Pub Date : 2024-08-13DOI: 10.1016/j.cca.2024.119922
Preeclampsia (PE) is a life-threatening disease of pregnancy and a prominent cause of neonatal and maternal mortality and morbidity. PE affects approximately 5–10% of pregnancies worldwide, posing significant risks to perinatal and maternal health. It is characterized by a variety of interconnected pathological cascades contributing to the stimulation of intravascular inflammation, oxidative stress (OS), endothelial cell activation, and syncytiotrophoblast stress that converge on a common pathway, ultimately resulting in disease progression. The present study was designed and executed to review the existing scientific literature, specifically focusing on the etiology (gestational diabetes mellitus and maternal obesity, insulin resistance, metabolic syndrome, maternal infection, periodontal disease, altered microbiome, and genetics), clinical presentations (hypertension, blood disorders, proteinuria, hepatic dysfunction, renal dysfunction, pulmonary edema, cardiac dysfunction, fetal growth restrictions, and eclampsia), therapeutic clinical biomarkers (creatinine, albuminuria, and cystatin C) along with their associations and mechanisms in PE. In addition, this study provides insights into the potential of nanomedicines for targeting these mechanisms for PE management and treatment. Inflammation, OS, proteinuria, and an altered microbiome are prominent biomarkers associated with progression and PE-related pathogenesis. Understanding the molecular mechanisms, exploring suitable markers, targeted interventions, comprehensive screening, and holistic strategies are critical to decreasing the incidence of PE and promoting maternal-fetal well-being. The present study comprehensively reviewed the etiology, clinical presentations, therapeutic biomarkers, and preventive potential of nanomedicines in the treatment and management of PE.
子痫前期(PE)是一种危及生命的妊娠疾病,也是导致新生儿和孕产妇死亡和发病的主要原因。全世界约有 5-10% 的妊娠会受到子痫前期的影响,对围产期和孕产妇的健康构成重大风险。PE 的特点是各种相互关联的病理级联反应刺激血管内炎症、氧化应激(OS)、内皮细胞活化和合胞滋养细胞应激,这些反应汇聚在一个共同的途径上,最终导致疾病进展。本研究旨在回顾现有的科学文献,尤其侧重于病因(妊娠糖尿病和孕产妇肥胖、胰岛素抵抗、代谢综合征、孕产妇感染、牙周病、微生物组改变和遗传学)、临床表现(高血压、血液紊乱、蛋白尿、肝功能异常、肾功能异常、肺水肿、心功能异常、胎儿生长受限和子痫)、治疗性临床生物标志物(肌酐、白蛋白尿和胱抑素 C)及其在 PE 中的关联和机制。此外,本研究还深入探讨了纳米药物针对这些机制进行 PE 管理和治疗的潜力。炎症、OS、蛋白尿和微生物组改变是与 PE 进展和相关发病机制有关的重要生物标志物。了解分子机制、探索合适的标记物、有针对性的干预措施、全面筛查和综合策略对于降低 PE 的发病率和促进母胎健康至关重要。本研究全面回顾了纳米药物在治疗和管理 PE 方面的病因、临床表现、治疗生物标志物和预防潜力。
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Pub Date : 2024-08-10DOI: 10.1016/j.cca.2024.119901
Background
Platelet contains growth factors that enhance tissue repair mechanisms, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF-AA and −AB), and transforming growth factor (TGF)-β. Autologous platelet-rich plasma (PRP) has been shown to significantly improve the treatment of tendon injuries compared with hyaluronic acid and placebo. The topic of agreement between platelet concentrations and growth factors has been covered in some previous studies, but growth factor levels did not correlate well with platelet concentrations.
Method
In this study, autologous PRP was prepared by concentrating platelets through a J6-MI centrifuge. The automatic hematology analyzer Sysmex XN-20 was used to analyze the platelet concentration in PRP, and the PRP growth factors were determined by ELISA, including PDGF, transforming growth factor- β1 (TGF-β1), and EGF. Statistical analysis was conducted on data from 107 patients who received autologous PRP using Pearson correlation analysis.
Results
Pearson correlation analysis revealed PDGF, TGF, and EGF had a strong positive correlation with the platelet concentration of the final PRP product (r = 0.697, p < 0.0001; r = 0.488, p < 0.0001; r = 0.572, p < 0.0001, respectively)
Conclusions
There was a strong positive correlation between the concentration of platelets in the final PRP product and the levels of PDGF-AB, TGF-β, and EGF. These results suggested straightforward and cost-effective growth factor tests can provide valuable information about platelet content in PRP.
