Blood Coagulation

血液凝固
  • 文章类型: Journal Article
    背景:子宫内膜异位症被认为是一种全身性疾病,循环中存在促炎细胞因子,导致子宫内膜异位症的高凝状态。目前,子宫内膜异位症分为四个阶段:I(最小),II(轻度),III(中度)和IV(重度)。这项研究的目的是探讨诊断为IV期子宫内膜异位症的患者中炎症标志物与凝血因子之间的相关性。
    方法:这项回顾性病例对照研究包括171例IV期子宫内膜异位症患者和184例对照。连续数据以平均值±标准偏差表示。使用Mann-WhitneyU和χ2检验比较各组间的中位数和频率。进行Spearman分析以确定测量参数之间的相关性。通过受试者工作特征(ROC)曲线测试区分子宫内膜瘤的参数的诊断价值。
    结果:IV期子宫内膜异位症患者活化部分凝血活酶时间(APTT)缩短,纤维蛋白原浓度(FIB)和中性粒细胞与淋巴细胞比值(NLR)升高。APTT与NLR呈负相关,FIB浓度与NLR呈正相关。ROC分析显示FIB曲线下面积(AUC)为0.766(95%置信区间:0.717-0.814),敏感性和特异性分别达到86.5和60.9%。分别。CA125和CA199的AUC为0.638(95%置信区间:0.578-0.697),0.71(95%置信区间:0.656-0.763),敏感性和特异性达到40.9和91.8%,分别为80.7%和56.5%。这些因素的组合显示出最高的AUC为0.895(0.862-0.927),灵敏度为88.9%,特异性为77.7%。
    结论:在本研究中,我们发现炎症因子与子宫内膜异位症IV期的APTT或FIB显著相关。此外,凝血因子联合CA125和CA199对于鉴别IV期子宫内膜异位症更可靠.
    BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV.
    METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve.
    RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%.
    CONCLUSIONS: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.
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  • 文章类型: Journal Article
    背景:去甲肾上腺素和去氧肾上腺素是围手术期治疗低血压的常用血管活性药物。内源性去甲肾上腺素的释放增加引起血栓前变化,而产妇通常处于高凝状态。因此,本试验旨在研究在椎管内麻醉下剖宫产的患者中,相同剂量的预防性输注去甲肾上腺素和去氧肾上腺素对血栓前反应的影响是否存在差异.
    方法:本试验将招募66名符合条件的产妇,并随机分配到去甲肾上腺素或去氧肾上腺素组。“研究药物”将从鞘内注射开始以15ml/h的速率施用。主要结果是血浆凝血因子VIII活性(FVIII:C),纤维蛋白原,和D-二聚体水平。次要结果包括血液动力学变量和脐动脉血pH值。
    结论:我们的研究是首次比较去甲肾上腺素和去氧肾上腺素对脊髓麻醉下剖宫产患者血栓前反应的影响。阳性或阴性结果都将有助于我们更好地了解血管活性药物对患者的影响。如果有任何差异,这项试验将为产妇在围手术期选择血管活性药物提供新的证据.
    背景:中国临床试验注册ChiCTR2300077164。2023年11月1日注册。https://www.chictr.org.cn/.
    BACKGROUND: Norepinephrine and phenylephrine are commonly used vasoactive drugs to treat hypotension during the perioperative period. The increased release of endogenous norepinephrine elicits prothrombotic changes, while parturients are generally in a hypercoagulable state. Therefore, this trial aims to investigate whether there is a disparity between equivalent doses of prophylactic norepinephrine infusion and phenylephrine infusion on prothrombotic response in patients undergoing cesarean section under spinal anesthesia.
    METHODS: Sixty-six eligible parturients will be recruited for this trial and randomly assigned to the norepinephrine or phenylephrine group. The \"study drug\" will be administered at a rate of 15 ml/h starting from the intrathecal injection. The primary outcome are plasma coagulation factor VIII activity (FVIII: C), fibrinogen, and D-dimer levels. The secondary outcomes include hemodynamic variables and umbilical artery blood pH value.
