RT-PCR, reverse transcription polymerase chain reaction

RT - PCR,逆转录聚合酶链反应
  • 文章类型: Journal Article
    接受肝移植作为终末期肝病的护理标准已导致供体同种异体移植物的严重短缺。为了扩大捐赠器官库,许多国家已经放宽了捐赠标准,包括延长标准捐赠者和循环系统死亡后捐赠。当使用标准静态冷藏(SCS)保存技术保存这些边缘肝脏时,它们具有较高的损伤风险。近年来,研究集中在优化器官保存技术以保护这些边缘肝脏。在过去的十年中,扩大的供体肝脏的机器灌注(MP)取得了长足的进步。研究表明,MP策略比SCS技术具有显著的优势,例如更长的保存时间,可行性评估和在植入前重新调整高风险同种异体移植物的潜力。在这篇评论文章中,我们讨论了MP在肝脏移植保存中的主题,重点介绍当前临床应用趋势。我们讨论了与低温MP技术相关的相关临床试验,常温MP,低温氧合MP,和受控的含氧复温。我们还讨论了离体疗法的潜在应用,这些疗法可能与将来在移植前进一步优化同种异体移植物有关。
    The acceptance of liver transplantation as the standard of care for end-stage liver diseases has led to a critical shortage of donor allografts. To expand the donor organ pool, many countries have liberalized the donor criteria including extended criteria donors and donation after circulatory death. These marginal livers are at a higher risk of injury when they are preserved using the standard static cold storage (SCS) preservation techniques. In recent years, research has focused on optimizing organ preservation techniques to protect these marginal livers. Machine perfusion (MP) of the expanded donor liver has witnessed considerable advancements in the last decade. Research has showed MP strategies to confer significant advantages over the SCS techniques, such as longer preservation times, viability assessment and the potential to recondition high risk allografts prior to implantation. In this review article, we address the topic of MP in liver allograft preservation, with emphasis on current trends in clinical application. We discuss the relevant clinical trials related to the techniques of hypothermic MP, normothermic MP, hypothermic oxygenated MP, and controlled oxygenated rewarming. We also discuss the potential applications of ex vivo therapeutics which may be relevant in the future to further optimize the allograft prior to transplantation.
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  • 文章类型: Journal Article
    尽管有关疫苗接种和先前感染引起的抗体反应的动力学和持久性的数据越来越多,对于给定的抗体定量水平是否与SARS-CoV-2感染或再感染的保护相关,目前尚不清楚.在这项研究中,我们在一大群美国患者中检测了SARS-CoV-2抗尖峰受体结合域(RBD)抗体滴度和随后的SARS-CoV-2逆转录聚合酶链反应(RT-PCR)检测.我们分析了22,204名个体的抗体测试结果,6.8%(n=1509)的人最终SARS-CoV-2RNA检测呈阳性,提示感染或再感染。绘制Kaplan-Meier曲线以理解各种水平的抗尖峰RBD抗体滴度(分类为离散范围)对随后的RT-PCR阳性率的影响。统计分析包括拟合Cox比例风险模型来估计年龄-,S抗体滴度的性别和暴露调整的危险比,使用每周邮政编码阳性率作为COVID-19暴露的代理。发现时间相关感染风险的最佳模型是基于对数抗体滴度水平的那些模型(HR=0.836(p<0.05))。当滴度被分类时,与抗体滴度>250结合抗体单位(BAU)相关的风险比为0.27(p<0.05,95%CI[0.18,0.41]),而与既往感染相关的风险比为0.20(p<0.05,95%CI[0.10,0.39])。Ab滴度<250BAU的Fisher精确比值比(OR)显示OR=2.84(p<0.05;95%CI:[2.30,3.53]),用于预测后续PCR测试的结果。当检查进行了峰值RBD抗体测定的现实世界患者队列时,抗体滴度水平与针对随后的SARS-CoV-2感染或再感染的保护相关。
    Despite a growing amount of data around the kinetics and durability of the antibody response induced by vaccination and previous infection, there is little understanding of whether or not a given quantitative level of antibodies correlates to protection against SARS-CoV-2 infection or reinfection. In this study, we examine SARS-CoV-2 anti-spike receptor binding domain (RBD) antibody titers and subsequent SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests in a large cohort of US-based patients. We analyzed antibody test results in a cohort of 22,204 individuals, 6.8% (n = 1,509) of whom eventually tested positive for SARS-CoV-2 RNA, suggesting infection or