Clinica Chimica Acta最新文献_第6页

Consistency study of IGF-1 detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and chemiluminescence immunoassay (CLIA) 基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）和化学发光免疫分析法（CLIA）检测IGF-1的一致性研究

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-11 DOI: 10.1016/j.cca.2026.120835

Wu Yan , Ruifang Shi , Wen Zheng , Wentao Yang , Francis Manyori Bigambo , Wei Pan , Wenjing Zhang , Xu Wang

Background

Insulin-like Growth Factor I (IGF-1) is crucial for growth, metabolism, and cell proliferation. Its detection is significant for diagnosing and monitoring various diseases. Chemiluminescence immunoassay (CLIA) is commonly used for IGF-1 detection but is prone to interference and variability. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) offers higher specificity and sensitivity but is less clinically applied. This study compared the consistency of serum IGF-1 levels detected by MALDI-TOF MS and CLIA.

Methods

A total of 660 serum samples from healthy individuals aged 0 to 90 years were included and analyzed using MALDI-TOF MS and CLIA methods. Initially, the MALDI-TOF MS results for the full cohort were assessed for agreement with age- and sex-specific reference intervals provided by the CLIA kit. Subsequently, a subset of 108 participants underwent paired testing under identical conditions to evaluate method comparability. The consistency between the two methods was evaluated using linear regression, the intraclass correlation coefficient (ICC), and Bland-Altman analysis.

Results

In most age groups, the results of IGF-1 concentration measured by MALDI-TOF MS fell within the reference range established by CLIA. A strong correlation (R² = 0.982) was observed between the two methods, with the regression equation defined as IGF-1_CLIA = 0.972 × IGF-1_{MALDI-TOF MS} + 5.041. The correlation coefficients were 0.994 in children and 0.985 in adults (P < 0.001), and ICC values exceeded 0.80, indicating high consistency. Bland-Altman analysis showed a mean difference of −0.25 ng/mL, with 95% limits of agreement ranging from −24.54 to 24.04 ng/mL, which falls within the clinically acceptable range.

Conclusions

MALDI-TOF MS shows good consistency with CLIA in detecting serum IGF-I levels, providing evidence for its clinical application.

背景：胰岛素样生长因子I （IGF-1）对生长、代谢和细胞增殖至关重要。它的检测对各种疾病的诊断和监测具有重要意义。化学发光免疫分析法（CLIA）通常用于IGF-1检测，但容易受到干扰和变化。基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）具有较高的特异性和敏感性，但临床应用较少。本研究比较了MALDI-TOF MS和CLIA检测血清IGF-1水平的一致性。方法：采用MALDI-TOF MS和CLIA方法对660例0 ~ 90 岁健康人的血清样本进行分析。最初，对整个队列的MALDI-TOF MS结果进行评估，以确定其与CLIA试剂盒提供的年龄和性别特异性参考区间是否一致。随后，108名参与者在相同条件下进行配对测试，以评估方法的可比性。采用线性回归、类内相关系数（ICC）和Bland-Altman分析评价两种方法的一致性。结果：在大多数年龄组中，MALDI-TOF MS测定的IGF-1浓度均在CLIA建立的参考范围内。两种方法之间存在较强的相关性（R2 = 0.982），回归方程定义为IGF-1CLIA = 0.972 × IGF-1MALDI-TOF MS + 5.041。结论：MALDI-TOF MS与CLIA检测血清IGF-I水平具有较好的一致性，为其临床应用提供了依据。

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引用次数: 0

MicroRNA-CRISPR biosensors for cancer diagnostics 用于癌症诊断的MicroRNA-CRISPR生物传感器

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-10 DOI: 10.1016/j.cca.2026.120837

Alaa H. Habib , Ziaullah Mirza Sain , Misbahuddin Rafeeq , Mohammed Matoog Karami , Hadeel A. Alsufyani , Johar Iqbal , Kamel Chaieb , Hisham N. Altayb , Muhammad Shahid Nadeem , Fahad A. Al-Abbasi , Imran Kazmi

