Journal of Clinical Laboratory Analysis最新文献_第5页

Can Albumin/Lymphocyte Ratio and MPV/Lymphocyte Ratio Serve as New Inflammatory Biomarkers in Patients With Hyperemesis Gravidarum? 白蛋白/淋巴细胞比值和MPV/淋巴细胞比值能否作为妊娠剧吐患者新的炎症生物标志物？

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-29 DOI: 10.1002/jcla.70129

Deniz Taşkıran, Orhan Ay

Objective

This study aimed to evaluate the diagnostic utility of the albumin/lymphocyte ratio (ALR) and mean platelet volume/lymphocyte ratio (MPVLR) novel inflammatory markers not previously studied in hyperemesis gravidarum (HG) as potential biomarkers in patients diagnosed with HG.

Patients and Methods

A total of 68 first-trimester pregnant women with clinically diagnosed HG and 78 healthy pregnant controls were included. Systemic inflammatory markers including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), albumin/fibrinogen ratio (AFR), fibrinogen/lymphocyte ratio (FLR), magnesium/lymphocyte ratio (MgLR), ALR, MPVLR, and systemic immune-inflammation index (SII) were calculated and compared between the two groups.

Results

Lymphocyte counts and ketonuria levels were significantly higher in the HG group. Conversely, ALR and MPVLR values were significantly lower in the HG group. MPVLR was identified as a potential diagnostic marker for HG with a cutoff value of 4.569, yielding a sensitivity of 54.4% and specificity of 44.9%. ALR demonstrated a cutoff value of 22.853 with a sensitivity of 61.8% and specificity of 38.5%.

Conclusions

In contrast to the previous literature, PLR and NLR levels were not elevated in HG patients. However, ALR and MPVLR previously unexamined in this population were significantly lower, suggesting a potential role in HG pathophysiology. The findings underscore the complexity and dynamic nature of inflammatory responses in HG, warranting further investigation.

目的：本研究旨在评价白蛋白/淋巴细胞比（ALR）和平均血小板体积/淋巴细胞比（MPVLR）这两种新型炎症标志物在妊娠呕吐（HG）诊断中的应用价值。患者和方法：共纳入68例临床诊断为HG的妊娠早期孕妇和78例健康孕妇对照。计算两组患者的全身炎症指标，包括中性粒细胞/淋巴细胞比值（NLR）、血小板/淋巴细胞比值（PLR）、白蛋白/纤维蛋白原比值（AFR）、纤维蛋白原/淋巴细胞比值（FLR）、镁/淋巴细胞比值（MgLR）、ALR、MPVLR和全身免疫炎症指数（SII）。结果：HG组淋巴细胞计数和尿酮水平明显增高。相反，HG组的ALR和MPVLR值明显降低。MPVLR被确定为HG的潜在诊断标志物，临界值为4.569，敏感性为54.4%，特异性为44.9%。ALR的截止值为22.853，敏感性为61.8%，特异性为38.5%。结论：与之前的文献相反，HG患者的PLR和NLR水平没有升高。然而，先前未在该人群中检测到的ALR和MPVLR明显较低，提示其在HG病理生理中的潜在作用。这些发现强调了HG炎症反应的复杂性和动态性，值得进一步研究。

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引用次数: 0

The Role of Viral and Bacterial Infections in the Etiology of Behçet's Disease 病毒和细菌感染在behaperet病病因学中的作用。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-29 DOI: 10.1002/jcla.70133

Mohsen Moghoofei, Hamid Pajavand, Razieh Shahbazi, Marzieh Rezaei, Elahe Taki

Background

Behçet's disease (BD) is a complex systemic vasculitis with a poorly understood etiology that involves genetic, environmental, and immunological factors. Increasing evidence suggests that viral and bacterial infections may trigger or exacerbate BD through immune-mediated pathways. This review aims to clarify how different infectious agents may contribute to BD pathogenesis.

Methods

For this review, articles addressing microbial involvement in BD were collected from established databases such as PubMed, Scopus, and Web of Science. Priority was given to studies evaluating classical pathogens—including Herpes simplex virus and Streptococcus spp.—as well as more recent agents such as SARS-CoV-2, Borrelia burgdorferi, and Helicobacter pylori. Findings from immunological, molecular, and clinical research were integrated to highlight shared mechanisms related to host–pathogen interactions.

