Journal of Clinical Laboratory Analysis最新文献_第8页

Application of Second-Generation Sequencing Technology in Lower Respiratory Tract Infection 第二代测序技术在下呼吸道感染中的应用

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-08-19 DOI: 10.1002/jcla.25090

Chong Wang, Shuo Yang, Qi Liu, Hongchao Liu, Shangjia Jin, Jiajia Zheng, Xiumei Xiao, Xin Hou, Jing Li, Sisi Ma, Liyan Cui

Background

Lower respiratory tract infection (LRTI) has long been an important threat to people's life and health, so the rapid diagnosis of LRTI is of great significance in clinical treatment. In recent years, the development of the sequencing technology provides a new direction for the rapid diagnosis of LRTI. In this review, the advantages and disadvantages of second-generation sequencing techniques represented by metagenomics next-generation sequencing (mNGS) and droplet digital polymerase chain reaction (ddPCR) in LRTI were reviewed. Furthermore, it offers insights into the future trajectory of this technology, highlighting its potential to revolutionise the field of respiratory infection diagnostics.

Objective

This review summarises developments in mechanistic research of second-generation sequencing technology their relationship with clinical practice, providing insights for future research.

Methods

Authors conducted a search on PubMed and Web of Science using the professional terms ‘Lower respiratory tract infection’ and ‘droplet digital polymerase chain reaction’ and ‘metagenomics next generation sequencing’. The obtained literature was then roughly categorised based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section.

Results

Different studies discussed the application of second-generation sequencing technology in LRTI from different angles, including the detection of pathogens of LRTI by mNGS and ddPCR, the prediction ability of drug-resistant bacteria, and comparison with traditional methods. We try to analyse the advantages and disadvantages of the second-generation sequencing technology by combing the research results of mNGS and ddPCR. In addition, the development direction of the second-generation sequencing technology is prospected.

背景：下呼吸道感染（LRTI）长期以来一直是威胁人们生命健康的重要疾病，因此快速诊断LRTI对临床治疗具有重要意义。近年来，测序技术的发展为 LRTI 的快速诊断提供了新的方向。本文综述了以元基因组学新一代测序（mNGS）和液滴数字聚合酶链反应（ddPCR）为代表的第二代测序技术在 LRTI 中的优缺点。此外，该综述还对这一技术的未来发展轨迹提出了见解，强调了其彻底改变呼吸道感染诊断领域的潜力：本综述总结了第二代测序技术的机理研究进展及其与临床实践的关系，为未来研究提供了启示：作者使用专业术语 "下呼吸道感染"、"液滴数字聚合酶链反应 "和 "元基因组学新一代测序 "在 PubMed 和 Web of Science 上进行了搜索。然后根据研究内容对获得的文献进行了粗略分类。相似的研究被归入相同的部分，并根据每个部分的关键词进行进一步搜索：不同的研究从不同角度探讨了二代测序技术在 LRTI 中的应用，包括 mNGS 和 ddPCR 对 LRTI 病原体的检测、耐药菌的预测能力以及与传统方法的比较。我们尝试结合 mNGS 和 ddPCR 的研究成果，分析第二代测序技术的优缺点。此外，还对第二代测序技术的发展方向进行了展望。

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引用次数: 0

Enhanced Commendable Sensitivity and Specificity for MSI in Colorectal Cancer by a New PCR-HRM Based 8-Loci MSI Assay 基于 PCR-HRM 的新型 8 个基因 MSI 检测法提高了结直肠癌 MSI 检测的灵敏度和特异性。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-08-12 DOI: 10.1002/jcla.25085

Xueping Xiang, Xiaojing Ma, Linlin Ying, Hong Zou

Background

This study evaluated the performance of the PCR-HRM assay by comparing it with immunohistochemistry (IHC) for mismatch repair (MMR) proteins and the PCR capillary electrophoresis (PCR-CE) methods.

