Clinica Chimica Acta最新文献_第9页

Exosomal RNA biomarkers in pancreatic ductal adenocarcinoma: Systematic review and meta-analysis. 胰腺导管腺癌的外泌体RNA生物标志物：系统回顾和荟萃分析。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-01 Epub Date: 2025-08-06 DOI: 10.1016/j.cca.2025.120532

Amir Tiyuri, Haniyeh Hatami, Zahra Mobarezi, Mina Zareardalan, Ghazal Salari, Aida Zandi Abbas Abadi, Marziyeh Mirzazad, Anahita Ebrahimi Mojaveri, Davod Jafari

Pancreatic cancer is a highly lethal malignancy, ranking tenth in incidence among all cancers and standing as the fourth leading cause of cancer-related mortality worldwide. This systematic review and meta-analysis evaluated the diagnostic performance of exosomal biomarkers for detecting pancreatic ductal adenocarcinoma (PDAC). A total of 1,666 records were identified through comprehensive searches in Scopus, Web of Science, and PubMed. After removing duplicates and screening titles, abstracts, and full texts, 15 studies comprising 1,961 individuals (971 PDAC patients and 990 controls) were included. The quality of studies was assessed using the QUADAS-2 tool, revealing potential biases mainly in patient selection and index test domains. Three biomarker categories were analyzed: exosomal microRNAs (exomiRs), cancer antigen 19-9 (CA 19-9), and glypican-1 (GPC1). ExomiRs demonstrated the highest pooled sensitivity (0.86; 95 % CI: 0.80-0.90) and lowest negative likelihood ratio (0.16; 95 % CI: 0.11-0.24), while CA 19-9 showed the highest specificity (0.91; 95 % CI: 0.84-0.95) and positive likelihood ratio (8.5; 95 % CI: 4.4-16.4). ExomiRs also had the highest diagnostic odds ratio (DOR = 35.4; 95 % CI: 18.7-67.0) and area under the SROC curve (AUC = 0.92; 95 % CI: 0.89-0.94), indicating superior diagnostic performance compared to CA 19-9 and GPC1 (AUC = 0.88 and 0.78, respectively). GPC1 consistently showed lower diagnostic metrics across all analyses. Deeks' funnel plot suggested no publication bias for CA 19-9 and GPC1, but indicated potential bias for exomiRs (P = 0.01). Overall, exomiRs appear to be promising non-invasive biomarkers for the early detection of PDAC, outperforming traditional and other exosome-based markers in diagnostic accuracy.

胰腺癌是一种高度致命的恶性肿瘤，在所有癌症的发病率中排名第十，是全球癌症相关死亡的第四大原因。本系统综述和荟萃分析评估了外泌体生物标志物检测胰腺导管腺癌（PDAC）的诊断性能。通过在Scopus、Web of Science和PubMed中进行综合检索，共确定了1666条记录。在删除重复和筛选标题、摘要和全文后，纳入了15项研究，包括1961名个体（971名PDAC患者和990名对照）。使用QUADAS-2工具评估研究质量，揭示主要在患者选择和指数测试领域的潜在偏差。分析了三种生物标志物类别：外泌体microRNAs （exomiRs）、癌抗原19-9 （CA 19-9）和glypican-1 （GPC1）。ExomiRs的总灵敏度最高(0.86；95 % CI: 0.80-0.90)和最低负似然比(0.16；95 % CI: 0.11-0.24)，而CA 19-9的特异性最高(0.91；95 % CI: 0.84-0.95)和正似然比(8.5；95 % ci: 4.4-16.4)。ExomiRs的诊断优势比也最高(DOR = 35.4；95 % CI: 18.7-67.0)和SROC曲线下面积(AUC = 0.92；95 % CI: 0.89-0.94)，与CA 19-9和GPC1 （AUC分别= 0.88和0.78）相比，显示出更好的诊断性能。GPC1在所有分析中始终显示较低的诊断指标。Deeks漏斗图显示CA 19-9和GPC1没有发表偏倚，但显示exomir有潜在偏倚（P = 0.01）。总的来说，在PDAC的早期检测中，外泌体似乎是有希望的非侵入性生物标志物，在诊断准确性方面优于传统的和其他基于外泌体的标志物。

{"title":"Exosomal RNA biomarkers in pancreatic ductal adenocarcinoma: Systematic review and meta-analysis.","authors":"Amir Tiyuri, Haniyeh Hatami, Zahra Mobarezi, Mina Zareardalan, Ghazal Salari, Aida Zandi Abbas Abadi, Marziyeh Mirzazad, Anahita Ebrahimi Mojaveri, Davod Jafari","doi":"10.1016/j.cca.2025.120532","DOIUrl":"10.1016/j.cca.2025.120532","url":null,"abstract":"<p><p>Pancreatic cancer is a highly lethal malignancy, ranking tenth in incidence among all cancers and standing as the fourth leading cause of cancer-related mortality worldwide. This systematic review and meta-analysis evaluated the diagnostic performance of exosomal biomarkers for detecting pancreatic ductal adenocarcinoma (PDAC). A total of 1,666 records were identified through comprehensive searches in Scopus, Web of Science, and PubMed. After removing duplicates and screening titles, abstracts, and full texts, 15 studies comprising 1,961 individuals (971 PDAC patients and 990 controls) were included. The quality of studies was assessed using the QUADAS-2 tool, revealing potential biases mainly in patient selection and index test domains. Three biomarker categories were analyzed: exosomal microRNAs (exomiRs), cancer antigen 19-9 (CA 19-9), and glypican-1 (GPC1). ExomiRs demonstrated the highest pooled sensitivity (0.86; 95 % CI: 0.80-0.90) and lowest negative likelihood ratio (0.16; 95 % CI: 0.11-0.24), while CA 19-9 showed the highest specificity (0.91; 95 % CI: 0.84-0.95) and positive likelihood ratio (8.5; 95 % CI: 4.4-16.4). ExomiRs also had the highest diagnostic odds ratio (DOR = 35.4; 95 % CI: 18.7-67.0) and area under the SROC curve (AUC = 0.92; 95 % CI: 0.89-0.94), indicating superior diagnostic performance compared to CA 19-9 and GPC1 (AUC = 0.88 and 0.78, respectively). GPC1 consistently showed lower diagnostic metrics across all analyses. Deeks' funnel plot suggested no publication bias for CA 19-9 and GPC1, but indicated potential bias for exomiRs (P = 0.01). Overall, exomiRs appear to be promising non-invasive biomarkers for the early detection of PDAC, outperforming traditional and other exosome-based markers in diagnostic accuracy.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120532"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803725","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

