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Integrated Transcriptomic and Metabolomic Analysis Revealed That Tryptophan Metabolism–Related Metabolites Are Biomarkers of Trastuzumab Resistance 转录组学和代谢组学综合分析显示,色氨酸代谢相关代谢物是曲妥珠单抗耐药的生物标志物。
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-11-04 DOI: 10.1002/jcla.70124
Xinxin Si, Hanzhe Wu, Yiwei Cao, Bangbang Wei, Juan Wei, Zhongcheng Wang, Changfei Mao

Background

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

Methods

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

Results

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

Conclusion

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

背景:曲妥珠单抗耐药强烈影响her2阳性乳腺癌患者的预后,色氨酸代谢在癌症进展和癌症预后中起关键作用。然而,her2阳性乳腺癌中曲妥珠单抗耐药与色氨酸代谢之间的关系尚不清楚。方法:4株her2阳性乳腺癌细胞株(TS: BT-474、SK-BR-3; TR: HCC1954、JIMT-1)在特定培养基中培养。通过预处理、离心、干燥和再溶解提取细胞、组织和血清中的代谢物。代谢物检测采用UPLC-MS/MS,色氨酸代谢相关基因表达检测采用qRT-PCR。采用t检验计算统计差异。通过R语言实现数据可视化、机器学习模型构建(RF、LASSO逻辑回归)和nomogram。结果:PLS-DA在色氨酸代谢相关基因表达(HAAO、KYNU、KMO、AFMID 4个差异表达基因)和代谢物丰度(5个差异丰度代谢物)上显示TS和TR乳腺癌细胞系存在明显差异。整合分析发现3-羟基苯甲酸、朱砂酸、犬尿氨酸和犬尿酸是潜在的代谢生物标志物。这四种代谢物在hc、TS和TR患者的血清中存在显著差异。采用LASSO法选取4个预测因子,并基于logistic回归构建了nomogram。最后,在组织中验证了生物标志物和相关基因。结论:我们从与色氨酸代谢相关的代谢物丰度和基因转录水平方面探讨了曲妥珠单抗耐药引起的变化。此外,这项工作为her2阳性乳腺癌患者曲妥珠单抗耐药的新型诊断生物标志物和预测模型提供了新的见解。
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引用次数: 0
Epithelial-Mesenchymal Transition States and Metabolic Reprogramming Related Signatures Predict Prognosis and Therapeutic Responses in HER2-Positive Breast Cancer 上皮-间质过渡状态和代谢重编程相关特征预测her2阳性乳腺癌的预后和治疗反应。
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-11-03 DOI: 10.1002/jcla.70119
Yuhui Zheng, Yinduo Zeng, Mengping Xi, Guoqiang Zhu, Jinyu Yang, Peng Cui, Guoqiang Wang, Yuzi Zhang, Chunwei Xu, Wenxian Wang, Shangli Cai, Li Wang, Xiaowen Wu

Background

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

Methods

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

Results

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

Conclusion

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

背景:上皮-间质转化(Epithelial-mesenchymal transition, EMT)和代谢重编程已被证明可调节HER2靶向治疗的耐药和肿瘤转移。我们旨在建立her2阳性乳腺癌emt相关和代谢相关的预后模型。方法:从TCGA数据库下载her2阳性乳腺癌的mRNA表达和临床信息。单样本基因集富集分析评分用于生成EMT亚型并识别EMT相关代谢途径。使用最小绝对收缩和选择算子(LASSO) Cox回归,基于emt相关代谢途径的差异表达基因(DEGs)建立预后风险评分,然后在外部队列(GSE96058)中进行验证。结果:EMT富集评分分化了her2阳性乳腺癌TCGA队列中的OS (p = 0.023; HR, 0.38; 95% CI, 0.16-0.9),并且与碳水化合物、氨基酸、核苷酸和三羧酸(TCA)循环途径相关(p)。结论:EMT和代谢重编程相关特征是her2阳性乳腺癌患者特异性预后和潜在治疗性生物标志物,值得进一步研究。
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引用次数: 0
Investigating the Factors Affecting the Commutability of Hemoglobin A1C Frozen Pooled Blood Materials 影响糖化血红蛋白冷冻池血材料交换性的因素研究。
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-31 DOI: 10.1002/jcla.70125
Kanokwan Ngueanchanthong, Napaporn Apiratmateekul, Supaporn Suparak, Nam K. Tran, Wanvisa Treebuphachatsakul

Background

Measurement of hemoglobin A1C (HbA1C) is essential for the diagnosis and treatment of diabetes mellitus (DM). Processed blood materials (PBMs), such as frozen pooled blood (FPB), are commonly used for External Quality Assessment (EQA). However, their commutability may be affected by factors such as hemolysis and matrix modification. This study evaluated FPB commutability and identified the factors influencing its performance in HbA1C measurements.

