Clinical Respiratory Journal最新文献_第4页

A Novel Scale for Diagnosis of Pulmonary Ground-Glass Nodules: A Multicenter and Ambispective Cohort Study 诊断肺磨玻璃结节的新型量表：一项多中心、前瞻性队列研究

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-11-09 DOI: 10.1111/crj.70027

Minhao Yu, Yalin Cheng, Tao Wen, Liming Zhang, Xiubo Wei, Yonghong Wang, Jiang Du, GuangKe Xie, Lei Bi

Background

A screening tool was devised to aid the diagnosis and treatment of ground-glass nodules (GGNs).

Methods

The current ambispective cohort study included retrospective collation of 20 variables synthesizing a patient's clinical characteristics, serum tumor markers, and CT results, which allowed division into noninvasive (benign, atypical adenomatous hyperplasia, and adenocarcinoma in situ) and invasive (minimally invasive and invasive adenocarcinomas) tumors to build a prediction nomogram and GGN screening scale. The model was verified internally. A prospective cohort of patients was randomly divided by envelope method into those assessed by the GGN screening scale and those assessed via CT values. The diagnostic efficiencies were compared to allow external verification of the model.

Result

A total of 223 patients with 225 GGNs were recruited into the retrospective cohort between January 2021 and December 2022. Multivariable analysis showed sex, diameter, air bronchogram, and vessel convergence sign to be independent factors for prediction of noninvasive and invasive GGNs. Internal verification showed the model had a sensitivity of 70.7% and specificity of 75.0% with the Youden index at 0.457 and area under the curve (AUC) of 0.793 (95% CI: 0.734–0.852). Calibration curves indicated good internal stability (p = 0.357). Between January 2023 and March 2023, 147 patients with 148 GGNs were recruited into the prospective cohort. External verification showed the model had a sensitivity of 92.4% and specificity of 40.0% with the Youden index at 0.324 and AUC of 0.678 (95% CI: 0.509–0.847). Calibration curves indicated good external stability (p = 0.088). The scale was shown to have a sensitivity of 75.00%, specificity of 37.50%, positive predictive value of 91.53%, negative predictive value of 14.29%, and accuracy of 71.25%.

Conclusion

The GGN screening scale has high sensitivity and accuracy, making it suitable for diagnosis of GGNs.

背景：为帮助诊断和治疗磨玻璃结节（GGN），设计了一种筛查工具：我们设计了一种筛查工具来帮助诊断和治疗磨玻璃结节（GGNs）：目前的前瞻性队列研究包括对患者的临床特征、血清肿瘤标志物和 CT 结果等 20 个变量进行回顾性整理，从而将肿瘤分为非侵袭性肿瘤（良性、非典型腺瘤性增生和原位腺癌）和侵袭性肿瘤（微侵袭性和侵袭性腺癌），以建立预测提名图和 GGN 筛查量表。该模型已经过内部验证。通过包络法将一组前瞻性患者随机分为通过 GGN 筛查量表评估的患者和通过 CT 值评估的患者。对诊断效率进行比较，以便对模型进行外部验证：结果：2021年1月至2022年12月期间，共有223名225个GGN的患者被纳入回顾性队列。多变量分析显示，性别、直径、气管造影和血管汇聚征是预测无创和有创 GGN 的独立因素。内部验证显示，该模型的灵敏度为 70.7%，特异度为 75.0%，尤登指数为 0.457，曲线下面积（AUC）为 0.793（95% CI：0.734-0.852）。校准曲线显示出良好的内部稳定性（p = 0.357）。2023 年 1 月至 2023 年 3 月期间，前瞻性队列招募了 147 名患者，其中有 148 名 GGN。外部验证显示，该模型的灵敏度为 92.4%，特异性为 40.0%，尤登指数为 0.324，AUC 为 0.678（95% CI：0.509-0.847）。校准曲线显示出良好的外部稳定性（p = 0.088）。该量表的灵敏度为 75.00%，特异度为 37.50%，阳性预测值为 91.53%，阴性预测值为 14.29%，准确度为 71.25%：GGN筛查量表具有较高的灵敏度和准确性，适用于GGN的诊断。

