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.     

PS联合CPAP治疗新生儿呼吸窘迫综合征临床研究

目的通过研究肺表面活性物质(PS)结合持续气道正压通气(CPAP)治疗新生儿呼吸窘迫综合征(NRDS)的治疗效果,进一步指导NRDS的临床治疗。方法选取于2017年4月-2018年10月间在本院收治的80例确诊为新生儿呼吸窘迫综合征的患儿作为研究对象,随机将患儿分为试验组和对照组,对照组给予持续气道正压通气治疗,试验组在对照组的基础上联合使用PS治疗。结果试验组对于呼吸窘迫缓解的有效率明显高于对照组,在气管插管内滴入PS治疗后试验组的血气情况明显优于对照组,且试验组患儿副作用发生率明显低于对照组,以上指标差异具有统计学意义,P <0.05。结论 PS结合CPAP在新生儿呼吸窘迫综合征的治疗中疗效很好。     

Clinical Guidance for the Management of Patients with Urothelial Cancers During the COVID-19 Pandemic – Rapid Review

The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness. In addition, staff illness and restructuring of services to deal with the crisis will inevitably place treatment capacities under significant strain. These guidelines aim to expand on those provided by NHS England regarding cancer care during the coronavirus pandemic by examining the known literature and provide guidance in managing patients with urothelial and rarer urinary tract cancers. In particular, they address the estimated risk and benefits of standard treatments and consider the alternatives in the current situation. As a result, it is recommended that this guidance will help form a framework for shared decision making with patients. Moreover, they do not advise a one-size-fits-all approach but recommend continual assessment of the situation with discussion within and between centres.     

逐瘀止血汤加减治疗慢性子宫内膜炎气虚血瘀证的疗效观察

目的 评价逐瘀止血汤加减对慢性子宫内膜炎（CE）气虚血瘀证患者妊娠结局的影响及对免疫炎症因子的调节作用。方法 将144例患者随机按数字表法分为观察组和对照组各72例。观察组脱落、失访4例，剔除2例，完成66例；对照组脱落、失访3例，剔除5例，完成65例。两组均给予抗感染治疗14 d。对照组口服妇科千金片，6片/次，3次/d。观察组内服逐瘀止血汤加减，1剂/d。两组疗程均为3个月，并随访6个月。记录治疗前后月经经量、经期和周期变化情况；进行治疗前后宫腔镜和阴道彩色多普勒超声检查，评价子宫内膜形态、子宫内膜容受性（CP）［子宫内膜厚度、阻力指数（RI），搏动指数（PI）和血流指数（FI）］等，并进行子宫内膜病理检查；进行治疗前后气虚血瘀证评分；检测治疗前后月经血白细胞介素-1β（IL-1β），IL-6和肿瘤坏死因子-α（TNF-α）水平和外周血测T淋巴亚群（CD3⁺，CD4⁺，CD8⁺）水平；随访记录妊娠情况和流产情况。进行安全性评价。结果 治疗后观察组经量、经期、周期和月经完全正常率均高于对照组（P<0.05）；观察组子宫内膜厚度和FI均高于对照组（P<0.01），RI和PI均低于对照组（P<0.01）；观察组月经血IL-1β，IL-6和TNF-α水平均低于对照组（P<0.01）；观察组CD3⁺，CD4⁺水平和CD4⁺/ CD8⁺均高于对照组（P<0.01），CD8⁺水平低于对照组（P<0.01）；在6个月随访期间，观察组妊娠率46.97%（31/66），高于对照组的27.69%（18/65）（χ²=5.197，P<0.05）；观察组子宫内膜形态疗效总有效率为96.97%（64/66），高于对照组的86.15%（56/65）（χ²=4.981，P<0.05）；观察组子宫内膜病理组织疗效总有效率为95.45%（63/66），高于对照组的84.62%（55/65）（χ²=4.304，P<0.05）；观察组综合临床疗效总有效率为93.94%（62/66），高于对照组的81.54%（55/65）（χ²=4.696，P<0.05）；两组治疗期间均未发现与中药相关不良反应。结论 逐瘀止血汤加减治疗CE气虚血瘀证患者，可调经月经、减轻临床症状，改善宫腔镜下内膜形态，调节全身和局部的免疫炎症反应，提高了CP，从而改善了妊娠结局，有着较好的综合疗效，且安全。     

产前超声诊断胎儿右房异构一例

本文报道产前超声诊断胎儿右房异构一例。孕妇孕24周产前超声检查发现胎儿左位心合并复杂心血管畸形(右心室双出口、房室间隔缺损、肺动脉发育不良、双侧上腔静脉、心下型完全型肺静脉异位引流)、胃泡位于腹腔右侧、中位肝、可疑无脾、腹主动脉与下腔静脉位于脊柱左侧、双侧支气管呈右侧支气管对称形态,综合考虑右房异构可能。引产后经尸体解剖证实脾脏发育不良、右房异构。右房异构常合并复杂心血管畸形,因此产前超声发现复杂心血管畸形时,应警惕右房异构的可能。右房异构病死率极高,产前诊断具有重要意义。     

针刺辅助治疗难治性肠易激综合征临床试验方案关键点设计的思考＊

肠易激综合征（Irritable bowel syndrome，IBS）是临床常见病、多发病，其治疗方法丰富，但部分患者疗效欠佳，发展成难治性IBS。目前国内外关于针灸治疗难治性IBS的临床随机对照试验尚不多见。本文立足试验方案设计的“PICOS”原则，从研究对象及诊断标准、干预措施、对照措施、结局指标四个方面入手，重点探讨针刺辅助治疗难治性肠易激综合征临床试验设计的关键要点。从选择特色优势病种、明确诊断标准、制定符合临床实际的干预方案、运用符合目标的安慰针刺、结合研究设计和目的选定结局指标几个角度，阐述试验相关环节设计的原因和思考。