Methods

HbA1C contents in 24 clinical blood samples (CBSs) and 10 PBMs, including FPBs, single-donor blood (SDB), and in vitro glycated blood (IGB), were analyzed using enzymatic (EN), capillary electrophoresis (CE), cation-exchange high-performance liquid chromatography (CE-HPLC), turbidimetric immunoassay (TI), and boronate affinity HPLC (BA-HPLC). EN served as the reference measurement procedure. Commutability was assessed using Deming regression and a 95% prediction interval. The hematocrit (HCT), visual appearance, plasma absorbance (PA), hemolysis index (HI), pH, and debris cells (DC) were analyzed.

Results

FPB1 and SDB were commutable across all measurement procedures. FPB2 and FPB4 were commutable with CE, CE-HPLC, and TI but non-commutable with BA-HPLC when HbA1C was ≥ 6.23%, as data points fell outside the tolerance limits of the Deming regression lines. Non-commutable PBMs showed higher PA and HI along with lower pH. DC affected HbA1C quantification using CE-HPLC.

Conclusions

Hemolysis, as assessed by PA and HI, affects FPB commutability. These factors should be considered in EQA programs, particularly for BA-HPLC. HCT and DC did not directly affect commutability; however, maintaining appropriate HCT levels and monitoring DC-related chromatographic interference are crucial for ensuring FPB reliability in HbA1C comparisons.

背景:糖化血红蛋白(HbA1C)的测定对糖尿病(DM)的诊断和治疗至关重要。处理过的血液材料(PBMs),如冷冻池血(FPB),通常用于外部质量评估(EQA)。然而,它们的可交换性可能受到溶血和基质修饰等因素的影响。本研究评估了FPB的可交换性,并确定了影响其在HbA1C测量中的性能的因素。方法:采用酶解法(EN)、毛细管电泳法(CE)、阳离子交换高效液相色谱法(CE-HPLC)、比浊免疫分析法(TI)、硼酸盐亲和高效液相色谱法(BA-HPLC)对24份临床血样(CBSs)和10份体外糖化血(IGB)进行HbA1C含量分析。EN作为参考测量程序。可交换性评估采用Deming回归和95%的预测区间。分析红细胞压积(HCT)、视觉外观、血浆吸光度(PA)、溶血指数(HI)、pH和碎片细胞(DC)。结果:FPB1和SDB在所有测量过程中均可交换。当HbA1C≥6.23%时,FPB2和FPB4与CE、CE- hplc和TI可交换,但与BA-HPLC不可交换,因为数据点超出了Deming回归线的容忍范围。非可交换PBMs显示较高的PA和HI以及较低的ph DC影响CE-HPLC的HbA1C定量。结论:溶血,如PA和HI评估,影响FPB的可交换性。这些因素应该在EQA程序中考虑,特别是BA-HPLC。HCT和DC不直接影响可交换性;然而,维持适当的HCT水平和监测与dc相关的色谱干扰对于确保FPB在HbA1C比较中的可靠性至关重要。
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引用次数: 0
Laboratory Data Analysis of Hemorrhagic Fever With Renal Syndrome Patients to Predict Disease Severity and Patient Prognosis 肾综合征出血热患者预测病情严重程度和预后的实验室数据分析。
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-27 DOI: 10.1002/jcla.70126
Hong Shi, Feng Du, Ting Wang, Zhendong Gu, Ting Ruan, Qiujian Zhao, Rui Xu, Yi Wang, Langxi Luo, Shaohua Wang, Liejun Jiang, Yaoni Li

Background

Hemorrhagic fever with renal syndrome (HFRS) is an endemic disease occurring in various parts of the world. Prompt access to care with proper treatment is essential for preventing patients from developing renal failure and unfavorite outcomes. This study aimed to elucidate laboratory parameters associated with HFRS severity and prognosis to predict disease course and initiate prompt clinical management.