Circulating microRNAs (miRNAs) are promising minimally invasive biomarkers for cancer and cardiovascular disorders. However, their low sequence length, low abundance, high sequence homology (including iso-miRs), and strong matrix and preanalytical effects in biofluids require highly sensitive and robust analytical technologies. CRISPR-Cas systems, particularly Cas12a, Cas12b, Cas13a, and Cas9, offer programmable nucleic acid recognition with high mismatch discrimination combined with collateral nuclease activity, enabling versatile signal amplification through fluorescence, electrochemical, electrochemiluminescent (ECL), photoelectrochemical (PEC), colorimetric, and lateral-flow readouts. This review critically evaluates the latest advances in CRISPR-based miRNA biosensors, emphasizing their analytical performance and translational potential in clinical diagnostics across plasma/serum, saliva, whole blood, and extracellular vesicle samples. The detection limits are typically within the femtomolar to attomolar range. The requirements for clinical translation are equally influenced by factors such as sample preparation, inhibitor tolerance, miRNA panel multiplexing, quantitative readout, and reagent stability. We compared CRISPR-based workflows with RT-qPCR and digital PCR and provided a roadmap for standardization and quality control, as well as the minimal analytical and clinical validation standards required for adopting CRISPR technology in clinical chemistry laboratories.

循环microRNAs （miRNAs）是癌症和心血管疾病的有前途的微创生物标志物。然而，它们的低序列长度、低丰度、高序列同源性（包括isomirs）以及在生物流体中的强基质和分析前效应需要高度敏感和强大的分析技术。CRISPR-Cas系统，特别是Cas12a、Cas12b、Cas13a和Cas9，提供可编程的核酸识别，具有高错配辨别能力，结合侧链核酸酶活性，通过荧光、电化学、电化学发光（ECL）、光电化学（PEC）、比色和侧流读出实现多功能信号放大。这篇综述批判性地评估了基于crispr的miRNA生物传感器的最新进展，强调了它们在血浆/血清、唾液、全血和细胞外囊泡样本的临床诊断中的分析性能和转化潜力。检测限通常在飞摩尔到原子摩尔范围内。临床翻译的要求同样受到样品制备、抑制剂耐受性、miRNA面板复用、定量读数和试剂稳定性等因素的影响。我们将基于CRISPR的工作流程与RT-qPCR和数字PCR进行了比较，并为标准化和质量控制提供了路线图，以及在临床化学实验室采用CRISPR技术所需的最低分析和临床验证标准。

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引用次数: 0

A novel CLPP variant in a Pakistani family with Perrault syndrome associated with recurrent fevers 一种新的CLPP变异在巴基斯坦家庭与佩诺特综合征相关的反复发烧。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-10 DOI: 10.1016/j.cca.2026.120832

Nisar Ahmad , Pingchuan Zhang , Muhammad Muzammal , Wasim Shah , Li Ran , Maryam Niaz , Jia-Da Li , Meichao Men

Perrault syndrome (PRLTS) is an autosomal recessive disease with sensorineural hearing loss and ovarian dysfunction in girls, and either a fluctuating neurological phenotype or not. PRLTS type 2 is known to be caused by pathogenic variants of the CLPP gene that encodes mitochondrial ATP-dependent protease. This paper involved clinical and genetic studies on a Pakistani family with PRLTS. Whole-exome sequencing identified a novel homozygous CLPP missense mutation (NM_006012.4: c.250 A > C; p.Ile84Leu). Its pathogenicity was assessed with the help of multiple sequence alignment, AlphaFold protein modeling, and docking with CLPX with the help of ClusPro. Auditory brainstem responses and tympanometry were in clinical assessment. The individuals were found to have a uniform phenotype of severe sensorineural hearing loss, mild intellectual disability, ataxia and frequent fever. There was one patient in whom the unilateral Eustachian tube dysfunction was hinted at by Tympanometry. At the molecular level, the identified CLPP variant involved a highly conserved residue. Structural modeling showed preserved protein architecture, whereas docking simulations revealed disrupted CLPP-CLPX interaction, suggesting a basis for impaired proteostasis. We report a novel CLPP missense variant (p.I84L) in a Pakistani family with PRLTS, expanding the mutational spectrum of CLPP. To the best of our knowledge, recurrent fever was reported in PRLTS for the first time, which expanded the PRLTS phenotype spectrum.