Simultaneous quantification of acetylsalicylic acid, clopidogrel, ticagrelor and their major metabolites in human plasma by liquid chromatography–tandem mass spectrometry 液相色谱-串联质谱法同时定量人血浆中乙酰水杨酸、氯吡格雷、替格瑞洛及其主要代谢物。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-31 DOI: 10.1016/j.cca.2025.120816

Wenqiang Wang , Lijiao Zhang , Ciren Baima , Shenghao Gao , Xiaoyu Sun , Xiaoguang Xu , Yunfeng Cao

In recent years, there has been a critical need for therapeutic drug monitoring (TDM) of antiplatelet agents. To address this, we developed a sensitive, rapid, and reliable liquid chromatography–tandem mass spectrometry (LC-MS/MS) method as a unified assay for the simultaneous quantification of aspirin (ASA), salicylic acid (SA), clopidogrel (CLP), its carboxylic acid metabolite (CLPM), ticagrelor (TGL), and its active metabolite AR-C124910XX for the first time. Plasma samples were pretreated by protein precipitation and separated on an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) with a total run time of 4 min. Mass spectrometry was performed in polarity-switching mode, and quantification was achieved using multiple reaction monitoring (MRM) with stable isotope-labeled internal standards (SA-d6, CLPM-d4, TGL-d7) for normalization. Method validation demonstrated excellent linearity over the range of 0.5–2000 ng/mL (R² ≥ 0.9938), with extraction recoveries of 98.2 %–107 % and negligible matrix effects. Stability testing indicated that all analytes were generally stable under clinically relevant conditions; however, ASA underwent rapid esterase-mediated hydrolysis at room temperature, forming SA as the major degradation product, whereas it remained relatively stable at 2–8 °C and was stable for at least 15 days at −80 °C. The method was successfully applied to plasma samples from 61 cardiovascular patients, confirming its utility for evaluating medication adherence as well as inter- and intra-individual variability in drug exposure. In conclusion, the developed LC-MS/MS method provides high sensitivity, high throughput, and robust performance, offering a powerful analytical tool to support individualized antiplatelet therapy.

近年来，对抗血小板药物的治疗性药物监测（TDM）的需求日益迫切。为了解决这一问题，我们首次建立了一种灵敏、快速、可靠的液相色谱-串联质谱（LC-MS/MS）方法，作为同时定量阿司匹林（ASA）、水杨酸（SA）、氯吡格雷（CLP）及其羧酸代谢物（CLPM）、替格瑞洛（TGL）及其活性代谢物AR-C124910XX的统一检测方法。血浆样品经蛋白沉淀预处理，在ACQUITY UPLC BEH C18色谱柱（2.1 × 50 mm, 1.7 μm）上分离，总运行时间为4 min。质谱分析采用极性切换模式，定量采用多反应监测（MRM），稳定同位素标记内标（SA-d6, CLPM-d4, TGL-d7）进行归一化。方法验证在0.5 ~ 2000 ng/mL范围内线性良好（R2 ≥ 0.9938），提取回收率为98.2% % ~ 107 %，基质效应可忽略不计。稳定性测试表明，所有分析物在临床相关条件下基本稳定；然而，ASA在室温下经过酯酶介导的快速水解，形成SA作为主要降解产物，而它在2-8 °C下保持相对稳定，在-80 °C下稳定至少15 天。该方法成功应用于61例心血管患者的血浆样本，证实了其在评估药物依从性以及药物暴露的个体间和个体内变异性方面的实用性。总之，所建立的LC-MS/MS方法具有高灵敏度、高通量和稳定的性能，为支持个体化抗血小板治疗提供了强有力的分析工具。

{"title":"Simultaneous quantification of acetylsalicylic acid, clopidogrel, ticagrelor and their major metabolites in human plasma by liquid chromatography–tandem mass spectrometry","authors":"Wenqiang Wang , Lijiao Zhang , Ciren Baima , Shenghao Gao , Xiaoyu Sun , Xiaoguang Xu , Yunfeng Cao","doi":"10.1016/j.cca.2025.120816","DOIUrl":"10.1016/j.cca.2025.120816","url":null,"abstract":"<div><div>In recent years, there has been a critical need for therapeutic drug monitoring (TDM) of antiplatelet agents. To address this, we developed a sensitive, rapid, and reliable liquid chromatography–tandem mass spectrometry (LC-MS/MS) method as a unified assay for the simultaneous quantification of aspirin (ASA), salicylic acid (SA), clopidogrel (CLP), its carboxylic acid metabolite (CLPM), ticagrelor (TGL), and its active metabolite AR-C124910XX for the first time. Plasma samples were pretreated by protein precipitation and separated on an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) with a total run time of 4 min. Mass spectrometry was performed in polarity-switching mode, and quantification was achieved using multiple reaction monitoring (MRM) with stable isotope-labeled internal standards (SA-d6, CLPM-d4, TGL-d7) for normalization. Method validation demonstrated excellent linearity over the range of 0.5–2000 ng/mL (R<sup>2</sup> ≥ 0.9938), with extraction recoveries of 98.2 %–107 % and negligible matrix effects. Stability testing indicated that all analytes were generally stable under clinically relevant conditions; however, ASA underwent rapid esterase-mediated hydrolysis at room temperature, forming SA as the major degradation product, whereas it remained relatively stable at 2–8 °C and was stable for at least 15 days at −80 °C. The method was successfully applied to plasma samples from 61 cardiovascular patients, confirming its utility for evaluating medication adherence as well as inter- and intra-individual variability in drug exposure. In conclusion, the developed LC-MS/MS method provides high sensitivity, high throughput, and robust performance, offering a powerful analytical tool to support individualized antiplatelet therapy.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"584 ","pages":"Article 120816"},"PeriodicalIF":2.9,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892119","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

