BACKGROUND & AIMS: :Near field scanning optical microscopy exploiting differential interference contrast enhancement is demonstrated. Beam splitting in the near field region is implemented using a dual color probe based on plasmonic color sorter idea. This provides the ability to illuminate two neighboring points on the sample simultaneously. It is shown that by modulating the two wavelengths employed in exciting such a probe, phase difference information can be retrieved through measuring the near field photoinduced force at the difference of the two modulation frequencies. This difference in frequency is engineered to correspond to the first resonant frequency of the cantilever, resulting in improved SNR, and sensitivity. The effect of both topographical and material changes in the proposed near field differential interference (NFDIC) technique are investigated for CNT and silica samples. This method is a promising technique for high contrast and high spatial resolution microscopy.

背景与目标： ：展示了利用差分干涉对比增强的近场扫描光学显微镜。使用基于等离激元颜色分类器思想的双色探针实现近场区域中的光束分离。这提供了同时照射样品上两个相邻点的能力。示出了通过调制在激发这样的探针中使用的两个波长，可以通过在两个调制频率的差处测量近场光感应力来检索相差信息。将该频率差设计为与悬臂的第一共振频率相对应，从而提高了SNR和灵敏度。对于碳纳米管和二氧化硅样品，研究了拟议的近场微分干涉（NFDIC）技术中形貌和材料变化的影响。该方法是用于高对比度和高空间分辨率显微镜的有前途的技术。

BACKGROUND & AIMS: :A recently developed multiple-beam interference microscopic technique has been used to visualize submicroscopic structures of Entamoeba histolytica and their movements in applied external electric fields. The movements were videorecorded and it was found that at low current (120 microA) pseudopods are filled with hyaline ectoplasm. At slightly higher current (about 150 microA), the amoeba stops extending the pseudopods and loosens its attachment to the surface. At higher currents (200 microA), it forms a cyst and remains immobile for a time. Before this stage is reached a narrow ring is formed around the nucleus due to alterations in the proteins to protect it.

背景与目标： ：最近开发的多光束干涉显微技术已用于可视化组织变形虫亚显微结构及其在外加电场中的运动。对运动进行了录像，发现在低电流（120微安）下，假足充满了透明的种质。在稍高的电流（约150微安）下，变形虫停止延伸假足，并使其与表面的附着变松。在更高的电流（200微安）下，它会形成一个囊肿，并在一段时间内保持静止。在此阶段之前，由于保护蛋白质的改变，在核周围形成了一个狭窄的环。

BACKGROUND & AIMS: :This report provides a brief tutorial on the underlying physical forces that lead to interference with hearing aids and assistive listening devices, as well as measurement issues and possible solutions to the problem.

背景与目标： ：此报告提供了简短的教程，介绍了导致助听器和辅助听力设备受到干扰的潜在物理力，以及测量问题和对该问题的可能解决方案。

BACKGROUND & AIMS: :Although natural images often include discordant information about object boundaries, the majority of research on texture segmentation has involved variation along a single dimension, e.g. colour, orientation, size. In this study, we examined orientation-based texture segmentation in the presence and absence of task-irrelevant colour variation. Previously, it had been shown that orientation-based texture segmentation was impaired if the elements, normally of one colour, were randomly allocated one of two colours (Morgan et al, 1992 Proceedings of the Royal Society of London, Series B 248 291-295). We found that this interference disappeared, however, when the spatial pattern of the colour variation was regular, as opposed to random, and when the elements were randomly positioned. We consider four models of how relevant and irrelevant texture information might combine to produce the interference effect, with special regard to these new findings. None of the models could account for the dependency of the interference effect on the spatial arrangement of colour and orientation in the texture. We suggest that inter-element separation and spatial-frequency selectivity are critical variables in the interference effect.

