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

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid 美罗培南导致丙戊酸血浆浓度下降对丙戊酸抗癫痫药效的影响

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-04-02 DOI: 10.1002/jcla.25025

Chunping Gu, Yongfang Zhang, Fumiao Yuan, Kaibin Huang, Zhenzhou Lin, Qiong Chen, Yan Chen, Yongming Wu, Dongmei Wang, Shengnan Wang

Objective

This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA.

Methods

We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group.

Results

The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 μg/mL) compared with that before co-administration (88.8 ± 13.6 μg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 μg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA–MEPM co-administration was not significantly different from that before co-administration (p = 0.291).

Conclusions

In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted.

Trial Registration

Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020

研究目的本研究旨在说明联合应用美罗培南（MEPM）引起的丙戊酸（VPA）血浆浓度下降是否会影响VPA的抗癫痫疗效：我们回顾性研究了2010年至2019年期间被诊断为癫痫状态或癫痫的住院患者的数据。筛选住院期间联合使用 VPA 和 MEPM 的患者并将其分配到暴露组，而联合使用 VPA 和其他广谱抗生素的患者则分配到对照组：暴露组和对照组分别包括 50 名和 11 名患者。结果：暴露组和对照组分别有 50 名和 11 名患者，在使用类似剂量的 VPA 时，VPA 的血浆浓度（24.6 ± 4.3 μg/mL）与联合用药前（88.8 ± 13.6 μg/mL，P）相比明显下降：在本研究中，合用 MEPM 导致的 VPA 血浆浓度降低并未影响 VPA 的抗癫痫疗效。对这一结论的解释应谨慎，还需要更多的研究：试验注册：中国临床试验注册中心：ChiCTR2000034567。注册日期：2020年7月10日。

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引用次数: 0

Assessment of Faecal Microbiota Transplant Stability in Deep-Freeze Conditions: A 12-Month Ex Vivo Viability Analysis 粪便微生物群移植在深冷条件下的稳定性评估：为期 12 个月的体外存活率分析

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-27 DOI: 10.1002/jcla.25023

Hana Soukupova, Veronika Rehorova, Ivana Cibulkova, Frantisek Duska

Background

Faecal microbiota transplantation (FMT) is an established treatment for Clostridioides difficile infection and is under investigation for other conditions. The availability of suitable donors and the logistics of fresh stool preparation present challenges, making frozen, biobanked stools an attractive alternative.

Aims

This study aimed to evaluate the long-term viability of bacterial populations in faecal samples stored at −80°C for up to 12 months, supporting the feasibility of using frozen grafts for FMT.

Methods

Fifteen faecal samples from nine healthy donors were processed, mixed with cryoprotectants and stored at −80°C. Samples were assessed at baseline and after 3, 6 and 12 months using quantitative culturing methods to determine the concentration of live bacteria.

Results

Quantitative analysis showed no significant decrease in bacterial viability over the 12-month period for both aerobic and anaerobic cultures (p = 0.09). At all timepoints, the coefficients of variability in colony-forming unit (CFU) counts were greater between samples (102 ± 21% and 100 ± 13% for aerobic and anaerobic cultures, respectively) than the variability between measurements of the same sample (30 ± 22% and 30 ± 19%).

Conclusions

The study confirmed that faecal microbiota can be preserved with high viability in deep-freeze storage for up to a year, making allogenic FMT from biobanked samples a viable and safer option for patients. However, a multidonor approach may be beneficial to mitigate the risk of viability loss in any single donor sample.