reinfection. Kaplan-Meier curves were plotted to understand the effect of various levels of anti-spike RBD antibody titers (classified into discrete ranges) on subsequent RT-PCR positivity rates. Statistical analyses included fitting a Cox proportional hazards model to estimate the age-, sex- and exposure-adjusted hazard ratios for S antibody titer, using zip-code positivity rates by week as a proxy for COVID-19 exposure. It was found that the best models of the temporally associated infection risk were those based on log antibody titer level (HR = 0.836 (p < 0.05)). When titers were binned, the hazard ratio associated with antibody titer >250 Binding Antibody Units (BAU) was 0.27 (p < 0.05, 95% CI [0.18, 0.41]), while the hazard ratio associated with previous infection was 0.20 (p < 0.05, 95% CI [0.10, 0.39]). Fisher exact odds ratio (OR) for Ab titers <250 BAU showed OR = 2.84 (p < 0.05; 95% CI: [2.30, 3.53]) for predicting the outcome of a subsequent PCR test. Antibody titer levels correlate with protection against subsequent SARS-CoV-2 infection or reinfection when examining a cohort of real-world patients who had the spike RBD antibody assay performed.
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  • 文章类型: Journal Article
    未经批准:维生素D最近引起了很大的争议,不是因为它具有吸收钙和维持骨骼健康的传统作用,但是由于其作为内分泌因子的非常规作用以及与其在不同组织中发现的特异性受体(VDR)相关时的影响程度。研究一直在努力寻找其在这些组织中的不同作用及其与不同临床或医学状况的联系,在这些案例中,它在女性生殖功能和生育能力中的作用,根据他们的研究结果,这些研究在支持和否认维生素D在生殖功能中的作用与拒绝这一假设之间存在冲突。
    未经评估:体外受精过程使我们能够研究可能的假设,因为这项技术提供了研究维生素D水平与体外受精结局之间关系的机会,从而为我们提供了维生素D与女性生育能力的关系的想法。为了研究这种关系,我们将我们的研究设计为横断面研究,以证实或否认这一说法.在所有情况下,使用电化学发光免疫分析法(ECLIA)测定血液和卵泡液中的维生素D,然后将IVF结局与血液中维生素D的水平进行比较。
    未经评估:维生素D的水平与鸡蛋的标准无关,例如鸡蛋的数量和鸡蛋的成熟率(MR),但它们与生育率(FR)具有统计学意义的相关性,同时,血液中维生素D的水平完全独立于临床妊娠率(CPR)。
    UNASSIGNED:当血液中的维生素D水平低于规定值时,血液中的维生素D水平会影响FR,维生素D与CPR无关.从长远来看,有更多关于维生素D的研究项目的空间。未来的研究可能包括对患者补充维生素D的病例对照研究,以及其与IVF结局相关性的研究。
    UNASSIGNED: Vitamin D has recently raised a great deal of controversy, not because of its traditional role of absorbing calcium and maintaining bone health, but because of its unconventional role as an endocrine factor and the extent of its impact when linked to its specific receptors (VDR) found in different tissues. Research has raced trying to find its different roles in those tissues and its association with different clinical or medical conditions, and among these cases, its role in reproductive functions and fertility in women, these studies conflicted between supporting and denying the role of vitamin D in reproductive function and rejecting this hypothesis according to the results of their study.
    UNASSIGNED: The in vitro fertilization process allowed us to study the possible hypotheses, as this technique provides an opportunity to study the relationship between vitamin D levels with the in vitro fertilization outcomes, thus providing us with an idea of the relationship of vitamin D with fertility in women. In order to study this relationship, we designed our research as a cross-sectional study to confirm or deny this claim. Vitamin D was measured in the blood and in the follicular fluid for all cases using the electrochemiluminescence immunoassay (ECLIA) for the assay of total vitamin D, then IVF outcomes were compared with the levels of vitamin D in the blood.
