mo, months

  • 文章类型: Journal Article
    胆道癌(BTC)是侵袭性上皮恶性肿瘤,可在胆道树的任何部位出现。尽管很罕见,在过去的40年里,它们的发病率和死亡率一直在稳步上升,强调需要改进当前的诊断和治疗策略。BTC在形态和分子水平上都显示出高的肿瘤间和肿瘤内异质性。这种复杂的异质性对有效的干预措施构成了实质性障碍。人们普遍认为,观察到的异质性可能是不同元素复杂相互作用的结果,包括风险因素,不同的分子改变和多个潜在的起源细胞。在实验模型中使用遗传谱系追踪系统已经确定了胆管细胞,肝细胞和/或祖细胞样细胞作为BTC的起源细胞。支持不同起源细胞假说的基因组证据正在增加。在这次审查中,我们关注BTC组织病理学亚型的最新进展,讨论当前的基因组证据,并概述谱系追踪研究,这些研究有助于围绕这些肿瘤的起源细胞的当前知识。
    Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.
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  • 文章类型: Journal Article
    背景:许多父母在早产儿出生后在新生儿重症监护病房(NICU)住院时会出现压力相关症状和抑郁症状。我们回顾了在单户家庭房(SFR)或开放式新生儿病房(OBU)住院的早产儿的父母健康状况的证据。
    方法:对于本系统综述和荟萃分析,我们搜索了MEDLINE,EMBASE,PsycINFO,Cochrane中央对照试验登记册(中央),WebofScience,Clinicaltrials.gov,和国际临床试验注册平台(ICTRP)数据库从开始到2019年11月22日,使用与早产和NICU设计相关的受控术语和文本词。我们纳入了随机和非随机研究,比较了接受SFR或OBU的早产儿父母的结局。使用CochraneCollaboration的随机对照试验的偏倚风险工具和非随机干预研究的偏倚风险工具(ROBINS-I)评估方法学质量。结果包括:父母的压力,满意,参与(存在/参与/皮肤对皮肤护理),自我效能感,父母-婴儿结合,抑郁症,焦虑,创伤后应激,赋权,以及以家庭为中心的护理程度。使用具有标准化平均差(SMD)的随机效应模型计算汇总估计值。PROSPERO注册:CRD42016050643。
    结果:我们确定了614种独特的出版物。11个研究人群(1,850名早产儿,包括1,549名母亲和379名父亲)。除一项研究外,所有研究都面临严重到严重的偏倚风险。SFR与更高水平的父母存在相关,参与,和皮肤对皮肤的护理。出院时,SFR与较低的压力水平相关(n=828父母,SMD-0·30,95CI-0·50;-0·09,p<0·004,I2=46%),特别是与NICU相关的应激(n=573,SMD-0·42,95CI-0·61;-0·23,p<0·0001,I2=0%)。在大多数研究中,更高水平的赋权,以家庭为中心的护理,对SFR感到满意。焦虑没有发现差异,父母与婴儿的联系,或者自我效能感。抑郁症很高(高达29%),但不同设置之间没有差异。没有研究描述创伤后应激。
    结论:单身家庭间似乎有利于父母的存在,参与,皮肤对皮肤的护理,减少与NICU相关的父母压力。
    BACKGROUND: Many parents develop stress-related symptoms and depression when their preterm infant is hospitalised in the neonatal intensive care unit (NICU) after birth. We reviewed the evidence of parent well-being with preterm infants hospitalised in single family rooms (SFRs) or in open bay neonatal units (OBUs).
    METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) databases from inception through 22 November 2019 using controlled terms and text words related to prematurity and NICU-design. We included randomised and non-randomised studies comparing outcomes in parents with preterm infants admitted to SFRs or OBUs. Methodological quality was assessed using Cochrane Collaboration\'s Risk of Bias Tool for randomised controlled trials and the Risk of Bias Tool for Non-Randomised Studies of Interventions (ROBINS-I). Outcomes included: parental stress, satisfaction, participation (presence/involvement/skin-to-skin care), self-efficacy, parent-infant-bonding, depression, anxiety, post-traumatic stress, empowerment, and degree of family-centred care. Summary estimates were calculated using random effects models with standardised mean differences (SMDs). PROSPERO registration: CRD42016050643.
    RESULTS: We identified 614 unique publications. Eleven study populations (1, 850 preterm infants, 1, 549 mothers and 379 fathers) were included. All but one study were at serious to critical risk of bias. SFRs were associated with higher levels of parental presence, involvement, and skin-to-skin care. Upon discharge, SFRs were associated with lower stress levels (n = 828 parents, SMD-0·30,95%CI -0·50;-0·09, p<0·004, I2=46%), specifically NICU-related stress (n = 573, SMD-0·42,95%CI -0·61;-0·23, p<0·0001, I2=0%). In majority of studies higher levels of empowerment, family-centred care, and satisfaction was present with SFRs. No differences were found for anxiety, parent-infant bonding, or self-efficacy. Depression was high (up to 29%) but not different between settings. No studies described post-traumatic stress.
    CONCLUSIONS: Single family rooms seem to facilitate parental presence, involvement, skin-to-skin care, and reduce NICU-related parental stress.