背景：粪便微生物群移植（FMT）是一种治疗艰难梭菌感染的成熟疗法，目前正在对其他疾病进行研究。目的：本研究旨在评估在零下 80 摄氏度下保存长达 12 个月的粪便样本中细菌群的长期存活率，以支持将冷冻移植物用于 FMT 的可行性：方法：对来自 9 名健康捐献者的 15 份粪便样本进行处理，与低温保护剂混合并保存在 -80°C 温度下。在基线和 3、6 和 12 个月后，使用定量培养方法对样本进行评估，以确定活细菌的浓度：结果：定量分析显示，在 12 个月期间，需氧和厌氧培养物的细菌存活率均无明显下降（p = 0.09）。在所有时间点上，样本间菌落形成单位（CFU）计数的变异系数（需氧培养物和厌氧培养物分别为 102 ± 21% 和 100 ± 13%）均大于同一样本测量值之间的变异系数（30 ± 22% 和 30 ± 19%）：该研究证实，粪便微生物群可在深冻储存中以较高的存活率保存长达一年之久，这使得从生物库样本中提取异基因 FMT 对患者来说是一种可行且更安全的选择。不过，多供体方法可能有利于降低任何单一供体样本活力丧失的风险。

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引用次数: 0

Analytical Performance Evaluation of a Digital Real-Time PCR for Quantifying Major BCR::ABL1 Transcripts 用于定量主要 BCR::ABL1 转录本的数字实时 PCR 的分析性能评估。

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-25 DOI: 10.1002/jcla.25034

Soo Jung Lee, Jong-Mi Lee, Ari Ahn, Sung-Eun Lee, Yuna Hong, Gun Dong Lee, Hyun-Woo Song, Min-Sik Song, Seung-Shick Shin, Myungshin Kim, Yonggoo Kim

Background

Accurate quantification of the BCR::ABL1 transcripts is essential for measurable residual disease (MRD) monitoring in chronic myeloid leukemia (CML) after tyrosine kinase inhibitor (TKI) treatment. This study evaluated the newly developed digital real-time PCR method, Dr. PCR, as an alternative reverse transcription-PCR (qRT-PCR) for MRD detection.

Methods

The performance of Dr. PCR was assessed using reference and clinical materials. Precision, linearity, and correlation with qRT-PCR were evaluated. MRD levels detected by Dr. PCR were compared with qRT-PCR, and practical advantages were investigated.

Results

Dr. PCR detected MRD up to 0.0032%^IS (MR4.5) with excellent precision and linearity and showed a strong correlation with qRT-PCR results. Notably, Dr. PCR identified higher levels of MRD in 12.7% (29/229) of patients than qRT-PCR, including six cases of MR4, which is a critical level for TKI discontinuation. Dr. PCR also allowed for sufficient ABL1 copies in all cases, while qRT-PCR necessitated multiple repeat tests in 3.5% (8/229) of cases.

Conclusion

Our study provides a body of evidence supporting the clinical application of Dr. PCR as a rapid and efficient method for assessing MRD in patients with CML under the current treatment regimen.

背景：酪氨酸激酶抑制剂（TKI）治疗后，BCR::ABL1转录本的精确定量对于监测慢性髓性白血病（CML）的可测量残留疾病（MRD）至关重要。本研究评估了新开发的数字实时 PCR 方法 Dr. PCR，将其作为 MRD 检测的反转录-PCR（qRT-PCR）替代方法：PCR的性能进行了评估。方法：使用参考和临床材料对 Dr. PCR 的性能进行了评估，并对其精确度、线性度以及与 qRT-PCR 的相关性进行了评价。将PCR博士检测到的MRD水平与qRT-PCR进行了比较，并对其实际优势进行了研究：结果：PCR 博士检测到的 MRD 高达 0.0032%IS (MR4.5)，精确度和线性度都非常好，而且与 qRT-PCR 结果有很强的相关性。值得注意的是，与 qRT-PCR 相比，PCR 博士在 12.7% 的患者（29/229）中发现了更高水平的 MRD，其中包括 6 例 MR4，而 MR4 是停用 TKI 的关键水平。PCR博士还在所有病例中检测到了足够的ABL1拷贝，而qRT-PCR在3.5%（8/229）的病例中需要多次重复检测：我们的研究为 Dr. PCR 的临床应用提供了大量证据，它是评估当前治疗方案下 CML 患者 MRD 的一种快速有效的方法。

