Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.     

Capsiate Intake with Exercise Training Additively Reduces Fat Deposition in Mice on a High-Fat Diet,but Not without Exercise Training

While exercise training (ET) is an efficient strategy to manage obesity, it is recommended with a dietary plan to maximize the antiobesity functions owing to a compensational increase in energy intake. Capsiate is a notable bioactive compound for managing obesity owing to its capacity to increase energy expenditure. We aimed to examine whether the antiobesity effects of ET can be further enhanced by capsiate intake (CI) and determine its effects on resting energy expenditure and metabolic molecules. Mice were randomly divided into four groups (n = 8 per group) and fed high-fat diet. Mild-intensity treadmill ET was conducted five times/week; capsiate (10 mg/kg) was orally administered daily. After 8 weeks, resting metabolic rate and metabolic molecules were analyzed. ET with CI additively reduced the abdominal fat rate by 18% and solely upregulated beta-3-adrenoceptors in adipose tissue (p = 0.013) but did not affect the metabolic molecules in skeletal muscles. Surprisingly, CI without ET significantly increased the abdominal fat rate (p = 0.001) and reduced energy expenditure by 9%. Therefore, capsiate could be a candidate compound for maximizing the antiobesity effects of ET by upregulating beta-3-adrenoceptors in adipose tissue, but CI without ET may not be beneficial in managing obesity.     

Dietary Supplementation of Tetracarpidium conophorum (African Walnut) Seed Enhances Muscle n‐3 Fatty Acids in Broiler Chickens

The influence of dietary Tetracarpidium conophorum (African Walnut) seed meal (TCSM) on fatty acids, productivity parameters, and physicochemical properties of breast and thigh muscles in broiler chickens are assessed. A total of 180, 28‐d‐old Arbor acre broiler chickens are randomly assigned to dietary treatments containing 0% (control), 2.5%, and 5% w/w TCSM, fed for 28 d, and euthanized. Dietary TCSM reduces (p < 0.05) feed intake, body weight gain (BWG), carcass weight, and abdominal fat. Diet does not affect feed efficiency and hematological parameters. The control birds have higher (p < 0.05) serum total cholesterol and triglycerides than do the supplemented birds. Diet has no effect on pH, water holding capacity, carbonyl and malondialdehyde contents, and organoleptic properties of breast and thigh muscles. The 5% TCSM has higher redness in breast muscle than do other treatments. Dietary TCSM improves (p < 0.05) the concentration of C18:3n‐3 (4.80–8.76% vs 1.56%), C20:5n‐3 (0.54–0.79% vs 0.39%), C22:5n‐3 (0.64–0.89% vs 0.18%), and C22:6n‐3 (0.75–0.97% vs 0.19%), and reduces (p <  0.05) the fat content (2.15–2.45% vs 3.15%) in breast and thigh muscles. Dietary TCSM enhances muscle n‐3 fatty acids without instigating oxidative deterioration, but reduces BWG in broiler chickens. Practical Application: Albeit that broiler meat is rich in polyunsaturated fatty acids (PUFA), its omega 6 (n‐6)/omega 3 (n‐3) is >4. Elevated n‐6/n‐3 could have adverse effect on human physiology thereby promoting the pathogenesis of certain diseases. This heightens the need to enhance the n‐3 PUFA content of broiler meat. Dietary TCSM induced up to a fourfold increase in n‐3 PUFA content of the breast and thigh muscles in broiler chickens. Moreover, dietary TCSM induced up to a tenfold decrease in the n‐6/n‐3 of the breast and thigh muscles in broiler chickens. This finding assumes great significance because the health concerns regarding dietary fat are the foremost factors responsible for the bad image suffered by meat. These results provide insights on the potential of TCSM to improve the nutritional quality without compromising the oxidative shelf life, organoleptic traits, and physicochemical properties of broiler meat.     

腹腔手术后重症患者心肌损伤的危险因素

目的探讨腹腔手术后重症患者心肌损伤的发生情况及可能的危险因素。方法回顾性分析北京大学人民医院2017年1月至2019年1月腹腔手术后重症患者的一般临床资料及心肌损伤情况,收集并观察基础病史、术中(手术时间、是否急诊手术、术中出血>800 ml和术中低血压等)及术后指标(改良氧合指数、血乳酸、急性肾损伤和术后24 h内使用升压药情况等)。根据术后是否发生心肌损伤,将患者分为心肌损伤组和非心肌损伤组,采用Logistic回归分析腹腔手术后重症患者心肌损伤的危险因素。结果在纳入的803例腹腔手术后重症患者中,心肌损伤发生率为17. 2%(138/803),而急性心肌梗死发生率仅为0. 9%(7/803)。单因素分析显示,慢性肾功能不全病史、手术时间、急诊手术、术中低血压、术后24 h内使用升压药、高APACHEⅡ评分及术后即刻急性肾损伤与术后重症患者心肌损伤相关(P<0. 05)。多因素回归分析显示,急诊手术(OR=3. 14,95%CI:1. 76～5. 60,P<0. 001)、术后24 h内使用升压药(OR=2. 26,95%CI:1. 23～4. 15,P=0. 008)、APACHEⅡ评分(OR=1. 05,95%CI:1. 01～1. 09,P=0. 008)和术后急性肾损伤(OR=3. 18,95%CI:1. 78～5. 69,P <0. 001)与腹腔手术后重症患者发生心肌损伤独立相关。结论重症患者腹腔手术后心肌损伤发生率高,急诊手术、术后24 h内使用升压药、高APACHEⅡ评分和术后急性肾损伤是导致腹腔手术后重症患者发生心肌损伤的独立危险因素。     

Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we elucidate the mechanisms of NET formation and their different implications in disease. We focused on autoinflammatory and cardiovascular disorders as the leading cause of death. Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms. Furthermore, NETosis can be considered as a source of autoantigens and maintains an inflammatory milieu promoting autoimmune diseases. Indeed, there is further need for research into the balance between NET induction, inhibition, and degradation in order to pharmacologically target NETs and their compounds without impairing the patient’s immune defense. This review may be of interest to both basic scientists and clinicians to stimulate translational research and innovative clinical approaches.     