    UNASSIGNED: the levels of vitamin D are not related to the criteria of eggs such as the number of eggs and the maturity rate (MR) of eggs, but they are correlated in a statistically significant manner with the fertility rate (FR), and at the same time the levels of vitamin D in the blood were completely independent of the clinical pregnancy rate (CPR).
    UNASSIGNED: blood vitamin D levels will affect the FR when its levels in the blood drop below a specified value, vitamin D did not correlate with the CPR. In the long run, there is scope for more research projects on vitamin D. Future research could include case-control studies of patients on vitamin D supplementation, and the study of its correlation with IVF outcomes.
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  • 文章类型: Journal Article
    未经证实:由于OmicronBA.1变体的快速传输,英格兰COVID-19的Omicron波在2022年1月达到顶峰。我们调查了2022年2月SARS-CoV-2疫情在英格兰人口中的传播和动态,年龄和主要SARS-CoV-2亚谱系。
    UNASSIGNED:在社区传播的实时评估-1(REACT-1)研究中,我们从94,950名参与者的随机样本中获得了数据,这些参与者在第18轮(2022年2月8日至3月1日)中通过RT-PCR获得了有效的喉咙和鼻子拭子结果。
    未经评估:我们估计加权平均SARS-CoV-2患病率为2.88%(95%可信区间[CrI]2.76-3.00),轮内有效复制数(R)总体为0.94(0·91-0.96)。虽然在儿童(5至17岁)和18至54岁的成年人中,整体加权患病率有所下降,我们观察到55岁及以上人群的加权患病率水平或增加,R为1.04(1.00-1.09).在确定亚谱系的1616个阳性样本中,一个(0.1%[0.0-0.3])对应于XEBA.1/BA.2重组,其余为Omicron:N=1047,64.8%(62.4-67.2)为BA.1;N=568,35.2%(32.8-37.6)为BA2。我们估计BA.2(vsBA.1)的R累加优势为0.38(0.34-0.41)。在阳性样本中,BA.2的比例最高的是伦敦。
    UNASSIGNED:2022年2月,英格兰的感染率仍然很高,老年人的感染率或增加,住院率上升。需要对调查和住院数据进行持续监测。
    未经批准:卫生和社会护理部,英格兰。
    UNASSIGNED: The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.
    UNASSIGNED: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).
    UNASSIGNED: We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0-0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1047, 64.8% (62.4-67.2) were BA.1; N=568, 35.2% (32.8-37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34-0.41). The highest proportion of BA.2 among positives was found in London.
    UNASSIGNED: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.
    UNASSIGNED: Department of Health and Social Care, England.
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  • 文章类型: Journal Article
    传染性SARS-CoV-2对许多社区的生活和健康产生了巨大影响。它在2019年初首次猖獗,到目前为止,全球报告了5.39亿例COVID-19。这让人想起1918年的流感大流行。然而,我们可以通过分析X射线或CT来检测COVID-19的感染病例,大概被认为是最便宜的方法。在最先进的卷积神经网络(CNN)的存在中,它将图像预处理技术与完全连接的层集成在一起,我们可以开发一个复杂的人工智能系统,取决于各种预先训练的模型。我们参与研究的每个预训练模型都承担了从许多验证来源的不同胸部图像数据集中提取一些特定特征的作用,如(Mendeley,Kaggle,和GitHub)。首先,对于从一开始就与CNN训练模型相关的CXR数据集,其中由从Conv2D层开始的四个层组成,它包括32个过滤器,紧随其后的是MaxPooling,之后,我们同样重申。我们使用了两种技术来避免过度概括,早期停止和辍学技术。毕竟,输出是一个神经元来分类两种情况的0或1,其次是一个sigmoid功能;此外,我们使用了Adam优化器,因为它的结果比其他优化器进行的结果更好;最终,我们通过使用混淆矩阵来引用我们的发现,分类报告(召回和精度),敏感性和特异性;在这种方法中,我们实现了96%的分类准确率。我们的三个集成预训练模型(VGG16,DenseNet201和DenseNet121)产生了98.81%的显着测试精度。此外,我们的合并模型(VGG16,DenseNet201)尽最大努力在CT图像上训练;该模型对(Normal/Covid-19)场景的二元分类的准确率为99.73%。将我们的结果与相关研究进行比较表明,我们提出的模型在各种性能指标方面都优于以前的CNN机器学习模型。我们与CT数据集相关的预训练模型获得了100%的F1评分,损失值大约为0.00268。