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引用次数: 0

A Systematic Literature Review on the Use of Dried Biofluid Microsampling in Patients With Kidney Disease 关于在肾病患者中使用干生物流体微采样的系统性文献综述。

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-25 DOI: 10.1002/jcla.25032

Megan K. Lamond, Andrew J. Chetwynd, Alan D. Salama, Louise Oni

Background

Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids, particularly dried capillary blood spots, are an accessible, easy-to-use technology that have seen increased utility in basic science research over the past decade. However, their use is yet to reach the kidney patient population clinically or in large-scale discovery science initiatives. The aim of this study was to systematically evaluate the existing literature surrounding the use of dried biofluids in kidney research.

Methods

A systematic literature review was conducted using three search engines and a predefined search term strategy. Results were summarised according to the collection method, type of biofluid, application to kidney disease, cost, sample stability and patient acceptability.

Results

In total, 404 studies were identified and 67 were eligible. In total, 34,739 patients were recruited to these studies with a skew towards male participants (> 73%). The majority of samples were blood, which was used either for monitoring anti-rejection immunosuppressive drug concentrations or for kidney function. Dried biofluids offered significant cost savings to the patient and healthcare service. The majority of patients preferred home microsampling when compared to conventional monitoring.

Conclusion

There is an unmet need in bringing dried microsampling technology to advance kidney disease despite its advantages. This technology provides an opportunity to upscale patient recruitment and longitudinal sampling, enhance vein preservation and overcome participation bias in research.

背景：肾脏疾病相当独特，因为缺乏与疾病活动相关的症状，因此需要依赖生物监测。干燥的生物流体，尤其是干燥的毛细血管血斑，是一种方便易用的技术，过去十年来在基础科学研究中的应用越来越广泛。然而，在临床上或在大规模的发现科学计划中，肾脏病人尚未使用这种技术。本研究旨在系统评估有关在肾脏研究中使用干生物液体的现有文献：方法：使用三个搜索引擎和预定义的搜索词策略进行了系统的文献综述。根据收集方法、生物液体类型、肾脏疾病应用、成本、样本稳定性和患者接受度对结果进行了总结：结果：总共确定了 404 项研究，其中 67 项符合条件。这些研究共招募了 34739 名患者，其中男性参与者占多数（超过 73%）。大部分样本为血液，用于监测抗排斥免疫抑制药物浓度或肾功能。干燥的生物液体可为患者和医疗服务节省大量成本。与传统的监测方法相比，大多数患者更倾向于在家中进行微型采样：结论：尽管干燥微采样技术具有诸多优势，但将其应用于肾脏疾病的需求仍未得到满足。这项技术为扩大患者招募和纵向采样、加强静脉保存和克服研究中的参与偏差提供了机会。

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引用次数: 0

Dynein Light Intermediate Chains Exhibit Different Arginine Methylation Patterns Dynein轻中间链表现出不同的精氨酸甲基化模式

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-25 DOI: 10.1002/jcla.25030

Weiwen Bu, Jie Di, Junkui Zhao, Ruming Liu, Yue Wu, Jie Ran, Te Li

Background

The motor protein dynein is integral to retrograde transport along microtubules and interacts with numerous cargoes through the recruitment of cargo-specific adaptor proteins. This interaction is mediated by dynein light intermediate chain subunits LIC1 (DYNC1LI1) and LIC2 (DYNC1LI2), which govern the adaptor binding and are present in distinct dynein complexes with overlapping and unique functions.

Methods

Using bioinformatics, we analyzed the C-terminal domains (CTDs) of LIC1 and LIC2, revealing similar structural features but diverse post-translational modifications (PTMs). The methylation status of LIC2 and the proteins involved in this modification were examined through immunoprecipitation and immunoblotting analyses. The specific methylation sites on LIC2 were identified through a site-directed mutagenesis analysis, contributing to a deeper understanding of the regulatory mechanisms of the dynein complex.