Methods

Retrospective analysis of laboratory data was performed on HFRS patients from December 2016 to January 2022 in Baoji City of Shaanxi Province in China using different statistical methods.

Results

The WBC and neutrophils in peripheral blood, RBC in urine sediments, blood, protein, and glucose in urine, PT/INR, aPTT, TT, AST, ALT, AST/ALT, MAO, AD, urea, creatinine, cystatin C, CK-MB, LDH, α-HBDH, mAST, triglycerides, glucose, amylase, ferritin, and PCT in serum increased in HFRS patients along with disease severity, while the lymphocytes, monocytes, platelets, plateletcrit, fibrinogen, serum total protein, albumin, HDL-c, magnesium, complement C3 and C4, IgG, triiodothyronine, thyroxine, and free triiodothyronine were reduced. Results also indicated that in uncured HFRS patients, the NEUT%, CRP, cast, PT/INR, aPTT, D-dimer, AST/ALT, CK-MB, LDH, α-HBDH, m-AST, ferritin, and PCT were significantly higher than in cured patients, while platelets, C3, and C4 in uncured patients were significantly lower than in cured patients. The NEUT%, CRP, AST/ALT, and LDH were associated with patients' prognosis.

Conclusions

Laboratory data are helpful in predicting HFRS patients' progress, severity, and prognosis, thus, these parameters are useful in guiding prompt clinical management of patients.

背景:肾综合征出血热(HFRS)是发生在世界各地的一种地方病。及时获得适当治疗的护理对于防止患者发生肾功能衰竭和不良后果至关重要。本研究旨在阐明与HFRS严重程度和预后相关的实验室参数,以预测病程并启动及时的临床治疗。方法:采用不同统计方法对2016年12月至2022年1月陕西省宝鸡市HFRS患者的实验室资料进行回顾性分析。结果:HFRS患者外周血白细胞、中性粒细胞、尿沉积物红细胞、血、蛋白、尿糖、PT/INR、aPTT、TT、AST、ALT、AST/ALT、MAO、AD、尿素、肌酐、胱抑制素C、CK-MB、LDH、α-HBDH、mAST、甘油三酯、葡萄糖、淀粉酶、铁蛋白、PCT随病情加重而升高,而淋巴细胞、单核细胞、血小板、血小板、纤维蛋白原、血清总蛋白、白蛋白、HDL-c、镁、补体C3、C4、IgG、三碘甲状腺原氨酸、甲状腺素、游离三碘甲状腺原氨酸被还原。结果还显示,未治愈的HFRS患者的NEUT%、CRP、cast、PT/INR、aPTT、d -二聚体、AST/ALT、CK-MB、LDH、α-HBDH、m-AST、铁蛋白、PCT均显著高于治愈患者,血小板、C3、C4均显著低于治愈患者。NEUT%、CRP、AST/ALT和LDH与患者预后相关。结论:实验室数据有助于预测HFRS患者的病情进展、严重程度和预后,有助于指导患者的临床及时处理。
{"title":"Laboratory Data Analysis of Hemorrhagic Fever With Renal Syndrome Patients to Predict Disease Severity and Patient Prognosis","authors":"Hong Shi,&nbsp;Feng Du,&nbsp;Ting Wang,&nbsp;Zhendong Gu,&nbsp;Ting Ruan,&nbsp;Qiujian Zhao,&nbsp;Rui Xu,&nbsp;Yi Wang,&nbsp;Langxi Luo,&nbsp;Shaohua Wang,&nbsp;Liejun Jiang,&nbsp;Yaoni Li","doi":"10.1002/jcla.70126","DOIUrl":"10.1002/jcla.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hemorrhagic fever with renal syndrome (HFRS) is an endemic disease occurring in various parts of the world. Prompt access to care with proper treatment is essential for preventing patients from developing renal failure and unfavorite outcomes. This study aimed to elucidate laboratory parameters associated with HFRS severity and prognosis to predict disease course and initiate prompt clinical management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective analysis of laboratory data was performed on HFRS patients from December 2016 to January 2022 in Baoji City of Shaanxi Province in China using different statistical methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The WBC and neutrophils in peripheral blood, RBC in urine sediments, blood, protein, and glucose in urine, PT/INR, aPTT, TT, AST, ALT, AST/ALT, MAO, AD, urea, creatinine, cystatin C, CK-MB, LDH, α-HBDH, mAST, triglycerides, glucose, amylase, ferritin, and PCT in serum increased in HFRS patients along with disease severity, while the lymphocytes, monocytes, platelets, plateletcrit, fibrinogen, serum total protein, albumin, HDL-c, magnesium, complement C3 and C4, IgG, triiodothyronine, thyroxine, and free triiodothyronine were reduced. Results also indicated that in uncured HFRS patients, the NEUT%, CRP, cast, PT/INR, aPTT, D-dimer, AST/ALT, CK-MB, LDH, α-HBDH, m-AST, ferritin, and PCT were significantly higher than in cured patients, while platelets, C3, and C4 in uncured patients were significantly lower than in cured patients. The NEUT%, CRP, AST/ALT, and LDH were associated with patients' prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Laboratory data are helpful in predicting HFRS patients' progress, severity, and prognosis, thus, these parameters are useful in guiding prompt clinical management of patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 23","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145377772","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
Evaluating the “PLT Clumps?” Flag Originating From Different Channels of the Sysmex XN Haematology Analyser: A Method for Rapidly Distinguishing Between Two Preanalytical Factors Affecting PLT Counting for Cancer Patients 评估“PLT团块?”来自Sysmex XN血液分析仪不同通道的标志:一种快速区分影响癌症患者PLT计数的两种分析前因素的方法。
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-25 DOI: 10.1002/jcla.70111
Danfei Xu, Na Zhao, Wenqi Tai, Jing Yang, Li Wang

