Clinica Chimica Acta最新文献_第4页

ALT-triggered reflex AST testing in health check-ups: A decision curve analysis 健康检查中alt触发反射性AST检测：决策曲线分析。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-03-15 Epub Date: 2026-01-20 DOI: 10.1016/j.cca.2026.120848

Shu-Mei Bai , Xu-Xiao Guo , Guo-Ming Zhang

Background

Aspartate aminotransferase (AST) is frequently co-ordered with alanine aminotransferase (ALT) in routine health check-ups, although universal AST testing may have a low clinical yield in asymptomatic individuals. We evaluated ALT-triggered reflex AST testing via decision curve analysis (DCA) to identify implementable screening policies.

Methods

We retrospectively analysed adult health check-up records with paired ALT and AST results. Reflex strategies were simulated in which AST was measured only when ALT exceeded predefined thresholds (15–60 U/L). Pathological AST was defined via sex-specific upper reference limits (URL). Clinical utility was assessed via DCA, where threshold probability (pt) represents the trade-off between unnecessary testing and missed pathological results. The primary analysis prespecified pt. = 1%, with pt. = 1%–5% examined in sensitivity analyses.

Results

Among 46,059 participants (20,489 females; 25,570 males), AST ≥ URL was observed in 5.52% of females and 7.35% of males. At pt. = 1%, DCA supported sex-specific ALT triggers of ≥19 U/L for females and ≥ 26 U/L for males. These policies reduced AST testing to 34.8% and 46.7%, respectively, while maintaining sensitivities of 97.9% and 98.0%, respectively. The number of individuals with pathological AST who would be missed under the reflex policy was 11.7 and 14.9 per 10,000 screened. Across low pt. ranges, reflex strategies consistently achieved greater net benefits than did universal testing.

Conclusions

ALT-triggered reflex AST testing can substantially reduce low-yield AST measurements during health check-ups with minimal loss of screening sensitivity. The DCA provides a transparent framework for selecting sex-specific, screening-oriented policy thresholds.

背景：在常规健康检查中，谷草转氨酶（AST）经常与丙氨酸转氨酶（ALT）共序，尽管普遍的AST检测在无症状个体中可能有较低的临床产量。我们通过决策曲线分析（DCA）评估alt触发的反射性AST检测，以确定可实施的筛查政策。方法回顾性分析成人健康体检记录中ALT和AST的配对结果。模拟反射策略，仅当ALT超过预定义阈值（15-60 U/L）时测量AST。病理AST通过性别特异性参考上限（URL）定义。通过DCA评估临床效用，其中阈值概率（pt）代表不必要的测试和错过的病理结果之间的权衡。初步分析预先指定pt. = 1%，在敏感性分析中检查pt. = 1%-5%。结果：在46059名参与者中（女性20489人，男性25570人），5.52%的女性和7.35%的男性存在AST ≥ URL。在pt. = 1%时，DCA支持女性≥19 U/L和男性 ≥ 26 U/L的性别特异性ALT触发。这些政策将AST检测分别降低到34.8%和46.7%，同时保持了97.9%和98.0%的敏感性。在反射政策下，病理性AST个体的漏诊率分别为11.7 / 10000和14.9 / 10000。在低pt范围内，反射策略始终比通用测试获得更大的净收益。结论：alt触发的反射性谷草转氨酶检测可以显著降低健康检查中谷草转氨酶的低产率，同时使筛查敏感性损失最小。DCA为选择特定性别、面向筛选的政策阈值提供了一个透明的框架。

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引用次数: 0

Oxidative stress in diabetic retinopathy 氧化应激在糖尿病视网膜病变中的作用

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-03-15 Epub Date: 2026-01-27 DOI: 10.1016/j.cca.2026.120871