Results

We found that LIC2 is specifically methylated at the arginine 397 residue, a reaction that is catalyzed by protein arginine methyltransferase 1 (PRMT1).

Conclusions

The distinct PTMs of the LIC subunits offer a versatile mechanism for dynein to transport diverse cargoes efficiently. Understanding how these PTMs influence the functions of LIC2, and how they differ from LIC1, is crucial for elucidating the role of dynein-related transport pathways in a range of diseases. The discovery of the arginine 397 methylation site on LIC2 enhances our insight into the regulatory PTMs of dynein functions.

背景：运动蛋白动力蛋白（dynein）是沿微管逆向运输不可或缺的部分，它通过招募货物特异性适配蛋白与许多货物相互作用。这种相互作用由动力蛋白轻中间链亚基 LIC1（DYNC1LI1）和 LIC2（DYNC1LI2）介导，它们控制适配体的结合，存在于不同的动力蛋白复合物中，具有重叠和独特的功能：我们利用生物信息学方法分析了 LIC1 和 LIC2 的 C 端结构域（CTD），发现它们具有相似的结构特征，但翻译后修饰（PTM）却各不相同。通过免疫沉淀和免疫印迹分析研究了LIC2的甲基化状态以及参与这种修饰的蛋白质。通过定点突变分析确定了 LIC2 上的特定甲基化位点，有助于加深对动力蛋白复合体调控机制的理解：结果：我们发现 LIC2 在精氨酸 397 残基上被特异性甲基化，该反应由蛋白精氨酸甲基转移酶 1（PRMT1）催化：结论：LIC 亚基的不同 PTM 为动力蛋白高效运输各种货物提供了一种多功能机制。了解这些 PTM 如何影响 LIC2 的功能，以及它们与 LIC1 的区别，对于阐明与动力蛋白相关的转运途径在一系列疾病中的作用至关重要。LIC2 上精氨酸 397 甲基化位点的发现增强了我们对动力蛋白功能调控 PTM 的洞察力。

{"title":"Dynein Light Intermediate Chains Exhibit Different Arginine Methylation Patterns","authors":"Weiwen Bu, Jie Di, Junkui Zhao, Ruming Liu, Yue Wu, Jie Ran, Te Li","doi":"10.1002/jcla.25030","DOIUrl":"10.1002/jcla.25030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The motor protein dynein is integral to retrograde transport along microtubules and interacts with numerous cargoes through the recruitment of cargo-specific adaptor proteins. This interaction is mediated by dynein light intermediate chain subunits LIC1 (DYNC1LI1) and LIC2 (DYNC1LI2), which govern the adaptor binding and are present in distinct dynein complexes with overlapping and unique functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using bioinformatics, we analyzed the C-terminal domains (CTDs) of LIC1 and LIC2, revealing similar structural features but diverse post-translational modifications (PTMs). The methylation status of LIC2 and the proteins involved in this modification were examined through immunoprecipitation and immunoblotting analyses. The specific methylation sites on LIC2 were identified through a site-directed mutagenesis analysis, contributing to a deeper understanding of the regulatory mechanisms of the dynein complex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that LIC2 is specifically methylated at the arginine 397 residue, a reaction that is catalyzed by protein arginine methyltransferase 1 (PRMT1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The distinct PTMs of the LIC subunits offer a versatile mechanism for dynein to transport diverse cargoes efficiently. Understanding how these PTMs influence the functions of LIC2, and how they differ from LIC1, is crucial for elucidating the role of dynein-related transport pathways in a range of diseases. The discovery of the arginine 397 methylation site on LIC2 enhances our insight into the regulatory PTMs of dynein functions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207045","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

INPP5E Regulates the Distribution of Phospholipids on Cilia in RPE1 Cells INPP5E 调节 RPE1 细胞纤毛上磷脂的分布。

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-21 DOI: 10.1002/jcla.25031

Denghui Zhai, Lamei Li, Cheng Chen, Xue Wang, Ruming Liu, Ying Shan

Background

Primary cilia are static microtubule-based structures protruding from the cell surface and present on most vertebrate cells. The appropriate localization of phospholipids is essential for cilia formation and stability. INPP5E is a cilia-localized inositol 5-phosphatase; its deletion alters the phosphoinositide composition in the ciliary membrane, disrupting ciliary function.