Perrault综合征（PRLTS）是一种常染色体隐性遗传病，伴有女童感音神经性听力损失和卵巢功能障碍，可伴有波动的神经表型或无波动。已知PRLTS 2型是由编码线粒体atp依赖性蛋白酶的CLPP基因的致病性变异引起的。本文对一个巴基斯坦PRLTS家族进行了临床和遗传学研究。全外显子组测序鉴定出一种新的纯合子CLPP错义突变（NM_006012.4: C .250 a > C; p.Ile84Leu）。通过多序列比对、AlphaFold蛋白建模、ClusPro与CLPX对接等方法评估其致病性。临床评价听性脑干反应和鼓室测量。这些个体被发现有一个统一的表型，严重感音神经性听力损失，轻度智力残疾，共济失调和频繁发烧。有一个病人单侧耳咽管功能障碍提示鼓室测量。在分子水平上，鉴定的CLPP变异涉及一个高度保守的残基。结构建模显示保留了蛋白质结构，而对接模拟显示CLPP-CLPX相互作用被破坏，这表明蛋白质平衡受损的基础。我们报告了一个新的CLPP错义变异（p.I84L）在巴基斯坦的一个PRLTS家族，扩大了CLPP的突变谱。据我们所知，PRLTS中首次报道了复发性发热，这扩大了PRLTS的表型谱。

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引用次数: 0

Evaluation of MASSARRAY technique in detecting mitochondrial disease mutations MASSARRAY技术检测线粒体疾病突变的评价。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-10 DOI: 10.1016/j.cca.2026.120820

Nahuda Chetu, Preyaporn Onsod, Budsaba Rerkamnuaychoke, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul

Mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA), leading to impaired energy production, cellular dysfunction, and tissue damage. Accurate and efficient detection of mitochondrial DNA (mtDNA) mutations is crucial for diagnosis and patient management. This study aimed to evaluate the performance of MassARRAY in detecting mtDNA mutations compared to the routinely used MLPA technique. 34 EDTA blood samples from patients with suspected mitochondrial disorders were analyzed using MassARRAY and MLPA methods. MassARRAY was customized to detect 14 mtDNA loci, while MLPA targeted six fixed genetic loci. Both techniques detected five positive cases: three with the m.11778G > A mutation (8.82%) and two with the m.14484 T > C mutation (5.88%). Additionally, MassARRAY uniquely identified the m.12026 A > G mutation and a heteroplasmic m.12258C > A variant (2.94%). MassARRAY also demonstrated advantages in terms of rapid turnaround time (approximately 8 h) and assay flexibility. In conclusion, MassARRAY offers a highly accurate and efficient alternative for detecting mtDNA mutations, with the added benefit of customizable probes. However, sequencing confirmation is recommended for broader mutation coverage.

线粒体疾病是由线粒体DNA （mtDNA）突变引起的，导致能量产生受损、细胞功能障碍和组织损伤。准确有效地检测线粒体DNA （mtDNA）突变对诊断和患者管理至关重要。本研究旨在评估MassARRAY在检测mtDNA突变方面的性能，并与常规使用的MLPA技术进行比较。采用MassARRAY和MLPA方法对34例疑似线粒体疾病患者的EDTA血样进行分析。MassARRAY定制检测14个mtDNA位点，MLPA检测6个固定基因位点。两种技术均检测到5例阳性，其中3例为m.11778G > A突变（8.82%），2例为m.14484 T > C突变（5.88%）。此外，MassARRAY唯一鉴定出m.12026 A > G突变和异质m.12258C > A突变（2.94%）。MassARRAY在快速周转时间（约8 h）和分析灵活性方面也显示出优势。总之，MassARRAY为检测mtDNA突变提供了一种高度准确和高效的替代方法，并具有可定制探针的额外好处。然而，对于更广泛的突变覆盖范围，建议进行测序确认。

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引用次数: 0

Optimized NMDAR autoantibody detection via combined NR1-4a LCBA and NR1/NR2 fusion FCBA 优化NR1-4a联合LCBA和NR1/NR2融合FCBA检测NMDAR自身抗体的方法。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-08 DOI: 10.1016/j.cca.2026.120834

Baoming He , Jing Gan , Junjuan Mao , Xiao Wang , Dong Yang , Tong Peng , Jianlin Liu , Xinying Jing , Li Meng , Quekun Peng

Background

Autoimmune encephalitis (AE) is a group of neurological disorders mediated by autoantibodies targeting proteins within the central nervous system, of which anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common. The current Cell-Based Assay (CBA) that is primarily used to detect NMDAR antibodies in clinical settings, however, exhibits several limitations, including both false-positive and false-negative results. The aim of this research is to improve the sensitivity and specificity of NMDAR antibody detection through optimization of the CBA detection model.