Background

This study investigated the accuracy of the “PLT Clumps?” flag triggered by different channels on the Sysmex XN haematology analyser in identifying two sample states and to optimize the platelet review strategy for cancer patients.

Methods

570 samples flagged “PLT Clumps?” in CBC + DIFF mode were analysed. After excluding clots, retesting was conducted in CBC + DIFF + PLT-F mode. The accuracy of the “PLT Clumps?” flag and its correlation with PLT aggregation (PA) or fibrin precipitation (FP) were evaluated. Low-platelet count samples were collected for a second blood draw to confirm whether pseudothrombocytopenia (PTCP) was present. The incidence and positive predictive value (PPV) of the “PLT Clumps?” flag across different tumours were also analysed.

Results

Among 85 verified cases (PA = 17, FP = 63), the overall PPV of the “PLT Clumps?” flag was 14.9% (85/570) in CBC + DIFF mode, 3.5% in WNR channel only, 73.9% in WDF channel only, and 94.4% in dual-channel. In CBC + DIFF + PLT-F mode, the overall PPV and NPV were 98.5% (65/66) and 97.0% (484/499), respectively. PA and FP accounted for 73.9% (17/23) and 26.1% (6/23) of the PLT-F-only flagged samples, respectively, and all WDF-only and dual-flagged cases were triggered by FP. The incidence of PTCP in samples flagged for “PLT Clumps?” in CBC + DIFF + PLT-F mode was 80%. Samples from patients with hepatobiliary tumours showed highest flagging rate (20.4%) but a lower PPV.

Conclusion

The correlation between “PLT Clumps?” flags originating from different channels and two common preanalytical factors interfering in PLT counting was analysed, and the platelet review strategy for cancer patients was optimized.

背景:本研究探讨了Sysmex XN血液学分析仪上不同通道触发的“PLT团块”标志在识别两种样品状态和优化癌症患者血小板审查策略方面的准确性。方法:对570例CBC + DIFF模式标记为“PLT团块”的样本进行分析。排除血块后,以CBC + DIFF + PLT-F模式重新检测。评估了“PLT团块”标记的准确性及其与PLT聚集(PA)或纤维蛋白沉淀(FP)的相关性。收集低血小板计数样本进行第二次抽血以确认是否存在假性血小板减少症(PTCP)。还分析了“PLT团块”标志在不同肿瘤中的发病率和阳性预测值(PPV)。结果:85例确诊病例(PA = 17, FP = 63)中,CBC + DIFF模式下“PLT块”标志的总PPV为14.9%(85/570),仅WNR通道为3.5%,仅WDF通道为73.9%,双通道为94.4%。CBC + DIFF + PLT-F模式下,总PPV和NPV分别为98.5%(65/66)和97.0%(484/499)。PA和FP分别占plt -f单标记样本的73.9%(17/23)和26.1%(6/23),所有wdf单标记和双标记病例均由FP触发。在CBC + DIFF + PLT- f模式中标记为“PLT团块”的样本中,PTCP的发生率为80%。来自肝胆肿瘤患者的样本显示最高的标记率(20.4%),但PPV较低。结论:分析来自不同通道的“血小板团块”标记与两种常见的干扰血小板计数的分析前因素的相关性,优化肿瘤患者血小板评价策略。
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引用次数: 0
Antifungal Resistance of Candida spp. Isolates From HIV/AIDS Patients in Iran 1999–2024: A Systematic Review and Meta-Analysis 1999-2024年伊朗HIV/AIDS患者念珠菌的抗真菌耐药性:一项系统综述和荟萃分析
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-24 DOI: 10.1002/jcla.70101
Aliasghar Fakhri-Demeshghieh, Ali Yousefipour, Yousef Bolouki, Mohammad Sadegh Bigdeli, Erfan Zamani, Amirreza Farajkhoda, Alireza Salmani, Farzad Katiraee, Saied Bokaie