Methods

The EGFP-2xP4M^SidM, PH^PLCδ1-EGFP, and SMO-tRFP plasmids were constructed by the Gateway system to establish a stable RPE1 cell line. The INPP5E KO RPE1 cell line was constructed with the CRISPR/Cas9 system. The localization of INPP5E and the distribution of PI(4,5)P₂ and PI4P were examined by immunofluorescence microscopy. The fluorescence intensity co-localized with cilia was quantified by ImageJ.

Results

In RPE1 cells, PI4P is localized at the ciliary membrane, whereas PI(4,5)P₂ is localized at the base of cilia. Knocking down or knocking out INPP5E alters this distribution, resulting in the distribution of PI(4,5)P₂ along the ciliary membrane and the disappearance of PI4P from the cilia. Meanwhile, PI(4,5)P₂ is located in the ciliary membrane labeled by SMO-tRFP.

Conclusions

INPP5E regulates the distribution of phosphoinositide on cilia. PI(4,5)P₂ localizes at the ciliary membrane labeled with SMO-tRFP, indicating that ciliary pocket membrane contains PI(4,5)P₂, and phosphoinositide composition in early membrane structures may differ from that in mature ciliary membrane.

背景：初级纤毛是从细胞表面伸出的基于微管的静态结构，存在于大多数脊椎动物细胞中。磷脂的适当定位对纤毛的形成和稳定性至关重要。INPP5E 是一种纤毛定位的肌醇 5-磷酸酶；它的缺失会改变纤毛膜中的磷脂组成，从而破坏纤毛的功能：方法：通过Gateway系统构建了EGFP-2xP4MSidM、PHPLCδ1-EGFP和SMO-tRFP质粒，以建立稳定的RPE1细胞系。利用 CRISPR/Cas9 系统构建了 INPP5E KO RPE1 细胞系。免疫荧光显微镜检测了 INPP5E 的定位以及 PI(4,5)P2 和 PI4P 的分布。用 ImageJ 对与纤毛共定位的荧光强度进行量化：结果：在 RPE1 细胞中，PI4P 定位于纤毛膜，而 PI(4,5)P2 定位于纤毛基部。敲低或敲除 INPP5E 会改变这种分布，导致 PI(4,5)P2 沿纤毛膜分布，PI4P 从纤毛中消失。同时，PI(4,5)P2位于SMO-tRFP标记的纤毛膜上：结论：INPP5E调节磷酸肌醇在纤毛上的分布。PI(4,5)P2定位于SMO-tRFP标记的纤毛膜上，这表明纤毛袋膜含有PI(4,5)P2，早期膜结构中的磷酸肌醇组成可能与成熟纤毛膜中的磷酸肌醇组成不同。

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引用次数: 0

Molecular Characterization of α- and β-Thalassemia Among Children Less Than 18 Years Old in Guizhou, China 中国贵州 18 岁以下儿童α-和β-地中海贫血的分子特征。

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-20 DOI: 10.1002/jcla.25022

Yan Li, Jiao Jin, Yuanyuan Tuo, Pei Huang, Jing Huang, Honglan Yang, Zhixu He

Background

Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have investigated the molecular characterization of α- and β-thalassemia in children from Guizhou, China.

Methods

Between January 2019 and December 2022, a total of 3301 children, aged 6 months to 18 years, suspected of having thalassemia underwent molecular analysis.