Results

The reviewed literature shows that microbial infections may influence BD through multiple interconnected mechanisms. A central concept is the possible cross-reactivity between microbial and human heat shock proteins (HSPs), which may activate Th1/Th17 cytokine pathways and enhance neutrophil activity. The review also highlights the dual functions of TRIM proteins in antiviral responses and inflammatory dysregulation, as well as the involvement of inflammasome activation and pattern recognition receptors (PRRs). These combined processes may help explain how infections initiate or intensify immune responses in BD.

Conclusion

By synthesizing current microbial and immune evidence, this review provides an updated perspective on BD immunopathogenesis and outlines testable mechanisms for future research. Understanding these links may support the development of more targeted therapeutic strategies.

背景：behet病（BD）是一种复杂的全身性血管炎，病因尚不清楚，涉及遗传、环境和免疫因素。越来越多的证据表明，病毒和细菌感染可能通过免疫介导途径触发或加剧双相障碍。本文旨在阐明不同的感染因子是如何导致双相障碍发病的。方法：在本综述中，从PubMed、Scopus和Web of Science等已建立的数据库中收集了有关微生物参与BD的文章。优先考虑评估经典病原体的研究，包括单纯疱疹病毒和链球菌，以及最近的病原体，如SARS-CoV-2、伯氏疏螺旋体和幽门螺杆菌。来自免疫学、分子和临床研究的发现被整合在一起，以突出与宿主-病原体相互作用相关的共同机制。结果：综述的文献表明，微生物感染可能通过多种相互关联的机制影响BD。一个核心概念是微生物和人热休克蛋白（HSPs）之间可能的交叉反应性，这可能激活Th1/Th17细胞因子途径并增强中性粒细胞活性。该综述还强调了TRIM蛋白在抗病毒反应和炎症失调中的双重功能，以及炎症小体激活和模式识别受体（PRRs）的参与。这些综合过程可能有助于解释感染如何启动或加强BD的免疫反应。结论：通过综合目前的微生物和免疫证据，本综述提供了BD免疫发病机制的最新视角，并概述了未来研究的可测试机制。了解这些联系可能有助于开发更有针对性的治疗策略。

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引用次数: 0

Performance Analysis of Clinical Chemistry Laboratory Using Sigma Metrics in the Total Testing Process at Dessie Comprehensive Specialized Hospital, Ethiopia 埃塞俄比亚Dessie综合专科医院临床化学实验室在总检测过程中使用Sigma指标的绩效分析。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-26 DOI: 10.1002/jcla.70134

Zewudu Mulatie, Endris Ebrahim, Mihreteab Alebachew, Alemu Gedefie, Bruktawit Eshetu, Mihret Tilahun, Habtu Debash, Yeshimebet Kassa, Ermiyas Alemayehu, Tesfaye Gessese

Background

Clinical laboratory test results in clinical decisions have become a fundamental element of clinical practice, with laboratory results influencing approximately 70% of decisions. The sigma metrics method is used to evaluate all stages of the testing process in clinical chemistry laboratories.

Objective

This study aims to assess the performance of the clinical chemistry laboratory using sigma metrics across the total test process at Dessie Comprehensive Specialized Hospital.

Methods

A cross-sectional study was conducted from July 1, 2024 to September 30, 2024. The study included all the eligible laboratory samples and corresponding test requests during the study period, selected using consecutive sampling techniques. Data for each variable were collected using a prepared checklist and record format by trained laboratory professionals. The data were entered into EPI Data version 3.1 and analyzed using Stata version 17. Laboratory performance was evaluated using the sigma metrics.

Result

The overall performance of the clinical chemistry laboratory was inadequate, with an overall sigma value of 2.9. The laboratory showed marginal performance in the analytical phase (3.5 sigma value) and low performance in the pre-analytical and post-analytical phases (2.8 and 2.9 sigma, respectively). However, most clinical chemistry parameters demonstrated satisfactory sigma metric values (≥ 3).