Results

A total of 224 patients with colorectal cancer participated in the study, with nearly half having mismatch repair deficiency (dMMR) tissues and the remainder possessing pMMR tissues. There was a 97.77% concordance between the PCR-HRM assay and IHC, and a 97.56% concordance between PCR-HRM and the PCR-CE assay. In comparison with IHC for dMMR proteins, the PCR-HRM demonstrated a sensitivity of 96.36% and a specificity of 99.12%. When juxtaposed with the PCR-CE assay, its sensitivity was 98.96% and specificity stood at 96.33%. The mutations observed in the microsatellite loci were uniformly distributed across all eight loci. Discrepant outcomes were more frequent in instances of MLH1 and PMS2 deficiency. Furthermore, the germline mutation status of MLH1, MSH2, PMS2, and MSH6 in 62 patients was ascertained using next-generation sequencing. All patients displaying MMR gene pathogenic mutations (N = 14) were identified as MSI-H by PCR-HRM, whereas those with MSS tissues (N = 43) did not exhibit MMR gene pathogenic mutations. Thus, the PCR-HRM method proficiently pinpoints tumors with verified germline MMR mutations, indicative of Lynch syndrome.

Conclusion

Conclusively, the PCR-HRM assay emerges as a swift and congruent diagnostic tool for microsatellite instability, boasting commendable sensitivity and specificity in colorectal cancer.

背景：这项研究通过比较PCR-HRM检测法与错配修复（MMR）蛋白免疫组化（IHC）法和PCR毛细管电泳（PCR-CE）法，评估了PCR-HRM检测法的性能：共有 224 名结直肠癌患者参与了研究，其中近一半患者的组织存在错配修复缺陷（dMMR），其余患者的组织存在 pMMR。PCR-HRM 检测与 IHC 检测的一致性为 97.77%，PCR-HRM 检测与 PCR-CE 检测的一致性为 97.56%。与 IHC 检测 dMMR 蛋白相比，PCR-HRM 的灵敏度为 96.36%，特异性为 99.12%。与 PCR-CE 检测法相比，其灵敏度为 98.96%，特异性为 96.33%。在微卫星位点上观察到的突变均匀分布在所有八个位点上。在 MLH1 和 PMS2 缺乏的情况下，异常结果更为常见。此外，62 名患者的 MLH1、MSH2、PMS2 和 MSH6 的种系突变状态也通过下一代测序得以确定。通过 PCR-HRM，所有显示 MMR 基因致病突变的患者（14 人）都被确定为 MSI-H，而那些有 MSS 组织的患者（43 人）则没有显示 MMR 基因致病突变。因此，PCR-HRM方法能有效地确定肿瘤是否存在已验证的种系MMR基因突变，这也是林奇综合征的指征：最后，PCR-HRM 检测是一种快速、一致的微卫星不稳定性诊断工具，在结直肠癌中具有值得称道的灵敏度和特异性。

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引用次数: 0

Changes in Red Cell Morphology and Haematological Laboratory Parameters Associated With Alectinib 与阿来替尼相关的红细胞形态学和血液学实验室参数的变化

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-08-12 DOI: 10.1002/jcla.25089

Ting Hon Stanford Li, Yin Kwan Jeannie Chik, Ka Yan Ng, Wai Shan Wong

Background

Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-mutated non-small-cell lung cancer. Recently, the association between alectinib and red cell morphological abnormalities has been reported in a few case series. This retrospective observational study aims to determine the frequency of occurrence of acanthocytosis in patients taking alectinib and to evaluate the red cell indices, biochemical markers of haemolysis and eosin-5-maleimide (EMA) binding assay results in patients receiving alectinib.

Methods

Patients who were on alectinib and had a complete blood count test performed in Queen Elizabeth Hospital Haematology Laboratory between 1 May 2021 and 31 August 2021 were included in the study. Haematological investigations that had been performed before and after the commencement of alectinib were reviewed.

Results

Fifty patients receiving alectinib were evaluated in this analysis. One hundred per cent of patients showed 3+ acanthocytes on the peripheral blood smears. Compared with the test results before starting alectinib, the post-alectinib blood tests showed a significantly lower haemoglobin concentration, red blood cell count and haematocrit; and a significantly higher mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and red cell distribution width. All the tested patients showed a marked reduction in EMA mean channel fluorescence compared with normal control.