Methods

In this research, recombinant vectors were constructed to express full-length, truncated, and fusion proteins of NMDA Receptor Subunit 1 (NR1) or/and NMDA Receptor Subunit 2B (NR2B). Six distinct models for CBA detection (Model I-Model VI) were established via transfection into CHO cells. A total of 36 serum (SER) and cerebrospinal fluid (CSF) samples from 18 anti-NMDAR patients were analyzed alongside 30 SER and CSF samples from individuals with other neurological disorders and 20 SER samples from healthy controls to systematically evaluate the detection efficacy across each model.

Results

The findings indicate that the Model IV (NR1-4a single subunit) exhibited optimal diagnostic sensitivity(true positive identified) at 100% by live cell-based assay (L-CBA). In contrast, Model V (NR1–1a Amino Terminal Domain (ATD) fused with NR2B ATD) displayed the highest technical sensitivity(titer detection limit) by the fixed cell-based assay (F-CBA), which was significantly superior to the other models (P < 0.05). The combined testing of Models IV and V resulted in a substantial enhancement of the overall performance of the assay. Specifically, the sample diagnostic sensitivity of the SER increased from 83.3% of traditional detection method(Model I) to 100% and the technical sensitivity was improved with highly significant difference to Model I(SER: P < 0.0001; CSF: P < 0.05).

Conclusion

The combined detection established in this research markedly improved both accuracy and reliability in NMDAR antibody detection, effectively addressing the limitations associated with traditional detection methods. This optimized detection provides a robust foundation for early diagnosis and therapeutic intervention in cases of NMDAR encephalitis, thereby enhancing patient prognosis.

背景：自身免疫性脑炎（AE）是一种由中枢神经系统内靶向蛋白的自身抗体介导的神经系统疾病，其中以抗n -甲基-d-天冬氨酸受体（NMDAR）脑炎最为常见。然而，目前主要用于临床检测NMDAR抗体的基于细胞的检测（CBA）存在一些局限性，包括假阳性和假阴性结果。本研究旨在通过优化CBA检测模型，提高NMDAR抗体检测的灵敏度和特异性。方法：构建重组载体，表达NMDA受体亚单位1 （NR1）或/和NMDA受体亚单位2B （NR2B）的全长、截断和融合蛋白。通过转染CHO细胞，建立了6种不同的CBA检测模型（模型i -模型VI）。共分析了来自18名抗nmdar患者的36份血清（SER）和脑脊液（CSF）样本，以及来自其他神经系统疾病患者的30份SER和CSF样本和来自健康对照者的20份SER样本，以系统地评估每种模型的检测效果。结果：研究结果表明，模型IV （NR1-4a单亚基）在活细胞检测（L-CBA）中表现出最佳的诊断敏感性（真阳性鉴定），为100%。模型V （NR1-1a氨基末端结构域（ATD）与NR2B ATD融合）在固定细胞法（F-CBA）中显示出最高的技术灵敏度（滴度检测限），显著优于其他模型（P ）结论：本研究建立的联合检测方法显著提高了NMDAR抗体检测的准确性和可靠性，有效解决了传统检测方法的局限性。这种优化的检测方法为NMDAR脑炎病例的早期诊断和治疗干预提供了坚实的基础，从而改善了患者的预后。

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引用次数: 0

Expansion of CKD diagnostics through biosensor technology: An early detection approach 通过生物传感器技术扩展CKD诊断：早期检测方法。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-08 DOI: 10.1016/j.cca.2026.120833

Ganesh Pd Sahu, Aniket Nandi, Atanu Saha, Swagnik Chakraborty, S.S. Ganti, Kalicharan Sharma