Can pharmacogenetics inform morphine dosing in the neonatal intensive care unit? A retrospective evaluation 药物遗传学可以告知新生儿重症监护病房吗啡的剂量吗？回顾性评价。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-30 DOI: 10.1016/j.cca.2025.120814

Anastasiya Mankouski , Luca Brunelli , Gwendolyn McMillin

Acutely ill infants in the neonatal intensive care unit (NICU) present with complex medical conditions necessitating individualized therapeutic strategies. These infants exhibit significant variability in gestational age, birth weight, organ maturity and drug metabolism, increasing the risk of adverse drug reactions. Morphine is commonly prescribed in the NICU and is associated with a wide range of dosing as well as a high risk of adverse events. The objective of this retrospective study was to explore the potential relevance of pharmacogenomics to morphine dosing for our local level III NICU. Infants admitted between March and December 2022 were enrolled. Residual EDTA blood collected during routine clinical care was retrieved, and DNA was extracted for 55 patients. Targeted genotyping was performed to detect the rs1799971G > A variant of OPRM1 and the rs4680 G > A variant of COMT. Morphine dosing details were retrieved from medical records, and they were compared to genotypes. Median morphine oral equivalents per day (mg/kg) trended with OPRM1 genotype: AA, 0.0916 (n = 40); AG, 0.1500 (n = 13); GG, 0.2284 (n = 2). Median morphine oral equivalents and the number of days of treatment trended with COMT genotype: GG, 0.1429 mg/kg, 4 days (n = 17); AG, 0.1231 mg/kg, 6 days (n = 22); AA, 0.0875 mg/kg, 8 days (n = 15). Extremely premature infants required the highest morphine doses for the longest duration. Although statistical significance of these findings was not achieved, our data suggest that further studies are warranted to determine whether pharmacogenomics may be beneficial to individualize morphine dose requirements and improve outcomes for acutely ill infants in the NICU.

新生儿重症监护病房（NICU）的急性患儿目前具有复杂的医疗条件，需要个性化的治疗策略。这些婴儿在胎龄、出生体重、器官成熟度和药物代谢方面表现出显著的差异，增加了药物不良反应的风险。在新生儿重症监护室，吗啡是常用的处方药物，其剂量范围广，不良事件风险高。本回顾性研究的目的是探讨药物基因组学与我们当地III级新生儿重症监护室吗啡剂量的潜在相关性。在2022年3月至12月期间入学的婴儿被录取。收集临床常规护理中采集的EDTA残留血，提取55例患者的DNA。进行靶向基因分型检测rs1799971G > A型OPRM1变异和rs4680 G > A型COMT变异。从医疗记录中检索吗啡的剂量细节，并将其与基因型进行比较。每日吗啡口服当量中位数（mg/kg）随OPRM1基因型变化趋势：AA， 0.0916 (n = 40)；AG, 0.1500 (n = 13)；GG = 0.2284 （n = 2）。COMT基因型吗啡口服当量中位数和治疗天数趋势为：GG， 0.1429 mg/kg， 4 天（n = 17）；AG 0.1231 mg/kg， 6 天（n = 22）；AA, 0.0875 mg/kg， 8 天（n = 15）。极度早产儿需要最大剂量的吗啡，持续时间最长。虽然这些发现没有统计学意义，但我们的数据表明，需要进一步的研究来确定药物基因组学是否有利于个性化吗啡剂量需求和改善新生儿重症监护病房急性患儿的预后。

{"title":"Can pharmacogenetics inform morphine dosing in the neonatal intensive care unit? A retrospective evaluation","authors":"Anastasiya Mankouski , Luca Brunelli , Gwendolyn McMillin","doi":"10.1016/j.cca.2025.120814","DOIUrl":"10.1016/j.cca.2025.120814","url":null,"abstract":"<div><div>Acutely ill infants in the neonatal intensive care unit (NICU) present with complex medical conditions necessitating individualized therapeutic strategies. These infants exhibit significant variability in gestational age, birth weight, organ maturity and drug metabolism, increasing the risk of adverse drug reactions. Morphine is commonly prescribed in the NICU and is associated with a wide range of dosing as well as a high risk of adverse events. The objective of this retrospective study was to explore the potential relevance of pharmacogenomics to morphine dosing for our local level III NICU. Infants admitted between March and December 2022 were enrolled. Residual EDTA blood collected during routine clinical care was retrieved, and DNA was extracted for 55 patients. Targeted genotyping was performed to detect the rs1799971G > A variant of <em>OPRM1</em> and the rs4680 G > A variant of <em>COMT</em>. Morphine dosing details were retrieved from medical records, and they were compared to genotypes. Median morphine oral equivalents per day (mg/kg) trended with <em>OPRM1</em> genotype: AA, 0.0916 (<em>n</em> = 40); AG, 0.1500 (<em>n</em> = 13); GG, 0.2284 (<em>n</em> = 2). Median morphine oral equivalents and the number of days of treatment trended with <em>COMT</em> genotype: GG, 0.1429 mg/kg, 4 days (<em>n</em> = 17); AG, 0.1231 mg/kg, 6 days (<em>n</em> = 22); AA, 0.0875 mg/kg, 8 days (<em>n</em> = 15). Extremely premature infants required the highest morphine doses for the longest duration. Although statistical significance of these findings was not achieved, our data suggest that further studies are warranted to determine whether pharmacogenomics may be beneficial to individualize morphine dose requirements and improve outcomes for acutely ill infants in the NICU.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120814"},"PeriodicalIF":2.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888544","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

Liposomal nano-formulations: advancement in lung cancer treatment 脂质体纳米制剂：肺癌治疗的进展。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-30 DOI: 10.1016/j.cca.2025.120813

Azzalfa Ashraf , Qurat ul Ain , Asmaa Qamar , Amina Nisar , Shumaila Arshad , Mulazim Hussain Asim , Hafiz Muhammad Irfan