Qiang Zou , Niu Niu , Leilei Sun , Xiaoyan Xu , Yu Wang , Hong Qin

Diabetic retinopathy (DR) remains a leading cause of blindness, with oxidative stress as a central pathogenic driver. However, the translation of this mechanistic knowledge into clinical diagnostics and targeted therapies has been hampered by inconsistent biomarkers and a simplistic view of redox balance. This critical review moves beyond cataloging oxidative markers to evaluate their biological specificity, analytical robustness, and compartmentalization between systemic circulation and the ocular microenvironment. We dissect the technical challenges of direct reactive species measurement and appraise established markers of macromolecular damage, lipid peroxidation adducts, protein carbonyls, and oxidized nucleic acids, emphasizing that analytical rigor is paramount for interpretability. Furthermore, we explore integrative pathways linking glycoxidation, inflammation, and VEGF in a feed-forward loop. A key translational hurdle is the poor correlation between systemic biomarkers and intraretinal oxidative events. We propose a future roadmap featuring a tiered “DR oxidative stress profile” that combines scalable systemic screening with pathway-specific panels and advanced ocular imaging. This refined approach aims to enable precision phenotyping, enriching clinical trials for mechanism-targeted therapies and ultimately paving the way for personalized antioxidant strategies tailored to the dominant oxidative axis in individual patients.

糖尿病视网膜病变（DR）仍然是失明的主要原因，氧化应激是主要的致病驱动因素。然而，将这种机制知识转化为临床诊断和靶向治疗一直受到不一致的生物标志物和氧化还原平衡的简单化观点的阻碍。这篇重要的综述超越了对氧化标记物的分类，评估了它们的生物特异性、分析稳健性以及体循环和眼微环境之间的区隔性。我们剖析了直接反应物种测量的技术挑战，并评估了大分子损伤、脂质过氧化加合物、蛋白质羰基和氧化核酸的已建立标记物，强调分析的严密性对可解释性至关重要。此外，我们探索了在前馈循环中连接糖氧化，炎症和VEGF的综合途径。一个关键的翻译障碍是系统生物标志物与视网膜内氧化事件之间的相关性较差。我们提出了一个未来的路线图，其特点是分层的“DR氧化应激谱”，将可扩展的系统筛查与通路特异性面板和先进的眼部成像相结合。这种改进的方法旨在实现精确的表型，丰富机制靶向治疗的临床试验，并最终为针对个体患者的主要氧化轴量身定制个性化抗氧化策略铺平道路。

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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 : 2026-03-15 Epub 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

Combining conventional hemogram and reticulocyte metrics enhances iron deficiency detection in asymptomatic individuals 结合常规和网织红细胞指标提高铁缺乏检测在无症状的个体。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-03-15 Epub Date: 2026-01-29 DOI: 10.1016/j.cca.2026.120877

Mugdha Gautam , Prashant Sharma , Arnab Pal , Pulkit Rastogi , Praveen Sharma , Alka Rani Khadwal , Manu Jamwal , Minakshi Gupta , Reena Das

Introduction

Iron deficiency (ID) is the most common micronutrient deficiency globally, often underdiagnosed due to nonspecific symptoms and limitations of standard laboratory tests. Reticulocyte-derived indices from modern hematology analyzers offer enhanced early detection of iron-restricted erythropoiesis.

Methods

We studied 103 self-reported asymptomatic healthy adults who underwent complete blood counts and reticulocyte analysis on XN-2000 analyzers (Sysmex Corp., Kobe, Japan). Detailed biochemical iron profile and vitamin B12/folate testing were done. Diagnostic performance of hematologic parameters was assessed and combinatorial logistic regression models and discriminant indices were developed.

Results

Participants' median age was 28 years (range 22–79); 69.9% (n = 72) were women. 54.4% (n = 56) had ID and 21.4% (n = 22) were anemic. Latent ID was detected in 34.9% (36/103). B12 and folate deficiencies were present in 41% and 40%, respectively - extensively overlapping with ID. Key individual indices for ID included RET-He, RET-Y, and RET-RBC-Y, each with area under the ROC curve (AUC) >85%. A comprehensive 21-variable logistic regression model yielded AUC 93.7% (95% C.I. 88.9–98.5), sensitivity 89.1%, and specificity 70.2%. A pared-down 3-variable model achieved AUC 90.1% (95% C.I. 84.1–96.1), sensitivity 87.5%, and specificity 70.9%. Of the two heuristic composite indices tested, one – [RDW-CV × PLT × 10⁵] / [RET-He × RET-RBC-Y × IRF-Y × RET-Y] - showed AUC 89.8% (95% C.I. 83.7–95.9), sensitivity 87%, and specificity 72.3%.