Conclusion

The hospital administration should provide training for all staff involved in laboratory sample collection and processing, focusing on quality control, reagent handling, and adherence to SOPs, along with continuous performance monitoring.

背景：临床实验室检测结果在临床决策中已成为临床实践的基本要素，实验室结果影响约70%的决策。西格玛度量法用于评估临床化学实验室测试过程的所有阶段。目的：本研究旨在利用西格玛指标评估德西综合专科医院临床化学实验室在整个测试过程中的表现。方法：于2024年7月1日至2024年9月30日进行横断面研究。本研究包括研究期间所有符合条件的实验室样本和相应的测试要求，采用连续采样技术选择。每个变量的数据由训练有素的实验室专业人员使用准备好的检查表和记录格式收集。数据输入EPI数据3.1版本，使用Stata版本17进行分析。使用sigma指标评估实验室表现。结果：临床化学实验室整体表现不佳，整体sigma值为2.9。实验室在分析阶段表现出边缘性（3.5 sigma值），在分析前和分析后阶段表现不佳（分别为2.8和2.9 sigma）。然而，大多数临床化学参数显示令人满意的西格玛度量值（≥3）。结论：医院管理部门应对所有参与实验室样品采集和处理的人员进行培训，重点是质量控制、试剂处理和遵守标准操作规程，并进行持续的绩效监控。

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引用次数: 0

Hyperuricemia Is Independently Associated With Hyperlipidemia in a Large Population-Based Study 在一项基于人群的大型研究中，高尿酸血症与高脂血症独立相关。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-25 DOI: 10.1002/jcla.70131

Ta-Jen Lin, Jia-In Lee, Szu-Chia Chen, Shu-Pin Huang, Jiun-Hung Geng

Background

Hyperlipidemia is a significant risk factor for cardiovascular diseases. Hyperuricemia has also been linked to adverse cardiometabolic outcomes, including dyslipidemia. The relationship between hyperuricemia and hyperlipidemia is of particular concern due to their combined impact on cardiovascular risk.

Methods

This study analyzed data from 119,037 participants in the Taiwan Biobank to explore the association between hyperuricemia and hyperlipidemia. The study compared baseline characteristics and metabolic profiles between participants with and without hyperuricemia. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with hyperlipidemia, focusing on hyperuricemia as an independent variable.

Results

The participants with hyperuricemia had a more adverse cardiometabolic profile, including a higher body mass index (BMI), a higher prevalence of smoking and alcohol consumption, hypertension, and diabetes, and a worse lipid profile. Univariate analysis showed significant associations between hyperlipidemia and age, BMI, smoking history, alcohol consumption, hypertension, diabetes, and hyperuricemia (OR: 1.706, 95% CI: 1.625–1.791, p < 0.001). In multivariate analysis, hyperuricemia remained an independent predictor of hyperlipidemia (OR: 1.102, 95% CI: 1.041–1.165, p < 0.001), along with age, BMI, smoking, alcohol consumption, hypertension, diabetes, and a lower estimated glomerular filtration rate.

Conclusion

Hyperuricemia is independently associated with hyperlipidemia, underscoring its role in the complex interplay of metabolic factors contributing to cardiovascular disease risk. Our findings highlight the importance of comprehensive risk factor management incorporating serum uric acid to mitigate the impact of hyperlipidemia and associated cardiovascular conditions.

背景：高脂血症是心血管疾病的重要危险因素。高尿酸血症也与不良的心脏代谢结果有关，包括血脂异常。高尿酸血症和高脂血症之间的关系特别值得关注，因为它们共同影响心血管风险。方法：本研究分析台湾生物库119,037名参与者的数据，探讨高尿酸血症与高脂血症之间的关系。该研究比较了高尿酸血症和非高尿酸血症参与者的基线特征和代谢特征。进行单因素和多因素logistic回归分析，以确定与高脂血症相关的因素，重点关注高尿酸血症作为一个独立变量。结果：高尿酸血症的参与者有更不利的心脏代谢特征，包括更高的身体质量指数（BMI），更高的吸烟和饮酒患病率，高血压和糖尿病，以及更差的脂质特征。单因素分析显示，高脂血症与年龄、BMI、吸烟史、饮酒、高血压、糖尿病和高尿酸血症之间存在显著相关性（OR: 1.706, 95% CI: 1.625-1.791, p）。结论：高尿酸血症与高脂血症独立相关，强调其在心血管疾病风险代谢因素复杂相互作用中的作用。我们的研究结果强调了综合危险因素管理的重要性，包括血清尿酸，以减轻高脂血症和相关心血管疾病的影响。