    CONCLUSIONS: Our study is the first trial comparing the effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Positive or negative results will all help us better understand the impact of vasoactive drugs on patients. If there are any differences, this trial will provide new evidence for maternal choice of vasoactive medications in the perioperative period.
    BACKGROUND: Chinese Clinical Trial Registry ChiCTR2300077164. Registered on 1 November 2023. https://www.chictr.org.cn/ .
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the intervention effect and mechanism of regulating miR-155 on young rats with dysfunction of blood coagulation.
    METHODS: Twenty-six healthy and clean SD male rats were selected to establish the coagulopathy models. Twenty-four rats successfully established models and were randomly divided into three groups: model group, up-regulated miR-155 group and down-regulated miR-155 group, with 8 rats in each group. The expression of miR-155 was detected by real-time fluorescence quantitative polymerase chain reaction. The changes of coagulation factors and coagulation indicators were observed. Liver pathological tissues were observed by HE staining. The expressions of HMGB1-RAGE/TLRs-NF-κB signaling pathway related proteins were detected by Western blot.
    RESULTS: Compared with model group, the expressions of HMGB1, RAGE, TLR2, TLR4 and NF-κB were significantly increased in up-regulated miR-155 group (all P < 0.05), while decreased in down-regulated miR-155 group (all P < 0.05). Compared with model group, the expressions of coagulation factor Ⅱ, Ⅶ, Ⅸ, and Ⅹ were significantly decreased in up-regulated miR-155 group (all P < 0.05), while increased in down-regulated miR-155 group (P < 0.05). There was no significant difference in the expression of coagulation factor Ⅺ among the three groups (P >0.05). Compared with model group, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower and fibrinogen (FIB) was higher in up-regulated miR-155 group (all P < 0.05), while in the down-regulated miR-155 group they were opposite.
    CONCLUSIONS: Down-regulation of miR-155 can effectively improve coagulation factors and coagulation indexes and inhibit inflammation in young rats with dysfunction of blood coagulopathy, and the mechanism may be related to HMGB1-RAGE/TLRs-NF-κB signaling pathway.
    UNASSIGNED: 调控miR-155对凝血功能障碍模型幼鼠的干预效果及作用机制研究.
    UNASSIGNED: 研究调控miR-155对凝血功能障碍模型幼鼠的干预效果及作用机制。.
    UNASSIGNED: 选取健康、清洁级SD雄性幼鼠26只,建立凝血功能障碍模型,成功24只随机分为模型、上调miR-155和下调miR-155共3组,每组各8只。实时荧光定量聚合酶链式反应检测各组幼鼠miR-155表达,观察各组幼鼠凝血因子水平、凝血指标变化,HE染色观察肝脏病理组织,Western blot法检测HMGB1-RAGE/TLRs-NF-κB信号通路相关蛋白表达。.
    UNASSIGNED: 与模型组比,上调miR-155组HMGB1、RAGE、TLR2、TLR4、NF-κB均明显增高(均P <0.05),而下调miR-155组表达均明显降低(均P <0.05)。与模型组比,上调miR-155组凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ表达均明显降低(均P <0.05),而下调miR-155组均表达升高(均P <0.05)。三组凝血因子Ⅺ表达差异比较无统计学意义(P >0.05)。与模型组比,上调miR-155组凝血酶原时间、活化部分凝血活酶水平较低,纤维蛋白原水平较高(均P <0.05),而下调miR-155组正好相反。.
    UNASSIGNED: 下调miR-155能有效改善凝血功能障碍幼鼠凝血因子水平及凝血指标,抑制炎症反应,其作用机制可能与HMGB1-RAGE/TLRs-NF-κB信号通路有关。.