背景与目标： ：虽然自然图像通常包含有关对象边界的不一致信息，但是大多数纹理分割研究都涉及沿单个维度的变化，例如颜色，方向，大小。在这项研究中，我们在存在和不存在与任务无关的颜色变化的情况下，检查了基于方向的纹理分割。以前的研究表明，如果通常将一种颜色的元素随机分配为两种颜色中的一种，则基于方向的纹理分割会受到损害（Morgan等人，《伦敦皇家学会学报，1992年》，系列B 248 291-295 ）。我们发现，当颜色变化的空间模式是规则的而不是随机的并且元素是随机放置时，这种干扰消失了。我们考虑了四个模型，这些模型将相关和不相关的纹理信息如何组合以产生干扰效果，并特别注意这些新发现。这些模型都无法说明干涉效应对纹理的颜色和方向的空间排列的依赖性。我们建议元素间分离和空间频率选择性是干扰效应中的关键变量。

BACKGROUND & AIMS: OBJECTIVE:To examine the relationships between a new scale, the Eating and Body Image Disturbances Academic Interference Scale (EBIDAIS), and measures of eating disturbance, body image, and academic achievement. METHOD:One thousand five hundred eighty-four college undergraduates completed the measures in an online survey and were awarded class credit for their participation. Measures included the Eating Disorder Inventory Bulimia, Drive for Thinness, Body Dissatisfaction, and Perfectionism subscales. Grade point average (GPA) was also reported. RESULTS:Academic interference and GPA were significantly correlated, indicating that higher interference scores were related to lower GPA. EBIDAIS was also significantly correlated with drive for thinness, bulimia, and body dissatisfaction, but was not significantly associated with perfectionism. The correlation between interference and GPA was substantially higher for a subsample of individuals who scored in the elevated range on eating and body dissatisfaction. CONCLUSION:Academic interference may be a relatively unexamined, but potentially important, outcome for individuals who experience eating problems and body image disturbance.

背景与目标： 目的：研究一种新的量表，饮食和身体图像干扰学术干扰量表（EBIDAIS）与饮食干扰，身体图像和学习成绩之间的关系。
方法：154名大学生完成了在线调查中的各项措施，并因参与而获得了课程信用。措施包括饮食失调清单贪食症，追求瘦身，身体不满和完美主义分量表。还报告了平均绩点（GPA）。
结果：学术干扰与GPA显着相关，表明较高的干扰评分与较低的GPA相关。 EBIDAIS与瘦弱，贪食症和身体不满的动机也有显着相关性，但与完美主义没有显着相关性。对于饮食和身体不满意评分在较高范围内的个人子样本，干扰与GPA之间的相关性显着更高。
结论：对于经历饮食问题和身体形象障碍的个人，学术干扰可能是相对未经检查的，但可能很重要。

BACKGROUND & AIMS: BACKGROUND & AIMS:Oestrogen and oestrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS:Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate half maximal inhibitory concentration values. To dissect how 17β-estradiol interferes with phases of hepatitis C virus life cycle, its effects were measured on the hepatitis C virus pseudo-particle system (viral entry), the subgenomic replicon N17/JFH1 and the replicon cell line Huh7-J17 (viral replication). Finally, in a dual-step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. RESULTS:Progesterone and testosterone showed no inhibitory effect on hepatitis C virus; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β-estradiol inhibited infection by 64%-67% (IC50 values 140-160 nmol/L). Fulvestrant reverted the inhibition by 17β-estradiol in a dose-dependent manner. 17β-estradiol exerted only a slight inhibition (<20%) on hepatitis C virus pseudo-particles, and had no effect on cells either transiently or stably (Huh7-J17 cells) expressing the N17/JFH1 replicon. In the dual-step infection model, a significant half maximal inhibitory concentration decline occurred between primary (134 nmol/L) and secondary (100 nmol/L) infections (P=.02), with extracellular hepatitis C virus RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. CONCLUSIONS:17β-estradiol inhibits hepatitis C virus acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the hepatitis C virus life cycle.