Conclusion

Our cohort revealed that alectinib caused significant acanthocytosis in all patients. Alectinib was also associated with changes in red cell indices and biochemical markers of haemolysis, compatible with a spherocytic and anisopoikilocytic morphology with haemolysis. Patients on alectinib had reduced EMA binding.

背景：阿来替尼是第二代无性淋巴瘤激酶（ALK）抑制剂，适用于治疗ALK突变的非小细胞肺癌。最近，阿来替尼与红细胞形态异常之间的关系在一些病例系列中有所报道。这项回顾性观察研究旨在确定服用阿来替尼的患者出现棘细胞增多症的频率，并评估接受阿来替尼治疗的患者的红细胞指数、溶血生化标志物和伊红-5-马来酰亚胺（EMA）结合测定结果：研究对象包括2021年5月1日至2021年8月31日期间服用阿来替尼并在伊丽莎白女王医院血液实验室进行过全血计数检测的患者。研究人员对开始使用阿来替尼前后进行的血液学检查进行了回顾：本次分析评估了50名接受阿来替尼治疗的患者。100%的患者外周血涂片显示有3+棘细胞。与开始使用阿来替尼前的检测结果相比，阿来替尼治疗后的血液检测结果显示血红蛋白浓度、红细胞计数和血细胞比容明显降低；平均血红蛋白、平均血红蛋白浓度和红细胞分布宽度明显升高。与正常对照组相比，所有受试患者的 EMA 平均通道荧光都明显降低：我们的队列显示，阿来替尼会导致所有患者出现明显的棘细胞增多。阿来替尼还与红细胞指数和溶血生化指标的变化有关，与球形红细胞和异型红细胞形态与溶血相一致。服用阿来替尼的患者EMA结合率降低。

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引用次数: 0

Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico 墨西哥西北部个体中 rs1051338 和 rs116928232 变异的频率。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-08-06 DOI: 10.1002/jcla.25083

Angélica Alejandra Hernández-Orozco, Lennon Melendez-Aranda, Sandra del Carmen Mendoza-Ruvalcaba, Francisco Javier Perea-Díaz, Jorge J. Cebolla, Pilar Giraldo, Aniel Jessica Leticia Brambila-Tapia, José Elías García-Ortíz

Background

LIPA, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic.

Methods

Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes.

Results

Allele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D′ = 1.03, p value = 0.56).

Conclusions

Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.

背景：LIPA位于染色体10q23.2-q23.3上，编码溶酶体酸性脂肪酶（LAL）（EC 3.1.1.13）。LIPA 基因的改变会导致溶酶体酸性脂肪酶缺乏症（LALD），这是一种先天性疾病，会导致脂质代谢异常，影响胆固醇和三酰甘油的降解。已有 40 多个 LIPA 变异被记录在案，但本研究只关注其中的两个。rs1051338 变体（NM_000235:c.46A>C）影响外显子 2 中的信号肽，而位于外显子 8 中的 rs116928232 则改变了剪接位点（NM_000235:c.894G>A），从而影响溶酶体酸性脂肪酶的活性。考虑到 LALD 的临床表现多种多样，而且主要由于饮食习惯，墨西哥人的肝脂肪变性发病率不断上升，因此在这一人群中对这些变异进行了调查，以发现潜在的诱因。本研究旨在揭示 rs1051338 和 rs116928232 在墨西哥西北部健康混血人群中的频率，这标志着在该人群中进行了一次重要的遗传学探索：方法：对 3100 名健康的混血人进行了这两个变异体的 PCR-RFLP 分析，并对变异体 rs116928232 进行了 Sanger 测序。此外，还进行了生物信息学分析，以预测蛋白质的变化：结果：rs1051338（FA = 0.39，p 值 = 0.15）和 rs116928232（FA = 0.0016，p 值 = 0.49）的等位基因频率与报告数据一致，而生物信息分析使我们能够确定在这两个变异体中观察到的蛋白质变化；最后，这两个变异体之间没有关联（归一化 D' = 1.03，p 值 = 0.56）：结论：等位基因频率与报道的数据非常吻合，蛋白质结构分析证实了变体对 LAL 酶功能的影响。值得注意的是，本研究是首次在墨西哥混血健康人群中对 rs1051338 和 rs116928232 进行分析。