{"title":"The growth factor content as an indicator of platelet counts in platelet-rich plasma","authors":"","doi":"10.1016/j.cca.2024.119901","DOIUrl":"10.1016/j.cca.2024.119901","url":null,"abstract":"<div><h3>Background</h3><p>Platelet contains growth factors that enhance tissue repair mechanisms, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF-AA and −AB), and transforming growth factor (TGF)-β. Autologous platelet-rich plasma (PRP) has been shown to significantly improve the treatment of tendon injuries compared with hyaluronic acid and placebo. The topic of agreement between platelet concentrations and growth factors has been covered in some previous studies, but growth factor levels did not correlate well with platelet concentrations.</p></div><div><h3>Method</h3><p>In this study, autologous PRP was prepared by concentrating platelets through a J6-MI centrifuge. The automatic hematology analyzer Sysmex XN-20 was used to analyze the platelet concentration in PRP, and the PRP growth factors were determined by ELISA, including PDGF, transforming growth factor- β1 (TGF-β1), and EGF. Statistical analysis was conducted on data from 107 patients who received autologous PRP using Pearson correlation analysis.</p></div><div><h3>Results</h3><p>Pearson correlation analysis revealed PDGF, TGF, and EGF had a strong positive correlation with the platelet concentration of the final PRP product (r = 0.697, p < 0.0001; r = 0.488, p < 0.0001; r = 0.572, p < 0.0001, respectively)</p></div><div><h3>Conclusions</h3><p>There was a strong positive correlation between the concentration of platelets in the final PRP product and the levels of PDGF-AB, TGF-β, and EGF. These results suggested straightforward and cost-effective growth factor tests can provide valuable information about platelet content in PRP.</p></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970744","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}
Pub Date : 2024-08-10DOI: 10.1016/j.cca.2024.119899
Oxylipins derived from polyunsaturated fatty acids (PUFAs) are important endogenous signaling molecules, but are little characterized in pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD). In this study, we identified novel plasma oxylipins associated with PH risk in COPD patients. The plasma oxylipin profiles of COPD patients without PH (COPD-noPH) or with PH (COPD-PH) were obtained from discovery and validation cohort, using the process of LC-MS/MS analysis. There was a significant decrease in the plasma levels of both free docosahexaenoic acid (DHA) and DHA-derived oxylipins in the COPD-PH group. The multivariable logistic regression model identified DHA and four DHA-derived oxylipins (13-HDHA, 10-HDHA, 8-HDHA and 16-HDHA) exhibited significant differences between the two groups after adjusting for sex, BMI, FEV1% predicted, and smoking status. The diagnostic value of these metabolites was further evaluated through ROC curve analysis. The transcriptome profiles in peripheral blood mononuclear cells (PBMCs) of COPD-PH patients and COPD-PH patients were detected through high-throughput sequencing. The enrichment analysis revealed that the upregulated differentially expressed genes (DEGs) were highly enriched in the interferon signaling pathway. In addition, DHA supplementation proved that DHA may inhibit the development of pH by reducing the secretion of interferons derived from PBMCs. This conjecture was further confirmed by the higher level of serum interferon-γ and interferon-α2 of COPD-PH patients than that of COPD-noPH patients. The present study highlights that decreased DHA and DHA-derived oxylipins levels are suggestive of a higher risk of pH development in COPD cases.
