Clinica Chimica Acta最新文献_第4页

Antibody response against HERV-K polymerase and envelope by patients with multiple sclerosis 多发性硬化症患者对HERV-K聚合酶和包膜的抗体反应。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-27 DOI: 10.1016/j.cca.2026.120870

Bruna Reimberg Flose , Kevin Cézar Nascimento Silva , Maria Aparecida Juliano , Virginia Fernandes Moça Trevisani , Carolina Nunes França , Marcelo Andreetta Corral , Luiz Henrique da Silva Nali , Marina Tiemi Shio

Introduction

Human Endogenous Retroviruses (HERVs) are viruses that have infected germ cells of our ancestors millions of years ago and compose 8% of human genome. The expression of HERVs is associated with neurological disorders such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). The humoral immune response against peptides from the envelope proteins, but not to polymerase, of HERV-K has been previously described. The aim of this study is to evaluate anti-HERV- K polymerase (pol) humoral response in patients with MS.

Methods

GenBank platform were used to select peptides with similarity above 50%, comparing HERV sequences (K or W) with the protein Myelin Oligodendrocyte Glycoprotein (MOG). The synthesized peptides were used in the ELISA test for anti-HERV-K (pol – polymerase) and W (env - envelope) antibodies in serum of patients with MS (31) and healthy population (54) with no history of autoimmune diseases.

Results

One peptide (pep) related to HERV-W env and 8 peptides of HERV-K env or pol were selected and synthesized. Validation of the indirect ELISA with sera from MS patients showed that there was immunoreactivity for all peptides compared to healthy population (p < 0.0001). HERV-K env peptide 5 (WSGNQTLETRD) and 7 (ECVANSAVIL) showed the highest values of sensitivity and specificity, as well as diagnostic accuracy with 95.16% and 96.77%, respectively. HERV-K pol peptides 6 (LGIPTYAM), 8 (VTHVPSFR) and 9 (STVKTFTYLD) have demonstrated high values of accuracy 82.26, 80.65 and 82.26, respectively. These cutoff values were used to calculate the ELISA index - EI. The MS samples had a higher EI compared to the healthy population for almost all peptides of HERV-K pol (p < 0.001).

Conclusion

The present work showed a humoral response related to HERV-K pol and env, as well as HERV-W env, by patients with MS. All diagnostic parameters are appreciable, which makes it possible to use this tool to better understand the mechanisms related to viral immunology in patients.

人类内源性逆转录病毒（herv）是数百万年前感染我们祖先生殖细胞的病毒，占人类基因组的8%。herv的表达与神经系统疾病有关，如多发性硬化症（MS）和肌萎缩侧索硬化症（ALS）。先前已经描述了针对HERV-K包膜蛋白肽的体液免疫反应，而不是针对HERV-K的聚合酶。方法：利用GenBank平台筛选相似度大于50%的肽段，将HERV序列（K或W）与髓鞘少突胶质细胞糖蛋白（MOG）进行比较。将合成的肽用于MS患者（31例）和无自身免疫性疾病史的健康人群（54例）血清中抗herv - k （pol - polymerase）和W （env - envelope）抗体的ELISA检测。结果：选择并合成了1个与HERV-W env相关的肽段（pep）和8个与HERV-K env或pol相关的肽段。对MS患者血清的间接ELISA验证表明，与健康人群相比，MS患者的所有多肽都具有免疫反应性（p ）。结论：本研究显示MS患者对HERV-K pol和env以及HERV-W env均有体液反应，所有诊断参数都很明显，这使得使用该工具更好地了解患者病毒免疫学相关机制成为可能。

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引用次数: 0

Multi-omics biomarker detection in smoking induced COPD 吸烟诱发COPD的多组学生物标志物检测

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-26 DOI: 10.1016/j.cca.2026.120868

Rahamat Unissa Syed , Mohammed Khaled Bin Break , Rihab Akasha , Nancy Mohammad Elafandy , Sally Hassan Abobaker , Amna abakar Suleiman Khalifa , Nayla Ahmed Mohammed Aboshouk , Afrah Nashmi Alghaythi , Lama Abdullah Altwalah , Rawabi Mohammed Menwer Aldhafeeri , Mohd Sajjad Ahmad Khan , Gaurav Gupta

