• 文章类型: Journal Article
    本文的目的是研究基于人口统计学和临床因素的相关基因位点(CYP2C9*3,VKORC1-1639G>A)的遗传多态性,并采用最大一后验贝叶斯方法构建符合中国汉族人群的华法林个体化剂量预测模型。最后,将所建模型与国内外广泛使用的模型进行对比分析。在这项研究中,从我们医院的646名合格受试者中收集了总共5467个INR测量值,并在Hamberg模型的基础上,采用最大后验贝叶斯方法构建符合中国汉族人群的华法林剂量预测模型。对模型进行了验证,并与国外模型进行了比较。这项研究发现,体重和同时使用胺碘酮对华法林的抗凝作用有显着影响。该模型可为汉族人群华法林的个体化、合理给药提供有效依据。在与不同华法林剂量预测模型的性能比较中,新模型具有最高的预测精度,预测比例高达72.56%。Huang模型预测的剂量最接近华法林的实际剂量。本研究建立的群体药动学和药效学模型能较好地反映汉族人群华法林给药后INR值的分布特征,并且性能优于文献中报道的模型。
    The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.
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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
    背景:咯血在急性肺栓塞(PE)中普遍存在,并显着影响临床决策。尽管在自身免疫性疾病患者中PE的报道越来越多,有限的研究调查了急性PE与咯血和自身免疫性疾病之间的关系.方法:回顾性研究2012年1月至2020年10月在北京协和医院(PUMCH)接受急性PE合并咯血的自身免疫性疾病患者。在有咯血和无咯血的患者之间进行了比较分析,以及患有自身免疫性疾病的人和没有自身免疫性疾病的人之间。临床特征,PE严重程度分层,咯血的量,初始抗凝管理,并对预后进行描述性分析。结果:该研究分析了896例诊断为急性PE的患者,其中105人(11.7%)出现咯血。PE患者的咯血经常与自身免疫性疾病相关(39%,41/105),更年轻的患者群体(42.0vs.52.7岁,P=0.002),低风险PE的患病率较高(53.7vs.28.1,P=0.008)与非自身免疫性疾病患者相比。多因素Logistic分析显示PE患者合并原发性或转移性肺癌,胸痛,年龄<48岁,慢性心力衰竭,自身免疫性疾病,肺部感染和男性更容易发生咯血。根据每日最大痰血量和PE风险分层对患者进行分组。大多数患者(73.2%)接受治疗剂量的抗凝治疗。在中度至大咯血和中高风险或高风险PE的患者中观察到不良预后。结论:咯血是PE患者较为常见的表现,在急性PE的诊断检查过程中,它的存在需要仔细分析潜在的合并症。在PE背景下,在自身免疫性疾病患者中发生咯血的情况下,针对原发病的主动管理策略至关重要.治疗决策应同时考虑PE严重程度分层和咯血量。
    Background: Hemoptysis is prevalent in acute pulmonary embolism (PE) and significantly influences clinical decision-making. Despite the increasing reports of PE in patients with autoimmune diseases, limited studies have investigated the association between acute PE with hemoptysis and autoimmune disease. Methods: The retrospective study aimed to investigate patients with autoimmune disease who presented with acute PE and hemoptysis at Peking Union Medical College Hospital (PUMCH) between January 2012 and October 2020. A comparative analysis was conducted between patients with and without hemoptysis, as well as between those with autoimmune diseases and those without. Clinical characteristics, PE severity stratification, the amount of hemoptysis, initial anticoagulation management, and prognosis were analyzed descriptively. Results: The study analyzed 896 patients diagnosed with acute PE, of whom 105 (11.7%) presented with hemoptysis. Hemoptysis in PE patients was frequently associated with autoimmune diseases (39%, 41/105), a younger patient population (42.0 vs. 52.7 years old, P =0.002), and a higher prevalence of low-risk PE (53.7 vs. 28.1, P=0.008) compared with non-autoimmune disease patients. Multivariate logistic analysis showed PE patients with primary or metastatic lung cancer, chest pain, age < 48 years old, chronic heart failure, autoimmune disease, pulmonary infection and male were more likely to develop hemoptysis. Patients were grouped based on maximum daily sputum blood volume and PE risk stratification. Most patients (73.2%) received therapeutic-dose anticoagulation. Poor prognosis is observed in patients with moderate to massive hemoptysis and intermediate-high-risk or high-risk PE. Conclusions: Hemoptysis is a relatively common manifestation in patients with PE, and its presence during the diagnostic workup of acute PE necessitates careful analysis of underlying comorbidities. In cases where hemoptysis occurs in individuals with autoimmune diseases in the context of PE, proactive management strategies targeting the primary disease are crucial. Therapeutic decisions should consider both PE severity stratification and the volume of hemoptysis.
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  • 文章类型: Case Reports
    背景:2019年冠状病毒病患者的血栓形成发生率很高,康复后血栓形成发生率降低。当冠状病毒疾病2019伴有容易血栓形成的疾病时,感染后血栓事件的风险可能增加.