{"title":"Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico","authors":"Angélica Alejandra Hernández-Orozco, Lennon Melendez-Aranda, Sandra del Carmen Mendoza-Ruvalcaba, Francisco Javier Perea-Díaz, Jorge J. Cebolla, Pilar Giraldo, Aniel Jessica Leticia Brambila-Tapia, José Elías García-Ortíz","doi":"10.1002/jcla.25083","DOIUrl":"10.1002/jcla.25083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>LIPA</i>, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in <i>LIPA</i> lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 <i>LIPA</i> variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Allele frequencies for rs1051338 (FA = 0.39, <i>p</i> value = 0.15) and rs116928232 (FA = 0.0016, <i>p</i> value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized <i>D</i>′ = 1.03, <i>p</i> value = 0.56).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 13-14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Importance of In Vitro Embryo Model Procedure Standardization 体外胚胎模型程序标准化的重要性。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-07-29 DOI: 10.1002/jcla.25082

Kubilay Doğan Kılıç, Zeynep Simge Yılmaz

In vivo studies offer a detailed understanding of organism functioning, surpassing the insights provided by in vitro studies. These experiments are crucial for comprehending disease emergence, progression, and associated mechanisms in humans, as well as for developing treatments. When choosing experimental models, factors such as genomic similarity, physiological relevance, ethical appropriateness, and economic feasibility must be considered. Standardized protocols enhance the reliability, and reproducibility of scientific methods, promoting the assessment of research in the scientific literature. Researchers conducting embryo studies should establish and document standardized protocols for increased data comparability. Standardization is vital for scientific validity, reproducibility, and comparability in both in vivo and in vitro studies, ensuring the accuracy and reliability of experimental results and advancing scientific knowledge.

体内研究能够详细了解生物体的功能，其洞察力远远超过体外研究。这些实验对于理解人类疾病的发生、发展和相关机制以及开发治疗方法至关重要。在选择实验模型时，必须考虑基因组相似性、生理相关性、伦理适宜性和经济可行性等因素。标准化方案可提高科学方法的可靠性和可重复性，促进科学文献对研究的评估。进行胚胎研究的研究人员应建立和记录标准化方案，以提高数据的可比性。标准化对于体内和体外研究的科学有效性、可重复性和可比性至关重要，可确保实验结果的准确性和可靠性，并促进科学知识的发展。

引用次数: 0

Unlocking Optimal Glycemic Interpretation: Redefining HbA1c Analysis in Female Patients With Diabetes and Iron-Deficiency Anemia Using Machine Learning Algorithms 解锁最佳血糖解释：利用机器学习算法重新定义糖尿病和缺铁性贫血女性患者的 HbA1c 分析。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-07-10 DOI: 10.1002/jcla.25087

Kadra Mohamed Abdillahi, Fatma Ceyla Eraldemir, Irfan Kösesoy

Objective

In response to the nuanced glycemic challenges faced by women with iron deficiency anemia (IDA) associated with diabetes, this study uses advanced machine learning algorithms to redefine hemoglobin (Hb)A1c measurement values. We aimed to improve the accuracy of glycemic interpretation by recognizing the critical interaction between erythrocytes, iron, and glycemic levels in this specific demographic group.

Methods

This retrospective observational study included 17,526 adult women with HbA1c levels recorded from 2017 to 2022. Samples were classified as diabetic, prediabetic, or non-diabetic based on HbA1c and fasting blood glucose (FBG) levels for distribution analysis without impacting model training. Support Vector Machines, Linear Regression, Random Forest, and K-Nearest Neighbor algorithms as machine learning (ML) methods were used to predict HbA1c levels. Following the training of the model, HbA1c values were predicted for the IDA samples using the trained model.

Results

According to our results, there has been a 0.1 unit change in HbA1c values, which has resulted in a clinical decision change in some patients.

