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Impact of rs599839 Polymorphism on Coronary Artery Disease Risk in Saudi Diabetic Patients. 沙特糖尿病患者 rs599839 多态性对冠心病风险的影响
4区 医学 Q3 Medicine Pub Date : 2024-08-07 eCollection Date: 2024-01-01 DOI: 10.1155/2024/8278727
Neda M Bogari, Ahmad O Babalghith, Zohor Asaad Azher, Ahmad Hasan Mufti, Abdellatif Bouazzaoui, Hussain Banni, Abdulelah Awaji Madkhali, Ahmed Alahmadi, Reem M Allam

Background: Coronary artery diseases may be affected by several genetic and nongenetic factors. Single-nucleotide polymorphism (SNP) rs599839 and type 2 diabetes mellitus (T2DM) can affect the occurrence and severity of coronary artery disease (CAD).

Methods: Our aim was to investigate how T2DM and the rs599839 variant affected serum lipid levels and the degree of CAD patients' coronary artery stenosis. rs599839 polymorphism genotyping was done on Saudi patients with coronary angiography performed previously. Patients enrolled were divided into group A (360 DM patients), group B (225 DM patients with CAD), and group C (190 healthy volunteers as control).

Results: Individuals with diabetes and CAD who possessed the GG genotype in rs599839 exhibited markedly reduced means of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG; 224.5, 116.2, and 221.4 versus 251.6, 131.3, and 261.7 mg/dl, p=0.003, 0.007, and 0.025, respectively) than AA genotype. The odds ratio and the confidence interval of 95% for G allele carriers of rs599839 were OR = 0.62, 95% CI: 0.41-0.82, and p=0.003, among diabetic patients with CAD.

Conclusions: In patients with diabetic CAD, the locus 1p13.3 polymorphism rs599839 was found to be substantially correlated with serum lipid levels. Furthermore, among Saudi patients with diabetes, the G allele of rs599839 variant lowers the CAD risk.

背景:冠状动脉疾病可能受到多种遗传和非遗传因素的影响。单核苷酸多态性(SNP)rs599839和2型糖尿病(T2DM)会影响冠状动脉疾病(CAD)的发生和严重程度:我们的目的是研究 T2DM 和 rs599839 变体如何影响血清脂质水平和 CAD 患者的冠状动脉狭窄程度。入组患者被分为 A 组(360 名糖尿病患者)、B 组(225 名患有 CAD 的糖尿病患者)和 C 组(190 名健康志愿者作为对照):结果:与 AA 基因型相比,rs599839 基因型为 GG 的糖尿病和 CAD 患者的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和甘油三酯(TG;分别为 224.5、116.2 和 221.4 对 251.6、131.3 和 261.7 mg/dl,P=0.003、0.007 和 0.025)均明显降低。在患有 CAD 的糖尿病患者中,rs599839 的 G 等位基因携带者的几率比和 95% 的置信区间分别为 OR = 0.62、95% CI:0.41-0.82 和 p=0.003:结论:在糖尿病并发心血管疾病患者中,1p13.3位点多态性rs599839与血清脂质水平密切相关。此外,在沙特籍糖尿病患者中,rs599839 变异的 G 等位基因可降低 CAD 风险。
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引用次数: 0
Corrigendum to "Fluvastatin Upregulates the α 1C Subunit of CaV1.2 Channel Expression in Vascular Smooth Muscle Cells via RhoA and ERK/p38 MAPK Pathways". 氟伐他汀通过 RhoA 和 ERK/p38 MAPK 途径上调血管平滑肌细胞中 CaV1.2 通道 α 1C 亚基的表达》的更正。
4区 医学 Q3 Medicine Pub Date : 2024-06-22 eCollection Date: 2024-01-01 DOI: 10.1155/2024/9875935
Qiu-Fang Ouyang, Ying Han, Zhi-Hong Lin, Hong Xie, Chang-Sheng Xu, Liang-Di Xie

[This corrects the article DOI: 10.1155/2014/237067.].

