摘要：Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory ***,the development of a model for effective drug screening is urgently *** the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug ***,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural ***,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo *** 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)*** screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional *** study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.

摘要：耐多药和广泛耐药结核病疫情升高的一个重要原因是病菌的传播与再感染,尤其是当患者同时也是HIV感染者时,传播与再感染更加严重。尽管传统的结核病感染控制措施已经开始广泛实施,但此策略在高负担国家人群密集地区仍显不足。长期的证据表明,结核病患者接受有效地治疗后,会迅速转为非传染性肺结核,反而是非结核病可疑者、未接受治疗的结核病患者成为传染的主因,因此,急需尽早发现并有效治疗这些患者。遏制传染的最重要措施是耐多药肺结核社区治疗模式,相对于基于医院和诊所的关怀模式,社区模式不仅更经济、更有效,而且也有利于感染控制。快速识别传染性病例,尤其是耐药病例,实施有效的完全督导下的治疗,对控制细菌在社区传播依然非常关键。在传统的干预手段中,我们使用简单的病人分诊和隔离策略,需要指出,隔离与诊所空间的设计和建造密切相关,同时需要考虑自然通风的利弊,简单机械通风系统,用于空气消毒的紫外线杀菌设备,医疗卫生工作者医用防护口罩的适合度测试及患者候诊时佩戴外科口罩。

摘要：背景：关于经皮冠状动脉介入治疗（percutaneous coronary intervention，PCI）前氯吡格雷预治疗的益处目前仍有争议，并且其使用亦未获得普遍认可。目的：于新近发生sT段抬高心肌梗死（sT—segment elevation myocardial infarction，sTEMI）的患者中确定PCI前氯吡格雷预治疗预防严重不良心血管事件的效果是否优于PCI时开始采用氯吡格雷治疗。设计、地点及参试者：CLARITY（PCI—Clopidogrel as Adjunctive Reperfusion Therapy）研究是一项于1863例患者中进行的前瞻性计划分析。这些患者均于CLARITY—TIMI（Thrombolysis in Myocardial Infarction）28试验中在血管造影后实施了PCI。CLARITY—TIMI28是一项在接受纤溶治疗的患者中进行的有关氯吡格雷效果的随机、双盲、安慰剂对照试验。患者于2003年2月至2004年10月入选自23个国家的319家医院。干预：患者服用阿斯匹林并于纤溶治疗时开始随机接受氯吡格雷（300mg负荷剂量，以后75mg，每日1次）或安慰剂，直至冠状动脉造影前为止。造影在开始研究药物后2～8天进行。接受冠脉支架的患者建议于诊断性血管造影后给予开标氯吡格雷（包括负荷剂量）。主要观测指标：一级终点为PCI至随机分组后30天心血管死亡、MI复发或脑卒中的复合发生率。二级终点包括在PCI之前发生的MI或脑卒中以及前述随机分组后30天相关终点。结果：氯吡格雷预治疗可显著降低PCI后心血管死亡、MI或脑卒中的发生率（34[3．6％]比58[6．2％]；校正优势比[odds ratio，OR]，0．54[95％CI，0．35—0．85]；P=0．008）。氯吡格雷预治疗还可降低PCI前MI或脑卒中的发生率（37[4．0％]比58[6．2％]；OR，0．62[95％CI，0．40～0．95]；P=0．03）。总体上，氯吡格雷预治疗可导致随机分组后30天心血管死亡、MI或脑卒中显著下降（70[7．5％]比112[12．0％]；校正OR，0．59[95％CI，0．43～0．81]；P=0．001；所需治疗例数=23）。TIMI严重或轻微出血的发生率未显著增加（（18[20％]比17[1．9％]；P〉0．99）。结论：氯吡格雷预治疗可显著降低PCI前后心血管死亡或缺血并发症，而严重或轻微出血无显著增加。这些数据为sTEMI患者早期使用氯吡格雷以及接受PCI的患者常规采用氯吡格雷预治疗方案提供了进一步的支持。

摘要：Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural *** in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted *** oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain *** study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with *** report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide ***,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase *** study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release ***,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal *** showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new *** findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated *** work thereby offers a promising avenue for the development of functional tissues with e

摘要：为了测量低场磁共振设备参数,该文提出一种对硬件要求不高,可以较快测量T1、T2数据的方法。通过对基本序列进行研究,充分利用由3个射频激发产生信号的信息,设计读取梯度对它们进行区分,完成了可以在一次扫描中同时测量T1、T2参数的刺激回波(stimulated echo,sTE)序列。该序列在0.3T低场设备上进行了包括水模和人体在内的测量实验,测量时间相对同时使用传统自旋回波序列(spin echo,sE)、反转恢复回波序列(inversion recovery,IR)减少一半。测量结果证明sTE是一种适合于低场环境参数测量使用的序列。