Results

Out of the total sample, 824 (25%) children were found to carry thalassemia mutations. The carrier rates of α-thalassemia, β-thalassemia, and α + β-thalassemia were determined as 8.1%, 15.6%, and 1.3%, respectively. Approximately 96.5% of the α-thalassemia gene mutations were --SEA (51%), αα^CS (20.9%), -α^3.7 (19.6%), and -α^4.2 (5.0%). The most prevalent mutations of β-thalassemia were β^CD17(A>T) (41.5%), β^{CD41-42(-TTCT)} (37.7%), and β^{IVS-II-654(C>T)} (11.3%). Additionally, we identified rare cases, including one case with αα^{Hb Nunobiki}/αα, two cases with triplicated α-thalassemia (one case with ααα/ααα and β^CD41-42/β^N and the other with ααα^-3.7/αα and βE ^CD26/β^N), and also one case with α ^Q-Thailandα/-α^4.2 and β^CD41-42/β^N.

Conclusions

Our study findings provide important insights into the heterogeneity of thalassemia carrier rates and molecular profiles among children in the Guizhou region. The findings support the development of prevention strategies to reduce the incidence of severe thalassemia in the future.

背景：地中海贫血是一种遗传性溶血性疾病，其并发症和后遗症对患者和社会都造成了巨大影响。但对中国贵州儿童α-和β-地中海贫血分子特征的研究有限：方法：2019年1月至2022年12月，对3301名6个月至18岁疑似地中海贫血患儿进行分子分析：结果：在所有样本中，发现824名（25%）儿童携带地中海贫血基因突变。α地中海贫血、β地中海贫血和α+β地中海贫血的携带率分别为 8.1%、15.6% 和 1.3%。约96.5%的α地中海贫血基因突变为--SEA（51%）、ααCS（20.9%）、-α3.7（19.6%）和-α4.2（5.0%）。β地中海贫血最常见的突变是βCD17(A>T)（41.5%）、βCD41-42(-TTCT)（37.7%）和βIVS-II-654(C>T)（11.3%）。此外，我们还发现了一些罕见病例，包括一例ααHb Nunobiki /αα，两例三重α地中海贫血（一例为ααα/ααα和βCD41-42 /βN，另一例为ααα-3.7 /αα和βE CD26 /βN），以及一例α Q-Thailand α/-α4.2和βCD41-42 /βN：我们的研究结果为了解贵州地区儿童地中海贫血携带率和分子特征的异质性提供了重要依据。研究结果有助于制定预防策略，降低重型地中海贫血的发病率。

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引用次数: 0

Association of the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) Polymorphisms With Risk of Coronary Artery Disease in Iranian Patients 伊朗患者的 ESR1 (rs9340799)、OLR1 (rs3736234)、LIPC (rs2070895)、VDR (rs2228570) 和 CETP (rs708272) 多态性与冠状动脉疾病风险的关系。

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-20 DOI: 10.1002/jcla.25026

Zahra Miri Karam, Abolfazl Yari, Atefeh Najmadini, Nima Norouzi Khorasani, Rezvan Attari, Saeideh Jafarinejad-Farsangi, Mohammad Ali Miri Karam, Hamid Najafipour, Kolsoum Saeidi

Background

Coronary artery disease (CAD) is a devastating illness and a leading cause of death worldwide, primarily caused by atherosclerosis resulting from a genetic-environmental interaction. This study aimed to investigate the relationship between the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) polymorphisms, lipid profile parameters, and CAD risk in a southeast Iranian population.

Methods

A total of 400 subjects (200 CAD patients with hyperlipidemia and 200 healthy controls) were enrolled in this case–control study. Five selected polymorphisms were genotyped using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique.