{"title":"Decreased plasma docosahexaenoic acid concentration in chronic obstructive pulmonary disease patients with pulmonary Hypertension: Findings from human lipidomics and transcriptomics analysis","authors":"","doi":"10.1016/j.cca.2024.119899","DOIUrl":"10.1016/j.cca.2024.119899","url":null,"abstract":"<div><p>Oxylipins derived from polyunsaturated fatty acids (PUFAs) are important endogenous signaling molecules, but are little characterized in pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD). In this study, we identified novel plasma oxylipins associated with PH risk in COPD patients. The plasma oxylipin profiles of COPD patients without PH (COPD-noPH) or with PH (COPD-PH) were obtained from discovery and validation cohort, using the process of LC-MS/MS analysis. There was a significant decrease in the plasma levels of both free docosahexaenoic acid (DHA) and DHA-derived oxylipins in the COPD-PH group. The multivariable logistic regression model identified DHA and four DHA-derived oxylipins (13-HDHA, 10-HDHA, 8-HDHA and 16-HDHA) exhibited significant differences between the two groups after adjusting for sex, BMI, FEV1% predicted, and smoking status. The diagnostic value of these metabolites was further evaluated through ROC curve analysis. The transcriptome profiles in peripheral blood mononuclear cells (PBMCs) of COPD-PH patients and COPD-PH patients were detected through high-throughput sequencing. The enrichment analysis revealed that the upregulated differentially expressed genes (DEGs) were highly enriched in the interferon signaling pathway. In addition, DHA supplementation proved that DHA may inhibit the development of pH by reducing the secretion of interferons derived from PBMCs. This conjecture was further confirmed by the higher level of serum interferon-γ and interferon-α2 of COPD-PH patients than that of COPD-noPH patients. The present study highlights that decreased DHA and DHA-derived oxylipins levels are suggestive of a higher risk of pH development in COPD cases.</p></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970743","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}
Pub Date : 2024-08-10DOI: 10.1016/j.cca.2024.119915
The physiological and clinical importance of Glutathione and Cysteamine is emphasized by their participation in a range of conditions, such as diabetes, cancer, renal failure, Parkinson’s disease, and hypothyroidism. This necessitates the requirement for accessible, expedited, and cost-efficient testing that can facilitate clinical diagnosis and treatment options. This article examines numerous techniques used to detect both glutathione and cysteamine. The discussed methods include electroanalytical techniques such as voltammetry and amperometry, which are examined for their sensitivity and ability to provide real-time analysis. Furthermore, this study investigates the accuracy of gas chromatography-mass spectrometry (GC–MS) and high-performance liquid chromatography (HPLC) in measuring the concentrations of glutathione and cysteamine. Additionally, the potential of new nanotechnology-based methods, such as plasmonic nanoparticles and quantum dots, to improve the sensitivity of detecting glutathione and cysteamine is emphasized.
{"title":"Unveiling thiol biomarkers: Glutathione and cysteamine","authors":"","doi":"10.1016/j.cca.2024.119915","DOIUrl":"10.1016/j.cca.2024.119915","url":null,"abstract":"<div><p>The physiological and clinical importance of Glutathione and Cysteamine is emphasized by their participation in a range of conditions, such as diabetes, cancer, renal failure, Parkinson’s disease, and hypothyroidism. This necessitates the requirement for accessible, expedited, and cost-efficient testing that can facilitate clinical diagnosis and treatment options. This article examines numerous techniques used to detect both glutathione and cysteamine. The discussed methods include electroanalytical techniques such as voltammetry and amperometry, which are examined for their sensitivity and ability to provide real-time analysis. Furthermore, this study investigates the accuracy of gas chromatography-mass spectrometry (GC–MS) and high-performance liquid chromatography (HPLC) in measuring the concentrations of glutathione and cysteamine. Additionally, the potential of new nanotechnology-based methods, such as plasmonic nanoparticles and quantum dots, to improve the sensitivity of detecting glutathione and cysteamine is emphasized.</p></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970745","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}
Pub Date : 2024-08-09DOI: 10.1016/j.cca.2024.119906
Mycoplasma pneumoniae can cause respiratory infections and pneumonia, posing a serious threat to the health of children and adolescents. Early diagnosis of Mycoplasma pneumoniae infection is crucial for clinical treatment. Currently, diagnostic methods for Mycoplasma pneumoniae infection include pathogen detection, molecular biology techniques, and bacterial culture, all of which have certain limitations. Here, we developed a rapid, simple, and accurate detection method for Mycoplasma pneumoniae that does not rely on large equipment or complex operations. This technology combines the CRISPR-Cas12a system with recombinase polymerase amplification (RPA), allowing the detection results to be observed through fluorescence curves and immunochromatographic lateral flow strips.It has been validated that RPA-CRISPR/Cas12a fluorescence analysis and RPA-CRISPR/Cas12-immunochromatographic exhibit no cross-reactivity with other common pathogens, and The established detection limit was ascertained to be as low as 102 copies/µL.Additionally, 49 clinical samples were tested and compared with fluorescence quantitative polymerase chain reaction, demonstrating a sensitivity and specificity of 100%. This platform exhibits promising clinical performance and holds significant potential for clinical application, particularly in settings with limited resources, such as clinical care points or resource-constrained areas.