背景与目标： 背景与目的：雌激素和雌激素介导的信号转导机制尚不完全清楚，可预防丙型肝炎病毒。我们旨在确定丙型肝炎病毒生命周期的哪个阶段受到雌激素的影响。
方法：将感染JFH1病毒（基因型2a）的Huh7细胞暴露于脱氢表雄酮，睾丸激素，孕酮和17β-雌二醇（经/不经其受体拮抗剂氟维司汀测试）。建立剂量反应曲线以计算最大抑制浓度的一半。为了剖析17β-雌二醇如何干扰丙型肝炎病毒生命周期的各个阶段，测量了其对丙型肝炎病毒假颗粒系统（病毒进入），亚基因组复制子N17 / JFH1和复制子细胞系Huh7-J17（病毒）的影响。复制）。最后，在两步感染模型中，从暴露于激素的感染细胞中收集的感染上清液被用于感染幼稚细胞。
结果：孕酮和睾丸激素对丙型肝炎病毒无抑制作用。脱氢表雄酮仅具有轻度抑制作用。相比之下，17β-雌二醇可将感染抑制64％-67％（IC50值为140-160nmol / L）。氟韦斯特兰以剂量依赖的方式逆转了17β-雌二醇的抑制作用。 17β-雌二醇仅对C型肝炎病毒假颗粒产生轻微抑制作用（<20％），对表达N17 / JFH1复制子的细胞（瞬时或稳定）（Huh7-J17细胞）没有影响。在双步感染模型中，主要（134nmol / L）和继发性（100nmol / L）感染（P = .02）之间出现最大抑制浓度显着降低一半（P = .02），细胞外丙型肝炎病毒RNA和感染力降低与细胞内对应物相比，程度更高。
结论：17β-雌二醇通过其细胞内受体抑制丙型肝炎病毒，主要干扰丙型肝炎病毒生命周期的后期阶段（组装/释放）。

BACKGROUND & AIMS: :Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma with poor prognosis. Its hallmark is the translocation t(11:14)q (13;32), leading to overexpression of cyclin D1, a positive regulator of the cell cycle. As cyclin D1 up-regulation is not sufficient for inducing malignant transformation, we combined DNA microarray and RNA interference (RNAi) approaches to identify novel deregulated genes involved in the progression of MCL. DNA microarray analysis identified 46 genes specifically up-regulated in MCL compared with normal B cells; 20 of these were chosen for further studies based on their cellular functions, such as growth and proliferation. The Granta 519 cell line was selected as an MCL in vitro model, to set up the RNAi protocol. To confirm the functionality of overexpression of the 20 disease-associated genes, they were knocked down using small interfering RNAs (siRNAs). In particular, knockdown of 3 genes, encoding the hepatoma-derived growth factor related protein 3 (HDGFRP3), the frizzled homolog 2 (FZD2), and the dual specificity phosphatase 5 (DUSP5), induced proliferative arrest in Granta 519 MCL cells. These genes emerged as functionally associated in MCL, in relation to growth and survival, and interfering with their function would increase insight into lymphoma growth regulation, potentially leading to novel clinical intervention modalities.

背景与目标： ：套细胞淋巴瘤（MCL）是非霍奇金淋巴瘤，预后较差。它的标志是易位t（11:14）q（13; 32），导致细胞周期蛋白D1（细胞周期的正向调节剂）的过表达。由于细胞周期蛋白D1的上调不足以诱导恶性转化，因此我们结合了DNA微阵列和RNA干扰（RNAi）方法来鉴定参与MCL进展的新型失调基因。 DNA微阵列分析鉴定出与正常B细胞​​相比在MCL中特异性上调的46个基因；根据它们的细胞功能（例如生长和增殖），选择了其中的20种进行进一步研究。选择Granta 519细胞系作为MCL体外模型，以建立RNAi方案。为了确认20种与疾病相关的基因过表达的功能，使用小型干扰RNA（siRNA）将它们敲低了。特别是敲除3个编码肝癌衍生的生长因子相关蛋白3（HDGFRP3），卷曲的同源物2（FZD2）和双重特异性磷酸酶5（DUSP5）的基因，可在Granta 519 MCL细胞中诱导增殖性停滞。这些基因在MCL中以与生长和存活有关的功能出现，并且干扰它们的功能将增加对淋巴瘤生长调节的了解，可能导致新的临床干预方式。

BACKGROUND & AIMS: :Exosomes are naturally occurring extracellular vesicles released by most mammalian cells in all body fluids. Exosomes are known as key mediators in cell-cell communication and facilitate the transfer of genetic and biochemical information between distant cells. Structurally, exosomes are composed of lipids, proteins, and also several types of RNAs which enable these vesicles to serve as important disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Recently, increasing attention has been focused on exosomes for the delivery of drugs, including therapeutic recombinant proteins, to various target tissues. Exosomes are also promising vehicles for the delivery of microRNAs and small interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as well as inefficient tissue specificity of currently available delivery strategies. This review highlights the most recent accomplishments and trends in the use of exosomes for the delivery of drugs and therapeutic RNA molecules.