Background

Antifungal resistance in Candida species in HIV/AIDS patients due to the scarcity of antifungal agents is important particularly in Iran with an estimate of 46,000 individuals living with HIV. This systematic review and meta-analysis aimed to determine the resistance rate of Candida spp. isolates from HIV/AIDS positive individuals in Iran from 1999 to 2024.

Methods

PubMed, Scopus, Web of Science, MagIran, Scientific Information Database, and Google Scholar were searched and the title-and-abstract screening was performed independently by two review authors. The risk of bias assessment and the data extraction were performed independently by two review authors. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020.

Results

From the retrieved 4925 references, 18 references belonging to 15 studies with 1318 Candida spp. isolates were included. The highest pooled resistance rate of Candida spp. was observed against clotrimazole (21%, 95% CI: 14–30, I2 = 67.29%) while the lowest pooled resistance rates of Candida spp. were observed against voriconazole, caspofungin, amphotericin B, and nystatin with the pooled estimates of 0%. At the species level, the highest pooled resistance rates were observed for Candida krusei against fluconazole (72%, 95% CI: 0%–100%) and itraconazole (38%, 95% CI: 17%–62%), and for Candida glabrata against clotrimazole (38%, 95% CI: 27%–50%).

Conclusions

The use of amphotericin B, caspofungin, and nystatin for the treatment of Candida spp. in HIV-AIDS patients in Iran is recommended based on clinical indication.

Trial Registration

PROSPERO ID: CRD42024540580

背景:由于抗真菌药物的缺乏,HIV/AIDS患者中念珠菌种类的抗真菌耐药性非常重要,特别是在伊朗,估计有46,000名HIV感染者。本系统综述和荟萃分析旨在确定1999年至2024年伊朗HIV/AIDS阳性个体中念珠菌分离株的耐药率。方法:检索PubMed、Scopus、Web of Science、MagIran、Scientific Information Database、谷歌Scholar,由两位综述作者独立进行标题和摘要筛选。偏倚风险评估和数据提取由两位综述作者独立完成。meta分析采用Freeman-Tukey双反正弦变换随机效应模型。本综述遵循2020年系统评价和荟萃分析的首选报告项目。结果:从检索到的4925篇文献中,共纳入18篇文献,共涉及念珠菌菌株1318株。念珠菌对克霉唑的综合耐药率最高(21%,95% CI: 14 ~ 30, I2 = 67.29%),对伏立康唑、卡泊芬净、两性霉素B和制霉菌素的综合耐药率最低,综合估计值为0%。在种水平上,克鲁氏念珠菌对氟康唑(72%,95% CI: 0% ~ 100%)和伊曲康唑(38%,95% CI: 17% ~ 62%)的总耐药率最高,光念珠菌对克霉唑(38%,95% CI: 27% ~ 50%)的总耐药率最高。结论:两性霉素B、卡泊真菌素和制霉菌素治疗伊朗HIV-AIDS患者念珠菌属感染具有临床适应症。试验注册:PROSPERO ID: CRD42024540580。
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引用次数: 0
Predictive Value of Laboratory Assays Toward Autoimmune Diseases 实验室检测对自身免疫性疾病的预测价值
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-23 DOI: 10.1002/jcla.70106
Kellen J. Begeman, Mark J. White, Elizabeth S. Moore, Heidi H. Ewen

Objective

With an increasing number of unmet medical needs for autoimmune diseases (AD) in the United States, it is important to assess the value of laboratory assays in diagnosis. Healthcare providers must understand general and specific laboratory results that can lead to an efficient diagnosis.