Discussion

Using ML to analyze HbA1c results in women with IDA may unveil distinctions among patients whose HbA1c values hover near critical medical decision thresholds. This intersection of technology and laboratory science holds promise for enhancing precision in medical decision-making processes.

研究目的针对糖尿病合并缺铁性贫血（IDA）妇女面临的细微血糖挑战，本研究采用先进的机器学习算法重新定义血红蛋白（Hb）A1c测量值。我们的目的是通过认识这一特殊人群中红细胞、铁和血糖水平之间的关键相互作用，提高血糖解释的准确性：这项回顾性观察研究纳入了 2017 年至 2022 年期间记录 HbA1c 水平的 17526 名成年女性。根据 HbA1c 和空腹血糖 (FBG) 水平将样本分类为糖尿病、糖尿病前期或非糖尿病，以便在不影响模型训练的情况下进行分布分析。支持向量机、线性回归、随机森林和 K-近邻算法作为机器学习 (ML) 方法用于预测 HbA1c 水平。模型训练完成后，使用训练好的模型预测 IDA 样本的 HbA1c 值：根据我们的结果，HbA1c 值变化了 0.1 个单位，这导致一些患者的临床决策发生了变化：讨论：使用 ML 分析患有 IDA 的女性患者的 HbA1c 结果可能会揭示 HbA1c 值在临界医疗决策阈值附近徘徊的患者之间的区别。这种技术与实验室科学的交叉有望提高医疗决策过程的精确性。

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引用次数: 0

A Study on Associations of Long Noncoding RNA HOTAIR Polymorphisms With Genetic Susceptibility to Chronic Kidney Disease 长非编码 RNA HOTAIR 多态性与慢性肾病遗传易感性的关联研究

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-07-03 DOI: 10.1002/jcla.25086

Mahdi Majidpour, Ramin Saravani, Saman Sargazi, Sara Sargazi, Mahdiyeh Harati-Sadegh, Shadi Khorrami, Mohammad Sarhadi, Ali Alidadi

Background

The importance of long noncoding RNAs (lncRNAs) in various biological processes has been increasingly recognized in recent years. This study investigated how gene polymorphism in HOX transcript antisense RNA (HOTAIR) lncRNA affects the predisposition to chronic kidney disease (CKD).

Methods

This study comprised 150 patients with CKD and 150 healthy controls. A PCR-RFLP and ARMS-PCR techniques were used for genotyping the five target polymorphisms.

Results

According to our findings, rs4759314 confers strong protection against CKD in allelic, dominant, and codominant heterozygote genetic patterns. Furthermore, rs3816153 decreased CKD risk by 78% when TT versus GG, 55% when GG+GT versus TT, and 74% when GT versus TT+GG. In contrast, the CC+CT genotype [odds ratio (OR) = 1.66, 95% confidence intervals (CIs) = 1.05–2.63] and the T allele (OR = 1.50, 95% CI = 1.06–2.11) of rs12826786, as well as the TT genotype (OR = 2.52, 95% CI = 1.06–5.98) of rs3816153 markedly increased the risk of CKD in the Iranian population. Although no linkage disequilibrium was found between the studied variants, the C_rs12826786T_rs920778G_rs1899663G_rs4759314G_rs3816153 haplotype was associated with a decreased risk of CKD by 86% (OR = 0.14, 95% CI = 0.03–0.66).

Conclusion

The rs920778 was not correlated with CKD risk, whereas the HOTAIR rs4759314, rs12826786, rs1899663, and rs3816153 polymorphisms affected the risk of CKD in our population. It seems essential to conduct repeated studies across various ethnic groups to explore the link between HOTAIR variants and their impact on the disease outcome.