Results

For all single nucleotide polymorphisms (SNPs), the population under study was in the Hardy–Weinberg equilibrium. The T-risk allele frequency of rs2228570 was associated with an increased risk of CAD. The TT and CT genotypes of rs2228570 had also been associated with the risk of CAD. Additionally, the TT genotype was associated with higher serum low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) levels. The GG genotype of the rs3736234 was associated with higher body mass index (BMI) and triglyceride (TG) levels, and the AA genotype of the rs708272 was associated with higher HDL-c levels. Based on these findings, we propose that the VDR (rs2228570) polymorphism was associated with serum HDL-c and LDL-c levels and may serve as potential risk factors for CAD within the Iranian population. Moreover, rs3736234 and rs708272 influence the concentrations of TG and HDL-c, respectively.

Conclusion

These findings provided insights into the complex interplay between genetic variations, cardiovascular risk, and lipid metabolism.

背景：冠状动脉疾病（CAD）是一种破坏性疾病，也是全球死亡的主要原因，其主要原因是遗传与环境相互作用导致的动脉粥样硬化。本研究旨在调查伊朗东南部人群中 ESR1 (rs9340799)、OLR1 (rs3736234)、LIPC (rs2070895)、VDR (rs2228570) 和 CETP (rs708272) 多态性、血脂谱参数和 CAD 风险之间的关系：这项病例对照研究共招募了 400 名受试者（200 名患有高脂血症的 CAD 患者和 200 名健康对照者）。采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术对所选的五个多态性进行了基因分型：在所有单核苷酸多态性（SNPs）中，研究人群均处于哈代-温伯格平衡状态。rs2228570的T风险等位基因频率与CAD风险增加有关。rs2228570 的 TT 和 CT 基因型也与患 CAD 的风险有关。此外，TT 基因型与较高的血清低密度脂蛋白胆固醇（LDL-c）和高密度脂蛋白胆固醇（HDL-c）水平有关。rs3736234 的 GG 基因型与较高的体重指数（BMI）和甘油三酯（TG）水平相关，而 rs708272 的 AA 基因型与较高的 HDL-c 水平相关。基于这些发现，我们认为 VDR（rs2228570）多态性与血清高密度脂蛋白胆固醇（HDL-c）和低密度脂蛋白胆固醇（LDL-c）水平有关，并可能成为伊朗人群患 CAD 的潜在风险因素。此外，rs3736234 和 rs708272 分别影响 TG 和 HDL-c 的浓度：这些研究结果有助于深入了解遗传变异、心血管风险和脂质代谢之间复杂的相互作用。

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引用次数: 0

Assessment of Bone Marrow Involvement in B-Cell non-Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next-Generation Sequencing 利用新一代测序的免疫球蛋白基因重排分析评估 B 细胞非霍奇金淋巴瘤的骨髓受累情况

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-20 DOI: 10.1002/jcla.25027

Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul Won Choi, Ha Nui Kim, Jung Ah Kwon, Soo-Young Yoon, Jung Yoon

Background

Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)–based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL.

Methods

A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI).

Results

Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%.

Conclusion

NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

背景：评估非霍奇金淋巴瘤（NHL）的骨髓受累情况（BMI）对于确定患者预后和治疗策略至关重要。我们评估了基于新一代测序（NGS）的免疫球蛋白（Ig）基因克隆性分析作为NHL骨髓受累评估辅助检测的预后价值：方法：纳入2019年至2022年间新诊断为B细胞NHL的124名患者的回顾性队列。使用 LymphoTrak IGH FR1 Assay 和 IGK Assay（Invivoscribe Technologies，San Diego，CA，USA）对骨髓穿刺样本进行基于 NGS 的 Ig 克隆性分析，并将结果与组织病理学 BMI（hBMI）进行比较：结果：在 124 例患者中，16.9%（21 例）检测出 hBMI。Ig克隆分析与组织病理学分析在IGH、IGK以及IGH或IGK的BMI方面的总体一致性分别为86.3%、92.7%和90.3%。IGH 或 IGK 基因克隆重排的正向一致性百分比最高（90.5%），而 IGK 基因克隆重排的负向一致性百分比最高（96.1%）。在预测 hBMI 方面，阳性预测值介于 59.1% 与 80.0% 之间，阴性预测值介于 91.3% 与 97.9% 之间：结论：基于 NGS 的克隆性分析是一种分析平台，与组织病理学分析的总体一致性很高。为了优化 BMI 检测在 B 细胞 NHL 中的诊断性能，可以考虑对 IGH 和 IGK 基因进行克隆重排分析评估。

