单纯 Ilizarov 环形外固定技术治疗合并骨筋膜室综合征的胫骨平台骨折

目的探讨单纯 Ilizarov 环形外固定技术治疗合并骨筋膜室综合征的胫骨平台骨折的疗效。方法2013 年 9 月—2017 年 3 月，收治 30 例合并骨筋膜室综合征的胫骨平台骨折患者，采用单纯 Ilizarov 环形外固定技术治疗。男 23 例，女 7 例；年龄 23～43 岁，平均 34.4 岁。致伤原因：交通事故伤 12 例，高处坠落伤 4 例，摔伤 8 例，重物砸伤 6 例。受伤至入院时间 1～12 h，平均 4.8 h。骨折 Schatzker 分型：Ⅱ型 1 例、Ⅲ型 3 例、Ⅳ型 10 例、Ⅴ型 7 例、Ⅵ型 9 例。30 例均因骨筋膜室综合征行切开减压；切开减压至手术时间为 10～15 d，平均 12.5 d。治疗后采用膝关节学会评分系统（KSS）及 Ilizarov 方法研究与应用协会（ASAMI）协议评价膝关节功能。结果手术时间 110～155 min，平均 123.1 min；术中出血量 100～500 mL，平均 245 mL；术后住院时间 3～5 d，平均 3.8 d。患者均获随访，随访时间 20～24 周，平均 22.7 周。除 2 例患者出现针道感染征象外，无其他并发症发生。X 线片复查显示骨折均愈合，愈合时间 10～20 周，平均 14.6 周。末次随访时，膝关节 KSS 临床评分总分为 70～95 分，平均 87.5 分；功能评分总分为 70～90 分，平均 79.0 分。参照 ASAMI 协议评价获优 24 例、良 3 例、可 2 例、差 1 例。结论对于合并骨筋膜室综合征的胫骨平台骨折，单纯 Ilizarov 环形外固定技术治疗后患者关节功能可以基本恢复且并发症少，是一项相对安全、有效的治疗方法。     

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.     

High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms

ObjectiveIdentifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA.MethodsPlasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair.ResultsA significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = −0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair.ConclusionsHigh levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.     

颞下颌关节强直动物模型中最大张口度与强直严重程度关系研究

目的　研究主、被动最大张口度（AMMO、PMMO）与颞下颌关节强直严重程度的关系。方法　选取28只健康雄性绵羊随机分为实验组和对照组，每组各14只。实验组绵羊双侧颞下颌关节模拟髁突矢状骨折，其中左侧翼外肌被切断以阻断其功能；对照组绵羊未进行手术。于术前及术后12、24周对所有绵羊体重、AMMO、PMMO、颞下颌关节形态学特点进行测量评估。结果　实验组只有右侧保留翼外肌功能的颞下颌关节发生了骨强直。术后12、24周，实验组绵羊AMMO、PMMO、极限距离均显著低于对照组，差异均有统计学意义（均P < 0.05）。实验组绵羊AMMO和PMMO与骨融合区宽度、长度、面积及钙化程度均呈负相关（均P < 0.05），其中骨融合区面积为主要影响因素（术后12、24周相关系数r分别为-0.94、-0.95）。结论　颞下颌关节强直动物模型中阻断翼外肌功能可阻止骨强直的发生；对于早期髁突矢状骨折，可通过牙合垫或牙合板进行张口训练，进而阻断翼外肌功能。当颞下颌关节发生骨强直时，骨融合区面积越大，张口受限越明显。     

Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles

A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure–activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures.