Noninvasive diagnostics

  • 文章类型: Journal Article
    胶质瘤由于其恶性性质,在肿瘤学中提出了重大挑战。积极的增长,频繁复发,以及血脑屏障造成的并发症.新兴研究揭示了肠道微生物群在影响健康和疾病中的关键作用。表明其对胶质瘤发病机制和治疗反应性的可能影响。本文就微生物群与胶质瘤从进展到侵袭的关系的现有证据和假设进行综述。通过讨论微生物群可能影响神经胶质瘤生物学的可能机制,本文为肿瘤靶向治疗和精准医学提供了新的途径.
    Gliomas pose a significant challenge in oncology due to their malignant nature, aggressive growth, frequent recurrence, and complications posed by the blood-brain barrier. Emerging research has revealed the critical role of gut microbiota in influencing health and disease, indicating its possible impact on glioma pathogenesis and treatment responsiveness. This review focused on existing evidence and hypotheses on the relationship between microbiota and glioma from progression to invasion. By discussing possible mechanisms through which microbiota may affect glioma biology, this paper offers new avenues for targeted therapies and precision medicine in oncology.
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  • 文章类型: Journal Article
    Givosiran是一种皮下给药,肝脏靶向RNA干扰(RNAi)治疗已被批准用于治疗急性肝性卟啉病(AHP)。AHP患者血浆同型半胱氨酸(高同型半胱氨酸血症)升高,据报道,吉沃西兰治疗可进一步增加某些患者的同型半胱氨酸水平。Givosiran治疗期间同型半胱氨酸升高的机制尚不清楚,但是据推测是由胱硫醚β-合酶(CBS)活性降低介导的,使用高半胱氨酸作为底物。基于液相色谱-串联质谱的测定适于测量循环CBS活性。使用从III期ENVISION研究中收集的血浆,测量CBS活性以直接评估其是否与givosiran治疗的患者的高半胱氨酸水平升高有关。吉沃西兰治疗后,CBS活性降低,高半胱氨酸和蛋氨酸水平与CBS活性成反比。服用含有维生素B6的补充剂后,CBS的辅因子,在试验期间的四名患者中,发现血浆CBS活性增加,反映了同型半胱氨酸水平的相应下降。这些结果支持以下假设:givosiran治疗后高半胱氨酸水平升高是由于CBS活性降低所致,补充维生素B6可通过增加CBS活性来降低高半胱氨酸水平。
    Givosiran is a subcutaneously administered, liver-targeted RNA interference (RNAi) therapeutic that has been approved for treating acute hepatic porphyria (AHP). Elevation in plasma homocysteine (hyperhomocysteinemia) has been reported in AHP patients, and treatment with givosiran has been reported to further increase homocysteine levels in some patients. The mechanism of homocysteine elevation during givosiran treatment is unknown, but has been hypothesized to be mediated by a reduction in activity of cystathionine β-synthase (CBS), which uses homocysteine as a substrate. A liquid chromatography-tandem mass spectrometry-based assay was adapted to measure circulating CBS activity. Using plasma collected from the Phase III ENVISION study, CBS activity was measured to directly evaluate whether it is associated with elevated homocysteine levels in givosiran-treated patients. CBS activity was reduced following givosiran treatment and both homocysteine and methionine levels were inversely correlated with CBS activity. Following administration of a supplement containing vitamin B6, a cofactor for CBS, in four patients during the trial, plasma CBS activity was found to increase, mirroring a corresponding decrease in homocysteine levels. These results support the hypothesis that elevated homocysteine levels following givosiran treatment result from a reduction of CBS activity and that vitamin B6 supplementation lowers homocysteine levels by increasing CBS activity.