Chronic obstructive pulmonary disease (COPD) is marked by heterogeneity, and traditional spirometric biomarkers fall short of fully capturing its underlying molecular complexity. This review discusses recent developments in multi-omics profiling, such as transcriptomics, proteomics, metabolomics, and epigenomics/acetylomics, to define biologically meaningful COPD endotypes and enhance their clinical categorization. Reproducible circulating protein markers identified in proteomic studies include surfactant protein D (SP-D), club cell secretory protein (CC16), fibrinogen, and inflammatory cytokines, which predict disease severity, risk of exacerbation, and mortality. Further evidence of dysregulated histone/protein acetylation and other post-translational modifications in chronic inflammation, steroid resistance, and disease progression is provided by epigenomic studies (such as DNA methylation, non-coding RNAs, and chromatin remodeling) and acetylomic analyses. Notably, integrative multi-omics solutions exhibit better outcomes than single-biomarker solutions by allowing the identification of molecular endotypes that are more likely to accommodate clinical heterogeneity. Nevertheless, it is significantly constrained by cohort and platform heterogeneity, including factors such as smoking exposure, age, comorbidities, treatment, and sample processing methods. Overall, the existing evidence highlights the importance of multi-omics integration in the further development of precision diagnostics and individualized management of COPD, bridging the gap between molecular pathology and clinical decision-making.

慢性阻塞性肺疾病（COPD）具有异质性，传统的肺活量测定生物标志物无法完全捕捉其潜在的分子复杂性。本文讨论了多组学分析的最新进展，如转录组学、蛋白质组学、代谢组学和表观基因组学/乙酰组学，以确定具有生物学意义的COPD内源性类型并加强其临床分类。在蛋白质组学研究中发现的可重复循环蛋白标志物包括表面活性剂蛋白D （SP-D）、俱乐部细胞分泌蛋白（CC16）、纤维蛋白原和炎症细胞因子，它们预测疾病严重程度、恶化风险和死亡率。表观基因组学研究（如DNA甲基化、非编码rna和染色质重塑）和乙酰化分析提供了组蛋白/蛋白乙酰化失调和其他翻译后修饰在慢性炎症、类固醇抵抗和疾病进展中的进一步证据。值得注意的是，综合多组学解决方案比单一生物标志物解决方案表现出更好的结果，因为它允许识别更有可能适应临床异质性的分子内型。然而，它明显受到队列和平台异质性的限制，包括吸烟暴露、年龄、合并症、治疗和样本处理方法等因素。总的来说，现有的证据强调了多组学整合在进一步发展COPD的精确诊断和个体化治疗中的重要性，弥合了分子病理学和临床决策之间的差距。

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引用次数: 0

Integrative metabolomics and proteomics of heat stress 热应激的综合代谢组学和蛋白质组学

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-26 DOI: 10.1016/j.cca.2026.120869

Shab M. Alkhoujah , Ruba A. Zenati , Munazza Ahmed , Ahmad Y. Abuhelwa , Shereen M. Aleidi , Mohammad A.Y. Alqudah , Waseem El-Huneidi , Eman Abu-Gharbieh , Zainab M. AlShareef , Karem H. Alzoubi , Yasser Bustanji , Mohammad H. Semreen

Heat stress (HS) is an escalating global health concern driven by climate change. Despite increasing epidemiologic recognition, the molecular mechanisms underlying HS pathophysiology remains poorly defined. This review systematically synthesizes metabolomic and proteomic findings to elucidate these mechanisms and identify molecular targets for intervention. Current management remains limited to symptomatic relief, with no targeted therapies available to prevent or reverse HS-induced injury. To address this gap, metabolomics and proteomics offer powerful approaches for elucidating the molecular and cellular mechanisms underlying HS responses. Metabolomic studies demonstrate that HS disrupts central energy metabolism, promotes lipid remodeling, elevates oxidative stress, alters amino acid and sulfur metabolism, disrupts hormone regulation, and induces hepatic stress. Complementary proteomics studies reveal significant upregulation of heat shock proteins (HSPs), particularly HSP70 and HSP90, as well as remodeling of inflammatory mediators, cytoskeletal proteins, and signaling pathways. Together, these omics-based findings highlight a coordinated reprogramming of metabolic pathways and proteomic signatures that underpins both susceptibility and adaptation to HS. This review explores recent metabolomic and proteomic investigations into HS, underscoring how integrative multiomics approaches provide a coherent view of its molecular complexity. By bridging metabolite–protein crosstalk with therapeutic exploration, the review highlights how these insights advance the identification of biomarkers and molecular targets, ultimately guiding the development of more precise interventions for HS.