According to the WHO statistical report of 2022, lung cancer has the highest cancer mortality rate with 1.8 million deaths annually. Conventional treatment options for lung cancer include chemotherapy, surgical treatment and radiotherapy. Chemotherapy is associated with various challenges of drug resistance and toxicity. Diagnosis of lung cancer is also difficult due to the non-specific symptoms that overlap with other respiratory disorders like chronic obstructive pulmonary disease (COPD). Nano-formulations and particularly liposomes, offer a modern approach to address these issues. These lipid-based nano-carriers can be equipped with imaging agents that help to establish accurate and timely diagnosis of lung cancers. Moreover, liposomes loaded with anti-cancer drugs and genetic materials for chemotherapy and gene therapy, respectively, have shown a high success rate in cell lines studies and clinical trials. Inhaled liposome formulations such as aerosols and nebulizers are another advanced approach that has been investigated over past few years. This review article will provide a comprehensive summary of liposomes as novel drug delivery system, their preparation, methods of drug-loading, and their key role for lung cancer treatment. Moreover, a comparative analysis of liposomes with other nanocarriers to treat lung cancer is provided. Lastly, we have communicated the diverse scope of liposomal aerosols in inhalation therapy and medical devices for application in lung cancer.

根据世界卫生组织2022年的统计报告，肺癌是癌症死亡率最高的疾病，每年有180万人死亡。肺癌的常规治疗方案包括化疗、手术治疗和放射治疗。化疗伴随着各种耐药性和毒性的挑战。肺癌的诊断也很困难，因为其非特异性症状与慢性阻塞性肺疾病（COPD）等其他呼吸系统疾病重叠。纳米制剂，特别是脂质体，提供了解决这些问题的现代方法。这些基于脂质的纳米载体可以配备显像剂，帮助建立准确和及时的肺癌诊断。此外，分别装载抗癌药物和用于化疗和基因治疗的遗传物质的脂质体在细胞系研究和临床试验中显示出很高的成功率。吸入脂质体制剂，如气雾剂和雾化器是过去几年研究的另一种先进方法。本文就脂质体作为新型给药系统的研究进展、制备方法、载药方法及其在肺癌治疗中的重要作用作一综述。此外，脂质体与其他纳米载体治疗肺癌的比较分析提供。最后，我们介绍了脂质体气雾剂在吸入治疗和肺癌医疗器械中的应用范围。

{"title":"Liposomal nano-formulations: advancement in lung cancer treatment","authors":"Azzalfa Ashraf , Qurat ul Ain , Asmaa Qamar , Amina Nisar , Shumaila Arshad , Mulazim Hussain Asim , Hafiz Muhammad Irfan","doi":"10.1016/j.cca.2025.120813","DOIUrl":"10.1016/j.cca.2025.120813","url":null,"abstract":"<div><div>According to the WHO statistical report of 2022, lung cancer has the highest cancer mortality rate with 1.8 million deaths annually. Conventional treatment options for lung cancer include chemotherapy, surgical treatment and radiotherapy. Chemotherapy is associated with various challenges of drug resistance and toxicity. Diagnosis of lung cancer is also difficult due to the non-specific symptoms that overlap with other respiratory disorders like chronic obstructive pulmonary disease (COPD). Nano-formulations and particularly liposomes, offer a modern approach to address these issues. These lipid-based nano-carriers can be equipped with imaging agents that help to establish accurate and timely diagnosis of lung cancers. Moreover, liposomes loaded with anti-cancer drugs and genetic materials for chemotherapy and gene therapy, respectively, have shown a high success rate in cell lines studies and clinical trials. Inhaled liposome formulations such as aerosols and nebulizers are another advanced approach that has been investigated over past few years. This review article will provide a comprehensive summary of liposomes as novel drug delivery system, their preparation, methods of drug-loading, and their key role for lung cancer treatment. Moreover, a comparative analysis of liposomes with other nanocarriers to treat lung cancer is provided. Lastly, we have communicated the diverse scope of liposomal aerosols in inhalation therapy and medical devices for application in lung cancer.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120813"},"PeriodicalIF":2.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888590","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

Label-free gold nanostar-based SERS with machine learning: A platform for detecting endometrial cancer-associated polyamine metabolites 基于机器学习的无标记金纳米星SERS：检测子宫内膜癌相关多胺代谢物的平台。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-29 DOI: 10.1016/j.cca.2025.120811

Biqing Chen , Zengkun Wang , Jiayin Gao, Haizhu Sun, Yinghan Zhao, Yan Liu, Jianyu Liu, Xiaohong Qiu

The occurrence and progression of endometrial cancer are closely associated with metabolic reprogramming, in which polyamine metabolites play a critical role in tumor cell proliferation and invasion. In this study, we developed a label free surface enhanced Raman scattering (SERS) detection platform based on gold nanostars (AuNS), integrated with machine learning algorithms, to achieve highly sensitive detection and precise identification of polyamine metabolites related to endometrial cancer. In complex biological matrices such as serum, the platform yielded stable and reproducible spectral fingerprints, with a detection limit at the nanogram level. Furthermore, by constructing a polyamine metabolite spectral database and introducing machine learning models, both the classification accuracy and AUC values exceeded 95 %, enabling effective discrimination of different metabolic states and mixed systems. Taken together, the AuNS SERS strategy combined with machine learning provides a rapid, non-invasive, and intelligent detection tool for the early diagnosis and metabolic subtyping of endometrial cancer, with significant clinical application potential.

子宫内膜癌的发生和发展与代谢重编程密切相关，其中多胺代谢物在肿瘤细胞增殖和侵袭中起着关键作用。在本研究中，我们开发了一种基于金纳米星（AuNS）的无标记表面增强拉曼散射（SERS）检测平台，结合机器学习算法，实现了对子宫内膜癌相关多胺代谢物的高灵敏度检测和精确鉴定。在复杂的生物基质中，如血清，该平台产生稳定且可重复的光谱指纹，检测限在纳克水平。此外，通过构建多胺代谢物光谱数据库并引入机器学习模型，分类精度和AUC值均超过95 %，能够有效区分不同代谢状态和混合系统。综上所述，AuNS SERS策略结合机器学习为子宫内膜癌的早期诊断和代谢亚型分型提供了一种快速、无创、智能的检测工具，具有重要的临床应用潜力。