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引用次数: 0

Rotational Thromboelastometry (ROTEM) Versus Conventional Coagulation Tests in Cirrhosis: Can We Reduce Plasma Transfusion Without ROTEM? 旋转血栓弹性测定法（ROTEM）与常规肝硬化凝血试验：不使用ROTEM能减少血浆输注吗？

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-25 DOI: 10.1002/jcla.70130

Nuanrat Cheerasiri, Ratchaneekorn Jantasing, Rapat Pittayanon, Ponlapat Rojnuckarin

Background

Periprocedural rotational thromboelastometry (ROTEM) could reduce transfusions while maintaining low bleeding risks in cirrhosis. However, it is unclear whether the benefits arise from higher transfusion thresholds, or ROTEM's ability to detect rebalanced hemostasis.

Method

This cohort study assessed the correlation between CCTs and ROTEM by analyzing blood samples from cirrhotic patients scheduled for elective endoscopy. Additionally, anticoagulant protein levels were measured to assess whether ROTEM shares the same limitations as CCTs.

Result

The study included 133 patients, 57% male, with a mean age of 62 years. High correlations were observed between prothrombin time ratio (PT-R) and EXTEM-CT (r = 0.73, p < 0.01), platelet count and EXTEM-MCF (r = 0.7, p < 0.01), fibrinogen and FIBTEM-MCF (r = 0.78, p < 0.01), and fibrinogen and EXTEM-MCF (r = 0.72, p < 0.01). Only 41.7% of patients with PT-R > 1.5 had EXTEM-CT exceeding the transfusion threshold (> 110 s), while all patients with PT-R > 1.8 showed prolonged EXTEM-CT. A platelet count ≤ 40.5 × 10⁹/L was associated with impaired EXTEM-MCF (< 40 mm). Patients with EXTEM-CT > 110 s had significantly lower protein C and antithrombin levels. Endoscopy revealed esophageal varices in 68 (52%) patients, with 23 (34%) requiring band ligation. No bleeding occurred within 2 weeks.

Conclusion

ROTEM correlates strongly with CCTs and does not overcome their limitations in detecting rebalanced hemostasis. Prophylactic transfusions based solely on abnormal ROTEM or CCTs should be avoided. However, increasing transfusion thresholds to PT-R > 1.8 and platelet count < 40 × 10⁹/L during active bleeding may help reduce unnecessary transfusions.

背景：围术期旋转血栓弹性测量（ROTEM）可以减少输血，同时保持肝硬化患者低出血风险。然而，目前尚不清楚这些益处是来自更高的输血阈值，还是ROTEM检测再平衡止血的能力。方法：本队列研究通过分析肝硬化患者择期内窥镜检查的血液样本来评估CCTs和ROTEM之间的相关性。此外，还测量了抗凝血蛋白水平，以评估ROTEM是否与cct具有相同的局限性。结果：研究纳入133例患者，其中57%为男性，平均年龄62岁。凝血酶原时间比（PT-R）与EXTEM-CT呈高度相关（r = 0.73, p = 1.5）， EXTEM-CT超过输血阈值（> 110 s），而所有PT-R > 1.8的患者EXTEM-CT均延长。血小板计数≤40.5 × 109/L与EXTEM-MCF受损相关（110 s蛋白C和抗凝血酶水平显著降低）。内镜检查显示68例（52%）患者出现食管静脉曲张，23例（34%）患者需要结扎。2周内未发生出血。结论：ROTEM与cct相关性强，不能克服cct在检测再平衡止血方面的局限性。应避免仅根据异常ROTEM或cct进行预防性输血。然而，在活动性出血期间提高输血阈值至PT-R bbb1.8和血小板计数9/L可能有助于减少不必要的输血。