{"title":"Establishment of a rapid detection method for Mycoplasma pneumoniae based on RPA-CRISPR-Cas12a technology","authors":"","doi":"10.1016/j.cca.2024.119906","DOIUrl":"10.1016/j.cca.2024.119906","url":null,"abstract":"<div><p>Mycoplasma pneumoniae can cause respiratory infections and pneumonia, posing a serious threat to the health of children and adolescents. Early diagnosis of Mycoplasma pneumoniae infection is crucial for clinical treatment. Currently, diagnostic methods for Mycoplasma pneumoniae infection include pathogen detection, molecular biology techniques, and bacterial culture, all of which have certain limitations. Here, we developed a rapid, simple, and accurate detection method for Mycoplasma pneumoniae that does not rely on large equipment or complex operations. This technology combines the CRISPR-Cas12a system with recombinase polymerase amplification (RPA), allowing the detection results to be observed through fluorescence curves and immunochromatographic lateral flow <span><span>strips.It</span><svg><path></path></svg></span> has been validated that RPA-CRISPR/Cas12a fluorescence analysis and RPA-CRISPR/Cas12-immunochromatographic exhibit no cross-reactivity with other common pathogens, and The established detection limit was ascertained to be as low as 10<sup>2</sup> copies/µL.Additionally, 49 clinical samples were tested and compared with fluorescence quantitative polymerase chain reaction, demonstrating a sensitivity and specificity of 100%. This platform exhibits promising clinical performance and holds significant potential for clinical application, particularly in settings with limited resources, such as clinical care points or resource-constrained areas.</p></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912035","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}
Pub Date : 2024-08-08DOI: 10.1016/j.cca.2024.119907
Background
Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions.
Methods
In this meta-analysis, we searched for urinary C–C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions.
Results
We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75–0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71–0.79),0.71 (95 % CI 0.67–0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83–0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup anal
{"title":"Persistent acute kidney injury biomarkers: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.cca.2024.119907","DOIUrl":"10.1016/j.cca.2024.119907","url":null,"abstract":"<div><h3>Background</h3><p>Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions.</p></div><div><h3>Methods</h3><p>In this <em>meta</em>-analysis, we searched for urinary C–C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, <em>meta</em>-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions.</p></div><div><h3>Results</h3><p>We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75–0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71–0.79),0.71 (95 % CI 0.67–0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to <em>meta</em>-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83–0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup anal","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009898124021600/pdfft?md5=3229d85b342d9c690917a3e421541b00&pid=1-s2.0-S0009898124021600-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.cca.2024.119903
Background and aims
DiGeorge syndrome (DGS) is a genetic disorder manifesting in polymorphic symptoms related to developmental abnormalities of various organs including thymus. DGS is caused by microdeletions in the 22q11.2 region between several low copy repeats (LCR) occurring in approximately 1 in 4000 live births. Diagnosis of DGS relies on phenotypic examination, qPCR, ultrasound, FISH, MLPA and NGS which can be relatively inaccurate, time-consuming, and costly.
Materials and methods
A novel multiplex droplet digital PCR (ddPCR) assay was designed, optimized and validated for detection and mapping 22q11.2 microdeletions by simultaneous amplification of three targets — TUPLE1, ZNF74, D22S936 — within the deletion areas and one reference target — RPP30 — as an internal control.
Results
The assay reliable identified microdeletions when the template concentration was >32 copies per reaction and successfully detected LCR22A-B, LCR22A-C, LCR22A-D, and LCR22B-C deletions in clinical samples from 153 patients with signs of immunodeficiency. In patients with the microdeletions, flow cytometry detected a significant increase in B-cell and natural killer cell counts and percentages, while T-cell percentages and T-cell receptor excision circle (TREC) numbers decreased.
Conclusion
The designed ddPCR assay is suitable for diagnosing DGS using whole blood and blood spots.