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引用次数: 0

Prognostic Nomogram for Predicting Survival in Asian Patients With Small-Cell Lung Cancer: A Comprehensive Population-Based Study and External Verification 预测亚洲小细胞肺癌患者生存期的预后提名图：基于人群的综合研究和外部验证。

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-11-09 DOI: 10.1111/crj.70021

Yuanli Xia, Jingjing Qu, Yufang Wang, Yanping Zhu, Jianying Zhou, Jianya Zhou

Background

The incidence of small cell lung cancer (SCLC) among Asian patients is on the rise. Nevertheless, there remains a deficiency in precise prognostic models tailored to the specific needs of this patient population. It is imperative to develop a novel nomogram aimed at forecasting the prognosis of Asian SCLC patients.

Methods

The SEER database supplied data on 661 Asian SCLC patients, who were then divided into training and internal validation sets through a random selection process. In addition, we identified 212 patients from a Chinese medical institution for the purpose of creating an external validation cohort. To forecast survival, we employed both univariate and multivariate analyses. The performance of our nomogram was assessed through calibration plots, the concordance index (C-index), and decision curve analysis (DCA).

Results

Five independent prognostic factors were determined and integrated into the nomogram. C-index values for the training and internal validation cohorts were 0.774 (95% confidence interval [CI] = 0.751–0.797) and 0.731 (95%CI = 0.690–0.772), respectively. In the external validation cohort, the C-index is 0.712 (95% CI = 0.655–0.7692). Calibration curves demonstrated highly accurate predictions. When compared to the AJCC staging system, our model exhibited improved net benefits in DCA. Furthermore, the risk stratification system effectively differentiated patients with varying survival risks.

Conclusion

We have created a novel nomogram for predicting the survival of Asian patients with SCLC. This nomogram has been subjected to external validation and has shown its superiority over the conventional TNM staging system. It offers a more precise and reliable means of forecasting the prognosis of Asian SCLC patients.

背景：小细胞肺癌（SCLC）在亚洲患者中的发病率呈上升趋势。然而，针对这一患者群体特殊需求的精确预后模型仍然不足。当务之急是开发一种新的提名图，用于预测亚洲 SCLC 患者的预后：方法：SEER数据库提供了661名亚裔SCLC患者的数据，然后通过随机选择的方法将这些患者分为训练集和内部验证集。此外，我们还从一家中国医疗机构找到了 212 名患者，以建立外部验证队列。为了预测生存率，我们采用了单变量和多变量分析。我们通过校准图、一致性指数（C-index）和决策曲线分析（DCA）对提名图的性能进行了评估：结果：确定了五个独立的预后因素，并将其整合到提名图中。训练队列和内部验证队列的 C-index 值分别为 0.774（95% 置信区间 [CI] = 0.751-0.797）和 0.731（95%CI = 0.690-0.772）。在外部验证队列中，C 指数为 0.712（95% CI = 0.655-0.7692）。校准曲线显示了高度准确的预测。与 AJCC 分期系统相比，我们的模型在 DCA 中显示出更好的净效益。此外，风险分层系统还能有效区分不同生存风险的患者：我们创建了一个新颖的提名图，用于预测亚洲 SCLC 患者的生存率。这一提名图已经过外部验证，并显示其优于传统的 TNM 分期系统。它为预测亚洲 SCLC 患者的预后提供了一种更精确、更可靠的方法。

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引用次数: 0

Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma 麦角胺以 KIF5A 为靶点促进肺腺癌的无丝分裂

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-11-08 DOI: 10.1111/crj.70020

Bin Bao, Xiaojun Yu, Wujun Zheng, Jiewei Sun

Background

Kinesin family member 5A (KIF5A) has been reported to be closely related to cancer progression. The aim of this study was to investigate the effect of KIF5A on lung adenocarcinoma (LUAD) and its potential molecular mechanisms.

Methods

Using bioinformatics analysis methods and molecular experiments, the expression of KIF5A in LUAD was analyzed, with its expression in attached and detached tumor cells assessed. Gene set enrichment analysis (GSEA) of KIF5A was carried out. The small molecular drug with the highest affinity for KIF5A was screened out through molecular docking experiments, which was validated through cellular thermal shift assay (CETSA). Quantitative polymerase chain reaction (qPCR) was employed to measure the expression levels of anoikis-repressing genes (BCL2, CAV1), as well as anoikis-inducing gene (PDCD4). CCK-8 assay was applied to examine cell viability. Cell colony formation experiments were utilized to evaluate cell proliferation ability.

