组各50例,观察组采用双球囊引产,对照组采用缩宫素进行引产,对比2组孕妇的总产程、宫颈成熟度、引产成功率和新生儿Apgar评分、并发症发生率等。结果观察组促宫颈成熟有效率(100%)、引产成功率(96%)均高于对照组(82%,74%),差异均有统计学意义(P<0.05),治疗后新生儿Apgar评分、并发症发生率差异均无统计学意义(P>0.05);宫颈Bishop评分观察组(9.12±1.42)高于对照组(7.92±1.56),观察组总产程(8.23±2.54)h,对照组(13.45±3.77)h,差异均有统计学意义(P<0.05)。结论双球囊用于妊娠引产效果显著,能明显促进宫颈成熟、缩短产程,保障分娩的顺利进行,安全可靠,值得在临床中推广。     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

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.