    The contagious SARS-CoV-2 has had a tremendous impact on the life and health of many communities. It was first rampant in early 2019 and so far, 539 million cases of COVID-19 have been reported worldwide. This is reminiscent of the 1918 influenza pandemic. However, we can detect the infected cases of COVID-19 by analysing either X-rays or CT, which are presumably considered the least expensive methods. In the existence of state-of-the-art convolutional neural networks (CNNs), which integrate image pre-processing techniques with fully connected layers, we can develop a sophisticated AI system contingent on various pre-trained models. Each pre-trained model we involved in our study assumed its role in extracting some specific features from different chest image datasets in many verified sources, such as (Mendeley, Kaggle, and GitHub). First, for CXR datasets associated with the CNN trained model from the beginning, whereby is comprised of four layers beginning with the Conv2D layer, which comprises 32 filters, followed by the MaxPooling and afterwards, we reiterated similarly. We used two techniques to avoid overgeneralization, the early stopping and the Dropout techniques. After all, the output was one neuron to classify both cases of 0 or 1, followed by a sigmoid function; in addition, we used the Adam optimizer owing to the more improved outcomes than what other optimizers conducted; ultimately, we referred to our findings by using a confusion matrix, classification report (Recall & Precision), sensitivity and specificity; in this approach, we achieved a classification accuracy of 96%. Our three integrated pre-trained models (VGG16, DenseNet201, and DenseNet121) yielded a remarkable test accuracy of 98.81%. Besides, our merged models (VGG16, DenseNet201) trained on CT images with the utmost effort; this model held an accurate test of 99.73% for binary classification with the (Normal/Covid-19) scenario. Comparing our results with related studies shows that our proposed models were superior to the previous CNN machine learning models in terms of various performance metrics. Our pre-trained model associated with the CT dataset achieved 100% of the F1score and the loss value was approximately 0.00268.
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  • 文章类型: Journal Article
    印度,世界上人口第二多的国家,1月16日开始了大规模疫苗接种运动,2021年。为了给13亿人接种疫苗,这项疫苗接种计划被称为世界上最大的疫苗接种运动。然而,由于COVID-19大流行和封锁导致血液储备枯竭,导致血液营地减少,叠加的关于推迟献血的规定构成了即将耗尽血液及其产品的风险。这将导致无法满足大流行后不可预测的血液需求模式。因此,为了防止手术和救生程序中可避免的血液短缺风险,应确保安全的存储系统。
    India, the second most populous country in the world, started its mass vaccination campaign on January 16th, 2021. With the aim to vaccinate 1.3 billion people, this vaccination programme was dubbed as the world\'s largest vaccination drive. However, with depleted blood stores due to the COVID-19 pandemic and lockdown leading to reduced blood camps, the superposed regulations on blood donation deferral poses an impending risk of depletion of blood and its products. This will lead to the inability in meeting unpredictable patterns of demand in blood requirement post-pandemic. Hence to prevent avoidable risks of blood shortage in surgeries and lifesaving procedures, a secure storage system should be ensured.
