基质金属蛋白酶12与肿瘤关系的研究进展

基质金属蛋白酶12(matrix metalloproteinase-12，MMP-12)是一类结构中含有锌离子和钙离子的蛋白水解酶类，可降解细胞外基质(extracellular matrix，ECM)成分。MMP-12 在多种肿瘤中呈现高表达，并与肿瘤的发生发展密切关联，参与了肿瘤的生成、转移、侵袭和免疫逃逸等多个过程。MMP-12与肿瘤的预后相关，其有希望成为肿瘤预后标志物和治疗的靶点。且近年来关于MMP的机制及其抑制剂的研究有了很大进展。本文将对近年来国内外的MMP-12与肿瘤的相关研究进展予以综述。     

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.     

Interstitial lung diseases in children

Interstitial lung disease (ILD) in children (chILD) is a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and the diseases share common features of inflammatory and fibrotic changes of the lung parenchyma that impair gas exchanges. The etiologies of chILD are numerous. In this review, we chose to classify them as ILD related to exposure/environment insults, ILD related to systemic and immunological diseases, ILD related to primary lung parenchyma dysfunctions and ILD specific to infancy. A growing part of the etiologic spectrum of chILD is being attributed to molecular defects. Currently, the main genetic mutations associated with chILD are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3 and NKX2-1. Other genetic contributors include mutations in MARS, CSF2RA and CSF2RB in pulmonary alveolar proteinosis, and mutations in TMEM173 and COPA in specific auto-inflammatory forms of chILD. However, only few genotype-phenotype correlations could be identified so far. Herein, information is provided about the clinical presentation and the diagnosis approach of chILD. Despite improvements in patient management, the therapeutic strategies are still relying mostly on corticosteroids although specific therapies are emerging. Larger longitudinal cohorts of patients are being gathered through ongoing international collaborations to improve disease knowledge and targeted therapies. Thus, it is expected that children with ILD will be able to reach the adulthood transition in a better condition.     

液相色谱-电喷雾串联质谱分析人全血中环孢素的基质效应评估及其机理探究

目的： 评估液相色谱-电喷雾串联质谱（LC-ESI-MS/MS）分析人全血中环孢素的基质效应，并探究其发生机理。方法： 全血裂解物的蛋白沉淀上清液用作全血基质。分别用乙腈水溶液和全血基质配制等浓度环孢素A（CyA）、环孢素C（CyC）的质控样品。分别在添加H⁺、NH₄⁺和Na⁺的流动相中，用LC-ESI-MS/MS的MRM模式检测质控样品中CyA，CyC的[M+H]⁺、[M+NH₄]⁺和[M+Na]⁺（M=CyA，CyC）峰面积，以其计算基质效应因子；用MS Scan模式检查质控样品中CyA、CyC色谱流出峰的质谱离子组成情况，用于判断基质效应原因。结果： 在添加H⁺、NH₄⁺和Na⁺的流动相中，全血基质中CyA、CyC基质效应因子分别为-76.6%~-54.0%、-86.0%~-55.3%和-42.8%~-34.1%。在加H⁺、加NH₄⁺流动相中，标准液加全血基质的CyA、CyC色谱峰的质谱中出现丰度很高的[M+Na]⁺和[M+K]⁺，在加Na⁺流动相中它们出现丰度很高的[M+K]⁺，而对应的定量离子[M+H]⁺、[M+NH₄]⁺或[M+Na]⁺的丰度显著降低。结论： 全血基质对环孢素的LC-ESI-MS/MS分析产生明显的基质效应，其原因与基质中Na⁺、K⁺同添加在流动相中用于辅助电离的H⁺、NH₄⁺或Na⁺竞争与环孢素加合，导致定量目标加合离子丰度显著降低有关。     

国产弹性蛋白酶浸泡法构建兔腹主动脉瘤及其随访

目的采用国产猪胰弹性蛋白酶溶液主动脉周浸泡法构建兔腹主动脉瘤(AAA)模型,并随访其长期稳定性。方法 24只新西兰兔随机分成两组,实验组(n=12)用10μL浓度为10 U/μL国产猪胰弹性蛋白酶溶液浸润主动脉近分叉处血管段30 min,对照组用10μL 0.9%氯化钠溶液浸润30 min。术前和术后5、15、40、100、150 d分别经耳缘静脉造影测量主动脉内径。术后5、15、150 d造影后每组分别处死4只兔作苏木精-伊红(HE)、弹力纤维EVG染色和免疫组化染色。结果实验组术后5 d均形成AAA,主动脉直径100 d内基本稳定,150 d时明显缩小;组织学上术后5 d血管壁严重破坏、结构紊乱,可见红细胞渗出和炎性细胞浸润,弹力纤维和平滑肌细胞明显减少甚至消失,15 d时血管结构规整,可见部分残留弹力纤维,未见炎性细胞,150 d时管腔变窄,内膜过度增生,可见大量平滑肌细胞增生和紊乱的新生弹力纤维。对照组均未见AAA形成,病理学无明显变化。结论国产猪胰弹性蛋白酶溶液浸泡法可诱导兔AAA形成,操作简单、安全、有效。该模型有自愈倾向,但100 d内基本稳定,有助于AAA机制研究。     

Modern Composite Materials and Technical Strategies in Posttraumatic Augmentation Rhinoplasty

The selection of ideal posttraumatic augmentation rhinoplasty materials and technical strategies has always been a pressing challenge.Owing to the complexity of the traumatic nasal anatomical structure,such procedures are more complicated than ordinary cosmetic rhinoplasty.The choice of reconstruction material should emphasize its inherent characteristics,such as biocompatibility,anti-infective ability,strength,and plasticity.With the development of rhinoplasty,the choice of material is less limited and composite materials have become mainstream.This review outlines current composite materials and techniques in posttraumatic augmentation rhinoplasty.