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  • 文章类型: Journal Article
    尽管已经取得了重大进展,仍然缺乏可靠的传感器,能够无创监测胆红素和诊断黄疸是最常见的新生儿疾病,特别是在护理点(POC),从婴儿的血液采样伴随着严重的挑战和担忧。在这里,第一次,使用易于制造/使用的测定,我们证明了将姜黄素包埋在纸内用于唾液中胆红素的非侵入性光学监测的能力。开发的传感器对胆红素的高度选择性传感归因于蓝光照射下的胆红素光异构化,能选择性恢复胆红素诱导的姜黄素猝灭荧光。我们还制造了一个支持物联网的手持式光电阅读器,用于测量和量化我们传感器的荧光和颜色信号。通过使用我们开发的智能唾液传感器对18名黄疸婴儿的唾液进行临床分析,证明它可以在POC应用中广泛用于胆红素监测,因为其结果与唾液和血液中的参考方法之间具有良好的相关性。我们开发的传感器符合所有世界卫生组织的确认标准,使其成为一个非常有前途的传感器,用于黄疸的智能无创诊断和治疗监测。肝炎,和其他胆红素诱导的POC神经系统疾病。
    Even though significant advances have been made, there is still a lack of reliable sensors capable of noninvasively monitoring bilirubin and diagnosing jaundice as the most common neonatal disease, particularly at the point-of-care (POC) where blood sampling from infants is accompanied by serious challenges and concerns. Herein, for the first time, using an easy-to-fabricate/use assay, we demonstrate the capability of curcumin embedded within paper for noninvasive optical monitoring of bilirubin in saliva. The highly selective sensing of the developed sensor toward bilirubin is attributed to bilirubin photoisomerization under blue light exposure, which can selectively restore the bilirubin-induced quenched fluorescence of curcumin. We also fabricated an IoT-enabled hand-held optoelectronic reader to measure and quantify the fluorescence and color signals of our sensor. Clinical analysis on the saliva of 18 jaundiced infants by using our developed smart salivary sensor proved that it is amenable to be widely exploited in POC applications for bilirubin monitoring as there are good correlations between its results with those of reference methods in saliva and blood. Meeting all WHO\'s REASSURED criteria by our developed sensor makes it a highly promising sensor for smart noninvasive diagnosis and therapeutic monitoring of jaundice, hepatitis, and other bilirubin-induced neurologic diseases at the POC.
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  • 文章类型: Journal Article
    Acute compartment syndrome (ACS) is defined by a disorder of the microcirculation due to a persistent pathological pressure increase within a muscle compartment. The ischemia of the tissue leads to an initially reversible functional impairment and finally irreversible damage of the musculature, nerves and other structures. Based on the understanding of the pathophysiology, the current diagnostic concepts and treatment using the so-called dermatofasciotomy of the affected muscle compartments can be derived. In addition to the suspicion of a possible ACS based on the medical history of the patient, the findings of the clinical examination are decisive. This review article gives a summary of all the essential aspects of the diagnostics. In clinically uncertain cases and for monitoring, an objectification of the findings using instrument-based techniques is increasingly required. Nowadays, invasive needle pressure measurement is available; however, due to limited reliability, specificity and sensitivity, these measurements only represent an aid to decision guidance supporting or advising against the indications for dermatofasciotomy. The increasing demands on making a certain diagnosis and justification of a surgical intervention from a legal point of view, substantiate the numerous scientific efforts to develop noninvasive instrument-based diagnostics. These methods are based either on detection of increasing intracompartmental pressure or decreasing perfusion pressure and microcirculation. The various measurement principles are summarized in a lucid form.
    UNASSIGNED: Das akute Kompartmentsyndrom (ACS) ist definiert durch eine Mikrozirkulationsstörung bei andauernder, pathologischer Druckerhöhung innerhalb einer Muskelloge. Durch die Ischämie des Gewebes kommt es zu einer anfangs reversiblen Funktionseinschränkung und schließlich zur irreversiblen Schädigung der Muskulatur, Nerven und weiterer Strukturen. Durch das Verständnis für die Pathophysiologie lassen sich die aktuellen diagnostischen Konzepte und die Therapie mithilfe der sog. Dermatofasziotomie der betroffenen Muskellogen ableiten. Neben einem Verdacht auf ein mögliches ACS aufgrund der positiven Anamnese ist der klinische Untersuchungsbefund entscheidend. Dieser Übersichtsartikel fasst alle wesentlichen Aspekte der Diagnostik zusammen. In klinisch nicht eindeutigen Fällen und zum Monitoring wird eine Objektivierung des Befundes durch apparative Techniken zunehmend gefordert. Heute steht uns die invasive Nadeldruckmessung zur Verfügung, die jedoch aufgrund einer limitierten Reliabilität, Sensitivität und Spezifität lediglich eine Entscheidungshilfe für oder gegen die Indikation zur Kompartmentspaltung darstellt. Der zunehmende Anspruch der sicheren Diagnosestellung und Rechtfertigung einer chirurgischen Intervention aus juristischer Sicht begründet die vielzähligen wissenschaftlichen Anstrengungen, eine nichtinvasive, apparative Diagnostik zu entwickeln. Die Methoden basieren entweder auf der Messung eines steigenden Logendrucks oder eines sinkenden Perfusionsdrucks und Mikrozirkulation. Die unterschiedlichen Messprinzipien werden in übersichtlicher Form zusammengefasst.