热应激（HS）是由气候变化引起的日益严重的全球健康问题。尽管越来越多的流行病学认识，潜在的HS病理生理的分子机制仍然不明确。这篇综述系统地综合了代谢组学和蛋白质组学的发现来阐明这些机制并确定干预的分子靶点。目前的治疗仍然局限于症状缓解，没有靶向治疗来预防或逆转hs引起的损伤。为了解决这一差距，代谢组学和蛋白质组学为阐明HS反应的分子和细胞机制提供了强有力的方法。代谢组学研究表明，HS破坏中枢能量代谢，促进脂质重塑，升高氧化应激，改变氨基酸和硫代谢，破坏激素调节，诱导肝脏应激。互补的蛋白质组学研究揭示了热休克蛋白（HSPs）的显著上调，特别是HSP70和HSP90，以及炎症介质、细胞骨架蛋白和信号通路的重塑。总之，这些基于组学的发现强调了代谢途径和蛋白质组学特征的协调重编程，这些特征支持HS的易感性和适应性。这篇综述探讨了最近对HS的代谢组学和蛋白质组学研究，强调了综合多组学方法如何提供其分子复杂性的连贯观点。通过将代谢蛋白串扰与治疗探索联系起来，综述强调了这些见解如何推进生物标志物和分子靶点的鉴定，最终指导HS更精确干预措施的发展。

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引用次数: 0

Plasma ceramides decreased in Gilbert's syndrome associated with healthy blood lipid phenotypes: A cross-sectional study 与健康血脂表型相关的吉尔伯特综合征血浆神经酰胺减少：一项横断面研究

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-25 DOI: 10.1016/j.cca.2026.120867

Haitian Yu , Chen Liang , Shan Tang , Dacheng Sheng , Jianxia Dong , Xinyue Chen , Zhongjie Hu , Zhongping Duan , Wei Hou , Sujun Zheng

Background

Sphingolipids play an important role in the development of multiple metabolic disease. However, no study explored the impact of bilirubin on sphingolipid metabolism in human. This study aims to investigate the plasma sphingolipid profiles and their association with blood lipids in mild hyperbilirubinemia (Gilbert's syndrome; GS) individuals.

Methods

This cross-sectional study enrolled 224 participants including 112 individuals with GS and 112 age- and gender-matched healthy controls. Liquid chromatography-mass spectrometry was employed to quantify 53 plasma sphingolipid metabolites in a subset of 55 GS and 55 age- and gender-matched healthy controls. OPLS-DA model was constructed using SIMCA 14.1 software to identify distinct plasma sphingolipid metabolites between two groups.

Results

The median age of 224 subjects was 35 years, with males comprising 29.5%. The GS group exhibited higher levels of total bilirubin and high-density lipoprotein cholesterol, along with lower levels of triglycerides (all P < 0.05). Analysis of plasma sphingolipid revealed significant differences in 14 sphingolipids between two groups. Compared to the healthy control group, the GS group had lower levels of Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/25:0), Cer(d18:1/26:0), Cer(d18:2/16:0), CerP(d18:1/22:0), HexCer(d18:1/22:0), HexCer(d18:1/24:1), HexCer(d18:1/24:0), LacCer(d18:1/16:0), as well as higher levels of CerP(d18:1/12:0), LacCer(d18:1/24:0), sphingosine-1-phosphate, and sphinganine (all P < 0.05). Correlation analysis of 110 subjects indicated that Cer(d18:1/25:0), Cer(d18:1/26:0), Cer(d18:2/16:0), CerP(d18:1/22:0), HexCer(d18:1/22:0), HexCer(d18:1/24:0) were positively correlated with total cholesterol. Additionally, sphinganine was positively correlated with high-density lipoprotein cholesterol and sphingosine 1-phosphate was negatively correlated with triglycerides (all P < 0.05).