Methods

A nonexperimental study using a retrospective design and data collected between 2018 and 2021 was completed to explore whether the presence of positive anti-ENA and anti-dsDNA antibodies in individuals with an autoimmune disorder (anti-ENA, N = 1495; anti-dsDNA, N = 1261) can be predicted by their demographics and selected general laboratory test results.

Results

For predicting anti-ENA, multiple logistic regression analysis χ2(1) = 237.62, p < 0.001 indicated antinuclear antibody (ANA), complement C3, globulin, monocyte-to-lymphocyte ratio (MLR), and blood urea nitrogen (BUN) were statistically associated with the probability of a positive anti-ENA result. The regression analysis had a sensitivity of 98.6% and a specificity measure of 16.1%. Regarding anti-dsDNA, multiple logistic regression analysis χ2(1) = 388.04, p < 0.001, indicated that complement C3, complement C4, pH, urine protein, and neutrophil-to-lymphocyte ratio (NLR) were statistically associated with the probability of a positive anti-dsDNA result. The regression analysis had a sensitivity of 77.7% and a specificity measure of 64.5%.

Conclusion

In diagnosing an AD, ANA, complement C3, globulin, MLR, and BUN are important factors in patients with a positive anti-ENA. In determining Systemic Lupus Erythematosus diagnosis, complement C3, complement C4, pH, urine protein, and NLR are important factors in patients with a positive anti-dsDNA.

目的:随着美国自身免疫性疾病(AD)未满足医疗需求的增加,评估实验室检测在诊断中的价值非常重要。医疗保健提供者必须了解可以导致有效诊断的一般和特定的实验室结果。方法:采用回顾性设计和2018 - 2021年间收集的数据,完成一项非实验研究,探讨自身免疫性疾病个体(抗ena, N = 1495;抗dsdna, N = 1261)中抗ena和抗dsdna抗体阳性的存在是否可以通过其人口统计学和选定的一般实验室检测结果来预测。结果:通过多元logistic回归分析,χ2(1) = 237.62, χ2(1) = 388.04, p结论:ANA、补体C3、球蛋白、MLR、BUN是诊断AD的重要因素。在判定系统性红斑狼疮诊断时,补体C3、补体C4、pH值、尿蛋白、NLR是抗dsdna阳性患者的重要因素。
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引用次数: 0
Quantitative Analysis of DNA Double-Strand Breaks in Genomic DNA Using Standard Curve Method 用标准曲线法定量分析基因组DNA双链断裂。
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-18 DOI: 10.1002/jcla.70123
Lihuang Guo, Hanying Dai, Jiancheng Li, Chenwei Li, Yue Huang, Keqian Xu

Background

DNA double-strand breaks (DSBs) are the most lethal and dangerous type of lesions with significant implications for both cellular function and organismal health. The number of DSBs (NDSBs) across the genome reflects DNA damage severity. However, current quantification methods mainly rely on next-generation sequencing, which is laborious and expensive. This study aims to provide a simple, low-cost, and high-throughput standard curve-based method for quantifying genome-wide DSBs.

Method

Genomic DNA from human, mouse, Arabidopsis, Saccharomyces cerevisiae, and Escherichia coli was digested by seven blunt-end restriction enzymes to generate DSB standards. Theoretical NDSBs for each standard were calculated based on restriction site frequency. Ligation-mediated quantitative PCR (LM-qPCR) was performed to obtain the Ct values, which were plotted against log-transformed NDSBs to construct standard curves. Method reliability was assessed by comparing results with neutral single-cell gel electrophoresis and γ-H2AX flow cytometry.

Results

All genomes were successfully digested by seven blunt-end restriction enzymes to produce standard DSB fragments. Standard curves demonstrated high linearity (R2 > 0.95), with intra- and inter-assay coefficients of variation of 1.101% and 2.528%, respectively. The detection limit was below 100 DSBs. Quantification results strongly correlated with traditional DSB detection methods (|r| > 0.9).

Conclusion

This standard curve-based method enables accurate, reproducible quantification of genome-wide DSBs in various organisms. It is simple, low-cost, and easily standardized, offering a promising tool for applications in genotoxicity testing, environmental exposure monitoring, and DNA damage research.