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  • 文章类型: Journal Article
    临床实践表明,预防血栓形成领域的关键未满足需求是无出血风险的抗凝治疗的可用性。已经广泛研究了针对FXIa或FXIIa的抑制剂,因为它们的低出血风险。然而,这些化合物是否产生协同作用尚未被探索。这里,使用SynergyFinder工具对活化的部分凝血活酶时间(aPTT)与不同比例的FXIa抑制剂PN2KPI和FXIIa抑制剂Infestin4进行分析,以确定协同抗凝作用.FeCl3诱导的颈动脉血栓形成小鼠模型和短暂的大脑中动脉闭塞(tMCAO)小鼠模型均显示,PN2KPI和Infestin4的组合有效剂量分别为28.57%和6.25%,分别,显著防止凝血,而且,双重抑制不会引起出血风险。
    UNASSIGNED: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.
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  • 文章类型: Journal Article
    三种多糖(SnNG,SnFS和SnFG)从Stichopusnaso的体壁中纯化。物理化学性质,包括单糖组成,分子量,硫酸盐含量,和光学旋转,被分析,证实SnFS和SnFG是海参中常见的硫酸多糖。SnFS的高度规则结构{3)-L-Fuc2S-(α1,}n通过其氧化降解产物的详细NMR分析确定。通过使用SnFG的β-消除解聚,三-,五-,octa-,亨德-,十四-,和十七糖从低分子量产物中获得。它们明确的结构证实SnFG具有{D-GalNAc4S6S-β(1,4)-D-GlcA}的骨架,并且每个GlcA残基用Fuc2S4S分枝。SnFS和SnFG都是结构上最简单的天然岩藻聚糖硫酸酯和岩藻糖基化糖胺聚糖,促进低价值海参S.Naso的应用。生物活性测定显示SnFG及其衍生的寡糖表现出有效的抗凝血和内在因子Xase(iXase)抑制。此外,与用Fuc3S4S单独支化的一系列寡糖的比较分析表明,在聚合度较低的寡糖中,例如八糖,Fuc2S4S导致APTT延长和iXase抑制的更大增加。随着聚合度的增加,硫酸化模式的影响减弱了,直到它被分子量的影响所掩盖。
    Three polysaccharides (SnNG, SnFS and SnFG) were purified from the body wall of Stichopus naso. The physicochemical properties, including monosaccharide composition, molecular weight, sulfate content, and optical rotation, were analyzed, confirming that SnFS and SnFG are sulfated polysaccharides commonly found in sea cucumbers. The highly regular structure {3)-L-Fuc2S-(α1,}n of SnFS was determined via a detailed NMR analysis of its oxidative degradation product. By employing β-elimination depolymerization of SnFG, tri-, penta-, octa-, hendeca-, tetradeca-, and heptadeca-saccharides were obtained from the low-molecular-weight product. Their well-defined structures confirmed that SnFG possessed the backbone of {D-GalNAc4S6S-β(1,4)-D-GlcA}, and each GlcA residue was branched with Fuc2S4S. SnFS and SnFG are both structurally the simplest version of natural fucan sulfate and fucosylated glycosaminoglycan, facilitating the application of low-value sea cucumbers S. naso. Bioactivity assays showed that SnFG and its derived oligosaccharides exhibited potent anticoagulation and intrinsic factor Xase (iXase) inhibition. Moreover, a comparative analysis with the series of oligosaccharides solely branched with Fuc3S4S showed that in oligosaccharides with lower degrees of polymerization, such as octasaccharides, Fuc2S4S led to a greater increase in APTT prolongation and iXase inhibition. As the degree of polymerization increases, the influence from the sulfation pattern diminishes, until it is overshadowed by the effects of molecular weight.