[This corrects the article DOI: 10.1155/2014/237067.].
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引用次数: 0
JAK2 as Predictor of Therapeutic Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib JAK2 作为伊马替尼治疗的慢性髓性白血病患者治疗反应的预测因子
4区 医学 Q3 Medicine Pub Date : 2024-04-12 DOI: 10.1155/2024/2906566
Indra Wijaya, Muhammad H. Bashari, Lelani Reniarti, Anita Rahmawati, Rully M. A. Roesli
Background. Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome. First-line tyrosine kinase inhibitor, imatinib, is the gold standard for treatment. However, there has been known unresponsiveness to treatment, especially due to the involvement of other genes, such as the Janus kinase 2 (JAK2) gene. This study aimed to evaluate the relationships between JAK2 levels and complete hematological response (CHR), as well as early molecular response (EMR) after 3 months of imatinib treatment in patients with chronic phase CML. Methods. Patients with Ph+ CML in the chronic phase (n = 40; mean age, 40 ± 11 years) were recruited to complete assessments consisting of clinical examination and blood test, including evaluation of complete blood counts and the JAK2 levels, at baseline and following 3 months of therapy with imatinib (at an oral dose of 400 mg per day). Subjects were divided into two groups according to the presence of CHR and EMR. Results. JAK2 gene levels, phosphorylated, and total JAK2 proteins at baseline were significantly lower in the group with the presence of CHR and EMR. In addition, baseline JAK2 levels, including JAK2 gene expression, phosphorylated, and total JAK2 proteins, were negatively correlated with the presence of CHR and EMR. Conclusions. Based on these findings, JAK2 levels may be a potential indicator for evaluating treatment response on imatinib due to its role in the pathophysiology of CML.
背景。慢性粒细胞白血病(CML)或慢性粒细胞白血病是一种骨髓增生性肿瘤,以费城(Ph+)染色体的存在为标志。一线酪氨酸激酶抑制剂伊马替尼是治疗的金标准。然而,已知有患者对治疗不敏感,特别是由于其他基因的参与,如 Janus 激酶 2(JAK2)基因。本研究旨在评估慢性期CML患者接受伊马替尼治疗3个月后,JAK2水平与完全血液学反应(CHR)以及早期分子反应(EMR)之间的关系。研究方法招募慢性期Ph+ CML患者(n = 40;平均年龄(40 ± 11)岁),在基线和伊马替尼(口服剂量为每天400毫克)治疗3个月后,完成包括临床检查和血液检测在内的评估,其中包括全血细胞计数和JAK2水平的评估。受试者根据是否存在CHR和EMR分为两组。研究结果在存在CHR和EMR的组别中,基线时的JAK2基因水平、磷酸化和总JAK2蛋白都明显较低。此外,基线JAK2水平(包括JAK2基因表达、磷酸化和总JAK2蛋白)与是否存在CHR和EMR呈负相关。结论。基于这些发现,JAK2水平可能是评估伊马替尼治疗反应的一个潜在指标,因为它在CML的病理生理学中起着重要作用。
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引用次数: 0
Significance of Estrogen/Progesterone Receptor Expression in Metaplastic Breast Carcinoma 变性乳腺癌中雌激素/孕激素受体表达的意义
4区 医学 Q3 Medicine Pub Date : 2024-04-03 DOI: 10.1155/2024/2540356
Atif Ali Hashmi, Bakhtawar Allauddin Mallick, Khushbakht Rashid, Umair Arshad Malik, Shamail Zia, Fazail Zia, Muhammad Irfan
