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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 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 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 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 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 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 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 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
Plasma non-targeted metabolomics unveils the metabolic signatures of trans-right ventricle in pulmonary arterial hypertension associated with atrial septal defect 血浆非靶向代谢组学揭示了肺动脉高压伴房间隔缺损患者经右心室的代谢特征。
IF 2.9 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2026-01-21 DOI: 10.1016/j.cca.2026.120849
Xifeng Qian , Yuanrui Deng , Tingting Guo , Xin Huang , Chaowu Yan , Xin Gao , Yan Wu , Song Hu , Jiangshan Tan , Lingtao Chong , Shengsong Zhu , Mingjie Ma , Mengting Ye , Xiaojian Wang , Jian Cao , Lu Hua

Background

Understanding metabolic evolution of right ventricle (RV) of pulmonary arterial hypertension associated with atrial septal defect (PAH-ASD) helps elucidate the underlying pathobiology and reveal disease-specific biomarkers. However, the exact metabolic profile of RV of PAH-ASD is scarce.

Objectives

This study aimed to unveil precisely the metabolic signatures of trans-RV of PAH-ASD through non-targeted metabolomics.

Methods

Participants with PAH-ASD were recruited and their blood samples were obtained from superior vena cava (SVC) and pulmonary artery (PA) through right cardiac catheterization. Non-targeted metabolomics analysis on the basis of UHPLC-MS/MS was utilized to generate the metabolomic signature of trans-RV by comparing the metabolites change from SVC to PA.

Results

1060 metabolites were detected from blood samples from 40 PAH-ASD participants. A total of 44 differential metabolites were identified based on screening criteria after flowing through the RH, including 10 metabolites with decreased levels and 34 metabolites with increased levels. Among them, phosphatidylcholines, sphingomyelins, AICARP, XMP, inosine 5’-Monophosphate, prostaglandin A1, oleoyl ethanolamide, tyramine, 2-phenylethylamine, 23-nordeoxycholic acid, LPI 20:4, and LPE 22:6 were discovered. Moreover, distinct metabolic perturbations, such as the change of sphingomyelins, inosine 5’-Monophosphate and LPE 22:6, was correlated with the significant clinical variables indicating RV dysfunction in clinical association analysis.

Conclusion

Our study correctly defined metabolic signatures indicating towards a metabolic pathogenesis of trans-RV of PAH-ASD, emphasizing the importance of these metabolites in promoting of RV dysfunction and devising therapeutic strategies.
背景:了解肺动脉高压合并房间隔缺损(PAH-ASD)右心室(RV)的代谢演变有助于阐明潜在的病理生物学和揭示疾病特异性生物标志物。然而,PAH-ASD中RV的确切代谢谱尚不清楚。目的:本研究旨在通过非靶向代谢组学精确揭示PAH-ASD反式rv的代谢特征。方法:招募PAH-ASD患者,通过右心导管从上腔静脉(SVC)和肺动脉(PA)采集血样。利用UHPLC-MS/MS基础上的非靶向代谢组学分析,通过比较SVC和PA的代谢物变化,生成trans-RV的代谢组学特征。结果:从40名PAH-ASD参与者的血液样本中检测到1060种代谢物。经过RH后,根据筛选标准共鉴定出44种差异代谢物,其中10种代谢物水平降低,34种代谢物水平升高。其中发现磷脂酰胆碱、鞘磷脂、AICARP、XMP、肌苷5′-单磷酸、前列腺素A1、油基乙醇酰胺、酪胺、2-苯乙胺、23-去氧胆酸、LPI 20:4、LPE 22:6。此外,在临床关联分析中,不同的代谢扰动,如鞘磷脂、肌苷5′-单磷酸和LPE 22:6的变化,与提示RV功能障碍的重要临床变量相关。结论:本研究正确定义了PAH-ASD反式右心室代谢机制的代谢特征,强调了这些代谢物在促进右心室功能障碍中的重要性,并制定了治疗策略。
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引用次数: 0
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 Pub 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
Validating CALIPER pediatric reference intervals in a U.S. population using retrospective outpatient data and RefineR 使用回顾性门诊数据和RefineR在美国人群中验证CALIPER儿科参考间隔。
IF 2.9 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2026-01-19 DOI: 10.1016/j.cca.2026.120846
Jillian Kodger , Thomas J.S. Durant , Nalan Yurtsever , Joe M. El-Khoury

Background

Accurate pediatric reference intervals (RIs) are critical for proper interpretation of laboratory results, yet their development is challenged by age-related physiological variation, limited sample sizes, and preanalytical variability. This study evaluates the applicability of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) RIs to a US-based, diverse pediatric outpatient population using both the RefineR inverse modeling approach and the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c recommended approach.