背景与目标： ：外来体是大多数哺乳动物细胞在所有体液中释放的天然存在的细胞外囊泡。外来体被称为细胞-细胞通讯中的关键介体，可促进远距离细胞之间遗传和生化信息的转移。在结构上，外泌体由脂质，蛋白质以及几种类型的RNA组成，这些RNA使这些囊泡可以用作重要的疾病生物标记。此外，由于外来体相对于常规的递送系统具有多种优势，因此已成为新型的药物和基因递送工具。近来，越来越多的注意力集中在用于将药物，包括治疗性重组蛋白，递送至各种靶组织的外泌体。外来体也是用于递送微小RNA和小的干扰RNA的有希望的载体，其通常由于这些RNA的快速降解以及当前可用的递送策略的低效率的组织特异性而受到阻碍。这篇综述着重介绍了使用外泌体递送药物和治疗性RNA分子的最新成就和趋势。

BACKGROUND & AIMS: AIMS:A switch in gene expression from MAT1A to MAT2A was found in liver cancer, suggesting that MAT2A plays an important role in facilitating cancer growth. MAT2A is an interesting target for antineoplastic therapy. The molecular mechanisms of silencing MAT2A by RNA interference inhibited cell growth and induced apoptosis in hepatoma cells was studied. METHODS:We investigated the effects of MAT2A on S-adenosyl-methionine (SAM) production, cell growth and apoptotic cell death in hepatoma cell lines (Bel-7402, HepG2, and Hep3B) using an RNA interference approach. RESULTS:The treatment of three hepatoma cell lines with small interfering RNA (siRNA) targeting to the MAT2A gene resulted in reducing the MAT II activity, facilitating SAM production, increasing SAM : SAH ratio, inhibiting cell growth and inducing cell apoptosis in hepatoma cells. In addition, silencing MAT2A gene resulted in the stimulation of MAT1A mRNA production, which was blocked by 3-deazaadenosine and l-ethionine, but not d-ethionine, suggesting that such effect was specific and mediated by upregulation of SAM level and SAM : S-adenosylethionine (SAH) ratio. CONCLUSION:Silencing MAT2A by sequence-specific small interfering RNA caused a switch of MAT gene expression from MAT2A to MAT1A, which led the content of SAM to change to a higher steady-state level that resulted in the inhibition of cell growth and the induction of apoptotic cell death in human hepatoma cells. These results also suggested that MAT2A may hold potential as a new target for liver cancer gene therapy.

背景与目标： 目的：在肝癌中发现了从MAT1A到MAT2A的基因表达转换，这表明MAT2A在促进癌症生长中起着重要作用。 MAT2A是抗肿瘤治疗的一个有趣目标。研究了RNA干扰沉默MAT2A抑制肝癌细胞生长并诱导其凋亡的分子机制。
方法：我们使用RNA干扰方法研究了MAT2A对肝癌细胞系（Bel-7402，HepG2和Hep3B）中S-腺苷甲硫氨酸（SAM）的产生，细胞生长和凋亡细胞死亡的影响。
结果：用靶向MAT2A基因的小干扰RNA（siRNA）处理三种肝癌细胞系可降低MAT II活性，促进SAM的产生，增加SAM：SAH的比例，抑制细胞生长并诱导肝癌细胞的细胞凋亡。此外，沉默MAT2A基因可刺激MAT1A mRNA的产生，该刺激被3-deazaadenosine和l-ethionine阻断，但未被d-ethionine阻断，这表明这种作用是特异的，并由SAM水平和SAM：S的上调介导。 -腺苷乙硫氨酸（SAH）比率。
结论：通过序列特异性小干扰RNA沉默MAT2A，导致MAT基因表达从MAT2A向MAT1A的转换，导致SAM的含量改变为较高的稳态水平，从而抑制了细胞的生长并诱导了细胞凋亡。人肝癌细胞中的凋亡细胞死亡。这些结果还表明，MAT2A可能具有作为肝癌基因治疗的新靶标的潜力。