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  • 文章类型: Journal Article
    描述3例肾移植术后盆腔放疗患者的特点和结果。
    肾移植(KT)受者的盆腔癌发病率正在上升。目前,它是导致死亡的主要原因。此外,治疗具有挑战性,因为解剖变异,合并症,和相关的治疗方法,这引起了使用放射治疗(RT)的担忧。由于尿道/输尿管狭窄和KT功能障碍的风险增加,不鼓励RT。
    我们回顾了2013年12月至2018年12月期间接受骨盆RT治疗的患者的电子健康记录和数字计划系统,以识别先前患有KT的患者。
    我们描述了三例成功的KT患者,其中现代技术允许对盆腔恶性肿瘤(2例前列腺癌和1例阴道癌)进行完全标准RT,有或没有选择性盆腔淋巴结RT,在短期和长期随访(长达60个月)没有同种异体移植物毒性。
    需要时,RT现代技术仍然是具有优异的肿瘤学结果和可接受的毒性的有效选择。医师应特别考虑在患者的特定设置中完成所有OAR剂量限制。最近的出版物推荐KT平均剂量<4Gy,但是靠近CTV使得这不可行。我们介绍了2例没有达到剂量限制的情况,和20个月的短期随访肾毒性尚未记录。我们建议KT尽可能低的平均剂量,但从不影响CTV的报道,由于复发性或进行性癌症疾病的死亡率超过了移植物损伤的风险。
    UNASSIGNED: Describe characteristics and outcomes of three patients treated with pelvic radiation therapy after kidney transplant.
    UNASSIGNED: The incidence of pelvic cancers in kidney transplant (KT) recipients is rising. Currently it is the leading cause of death. Moreover, treatment is challenging because anatomical variants, comorbidities, and associated treatments, which raises the concern of using radiotherapy (RT). RT has been discouraged due to the increased risk of urethral/ureteral stricture and KT dysfunction.
    UNASSIGNED: We reviewed the electronic health records and digital planning system of patients treated with pelvic RT between December 2013 and December 2018 to identify patients with previous KT.
    UNASSIGNED: We describe three successful cases of KT patients in which modern techniques allowed full standard RT for pelvic malignances (2 prostate and 1 vaginal cancer) with or without elective pelvic nodal RT, without allograft toxicity at short and long follow-up (up to 60 months).
    UNASSIGNED: When needed, RT modern techniques remain a valid option with excellent oncologic results and acceptable toxicity. Physicians should give special considerations to accomplish all OAR dose constraints in the patient\'s specific setting. Recent publications recommend KT mean dose <4 Gy, but graft proximity to CTV makes this unfeasible. We present 2 cases where dose constraint was not achieved, and to a short follow-up of 20 months renal toxicity has not been documented. We recommend the lowest possible mean dose to the KT, but never compromising the CTV coverage, since morbimortality from recurrent or progressive cancer disease outweighs the risk of graft injury.
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  • 文章类型: Journal Article
    背景:钒(V)是一种对哺乳动物生物体具有广泛影响的元素。鉴于其在医学中的应用,这种金属形成有机金属化合物的能力有助于增加对其各种有机配合物的多向生物活性的研究数量。
    目的:这篇综述旨在总结V的药理潜力及其抗病毒潜在机制的知识现状,抗菌,抗寄生虫,抗真菌,抗癌,抗糖尿病,抗高胆固醇血症,心脏保护,和神经保护活性以及与使用该元素治疗肥胖症的可能性有关的食欲调节机制。V的毒理学潜力及其毒性作用机制,这些还没有得到充分的认识,以及关于这种金属的重要性的关键信息,它的生理作用,以及时间表上某些方面的新陈代谢也被收集。该报告还旨在审查V在植入学和工业部门中的使用,强调人类健康危害,并收集有关V的进一步研究方向及其与Mg的相互作用及其特征的数据。
    结论:对V的多方向研究表明,仍需要进一步分析才能将该元素用作金属药物来对抗某些危及生命的疾病。研究V与Mg,这表明这两个元素都能够以交互方式调节响应也是必要的,因为这些研究的结果可能不仅有助于识别V毒性的新标志物,并阐明它们之间潜在的相互作用机制,从而提高了金属对现代疾病的医学应用,但它们也可能有助于制定有效保护人类免受环境/职业V暴露的原则。
    BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine.
    OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character.
    CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.
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  • 文章类型: Journal Article
    肺癌是全世界癌症相关死亡的最常见原因。单独放疗或联合化疗是局部晚期非小细胞肺癌(NSCLC)的标准治疗方法。目前,尚无具有临床实用性的预测性标志物来指导接受放疗的NSCLC患者的治疗决策。此类标志物的鉴定将允许考虑更有效治疗的治疗选择。为了能够识别适当的蛋白质生物标志物,我们在放疗前和放疗过程中从非小细胞肺癌患者收集血浆样本,进行纵向比较,该方案具有足够的有效发现蛋白质组学功效.使用8通道等压标签串联质谱发现蛋白质组学平台,将存活>18mo的患者放疗前和放疗期间的血浆样品与存活<14mo的患者的相同时间点进行比较。超过650种蛋白质被检测和相对定量。选择在放疗期间显示变化的蛋白质用于使用基于正交抗体的方法进行验证。在单独的患者队列中验证了这些蛋白质中的两种:CRP和LRG1的组合值显示了放疗治疗一周后延长生存期的高度显着指示。
    Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment.
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