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  • 文章类型: Journal Article
    UNASSIGNED:南非是2020年SARS-CoV-2病例记录最多的非洲国家,经历了2波感染。在第一波中,诊断主要基于逆转录连接PCR(RT-PCR).雅培PanBio抗原测试在第二波中进行,这可能是由B.1.351变体的出现驱动的。在2020年11月中旬评估时,B.1.351是纳尔逊·曼德拉湾的主要流行病毒,在东开普省。
    UNASSIGNED:首先验证了使用的PanBio抗原拭子(从具有遗传特征病毒的患者收集)适用于PCR。然后进行前瞻性研究以评估该领域的测定性能。在流动社区测试中心对677名流动患者进行了测试。保留使用过的拭子并通过RT-PCR进行测试。
    未经验证:在初始验证期间,发现专有裂解缓冲液中使用的拭子适用于PCR,其次,PB测定可靠地检测感染B.1.351的患者。在实地研究中,146例RT-PCR阳性个体,101例临床RTD阳性。RTD的敏感性为69.2%(95CI61.4,75.8),特异性为99.0%(95CI98.8,99.3)。敏感性取决于临床样本中病毒RNA的含量,由PCR循环阈值(CT)值反映。
    UNASSIGNED:该检测方法在初始验证和现场测试中可靠地检测了卧床患者的B.1.351感染。在田野里,在预期最具传染性的高病毒载量患者中,检测灵敏度>90%.阴性和阳性预测值也>90%。
    UNASSIGNED: South Africa was the African country with the most recorded cases of SARS-CoV-2 during 2020, experiencing 2 waves of infection. During the first wave, diagnostics were largely based on reverse transcription-linked PCR (RT-PCR). The Abbott PanBio antigen test was deployed during the 2nd wave which may have been driven by emergence of the B.1.351 variant. At the time of evaluation in mid-November 2020, B.1.351 was the dominant circulating virus in Nelson Mandela Bay, in the Eastern Cape Province.
    UNASSIGNED: Used PanBio antigen swabs (collected from patients with genetically characterised virus) were first validated as suitable for PCR. A prospective study was then undertaken to evaluate assay performance in the field. Testing was conducted at mobile community testing centres on 677 ambulant patients. Used swabs were kept and tested by RT-PCR.
    UNASSIGNED: During initial validation, used swabs in proprietary lysis buffer were found to be suitable for PCR and secondly, the PB assay reliably detected patients infected with B.1.351. In the field study, of 146 RT-PCR positive individuals, 101 were RTD positive in the clinic. The RTD had a sensitivity of 69.2% (95%CI 61.4, 75.8) and specificity of 99.0% (95%CI 98.8, 99.3). Sensitivity was dependent on the amount of viral RNA in clinical samples, as reflected by the PCR cycle threshold (CT) value.
    UNASSIGNED: The assay reliably detected B.1.351 infections in ambulatory ill patients during initial validation and in field testing. In the field, assay sensitivity was >90% in patients with high viral loads who are expected to be most infectious. Negative and positive predictive values were also >90%.
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  • 文章类型: Journal Article
    未经评估:在这项研究中,我们的目的是确定COVID-19大流行对城市医疗中心胸外科手术患者提供护理的影响。
    UNASSIGNED:对2019年5月1日至2020年12月31日的所有胸外科病例进行了回顾性分析。人口特征,术前手术适应症,程序,最终病理诊断,并记录围手术期结局.手术病例普查,相关辅助服务,和门诊胸科诊所从我们的机构数据库获得。
    未经批准:本研究纳入了6119例病例(329例COVID-19和290例COVID-19,减少了11.8%)。在2个队列中,胸腔手术类型或围手术期结局没有差异。在COVID-19期间的前半部分,胸外科手术病例的减少时间延长(基线的50%),随后在后半部,手术体积恢复到基线的110%。在上半年,肿瘤适应症的病例发生率相似,而在下半年,良性病例更多。恰逢我们的机器人前肠手术计划的启动。在大流行期间接受手术后,我们的患者均未在出院后14天内报告COVID-19症状。
    未经评估:在COVID-19的最初激增期间,虽然手术服务暂时关闭,我们的医疗保健系统继续为胸外科手术患者提供安全的护理,特别是那些有肿瘤适应症的。自从分阶段重新开放以来,我们经历了手术量和病例组合的反弹,最终减轻大流行对胸外科护理的最初负面影响。
    UNASSIGNED: In this study we aimed to determine the effect of the COVID-19 pandemic on the delivery of care for thoracic surgical patients at an urban medical center.