Conclusion

This study demonstrated that plasma ceramide levels decreased in Gilbert's syndrome, which correlates with a favorable blood lipid profile.

背景：鞘脂在多种代谢性疾病的发生发展中起重要作用。然而，尚无研究探讨胆红素对人体鞘脂代谢的影响。本研究旨在探讨轻度高胆红素血症（吉尔伯特综合征；GS）患者血浆鞘脂谱及其与血脂的关系。方法：这项横断面研究纳入了224名参与者，其中包括112名GS患者和112名年龄和性别匹配的健康对照组。采用液相色谱-质谱法定量了55名GS和55名年龄和性别匹配的健康对照者的53种血浆鞘脂代谢物。采用SIMCA 14.1软件建立OPLS-DA模型，鉴定两组不同的血浆鞘脂代谢物。结果：224例受试者中位年龄为35 岁，男性占29.5%。GS组表现出较高的总胆红素和高密度脂蛋白胆固醇水平，以及较低的甘油三酯水平(所有P 结论：该研究表明吉尔伯特综合征患者血浆神经酰胺水平下降，这与良好的血脂状况有关。

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引用次数: 0

The impact of thyroid dysfunction on COVID-19 severity and mortality: A systematic review and Meta-Analysis 甲状腺功能障碍对COVID-19严重程度和死亡率的影响：系统综述和荟萃分析

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-25 DOI: 10.1016/j.cca.2026.120851

İpek Dağdeviren , Meliha Melin Uygur , Elif Çiğdem Keleş

Thyroid function abnormalities have been increasingly reported in patients with coronavirus disease 2019 (COVID-19), yet the clinical significance of these alterations remains uncertain. Because early identification of individuals at risk for severe illness is essential, this study systematically evaluated the association between thyroid dysfunction and COVID-19 severity. A comprehensive search of major databases identified 4260 records, of which 13 observational studies met the eligibility criteria, yielding a total of 2829 patients from diverse geographical regions. Mild, moderate, and non-ICU patients were categorized as the non-severe group, while the severe-to-critical group included patients classified as severe or critical, those requiring ICU admission, or hospitalized in dedicated COVID-19 wards according to the criteria used in the original studies.

The pooled analysis demonstrated that total and free triiodothyronine (TT3 and FT3) levels were consistently lower in patients with more severe disease, and thyroid dysfunction was associated with 4.8-fold higher odds of severe-to-critical COVID-19. Although thyroid-stimulating hormone (TSH) levels were reduced in patients with COVID-19 compared with non-infected individuals, TSH alone did not predict disease severity. Higher TT3 and FT3 concentrations were consistently associated with a milder clinical course.

These findings suggest that thyroid function tests may provide useful prognostic information in patients with COVID-19. The observed hormonal patterns may reflect alterations along the hypothalamic–pituitary–thyroid axis; however, this interpretation remains hypothetical and requires confirmation through studies incorporating direct pituitary hormone assessment.

Low TT3 and FT3 levels appear to be associated with worse clinical outcomes in COVID-19 patients, suggesting their potential utility as prognostic indicators. However, further prospective studies are needed before recommending routine monitoring for clinical management.