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  • 文章类型: Journal Article
    血液采集和活检等侵入性方法通常用于检测肝肾功能,这是痛苦的,耗时,需要训练有素的人员,并且可能不容易让人们进行例行检查。肝脏和肾脏疾病的早期诊断可以预防严重症状,并确保更好地管理这些患者。呼吸和汗液分析等新兴方法已显示出作为疾病诊断的非侵入性方法的潜力。在众多标记中,氨通常被用作监测肝脏和肾脏功能的生物标志物。在这篇综述中,我们提供了对人体氨气产生和排出的见解,可能使用氨作为生物标志物和分析设备的不同疾病,如化学电阻气体传感器,用于非侵入性监测这种气体。审查还提供了对不同材料的理解,用于开发这种多功能传感器的掺杂剂和衬底。最后,讨论了当前的挑战和未来可能的趋势。
    Invasive methods such as blood collection and biopsy are commonly used for testing liver and kidney function, which are painful, time-consuming, require trained personnel, and may not be easily accessible to people for their routine checkup. Early diagnosis of liver and kidney diseases can prevent severe symptoms and ensure better management of these patients. Emerging approaches such as breath and sweat analysis have shown potential as non-invasive methods for disease diagnosis. Among the many markers, ammonia is often used as a biomarker for the monitoring of liver and kidney functions. In this review we provide an insight into the production and expulsion of ammonia gas in the human body, the different diseases that could potentially use ammonia as biomarker and analytical devices such as chemiresistive gas sensors for non-invasive monitoring of this gas. The review also provides an understanding into the different materials, doping agents and substrates used to develop such multifunctional sensors. Finally, the current challenges and the possible future trends have been discussed.
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  • 文章类型: Journal Article
    高光谱成像(HSI)无缝集成了成像和光谱学,同时捕获空间和光谱数据。随着在医学诊断中的广泛应用,HSI是一种非侵入性工具,可用于了解组织特征。生物组织的独特光谱曲线使HSI与传统显微镜在实现体内组织分析方面不同。尽管有潜力,现有的HSI技术面临着诸如对齐问题、低光吞吐量,和组织加热由于强烈的照明。本研究引入了一种创新的HSI系统,该系统具有无缝集成到常规光学仪器中的有源顺序带通照明。主要重点是使用多元线性回归分析动物组织样品中的氧合血红蛋白和脱氧血红蛋白饱和度。这种方法有望增强非侵入性医疗诊断。系统的一个关键特征,有源带通照明,有效防止组织过热,从而加强其对医疗应用的适用性。
    Hyperspectral Imaging (HSI) seamlessly integrates imaging and spectroscopy, capturing both spatial and spectral data concurrently. With widespread applications in medical diagnostics, HSI serves as a noninvasive tool for gaining insights into tissue characteristics. The distinctive spectral profiles of biological tissues set HSI apart from traditional microscopy in enabling in vivo tissue analysis. Despite its potential, existing HSI techniques face challenges such as alignment issues, low light throughput, and tissue heating due to intense illumination. This study introduces an innovative HSI system featuring active sequential bandpass illumination seamlessly integrated into conventional optical instruments. The primary focus is on analyzing oxyhemoglobin and deoxyhemoglobin saturation in animal tissue samples using multivariate linear regression. This approach holds promise for enhancing noninvasive medical diagnostics. A key feature of the system, active bandpass illumination, effectively prevents tissue overheating, thereby bolstering its suitability for medical applications.