背景和目的:迪乔治综合征(DGS)是一种遗传性疾病,表现为与胸腺等多个器官发育异常有关的多形性症状。DGS是由22q11.2区域几个低拷贝重复序列(LCR)之间的微缺失引起的,大约每4000个活产婴儿中就有1例。DGS 的诊断依赖于表型检查、qPCR、超声波、FISH、MLPA 和 NGS,这些方法可能相对不准确、耗时且昂贵:设计、优化并验证了一种新型多重液滴数字 PCR(ddPCR)检测方法,通过同时扩增缺失区内的三个靶标(TUPLE1、ZNF74、D22S936)和一个参考靶标(RPP30)作为内部对照,检测并绘制 22q11.2 微缺失图:当每次反应的模板浓度大于 32 个拷贝时,该检测方法能可靠地识别微缺失,并在 153 名有免疫缺陷症状的患者的临床样本中成功检测出 LCR22A-B、LCR22A-C、LCR22A-D 和 LCR22B-C 缺失。在微缺失患者中,流式细胞术检测到 B 细胞和自然杀伤细胞的数量和百分比显著增加,而 T 细胞百分比和 T 细胞受体切割圈(TREC)数量减少:结论:设计的 ddPCR 检测方法适用于使用全血和血斑诊断 DGS。
{"title":"Multiplex droplet digital PCR for 22q11.2 microdeletions screening and DiGeorge syndrome diagnostics","authors":"","doi":"10.1016/j.cca.2024.119903","DOIUrl":"10.1016/j.cca.2024.119903","url":null,"abstract":"<div><h3>Background and aims</h3><p>DiGeorge syndrome (DGS) is a genetic disorder manifesting in polymorphic symptoms related to developmental abnormalities of various organs including thymus. DGS is caused by microdeletions in the 22q11.2 region between several low copy repeats (LCR) occurring in approximately 1 in 4000 live births. Diagnosis of DGS relies on phenotypic examination, qPCR, ultrasound, FISH, MLPA and NGS which can be relatively inaccurate, time-consuming, and costly.</p></div><div><h3>Materials and methods</h3><p>A novel multiplex droplet digital PCR (ddPCR) assay was designed, optimized and validated for detection and mapping 22q11.2 microdeletions by simultaneous amplification of three targets — <em>TUPLE1</em>, <em>ZNF74</em>, D22S936 — within the deletion areas and one reference target — <em>RPP30</em> — as an internal control.</p></div><div><h3>Results</h3><p>The assay reliable identified microdeletions when the template concentration was >32 copies per reaction and successfully detected LCR22A-B, LCR22A-C, LCR22A-D, and LCR22B-C deletions in clinical samples from 153 patients with signs of immunodeficiency. In patients with the microdeletions, flow cytometry detected a significant increase in B-cell and natural killer cell counts and percentages, while T-cell percentages and T-cell receptor excision circle (TREC) numbers decreased.</p></div><div><h3>Conclusion</h3><p>The designed ddPCR assay is suitable for diagnosing DGS using whole blood and blood spots.</p></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912036","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}
Pub Date : 2024-08-08DOI: 10.1016/j.cca.2024.119905
Objectives
The quality control of serological assays remains controversial. The aim of this project was to describe the problems associated with a working model for controlling these assays and solutions, including using a source of well-defined targets and acceptable limits, a process to identify lot-to-lot reagent variation and an interpretation of the result that accounted for the clinical situation. False-negative results are problematic but can be reduced by identifying and comparing reagent lot variation with previous results.
Methods
The components of the Quality Assurance strategy are the following: Lot-to-lot reagent and calibrator variation assessment; dynamic, big-data approach to determine accurate targets and acceptable limits for manufacturer-provided QC material; negative QC monitoring process; use of commutable EQA with a sufficient method subgroup size to assess bias; clinical assessment of any statistically flagged error; and provision of support to the clinician for the interpretation of results.
Results
The model described has been used for twelve months, and acceptable variation has been maintained.
Conclusions
The paper presents a solution that emphasizes the early detection of reagent lot variation and patient risk rather than instrument control.
Reducing the risk of a false result to patients requires optimal assay quality control and an effective mechanism to support the clinician’s use of these results in diagnosis and monitoring. The problems of serological assays are well-known, but there remain few integrated solutions in the literature.