2019冠状病毒病（COVID-19）患者中甲状腺功能异常的报道越来越多，但这些改变的临床意义仍不确定。由于早期识别有严重疾病风险的个体至关重要，因此本研究系统地评估了甲状腺功能障碍与COVID-19严重程度之间的关系。通过对主要数据库的全面检索，确定了4260条记录，其中13项观察性研究符合入选标准，共纳入来自不同地理区域的2829例患者。轻度、中度和非ICU患者被归类为非重症组，而严重至危重组包括根据原始研究中使用的标准被归类为严重或危重、需要ICU住院或在COVID-19专用病房住院的患者。合并分析表明，疾病较严重的患者总和游离三碘甲状腺原氨酸（TT3和FT3）水平持续较低，甲状腺功能障碍与重症至危重型COVID-19的几率增加4.8倍相关。尽管与未感染的个体相比，COVID-19患者的促甲状腺激素（TSH）水平降低，但TSH本身并不能预测疾病的严重程度。较高的TT3和FT3浓度始终与较轻的临床病程相关。这些发现表明，甲状腺功能检查可能为COVID-19患者提供有用的预后信息。所观察到的激素模式可能反映了沿下丘脑-垂体-甲状腺轴的改变；然而，这种解释仍然是假设的，需要通过结合直接垂体激素评估的研究来证实。低TT3和FT3水平似乎与COVID-19患者较差的临床结果相关，表明它们作为预后指标的潜在效用。然而，在推荐常规监测用于临床管理之前，需要进一步的前瞻性研究。

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引用次数: 0

The oxalobiome: unraveling the role of gut microbiota in oxalate metabolism and its implications for kidney health and disease management 草酸组：揭示肠道微生物群在草酸代谢中的作用及其对肾脏健康和疾病管理的影响。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-24 DOI: 10.1016/j.cca.2026.120852

David Mburu , Sumeet Kumar , Yanzhe Wang , Asadoor Amirkhani Namagerdi , Karoona Bai , Bilal Ali , Ahmed Minalla , Karina Ordaya Gonzales , Khalid A. Abdelhalim

The oxalobiome, comprising microbial communities involved in oxalate metabolism, plays a critical role in maintaining oxalate homeostasis and preventing associated health issues, particularly calcium oxalate nephrolithiasis. Key organisms, notably Oxalobacter formigenes, are essential for degrading oxalate, yet their abundance is influenced by factors such as diet, genetics, and antibiotic use. Recent advances in research have elucidated the complex interactions between the gut microbiome and oxalate metabolism, highlighting the potential for therapeutic interventions. Innovative strategies, including RNA interference therapies (e.g., lumasiran, nedosiran), engineered probiotics, and gene-editing technologies, show promise in managing conditions like primary hyperoxaluria. However, challenges remain, including limitations in oxalate measurement techniques and variability in microbial populations. Multi-omics approaches and metagenomic analyses have enhanced our understanding of the oxalobiome, revealing novel microbial taxa and metabolic pathways involved in oxalate degradation. Despite the potential of emerging therapies, clinical translation is still in its infancy, necessitating further research to establish efficacy and safety. Future studies should focus on mechanistic insights, standardized methodologies, and targeted microbiome-based therapies to optimize management strategies for hyperoxaluria and related systemic diseases. A comprehensive understanding of the oxalobiome is essential for developing precision medicine approaches that effectively address oxalate dysregulation and improve patient outcomes.

草酸菌群由参与草酸代谢的微生物群落组成，在维持草酸体内平衡和预防相关健康问题，特别是草酸钙肾结石方面起着关键作用。关键生物，特别是formigenes草酸杆菌，对降解草酸盐至关重要，但它们的丰度受到饮食、遗传和抗生素使用等因素的影响。最近的研究进展已经阐明了肠道微生物群和草酸代谢之间复杂的相互作用，强调了治疗干预的潜力。包括RNA干扰疗法（如lumasiran、nedosiran）、工程益生菌和基因编辑技术在内的创新策略，在治疗原发性高血氧症等疾病方面显示出希望。然而，挑战仍然存在，包括草酸测量技术的局限性和微生物种群的可变性。多组学方法和宏基因组学分析增强了我们对草酸生物组的理解，揭示了新的微生物分类群和参与草酸降解的代谢途径。尽管新兴疗法具有潜力，但临床转化仍处于起步阶段，需要进一步研究以确定有效性和安全性。未来的研究应集中在机制的见解，标准化的方法和靶向微生物为基础的治疗，以优化管理策略的高草酸尿和相关的系统性疾病。全面了解草酸组对于开发精确医学方法有效解决草酸盐失调和改善患者预后至关重要。