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引用次数: 0

Protein Induced by Vitamin K Absence or Antagonist-II: Significantly Elevated in Obstructive Jaundice and Sepsis Patients Without Hepatocellular Carcinoma 缺乏维生素K或拮抗剂ii诱导的蛋白：在无肝细胞癌的梗阻性黄疸和败血症患者中显著升高。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-13 DOI: 10.1002/jcla.70128

Ke Zhang, Xiarui Ye, Xianran Fu

Background

PIVKA-II is a promising diagnostic and prognostic biomarker for HCC. However, a particular PIVKA-II variant can be abnormally elevated in patients with obstructive jaundice or sepsis, complicating its interpretation in HCC conditions.

Methods

This study aimed to investigate the distribution and positive rates of serum PIVKA-II and AFP in patients with obstructive jaundice or sepsis, and to explore their relationships with laboratory tests, particularly coagulation function indexes. The receiver operating characteristic (ROC) curve was used to determine the cut-off, specificity and sensitivity of PIVKA-II in diagnosing HCC.

Results

In patients with obstructive jaundice and sepsis, PIVKA-II was significantly positively correlated with PT and INR. When the cut-off was 42.17 mAU/mL, the sensitivity and specificity of PIVKA-II in diagnosing HCC were 74.69% and 70.17%, respectively. There was no difference in PIVKA-II concentration between HCC and obstructive jaundice. PIVKA-II levels in obstructive jaundice and sepsis were significantly higher than those in healthy controls. Except for healthy individuals, the positive rate of serum PIVKA-II was significantly higher than that of AFP among the other three groups, and patients with obstructive jaundice had the highest positive rate of PIVKA-II.

Conclusions

The PIVKA-II produced by HCC may differ from that produced by obstructive jaundice and sepsis. Given that PIVKA-II levels are abnormally elevated in patients with obstructive jaundice and sepsis, the results should be interpreted with caution in patients with HCC combined with these diseases.

背景：PIVKA-II是一种很有前景的HCC诊断和预后生物标志物。然而，在梗阻性黄疸或败血症患者中，一种特殊的PIVKA-II变异可能异常升高，使其在HCC条件下的解释复杂化。方法：本研究旨在观察梗阻性黄疸或败血症患者血清PIVKA-II和AFP的分布及阳性率，并探讨其与实验室检查特别是凝血功能指标的关系。采用受试者工作特征（ROC）曲线确定PIVKA-II诊断HCC的截止点、特异性和敏感性。结果：在梗阻性黄疸合并脓毒症患者中，PIVKA-II与PT、INR呈显著正相关。截止值为42.17 mAU/mL时，PIVKA-II诊断HCC的敏感性和特异性分别为74.69%和70.17%。肝细胞癌与梗阻性黄疸之间PIVKA-II浓度无差异。阻塞性黄疸和败血症患者的PIVKA-II水平明显高于健康对照组。除健康人外，其余三组血清PIVKA-II阳性率均显著高于AFP，其中梗阻性黄疸患者血清PIVKA-II阳性率最高。结论：HCC产生的PIVKA-II可能不同于梗阻性黄疸和败血症产生的PIVKA-II。鉴于PIVKA-II水平在梗阻性黄疸和败血症患者中异常升高，HCC合并这些疾病的患者应谨慎解释该结果。

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引用次数: 0

Correction to “Reference Intervals for Lead, Arsenic, Mercury, and Cadmium in the Population of Southwest China: A Comparative Study of Direct and Indirect Sampling Techniques” 修正“中国西南地区人口铅、砷、汞和镉的参考区间：直接和间接抽样技术的比较研究”。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-10 DOI: 10.1002/jcla.70127

M. Nie, H. Du, T. Xie, et al., “Reference Intervals for Lead, Arsenic, Mercury, and Cadmium in the Population of Southwest China: A Comparative Study of Direct and Indirect Sampling Techniques,” Journal of Clinical Laboratory Analysis 39, no. 19 (2025): e70096, https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70096.