    UNASSIGNED: A retrospective analysis of all thoracic surgical cases from May 1, 2019, to December 31, 2020, was conducted. Demographic characteristics, preoperative surgical indications, procedures, final pathologic diagnoses, and perioperative outcomes were recorded. A census of operative cases, relevant ancillary services, and outpatient thoracic clinics were obtained from our institutional database.
    UNASSIGNED: Six hundred nineteen cases were included in this study (329 pre-COVID-19 and 290 COVID-19, representing an 11.8% reduction). There were no differences in type of thoracic procedures or perioperative outcomes among the 2 cohorts. Prolonged reduction of thoracic surgical cases (50% of baseline) during the first half of the COVID-19 period was followed by a resurgence of surgical volumes to 110% of baseline in the second half. A similar incidence of cases were performed for oncologic indications during the first half whereas more benign cases were performed in the second half, coinciding with the launch of our robotic foregut surgery program. After undergoing surgery during the pandemic, none of our patients reported COVID-19 symptoms within 14 days of discharge.
    UNASSIGNED: During the initial surge of COVID-19, while there was temporary closure of operative services, our health care system continued to provide safe care for thoracic surgery patients, particularly those with oncologic indications. Since phased reopening, we have experienced a rebound of surgical volume and case mix, ultimately mitigating the initial negative effect of the pandemic on delivery of thoracic surgical care.
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  • 文章类型: Journal Article
    背景:关于SARS-CoV-2感染中的病毒传播,定义活病毒脱落的持续时间是重要的,背景是目前全世界努力修订隔离政策和确定传染性持续时间。
    方法:在这篇综述中,我们搜索了包括Medline和google学者在内的数据库,以查找2020年1月至2022年1月之间发表的研究文章。我们包括病例报告,案例系列,横截面,队列,和随机对照试验,报道了活的SARS-CoV-2病毒脱落的持续时间。在评估纳入标准后,共纳入32篇(2721例患者)。
    结果:该综述显示,成功分离病毒的最后一天的中位数为11(8.5-14.595%CI),20(9.0-57.595CI),一般人群为20(9.0-10395CI),危重患者和免疫功能低下的个体,分别,与延长的病毒脱落之间的显著关联,疾病严重程度(P值0.024)和免疫抑制状态(P值0.023)。可培养病毒的CTv相应的较高临界值在26.25和34.00之间(95%置信区间),中位数为30.5,当危重(25.0-37.3795CI)和免疫受损患者(20.0-37.8295CI)被排除时,观察到更高的值。这一偏差分别没有统计学意义(P-值0.997和0.888).
    结论:我们的综述强调,仅在康复患者中重复SARS-CoV-2病毒RNA测试对于确定感染性并不重要,并强调基于宿主因素和组合症状和基于测试的方法的分离决策的个性化,后者受益于最近引入的快速抗原测试的大部分相关性。我们在审查中的发现也反对最近的CDC指南,关于缩短可传播病毒最后几天的隔离时间,因此,在修订此类协议时应谨慎行事。
    BACKGROUND: The duration of viable viral shedding is important to be defined in regards of viral transmission in SARS-CoV-2 infection with the backdrop of the current worldwide effort for revising isolation polices and establishing the duration of infectiousness.
    METHODS: In this review we searched databases including Medline and google scholar for research articles published between January 2020 and January 2022. We included case reports, case series, cross sectional, cohort, and randomized control trials that reported the duration of shedding of viable SARS-CoV-2 virus. After evaluating the criteria for inclusion, 32 articles (2721 patients) were included.
    RESULTS: This review showed that the median for the last day of successful viral isolation was 11 (8.5-14.5 95% CI) , 20 (9.0-57.5 95 %CI), 20 (9.0-103 95 %CI) for the general population, critical patients and immunocompromised individuals, respectively, with significant association between prolonged viral shedding, disease severity (P-Value 0.024) and immunosuppressive status (P-Value 0.023).The corresponding higher cutoff of CTv to culturable virus ranged between 26.25 and 34.00 (95% confidence interval) with median of 30.5, and higher values were observed when critical (25.0-37.37 95 %CI) and immunocompromised patients (20.0-37.82 95 %CI) have been excluded, this deviation did not represent a statistical significance (P-Value 0.997 and 0.888) respectively.