Chronic kidney disease (CKD) is a complicated global health disease that causes serious health issues like kidney failure and heart-related problems. These complications make the conditions worse for the patients and also increase the mortality rate globally, which is 41.5% since 1990. Most individuals are not aware that they have renal disease until it is highly advanced because it doesn't show any symptoms in its early stages. The prevalence of CKD is higher than average, and replacement therapy is required for the majority of individuals who have reached stage 5. Various diagnostic techniques have been developed for the detection of CKD, but they are not user-friendly and are much costlier. Therefore, the early detection of CKD through biosensor-based techniques has been used to decrease the overall burden to prevent patients from developing serious renal problems. The emergence of biosensors is one of the most promising solutions, offering a cost-effective and precise method for the early detection of various diseases. In this review, we have systematically compiled the current data since the last ten years (2015–2025), complications, traditional vs modern techniques, recent biomarkers and biosensor-based techniques, which include various classes of biosensors, including electrochemical, optical, fluorescent/colorimetric, and AI-assisted biosensors.

慢性肾脏疾病（CKD）是一种复杂的全球性健康疾病，可导致严重的健康问题，如肾衰竭和心脏相关问题。这些并发症使患者的病情恶化，也增加了全球死亡率，自1990年以来为41.5%。大多数人直到病情发展到晚期才意识到自己患有肾病，因为在早期阶段没有任何症状。CKD的患病率高于平均水平，大多数达到5期的患者需要替代治疗。各种诊断技术已经开发出来用于检测CKD，但它们都不是用户友好的和昂贵得多。因此，通过基于生物传感器的技术早期检测CKD已被用于减少总体负担，以防止患者发生严重的肾脏问题。生物传感器的出现是最有希望的解决方案之一，为各种疾病的早期检测提供了一种具有成本效益和精确的方法。在这篇综述中，我们系统地汇编了过去十年（2015-2025）的当前数据、并发症、传统与现代技术、最新的生物标志物和基于生物传感器的技术，其中包括各种类型的生物传感器，包括电化学、光学、荧光/比色和人工智能辅助生物传感器。

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引用次数: 0

C-peptide in polycystic ovary syndrome 多囊卵巢综合征中的c肽

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-08 DOI: 10.1016/j.cca.2026.120829

Faezeh Mahd Gharebagh , Sana Najafi , Asra Zeinalpour , Rozhina Sadat Pirouzmand , Hojat Ghasemnejad-Berenji , Mortaza Taheri-Anganeh

Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age, characterized by irregular menstruation, hyperandrogenism, and the presence of ovarian cysts. The fundamental pathophysiology is intricate, encompassing insulin resistance, hyperinsulinemia, and impaired hormonal control. C-peptide, a consequence of insulin production, has emerged as a valuable biomarker for evaluating insulin resistance and beta-cell functionality in PCOS. Although previously deemed biologically inactive, current research indicates that C-peptide actively participates in cellular signaling, initiating pathways such as calcium-dependent signaling and endothelial nitric oxide synthase. Increased C-peptide levels in PCOS signify hyperinsulinemia and insulin resistance, which exacerbate the syndrome's metabolic and reproductive disorders. Clinical data substantiates the utilization of C-peptide as a diagnostic instrument, especially in assessing insulin resistance in non-obese PCOS patients, where conventional metrics such as body mass index (BMI) may be inapplicable. Nonetheless, obstacles persist in the standardization of C-peptide testing methodologies, and its interpretation may be affected by extrinsic factors like pharmaceutical interventions or concomitant conditions like obesity and diabetes. Individualized diagnostic methods are necessary due to the phenotypic variability of PCOS, which results in varying C-peptide levels among distinct subtypes. Future research must concentrate on enhancing diagnostic procedures, investigating the significance of C-peptide in the long-term management of PCOS, and elucidating its potential as a predictive biomarker for associated metabolic disorders. This review emphasizes the necessity for additional investigations of C-peptide in clinical practice to enhance diagnostic and therapeutic approaches for PCOS.