背景：近年来，长非编码RNA（lncRNA）在各种生物学过程中的重要性日益得到认可。本研究探讨了HOX转录本反义RNA（HOTAIR）lncRNA的基因多态性如何影响慢性肾脏病（CKD）的易感性：该研究由150名CKD患者和150名健康对照者组成。方法：该研究包括 150 名 CKD 患者和 150 名健康对照，采用 PCR-RFLP 和 ARMS-PCR 技术对五个目标多态性进行基因分型：结果：根据我们的研究结果，rs4759314 在等位基因、显性和隐性杂合子遗传模式中对 CKD 有很强的保护作用。此外，rs3816153 在 TT 对 GG、GG+GT 对 TT 和 GT 对 TT+GG 的情况下，可将 CKD 风险分别降低 78%、55% 和 74%。相比之下，rs12826786的CC+CT基因型[几率比（OR）=1.66，95%置信区间（CI）=1.05-2.63]和T等位基因（OR=1.50，95% CI=1.06-2.11）以及rs3816153的TT基因型（OR=2.52，95% CI=1.06-5.98）明显增加了伊朗人群罹患CKD的风险。虽然在所研究的变异之间没有发现连接不平衡，但 Crs12826786Trs920778Grs1899663Grs4759314Grs3816153 单倍型与 CKD 风险降低 86% 相关（OR = 0.14，95% CI = 0.03-0.66）：rs920778与CKD风险无关，而HOTAIR rs4759314、rs12826786、rs1899663和rs3816153多态性会影响我国人群的CKD风险。看来有必要在不同种族群体中进行重复研究，以探索 HOTAIR 变体之间的联系及其对疾病结果的影响。

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引用次数: 0

Importance of CD71+ Erythrocyte Cell Levels in Prognosis in Patients With β-Thalassemia CD71+红细胞水平对β-地中海贫血患者预后的重要性

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-26 DOI: 10.1002/jcla.25084

Gizem Zorlu Görgülügil, Ayşegül Uğur Kurtoğlu, Sevcan Uğur, Erdal Kurtoğlu

Background/Objectives

CD71⁺ erythroid cells (CECs) are immature red blood cells (proerythroblasts, erythroblasts, and reticulocytes). CECs play an important role in the development of sepsis and cancer by causing immunosuppression. We examined the CEC levels in the peripheral blood of beta thalassemia (βThal) patients and investigated the relationship between CECs and the clinical status of the patients, especially splenectomy.

Methods

Sixty-eight patients with βThal (46 splenectomized and 22 nonsplenectomized) and 15 healthy controls were included in this study. The hemogram parameters, ferritin, and CECs (flow cytometry method) were measured.

Results

It was observed that the CEC level in the patient group was significantly higher than the control group (p < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy (p < 0.05). CEC levels were higher in patients with nontransfusion-dependent βT (NTD-βThal) than in patients with transfusion-dependent βT (TD-βThal) (p < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy in both TD-βThal and NTD-βThal groups (p < 0.05). There was a moderate-negative correlation was detected between CECs and Hb levels (r = −0.467; p < 0.05).

Conclusions

High CEC levels in βThal patients develop as a result of ineffective erythropoiesis. We think that keeping CEC levels under control is important for prognosis, especially in patients with splenectomy.

背景/目的：CD71+ 红细胞（CECs）是未成熟红细胞（原红细胞、红细胞和网织红细胞）。CEC 通过引起免疫抑制，在败血症和癌症的发生发展中发挥着重要作用。我们检测了β地中海贫血（βThal）患者外周血中的CEC水平，并研究了CEC与患者临床状况（尤其是脾切除术）之间的关系：本研究共纳入 68 名β地中海贫血患者（46 名脾切除患者和 22 名非脾切除患者）和 15 名健康对照者。研究人员对血液图参数、铁蛋白和 CECs（流式细胞术法）进行了测量：结果显示：患者组的 CEC 水平明显高于对照组（Pβ-Thal患者的高CEC水平是红细胞生成无效的结果。我们认为，控制 CEC 水平对预后非常重要，尤其是对接受脾切除术的患者。