Conclusion

In a cohort with high rates of nutritional deficiency, cost-effective equations combining conventional and advanced reticulocyte indices demonstrated strong diagnostic utility for screening ID, with potential for broader application in resource-limited settings.

铁缺乏症（ID）是全球最常见的微量营养素缺乏症，由于非特异性症状和标准实验室检查的局限性，经常未得到诊断。网状红细胞衍生指数从现代血液学分析仪提供增强早期检测铁限制性红细胞。方法：我们研究了103名自我报告无症状的健康成年人，他们用XN-2000分析仪（Sysmex Corp., Kobe, Japan）进行了全血细胞计数和网织红细胞分析。详细的生化铁谱和维生素B12/叶酸检测。评估血液学参数的诊断性能，并建立组合逻辑回归模型和判别指标。结果：参与者的中位年龄为28 岁（范围22-79）；69.9% （n = 72）为女性。54.4% （n = 56）为ID， 21.4% （n = 22）为贫血。潜伏ID检出率为34.9%（36/103）。B12和叶酸缺乏症分别占41%和40%，与缺乏症广泛重叠。ID的关键个体指标包括RETHe、RETY和RET-RBC-Y， ROC曲线下面积（AUC）均为85%。综合21变量logistic回归模型的AUC为93.7% (95% ci为88.9-98.5)，灵敏度为89.1%，特异性为70.2%。精简的3变量模型达到AUC 90.1% (95% ci 84.1-96.1)，敏感性87.5%，特异性70.9%。在两项启发式综合指标中，[RDW-CV × PLT × 105]/ [RET-He × RET-RBC-Y × IRF-Y × RET-Y]的AUC为89.8% (95% C.I. 83.7-95.9)，灵敏度为87%，特异性为72.3%。结论：在营养缺乏率高的队列中，结合传统和先进网织红细胞指数的成本效益方程显示出筛查ID的强大诊断效用，在资源有限的环境中具有更广泛的应用潜力。

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引用次数: 0

Development of machine learning-driven non-invasive diagnostic models for idiopathic membranous nephropathy in Chinese patients 机器学习驱动的中国特发性膜性肾病无创诊断模型的建立。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-03-15 Epub Date: 2026-02-02 DOI: 10.1016/j.cca.2026.120882

Qian Wang , Xiaolong Wang , Shibin Su , Weiguang Zhang , Quan Hong , Qiang Lyu , Shuwei Duan , Ying Zheng , Guichun Tang , Pu Chen , Jiaona Liu , Chengliang Yin , Jinlong Shi , Guangyan Cai , Xiangmei Chen , Zheyi Dong

Background

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome and end-stage renal disease, but the gold-standard diagnostic method is invasive. This study aims to develop a non-invasive diagnostic model for IMN, focus on the diagnostic value of anti-phospholipase A2 receptor antibody (anti-PLA2R-Ab).

Patients and methods

In this single-center retrospective study,we included 9524 patients with chronic kidney disease patients who received renal biopsies, extracted 139 clinicopathological data from their records, and divided them into two groups based on pathological results.Renal biopsy cases were collected to form an independent external validation cohort.Seven machine learning methods were used to develop and verify models, and anti-PLA2R-Ab data were used to optimize and evaluate these models. Seventy percent of the patients were used for training, and the other 30% for verification. The area under the receiver operating characteristic curve, F1-score, accuracy, and confusion matrix were used to evaluate the diagnostic performance of the models.

Results

We analyzed 8840 patients and 10 indicators, excluding anti-PLA2R-Ab, to develop and validate diagnostic models, and then analyzed 2457 patients and 6 indicators, including anti-PLA2R-Ab, to develop and validate optimized models. With or without anti-PLA2R-Ab, the CatBoost model provided more accurate diagnosis of IMN (internal vs. external verification AUC:0.921 vs.0.901 and 0.950 vs.0.904, respectively) than anti-PLA2R-Ab alone (AUC: 0.867).

Conclusion

The CatBoost model was an accurate and non-invasive method that provided better diagnosis of IMN than anti-PLA2R-Ab in Chinese patients. This model is especially when anti-PLA2R-Ab testing and kidney biopsy are difficult or impossible.