    方法:我们报告了一名24岁的中国女性,患有系统性红斑狼疮,2019年从冠状病毒疾病中恢复后出现数字缺血性坏疽。其发病机制与系统性红斑狼疮的临床特点有关,2019年冠状病毒病引起的高凝状态,以及病毒感染引起的二次打击。
    结论:自身免疫性疾病患者应警惕由严重急性呼吸道综合征冠状病毒2和其他病毒引起的自身免疫性疾病。对这些患者的治疗应严格规范,应选择适当的抗凝方法以防止血栓形成。
    BACKGROUND: Patients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase.
    METHODS: We report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection.
    CONCLUSIONS: Patients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.
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  • 文章类型: Journal Article
    背景:肺炎支原体肺炎是儿童常见的呼吸道感染。然而,与肺炎支原体肺炎相关的塑性支气管炎血栓栓塞的发生极为罕见.本病例系列介绍了5例肺炎支原体肺炎患儿发生血栓栓塞和塑性支气管炎。临床表现,诊断方法,并讨论了管理策略。
    方法:对某儿科医院的病历进行回顾性分析。患者人口统计学,临床特征,实验室发现,成像结果,治疗方式,并收集结果。
    结果:我们的病例系列中的患者出现不同程度的呼吸窘迫,咳嗽,和发烧。影像学检查显示,肺动脉闭塞有血栓栓塞的证据。通过支气管镜观察支气管管型。实验室测试表明D-二聚体水平和纤维蛋白原降解产物升高。所有患者均接受低分子肝素抗凝和支持治疗的组合。
    结论:在儿童中,与肺炎支原体肺炎相关的可塑性支气管炎血栓栓塞是一种罕见但潜在的严重并发症。及时的识别和管理对于改善患者预后至关重要。这个病例系列突出了不同的临床表现,诊断挑战,以及这个独特的临床实体的治疗策略。需要进一步的研究来更好地了解这种疾病的发病机理和最佳管理。
    BACKGROUND: Mycoplasma pneumoniae pneumonia is a common respiratory infection among children. However, the occurrence of thromboembolism with plastic bronchitis in association with Mycoplasma pneumoniae pneumonia is extremely rare. This case series presents five cases of children with Mycoplasma pneumoniae pneumonia who developed thromboembolism and plastic bronchitis. The clinical presentation, diagnostic approach, and management strategies are discussed.
    METHODS: A retrospective analysis was conducted on medical records from a pediatric hospital. Patient demographics, clinical features, laboratory findings, imaging results, treatment modalities, and outcomes were collected.
    RESULTS: The patients in our case series presented with varying degrees of respiratory distress, cough, and fever. Imaging studies revealed evidence of thromboembolism based on pulmonary artery occlusion. Bronchial casts were observed by bronchoscopy. Laboratory tests demonstrated elevated D-dimer levels and fibrinogen degradation products. All patients received a combination of low molecular weight heparin anticoagulation and supportive care.
    CONCLUSIONS: Thromboembolism with plastic bronchitis associated with Mycoplasma pneumoniae pneumonia is a rare but potentially serious complication in children. Prompt recognition and management are crucial for improving patient outcomes. This case series highlights the diverse clinical presentations, diagnostic challenges, and treatment strategies for this unique clinical entity. Further research is needed to better understand the pathogenesis and optimal management of this condition.
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  • 文章类型: Journal Article
    硫酸乙酰肝素(HS)的生物活性与其分子量密切相关,硫酸化的程度和模式和均匀性。用于合成低分散性的均质糖链的现有方法涉及多个步骤并且需要逐步分离和纯化过程。这里,我们设计了一种用于包封糖基转移酶的介孔金属有机胶囊,并获得了能够酶催化聚合反应的微反应器,以制备低分散性的均相肝素,HS和肝素的前体。由于糖链延伸发生在微反应器的孔中,低分子量肝素可以通过空间限制催化合成。此外,糖基化副产物,尿苷二磷酸(UDP),可以与金属有机胶囊的暴露金属位点螯合,抑制反式切割以降低分子量分散性。这种微反应器提供了效率的优点,可重用性,并且消除了对逐步分离和纯化过程的需要。使用合成的肝素,我们进一步成功地制备了低分散性的均相6-O-硫酸化HS,其分子量约为6kDa,多分散指数(PDI)为1.032。值得注意的是,产生的HS表现出最小的抗凝血活性,其与成纤维细胞生长因子1的结合亲和力与低分子量肝素相当。
    The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins.
