Circulating and tissue microRNAs as a potential diagnostic biomarker in patients with thrombotic events

Venous and arterial thrombosis are conditions that have a considerable burden if left untreated. The hypoxia-induced by the occluded vessel can disrupt the circulation of any organ, the cornerstone of treating thrombosis is rapid diagnosis and appropriate treatment. Diagnosis of thrombosis may be made by using laboratory tests or imaging techniques in individuals who have clinical manifestations of a thrombotic event. The use of serum micro ribonucleic acids (RNAs) has recently been applied to the diagnosis of thrombosis. These small RNA molecules are emerging as new diagnostic markers but have had very limited applications in vascular disease. Most of the articles provided various microRNAs with different levels of accuracy. However, there remains a lack of an appropriate panel of the most specific microRNA in the literature. The purpose of the present review was to summarize the existing data on the use of microRNAs as a diagnostic biomarker for venous thrombosis.     

早期规范康复训练在缺血性脑卒中患者中的应用价值

目的:研究早期规范康复训练在缺血性脑卒中患者的临床应用价值.方法:160例缺血性脑卒中患者分为观察组和对照组各80例,两组患者均采用常规治疗,治疗组在此基础上进行72小时内进行康复训练,对照组在15～30天左右进行康复训练,观察两组患者临床神经功能缺损程度采,日常生活活动能力及肢体运动功能的改善情况.结果:两组患者治疗前神经功能缺损程度,日常生活活动能力及肢体运动功能差异无明显的统计学意义(P＞0.05),经过康复训练两组患者各项功能均较治疗前有明显的提高,并且观察组提高水平明显高于对照组,差异具有明显的统计学意义(P＜0.01).结论:早期与晚期康复均可促进缺血性脑卒中患者各种功能的恢复,但是早期康复的临床疗效明显优于晚期康复训练.     

关节置换术后抗凝药物预防深静脉血栓及相关并发症的临床研究进展

抗凝药物有助于预防全髋关节置换术和全膝关节置换术后深静脉血栓形成,临床上最常使用的传统抗凝药物如低分子肝素、华法林等可以起到很好的预防效果。目前有一类新的口服抗凝药物已经用于临床,为关节置换术后患者带来了一种更方便、安全和有效预防血栓的治疗选择。本篇综述主要针对传统抗凝药物低分子肝素及维生素K拮抗剂,直接凝血酶抑制剂达比加群,以及选择性Xa因子抑制剂利伐沙班和阿哌沙班,对迄今为止传统抗凝药物在全髋关节置换术和全膝关节置换术患者中的临床使用经验、优缺点、以及新型口服抗凝药物最新临床用药进展进行综述,为关节置换术后患者预防深静脉血栓提供用药参考。     

血栓弹力图预测下肢骨折围手术期深静脉血栓的应用研究

目的:探讨血栓弹力图(TEG)预测下肢骨折围手术期深静脉血栓的临床价值。方法:选择在我院进行体检的健康志愿献血者作为对照组(Ⅰ),同时选择82例在我院进行骨科手术的下肢骨折患者作为实验组(Ⅱ)。分别在骨折后第2天、手术当天、术后第3天、术后第7天和术后第10天进行血栓弹力图检测,比较实验组(Ⅱ)与对照组(Ⅰ)TEG各参数差异,并对所有数据进行相关性分析。结果:实验组(Ⅱ)82例研究对象中有63例(76.83%)于术后一周内出现高凝状态。与对照组(Ⅰ)比较,实验组(Ⅱ)骨折第2天、手术当天、术后第3天、术后第7天和术后第10天R、K缩短,Angle角、MA、CI值均延长。与手术当日比较,实验组(Ⅱ)术后第3天、术后第7天R和K明显缩短,Angle角、MA、CI值均明显延长(P0.05),与术后第3天、术后第7天比较,术后第10天R、K延长,Angle角、MA、CI值有缩短趋势。结论:血栓弹力图能及时准确监测下肢骨折患者凝血状态变化情况,及时预测下肢深静脉血栓(LDVT)发生风险,为抗凝药物的合理使用提供参考依据。     

Increased level of fibrinogen chains in the proteome of blood platelets in secondary progressive multiple sclerosis patients

Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.     

In vivo monitoring of thrombosis in mice by optical coherence tomography

The objective of this study is to establish a novel method for continuously monitoring thrombus progression with various outcome measures and to assess the efficacy of antithrombotic drugs in murine thrombosis model in mice. In the study, thrombus was induced in the femoral vein of mice by FeCl₃ and monitored over time by spectral‐domain optical coherence tomography (OCT). Three‐dimensional images of thrombi with or without heparin as an antithrombotic agent were obtained from OCT angiography. In addition, several parameters of thrombi were analyzed and compared between control and anticoagulant groups. By using OCT, we were able to trace thrombus generation in the same mouse in real time. We found that in our model heparin reduced thrombus size by ~60% and thrombus cross‐sectional area by 50%. OCT results also show that both time to thrombus size (>0.02mm³) and time to occlusion (>30%) were significantly reduced after heparin addition. This study demonstrates that OCT reliably monitors thrombus generation and progression from various aspects including thrombus size. This enables us to measure the kinetic of thrombosis more accurately, and effectively evaluate the efficacy and activities of antithrombotic drugs. This model may represent a useful tool in antithrombotic drug discoveries in preclinical studies.      