背景:DNA双链断裂(DSBs)是最致命和危险的病变类型,对细胞功能和机体健康都有重要影响。基因组中dsb (ndsb)的数量反映了DNA损伤的严重程度。然而,目前的定量方法主要依赖于下一代测序,该方法既费力又昂贵。本研究旨在提供一种简单、低成本、高通量的基于标准曲线的全基因组dsb定量方法。方法:用7种钝端限制性内切酶酶切人、小鼠、拟南芥、酿酒酵母和大肠杆菌基因组DNA,制备DSB标准品。每个标准的理论ndsb是基于限制场址频率计算的。采用连接介导的定量PCR (LM-qPCR)获得Ct值,并将其与对数变换的ndsb进行绘图以构建标准曲线。通过与中性单细胞凝胶电泳和γ-H2AX流式细胞术结果的比较,评估方法的可靠性。结果:所有基因组经7种钝端限制性内切酶成功酶切得到标准的DSB片段。标准曲线线性度高(R2 > 0.95),组内和组间变异系数分别为1.101%和2.528%。检出限在100 DSBs以下。定量结果与传统DSB检测方法相关性强(|r| > 0.9)。结论:这种基于标准曲线的方法能够准确、可重复地定量测定各种生物的全基因组dsb。它简单,低成本,易于标准化,为基因毒性测试,环境暴露监测和DNA损伤研究提供了一个有前途的工具。
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引用次数: 0
Detection of blaNDM-1 and blaIMP-1 Metallo-β-Lactamases in Meropenem-Resistant Clinical Escherichia coli Isolates Using Modified Carbapenem Inactivation Method (mCIM) and PCR Techniques 改良碳青霉烯灭活法(mCIM)和PCR技术检测耐美罗培烯临床大肠埃希菌中blaNDM-1和blaIMP-1金属β-内酰胺酶
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-17 DOI: 10.1002/jcla.70100
Mehdi Roshdi Maleki

Introduction

Escherichia coli, a member of the Enterobacteriaceae family, is a leading cause of various infections. Carbapenems, a potent class of β-lactam antibiotics, serve as the last line of defense against multidrug-resistant bacteria. However, the global rise of carbapenemase-producing E. coli (CP-Ec), particularly metallo-β-lactamases (MBLs), poses a significant public health concern. This study aimed to determine the prevalence of blaNDM-1 and blaIMP-1 genes in E. coli strains isolated from clinical samples.

Methods

A cross-sectional study was conducted on 80 meropenem-resistant E. coli strains isolated from clinical samples. Bacterial identification was performed using biochemical tests, including IMViC. Carbapenemase production was assessed using the modified carbapenem inactivation method (mCIM). Genotypic analysis of carbapenem-resistant strains was conducted via polymerase chain reaction (PCR) to detect blaNDM-1 and blaIMP-1 genes.

Results

The mCIM phenotypic test identified 46.25% (37/80) of isolates as carbapenemase producers. PCR analysis revealed that blaNDM-1 was more prevalent than blaIMP-1 (48.65% vs. 16.22%). Four isolates (10.81%) carried both genes. Notably, 35.14% (13/37) of meropenem-resistant E. coli isolates tested negative for both blaNDM-1 and blaIMP-1, indicating the possible involvement of other carbapenemase genes such as blaVIM or non-carbapenemase mechanisms.

Conclusion

The detection of blaNDM-1 and blaIMP-1 genes in E. coli highlights the alarming spread of carbapenem resistance. The presence of resistant strains lacking these genes suggests additional resistance mechanisms, warranting further investigation.