{"title":"Importance of CD71+ Erythrocyte Cell Levels in Prognosis in Patients With β-Thalassemia","authors":"Gizem Zorlu Görgülügil, Ayşegül Uğur Kurtoğlu, Sevcan Uğur, Erdal Kurtoğlu","doi":"10.1002/jcla.25084","DOIUrl":"10.1002/jcla.25084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>CD71<sup>+</sup> erythroid cells (CECs) are immature red blood cells (proerythroblasts, erythroblasts, and reticulocytes). CECs play an important role in the development of sepsis and cancer by causing immunosuppression. We examined the CEC levels in the peripheral blood of beta thalassemia (βThal) patients and investigated the relationship between CECs and the clinical status of the patients, especially splenectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty-eight patients with βThal (46 splenectomized and 22 nonsplenectomized) and 15 healthy controls were included in this study. The hemogram parameters, ferritin, and CECs (flow cytometry method) were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It was observed that the CEC level in the patient group was significantly higher than the control group (<i>p</i> < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy (<i>p</i> < 0.05). CEC levels were higher in patients with nontransfusion-dependent βT (NTD-βThal) than in patients with transfusion-dependent βT (TD-βThal) (<i>p</i> < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy in both TD-βThal and NTD-βThal groups (<i>p</i> < 0.05). There was a moderate-negative correlation was detected between CECs and Hb levels (<i>r</i> = −0.467; <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High CEC levels in βThal patients develop as a result of ineffective erythropoiesis. We think that keeping CEC levels under control is important for prognosis, especially in patients with splenectomy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis-4 鉴定与肾炎-4（Nephronophthisis-4）相关的 NPHP4 中一个新的缺失变异（c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4）。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-19 DOI: 10.1002/jcla.25077

Zahra Miri Karam, Atieh Karimi Gohari, Mohammad Javad Rezazadeh Khabaz, Abolfazl Yari, Seyed Mahdi Emami Meybodi, Rezvan Attari, Maryam Torabi, Farzane Vafaeie, Fateme Moradi Moraddahande, Sara Amiri, Kolsoum Saeidi

Background

Nephronophthisis-4 (NPHP4) is an inherited renal ciliopathy described by renal fibrosis and progressive impairment of kidney function. This study aimed to investigate the genetic basis and clinical manifestations of NPHP4 in two Iranian siblings.

Methods

The proband was a 27-year-old male with features of end-stage renal disease, including anemia, uremia, polyuria, and polydipsia. It is worth mentioning that he has a 22-year-old sister with a similar presentation. Clinical diagnosis procedures, such as renal biopsy, brain imaging, blood and urine tests, cardiac evaluation, ophthalmic inspection, and auditory function assessment, were carried out to evaluate organ involvement and potential comorbidities. Whole-exome sequencing (WES) and segregation analysis were performed to identify and confirm genetic variants associated with the condition. Computational variant analysis was conducted to evaluate the pathogenicity of the candidate variant. Furthermore, the SWISS-MODEL server was utilized for protein modeling.

Results

The brain, cardiac, ocular, and auditory functions were normal. Renal biopsy of the proband showed chronic interstitial inflammation and fibrosis. We found a novel homozygous 7-base pair deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of NPHP4 by WES. Segregation analysis confirmed homozygosity for the NPHP4 variant in affected individuals and heterozygous carrier status in parents, supporting autosomal recessive inheritance. 3D protein modeling indicated significant structural changes due to the variant.

Conclusion

This study expands the genetic causes and phenotypic spectrum of nephronophthisis-4 and reveals the importance of genetic analysis in diagnosing and managing rare inherited kidney disorders, particularly those involving consanguinity.