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引用次数: 0

Saliva Speaks: A Critical Analysis of Salivary Biomarkers as an Early Oral Cancer Diagnostic Tool 唾液生物标志物在早期口腔癌诊断中的应用。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-24 DOI: 10.1016/j.cca.2026.120853

Bidisha Kongor, Ritam Chatterjee

Saliva is an easily accessible bio-fluid which consists of various diagnostic components that can reflect any tumor-related changes, offering a promising non-invasive approach for more accurate and early detection of oral cancer. The primary aim of this review is to provide an integrative evaluation of salivary biomarkers for oral cancer by combining qualitative synthesis with a semi-quantitative analysis of various diagnostic parameters. The work highlights biomarker trends by understanding their diagnostic potential across molecular categories through the visual representation of these quantitative data in bar graphs and heatmaps. Comprehensive literature evaluation was performed by using search engines like Pubmed, Science Direct, Google Scholar etc. on the topic of using salivary biomarkers as an oral cancer detection tool. Relevant data on study design, demographic information, sample type, analytical method, biomarker significance etc. were qualitatively summarized. Quantitative parameters including sensitivity, specificity, accuracy and p-values were either extracted or calculated from selected studies and visualized through bar graphs and heatmaps to facilitate comparative interpretation of diagnostic performance. Multiple salivary biomarkers were identified across genomic, transcriptomic, proteomic, metabolomic, and metagenomic levels, each showing significant involvement in molecular alterations and metabolic pathway dysregulation linked to oral malignancies. This review offers a novel semi-quantitative approach that bridges comprehensive literature summarization with diagnostic data interpretation. By integrating quantitative indices into bar graphs and heatmaps, it enables rapid visual comparison of salivary biomarker performance by revealing high-performing candidates of early oral cancer detection. Thus, saliva-based diagnostics hold great potential as a non-invasive, cost-effective reliable alternative to the conventional oral cancer detection methods.

唾液是一种容易获得的生物液体，它由各种诊断成分组成，可以反映任何肿瘤相关的变化，为更准确和早期检测口腔癌提供了一种有前途的非侵入性方法。本综述的主要目的是通过对各种诊断参数的定性合成和半定量分析相结合，提供口腔癌唾液生物标志物的综合评估。这项工作通过在条形图和热图中可视化地表示这些定量数据，了解生物标志物在分子类别中的诊断潜力，从而突出了生物标志物的趋势。利用Pubmed、Science Direct、谷歌Scholar等搜索引擎对唾液生物标志物作为口腔癌检测工具进行综合文献评价。对研究设计、人口学信息、样本类型、分析方法、生物标志物意义等相关数据进行定性总结。从选定的研究中提取或计算定量参数，包括灵敏度、特异性、准确性和p值，并通过条形图和热图进行可视化，以便对诊断性能进行比较解释。在基因组学、转录组学、蛋白质组学、代谢组学和宏基因组学水平上鉴定出多种唾液生物标志物，每种标志物都显示出与口腔恶性肿瘤相关的分子改变和代谢途径失调的显著参与。本综述提供了一种新颖的半定量方法，将综合文献总结与诊断数据解释联系起来。通过将定量指标整合到条形图和热图中，它可以通过揭示早期口腔癌检测的高性能候选物来快速直观地比较唾液生物标志物的性能。因此，基于唾液的诊断作为一种非侵入性的、具有成本效益的、可靠的替代传统口腔癌检测方法具有很大的潜力。

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引用次数: 0

Circulating biomarkers in leukemia 白血病中的循环生物标志物。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-23 DOI: 10.1016/j.cca.2026.120865

Aiyun Dong , Mehdi Jahedi Zargar , Amirhossein Mirzazadeh , Mohammad Navid Khaksari , Mobina Nazari , Niloofar Pilehvari , Hamed Soleimani Samarkhazan