简介:大肠杆菌是肠杆菌科的一员,是各种感染的主要原因。碳青霉烯类是一种有效的β-内酰胺类抗生素,是抵御多重耐药细菌的最后一道防线。然而,产生碳青霉烯酶的大肠杆菌(CP-Ec),特别是金属β-内酰胺酶(MBLs)的全球上升,引起了重大的公共卫生问题。本研究旨在确定blaNDM-1和blaIMP-1基因在临床分离的大肠杆菌菌株中的流行程度。方法:对临床分离的80株美罗培尼耐药大肠杆菌进行横断面研究。细菌鉴定采用生化试验,包括IMViC。采用改良碳青霉烯酶失活法(mCIM)评价碳青霉烯酶的产量。采用聚合酶链反应(PCR)对碳青霉烯耐药菌株进行基因型分析,检测blaNDM-1和blaIMP-1基因。结果:mCIM表型试验鉴定46.25%(37/80)的分离株为碳青霉烯酶产生菌。PCR分析显示blaNDM-1比blaIMP-1更普遍(48.65%比16.22%)。4株(10.81%)同时携带两个基因。值得注意的是,35.14%(13/37)的耐美洛苯烯大肠杆菌分离株blaNDM-1和blaIMP-1检测均为阴性,表明可能涉及其他碳青霉烯酶基因,如blaVIM或非碳青霉烯酶机制。结论:在大肠杆菌中检测到blaNDM-1和blaIMP-1基因,表明碳青霉烯类耐药的传播具有警示意义。缺乏这些基因的耐药菌株的存在表明存在其他的耐药机制,值得进一步研究。
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引用次数: 0
Severe Malnutrition Identified by the Controlling Nutritional Status (CONUT) Score Is Associated With Prolonged Intensive Care Unit (ICU) Stay in Pneumonia Complicated With Respiratory Failure Patients Who Underwent Invasive Mechanical Ventilation 通过控制营养状况(CONUT)评分确定的严重营养不良与肺炎合并呼吸衰竭患者接受有创机械通气的重症监护病房(ICU)住院时间延长有关。
IF 2.9 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-10-14 DOI: 10.1002/jcla.70109
Zhijuan Zheng, Guixia Peng, Yue Xiao

Background

Mechanical ventilation is an effective method to improve the ventilation of patients with severe pneumonia and respiratory failure. The length of intensive care unit (ICU) stay reflects the treatment effectiveness of patients. This study was to evaluate the relationship between Controlled Nutritional Status (CONUT) score and prolonged ICU stay in patients with pneumonia complicated by respiratory failure who underwent invasive mechanical ventilation.

Methods

1994 patients who underwent invasive mechanical ventilation were retrospectively analyzed. Medical records (age, gender, body mass index, smoking, drinking, hypertension, diabetes mellitus, lung diseases, blood transfusion, and serum albumin, lymphocyte, cholesterol levels) were collected. The threshold for prolonged ICU stay was defined based on the third quartile (75th percentile) of length of ICU stay. The relationship between CONUT and prolonged ICU stay was analyzed.

Results

The mean ICU stay of patients was 6.6 (3.9, 11.6) days; there were 1495 (75.0%) patients without prolonged ICU stay (< 11.6 days) and 499 (25.0%) with prolonged ICU stay (≥ 11.6 days). The proportion of CONUT severe grade in patients with prolonged ICU stay was higher than that in patients without prolonged ICU stay. Logistic regression analysis showed that CONUT severe grade (odds ratio (OR): 1.298, 95% confidence interval (CI): 1.024–1.646, p = 0.031), smoking (OR: 1.475, 95% CI: 1.105–1.968, p = 0.008), and blood transfusion (OR: 2.981, 95% CI: 2.406–3.694, p < 0.001) were independently associated with prolonged ICU stay.

Conclusions

CONUT severe grade, smoking, and blood transfusion were independently associated with prolonged ICU stay in pneumonia with respiratory failure patients who underwent invasive mechanical ventilation.

背景:机械通气是改善重症肺炎合并呼吸衰竭患者通气的有效方法。重症监护病房(ICU)的住院时间长短反映了患者的治疗效果。本研究旨在评估肺炎合并呼吸衰竭行有创机械通气患者的控制营养状态(CONUT)评分与延长ICU住院时间的关系。方法:对1994例有创机械通气患者进行回顾性分析。收集医疗记录(年龄、性别、体重指数、吸烟、饮酒、高血压、糖尿病、肺部疾病、输血、血清白蛋白、淋巴细胞、胆固醇水平)。延长ICU住院时间的阈值根据ICU住院时间的第三个四分位数(第75个百分位数)确定。分析CONUT与ICU住院时间延长的关系。结果:患者平均ICU住院时间6.6 (3.9,11.6)d;1495例(75.0%)患者未延长ICU住院时间。结论:肺炎合并呼吸衰竭患者行有创机械通气时,CONUT严重程度、吸烟和输血与延长ICU住院时间独立相关。
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引用次数: 0
期刊
Journal of Clinical Laboratory Analysis
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