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引用次数: 0

Dissociation Phenomenon of Erythrocyte Agglutination and Its Application to Assay of Functional Activity of the Complement System in Clinical Laboratory 红细胞凝集的解离现象及其在临床实验室检测补体系统功能活性中的应用。

IF 2.7 4区医学 Q1 Health Professions

Journal of Clinical Laboratory Analysis

Pub Date : 2024-03-20 DOI: 10.1002/jcla.25028

Xuewei Ding, Lina Liu, Guang Yang, Hui Liu

Objective

The objective of the study was to validate the dissociation phenomenon of erythrocyte agglutination which is based on erythrocyte fragments and to apply it in the functional activity assay of the complement system.

Methods

The dissociation–agglutination effect of erythrocyte fragments was validated by detecting the number of free erythrocytes after the action of erythrocyte fragments on agglutinated erythrocytes. The number of free erythrocytes produced after hemolysis of agglutinated erythrocytes caused by complements and complement activators(CAs) was detected by auto hematology analyzer and the results were indicated by mean hemoglobin concentration of erythrocytes (MCHC). We optimized the test conditions and validated the inter-batch stability, explored the resolution of the assay method, and assayed for the total complement activity (AC) and the CAs activated complement activity (ACA) in serum from patients and healthy individual groups.

Results

Erythrocyte fragments have a dissociative effect on agglutinated erythrocytes. The auto hematology analyzer was able to detect AC and ACA, where AC showed an inverse correlation with MCHC, and ACA demonstrated a positive correlation with MCHC. The inter-batch CV of AC, ACA, and ACA/AC was found to be 5%, 9%, and 11.7%, respectively, with good stability. The study found that serum samples from acute phase reaction patients showed significant differences in ACA compared with healthy individuals, with a p value of 0.018; serum samples from patients with nephrotic syndrome showed significant differences in AC, ACA, and ACA/AC compared with healthy individuals, with p values of 0.014, 0.002, and 0.041, respectively.

Conclusion

Erythrocyte fragments have dissociation–agglutination effect. The complement system immunological functional detection method, based on this effect, has potential clinical application value due to its sensitivity and accuracy.

研究目的研究目的是验证基于红细胞片段的红细胞凝集解离现象，并将其应用于补体系统的功能活性测定：方法：通过检测红细胞碎片作用于凝集红细胞后游离红细胞的数量来验证红细胞碎片的解离-凝集效应。用自动血液分析仪检测补体和补体激活剂（CAs）对凝集红细胞溶血后产生的游离红细胞数量，结果用红细胞平均血红蛋白浓度（MCHC）表示。我们优化了检测条件，验证了批间稳定性，探索了检测方法的分辨率，并检测了患者和健康人血清中的总补体活性（AC）和CAs激活的补体活性（ACA）：结果：红细胞碎片对凝集的红细胞有解离作用。自动血液分析仪能检测出 AC 和 ACA，其中 AC 与 MCHC 呈反相关，而 ACA 与 MCHC 呈正相关。研究发现，AC、ACA 和 ACA/AC 的批间 CV 分别为 5%、9% 和 11.7%，稳定性良好。研究发现，急性期反应患者血清样本的 ACA 与健康人相比有显著差异，P 值为 0.018；肾病综合征患者血清样本的 AC、ACA 和 ACA/AC 与健康人相比有显著差异，P 值分别为 0.014、0.002 和 0.041：结论：红细胞碎片具有解离-凝集作用。结论：红细胞碎片具有解离-凝集效应，基于该效应的补体系统免疫功能检测方法因其灵敏性和准确性而具有潜在的临床应用价值。

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引用次数: 0