{"title":"Quality control for serological testing","authors":"","doi":"10.1016/j.cca.2024.119905","DOIUrl":"10.1016/j.cca.2024.119905","url":null,"abstract":"<div><h3>Objectives</h3><p>The quality control of serological assays remains controversial. The aim of this project was to describe the problems associated with a working model for controlling these assays and solutions, including using a source of well-defined targets and acceptable limits, a process to identify lot-to-lot reagent variation and an interpretation of the result that accounted for the clinical situation. False-negative results are problematic but can be reduced by identifying and comparing reagent lot variation with previous results.</p></div><div><h3>Methods</h3><p>The components of the Quality Assurance strategy are the following: Lot-to-lot reagent and calibrator variation assessment; dynamic, big-data approach to determine accurate targets and acceptable limits for manufacturer-provided QC material; negative QC monitoring process; use of commutable EQA with a sufficient method subgroup size to assess bias; clinical assessment of any statistically flagged error; and provision of support to the clinician for the interpretation of results.</p></div><div><h3>Results</h3><p>The model described has been used for twelve months, and acceptable variation has been maintained.</p></div><div><h3>Conclusions</h3><p>The paper presents a solution that emphasizes the early detection of reagent lot variation and patient risk rather than instrument control.</p><p>Reducing the risk of a false result to patients requires optimal assay quality control and an effective mechanism to support the clinician’s use of these results in diagnosis and monitoring. The problems of serological assays are well-known, but there remain few integrated solutions in the literature.</p></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912047","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}
Pub Date : 2024-08-06DOI: 10.1016/j.cca.2024.119904
Background
A poor prognosis is associated with atherosclerotic plaque rupture (PR) despite after conventional therapy for patients with acute coronary syndrome (ACS). Timely identification of PR improves the risk stratification and prognosis of ACS patients.
Methods
A derivation cohort of 110 patients with ACS who underwent pre-intervention optical coherence tomography (OCT) were matched 1:1 to the PR and intact fibrous cap (IFC) groups according to traditional risk factors. Candidate PR proteins were identified via mass spectrometry (MS)-based proteomics using unbiased machine learning methods and were further validated by enzyme-linked immunosorbent assay (ELISA) in an external validation cohort of 85 patients with ACS. The performance of candidate biomakers was assessed using the receiver operating characteristic curve analysis.
Results
1121 proteins were identified and 535 filtered proteins were used for analysis. Nine candidate proteins were screened by five machine learning algorithms. Three proteins (APOC3, RAB39A, and KNG1) were significantly different between the PR and IFC in validation cohort. The performance of plasm APOC3, RAB39A, and KNG1 for differentiating PR and IFC was superior to that of the conventional biomarkers and risk factors.
Conclusion
The proteins (APOC3, RAB39A, and KNG1) serve as a potential novel diagnostic tool to identify PR in ACS patients.
{"title":"Derivation and external validation of mass spectrometry-based proteomic model using machine learning algorithms to predict plaque rupture in patients with acute coronary syndrome","authors":"","doi":"10.1016/j.cca.2024.119904","DOIUrl":"10.1016/j.cca.2024.119904","url":null,"abstract":"<div><h3>Background</h3><p>A poor prognosis is associated with atherosclerotic plaque rupture (PR) despite after conventional therapy for patients with acute coronary syndrome (ACS). Timely identification of PR improves the risk stratification and prognosis of ACS patients.</p></div><div><h3>Methods</h3><p>A derivation cohort of 110 patients with ACS who underwent pre-intervention optical coherence tomography (OCT) were matched 1:1 to the PR and intact fibrous cap (IFC) groups according to traditional risk factors. Candidate PR proteins were identified via mass spectrometry (MS)-based proteomics using unbiased machine learning methods and were further validated by enzyme-linked immunosorbent assay (ELISA) in an external validation cohort of 85 patients with ACS. The performance of candidate biomakers was assessed using the receiver operating characteristic curve analysis.</p></div><div><h3>Results</h3><p>1121 proteins were identified and 535 filtered proteins were used for analysis. Nine candidate proteins were screened by five machine learning algorithms. Three proteins (APOC3, RAB39A, and KNG1) were significantly different between the PR and IFC in validation cohort. The performance of plasm APOC3, RAB39A, and KNG1 for differentiating PR and IFC was superior to that of the conventional biomarkers and risk factors.</p></div><div><h3>Conclusion</h3><p>The proteins (APOC3, RAB39A, and KNG1) serve as a potential novel diagnostic tool to identify PR in ACS patients.</p></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009898124021570/pdfft?md5=6e88d0e1cedb61ba7a71188a3d93325c&pid=1-s2.0-S0009898124021570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}