{"title":"Label-free gold nanostar-based SERS with machine learning: A platform for detecting endometrial cancer-associated polyamine metabolites","authors":"Biqing Chen , Zengkun Wang , Jiayin Gao, Haizhu Sun, Yinghan Zhao, Yan Liu, Jianyu Liu, Xiaohong Qiu","doi":"10.1016/j.cca.2025.120811","DOIUrl":"10.1016/j.cca.2025.120811","url":null,"abstract":"<div><div>The occurrence and progression of endometrial cancer are closely associated with metabolic reprogramming, in which polyamine metabolites play a critical role in tumor cell proliferation and invasion. In this study, we developed a label free surface enhanced Raman scattering (SERS) detection platform based on gold nanostars (AuNS), integrated with machine learning algorithms, to achieve highly sensitive detection and precise identification of polyamine metabolites related to endometrial cancer. In complex biological matrices such as serum, the platform yielded stable and reproducible spectral fingerprints, with a detection limit at the nanogram level. Furthermore, by constructing a polyamine metabolite spectral database and introducing machine learning models, both the classification accuracy and AUC values exceeded 95 %, enabling effective discrimination of different metabolic states and mixed systems. Taken together, the AuNS SERS strategy combined with machine learning provides a rapid, non-invasive, and intelligent detection tool for the early diagnosis and metabolic subtyping of endometrial cancer, with significant clinical application potential.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120811"},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877424","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

Next-generation nano-biosensors for hepatocellular carcinoma 用于肝细胞癌的下一代纳米生物传感器。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-27 DOI: 10.1016/j.cca.2025.120805

Qamar Abuhassan , Kamel Saleh , R. Roopashree , Jaya Bhanu Kanwar , T. Sudhakar , Vipasha Sharma , Ashish Singh Chauhan , Saida Khaitova

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and the limited sensitivity of conventional biomarkers. The emergence of nanomaterial-based biosensors offers transformative potential for precision diagnostics by integrating advanced physicochemical properties with molecular recognition strategies. This narrative review current progress in next-generation nanomaterial biosensors, including carbon nanostructures, metal–organic frameworks, quantum dots, and plasmonic nanoparticles, highlighting their roles in enhancing the sensitivity, specificity, and multiplexed detection of HCC-associated biomarkers such as alpha-fetoprotein, glypican-3, and circulating nucleic acids. We discuss innovative design principles, translational challenges, and clinical validation pathways, emphasizing how nanomaterial-enabled platforms can bridge the gap between laboratory innovation and bedside application. By critically evaluating technological advances and unmet clinical needs, this review underscores the promise of nanomaterial biosensors in enabling earlier detection, personalized monitoring, and improved prognostic assessment of HCC, ultimately advancing precision oncology.

肝细胞癌（HCC）仍然是世界范围内癌症相关死亡的主要原因，主要是由于晚期诊断和传统生物标志物的敏感性有限。基于纳米材料的生物传感器的出现通过将先进的物理化学特性与分子识别策略相结合，为精确诊断提供了变革性的潜力。本文综述了下一代纳米材料生物传感器的最新进展，包括碳纳米结构、金属有机框架、量子点和等离子体纳米粒子，强调了它们在提高hcc相关生物标志物（如甲胎蛋白、甘聚糖-3和循环核酸）的灵敏度、特异性和多路检测方面的作用。我们讨论了创新的设计原则、转化挑战和临床验证途径，强调了纳米材料平台如何弥合实验室创新和床边应用之间的差距。通过批判性地评估技术进步和未满足的临床需求，本综述强调了纳米材料生物传感器在HCC早期检测、个性化监测和改善预后评估方面的前景，最终推动了精准肿瘤学的发展。

{"title":"Next-generation nano-biosensors for hepatocellular carcinoma","authors":"Qamar Abuhassan , Kamel Saleh , R. Roopashree , Jaya Bhanu Kanwar , T. Sudhakar , Vipasha Sharma , Ashish Singh Chauhan , Saida Khaitova","doi":"10.1016/j.cca.2025.120805","DOIUrl":"10.1016/j.cca.2025.120805","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and the limited sensitivity of conventional biomarkers. The emergence of nanomaterial-based biosensors offers transformative potential for precision diagnostics by integrating advanced physicochemical properties with molecular recognition strategies. This narrative review current progress in next-generation nanomaterial biosensors, including carbon nanostructures, metal–organic frameworks, quantum dots, and plasmonic nanoparticles, highlighting their roles in enhancing the sensitivity, specificity, and multiplexed detection of HCC-associated biomarkers such as alpha-fetoprotein, glypican-3, and circulating nucleic acids. We discuss innovative design principles, translational challenges, and clinical validation pathways, emphasizing how nanomaterial-enabled platforms can bridge the gap between laboratory innovation and bedside application. By critically evaluating technological advances and unmet clinical needs, this review underscores the promise of nanomaterial biosensors in enabling earlier detection, personalized monitoring, and improved prognostic assessment of HCC, ultimately advancing precision oncology.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120805"},"PeriodicalIF":2.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854671","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

Tamm-Horsfall protein biosensors for management of nephrolithiasis Tamm-Horsfall蛋白生物传感器用于肾结石的管理。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-26 DOI: 10.1016/j.cca.2025.120810

Waleed Hassan Almalki , Imran Kazmi , Alzarea Sami I , Omar Awad Alsaidan , A. Rekha , Nadeem Sayyed , Surya Nath Pandey , Sachin Kumar Singh , Gaurav Gupta , Salem Salman Almujri