BACKGROUND & AIMS: :Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds the receptors in the APC/T cell synapse and causes increased proliferation of T cells and a cytokine storm syndrome in vivo. Exposure to the toxin can be lethal and cause significant pathology in humans. The lack of effective therapies for SEB exposure remains an area of concern, particularly in scenarios of acute mass casualties. We hypothesized that blockade of the T cell costimulatory signal by the CTLA4-Ig synthetic protein (abatacept) could prevent SEB-dependent pathology. In this article, we demonstrate mice treated with a single dose of abatacept 8 h post SEB exposure had reduced pathology compared with control SEB-exposed mice. SEB-exposed mice showed significant reductions in body weight between days 4 and 9, whereas mice exposed to SEB and also treated with abatacept showed no weight loss for the duration of the study, suggesting therapeutic mitigation of SEB-induced morbidity. Histopathology and magnetic resonance imaging demonstrated that SEB mediated lung damage and edema, which were absent after treatment with abatacept. Analysis of plasma and lung tissues from SEB-exposed mice treated with abatacept demonstrated significantly lower levels of IL-6 and IFN-γ (p < 0.0001), which is likely to have resulted in less pathology. In addition, exposure of human and mouse PBMCs to SEB in vitro showed a significant reduction in levels of IL-2 (p < 0.0001) after treatment with abatacept, indicating that T cell proliferation is the main target for intervention. Our findings demonstrate that abatacept is a robust and potentially credible drug to prevent toxic effects from SEB exposure.

背景与目标： ：葡萄球菌肠毒素B（SEB）是一种细菌超抗原，可与APC / T细胞突触中的受体结合，并在体内引起T细胞增殖增加和细胞因子风暴综合症。接触毒素可能致命，并在人类中引起重大病理。缺乏有效的SEB暴露疗法仍然是一个令人关注的领域，特别是在大量人员伤亡的情况下。我们假设CTLA4-Ig合成蛋白（abatacept）阻断T细胞共刺激信号可以预防SEB依赖的病理。在本文中，我们证明与暴露于对照SEB的小鼠相比，SEB暴露8 h后用单剂量的abatacept治疗的小鼠的病理学降低。暴露于SEB的小鼠在第4天到第9天之间体重显着降低，而暴露于SEB并接受阿巴西普治疗的小鼠在研究期间未见体重减轻，这表明SEB所致发病率的治疗性缓解。组织病理学和磁共振成像显示SEB介导的肺损伤和水肿，在用abatacept治疗后不存在。对接受abatacept治疗的SEB暴露小鼠的血浆和肺组织的分析表明，IL-6和IFN-γ的水平显着降低（p <0.0001），这可能导致较少的病理。另外，人和小鼠PBMC体外暴露于SEB时，用abatacept治疗后IL-2水平显着降低（p <0.0001），这表明T细胞增殖是干预的主要目标。我们的发现表明，abatacept是一种强大的且可能可信的药物，可防止SEB暴露引起的毒性作用。

BACKGROUND & AIMS: Objectives:Drug-laboratory test interactions (DLTIs) are one of the major sources of laboratory errors. Calcium dobesilate (CaD) interference on serum creatinine testing is a widespread problem that has long been ignored in China. A national EQA-based survey was launched to investigate the current status of CaD interference on creatinine routine methods used in China and enhance the education of CaD interference in clinical laboratories. Methods:A descriptive survey was developed to characterize the status quo of Chinese laboratory professionals' cognition to CaD interference. Four of survey samples which were spiked with/without interference additive were shipped to 175 participant laboratories. The target reference values from a reference measurement procedure were compared against the results from participating laboratories to evaluate the CaD interference on serum creatinine measurements using enzymatic method or Jaffé method. Results:The lack of knowledge of DLTIs and the barriers to collect information from pharmacological and laboratory data systems had become the main problems on implementing DLTIs education in China. A significant negative influence of CaD on enzymatic method was observed regardless of measurement platforms. Jaffé method was generally free from interaction with CaD but showed poor precision and accuracy at low creatinine concentrations. Conclusions:More efforts should be made to enhance the education of DLTIs in clinical laboratories in China.