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  • 文章类型: Journal Article
    唾液有可能在标准医学诊断中与针头一起工作。然而,旨在破译唾液与身体其他系统之间的生化交流的研究数量仍然非常有限。这项研究的目的是通过在温和条件下确定唾液pH值与血清生化参数之间的相关性来研究唾液与血清之间的流体相互作用。最终,使用唾液可以提供无压力的诊断工具,但更雄心勃勃的是,唾液的pH值可能是一种真正具有成本效益的筛查工具,可能会极大地受益于无法进入医疗保健和诊断实验室的地区。从随机选择的43名儿童(7-12岁)收集唾液和血液样本,住在吉达,没有肥胖和慢性或全身的身体和口腔疾病。进行了完整的血清生化分析,并且在收集时立即测量所有样品的唾液pH。使用单变量和多元线性回归模型研究唾液pH与血清生化参数之间的相关性。我们的结果表明,pH与总蛋白呈微弱的正相关,与尿素呈微弱的负相关。弱相关性表明存在更多的血清因子,需要使用逐步多元线性回归来研究其对pH的影响。多重线性模型计算的唾液pH值接近测量值,证明其使用血清参数预测唾液pH值的可能能力。回归模型使用血清生化物质对唾液pH值的成功预测反映了体液参数之间的显着相关性,并邀请更多的研究来阐明这些关系。
    Saliva has the potential to work alongside needles in standard medical diagnosis. Yet the number of studies aimed at deciphering the biochemical communication between saliva and the rest of the body\'s systems is still very limited. The aim of this study is to investigate the interfluid interaction between saliva and serum by determining the correlation between saliva pH and serum biochemical parameters under mild conditions. Ultimately, using saliva may provide a stress-free diagnostic tool, but more ambitiously, the pH of saliva could present a genuine cost-effective screening tool that may immensely benefit areas with limited access to health care and diagnostic labs. Saliva and blood samples were collected from 43 randomly selected children (7-12 years), living in Jeddah, free from obesity and chronic or systemic body and mouth diseases. A complete serum biochemical analysis was performed, and the salivary pH of all samples was measured immediately at the time of collection. The correlations between saliva pH and serum biochemical parameters were investigated using Univariate and multiple linear regression models. Our results showed that pH has a weak significant positive correlation with total protein and a negative weak significant correlation with urea. Weak correlations suggest the existence of more serum factors to be investigated for their effect on the pH using a stepwise multiple linear regression. The multiple linear models\' calculated saliva pH values were close to the measured values, demonstrating its possible capacity to predict saliva pH using serum parameters. The regression model\'s successful prediction of saliva pH using serum biochemicals reflects the significant correlations between the body fluids\' parameters and invites more research to elucidate these relationships.
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  • 文章类型: Journal Article
    背景:唾液外泌体分析提供了一种非侵入性和全面的方法,在口腔癌诊断和预后中具有潜在的应用。口腔癌的早期发现仍然是提高生活质量的关键问题,特别是对于消费烟草和有更大的患病风险的个人。目前的研究调查了唾液外泌体在筛查吸烟者口腔癌早期症状和转化方面的潜力。
    方法:三个研究组(非吸烟者作为对照,吸烟者作为高风险烟草消费者,和口腔癌)(n=120)通过动态光散射进行,和纳米粒子跟踪分析。对于分子表征,利用EXOCET和傅里叶变换红外光谱法。使用Western印迹评估外泌体表面蛋白CD63的表达。
    结果:唾液外泌体在对照组和烟草消费者之间表现出明显的大小差异。分化超出了外泌体大小,并包括浓度和生物分子组成的变化,通过FTIR筛选确定。与健康组相比,烟草消费者和口腔癌组显示出明显更大和更浓缩的外泌体。
    结论:我们的研究提供了强有力的证据,证明唾液外泌体的特性可以作为可靠的非侵入性生物标志物,用于区分烟草消费者与非吸烟者和口腔癌患者。我们的结果强调了基于外泌体的诊断在高危人群早期口腔癌检测中的潜力。烟草消费者外泌体的较大尺寸和较高浓度表明与从健康细胞到异常细胞的转化相关的细胞分泌物的早期变化。
    BACKGROUND: Salivary exosome analysis provides a noninvasive and comprehensive approach with potential applications in oral cancer diagnosis and prognosis. The early detection of oral cancer has remained a critical concern in enhancing the quality of life, especially for individuals who consume tobacco and are at greater risk of developing the disease. The current study investigates the potential of salivary exosomes in screening smokers for early signs and transformations of oral cancer.
    METHODS: Morphological characterization of salivary exosomes among three study groups (non-smokers as control, smokers as high-risk tobacco consumers, and Oral cancer) (n = 120) was carried out through dynamic light scattering, and nanoparticle tracking analysis. For molecular characterization, EXOCET and Fourier transform infrared spectroscopy methods were utilized. The expression of the exosomal surface protein CD63 was evaluated using Western blotting.
    RESULTS: Salivary exosomes exhibit noticeable differences in size between control group and tobacco consumers. The differentiation extended beyond exosome size and included variations in concentration and bio-molecular composition, as determined by FTIR screening. Tobacco consumers and oral cancer groups showed significantly larger and more concentrated exosomes compared to the healthy group.
    CONCLUSIONS: Our study provides strong evidence that the properties of salivary exosomes can serve as reliable noninvasive biomarkers for distinguishing tobacco consumers from non-smokers and oral cancer patients. Our results underscore the potential of exosome-based diagnostics in early oral cancer detection for high-risk individuals. The larger size and higher concentration of exosomes in tobacco consumers indicate early changes in cell secretions associated with the transformation from healthy to abnormal cells.