Nephrolithiasis is a common urological condition characterized by kidney stone formation and complex metabolic imbalances. Uromodulin (Tamm-Horsfall protein, THP) is the principal urinary glycoprotein and a promising risk-stratifying biomarker and long-term follow-up marker for nephrolithiasis. This review examines the dual action of THP in stone disease. The normal glycosylated form of THP can inhibit the formation of calcium oxalate crystals, whereas structurally modified or hypoglycosylated THP can promote crystal adhesion and aggregation. We provide a critical comparison between conventional immunoassays and emerging THP biosensors with respect to analytical performance, selectivity, and preanalytical requirements for the measurement of urine with reasonable reliability. Electrochemical and optical biosensors, as well as nanomaterials, are increasingly being used in biosensors, with graphene, gold nanoparticles (AuNPs), and tantalum oxide. Non-Faradaic impedance (Ta₂O₅-passivated interdigitated electrodes) has been demonstrated to detect a 0.5 ng/mL LOD in artificial urine, and printed impedance sensors and AuNP-based lateral-flow formats have a typical LOD of 25 to 80 ng/mL and have been demonstrated using minimally processed urine (e.g., centrifugation and/or dilution), instead of crude samples. Since urinary THP is usually in the mg L⁻¹ range, sub-ng/mL sensitivity cannot be understood in standard terms of detectability, but in terms of special use-cases (e.g., highly diluted samples, low-THP phenotypes, or quantitative low-end monitoring), it can be detected. In conclusion, we examined several significant limitations to translation, including biological variability (such as hydration status, infection, and circadian variations), the influence of the matrix, the lack of calibration and traceability, and the imperative for prospective clinical validation. Although microfluidics and digital presentation facilitate point-of-care tracking, the integration of AI/ML is not yet prevalent.

肾结石是一种常见的泌尿系统疾病，其特征是肾结石形成和复杂的代谢失衡。尿调蛋白（Tamm-Horsfall protein， THP）是肾结石的主要糖蛋白，也是一种有前景的风险分层生物标志物和长期随访标志物。本文综述了THP在结石疾病中的双重作用。正常糖基化形式的THP可以抑制草酸钙晶体的形成，而结构修饰或低糖基化的THP可以促进晶体的粘附和聚集。我们对传统的免疫测定法和新兴的THP生物传感器在分析性能、选择性和分析前要求方面进行了比较，并提供了合理的可靠性。电化学和光学生物传感器以及纳米材料越来越多地应用于生物传感器中，如石墨烯、金纳米颗粒（AuNPs）和氧化钽。非法拉第阻抗（ta2o5钝化的指间电极）已被证明可以检测人工尿液中0.5 ng/mL的LOD，印刷阻抗传感器和基于aunp的横向流格式的典型LOD为25至80 ng/mL，并已被证明可以使用最低限度处理的尿液（例如，离心和/或稀释），而不是原始样品。由于尿THP通常在mg L-1范围内，低于ng/mL的灵敏度不能用标准的可检测性来理解，但在特殊用例（例如，高度稀释的样品，低THP表型或定量低端监测）中，可以检测到。总之，我们研究了翻译的几个重要限制，包括生物变异性（如水合状态、感染和昼夜变化）、基质的影响、缺乏校准和可追溯性，以及前瞻性临床验证的必要性。虽然微流体和数字演示促进了护理点跟踪，但人工智能/机器学习的集成尚未普及。

{"title":"Tamm-Horsfall protein biosensors for management of nephrolithiasis","authors":"Waleed Hassan Almalki , Imran Kazmi , Alzarea Sami I , Omar Awad Alsaidan , A. Rekha , Nadeem Sayyed , Surya Nath Pandey , Sachin Kumar Singh , Gaurav Gupta , Salem Salman Almujri","doi":"10.1016/j.cca.2025.120810","DOIUrl":"10.1016/j.cca.2025.120810","url":null,"abstract":"<div><div>Nephrolithiasis is a common urological condition characterized by kidney stone formation and complex metabolic imbalances. Uromodulin (Tamm-Horsfall protein, THP) is the principal urinary glycoprotein and a promising risk-stratifying biomarker and long-term follow-up marker for nephrolithiasis. This review examines the dual action of THP in stone disease. The normal glycosylated form of THP can inhibit the formation of calcium oxalate crystals, whereas structurally modified or hypoglycosylated THP can promote crystal adhesion and aggregation. We provide a critical comparison between conventional immunoassays and emerging THP biosensors with respect to analytical performance, selectivity, and preanalytical requirements for the measurement of urine with reasonable reliability. Electrochemical and optical biosensors, as well as nanomaterials, are increasingly being used in biosensors, with graphene, gold nanoparticles (AuNPs), and tantalum oxide. Non-Faradaic impedance (Ta<sub>2</sub>O<sub>5</sub>-passivated interdigitated electrodes) has been demonstrated to detect a 0.5 ng/mL LOD in artificial urine, and printed impedance sensors and AuNP-based lateral-flow formats have a typical LOD of 25 to 80 ng/mL and have been demonstrated using minimally processed urine (e.g., centrifugation and/or dilution), instead of crude samples. Since urinary THP is usually in the mg L<sup>−1</sup> range, sub-ng/mL sensitivity cannot be understood in standard terms of detectability, but in terms of special use-cases (e.g., highly diluted samples, low-THP phenotypes, or quantitative low-end monitoring), it can be detected. In conclusion, we examined several significant limitations to translation, including biological variability (such as hydration status, infection, and circadian variations), the influence of the matrix, the lack of calibration and traceability, and the imperative for prospective clinical validation. Although microfluidics and digital presentation facilitate point-of-care tracking, the integration of AI/ML is not yet prevalent.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120810"},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849115","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

Integrating molecular diagnostics and artificial intelligence in chronic microbial disease 整合分子诊断和人工智能在慢性微生物疾病中的应用。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-26 DOI: 10.1016/j.cca.2025.120803

Bandita Dutta, Rina Ray Ray

Chronic microbial diseases, often driven by biofilm formation, pose a persistent global health burden due to their complex diagnosis, resistance mechanisms, and prolonged disease courses. Conventional diagnostic methods are time-consuming and often insufficient for early, precise detection and prognosis. Recent advances in molecular diagnostics, including PCR, hybridization, next-generation sequencing, and CRISPR-based assays, have enabled rapid, non-invasive, and highly sensitive detection of pathogens and resistance markers. Complementary “omics” technologies, like genomics, proteomics, and metabolomics, provide deeper insights into disease pathways, aiding in personalized treatment strategies. Furthermore, the integration of artificial intelligence (AI) and big data analytics enhances the interpretation of complex molecular datasets, enabling pattern recognition, risk prediction, and tailored therapeutic decisions. This manuscript reviews current tools and emerging technologies for the diagnosis and prognosis of chronic microbial diseases, highlighting the transformative potential of AI-driven precision medicine to improve patient outcomes through early detection, individualized treatment, and better disease management.