Introduction. Metaplastic breast carcinoma (MBC) is a rare subgroup of breast neoplasms associated with adverse outcomes because of its aggressive nature. Typically, MBCs show triple-negative hormone receptor (HR) status. Determining the HR status of breast cancer is an integral part because it is an important prognostic factor and helps in the treatment course of the disease. This study aimed to determine the HR status of MBC, its significance, and its association with various clinicopathological parameters. Methods. This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital. A total of 140 biopsy-proven cases of MBC were enrolled in the study. Clinical and pathological data were retrieved from the institutes’ archives. Immunohistochemical studies were conducted to determine the estrogen receptor (ER) and progesterone receptor (PR) status. Results. The mean age of MBC in our population was found to be 52.18 ± 12.19 years. The HR positivity rate in our population was found to be 32.9%. A significant association was found between HR status and tumor laterality, tumor size, tumor grade, tumor stage, and recurrence. ER/PR-negative MBCs were most probably associated with higher grade and higher tumor stage and were larger in size (6.62 ± 3.43 cm) than ER/PR-positive MBCs (4.20 ± 1.88 cm). Moreover, ER/PR-positive MBCs showed a higher recurrence rate than ER/PR-negative MBCs (43.5% vs. 25.5%, respectively). No statistically significant relationship was found between HR status and patient age, histological subtype, or survival rate. Conclusion. MBC is a rare breast neoplasm. MBC was found to be triple negative in most cases, but a significant percentage were HR (ER/PR) positive. Moreover, we found an association between HR status and various clinicopathological features, indicating that HR status is a significant predictor of MBC prognosis.
简介移行细胞乳腺癌(MBC)是乳腺肿瘤中的一个罕见亚组,因其侵袭性强而导致不良后果。MBC通常表现为激素受体(HR)三阴性。确定乳腺癌的激素受体状态是不可或缺的一部分,因为这是一个重要的预后因素,有助于疾病的治疗过程。本研究旨在确定 MBC 的 HR 状态、其重要性及其与各种临床病理参数的关系。研究方法这是一项在利亚卡特国立医院组织病理学部进行的回顾性研究。共有 140 例经活检证实的 MBC 病例参与研究。临床和病理数据均来自医院档案。免疫组化研究用于确定雌激素受体(ER)和孕激素受体(PR)的状态。结果我们发现,MBC患者的平均年龄为(52.18 ± 12.19)岁。HR阳性率为32.9%。HR状态与肿瘤侧位、肿瘤大小、肿瘤分级、肿瘤分期和复发之间存在明显关联。与ER/PR阳性的MBC(4.20 ± 1.88厘米)相比,ER/PR阴性的MBC很可能与肿瘤分级更高、肿瘤分期更高和肿瘤体积更大(6.62 ± 3.43厘米)有关。此外,ER/PR 阳性 MBC 的复发率高于ER/PR 阴性 MBC(分别为 43.5% 对 25.5%)。HR状态与患者年龄、组织学亚型或存活率之间没有统计学意义上的关系。结论:MBC是一种罕见的乳腺肿瘤。MBC是一种罕见的乳腺肿瘤。在大多数病例中,MBC 为三阴性,但有相当比例的病例为 HR(ER/PR)阳性。此外,我们还发现 HR 状态与各种临床病理特征之间存在关联,这表明 HR 状态是预测 MBC 预后的一个重要指标。
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引用次数: 0
Determination of Tumor Marker Screening for Lung Cancer Using ROC Curves 利用 ROC 曲线确定肺癌肿瘤标记物筛查方法
4区 医学 Q3 Medicine Pub Date : 2024-03-21 DOI: 10.1155/2024/4782618
Xiaofeng Dou, Jiachen Lu, Yingying Yu, Yaohui Yi, Ling Zhou