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  • 文章类型: Journal Article
    粘土矿物由于其独特的晶体结构作为生物医用材料而受到广泛关注,形态丰富,生物相容性好。然而,关于丰富的天然混合粘土矿床的相关研究几乎没有报道。在这里,基于草酸作用不同时间的结构演变,系统地研究了由一维凹凸棒石和多重二维粘土组成的天然混合三维凹凸棒石粘土(MDAPT)的止血性能。止血评估结果表明,草酸浸出1h的MDAPT凝血时间最短(134±12.17s),与对照组相比,180s和120s时的相对血红蛋白吸光度分别降低15.09%和41.74%,分别,体外凝血指数增加19.45%,以及MDAPT获得的最短出血时间(158.5±6.9s),与空白组和YNBY组相比,体内失血减少了近66%和31%。这种改进主要归因于层状非膨胀伊利石的协同作用,和纳米棒状凹凸棒石。此外,MDAPT的快速止血也是由于对血液的超疏水性质的联合作用,减少失血,表面负电荷,MDAPT结构骨架中的金属离子,促进血小板活化的平均增加21%。结果表明,MDAPT可以作为一种有前途的高效无机止血材料,为实现天然混合黏土资源的高值利用提供了可行的策略。
    Clay minerals have attracted wide attention as biomedical materials due to the unique crystal structure, abundant morphology and good biocompatibility. However, the relevant studies on the abundant natural mixed clay deposits were scarcely reported. Herein, the hemostatic performance of natural mixed-dimensional attapulgite clay (MDAPT) composed of one-dimensional attapulgite and multiple two-dimensional clay were systematically investigated based on the structural evolution using oxalic acid for different time. The results of hemostatic evaluation showed that MDAPT leached by oxalic acid with 1 h presented the shortest clotting time (134 ± 12.17 s), a 15.09 % and 41.74 % reduction of relative hemoglobin absorbance at 180 s and 120 s when compared with the control group, respectively, and an increase of 19.45 % of the blood clotting index in vitro, as well as MDAPT obtained the shortest bleeding time (158.5 ± 6.9 s), nearly 66 % and 31 % reduction blood loss as compared to the blank group and the YNBY group in vivo. This improvement was primarily ascribed to the synergistic effect of lamellar non-expandable illite, and nano rod-like attapulgite. Furthermore, the rapid hemostasis of MDAPT was also due to the joint effect of superhydrophobic property toward blood, minimizing blood loss, surface negative charge, metal ions from MDAPT structural skeleton, promoting an average increase of 21 % for platelet activation. The results suggested that MDAPT could be served as a promising efficient inorganic hemostatic materials, which provided a feasible strategy to realize the high-valued utilization of natural mixed clay resources.
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  • 文章类型: Journal Article
    在这项研究中,我们采用了一种将光学相干断层扫描(OCT)与U-Net和视觉几何组(VGG)-Net框架集成在卷积神经网络中的方法,用于动态凝血过程中的三维全血的定量表征.VGG-Net架构,用于识别三个不同的凝血阶段的血滴,包括液滴,凝胶化,和凝固达到高达99%的精度。此外,U-Net架构在有效分割全血的未凝固和凝固部分方面表现出熟练的能力,以及背景。值得注意的是,参数,如未凝固的和凝固的全血段的体积被成功地用于凝固过程的精确定量,这很好地表明了未来临床诊断和分析的潜力。
    In this study, we employed a method integrating optical coherence tomography (OCT) with the U-Net and Visual Geometry Group (VGG)-Net frameworks within a convolutional neural network for quantitative characterization of the three dimensional whole blood during the dynamic coagulation process. VGG-Net architecture for the identification of blood droplets across three distinct coagulation stages including drop, gelation, and coagulation achieves an accuracy of up to 99%. In addition, the U-Net architecture demonstrated proficiency in effectively segmenting uncoagulated and coagulated portions of whole blood, as well as the background. Notably, parameters such as volume of uncoagulated and coagulated segments of the whole blood were successfully employed for the precise quantification of the coagulation process, which indicates well for the potential of future clinical diagnostics and analyses.