Methods

Outpatient laboratory data from 51,863 patients under 19 years of age were collected from a single institution between January 2023 and December 2024. Nine commonly ordered chemistry analytes were evaluated. RIs were derived using both RefineR and CLSI guidelines with bootstrap resampling. These were compared to CALIPER RIs using a color-coded flagging system based on 95% confidence intervals and total allowable error (TAE).

Results

RefineR-based RIs aligned with CALIPER values in 86 out of 88 age- and gender-specific analyte groups, whereas CLSI-derived RIs aligned in 79 out of 88. Notable discrepancies involved alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and blood urea nitrogen, often influenced by known preanalytical and physiological variables such as sample type, body mass index (BMI), and hydration status.

Conclusions

RefineR demonstrated superior alignment with CALIPER RIs compared to CLSI guidelines, highlighting its robustness in outpatient pediatric populations. Given its tolerance to mixed data and skewed distributions, RefineR offers a more practical and accurate method for deriving population-specific RIs in pediatric laboratory medicine, and helps verify the implementation of external RIs, such as CALIPER.
背景:准确的儿科参考区间(RIs)对于正确解释实验室结果至关重要,但其发展受到年龄相关生理变化、有限样本量和分析前变异性的挑战。本研究使用RefineR逆建模方法和临床与实验室标准协会(CLSI) EP28-A3c推荐方法,评估加拿大儿科参考区间RIs (CALIPER)实验室倡议在美国不同儿科门诊人群中的适用性。方法:2023年1月至2024年12月,从一家机构收集51863例年龄在19岁以下 患者的门诊实验室数据。对9种常用化学分析物进行了评价。RIs是使用RefineR和CLSI指南和自举重采样得到的。使用基于95%置信区间和总允许误差(TAE)的颜色编码标记系统将这些与CALIPER RIs进行比较。结果:基于refiner的RIs在88个年龄和性别特定分析组中有86个与CALIPER值一致,而clsi衍生的RIs在88个组中有77个与CALIPER值一致。显著差异包括丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶和血尿素氮,通常受到已知的分析前和生理变量的影响,如样品类型、体重指数(BMI)和水合状态。结论:与CLSI指南相比,RefineR与CALIPER RIs的一致性更好,突出了其在门诊儿科人群中的稳健性。鉴于RefineR对混合数据和偏态分布的容忍,它为儿科检验医学中获得人群特异性RIs提供了一种更实用、更准确的方法,并有助于验证外部RIs(如CALIPER)的实施。
{"title":"Validating CALIPER pediatric reference intervals in a U.S. population using retrospective outpatient data and RefineR","authors":"Jillian Kodger ,&nbsp;Thomas J.S. Durant ,&nbsp;Nalan Yurtsever ,&nbsp;Joe M. El-Khoury","doi":"10.1016/j.cca.2026.120846","DOIUrl":"10.1016/j.cca.2026.120846","url":null,"abstract":"<div><h3>Background</h3><div>Accurate pediatric reference intervals (RIs) are critical for proper interpretation of laboratory results, yet their development is challenged by age-related physiological variation, limited sample sizes, and preanalytical variability. This study evaluates the applicability of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) RIs to a US-based, diverse pediatric outpatient population using both the RefineR inverse modeling approach and the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c recommended approach.</div></div><div><h3>Methods</h3><div>Outpatient laboratory data from 51,863 patients under 19 years of age were collected from a single institution between January 2023 and December 2024. Nine commonly ordered chemistry analytes were evaluated. RIs were derived using both RefineR and CLSI guidelines with bootstrap resampling. These were compared to CALIPER RIs using a color-coded flagging system based on 95% confidence intervals and total allowable error (TAE).</div></div><div><h3>Results</h3><div>RefineR-based RIs aligned with CALIPER values in 86 out of 88 age- and gender-specific analyte groups, whereas CLSI-derived RIs aligned in 79 out of 88. Notable discrepancies involved alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and blood urea nitrogen, often influenced by known preanalytical and physiological variables such as sample type, body mass index (BMI), and hydration status.</div></div><div><h3>Conclusions</h3><div>RefineR demonstrated superior alignment with CALIPER RIs compared to CLSI guidelines, highlighting its robustness in outpatient pediatric populations. Given its tolerance to mixed data and skewed distributions, RefineR offers a more practical and accurate method for deriving population-specific RIs in pediatric laboratory medicine, and helps verify the implementation of external RIs, such as CALIPER.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120846"},"PeriodicalIF":2.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017669","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
期刊
Clinica Chimica Acta
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