Biocompatibility of surface treated pure titanium and titanium alloy by<Emphasis Type="Italic">in vivo</Emphasis> and<Emphasis Type="Italic">in vitro</Emphasis> test

In the present study, commercial pure Ti and Ti-6Al-4V alloy specimens with and without alkali and heat treatments were implanted in the abdominal connective tissue of mice. Conventional stainless steel 316L was also implanted for comparison. After three months, their biocompatibility was evaluated byin vitro andin vivo experiments. Surface structural changes of specimens due to the alkali treatment and soaking in Hank’s solution were analyzed by XRD, SEM, XPS and AES. An apatite layer, which accelerates the connection with bone, was formed more easily on the alkali treated specimens than the non-treated specimens. The number of macrophages, which is known to increase as the inflammatory reaction proceeds, was much lower for the alkali and heat treated specimens than for the others. The average thickness of the fibrous capsule formed around the implant was much thinner for the alkali and heat treated specimens than for the others.     

深度学习在主动脉中膜变性病理图像分类中的应用

胸主动脉瘤和夹层（TAAD）是严重的心血管疾病之一,而中膜变性（MD）的组织学改变对疾病的诊断及早期干预具有重要的临床意义。针对病理图像的高度复杂性使得MD的诊断过程耗时费力且一致性差的问题,提出了一种基于深度学习的病理图像分类方法,并将其应用于四种MD病变类型以进行性能验证。该方法使用了一种改进的基于GoogLeNet的卷积神经网络模型,首先采用迁移学习来将先验知识应用于TAAD病理图像的表达,然后使用Focal loss和L2正则化来解决数据不平衡问题,从而进一步优化模型性能。实验结果表明,所提模型的平均四分类准确率达到98.78%,表现出较好的泛化性能。可见所提方法可以有效地提升病理学家的诊断效率。     

不同破口大小对B型主动脉夹层假腔内压力的影响

为了研究夹层内的血流动力学变化对夹层转归的重要影响,并期望为临床判断主动脉夹层发展及转归提供理论依据,通过3D打印技术制作不同出入口比例及破口大小的B型主动脉夹层模型,对主动脉夹层内血流变化进行模拟,并测量观察主动脉夹层模型假腔内压力变化及流场情况.真腔内固定压力为18.620、21.280 k Pa两组中,不同破口比例的假腔入口压力比普遍均小于夹层模型内其他假腔位置,且压力值低于真腔压力;真腔内压力为23.940 k Pa组中,破口比例为2∶1的夹层模型内假腔压力比较其他破口比例模型的压力比明显升高;所有模型真腔固定水压为21.280、23.940 k Pa下均可观测到同真腔压力下,真腔流速更快,其内部压力低于假腔.同一模型中,假腔压力普遍低于真腔压力;相同压力下,原发破口大的模型假腔流速相对较低,而涡流明显;相同模型相同压力下,假腔流速低于真腔,假腔的涡流更为明显,复杂的涡流和旋动对壁面造成冲击进而使假腔破裂风险增加.     

窦管交界和窦部直径对主动脉瓣关闭功能影响

为了探讨窦管交界和窦部直径对主动脉瓣关闭功能的影响,首先按照Labrosse提供的临床手术指导尺寸,建立基本的主动脉根部几何模型;改变窦管交界直径(分别为基本模型的1.2倍和0.8倍)、窦部直径(分别为基本模型的1.2倍和0.8倍)以及窦管交界直径和窦部直径(均为基本模型的1.2倍),共建立6组几何模型.窦部和瓣叶均施加0~10.665 kPa线性变化的压力负载,用计算机数值模拟的方法定量研究主动脉根部从接近关闭到完全关闭过程中,模型受到的最大应力数值和位置、瓣环直径变化以及对合区域面积比.计算结果表明:6组模型的主动脉根部最大应力值均出现在瓣叶和窦部接合位置,且最大应力值的范围是567~601 kPa,与Marom、Labrosse和Katayama的计算结果接近;窦管交界直径增大为基本模型的1.2倍时,瓣环直径扩大8.3%;6组模型的对合区域面积比计算结果相对变化不超过5%.结果表明:窦管交界变化比窦部直径变化对瓣环直径的影响大,而同样的主动脉根部结构,增大瓣环直径会减少瓣叶的有效对合,从而影响主动脉瓣关闭功能.     

Proteomics in aortic aneurysm – What have we learnt so far?

Aortic aneurysm is a deceptively indolent disease that can cause severe complications such as aortic rupture and dissection. In the normal aorta, vascular smooth muscle cells within the medial layer produce and sustain the extracellular matrix (ECM) that provides structural support but also retains soluble growth factors and regulates their distribution. Although the ECM is an obvious target to identify molecular processes leading to structural failure within the vessel wall, an in-depth proteomics analysis of this important sub-proteome has not been performed. Most proteomics analyses of the vasculature to date used homogenized tissue devoid of spatial information. In such homogenates, quantitative proteomics comparisons are hampered by the heterogeneity of clinical samples (i.e. cellular composition) and the dynamic range limitations stemming from highly abundant cellular proteins. An unbiased proteomics discovery approach targeting the ECM instead of the cellular proteome may decipher the complex, multivalent signals that are presented to cells during aortic remodelling. A better understanding of the ECM in healthy and diseased vessels will provide important pathogenic insights and has potential to reveal novel biomarkers.