摘要：Context: Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. Objective: To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women. Design, setting, and Participants: In the women’s Health study conducted between 1992 and 2004, 39 876 apparently healthy Us women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2×2 factorial design, and were followed up for an average of 10.1 years. Intervention: Administration of 600 IU of natural-source vitamin E on alternate days. Main Outcome Measures: Primary outcomes were a composite end point of first major cardiovascular event(nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer. Results: During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7%risk reduction(relative risk[RR], 0.93; 95%confidence interval[CI], 0.82-1.05; P=.26). There were no significant effects on the incidences of myocardial infarction(RR, 1.01; 95%CI, 0.82-1.23; P=.96) or stroke(RR, 0.98; 95%CI, 0.82-1.17; P=.82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24%reduction(RR, 0.76; 95%CI, 0.59-0.98; P=.03). There was no significant effect on the incidences of total cancer(1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95%CI, 0.94-1.08; P=.87) or breast(RR, 1.00; 95%CI, 0.90-1.12; P=.95), lung(RR, 1.09; 95%CI, 0.83-1.44; P=.52), or colon cancers(RR, 1.00; 95%CI, 0.77-1.31; P=.99). Cancer deaths also did not differ sign

摘要：背景：尽管人们对动脉粥样硬化血栓形成已有新的认识，但是，预测女性心血管事件的方法在很大程度上仍依赖于传统的危险因素。目的：根据新旧危险因素对女性心血管疾病危险评估法进行改进并予验证。设计、地点及参试者：于24558名健康的≥45岁的美国女性中对35个危险因素进行评估分析。随访中位时间为10．2年（截至2004年5月），观察心血管事件（复合终点包括心肌梗死、缺血性卒中、冠状动脉血运重建以及心血管死亡）的发生率。随机使用三分之二女性队列（推导队列，n=16400）的资料推导新的危险计算方法，然后将其结果与其余三分之一女性队列（验证队列，n=8158）的实际情况进行比较，借此对新计算方法的有效性进行验证。主要观测指标：根据BIC（Bayes Information Criterion）最小化原则在推导队列中建立最适简易预测模型。在验证队列中比较10年心血管事件的预测发生率与实际发生率。对新的计算方法和根据成人胆固醇治疗计划Ⅲ（ATP-Ⅲ）危险评分协变量产生的模型亦进行比较。结果：与ATP-Ⅲ危险评分协变量模型相比，在推导队列中，有1个最适模型（模型A）和1个临床简化模型（模型B，雷诺危险评分）具有较低的BIC评分。在验证队列中，应用模型A及模型B时，所有拟和、判别及校准指标均获改善。举例而言，根据ATP-Ⅲ危险评分标准，在非糖尿病女性参试者中，有603人10年心血管疾病危险为5％～10％，156人10年心血管疾病危险为10％～20％；而根据模型A，则可将其中的379人（50％）重新归类为更符合实际事件发生率的更高或更低的危险级别；根据年龄、收缩压、糖化血红蛋白A1c（如果患糖尿病）、吸烟、总胆固醇和高密度脂蛋白胆固醇、超敏C-反应蛋白以及60岁前心肌梗死家族史产生的简化模型B也能达到相似的效果。对于ATP-Ⅲ评分划归为极低危险组女性，采用两种新的计算方法并无明显不同。结论：我们推出了两种可大大改善心血管事件危险预测准确性的临床计算方法。验证结果表明，这两种方法可将40％～50％的传统中危组女性重新划归为高危组或低危组。

摘要：目的:在大样本队列中研究性格测试指标与心血管疾病和癌症风险的关系。设计:基于人群的队列随访研究。地点:德国海德堡。参与者:1992—1995年间5114例年龄在40～65岁的男性和女性。

摘要：Context: Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. Objective: To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women. Design, setting, and Participants: In the women’s Health study conducted between 1992 and 2004, 39 876 apparently healthy Us women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2×2 factorial design, ane were followed up for an average of 10.1 years. Intervention: Administration of 600 IU of natural-source vitamin E on alternate days. Main Outcome Measures: Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer. Results: During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7%risk reduction (relative risk [RR], 0.93; 95%confidence interval [CI], 0.82-1.05; P=.26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01; 95%CI, 0.82-1.23; P=.96) or stroke (RR, 0.98; 95%CI, 0.82-1.17; P=.82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24%reduction (RR, 0.76; 95%CI, 0.59-0.98; P=.03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95%CI, 0.94-1.08; P=.87) or breast (RR, 1.00; 95%CI, 0.90-1.12; P=.95), lung (RR, 1.09; 95%CI, 0.83-1.44; P=.52), or colon cancers (RR, 1.00; 95%CI, 0.77-1.31; P=.99). Cancer deaths also did not

摘要：背景:关于甘油三酯(TG)与新发心血管事件的关系尚无定论。尽管通常是检测空腹TG,然而餐后高甘油三酯血症可能是动脉粥样硬化(As)的重要相关因素。目的:研究TG水平(空腹vs餐后)与未来心血管事件的相关性。设计。