    CONCLUSIONS: Our review highlights that repeating SARS-CoV-2 viral RNA test solely in recovering patients has no importance in determining infectivity and emphasizes the individualization of de-isolation decisions based on the host factors and a combined symptom and testing-based approaches with the later benefiting most of correlation with recently introduced rapid antigen test. Our finding in the review also opposes the most recent CDC Guidance on shortening isolation duration in term of the last days of viable transmissible virus, therefore caution should be considered when revising such protocols.
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  • 文章类型: Journal Article
    癌症的发展通常是由于各种失调的分子机制影响可以控制正常细胞生长的基因而发生的。信号转导和转录激活因子3(STAT3)通路,一旦异常激活,可以通过调节许多致癌基因的转录来促进致癌作用。
    这里,我们使用不同的肿瘤细胞系和异种移植小鼠模型,通过调节致癌STAT3信号通路,评估了fangchinoline(FCN)对减轻肿瘤生长和存活的影响.
    为了评估FCN对STAT3级联的作用,蛋白质水平通过蛋白质印迹分析和电泳迁移率变化分析(EMSA)进行分析.通过免疫细胞化学检测STAT3的易位。此后,通过GSH/GSSG测定和H2DCF-DA测量FCN诱导的ROS。使用Western印迹分析和流式细胞术分析FCN诱导的细胞凋亡以进行各种测定。最后,在骨髓瘤模型中评估了FCN的体内抗癌作用.
    我们注意到FCN消除了STAT3和上游信号(JAK1/2和Src)的蛋白质表达水平。此外,FCN还减弱了STAT3的DNA结合能力及其易位到细胞核中。它改变了上游信号蛋白的水平,增加SHP-1水平,并诱导U266细胞大量凋亡。FCN还促进了肿瘤细胞中活性氧(ROS)的产生增加,并改变了GSSG/GSH比率。此外,FCN在临床前骨髓瘤模型中有效地消除肿瘤进展和STAT3激活。
    总的来说,这项研究表明,FCN可能具有改变异常STAT3激活和诱导恶性细胞细胞死亡的巨大潜力,并通过促氧化剂依赖性分子机制抑制癌症的发病和生长.
    The development of cancer generally occurs as a result of various deregulated molecular mechanisms affecting the genes that can control normal cellular growth. Signal transducer and activator of transcription 3 (STAT3) pathway, once aberrantly activated can promote carcinogenesis by regulating the transcription of a number of oncogenic genes.
    Here, we evaluated the impact of fangchinoline (FCN) to attenuate tumor growth and survival through modulation of oncogenic STAT3 signaling pathway using diverse tumor cell lines and a xenograft mouse model.
    To evaluate the action of FCN on STAT3 cascade, protein levels were analyzed by Western blot analysis and electrophoretic mobility shift assay (EMSA). Translocation of STAT3 was detected by immunocytochemistry. Thereafter, FCN-induced ROS was measured by GSH/GSSG assay and H2DCF-DA. FCN-induced apoptosis was analyzed using Western blot analysis and flow cytometry for various assays. Finally, anti-cancer effects of FCN in vivo was evaluated in a myeloma model.
    We noted that FCN abrogated protein expression levels of STAT3 and upstream signals (JAK1/2 and Src). In addition, FCN also attenuated DNA binding ability of STAT3 and its translocation into the nucleus. It altered the levels of upstream signaling proteins, increased SHP-1 levels, and induced substantial apoptosis in U266 cells. FCN also promoted an increased production of reactive oxygen species (ROS) and altered GSSG/GSH ratio in tumor cells. Moreover, FCN effectively abrogated tumor progression and STAT3 activation in a preclinical myeloma model.
    Overall, this study suggests that FCN may have a tremendous potential to alter abnormal STAT3 activation and induce cell death in malignant cells along with causing the suppression of pathogenesis and growth of cancer through a pro-oxidant dependent molecular mechanism.
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