Liquid biopsy is a minimally invasive approach that analyzes circulating biomarkers, including cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and extracellular vesicles (EVs), to provide real-time information about the genetic and epigenetic state of hematologic malignancies. Compared with bone-marrow biopsy, blood-based assays enable serial sampling and can better capture temporal changes and spatial heterogeneity. Advances in high-throughput sequencing and digital PCR have improved detection sensitivity for minimal residual disease (MRD), clonal evolution, and resistance mutations. Integration of circulating biomarkers into clinical care may support personalized treatment decisions and earlier relapse detection, but barriers remain: assay standardization, biological variability, and interpretation of low-frequency variants. Interpretation of existing clinical studies suggests that ctDNA kinetics (for example, early on-treatment clearance vs persistent detection) frequently correlate with progression-free and overall survival (OS) in lymphoid and myeloid malignancies, supporting ctDNA as a candidate early surrogate of treatment benefit; however, sensitivity differs by disease biology (marrow-predominant AML vs nodal lymphomas) and therefore ctDNA should be used in combination with marrow-based MRD and leukocyte sequencing until prospective standardization is established. This review summarizes current technologies, clinical applications, and translational opportunities for circulating biomarkers in leukemia and discusses outstanding challenges for clinical implementation.

液体活检是一种微创方法，可分析循环生物标志物，包括游离细胞DNA （cfDNA）、循环肿瘤DNA （ctDNA）、microrna （miRNAs）和细胞外囊泡（ev），以提供有关血液系统恶性肿瘤遗传和表观遗传状态的实时信息。与骨髓活检相比，血液检测能够进行连续采样，并能更好地捕捉时间变化和空间异质性。高通量测序和数字PCR技术的进步提高了微小残留病（MRD）、克隆进化和耐药突变的检测灵敏度。将循环生物标志物整合到临床护理中可以支持个性化治疗决策和早期复发检测，但仍然存在障碍：检测标准化、生物学变异性和低频变异的解释。对现有临床研究的解释表明，ctDNA动力学（例如，早期治疗清除率与持续检测）通常与淋巴和髓系恶性肿瘤的无进展和总生存期（OS）相关，支持ctDNA作为治疗获益的候选早期替代品；然而，敏感性因疾病生物学而异（骨髓型AML vs淋巴结型淋巴瘤），因此ctDNA应与基于骨髓的MRD和白细胞测序联合使用，直到建立前瞻性标准化。本文综述了白血病循环生物标志物的当前技术、临床应用和转化机会，并讨论了临床实施的突出挑战。

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引用次数: 0

Identification of diabetic kidney disease biomarkers via iTRAQ plasma proteomics analysis 通过iTRAQ血浆蛋白质组学分析鉴定糖尿病肾病生物标志物。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-23 DOI: 10.1016/j.cca.2026.120866

Juan Yuan , Man Zhan , Xinglai Zhang , Xixiao Lin , Wei Lu , Xi Yan , Zhiyuan Liang , Yuan Sun , Minshan Su , Liming Shen , Haiying Li

Diabetic kidney disease (DKD) is a major diabetic complication that often progresses to end-stage renal disease and causes high mortality. Early diagnosis is essential for effective prevention and treatment. To explore the underlying mechanisms of DKD and identify plasma biomarkers for early diagnosis. In this study, healthy adults and individuals with diabetes mellitus (classified into normal albuminuria (NA), microalbuminuria (MI), and macroalbuminuria (MA) groups) were recruited. Plasma samples were collected from all participants, and 12 subjects per group were then randomly selected as a discovery cohort for proteomic analysis. Proteomics identified 95 differentially expressed proteins (DEPs) among the groups. These DEPs associated pathways evolved in a stage-specific manner in which inflammation dominated the early NA/Ctrl stage, complement and coagulation cascades became the main drivers during MI/NA, and MA/MI exhibited newly emerged disturbances in oxidative detoxification, lysosomal function, and nitrogen metabolism alongside sustained complement and coagulation changes. Among them, the complement and coagulation cascades were closely related to DKD progression. Through hub protein analysis, five proteins (FGG, ITIH4, A2M, C3, and APOE) that showed consistent trends across disease stages were identified as potential diagnostic biomarkers for DKD. Our research provides new insights into the mechanisms and early diagnosis of DKD.