背景与目标： 目的：药物-实验室测试相互作用（DLTI）是实验室错误的主要来源之一。苯磺酸钙（CaD）对血清肌酐检测的干扰是一个普遍的问题，在中国长期以来一直被忽略。开展了一项基于全国EQA的调查，以调查CaD干扰在中国使用的肌酐常规方法的现状，并加强对临床实验室中CaD干扰的教育。
方法：进行描述性调查，以表征中国实验室专业人员对CaD干扰的认知状况。掺加或不掺入干扰添加剂的四个调查样品被运到175个参与实验室。将来自参考测量程序的目标参考值与参与实验室的结果进行比较，以评估CaD对使用酶法或Jaffé方法进行的血清肌酐测量的干扰。
结果：缺乏对DLTIs的了解以及从药理学和实验室数据系统收集信息的障碍已成为在中国实施DLTIs教育的主要问题。无论使用何种测量平台，都可以观察到CaD对酶法的显着负面影响。 Jaffé方法通常不与CaD相互作用，但在低肌酐浓度下显示出较差的精密度和准确性。
结论：应加大力度加强我国临床实验室对DLTIs的教育。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Avian influenza virus H5N1 causes widespread infection in the birds and human respiratory tract, but existing vaccines and drug therapy are of limited value. Here we show that small interfering RNAs (siRNAs) specific for conserved regions of the viral genome can potently inhibit influenza virus production in cell lines, embryonated chicken eggs and BALB/c mice. siRNA expression plasmid pBabe-Super was chosen in the study, which directed the synthesis of small interfering RNAs in cells. The inhibition depended on the presence of a functional antisense strand in the small interfering RNA duplex, suggesting that viral mRNA is the target of RNA interference (RNAi). Among the three small interfering RNA expression plasmids we designed, we found that small interfering RNA for nucleocapsid protein (NP) had a specific effect in inhibiting the accumulation of RNAs in infected cells because of a critical requirement for newly synthesized nucleocapsid proteins in avian influenza viral RNA transcription and replication. The findings reveal that newly synthesized nucleocapsid, polymerase A (PA) and polymerase B1 (PB1) proteins are required for avian influenza virus transcription and replication and provide a basis for the development of small interfering RNAs as prophylaxis and therapy for avian influenza infection in birds and humans.

背景与目标： ：H5N1禽流感病毒在鸟类和人类呼吸道中引起广泛感染，但现有的疫苗和药物疗法的价值有限。在这里，我们显示了特异性针对病毒基因组保守区的小干扰RNA（siRNA）可以有效抑制细胞系，胚胎鸡卵和BALB / c小鼠中的流感病毒产生。在研究中选择了siRNA表达质粒pBabe-Super，该质粒指导细胞中小的干扰RNA的合成。抑制取决于小干扰RNA双链体中功能性反义链的存在，表明病毒mRNA是RNA干扰（RNAi）的靶标。在我们设计的三种小分子干扰RNA表达质粒中，我们发现对于核衣壳蛋白（NP）的小分子干扰RNA在抑制感染细胞中RNA的积累方面具有特定作用，因为对禽流感病毒中新合成的核衣壳蛋白的关键需求RNA转录和复制。研究结果表明，新合成的核衣壳，聚合酶A（PA）和聚合酶B1（PB1）蛋白是禽流感病毒转录和复制所必需的，并为开发小干扰RNA作为预防和治疗禽流感的方法奠定了基础。和人类。