Introduction. Lung cancer ranks first among malignant tumors worldwide and is a leading cause of cancer-related mortality in both men and women. Combining tumor marker testing is a strategy to screen individuals at high risk of pulmonary cancer and minimize pulmonary cancer mortality. Therefore, tumor marker screening is crucial. In this study, we analyzed combinations of tumor markers for lung cancer screening using receiver operating characteristic (ROC) curve analysis. Methods. A retrospective descriptive study was conducted on patients diagnosed with lung cancer, as well as healthy and benign lung diseases, using data from the China Huludao Central Hospital database between January 2016 and July 2022. The t-test and ROC curve were utilized to assess the effectiveness of individual tumor marker and the combination of multiple tumor markers. Tumor markers are molecular products metabolized and secreted by tumor tissues, characterized by cells or body fluids. They serve as indicators of tumor stage and grading, monitor treatment response, and predict recurrence. Results. In this study, 267 healthy participants, 385 patients with benign lesions, and 296 patients with lung cancer underwent tumor marker screening. The sensitivity of five tumor markers—CEA, CYFRA21-1, NSE, pro-GRP, and CA125—was found to be <55%. This study revealed that a single tumor marker had limited value in lung cancer screening. However, combining two or more markers yielded varying area under the curves (AUC), with no significant impact on screening accuracy. The combination of CEA + CA125 demonstrated the highest accuracy for lung cancer screening in healthy participants. At a cutoff of 0.447 for CEA + CA125, the combination showed a sensitivity of 0.676 and specificity of 0.846 for lung cancer screening. Conversely, for patients with benign lung lesions, the optimal combination was CEA + NSE, with a cutoff of 0.393, yielding a sensitivity of 0.645 and specificity of 0.766 for lung cancer screening. Conclusion. The five tumor markers—CEA, CA125, CY211, NSE, GRP—show promising results in screening healthy individuals and patients with lung cancer. However, only CEA, NSE, and GRP effectively differentiate patients with benign lung lesions from those with lung cancer. A single tumor marker has limited utility in detecting and screening for lung cancer and should be combined with other tumor markers. CEA + CA125 emerges as a superior tumor marker for distinguishing healthy individuals from those with lung cancer, whereas the CEA + NSE combination is more effective in identifying tumor markers in patients with benign lung lesions and lung cancer.
导言。肺癌在全球恶性肿瘤中排名第一,是导致男性和女性癌症相关死亡的主要原因。结合肿瘤标志物检测是筛查肺癌高危人群并最大限度降低肺癌死亡率的一种策略。因此,肿瘤标志物筛查至关重要。在本研究中,我们使用接收器操作特征曲线(ROC)分析方法对肺癌筛查中的肿瘤标志物组合进行了分析。方法:回顾性描述性研究利用中国葫芦岛市中心医院数据库2016年1月至2022年7月期间的数据,对确诊为肺癌的患者以及健康和良性肺部疾病患者进行回顾性描述性研究。采用t检验和ROC曲线评估单个肿瘤标志物和多个肿瘤标志物组合的有效性。肿瘤标志物是肿瘤组织代谢和分泌的分子产物,以细胞或体液为特征。它们可作为肿瘤分期和分级、监测治疗反应和预测复发的指标。研究结果在这项研究中,267 名健康参与者、385 名良性病变患者和 296 名肺癌患者接受了肿瘤标志物筛查。结果发现,五种肿瘤标志物--CEA、CYFRA21-1、NSE、pro-GRP 和 CA125--的敏感性为 55%。这项研究表明,单一肿瘤标志物在肺癌筛查中的价值有限。然而,将两种或两种以上的标记物结合在一起会产生不同的曲线下面积(AUC),对筛查准确性没有显著影响。在健康参与者中,CEA + CA125 组合的肺癌筛查准确率最高。当 CEA + CA125 的临界值为 0.447 时,该组合对肺癌筛查的灵敏度为 0.676,特异度为 0.846。相反,对于肺部良性病变患者来说,最佳组合是 CEA + NSE,临界值为 0.393,对肺癌筛查的灵敏度为 0.645,特异度为 0.766。结论五种肿瘤标志物--CEA、CA125、CY211、NSE、GRP--在筛查健康人和肺癌患者方面显示出良好的效果。然而,只有 CEA、NSE 和 GRP 能有效区分肺部良性病变和肺癌患者。单一肿瘤标志物在检测和筛查肺癌方面的作用有限,应与其他肿瘤标志物结合使用。CEA + CA125 是区分健康人和肺癌患者的最佳肿瘤标记物,而 CEA + NSE 组合则能更有效地识别肺部良性病变和肺癌患者的肿瘤标记物。