多囊卵巢综合征（PCOS）是育龄妇女常见的内分泌疾病，以月经不调、雄激素分泌过多和卵巢囊肿为特征。基本的病理生理是复杂的，包括胰岛素抵抗、高胰岛素血症和激素控制受损。c肽是胰岛素产生的结果，已成为评估多囊卵巢综合征胰岛素抵抗和β细胞功能的有价值的生物标志物。虽然以前认为c肽没有生物学活性，但目前的研究表明，c肽积极参与细胞信号传导，启动钙依赖性信号传导和内皮型一氧化氮合酶等途径。多囊卵巢综合征患者c肽水平升高意味着高胰岛素血症和胰岛素抵抗，这加剧了多囊卵巢综合征的代谢和生殖障碍。临床数据证实了c肽作为诊断工具的应用，特别是在评估非肥胖多囊卵巢综合征患者的胰岛素抵抗时，传统的指标如体重指数（BMI）可能不适用。尽管如此，c肽检测方法的标准化仍然存在障碍，其解释可能受到外部因素的影响，如药物干预或肥胖和糖尿病等伴随疾病。由于多囊卵巢综合征的表型可变性，导致不同亚型的c肽水平不同，因此个性化的诊断方法是必要的。未来的研究必须集中在改进诊断程序，调查c肽在多囊卵巢综合征长期治疗中的意义，并阐明其作为相关代谢紊乱的预测生物标志物的潜力。本文强调了在临床实践中进一步研究c肽以提高多囊卵巢综合征的诊断和治疗方法的必要性。

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引用次数: 0

Circulating suPAR as a noninvasive biomarker of fibrosis and immune activation in autoimmune liver diseases 循环suPAR作为自身免疫性肝病中纤维化和免疫激活的无创生物标志物。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-06 DOI: 10.1016/j.cca.2026.120831

Fuguo Zhan , Tianbin Chen , Jun Liang , Can Liu , Mingdong Huang , Longguang Jiang

Aim

Noninvasive assessment of fibrosis in autoimmune liver diseases (AILDs) remains challenging. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic immune activation, but its role in AILDs is unclear. This study aimed to evaluate the diagnostic performance of circulating suPAR in AILDs and its association with fibrosis severity and immune activation.

Methods

A retrospective study included 117 patients with AILDs (n = 61), chronic hepatitis B (CHB, n = 33), metabolic dysfunction-associated steatotic liver disease (MASLD, n = 23), and 44 healthy controls. Serum suPAR was measured by chemiluminescent immunoassay. Correlations with fibrosis indices (APRI, FIB-4), liver stiffness measurement (LSM), and IgG were assessed. ROC analysis evaluated diagnostic accuracy.

Results

Serum suPAR was significantly higher in AILDs than in controls, CHB, and MASLD (median 5.16 vs. 3.58, 3.92, and 3.13 ng/mL; all P < 0.001). suPAR correlated strongly with APRI (r = 0.66), FIB-4 (r = 0.65), and LSM (r = 0.62), and modestly with IgG (r = 0.31). ROC analysis demonstrated robust discrimination between AILDs and controls (AUC = 0.839), CHB (AUC = 0.724), and MASLD (AUC = 0.944). Patients with higher suPAR levels exhibited more advanced fibrosis and greater biochemical evidence of liver injury.

Conclusions

Circulating suPAR is elevated in AILDs, reflecting fibrosis and immune activation. suPAR provides complementary, antibody-independent diagnostic value and may serve as a noninvasive biomarker for differentiating AILDs from CHB and MASLD in clinical practice.

目的：自身免疫性肝病（AILDs）纤维化的无创评估仍然具有挑战性。可溶性尿激酶纤溶酶原激活剂受体（suPAR）是全身免疫激活的标志物，但其在AILDs中的作用尚不清楚。本研究旨在评估循环suPAR在AILDs中的诊断性能及其与纤维化严重程度和免疫激活的关系。方法：回顾性研究纳入117例AILDs（ = 61）、慢性乙型肝炎（CHB， = 33）、代谢功能障碍相关脂肪变性肝病（MASLD， = 23）患者和44例健康对照。采用化学发光免疫分析法测定血清suPAR。评估与纤维化指数（APRI、FIB-4）、肝硬度测量（LSM）和IgG的相关性。ROC分析评估诊断的准确性。结果：aild患者血清suPAR明显高于对照组、CHB和MASLD患者（中位数5.16 vs. 3.58、3.92和3.13 ng/mL； P均为 ）结论：循环suPAR在aild患者中升高，反映了纤维化和免疫激活。suPAR提供了互补的、独立于抗体的诊断价值，可能在临床实践中作为区分aild与CHB和MASLD的非侵入性生物标志物。