不同剂量右美托咪定静脉维持对重型颅脑损伤患者术后生命体征、免疫功能和血清神经细胞因子的影响

摘要 目的：观察不同剂量右美托咪定静脉维持在重型颅脑损伤患者中的应用价值。方法：选取2018年9月~2020年9月期间江苏大学附属宜兴市人民医院麻醉与重症医学科接收的重型颅脑损伤患者96例,根据随机数字表法分为三组：A组（右美托咪定剂量为0.3μg/kg?h）、B组（右美托咪定剂量为0.5 μg/kg?h）和C组（右美托咪定剂量为0.7 μg/kg?h）,各32例。观察三组患者不同时间点的生命体征、免疫功能、镇静镇痛情况、血清神经细胞因子,记录三组不良反应发生情况。结果：B组、C组术后24 h、术后72 h的心率（HR）、呼吸频率（RR）、平均动脉压（MAP）低于A组（P<0.05）。B组、C组术后24 h、术后72 h的Ramsay镇静评分、视觉模拟评分法（VAS）评分低于A组（P<0.05）。B组、C组术后24 h、术后72 h的CD3⁺、CD4⁺/CD8⁺高于A组（P<0.05）。B组、C组术后24 h、术后72 h的神经元特异性烯醇化酶（NSE）、中枢神经特异性蛋白（S100β）低于A组（P<0.05）。C组的不良反应总发生率高于A组、B组（P<0.05）。结论：重型颅脑损伤患者术中给予右美托咪定剂量为0.5 μg/kg?h、0.7 μg/kg?h维持,可有效维持患者生命体征平稳,促进患者免疫功能和血清神经细胞因子水平改善,但0.7 μg/kg?h剂量的右美托咪定使用后不良反应发生率相对更高。     

Cardiorespiratory performance in salmonids during exercise at high temperature: insights into cardiovascular design limitations in fishes

Studies in the laboratory with salmonids and now in the field with wild salmon clearly show that critical swimming performance has an optimum temperature. This temperature optimum is coincident with maximum aerobic scope and maximum cardiac scope. At a temperature that is higher than this optimum, however, whole animal performance declines abruptly. Evidence is presented here to suggest that this is directly associated with a decline in cardiac scope which limits oxygen supply to tissues. It is further suggested that the decline in maximum cardiac performance could reflect problems with the heart's own oxygen supply. The reasoning behind this suggestion is that, at temperatures at or below the optimum and probably because of a limitation on oxygen diffusion in skeletal muscle during exercise, venous oxygen does not fall below a threshold level during exercise, and so the heart receives just enough oxygen for its own muscular activity via the cardiac circulation (i.e. the venous return to the heart). However, because high temperature favours increased oxygen extraction by skeletal muscle, which consequently lowers venous oxygen, cardiac oxygen supply may become insufficient to meet cardiac oxygen demand. The hypoxic myocardium then cannot maintain cardiac scope and internal oxygen delivery to tissue declines.     

The Blood Platelet as a Model for Regulating Blood Coagulation on Cell Surfaces and Its Consequences

Platelets actively participate in regulating thrombin production following physical or chemical injury to blood vessels. Injury to blood vessels initiates activation of the large numbers of platelets that appear in the subendothelium where they become exposed to tissue factor and to molecules adhesive for platelets and normally found in the extracellular matrix. The complex of plasma factor VIIa with extravascular tissue factor both initiates and localizes thrombin production on platelets and on extravascular cells. Thrombin production at these sites in turn enhances platelet activation and the subsequent hemostatic plug formation to minimize bleeding. Thrombin production and platelet activation also initiate the process of wound healing requiring thrombin-dependent cell activation and platelet-dependent formation of new blood vessels (angiogenesis). Activated platelets release from their storage granules several proteins and other factors that regulate local thrombin formation and the responses of blood vessel cells to injury to assure hemostasis and effective wound healing. Failure to localize and adequately regulate thrombin production and/or platelet activation can have pathological consequences, including the development and propagation of atherosclerosis and enhancement of tumor development. The primary basis for the pathological consequences of the failure to adequately regulate thrombin production is that the multi-functional thrombin activates several types of cells to initiate their mitogenesis. Mitogenesis precedes many of the undesirable consequences of poorly regulated thrombin production and platelet activation. In addition, activated platelets release a variety of products which influence the functions of several cell types to the extent that inadequate regulation of platelet activation (by excessive thrombin production) could contribute to the pathogenesis of acute and chronic arterial thrombosis and to tumor development. Activated platelets participate in tumor development by releasing several factors that positively (and negatively) regulate blood vessel formation.     

Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.