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引用次数: 0
Plasma microRNA-320c as a Potential Biomarker for the Severity of Knee Osteoarthritis and Regulates cAMP Responsive Element Binding Protein 5 (CREB5) in Chondrocytes 血浆 microRNA-320c 是膝骨关节炎严重程度的潜在生物标记物,可调控软骨细胞中的 cAMP 响应元件结合蛋白 5 (CREB5)
4区 医学 Q3 Medicine Pub Date : 2024-03-20 DOI: 10.1155/2024/9936295
Rongwei Zhou, Like Zhao, Qian Wang, Yongjing Cheng, Miao Song, Cibo Huang
Objective. Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the expression of plasma microRNA-320c (miR-320c) in patients with knee OA and to explore the clinical value and potential mechanism of miR-320c in knee OA. Methods. Forty knee OA patients and 20 healthy controls were enrolled. The levels of plasma miR-320c and plasma inflammatory cytokines were measured by real-time PCR or ELISA. Correlations of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and cytokine levels with the miR-320c expression level were evaluated by Pearson correlation analysis. Then, a receiver operating characteristic (ROC) curve was drawn to analyse the diagnostic value of miR-320c in OA. Finally, the interaction of miR-320c and cAMP responsive element binding protein 5 (CREB5) was determined using a luciferase reporter assay, and the effect of CREB5 on the cAMP pathway was assessed. Results. The expression level of plasma miR-320c was significantly higher in OA patients than in healthy controls (). The increased plasma miR-320c level was positively correlated with the WOMAC score (r = 0.796,
目的。骨关节炎(OA)是一种众所周知的常见关节疾病,但治疗方法有限。本研究旨在调查膝关节 OA 患者血浆 microRNA-320c (miR-320c)的表达,并探讨 miR-320c 在膝关节 OA 中的临床价值和潜在机制。研究方法40例膝关节OA患者和20例健康对照组。采用实时 PCR 或 ELISA 方法测定血浆 miR-320c 和血浆炎性细胞因子的水平。通过皮尔逊相关分析评估了西安大略和麦克马斯特大学骨关节炎指数(WOMAC)评分和细胞因子水平与 miR-320c 表达水平的相关性。然后,绘制接收器操作特征曲线(ROC)来分析 miR-320c 在 OA 中的诊断价值。最后,利用荧光素酶报告实验确定了 miR-320c 与 cAMP 反应元件结合蛋白 5(CREB5)的相互作用,并评估了 CREB5 对 cAMP 通路的影响。结果发现OA 患者血浆 miR-320c 的表达水平明显高于健康对照组()。血浆 miR-320c 水平的升高与 OA 患者的 WOMAC 评分(r = 0.796,)、血浆白细胞介素(IL)-1β(r = 0.814,)和 IL-6 (r = 0.695,)水平呈正相关。ROC 曲线分析表明,血浆 miR-320c 对 OA 的诊断准确率相对较高。此外,荧光素酶报告实验结果表明,miR-320c 通过与 CREB5 3′-非翻译区结合来调节 CREB5 的表达。此外,抑制 CREB5 能显著降低 c-fos 和 c-jun 的表达水平。结论我们的研究结果表明,血浆 miR-320c 可能是预测膝关节 OA 严重程度的潜在新指标,而且 miR-320c 可能通过靶向 CREB5 抑制 cAMP 通路,在 OA 发病机制中发挥重要作用。
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引用次数: 0
Assessment of Antioxidant Enzyme Superoxide Dismutase (SOD) in Oral Cancer: Systematic Review and Meta-Analysis 评估口腔癌中的抗氧化酶超氧化物歧化酶 (SOD):系统回顾与元分析
4区 医学 Q3 Medicine Pub Date : 2024-03-16 DOI: 10.1155/2024/2264251
Khadijah Mohideen, Krithika Chandrasekaran, Kareema M, Jeyanthikumari T, Safal Dhungel, Snehashish Ghosh
