Relationship between tRNA-derived fragments and human cancers

tRNA-derived fragments, a class of small noncoding RNAs (sncRNAs), have been identified in numerous studies in recent years. tRNA-derived fragments are classified into two main groups, including tRNA halves (tiRNAs) and tRNA-derived small RNA fragments (tRFs), according to different cleavage positions of the precursor or mature tRNAs. Instead of random tRNA degradation debris, a growing body of evidence has shown that tRNA-derived fragments are precise products of specific tRNA modifications and play important roles in biological activities, such as regulating protein translation, affecting gene expression, and altering immune signaling. Recently, the relations between tRNA-derived fragments and the occurrence of human diseases, especially cancers, have generated wide interest. It has been demonstrated that tRNA-derived fragments are involved in cancer cell proliferation, metastasis, progression and survival. In this review, we will describe the biogenesis of tRNA-derived fragments, the distinct expression and function of tRNA-derived fragments in the development of cancers, and their emerging roles as diagnostic and prognostic biomarkers and precise targets of future treatments.     

小儿腹股沟斜疝日间手术与专科住院手术的卫生经济学评价

目的对小儿日间手术模式和专科住院手术模式的卫生经济学进行评价,为小儿腹股沟斜疝手术的优选和决策提供参照依据。方法收集2016年6月至2017年7月间所有在重庆医科大学附属儿童医院治疗且符合纳入标准的单侧腹股沟斜疝患儿的临床资料,其中日间手术患儿324例(日间组),专科住院手术患儿65例(专科组)。比较两种手术模式下的患儿一般资料、治疗指标、容错情况、术后需要留院处理的并发症发生率、复发率、院内的感染等卫生效果指标;比较两种模式的HCAHPS优化星表满意度、住院时间、住院费用等卫生经济学指标。统计分析两种模式的成本-效果:治疗效果权重W、治疗效果指数(EI)、成本-效果比(CER)。结果日间外科组和专科组在性别、区域方面的差异无统计学意义,专科组年龄分布更广。日间组与专科组占用床位时间分别为(23.17±0.49)h和(112.06±19.75)h,差异具有统计学意义(P<0.01);两组的医疗费用分别为(3372±430)元和(6063±2104)元,差异具有统计学意义(P<0.01)。两组麻醉分级ASA比例的差异具有统计学意义,两组术后并发症发生率的差异无统计学意义(P>0.05)。日间组与专科组治疗EI分别为0.98和1.02,CER分别为3305和6184,日间组经济学效益较大。结论日间手术的成本-效果优于专科住院手术模式,患儿满意度和术后复发率与专科住院模式的差异无统计学意义,推荐符合日间手术指征的患儿采用该模式。     

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

     

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

BackgroundIn the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.MethodsMicroarray data of rat gene expression profiles under accession number {"type":"entrez-geo","attrs":{"text":"GSE28545","term_id":"28545"}}GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.ResultsThree hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.ConclusionsThese key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.     

支持向量机法及其在中药研究中的应用

在中医药现代化进程中，有效地结合现代科学技术手段对传统中医药进行更为合理的分析是一个重要研究方向。计算机科学技术与人工智能算法在中医药研究领域已取得长足发展，尤其是分类算法所具有的快速鉴别和分析能力，使其在复杂的中医药研究体系中发挥举足轻重的作用。对支持向量机分类算法及其结合其他算法在解决中医药相关领域问题方面及成果进行综述，以相关智能算法为基础探讨中医药研究过程中的诸多难题，为推动中医药现代化进程提供支撑。