目的:研究lncRNA SNHG7在神经母细胞瘤(neuroblastoma，NB)进展中的作用，以及SNHG7-miR-653-5p-STAT2反馈通路在神经母细胞瘤进展中的调节作用。方法:从青岛大学附属医院收治的NB患儿体内获得92对NB组织及相邻非肿瘤组织。采用qRT-PCR检测SNHG7在神经母细胞瘤肿瘤组织及细胞中的表达情况。采用Kaplan-Meier分析神经母细胞瘤患儿的总体存活率。采用比色法(MTT法)和集落形成法检测SNHG7对SK-N-SH和SH-SY5Y细胞的作用。采用Transwell侵袭及迁移试验检测SK-N-SH和SH-SY5Y细胞的侵袭和迁移能力。采用荧光素酶检测miR-653-5p和SNHG7、STAT2之间的作用。采用RIP测定及RNA下拉测定检验SNHG7和miR-653-5p在NB中的相对表达情况。采用 Spearman相关分析探究SNHG7与miR-653-5p、STAT2的相关性。 结果:qRT-PCR显示，92对NB组织及相邻非肿瘤组织中，肿瘤组织( n＝53)中SNHG7的表达量高于非肿瘤组织( n＝39)。SNHG7高表达的NB患儿( n＝53)总生存期随月份的增加而逐渐降低，SNHG7低表达的NB患儿( n＝39)总生存期随月份的增加也逐渐降低，两组差异有统计学意义( P＝0.004)。细胞功能试验：①MTT法和集落形成法检测结果显示，SNHG7的下调对SK-N-SH和SH-SY5Y细胞的存活和增殖有明显抑制作用；②Transwell试验检测结果显示，敲低SNHG7可明显抑制SK-N-SH和SH-SY5Y细胞的细胞迁移和侵袭能力( P<0.05); ③荧光素酶检测显示，miR-653-5p能降低SNHG7-WT(野生型)的荧光素酶活性，且miR-653-5p与STAT2-WT(野生型)之间存在特异性的相互作用。 Spearman相关分析显示：①NB组织中SNHG7与miR-653-5p表达水平呈负相关( r＝-0.281， P＝0.007); ②STAT2的表达量与NB组织中miR-653-5p表达水平呈负相关( r＝-0.295， P＝0.004)，STAT2的表达量与NB组织中SNHG7表达水平呈正相关( r＝0.296， P＝0.004)。 结论:SNHG7通过miR-653-5p/STAT2通路促使NB进展，这为NB提供了一个新的治疗靶点和预测预后的生物标志物。

目的:分析儿童肿瘤引发高血压与心肌肥厚的相关因素，并探讨其诊治策略。方法:回顾性分析浙江大学医学院附属儿童医院于2015—2020年收治的3例儿童肿瘤合并高血压与心肌肥厚患儿的临床资料，观察年龄、病理类型、肿瘤大小以及位置等与高血压及心肌肥厚发生的关系，总结其综合治疗经验与预后。结果:3例患儿发病时年龄均<1岁，均因腹部肿物就诊，均合并高血压，超声均提示明显的心肌肥厚和左室射血功能下降。3例肿瘤类型分别为神经母细胞瘤、肾母细胞瘤和畸胎瘤。均于术前予降压、强心等综合治疗，在血压相对平稳的情况下均顺利完成手术治疗。术后血压均逐步恢复正常，心肌肥厚逐步缓解，心功能逐步改善。结论:不同肿瘤可能通过不同机制引发高血压，小婴儿高血压较难早期发现，持续高血压可能引发心肌肥厚和心功能不全。切除肿瘤是缓解高血压、改善心肌肥厚及心功能的根本性治疗手段。小婴儿心肌肥厚在尽早干预下可有较大机会逆转。

神经母细胞瘤是儿童最常见的颅外实体肿瘤，来源于肾上腺髓质或交感神经节。先天性神经母细胞瘤约占神经母细胞瘤患儿总数的5%，大多数患儿于出生后1个月内确诊。与1岁以上神经母细胞瘤患儿相比，新生儿神经母细胞瘤有其独特的病程。本文就先天性神经母细胞瘤的发病机制、临床表现、治疗方法以及预测患儿长期预后的生物学因素进行综述。