Objective. The present article aims to comprehensively review the existing literature on superoxide dismutase (SOD) levels, an antioxidant enzyme, in oral cancer. Method. An extensive literature search was conducted across various databases, including PubMed, Wiley Online Library, Science Direct, and Cross Reference, spanning 1998–2023. At the outset, 1,177 articles were initially identified, and 907 studies were excluded due to irrelevance or duplication of the research question. Subsequently, 270 articles underwent screening evaluation, resulting in the selection of 85 articles meeting the inclusion criteria. Following this, 68 articles underwent a full-text comprehensive assessment, and ultimately, 39 were chosen for data extraction. The risk of bias in the designated articles was assessed using the Newcastle–Ottawa Scale. Finally, 13 studies were meticulously selected, offering consistent data for the ensuing meta-analysis. Meta-analysis was executed using comprehensive meta-analysis (CMA) version 3 software (Bio Stat Inc., Englewood, NJ, USA). The meta-analysis findings revealed a statistically significant decrease in SOD levels in both erythrocyte samples () and tissue samples (
研究目的本文旨在全面回顾有关口腔癌抗氧化酶--超氧化物歧化酶(SOD)水平的现有文献。方法。我们在各种数据库(包括 PubMed、Wiley Online Library、Science Direct 和 Cross Reference)中进行了广泛的文献检索,时间跨度为 1998-2023 年。首先,初步确定了 1,177 篇文章,其中 907 篇研究因与研究问题不相关或重复而被排除。随后,对 270 篇文章进行了筛选评估,最终选出 85 篇符合纳入标准的文章。随后,对 68 篇文章进行了全文综合评估,最终选出 39 篇进行数据提取。采用纽卡斯尔-渥太华量表对指定文章的偏倚风险进行了评估。最后,精心挑选出 13 项研究,为接下来的荟萃分析提供一致的数据。荟萃分析使用综合荟萃分析(CMA)第 3 版软件(Bio Stat Inc.)荟萃分析结果显示,与正常对照组相比,口腔癌(OSCC)患者红细胞样本()和组织样本()中的 SOD 水平均有统计学意义上的显著下降。相反,对唾液样本的三项研究分析表明,与健康对照组相比,口腔癌组的 SOD 含量明显增加()。结论本系统综述强调了在不同生物样本中观察到的口腔癌患者 SOD 水平的显著下降,表明氧化应激(OS)过多。需要进行更多的研究,以深入探讨口腔癌队列中 SOD 水平与临床病理预后指标之间的关系。这些研究有可能极大地促进以 OS 为基础的预后工具的开发,从而指导治疗规划策略。
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引用次数: 0
Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value 结直肠癌中的循环核酸:诊断和预后价值
4区 医学 Q3 Medicine Pub Date : 2024-02-13 DOI: 10.1155/2024/9943412
Somayeh Igder, Mozhdeh Zamani, Shima Fakher, Morvarid Siri, Hassan Ashktorab, Negar Azarpira, Pooneh Mokarram
Colorectal cancer (CRC) is the third most prevalent cancer in the world and the fourth leading cause of cancer-related mortality. DNA (cfDNA/ctDNA) and RNA (cfRNA/ctRNA) in the blood are promising noninvasive biomarkers for molecular profiling, screening, diagnosis, treatment management, and prognosis of CRC. Technological advancements that enable precise detection of both genetic and epigenetic abnormalities, even in minute quantities in circulation, can overcome some of these challenges. This review focuses on testing for circulating nucleic acids in the circulation as a noninvasive method for CRC detection, monitoring, detection of minimal residual disease, and patient management. In addition, the benefits and drawbacks of various diagnostic techniques and associated bioinformatics tools have been detailed.