BACKGROUND & AIMS: Objectives:Hemoglobin (Hb) variants remain an important cause of erroneous HbA1c results. We present an approach to overcome the interference of Hb variants on HbA1c measurements using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods:Samples containing or not containing Hb variants were analyzed for HbA1c using an MALDI-TOF MS system (QuanTOF) and a boronate affinity comparative method (Ultra2). For QuanTOF, two sets of HbA1c values were obtained through α- and β-chain glycation. Results:A robust correlation between the glycation degrees of the α- and β-chains was found, and HbA1c values derived from α- and β-chain glycation correlated well with the Ultra2 results. Statistically significant differences (p<0.01) were found for all the Hb variants tested. When using the conventional β-chain glycation to determine HbA1c, clinically significant differences were only found among samples containing β-chain variants detected by QuanTOF (i.e., Hb J-Bangkok, Hb G-Coushatta, and Hb G-Taipei). In contrast, based on α-chain glycation, no clinically significant differences were found for these three variants. Conclusions:In addition to conventional β-chain glycation, α-chain glycation can be used to calculate HbA1c values. The interference of Hb variants on HbA1c quantification can be overcome by employing the glycation of the globin chain without a genetic variant to estimate HbA1c values.

背景与目标： 目的：血红蛋白（Hb）变异仍然是导致错误的HbA1c结果的重要原因。我们提出了一种使用基质辅助激光解吸/电离飞行时间质谱仪（MALDI-TOF MS）来克服Hb变体对HbA1c测量的干扰的方法。
方法：使用MALDI-TOF MS系统（QuanTOF）和硼酸酯亲和比较方法（Ultra2）对包含或不包含Hb变体的样品进行HbA1c分析。对于QuanTOF，通过α和β链糖基化获得了两组HbA1c值。
结果：发现α链和β链的糖基化程度之间存在强相关性，并且α链和β链糖基化得到的HbA1c值与Ultra2结果具有很好的相关性。在所有测试的Hb变体中发现统计学上的显着差异（p <0.01）。当使用常规的β链糖基化来确定HbA1c时，仅在包含通过QuanTOF检测到的β链变体的样品（即Hb J-Bangkok，Hb G-Coushatta和Hb G-Taipei）中发现临床上的显着差异。相反，基于α链糖基化，这三个变体没有发现临床上的显着差异。
结论：除常规的β链糖基化外，α链糖基化还可用于计算HbA1c值。 Hb变体对HbA1c定量的干扰可以通过不带遗传变体的球蛋白链糖基化来估计HbA1c值来克服。

BACKGROUND & AIMS: :Five monoclonal antibodies (MAbs) directed against antigenic domains on thyroglobulin (Tg) not recognized by most anti-Tg human autoantibodies (aAbs) have been used to develop an improved IRMA for serum Tg with a limit of detection of 0.2 micrograms/L. Samples are incubated for 3 h in tubes coated with four anti-Tg MAbs. After washing, the tubes are incubated with the tracer MAb for 20 h at room temperature. Dilution and reproducibility tests demonstrated assay reliability. Tests performed on samples with (n = 361) or without (n = 283) aAbs showed that the TG IRMA Pasteur is largely independent of the marked interference generally caused by aAbs. These results were confirmed with an extended population of 2759 samples. For a cutoff of 1 micrograms/L, sensitivity and specificity were 0.97 and 1, respectively, in a follow-up of differentiated thyroid carcinoma in patients treated by total thyroidectomy.

背景与目标： ：针对甲状腺球蛋白（Tg）抗原域的五种单克隆抗体（MAb）已被大多数抗Tg人自身抗体（aAbs）识别，已被用于开发改良的IRMA用于血清Tg，检测限为0.2微克/升。将样品在涂有四种抗Tg MAb的试管中孵育3小时。洗涤后，将试管与示踪剂单克隆抗体在室温下孵育20小时。稀释和重现性测试证明了测定的可靠性。对有（n = 361）或没有（n = 283）aAbs的样品进行的测试表明，TG IRMA Pasteur在很大程度上与通常由aAbs引起的明显干扰无关。这些结果在2759个样本中得到了证实。对于全甲状腺切除术治疗的分化型甲状腺癌的随访，对于1微克/升的临界值，敏感性和特异性分别为0.97和1。