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  • 文章类型: Review
    目的:胶质母细胞瘤(GBM)是一种侵袭性原发性脑肿瘤,5年生存率低于5%。治疗反应评估可能是具有挑战性的,因为在临床上和在成像上模拟真实肿瘤进展的炎性假性进展。开发额外的非侵入性检测是至关重要的。在这篇文章中,作者回顾了可用于开发GBM液体活检的各种生物标志物,除了优势,局限性,未来的应用。此外,他们提出了一种潜在的液体活检设计,该设计基于靶向非肿瘤性细胞外囊泡的基于细胞外囊泡的液体活检.
    方法:作者通过检索PubMed,Scopus,和谷歌学者数据库。文章评估了生物标志物的类型,隔离方法,分析技术,和临床相关性。
    结果:最近的工作表明,血浆的液体活检,血,和/或CSF有望作为可用于诊断复发的非侵入性临床工具,评估治疗反应,并预测GBM患者的预后。GBM的液体活检主要集中在细胞外囊泡,无细胞肿瘤核酸,和全细胞分离物作为局灶性生物标志物。GBM肿瘤特征是通过分析肿瘤基因突变产生的,独特的RNA表达,以及代谢和蛋白质组学改变。液体活检捕获肿瘤异质性,识别可能无法通过手术活检标本检测到的GBM肿瘤的改变。最后,生物标志物负荷可用于评估GBM的治疗反应和复发。
    结论:液体活检为无侵入性手术监测GBM的治疗反应和复发提供了一个有希望的途径。尽管必须采取额外的措施将液体活检带入诊所,原理验证研究和隔离方法是有希望的。最终,CSF和/或基于血浆的液体活检可能是神经外科医生在不久的将来治疗和管理GBM患者的有力工具。
    Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle-based liquid biopsy targeting nonneoplastic extracellular vesicles.
    The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance.
    Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM.
    Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon\'s arsenal in the near future for the treatment and management of GBM patients.
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  • 文章类型: Journal Article
    易于收集样品,生理相关性,以及非侵入性和纵向监测人体的能力是可穿戴汗液传感器的一些关键属性。示例通常包括嵌入在专用微流体中的可逆传感器或一次性传感器阵列,用于汗液的时间分析。然而,将该领域发展到真正代表“皮肤实验室”技术的水平,将需要结合高级功能,使用户可以自由地(1)选择进行样品分析的精确时间,以及(2)从嵌入在设备中的阵列中选择传感器以进行特定条件的样品分析。这里,我们在提供这种功能的可穿戴微流体平台中引入了新概念。所描述的技术涉及一系列手指驱动泵,阀门,和传感器结合在软,可穿戴微流体。进入的汗液收集在入口腔室中,并且可以由用户在他们选择时进行分析。按需汗液分析物评估是通过拉动薄突片以激活泵来实现的,该泵打开阀并允许汇集的汗液进入嵌入有用于所需分析物的传感器的腔室。这篇文章描述了一个彻底的表征平台,证明了泵的鲁棒性,阀门,并在模仿现实生活场景的条件下感知设备的各个方面。为期两天的人类试点研究验证了该系统,并说明了该设备按需提供的能力,纵向,和多分析物传感。我们的工作代表了具有这种按需传感功能的可穿戴系统的第一个示例,并为汗液传感开辟了令人兴奋的途径,以获取对人体生理的新见解。
    Easy sample collection, physiological relevance, and ability to noninvasively and longitudinally monitor the human body are some of the key attributes of wearable sweat sensors. Examples typically include reversible sensors or an array of single-use sensors embedded in specialized microfluidics for temporal analysis of sweat. However, evolving this field to a level that truly represents \"lab-on-skin\" technology will require the incorporation of advanced functionalities that give the user the freedom to (1) choose the precise time for performing sample analysis and (2) select sensors from an array embedded within the device for performing condition-specific sample analysis. Here, we introduce new concepts in wearable microfluidic platforms that offer such capabilities. The described technology involves a series of finger-actuated pumps, valves, and sensors incorporated within soft, wearable microfluidics. The incoming sweat collects in the inlet chamber and can be analyzed by the user at the time of their choosing. On-demand sweat analyte assessment is achieved by pulling a thin tab to activate a pump which opens a valve and allows the pooled sweat to enter a chamber embedded with sensors for the desired analytes. The article describes a thorough characterization of the platform that demonstrates the robustness of the pumping, valving, and sensing aspects of the device under conditions mimicking real-life scenarios. A two-day-long human pilot study validates the system and illustrates the device\'s ability to offer on-demand, longitudinal, and multianalyte sensing. Our work represents the first example of a wearable system with such on-demand sensing capabilities and opens exciting avenues in sweat sensing for acquiring new insights into human physiology.
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