顶天立地服务需求 注重内涵创建一流——首都医科大学建校60周年教育教学与人才培养成果回顾

首都医科大学通过60年辛勤耕耘、精益求精，秉承“顶天立地”的人才培养理念，为社会培养了大批高水平的学术型与应用型医药卫生人才。回顾学校60年来本专科教育、全科医学教育、国际教育、研究生教育的人才培养成果，以总结经验并鼓舞全体首医人进一步求真务实、凝心聚力、积极进取、追求卓越，努力将学校建设成为国际一流的研究型医科大学。     

In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles

Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.     

TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐κB

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFβ

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

妇科腹腔镜围手术期碳水化合物口服疗法对术后胰岛素抵抗影响的研究

目的观察妇科腹腔镜手术围术期碳水化合物口服疗法和传统禁饮食方案两种不同的临床处理措施对于术后胰岛素抵抗（IR）的影响。 方法选取2018年2月至8月入住徐州医科大学附属医院妇科，行腹腔镜下全子宫切除手术的非糖尿病患者共98例，将采用围术期碳水化合物口服疗法者作为观察组（50例），采用传统禁饮食方案者作为对照组（48例）。检测所有病例的术前、术后第1天及第3天的空腹血糖（FPG）及空腹胰岛素（FINS），并利用稳态模式评估法计算稳态模型胰岛素抵抗指数（HOME-IR）。对于观察组与对照组患者术前、术后第1天和术后第3天的FPG、FINS和HOME-IR等指标，组间比较采用独立样本t检验。两组患者术后腹胀、术后24 h通气、术后发热的发生情况的比较采用确切概率法检验。 结果观察组与对照组比较，术前和术后第1天FPG差异无统计学意义（P均>0.05），术后第3天FPG明显降低［（4.34±0.59）mmol/L vs （4.96±0.64）mmol/L］，差异有统计学意义（t=-4.96，P=0.002）。观察组与对照组比较，术前和术后第1天FINS差异无统计学意义（P均>0.05），术后第3天FINS明显降低［（45.39±13.55）mIU/L vs （51.18±9.34） mIU/L］，差异有统计学意义（t=-2.46，P=0.033）。观察组与对照组比较，术前HOME-IR差异无统计学意义（P>0.05），术后第1天和术后第3天HOME-IR明显降低［（13.08±4.80）vs （15.03±4.11）；（9.37±3.65）vs （11.30±2.55）］，差异有统计学意义（t=-0.69，P=0.042；t=-3.99，P=0.033）。两组患者术后其他观察指标比较，观察组术后24 h通气率与对照组比较明显增高（76.0% vs 64.6%），差异有统计学意义（P=0.045）。两组患者在术后腹胀、术后发热的发生率方面差异无统计学意义（P均>0.05）。两组患者均未发生术中误吸。 结论妇科腹腔镜手术围术期应用碳水化合物口服疗法较传统禁饮食方案，能有效减轻术后IR程度，促进术后康复进程，且不增加围术期并发症的发生率。