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  • 文章类型: Journal Article
    来自海参的硫酸化岩藻聚糖主要由L-岩藻糖和硫酸基团组成。最近的研究已经证实硫酸化岩藻聚糖的结构主要由重复单元组成,通常是四糖。然而,越来越多的证据表明存在具有异质单元的不规则结构域,但尚未被广泛研究.此外,作为海参营养价值的关键贡献者,硫酸化的岩藻聚糖表现出一系列的生物活性,如抗炎,抗癌,降血脂,抗高血糖,抗氧化剂,和抗凝血性能。这些生物活性受到硫酸化岩藻聚糖的结构特征的深刻影响,包括硫酸酯基团的分子量和分布模式。最新研究表明硫酸化的岩藻聚糖分散在海参体壁的细胞外基质中。本文旨在综述原位分布的研究进展,结构,结构阐明策略,功能,和硫酸化岩藻聚糖的构效关系,尤其是在过去的十年里。它还提供了对硫酸化岩藻聚糖研究和开发中的主要挑战和潜在解决方案的见解。此外,预计岩藻聚糖酶和碳水化合物结合模块在推进该领域中起关键作用。
    Sulfated fucan from sea cucumber is mainly consists of L-fucose and sulfate groups. Recent studies have confirmed that the structure of sulfated fucan mainly consists of repeating units, typically tetrasaccharides. However, there is growing evidence indicating the presence of irregular domains with heterogeneous units that have not been extensively explored. Moreover, as a key contributor to the nutritional benefits of sea cucumbers, sulfated fucan demonstrates a range of biological activities, such as anti-inflammatory, anticancer, hypolipidemic, anti-hyperglycemic, antioxidant, and anticoagulant properties. These biological activities are profoundly influenced by the structural features of sulfated fucan including molecular weight and distribution patterns of sulfate groups. The latest research indicates that sulfated fucan is dispersed in the extracellular matrix of the body wall of sea cucumbers. This article aimed to review the research progress on the in-situ distribution, structures, structural elucidation strategies, functions, and structure-activity relationships of sulfated fucan, especially in the last decade. It also provided insights into the major challenges and potential solutions in the research and development of sulfated fucan. Moreover, the fucanase and carbohydrate binding modules are anticipated to play pivotal roles in advancing this field.
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  • 文章类型: Journal Article
    背景:红细胞(RBC)作为脊髓损伤(SCI)患者深静脉血栓形成(DVT)的潜在独立危险因素的作用仍不确定。本研究旨在阐明该人群中RBC计数与DVT发病率之间的关联。
    方法:对2017年1月1日至2021年12月31日康复医学科收治的576例SCI患者进行回顾性分析。排除后,对319例患者进行了分析,其中发现了94例DVT。
    结果:受伤方式,D-二聚体和抗凝治疗是显著的协变量(P<0.05)。年龄,纤维蛋白原,D-二聚体,抗凝治疗和美国脊髓损伤协会损害量表(AIS)评分与RBC计数和DVT发生率相关(P<0.05)。调整这些因素,红细胞计数增加1.00×10^12/L与DVT发生率降低45%相关(P=0.042),在4.56×10^12/L处与枢轴呈“U”形关系(P<0.05)。
    结论:RBC计数低于4.56×10^12/L作为DVT的保护因素,而高于此阈值的计数会带来风险。这些发现可以为SCI患者DVT预防策略的制定提供信息,强调需要有针对性地监测和管理RBC计数。
    BACKGROUND: The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain. This study aims to clarify the associations between RBC counts and DVT incidence among this population.
    METHODS: A retrospective analysis was performed on 576 patients with SCI admitted to the rehabilitation medicine department from January 1, 2017 to December 31, 2021. After exclusions, 319 patients were analyzed, among which 94 cases of DVT were identified.
    RESULTS: Mode of injury, D-dimer and anticoagulant therapy were significant covariates (P < 0.05). Age, fibrinogen, D-dimer, anticoagulant therapy and American Spinal Cord Injury Association impairment scale (AIS) grades were associated with RBC counts and DVT incidence (P < 0.05). Adjusting for these factors, a 1.00 × 10^12/L increase in RBC counts correlated with a 45% decrease in DVT incidence (P = 0.042), revealing a \"U\" shaped relationship with a pivot at 4.56 × 10^12/L (P < 0.05).
    CONCLUSIONS: RBC counts below 4.56 × 10^12/L serve as a protective factor against DVT, while counts above this threshold pose a risk. These findings could inform the development of DVT prevention strategies for patients with SCI, emphasizing the need for targeted monitoring and management of RBC counts.
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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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  • 文章类型: Journal Article
    这篇综述使用传统和网络荟萃分析(NMA)对血栓栓塞性疾病儿童的抗血栓治疗进行了全面研究。我们搜查了PubMed,Embase,科克伦图书馆,WebofScienceandClinicalTrials.gov数据库从成立到2月26日,2023年。最终纳入16项随机对照试验。在预防血栓栓塞事件(TEs)中,与不使用抗凝剂相比,使用抗凝剂的TE风险较低(相对危险度(RR)0.73,95%CI0.56~0.94),轻微出血风险较高(RR1.43,95%CI1.09~1.86).在治疗TEs时,直接口服抗凝剂(DOAC)在疗效和安全性结局方面均不劣于标准抗凝.在NMA,利伐沙班和阿哌沙班的TEs和严重或临床相关的非严重出血风险最低.根据疗效和安全性的总体评估,达比加群可能是儿童血栓栓塞性疾病的最佳选择。本研究结果将为临床药物选择提供参考和建议。
    This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.
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