糖尿病肾病（DKD）是一种主要的糖尿病并发症，经常发展为终末期肾脏疾病，并导致高死亡率。早期诊断对于有效预防和治疗至关重要。探讨DKD的潜在机制，并确定早期诊断的血浆生物标志物。本研究招募了健康成人和糖尿病患者（分为正常蛋白尿（NA）、微量蛋白尿（MI）和大量蛋白尿（MA）组）。收集所有参与者的血浆样本，然后每组随机选择12名受试者作为发现队列进行蛋白质组学分析。蛋白质组学鉴定了组间95个差异表达蛋白（DEPs）。这些DEPs相关通路以一种特定阶段的方式进化，其中炎症主导了NA/Ctrl早期阶段，补体和凝血级联成为MI/NA期间的主要驱动因素，MA/MI在氧化解毒、溶酶体功能和氮代谢方面表现出新出现的紊乱，同时持续的补体和凝血变化。其中，补体级联和凝血级联与DKD进展密切相关。通过枢纽蛋白分析，五种蛋白（FGG、ITIH4、A2M、C3和APOE）在疾病分期中表现出一致的趋势，被确定为DKD的潜在诊断生物标志物。我们的研究为DKD的发病机制和早期诊断提供了新的见解。

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引用次数: 0

Analytical performance evaluation and reference limits establishment of a new chemiluminescence growth stimulation expressed Gene 2 Assay 新的化学发光生长刺激表达基因2测定法的分析性能评价及参考限的建立。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-22 DOI: 10.1016/j.cca.2026.120850

Litao Zhang , Chenbin Zhang , Xin Shu , Jiajia Zhu , Hui Wang , Ting Deng , Yisha Jing , Haiyan Liu , Zhenlu Zhang

Background and objectives

Growth stimulation expressed gene 2 (ST2) is an established biomarker for assessing myocardial fibrosis and ventricular remodeling in heart disease. This study aimed to comprehensively evaluate the analytical performance of a novel chemiluminescent immunoassay (CLIA) for ST2 and to establish its reference limits.

Methods

Analytical performance, including precision, detection capability, linearity, interference, and sample type correlation, was validated according to CLSI guidelines. A method comparison was conducted with the Presage ST2 ELISA (Critical Diagnostics). Sex-specific 99th percentile upper reference limits (URLs) were established from 1592 healthy adults.

Results

The ST2 (CLIA) assay demonstrated high precision, with both repeatability and reproducibility CVs < 5%. The limits of blank (LoB), detection (LoD), and quantitation (LoQ) were within the claimed specifications. The assay showed excellent linearity from 2.00 to 2000 ng/mL (r > 0.99). No significant interference was observed, and correlations between different sample types were high (r > 0.99). Method comparison with the Presage ST2 assay yielded a regression equation of y = 1.0365x - 1.9307 (r = 0.9760). The 99th percentile URLs were 42.3 ng/mL for males, 36.2 ng/mL for females, and 37.7 ng/mL for the overall cohort.

Conclusions

The Mindray ST2 chemiluminescent immunoassay exhibits robust analytical performance, meeting the demands of clinical practice with high precision, sensitivity, and specificity. The established reference intervals support its application for precise patient stratification.

背景和目的：生长刺激表达基因2 （Growth stimulation expressed gene 2, ST2）是评估心脏病患者心肌纤维化和心室重构的生物标志物。本研究旨在综合评价一种新型化学发光免疫分析法（CLIA）对ST2的分析性能，并建立其参考限。方法：根据CLSI指南对分析性能进行验证，包括精密度、检测能力、线性度、干扰度和样品类型相关性。与Presage ST2 ELISA （Critical Diagnostics）进行方法比较。结果：ST2 （CLIA）检测结果精密度高，重复性和再现性均良好（CVs  0.99）。无显著干扰，不同样本类型间相关性高（r > 0.99）。方法与Presage ST2法比较得到y = 1.0365x - 1.9307 （r = 0.9760）的回归方程。男性的第99百分位url为42.3 ng/mL，女性为36.2 ng/mL，整个队列为37.7 ng/mL。结论：迈瑞ST2化学发光免疫分析法具有良好的分析性能，具有较高的精密度、灵敏度和特异性，满足临床应用的需要。已建立的参考区间支持其用于精确患者分层的应用。

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引用次数: 0