背景：肾炎-4（Nephronophthis-4，NPHP4）是一种遗传性肾纤毛病，表现为肾脏纤维化和进行性肾功能损害。本研究旨在调查两个伊朗兄弟姐妹中 NPHP4 的遗传基础和临床表现：原发性肾病患者是一名 27 岁的男性，具有终末期肾病的特征，包括贫血、尿毒症、多尿和多饮。值得一提的是，他有一个 22 岁的妹妹也有类似表现。临床诊断程序包括肾活检、脑成像、血液和尿液检查、心脏评估、眼科检查和听觉功能评估，以评估器官受累情况和潜在的合并症。进行了全外显子组测序（WES）和分离分析，以识别和确认与该疾病相关的基因变异。还进行了计算变异分析，以评估候选变异的致病性。此外，还利用 SWISS-MODEL 服务器进行了蛋白质建模：大脑、心脏、眼睛和听觉功能正常。该患者的肾活检结果显示存在慢性间质性炎症和纤维化。我们通过WES发现NPHP4第21外显子存在一个新的7碱基对同源缺失（c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4）。分离分析证实，患者为 NPHP4 变体的同基因携带者，其父母为杂合子携带者，支持常染色体隐性遗传。三维蛋白质建模显示，该变异体导致了明显的结构变化：本研究拓展了肾炎-4 的遗传原因和表型谱，揭示了遗传分析在诊断和管理罕见遗传性肾脏疾病，尤其是涉及近亲结婚的疾病中的重要性。

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引用次数: 0

The Rising Tide of Antibiotic Resistance: A Study on Extended-Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae 抗生素耐药性的浪潮：对广谱β-内酰胺酶和碳青霉烯耐药大肠埃希菌和肺炎克雷伯菌的研究。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-17 DOI: 10.1002/jcla.25081

Hasan Ejaz, Muhammad Usman Qamar, Aisha Farhana, Sonia Younas, Alia Batool, Durreshahwar Lone, Muhammad Atif, Mashael W. Alruways, Muharib Alruwaili, Ismail Hamad, Samy Selim, Bi Bi Zainab Mazhari, Ali Farooq, Kashaf Junaid

Background

The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings.

Methods

From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR.

Results

Of the 227 clinical isolates, 145 (63.8%) were Klebsiella pneumoniae and 82 (36.1%) were Escherichia coli; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing E. coli were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of E. coli isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing K. pneumoniae were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) K. pneumoniae were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) E. coli isolates were positive for bla_CTX-M, 11 (18.9%) for bla_TEM, and 8 (33.3%) for bla_NDM. Forty-six (52.3%) K. pneumoniae isolates had bla_CTX-M, 27 (18.6%) bla_TEM, and 26 (68.4%) bla_NDM.

Conclusion

This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.

背景：产广谱β-内酰胺酶（ESBL）和耐碳青霉烯类肠杆菌（CRE）在全球的蔓延引起了人们的极大关注。抗菌药耐药性基因的获得会导致对多种抗生素产生耐药性，从而限制了治疗方案的选择。我们旨在研究 ESBL 产菌和 CRE 在临床环境中的传播情况：方法：从临床样本中获得 227 株产 ESBL 和 CRE 分离物。用 VITEK 2 对几种抗生素进行抗菌谱检测，并通过 PCR 鉴定获得的耐药基因：在 227 例临床分离菌中，145 例（63.8%）为肺炎克雷伯菌，82 例（36.1%）为大肠埃希菌；76 例（33.4%）从尿液中分离，57 例（25.1%）从脓拭子中分离，53 例（23.3%）从血液样本中分离。共有 58 个（70.7%）产生 ESBL 的大肠埃希氏菌对β-内酰胺类药物（碳青霉烯类除外）耐药，17.2% 的大肠埃希氏菌对阿米卡星耐药；29.2% 的大肠埃希氏菌对碳青霉烯类耐药。共有 106 株（73.1%）产生 ESBL 的肺炎双球菌对除碳青霉烯类以外的所有β-内酰胺类药物耐药，66.9%对环丙沙星耐药；38 株（26.2%）肺炎双球菌对碳青霉烯类耐药。可乐定是对这两种细菌类型最有效的抗生素。有 12 个（20.6%）大肠杆菌分离物对 blaCTX-M 呈阳性，11 个（18.9%）对 blaTEM 呈阳性，8 个（33.3%）对 blaNDM 呈阳性。46例（52.3%）肺炎克雷伯菌分离物对 blaCTX-M 呈阳性，27 例（18.6%）对 blaTEM 呈阳性，26 例（68.4%）对 blaNDM 呈阳性：结论：本研究发现耐药性 ESBL 产物和 CRE 的流行率很高，这凸显了有针对性地使用抗生素来对抗耐药性的必要性。

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引用次数: 0