结直肠癌(CRC)是世界上发病率第三高的癌症,也是导致癌症相关死亡的第四大原因。血液中的 DNA(cfDNA/ctDNA)和 RNA(cfRNA/ctRNA)是很有前途的无创生物标记物,可用于 CRC 的分子剖析、筛查、诊断、治疗管理和预后。技术的进步能够精确检测血液循环中的遗传和表观遗传异常,即使是微量的异常,也能克服其中的一些挑战。本综述将重点讨论循环核酸检测作为一种无创方法,用于 CRC 检测、监测、最小残留病检测和患者管理。此外,还详细介绍了各种诊断技术和相关生物信息学工具的优缺点。
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引用次数: 0
Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios in Distinguishing Lung Cancer in People with HIV 中性粒细胞-淋巴细胞和血小板-淋巴细胞比率在鉴别艾滋病毒感染者肺癌中的作用
4区 医学 Q3 Medicine Pub Date : 2024-01-23 DOI: 10.1155/2024/8822024
Joseph Baruch Baluku, Sharon Namiiro, Brenda Namanda, Martin Nabwana, Irene Andia-Biraro, William Worodria, Robert Salata, Sayoki Mfinanga, Stanton Gerson, Bruce Kirenga
Objective. The neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer. Methods. This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves. Results. Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38–51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14–7.71) vs. 0.92 (0.67–1.09), ). Similarly, the PLR was higher among cases than controls (237.5 (177.8–361.6) vs. 123.6 (100.6–155.4),
目的。中性粒细胞-淋巴细胞比值(NLR)和血小板-淋巴细胞比值(PLR)在区分肺癌患者和健康人方面具有良好的诊断准确性,主要是在 HIV 阴性人群中。我们测定了 NLR 和 PLR 在区分患有肺癌和未患有肺癌的 HIV 感染者(PLWH)方面的灵敏度(Se)、特异度(Sp)和曲线下面积(AUC)。方法。这是对二手数据的比较分析。病例是在乌干达癌症研究所接受治疗的患有肺癌的艾滋病病毒感染者。对照组是从乌干达三家 HIV 诊所随机抽取的未患肺癌的 PLWH。使用接收器操作特征曲线(ROC)对 Se、Sp 和 AUC 进行分析并确定最佳临界值。结果。在 115 名 PLWH(18 名病例和 97 名对照)中,83 名(72.2%)为女性,110 名(95.7%)接受了抗逆转录病毒疗法,年龄中位数(IQR)为 46(38-51)岁。病例的 NLR 中位数(IQR)高于对照组(3.53 (3.14-7.71) vs. 0.92 (0.67-1.09),)。同样,病例的 PLR 也高于对照组(237.5 (177.8-361.6) vs. 123.6 (100.6-155.4),)。以 2.44 为临界值,NLR 的 Se、Sp 和 AUC 分别为 87.5%(95% CI:61.7%-98.4%)、100%(95% CI:96.2%-100%)和 0.94(95% CI:0.85-1.00)。同样,以 196.3 为临界值,PLR 的 Se、Sp 和 AUC 分别为 75% (95% CI: 47.6%-92.7%) 、87.2% (95% CI: 78.8%-93.2%) 和 0.81 (95% CI: 0.70-0.93, )。结论NLR和PLR可区分患有肺癌和未患有肺癌的肺癌患者,对有呼吸道症状的肺癌患者很有用,因为肺癌很容易被误诊为其他肺部病变。
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引用次数: 0
Examining the Association of Rare Allelic Variants in Urate Transporters SLC22A11, SLC22A13, and SLC17A1 with Hyperuricemia and Gout 研究尿酸盐转运体 SLC22A11、SLC22A13 和 SLC17A1 的罕见等位基因变异与高尿酸血症和痛风的关系
4区 医学 Q3 Medicine Pub Date : 2024-01-06 DOI: 10.1155/2024/5930566
Jiří Vávra, Kateřina Pavelcová, Jana Mašínová, Lenka Hasíková, Eliška Bubeníková, Aneta Urbanová, Andrea Mančíková, Blanka Stibůrková