背景：特发性膜性肾病（IMN）是肾病综合征和终末期肾病的主要病因，但其金标准诊断方法是侵入性的。本研究旨在建立IMN的无创诊断模型，重点探讨抗磷脂酶A2受体抗体（anti-PLA2R-Ab）的诊断价值。患者和方法：在这项单中心回顾性研究中，我们纳入9524例接受肾活检的慢性肾脏疾病患者，从其记录中提取139例临床病理资料，并根据病理结果将其分为两组。收集肾活检病例，形成一个独立的外部验证队列。使用7种机器学习方法开发和验证模型，并使用anti-PLA2R-Ab数据对这些模型进行优化和评估。70%的患者用于培训，另外30%用于验证。使用受试者工作特征曲线下面积、f1评分、准确率和混淆矩阵来评估模型的诊断性能。结果：我们分析了8840例患者和10项指标（不包括抗pla2r - ab）建立并验证了诊断模型，然后分析了2457例患者和6项指标（包括抗pla2r - ab）建立并验证了优化模型。无论是否使用抗pla2r - ab， CatBoost模型比单独使用抗pla2r - ab （AUC: 0.867）更准确地诊断IMN（内部与外部验证AUC分别为0.921 vs.0.901和0.950 vs.0.904）。结论：CatBoost模型是一种准确、无创的诊断IMN的方法，其诊断效果优于抗pla2r - ab。这种模式尤其适用于抗pla2r - ab检测和肾活检困难或不可能的情况。

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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 : 2026-03-15 Epub 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

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 : 2026-03-15 Epub 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

Comparison of manual with artificial intelligence-aided interpretation of ANA HEp-2 IIF assay patterns in a clinical diagnostics lab 临床诊断实验室人工与人工智能辅助解释ANA HEp-2 IIF分析模式的比较

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-03-15 Epub Date: 2026-01-31 DOI: 10.1016/j.cca.2026.120881

Jonas Schmidt , Sarina Weiß , Frithjof Blessing , Josef Blessing , Peter Schierack , Stefan Rödiger , Rico Hiemann , Dirk Roggenbuck

Objectives

Detection of antinuclear antibody (ANA) via indirect immunofluorescence (IIF) on HEp-2 cells is a screening test for the serological diagnosis of systemic autoimmune rheumatic diseases. Automated interpretation of ANA classification by novel artificial intelligence (AI)-aided pattern recognition was compared with expert reading under routine conditions.

Methods

Consecutive serum samples of 2671 individuals referred to a routine laboratory were analysed for ANA titers and patterns using the automated interpretation system akironNeo. AI-based ANA detection was compared with independent classification by two experienced immunologists according to the international consensus on ANA patterns (ICAP) competence level.

Results

Overall, a good agreement (κ > 0.60) between the different evaluators both for positive/negative classification of ANA fluorescence images as well as for the pattern classification of positive samples with a titer ≥ 1:320 was observed. Positive/negative differentiation at different cut-offs revealed κ values from 0.584 to 0.760 whereas corresponding pattern recognition for interphase, metaphase and cytoplasmic patterns demonstrated κ values from 0.560 to 0.736 for samples scored as positive by all three evaluators.

Conclusions

The AI-based software showed a similar performance compared to human observers. AI-aided ANA image analysis can facilitate the diagnostic workflow of ANA IIF assays and reduce subjectivity during image classification.

目的：间接免疫荧光法（IIF）检测HEp-2细胞抗核抗体（ANA）是系统性自身免疫性风湿病血清学诊断的筛选试验。采用新型人工智能（AI）辅助模式识别对ANA分类进行自动判读，并与常规条件下的专家判读进行比较。方法：使用akironNeo自动判读系统分析2671例常规实验室连续血清样本的ANA滴度和模式。根据国际上对ANA （ICAP）能力水平的共识，由两位经验丰富的免疫学家对基于ai的ANA检测与独立分类进行比较。结果：总的来说，不同的评估器在ANA荧光图像的阳性/阴性分类以及滴度≥ 1:20 20的阳性样本的模式分类方面都有很好的一致性（κ > 0.60）。在不同的截断值下，阳性/阴性分化的κ值从0.584到0.760不等，而对间期、中期和细胞质模式的相应模式识别显示，被所有三个评估器评分为阳性的样本的κ值从0.560到0.736不等。结论：与人类观察者相比，基于人工智能的软件表现出相似的表现。人工智能辅助ANA图像分析可以简化ANA IIF分析的诊断工作流程，减少图像分类过程中的主观性。