In the footnote, the author's name listed as “Manging Nie” should be “Manqing Nie” and the corrected text should read as below:

Manqing Nie and Hang Du are co-first authors, contributed equally to this study and are listed as first authors.

In Tables 3 and 4, as the 90% confidence intervals (CIs) were calculated using bootstrap resampling, the column headings currently labeled “LL (95% CI)” and “UL (95% CI)” in both tables should be updated to “LL (90% CI)” and “UL (90% CI)”, respectively.

We apologize for this error.

聂明，杜华，谢涛，等，“中国西南地区人群铅、砷、汞和镉参考区间的直接和间接采样技术比较研究”，《临床检验杂志》第39期。19 (2025): e70096, https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70096.In脚注中，作者姓名“manching Nie”应为“Manqing Nie”，更正后的文字应为：Manqing Nie和Hang Du为共同第一作者，对本研究的贡献相同，列为第一作者。在表3和表4中，由于使用bootstrap重采样计算了90%置信区间（CI），因此两个表中当前标记为“LL （95% CI）”和“UL （95% CI）”的列标题应分别更新为“LL （90% CI）”和“UL （90% CI）”。我们为这个错误道歉。

引用次数: 0

Integrated Transcriptomic and Metabolomic Analysis Revealed That Tryptophan Metabolism–Related Metabolites Are Biomarkers of Trastuzumab Resistance 转录组学和代谢组学综合分析显示，色氨酸代谢相关代谢物是曲妥珠单抗耐药的生物标志物。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-04 DOI: 10.1002/jcla.70124

Xinxin Si, Hanzhe Wu, Yiwei Cao, Bangbang Wei, Juan Wei, Zhongcheng Wang, Changfei Mao

Background

Trastuzumab resistance strongly affects the prognosis of HER2-positive breast cancer patients, and tryptophan metabolism plays a key role in cancer progression and cancer prognosis. However, the relationship between trastuzumab resistance and tryptophan metabolism in HER2-positive breast cancer remains unclear.

Methods

Four HER2-positive breast cancer cell lines (TS: BT-474, SK-BR-3; TR: HCC1954, JIMT-1) were cultured in specific media. Metabolites from cells, tissues, and serum were extracted via pretreatment, centrifugation, drying, and redissolution. UPLC-MS/MS was used for metabolite detection, while tryptophan metabolism-related gene expression was measured using qRT-PCR. T-test was used to calculate statistical differences. Data visualization, machine learning models construction (RF, LASSO logistic regression), and nomogram were achieved through R language.

Results

PLS-DA showed distinct separation between TS and TR breast cancer cell lines in tryptophan metabolism-related gene expression (four differentially expressed genes: HAAO, KYNU, KMO, AFMID) and metabolite abundance (five differentially abundant metabolites). Integration analysis identified 3-hydroxyanthranilic acid, cinnabarinic acid, kynurenine, and kynurenic acid as potential metabolic biomarkers. These four metabolites differed significantly in serum of HCs, TS and TR patients. Four predictors were selected by LASSO, and a nomogram was constructed based on logistic regression. Finally, biomarkers and related genes were validated in tissues.

Conclusion

Our explored the changes induced by trastuzumab resistance in terms of metabolite abundance and gene transcription levels associated with tryptophan metabolism. Furthermore, this work provided new insights into novel diagnostic biomarkers and prediction models of trastuzumab resistance in HER2-positive breast cancer patients.