目的 探究抑肝散对阿尔茨海默病(AD)的治疗作用,通过网络药理学方法预测其机制,并进行实验验证.方法 以D-半乳糖诱导AD小鼠模型,通过水迷宫和八臂迷宫实验考察抑肝散(400、800mg·kg-1)对AD小鼠学习记忆功能的影响,并通过实时荧光定量PCR(qRT-PCR)法分析AD小鼠脑组织中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)的mRNA表达变化.通过中药系统药理学数据分析平台(TCMSP)对抑肝散的组方药材柴胡、甘草、川芎、当归、白术、茯苓和钩藤进行活性成分筛选,采用GeneCards等数据库获取AD疾病靶点,筛选其核心靶点,并对核心靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,分别获取核心靶点涉及的生物过程(BP)、分子功能(MF)和细胞组分(CC)以及KEGG信号通路.小鼠神经母细胞瘤Neuro-2a细胞和RAW264.7 巨噬细胞分别与H2O2和抑肝散(3、6 μg·mL-1)共培养,观察抑肝散对Neuro-2a细胞体外增殖和凋亡的影响,及对Neuro-2a细胞Caspase-3和Caspase-8活性、活性氧(ROS)、谷胱甘肽(GSH)、丙二醛(MDA)、超氧化物歧化酶(SOD)和线粒体膜电位(MMP)的影响;观察抑肝散对RAW264.7细胞TNF-α和IL-1β、IL-2、IL-6表达的影响,对网络药理学结果进行验证.结果 抑肝散可缓解AD小鼠学习记忆功能损伤,通过网络药理学技术筛选得到抑肝散治疗AD的活性成分159个,度值前10位的化合物分别是槲皮素、山柰酚、异鼠李素、β-谷甾醇、豆甾醇、7-甲氧基异黄酮、芒柄花素、柚皮素、美迪紫檀素和甘草查尔酮A,筛选得到核心靶点227个,度值排名前10的核心靶点为丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、白细胞介素6(IL6)、肿瘤蛋白P53(TP53)、白细胞介素1β(IL1B)、雌激素受体1(ESR1)、原癌基因(JUN)、前列腺素氧化环化酶2(PTGS2)、半胱氨酸蛋白酶3(CASP3)和信号转导和转录激活因子3(STAT3).生物信息学分析发现抑肝散治疗AD与糖基化终末产物/糖基化终末产物受体和脂质和动脉粥样硬化等信号通路有关.动物实验结果显示,抑肝散可改善AD模型小鼠学习记忆功能损伤,下调AD小鼠脑组织中IL-1β、IL-2、IL-6、TNF-α mRNA表达;细胞实验结果显示,抑肝散显著缓解H2O2对Neuro-2a细胞的增殖抑制作用和凋亡诱导作用(P＜0.05),降低Caspase-3、Caspase-8活性(P＜0.05),降低细胞MDA和ROS水平(P＜0.05),升高MMP及GSH水平;抑肝散对H2O2诱导的RAW264.7细胞TNF-α和IL-1β、IL-2、IL-6升高具有显著抑制作用(P＜0.05).结论 抑肝散通过缓解学习记忆功能损伤和氧化损伤发挥治疗AD作用.

Fufang Danshen (FFDS or Compound Danshen) consists of three Chinese herbs Danshen (Salviae miltiorrhizae radix et rhizome), Sanqi (Notoginseng radix et rhizome) and Tianranbingpian (Borneolum, or D-borneol), which has been show to significantly improve the function of the nervous system and brain metabolism. In this study we explored the possible mechanisms underlying the therapeutic effects of the combination of the effective components of FFDS (Tan IIA, NG-R1 and Borneol) in the treatment of Alzheimer's disease (AD) based on network pharmacology. We firstly constructed AD-related FFDS component protein interaction networks, and revealed that macrophage migration inhibitory factor (MIF) might regulate neuronal apoptosis through Bad in the progression of AD. Then we investigated the apoptosis-inducing effects of MIF and the impact of the effective components of FFDS in human neuroblastoma SH-SY5Y cells. We observed the characteristics of a "Pendular state" of MIF, where MIF (8 ng/mL) increased the ratio of p-Bad/Bad by activating Akt and the IKKα/β signaling pathway to assure cell survival, whereas MIF (50 ng/mL) up-regulated the expression of Bad to trigger apoptosis of SH-SY5Y cells. MIF displayed neurotoxicity similar to Ap1-42, which was associated with the MIF-induced increased expression of Bad. Application of the FFDS composite solution significantly decreased the expression levels of Bad, suppressed MIF-induced apoptosis in SH-SY5Y cells. In a D-galactose- and AICI3-induced AD mouse model, administration of the FFDS composite solution significantly improved the learning and memory, as well as neuronal morphology, and decreased the serum levels of INF-γ. Therefore, the FFDS composite solution exerts neuroprotective effects through down-regulating the level of Bad stimulated by MIF.

The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its under-lying mechanism of action is unknown. To determine whether the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like epichlorohydrin-related protein-1 (Keap1) signaling pathway, amyloid β-peptide 25–35 (Aβ25–35) was used to induce Alzheimer’s disease-like pathological changes in SH-SY5Y neuroblastoma cells. Cells were then treated with trichostatin A. The effects of trichostatin A on the expression of Keap1 and Nrf2 were detected by real-time quantitative polymerase chain reaction, western blot assays and immunofluorescence. Total antioxidant capacity and autophagy activity were evaluated by total antioxidant capacity assay kit and light chain 3-I/II levels, respectively. We found that trichostatin A increased cell viability and Nrf2 expression, and decreased Keap1 expression in SH-SY5Y cells. Furthermore, trichostatin A increased the expression of Nrf2-related target genes, such as superoxide dismutase, NAD(P)H quinone dehydrogenase 1 and glutathione S-transferase, thereby increasing the total antioxidant capacity of SH-SY5Y cells and inhibiting amyloid β-peptide-induced autophagy. Knockdown of Keap1 in SH-SY5Y cells further increased trichostatin A-induced Nrf2 expression. These results indicate that the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the Keap1-Nrf2 pathway. The mechanism for this action may be that trichostatin A increases cell viability and the antioxidant capacity of SH-SY5Y cells by alleviating Keap1-mediated inhibition Nrf2 signaling, thereby alleviating amyloid β-peptide-induced cell damage.