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引用次数: 0

Exosomal microRNA biomarkers in ovarian cancer detection: systematic review and meta-analysis 外泌体microRNA生物标志物在卵巢癌检测中的应用：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 : 2026-03-15 Epub Date: 2025-12-06 DOI: 10.1016/j.cca.2025.120771

Qidan Huang , Jieping Chen , Jingsong Huang

Background

Ovarian cancer (OC) is the deadliest gynecologic malignancy, mainly due to late-stage diagnosis and the limited accuracy of biomarkers such as Carbohydrate Antigen 125 and Human Epididymis Protein 4. Exosomal microRNAs are promising non-invasive biomarkers for early OC detection. This study assessed the diagnostic accuracy of these methods through a systematic review and meta-analysis.

Methods

PubMed, EMBASE, and Web of Science were searched for studies indexed to 29 June 2025 using predefined MeSH and free-text terms. Studies were screened in Rayyan under a PICO framework. Reviewers extracted data on study design, exosomal miRNAs, sample type, detection method, and diagnostic performance. Quality was assessed using a modified QUADAS-2 tool. Meta-analysis in STATA (“MIDAS” package) calculated pooled sensitivity, specificity, and area under the summary ROC (SROC) curve. Heterogeneity was evaluated using the I² statistic, and publication bias was assessed with Deeks' funnel-plot test.

Results

Twenty-seven studies met inclusion criteria; diagnostic data from 16 cohorts were pooled. Sensitivity and specificity were 0.82 (95 % CI: 0.76–0.86) and 0.81 (95 % CI: 0.75–0.86), with an SROC area of 0.88. No publication bias was detected.

Conclusion

Exosomal miRNAs show strong diagnostic accuracy for non-invasive OC detection. Standardized methods and prospective validation are required for clinical application.

背景：卵巢癌（OC）是最致命的妇科恶性肿瘤，主要是由于晚期诊断和生物标志物如碳水化合物抗原125和人类附睾蛋白4的准确性有限。外泌体microrna是一种很有希望用于早期卵巢癌检测的非侵入性生物标志物。本研究通过系统回顾和荟萃分析评估了这些方法的诊断准确性。方法：使用预定义的MeSH和自由文本术语检索PubMed、EMBASE和Web of Science，检索索引为2025年6月29日的研究。在PICO框架下对Rayyan的研究进行了筛选。审稿人提取了研究设计、外泌体mirna、样本类型、检测方法和诊断性能方面的数据。使用改进的QUADAS-2工具评估质量。STATA（“MIDAS”包）的荟萃分析计算了汇总的敏感性、特异性和总结ROC曲线下的面积。采用I2统计量评估异质性，采用Deeks漏斗图检验评估发表偏倚。结果：27项研究符合纳入标准；汇集了16个队列的诊断数据。敏感性和特异性分别为0.82（95 % CI: 0.76-0.86）和0.81(95 % CI: 0.75-0.86)， SROC面积为0.88。未发现发表偏倚。结论：外泌体miRNAs在无创OC检测中具有较强的诊断准确性。临床应用需要标准化方法和前瞻性验证。

{"title":"Exosomal microRNA biomarkers in ovarian cancer detection: systematic review and meta-analysis","authors":"Qidan Huang , Jieping Chen , Jingsong Huang","doi":"10.1016/j.cca.2025.120771","DOIUrl":"10.1016/j.cca.2025.120771","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) is the deadliest gynecologic malignancy, mainly due to late-stage diagnosis and the limited accuracy of biomarkers such as Carbohydrate Antigen 125 and Human Epididymis Protein 4. Exosomal microRNAs are promising non-invasive biomarkers for early OC detection. This study assessed the diagnostic accuracy of these methods through a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>PubMed, EMBASE, and Web of Science were searched for studies indexed to 29 June 2025 using predefined MeSH and free-text terms. Studies were screened in Rayyan under a PICO framework. Reviewers extracted data on study design, exosomal miRNAs, sample type, detection method, and diagnostic performance. Quality was assessed using a modified QUADAS-2 tool. Meta-analysis in STATA (“MIDAS” package) calculated pooled sensitivity, specificity, and area under the summary ROC (SROC) curve. Heterogeneity was evaluated using the I<sup>2</sup> statistic, and publication bias was assessed with Deeks' funnel-plot test.</div></div><div><h3>Results</h3><div>Twenty-seven studies met inclusion criteria; diagnostic data from 16 cohorts were pooled. Sensitivity and specificity were 0.82 (95 % CI: 0.76–0.86) and 0.81 (95 % CI: 0.75–0.86), with an SROC area of 0.88. No publication bias was detected.</div></div><div><h3>Conclusion</h3><div>Exosomal miRNAs show strong diagnostic accuracy for non-invasive OC detection. Standardized methods and prospective validation are required for clinical application.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120771"},"PeriodicalIF":2.9,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR/Cas9 and reproductive failure: applications, ethical challenges, and future perspectives in human germline genome editing CRISPR/Cas9和生殖失败：在人类种系基因组编辑中的应用、伦理挑战和未来展望