背景：曲妥珠单抗耐药强烈影响her2阳性乳腺癌患者的预后，色氨酸代谢在癌症进展和癌症预后中起关键作用。然而，her2阳性乳腺癌中曲妥珠单抗耐药与色氨酸代谢之间的关系尚不清楚。方法：4株her2阳性乳腺癌细胞株（TS: BT-474、SK-BR-3; TR: HCC1954、JIMT-1）在特定培养基中培养。通过预处理、离心、干燥和再溶解提取细胞、组织和血清中的代谢物。代谢物检测采用UPLC-MS/MS，色氨酸代谢相关基因表达检测采用qRT-PCR。采用t检验计算统计差异。通过R语言实现数据可视化、机器学习模型构建（RF、LASSO逻辑回归）和nomogram。结果：PLS-DA在色氨酸代谢相关基因表达（HAAO、KYNU、KMO、AFMID 4个差异表达基因）和代谢物丰度（5个差异丰度代谢物）上显示TS和TR乳腺癌细胞系存在明显差异。整合分析发现3-羟基苯甲酸、朱砂酸、犬尿氨酸和犬尿酸是潜在的代谢生物标志物。这四种代谢物在hc、TS和TR患者的血清中存在显著差异。采用LASSO法选取4个预测因子，并基于logistic回归构建了nomogram。最后，在组织中验证了生物标志物和相关基因。结论：我们从与色氨酸代谢相关的代谢物丰度和基因转录水平方面探讨了曲妥珠单抗耐药引起的变化。此外，这项工作为her2阳性乳腺癌患者曲妥珠单抗耐药的新型诊断生物标志物和预测模型提供了新的见解。

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引用次数: 0

Epithelial-Mesenchymal Transition States and Metabolic Reprogramming Related Signatures Predict Prognosis and Therapeutic Responses in HER2-Positive Breast Cancer 上皮-间质过渡状态和代谢重编程相关特征预测her2阳性乳腺癌的预后和治疗反应。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-11-03 DOI: 10.1002/jcla.70119

Yuhui Zheng, Yinduo Zeng, Mengping Xi, Guoqiang Zhu, Jinyu Yang, Peng Cui, Guoqiang Wang, Yuzi Zhang, Chunwei Xu, Wenxian Wang, Shangli Cai, Li Wang, Xiaowen Wu

Background

Epithelial-mesenchymal transition (EMT) and metabolic reprogramming have been shown to regulate HER2 targeted therapy resistance and tumor metastasis. We aimed to establish an EMT-associated and metabolic-related prognostic model in HER2-positive breast cancer.

Methods

mRNA expression and clinical information for HER2-positive breast cancer are downloaded from the TCGA database. The single sample gene set enrichment analysis score was used to generate EMT subtypes and identify EMT-related metabolic pathways. A prognostic risk score was developed based on the differentially expressed genes (DEGs) of the EMT-associated metabolic pathways using least absolute shrinkage and selection operator (LASSO) Cox regression and then validated in an external cohort (GSE96058).

Results

The EMT enriched scores differentiated the OS in the HER2-positive breast cancer TCGA cohort (p = 0.023; HR, 0.38; 95% CI, 0.16–0.9), which was also associated with the carbohydrate, amino acid, nucleotide, and tricarboxylic acid (TCA) cycle pathways (p < 0.05). A total of 10 genes based on the DEGs between the metabolic groups were used to construct the prognosis model. Patients with low-risk metabolic scores showed longer OS compared to those with high-risk metabolic scores (p < 0.001; HR, 0.09; 95% CI, 0.03–0.31). The association between OS and the metabolism score remained significant in the multivariable Cox regression (p < 0.001; HR, 0.08; 95% CI, 0.03–0.22). Similar results were observed in the validation cohort (p = 0.002; HR, 0.34; 95% CI, 0.16–0.69).

Conclusion

EMT and metabolic reprogramming-related features are specific prognostic and potential therapeutic biomarkers for HER2-positive breast cancer patients, which warrant further studies.

背景：上皮-间质转化（Epithelial-mesenchymal transition， EMT）和代谢重编程已被证明可调节HER2靶向治疗的耐药和肿瘤转移。我们旨在建立her2阳性乳腺癌emt相关和代谢相关的预后模型。方法：从TCGA数据库下载her2阳性乳腺癌的mRNA表达和临床信息。单样本基因集富集分析评分用于生成EMT亚型并识别EMT相关代谢途径。使用最小绝对收缩和选择算子（LASSO） Cox回归，基于emt相关代谢途径的差异表达基因（DEGs）建立预后风险评分，然后在外部队列（GSE96058）中进行验证。结果：EMT富集评分分化了her2阳性乳腺癌TCGA队列中的OS (p = 0.023； HR, 0.38; 95% CI, 0.16-0.9)，并且与碳水化合物、氨基酸、核苷酸和三羧酸（TCA）循环途径相关(p)。结论：EMT和代谢重编程相关特征是her2阳性乳腺癌患者特异性预后和潜在治疗性生物标志物，值得进一步研究。