慢性微生物疾病通常由生物膜形成驱动，由于其复杂的诊断、耐药机制和延长的病程，造成了持续的全球健康负担。传统的诊断方法耗时长，而且往往不足以进行早期、精确的检测和预后。分子诊断的最新进展，包括PCR、杂交、下一代测序和基于crispr的检测，已经能够快速、无创和高度敏感地检测病原体和耐药性标记。互补的“组学”技术，如基因组学、蛋白质组学和代谢组学，提供了对疾病途径的更深入了解，有助于个性化治疗策略。此外，人工智能（AI）和大数据分析的集成增强了对复杂分子数据集的解释，实现了模式识别、风险预测和量身定制的治疗决策。本文回顾了目前用于慢性微生物疾病诊断和预后的工具和新兴技术，强调了人工智能驱动的精准医疗的变革潜力，通过早期发现、个性化治疗和更好的疾病管理来改善患者的预后。

{"title":"Integrating molecular diagnostics and artificial intelligence in chronic microbial disease","authors":"Bandita Dutta, Rina Ray Ray","doi":"10.1016/j.cca.2025.120803","DOIUrl":"10.1016/j.cca.2025.120803","url":null,"abstract":"<div><div>Chronic microbial diseases, often driven by biofilm formation, pose a persistent global health burden due to their complex diagnosis, resistance mechanisms, and prolonged disease courses. Conventional diagnostic methods are time-consuming and often insufficient for early, precise detection and prognosis. Recent advances in molecular diagnostics, including PCR, hybridization, next-generation sequencing, and CRISPR-based assays, have enabled rapid, non-invasive, and highly sensitive detection of pathogens and resistance markers. Complementary “omics” technologies, like genomics, proteomics, and metabolomics, provide deeper insights into disease pathways, aiding in personalized treatment strategies. Furthermore, the integration of artificial intelligence (AI) and big data analytics enhances the interpretation of complex molecular datasets, enabling pattern recognition, risk prediction, and tailored therapeutic decisions. This manuscript reviews current tools and emerging technologies for the diagnosis and prognosis of chronic microbial diseases, highlighting the transformative potential of AI-driven precision medicine to improve patient outcomes through early detection, individualized treatment, and better disease management.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120803"},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848962","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

Endothelial Glycocalyx biomarkers in acute lung injury 急性肺损伤中的内皮糖萼生物标志物

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-26 DOI: 10.1016/j.cca.2025.120804

M. Arockia Babu , A. Rekha , Kavita Goyal , Soumya V. Menon , Subhashree Ray , Prerna Uniyal , Chandana Maji , Abida Khan

Endothelial glycocalyx (eGC) degradation contributes to vascular and pulmonary dysfunction in acute lung injury (ALI). This study provides a comprehensive review of the structure of the endothelial glycocalyx (eGC) and the mechanisms underlying its injury. Additionally, it evaluates biomarkers indicative of glycocalyx disruption that have been investigated for clinical use, including syndecan-1, heparan sulfate, and hyaluronan. These biomarkers have been studied in both circulating and airway compartments, with some studies reporting signal size-dependent variations in their levels. Laboratory measurement methods, specifically immunoassays and mass spectrometry, are examined with an emphasis on preanalytical variables, analytical performance, interference, and existing deficiencies in standardization, calibration, and traceability. These deficiencies contribute to the challenges in achieving comparability across different studies. Subsequently, we assessed the evidence regarding the clinical utility of risk stratification and outcome prediction in the context of ALI/ARDS and sepsis heterogeneity, focusing on cohort characteristics, sampling intervals, and sample types. In conclusion, we propose the implementation of novel glycocalyx-stabilizing treatments and future advancements, such as multi-marker panels and their integration with microvascular imaging. Generally, the standardization of protocols and establishment of reporting systems are essential prerequisites for the incorporation of these biomarkers into routine clinical laboratory and intensive care unit workflows as reliable tools.

内皮糖萼（eGC）降解有助于急性肺损伤（ALI）的血管和肺功能障碍。本研究对内皮糖萼（eGC）的结构及其损伤机制进行了全面的综述。此外，它还评估了用于临床研究的糖萼破坏的生物标志物，包括syndecan-1、硫酸肝素和透明质酸。这些生物标志物已经在循环和气道室中进行了研究，一些研究报告了其水平的信号大小依赖性变化。实验室测量方法，特别是免疫测定法和质谱法，重点是分析前变量、分析性能、干扰和标准化、校准和可追溯性方面的现有缺陷。这些缺陷导致了在不同研究之间实现可比性的挑战。随后，我们评估了在ALI/ARDS和脓毒症异质性背景下风险分层和结果预测的临床应用证据，重点关注队列特征、采样间隔和样本类型。总之，我们建议实施新的糖萼稳定治疗和未来的进展，如多标记面板及其与微血管成像的集成。一般来说，将这些生物标志物作为可靠的工具纳入常规临床实验室和重症监护病房工作流程，方案的标准化和报告系统的建立是必不可少的先决条件。

{"title":"Endothelial Glycocalyx biomarkers in acute lung injury","authors":"M. Arockia Babu , A. Rekha , Kavita Goyal , Soumya V. Menon , Subhashree Ray , Prerna Uniyal , Chandana Maji , Abida Khan","doi":"10.1016/j.cca.2025.120804","DOIUrl":"10.1016/j.cca.2025.120804","url":null,"abstract":"<div><div>Endothelial glycocalyx (eGC) degradation contributes to vascular and pulmonary dysfunction in acute lung injury (ALI). This study provides a comprehensive review of the structure of the endothelial glycocalyx (eGC) and the mechanisms underlying its injury. Additionally, it evaluates biomarkers indicative of glycocalyx disruption that have been investigated for clinical use, including syndecan-1, heparan sulfate, and hyaluronan. These biomarkers have been studied in both circulating and airway compartments, with some studies reporting signal size-dependent variations in their levels. Laboratory measurement methods, specifically immunoassays and mass spectrometry, are examined with an emphasis on preanalytical variables, analytical performance, interference, and existing deficiencies in standardization, calibration, and traceability. These deficiencies contribute to the challenges in achieving comparability across different studies. Subsequently, we assessed the evidence regarding the clinical utility of risk stratification and outcome prediction in the context of ALI/ARDS and sepsis heterogeneity, focusing on cohort characteristics, sampling intervals, and sample types. In conclusion, we propose the implementation of novel glycocalyx-stabilizing treatments and future advancements, such as multi-marker panels and their integration with microvascular imaging. Generally, the standardization of protocols and establishment of reporting systems are essential prerequisites for the incorporation of these biomarkers into routine clinical laboratory and intensive care unit workflows as reliable tools.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120804"},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838151","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