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-03-15 Epub Date: 2026-01-29 DOI: 10.1016/j.cca.2026.120875

Wasim Shah , Mujahid Hussain , Ayesha Serwat , Muhammad Bilal , Yousaf Raza , Abu Mansoor , Ahmad Faraz

Reproductive failure affects millions of couples worldwide and frequently arises from genetic defects that impair gametogenesis, fertilization, or early embryonic development. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing technology has emerged as a powerful experimental platform for dissecting infertility-associated genes and, in principle, correcting pathogenic variants in germline cells or preimplantation embryos. This review critically examines current applications of CRISPR/Cas9 in reproductive biology, including disease modeling in animal systems, editing of spermatogonial stem cells (SSCs), manipulation of oocytes and zygotes, and proof-of-concept studies in human embryos.

Particular emphasis is placed on the major technical barriers that currently preclude clinical translation, including off-target mutagenesis, embryo mosaicism, and the low efficiency of homology-directed repair relative to non-homologous end joining. Limitations related to delivery strategies, DNA damage responses, chromosomal rearrangements, and the genetic heterogeneity of infertility are also evaluated. Comparative discussion highlights how germline editing differs fundamentally from somatic CRISPR therapies that have already reached clinical application in hematologic disorders.

The review further analyzes ethical and regulatory challenges associated with heritable genome modification, including long-term safety, consent across generations, international governance disparities, and the continued reliance on assisted reproductive technologies combined with preimplantation genetic testing as safer clinical alternatives. Collectively, current evidence indicates that CRISPR/Cas9 remains primarily a research tool for elucidating reproductive biology rather than an imminent therapeutic option for human infertility. Continued technological refinement, rigorous preclinical validation, and globally harmonized oversight will be essential before germline applications can be ethically or clinically justified.

生殖失败影响着全世界数以百万计的夫妇，通常是由于遗传缺陷影响配子发生、受精或早期胚胎发育而引起的。聚类规则间隔短回文体重复序列(CRISPR)/CRISPR相关蛋白9 （Cas9）基因组编辑技术已经成为一个强大的实验平台，用于解剖不孕症相关基因，原则上可以纠正种系细胞或植入前胚胎中的致病变异。本文综述了目前CRISPR/Cas9在生殖生物学中的应用，包括动物系统中的疾病建模、精原干细胞（ssc）的编辑、卵母细胞和受精卵的操作以及人类胚胎的概念验证研究。特别强调的是目前阻碍临床翻译的主要技术障碍，包括脱靶突变，胚胎镶嵌，以及相对于非同源末端连接的同源定向修复的低效率。与分娩策略、DNA损伤反应、染色体重排和不孕症的遗传异质性相关的局限性也进行了评估。比较讨论强调了生殖系编辑与已经在血液病中达到临床应用的体细胞CRISPR治疗有何根本不同。这篇综述进一步分析了与遗传性基因组修饰相关的伦理和监管挑战，包括长期安全性、跨代同意、国际治理差异，以及继续依赖辅助生殖技术结合植入前基因检测作为更安全的临床选择。总的来说，目前的证据表明，CRISPR/Cas9仍然主要是一种阐明生殖生物学的研究工具，而不是人类不孕症的迫在眉睫的治疗选择。持续的技术改进、严格的临床前验证和全球统一的监督将是必要的，才能在伦理或临床证明生殖系应用是合理的。

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引用次数: 0