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引用次数: 0

Investigating the Factors Affecting the Commutability of Hemoglobin A1C Frozen Pooled Blood Materials 影响糖化血红蛋白冷冻池血材料交换性的因素研究。

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2025-10-31 DOI: 10.1002/jcla.70125

Kanokwan Ngueanchanthong, Napaporn Apiratmateekul, Supaporn Suparak, Nam K. Tran, Wanvisa Treebuphachatsakul

Background

Measurement of hemoglobin A_1C (HbA_1C) is essential for the diagnosis and treatment of diabetes mellitus (DM). Processed blood materials (PBMs), such as frozen pooled blood (FPB), are commonly used for External Quality Assessment (EQA). However, their commutability may be affected by factors such as hemolysis and matrix modification. This study evaluated FPB commutability and identified the factors influencing its performance in HbA_1C measurements.

Methods

HbA_1C contents in 24 clinical blood samples (CBSs) and 10 PBMs, including FPBs, single-donor blood (SDB), and in vitro glycated blood (IGB), were analyzed using enzymatic (EN), capillary electrophoresis (CE), cation-exchange high-performance liquid chromatography (CE-HPLC), turbidimetric immunoassay (TI), and boronate affinity HPLC (BA-HPLC). EN served as the reference measurement procedure. Commutability was assessed using Deming regression and a 95% prediction interval. The hematocrit (HCT), visual appearance, plasma absorbance (PA), hemolysis index (HI), pH, and debris cells (DC) were analyzed.

Results

FPB1 and SDB were commutable across all measurement procedures. FPB2 and FPB4 were commutable with CE, CE-HPLC, and TI but non-commutable with BA-HPLC when HbA_1C was ≥ 6.23%, as data points fell outside the tolerance limits of the Deming regression lines. Non-commutable PBMs showed higher PA and HI along with lower pH. DC affected HbA_1C quantification using CE-HPLC.

Conclusions

Hemolysis, as assessed by PA and HI, affects FPB commutability. These factors should be considered in EQA programs, particularly for BA-HPLC. HCT and DC did not directly affect commutability; however, maintaining appropriate HCT levels and monitoring DC-related chromatographic interference are crucial for ensuring FPB reliability in HbA_1C comparisons.

背景：糖化血红蛋白（HbA1C）的测定对糖尿病（DM）的诊断和治疗至关重要。处理过的血液材料（PBMs），如冷冻池血（FPB），通常用于外部质量评估（EQA）。然而，它们的可交换性可能受到溶血和基质修饰等因素的影响。本研究评估了FPB的可交换性，并确定了影响其在HbA1C测量中的性能的因素。方法：采用酶解法（EN）、毛细管电泳法（CE）、阳离子交换高效液相色谱法（CE-HPLC）、比浊免疫分析法（TI）、硼酸盐亲和高效液相色谱法（BA-HPLC）对24份临床血样（CBSs）和10份体外糖化血（IGB）进行HbA1C含量分析。EN作为参考测量程序。可交换性评估采用Deming回归和95%的预测区间。分析红细胞压积（HCT）、视觉外观、血浆吸光度（PA）、溶血指数（HI）、pH和碎片细胞（DC）。结果：FPB1和SDB在所有测量过程中均可交换。当HbA1C≥6.23%时，FPB2和FPB4与CE、CE- hplc和TI可交换，但与BA-HPLC不可交换，因为数据点超出了Deming回归线的容忍范围。非可交换PBMs显示较高的PA和HI以及较低的ph DC影响CE-HPLC的HbA1C定量。结论：溶血，如PA和HI评估，影响FPB的可交换性。这些因素应该在EQA程序中考虑，特别是BA-HPLC。HCT和DC不直接影响可交换性；然而，维持适当的HCT水平和监测与dc相关的色谱干扰对于确保FPB在HbA1C比较中的可靠性至关重要。

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引用次数: 0