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  • 文章类型: Journal Article
    在临床治疗中使用药用水蛭已经有很长时间了,因为它最初被认为具有抗凝血酶作用。这些作用是由于水蛭在附着于人类皮肤时持续吸血的能力。根据中国药典,中药中使用的水蛭主要包括惠特曼,HirudoNipponiaWhitman,和尖刺Whitmania,但是后两个物种相对稀缺。水蛭的主要成分是蛋白质和肽类大分子。根据它们的药理作用可以将它们分为两类。一组由直接靶向凝血系统的活性成分组成,比如水蛭素,肝素,和组胺,这是众所周知的。另一组包括蛋白酶抑制剂组分如Decorsin和Hementin。其中,水蛭唾液腺分泌的水蛭素是最有效的凝血酶抑制剂,在发现肝素之前,它是防止血液凝固的唯一药物。此外,水蛭在各种中药配方中起着重要作用。近几十年来,药用水蛭已应用于抗炎治疗等领域,心血管疾病管理,抗肿瘤治疗,和许多其他医疗条件。在这次审查中,我们全面概述了水蛭在各种医疗条件下的历史历程和药物应用,强调其在中药中的药学意义。这篇综述为探索涉及在各种疾病中使用水蛭的其他治疗机会以及阐明其未来研究的潜在机制提供了宝贵的见解。
    The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were due to the ability of the leech to continuously suck blood while attached to human skin. According to Chinese Pharmacopoei, leeches used in traditional Chinese medicine mainly consist of Whitmania pigra Whitman, Hirudo nipponia Whitman, and Whitmania acranulata, but the latter two species are relatively scarce. The main constituents of leeches are protein and peptide macromolecules. They can be categorized into two categories based on their pharmacological effects. One group consists of active ingredients that directly target the coagulation system, such as hirudin, heparin, and histamine, which are widely known. The other group comprises protease inhibitor components like Decorsin and Hementin. Among these, hirudin secreted by the salivary glands of the leech is the most potent thrombin inhibitor and served as the sole remedy for preventing blood clotting until the discovery of heparin. Additionally, leeches play a significant role in various traditional Chinese medicine formulations. In recent decades, medicinal leeches have been applied in fields including anti-inflammatory treatment, cardiovascular disease management, antitumor treatment, and many other medical conditions. In this review, we present a comprehensive overview of the historical journey and medicinal applications of leeches in various medical conditions, emphasizing their pharmaceutical significance within traditional Chinese medicine. This review offers valuable insights for exploring additional therapeutic opportunities involving the use of leeches in various diseases and elucidating their underlying mechanisms for future research.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    对于D-二聚体水平升高的儿科患者,仍然没有最佳的抗凝方案用于连续肾脏替代治疗(CRRT)和局部柠檬酸抗凝(RCA)。我们旨在评估不同抗凝策略对这些患者CRRT过滤器凝血风险的影响。接受CRRT的儿科患者根据CRRT前D-二聚体水平和抗凝剂进行回顾性分组:D-RCA组(D-二聚体正常,仅限RCA,n=22),D+RCA组(D-二聚体升高,仅限RCA,n=50),D+RCA+全身肝素抗凝(SHA)组(D-二聚体升高,RCA与SHA相结合,n=55)。比较各组的滤器凝血风险和出血发生率。在群体中,D+RCA+SHA组过滤器寿命最长;此外,同时使用低剂量肝素抗凝治疗并没有增加出血的发生率.此外,同时肝素抗凝与滤器凝血风险降低相关.相反,高的CRRT前血红蛋白和D-二聚体水平以及>0.4mmol/L的滤器后离子钙水平与滤器凝血风险增加相关.RCA联合小剂量肝素抗凝能降低D-二聚体水平升高的CRRT患者凝血风险,延长滤器寿命,且不增加出血风险。
    There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.
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