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引用次数: 0

Circulating microRNA electrochemical assays in thyroid cancer 循环microRNA在甲状腺癌中的电化学测定。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-06 DOI: 10.1016/j.cca.2026.120828

Muteb Alanazi , Jowaher Alanazi , Tareq Nafea Alharby , Abdullah S. Alhamed , Sameer Shaikh

Thyroid cancer is the most prevalent endocrine malignancy; however, it is difficult to preoperatively distinguish between benign and malignant nodules and to ensure reliable surveillance after therapy. Circulating microRNAs (miRNAs) provide a minimally invasive molecular signal for testing, although conventional qPCR and sequencing pipeline technologies have cost, labor, and standardization challenges. This review summarizes the progress in the electrochemical biosensing of thyroid-relevant miRNAs along sample-to-clinic continuum. Signal recovery is strongly determined by preanalytical variables such as matrix selection (serum, plasma, whole blood, or extracellular vesicles), hemolysis control, storage conditions, extraction chemistry, spike-in controls, and normalization strategy using exogenous and endogenous controls. Yield can be further stabilized by the enrichment of extracellular vesicles, low-input protocols, and the reduction of batch effects. Analytically, voltammetric, impedimetric, electrochemiluminescent, and photoelectrochemical formats use rational probe design with nanostructured interfaces, such as gold nanoparticles, graphene derivatives, and MXenes, along with catalytic amplification duplex-specific nuclease (DSN), hybridization chain reaction (HCR), catalytic hairpin assembly (CHA), or CRISPR modules. While many platforms report ultra-low analytical limits of detection (femtomolar to attomolar) and wide linear ranges in buffer or spiked matrices, fewer studies have established functional sensitivity and clinical detection rates in unprocessed patient serum/plasma, where endogenous inhibitors and biological heterogeneity can dominate performance. Recurring signatures, such as miR-146b, miR-221, miR-222, and miR-21, have been shown to aid in early diagnosis, risk stratification, and postoperative follow-ups, whereas multiplex panels and cartridge-based platforms have been shown to be resilient to biological heterogeneity and complement cytology, mutation panels, and thyroglobulin, particularly in indeterminate Bethesda III or IV nodules and antibody-interfered follow-ups. The remaining limitations are inter-study method variation, poor inter-center validation, and unclear regulatory mechanisms of these miRNAs. An effective roadmap will focus on balanced collection and processing, preset thresholds with external calibration and commutable references, and blind prospective trials integrated into clinical practice with decision curve and health-economic analyses to speed up translation.

甲状腺癌是最常见的内分泌恶性肿瘤；然而，术前很难区分良性和恶性结节，也很难确保治疗后的可靠监测。尽管传统的qPCR和测序流水线技术存在成本、劳动力和标准化方面的挑战，但循环microRNAs （miRNAs）为检测提供了一种微创分子信号。本文综述了甲状腺相关mirna在样品到临床连续体的电化学生物传感方面的进展。信号恢复在很大程度上取决于分析前变量，如基质选择（血清、血浆、全血或细胞外囊泡）、溶血控制、储存条件、提取化学、峰值控制以及使用外源性和内源性控制的归一化策略。通过细胞外囊泡的富集、低投入方案和批次效应的减少，产量可以进一步稳定。分析上，伏安法、阻抗法、电化学发光法和光电化学格式使用合理的探针设计与纳米结构界面，如金纳米颗粒、石墨烯衍生物和MXenes，以及催化扩增双链特异性核酸酶（DSN）、杂交链反应（HCR）、催化发夹组装（CHA）或CRISPR模块。虽然许多平台报告了超低的分析检测限（飞摩尔到毫摩尔）和缓冲液或加标基质的宽线性范围，但在未经处理的患者血清/血浆中建立功能敏感性和临床检出率的研究较少，其中内源性抑制剂和生物异质性可能主导性能。反复出现的标记，如miR-146b、miR-221、miR-222和miR-21，已被证明有助于早期诊断、风险分层和术后随访，而多重小组和基于盒的平台已被证明对生物异质性和补体细胞学、突变小组和甲状腺球蛋白具有弹性，特别是在不确定的Bethesda III或IV型结节和抗体干扰的随访中。其余的限制是研究方法之间的差异，中心间验证不佳，以及这些mirna的调控机制不明确。有效的路线图将侧重于平衡收集和处理，预置阈值，外部校准和可交换参考，以及通过决策曲线和健康经济分析将盲法前瞻性试验纳入临床实践，以加快翻译速度。