Genetic variations in urate transporters play a significant role in determining human urate levels and have been implicated in developing hyperuricemia or gout. Polymorphism in the key urate transporters, such as ABCG2, URAT1, or GLUT9 was well-documented in the literature. Therefore in this study, our objective was to determine the frequency and effect of rare nonsynonymous allelic variants of SLC22A11, SLC22A13, and SLC17A1 on urate transport. In a cohort of 150 Czech patients with primary hyperuricemia and gout, we examined all coding regions and exon–intron boundaries of SLC22A11, SLC22A13, and SLC17A1 using PCR amplification and Sanger sequencing. For comparison, we used a control group consisting of 115 normouricemic subjects. To examine the effects of the rare allelic nonsynonymous variants on the expression, intracellular processing, and urate transporter protein function, we performed a functional characterization using the HEK293A cell line, immunoblotting, fluorescent microscopy, and site directed mutagenesis for preparing variants in vitro. Variants p.V202M (rs201209258), p.R343L (rs75933978), and p.P519L (rs144573306) were identified in the SLC22A11 gene (OAT4 transporter); variants p.R16H (rs72542450), and p.R102H (rs113229654) in the SLC22A13 gene (OAT10 transporter); and the p.W75C variant in the SLC17A1 gene (NPT1 transporter). All variants minimally affected protein levels and cytoplasmic/plasma membrane localization. The functional in vitro assay revealed that contrary to the native proteins, variants p.P519L in OAT4 (), p.R16H in OAT10 (
尿酸盐转运体的基因变异在决定人体尿酸盐含量方面起着重要作用,并与高尿酸血症或痛风的发病有关。主要尿酸盐转运体(如 ABCG2、URAT1 或 GLUT9)的多态性在文献中有大量记载。因此,在本研究中,我们的目标是确定 SLC22A11、SLC22A13 和 SLC17A1 的罕见非同义等位基因变异的频率及其对尿酸盐转运的影响。在 150 名原发性高尿酸血症和痛风的捷克患者中,我们使用 PCR 扩增和 Sanger 测序技术检测了 SLC22A11、SLC22A13 和 SLC17A1 的所有编码区和外显子内含子边界。为了进行比较,我们使用了由 115 名正常尿酸血症患者组成的对照组。为了研究罕见等位基因非同义变异对尿酸盐转运蛋白的表达、胞内处理和功能的影响,我们使用 HEK293A 细胞系、免疫印迹法、荧光显微镜和体外定点诱变法对变异进行了功能表征。在 SLC22A11 基因(OAT4 转运体)中发现了变体 p.V202M(rs201209258)、p.R343L(rs75933978)和 p.P519L(rs144573306);在 SLC22A11 基因(OAT4 转运体)中发现了变体 p.R16H(rs725933978)和 p.P519L(rs144573306)。R16H(rs72542450)和 p.R102H(rs113229654);以及 SLC17A1 基因(NPT1 转运体)中的 p.W75C 变体。所有变体对蛋白质水平和细胞质/质膜定位的影响都很小。体外功能测试显示,与原生蛋白相反,OAT4()中的p.P519L变体、OAT10()中的p.R16H变体和NPT1转运体()中的p.W75C变体大大限制了尿酸盐转运活性。我们的研究结果有助于更好地了解:(1)尿酸转运体相关高尿酸血症/痛风的风险;(2)尿酸在肾脏中的处理。
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Disease Markers
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