Plasma and cerebrospinal fluid correlation for tryptophan and its metabolites and their expression in neurodegenerative, demyelinating, infectious diseases and CNS tumors 血浆和脑脊液中色氨酸及其代谢物的相关性及其在神经退行性、脱髓鞘、传染病和中枢神经系统肿瘤中的表达

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-25 DOI: 10.1016/j.cca.2025.120807

Yuhang Deng , Fenghao Xie , Yongjie Guan , Wenqing Wu , Sumei Han , Haoqin Jiang , Ming Guan

Background

To clarify the cerebrospinal fluid (CSF) and plasma correlation for tryptophan and its major metabolites in real clinical setting, and to explore their expression across common types of neurological disorders.

Methods

181 paired CSF and plasma samples from patients with neurological diseases and 67 plasma samples from healthy controls were collected. Tryptophan, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), melatonin, and kynurenic acid (KYNA) in those samples were measured using LC-MS/MS. Age- and sex-effects on plasma levels of those analytes were evaluated in healthy control. Pearson correlation analysis was used to assess CSF and plasma correlation. Patients were grouped into neurodegenerative, demyelinating, tumors, and infectious diseases for group comparisons.

Results

CSF and plasma correlation were weak but still statistically significant for most analytes (r = 0.15–0.3, p < 0.05); but no significant correlation was observed for 5-HIAA. In healthy controls plasma tryptophan and was higher in males than in females, but 5-HIAA was higher in females. The plasma concentrations of these analytes showed no significant differences among different diseases, nor between the disease groups and the control group. However, the level of 5-HIAA were significantly lower in all disease groups compared with the control group. By contrast, CSF tryptophan and KYNA levels in patients with CNS tumors were significantly higher than in patients with other diseases.

Conclusions

Plasma tryptophan and its metabolites do not reliably reflect their CSF levels. The selective elevation of CSF tryptophan and KYNA in tumor patients may reflect tumor-associated changes in metabolism, but their biological significance requires further investigation.

背景：明确脑脊液（CSF）和血浆中色氨酸及其主要代谢物在真实临床环境中的相关性，并探讨其在常见类型神经系统疾病中的表达。方法收集181例神经系统疾病患者配对脑脊液和血浆样本，67例健康对照者血浆样本。采用LC-MS/MS检测色氨酸、血清素、5-羟基吲哚乙酸（5-HIAA）、褪黑素和犬尿酸（KYNA）含量。在健康对照中评估了年龄和性别对这些分析物血浆水平的影响。Pearson相关性分析评价脑脊液与血浆的相关性。将患者分为神经退行性疾病、脱髓鞘疾病、肿瘤疾病和感染性疾病进行组间比较。结果scsf与血浆相关性较弱，但多数分析结果仍有统计学意义（r = 0.15 ~ 0.3, p < 0.05）；但5-HIAA无显著相关性。在健康对照中，男性血浆色氨酸含量高于女性，但5-HIAA在女性中较高。这些分析物的血浆浓度在不同疾病之间没有显着差异，在疾病组和对照组之间也没有显着差异。但与对照组相比，各疾病组5-HIAA水平均显著降低。相比之下，中枢神经系统肿瘤患者脑脊液色氨酸和KYNA水平明显高于其他疾病患者。结论血浆色氨酸及其代谢物不能可靠地反映脑脊液水平。肿瘤患者脑脊液色氨酸和KYNA的选择性升高可能反映了肿瘤相关的代谢变化，但其生物学意义有待进一步研究。

{"title":"Plasma and cerebrospinal fluid correlation for tryptophan and its metabolites and their expression in neurodegenerative, demyelinating, infectious diseases and CNS tumors","authors":"Yuhang Deng , Fenghao Xie , Yongjie Guan , Wenqing Wu , Sumei Han , Haoqin Jiang , Ming Guan","doi":"10.1016/j.cca.2025.120807","DOIUrl":"10.1016/j.cca.2025.120807","url":null,"abstract":"<div><h3>Background</h3><div>To clarify the cerebrospinal fluid (CSF) and plasma correlation for tryptophan and its major metabolites in real clinical setting, and to explore their expression across common types of neurological disorders.</div></div><div><h3>Methods</h3><div>181 paired CSF and plasma samples from patients with neurological diseases and 67 plasma samples from healthy controls were collected. Tryptophan, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), melatonin, and kynurenic acid (KYNA) in those samples were measured using LC-MS/MS. Age- and sex-effects on plasma levels of those analytes were evaluated in healthy control. Pearson correlation analysis was used to assess CSF and plasma correlation. Patients were grouped into neurodegenerative, demyelinating, tumors, and infectious diseases for group comparisons.</div></div><div><h3>Results</h3><div>CSF and plasma correlation were weak but still statistically significant for most analytes (<em>r</em> = 0.15–0.3, <em>p</em> < 0.05); but no significant correlation was observed for 5-HIAA. In healthy controls plasma tryptophan and was higher in males than in females, but 5-HIAA was higher in females. The plasma concentrations of these analytes showed no significant differences among different diseases, nor between the disease groups and the control group. However, the level of 5-HIAA were significantly lower in all disease groups compared with the control group. By contrast, CSF tryptophan and KYNA levels in patients with CNS tumors were significantly higher than in patients with other diseases.</div></div><div><h3>Conclusions</h3><div>Plasma tryptophan and its metabolites do not reliably reflect their CSF levels. The selective elevation of CSF tryptophan and KYNA in tumor patients may reflect tumor-associated changes in metabolism, but their biological significance requires further investigation.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120807"},"PeriodicalIF":2.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838150","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