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引用次数: 0

Investigating the diagnostic significance of serum NRCAM in small cell lung cancer 探讨血清NRCAM对小细胞肺癌的诊断意义。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-06 DOI: 10.1016/j.cca.2025.120815

Yinyi Chen , Kexin Han , Liping Wei , Xinlu Sun , Yanzhao Liu , Qunxia Wang , Yang Wu , Simei Chen , Jianlin Yu , Yi Luo , Lili Wen , Liming Tan

Objective

This study aims to investigate the clinical significance of serum neuronal cell adhesion molecule (NRCAM) in small cell lung cancer (SCLC) diagnosis.

Methods

Serum NRCAM levels were measured using enzyme-linked immunosorbent assay in 80 SCLC patients, 98 patients with non-small cell lung cancer (NSCLC), 73 patients with pulmonary nodules (PN) and 56 healthy controls. Neuron specific enolase (NSE) and progastrin-releasing peptide (ProGRP) expression were detected using chemiluminescence immunoassay.

Results

(1) Significant differences were detected in serum NRCAM, NSE and ProGRP levels among the groups (P < 0.05), with the highest levels observed in SCLC patients. (2) Correlation assessment revealed that serum NRCAM concentrations were positively correlated with smoking (r = 0.39) and lymph node metastasis (r = 0.37) (both P < 0.01). (3) NRCAM concentration was positively correlated with the clinical stage of SCLC, being significantly lower in stages I-II compared to stages III-IV (P < 0.01), and was remarkably lower in the non-metastatic group of SCLC relative to the metastatic group (P < 0.01). (4) Compared to the NSCLC group, ProGRP exhibited the largest area under the receiver operating characteristic curve (AUC) and the highest sensitivity for SCLC diagnosis, with values of 0.86 and 76 %, respectively. NRCAM had the highest specificity for SCLC diagnosis (94 %). Compared to the PN group, NRCAM exhibited a larger AUC (0.81) and higher sensitivity (74 %) for SCLC diagnosis. Conversely, NSE displayed a higher specificity for SCLC diagnosis (93 %). The combined diagnostic approach using NRCAM, NSE, and ProGRP yielded the largest AUC and the highest sensitivity, at 0.94 and 91 %, respectively. (5) Binary logistic regression analysis revealed that smoking and lymph node metastasis were potential risk factors influencing serum NRCAM levels.

Conclusions

NRCAM possess significant potential for diagnosing SCLC and distinguishing SCLC from NSCLC and PN. Moreover, the combination detection of NRCAM, NSE, and ProGRP may enhance diagnostic performance, offering a novel clinical strategy for SCLC.

目的：探讨血清神经细胞粘附分子（NRCAM）在小细胞肺癌（SCLC）诊断中的临床意义。方法：采用酶联免疫吸附法测定80例SCLC患者、98例非小细胞肺癌（NSCLC）患者、73例肺结节（PN）患者和56例健康对照者血清NRCAM水平。采用化学发光免疫分析法检测神经元特异性烯醇化酶（NSE）和原胃泌素释放肽（ProGRP）的表达。结果：(1)各组患者血清NRCAM、NSE、ProGRP水平差异有统计学意义（P ）结论：NRCAM对SCLC的诊断、SCLC与NSCLC、PN的鉴别具有重要意义。此外，NRCAM、NSE和ProGRP联合检测可提高SCLC的诊断效果，为SCLC的临床诊断提供了一种新的策略。

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引用次数: 0