Results

We observed that KIF5A was highly upregulated in LUAD tissues and cells, with a higher level detected in detached LUAD cells. By resorting to bioinformatics analysis, we discovered that KIF5A was abundant in the anoikis pathway. Knocking down KIF5A reinforced anoikis in LUAD. Further screening identified Ergotamine as the small molecular drug with the highest affinity for KIF5A. The CETSA confirmed the binding relationship between the two. In addition, Ergotamine has a promoting effect on the anoikis of LUAD, while overexpression of KIF5A reversed the effects of Ergotamine on LUAD cells.

Conclusion

This project uncovered that the small molecular drug Ergotamine targets and inhibits the expression of KIF5A. Downregulated KIF5A can enhance the anoikis of LUAD. Our results supported the inhibition of KIF5A as an attractive therapeutic strategy for LUAD. This finding provides a new innovative pathway for the treatment of LUAD and offers a strong theoretical basis for the development of therapeutic drugs targeting KIF5A.

背景：据报道，驱动蛋白家族成员 5A（KIF5A）与癌症进展密切相关。本研究旨在探讨 KIF5A 对肺腺癌（LUAD）的影响及其潜在的分子机制：方法：采用生物信息学分析方法和分子实验，分析了 KIF5A 在 LUAD 中的表达，评估了其在附着和脱落的肿瘤细胞中的表达。对KIF5A进行了基因组富集分析（GSEA）。通过分子对接实验筛选出与KIF5A亲和力最高的小分子药物，并通过细胞热转移试验（CETSA）进行验证。定量聚合酶链式反应（qPCR）用于检测抑制厌氧基因（BCL2、CAV1）和诱导厌氧基因（PDCD4）的表达水平。CCK-8 检测法用于检查细胞活力。细胞集落形成实验用于评估细胞增殖能力：结果：我们观察到 KIF5A 在 LUAD 组织和细胞中高度上调，在离体的 LUAD 细胞中检测到更高的水平。通过生物信息学分析，我们发现KIF5A在anoikis通路中含量丰富。敲除 KIF5A 会加强 LUAD 的厌氧作用。进一步筛选发现，麦角胺是与KIF5A亲和力最高的小分子药物。CETSA 证实了两者之间的结合关系。此外，麦角胺对LUAD的无丝分裂有促进作用，而KIF5A的过表达则逆转了麦角胺对LUAD细胞的影响：本项目发现小分子药物麦角胺能靶向抑制KIF5A的表达。结论：本项目发现小分子药物麦角胺能靶向抑制 KIF5A 的表达，而下调 KIF5A 能增强 LUAD 的厌氧反应。我们的研究结果支持将抑制 KIF5A 作为一种有吸引力的 LUAD 治疗策略。这一发现为治疗 LUAD 提供了一条新的创新途径，并为开发针对 KIF5A 的治疗药物提供了坚实的理论基础。

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引用次数: 0

IGF2BP3/CTCF Axis–Dependent NT5DC2 Promotes M2 Macrophage Polarization to Enhance the Malignant Progression of Lung Squamous Cell Carcinomas IGF2BP3/CTCF轴依赖性NT5DC2促进M2巨噬细胞极化，从而加强肺鳞癌的恶性进展

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-11-06 DOI: 10.1111/crj.70031

Jifeng Sun, Hao Wang, Ran Zhang, Xiaoxuan Sun, Zhanbo Wu, Jun Wang, Yuwen Wang

<div> <section> <h3> Background</h3> <p>Lung squamous cell carcinoma (LUSC) is a type of lung cancer that develops in the squamous cells. It is known to be promoted by the activation of various signaling pathways and the dysregulation of key regulatory molecules. One such molecule, 5′-nucleotidase domain containing 2 (NT5DC2), has been identified as a critical regulator in various cancers including lung cancer. However, there are no data regarding its role in LUSC.</p> </section> <section> <h3> Methods</h3> <p>The mRNA expression of insulin-like growth factor 2 mRNA–binding protein 3 (IGF2BP3), CCCTC-binding factor (CTCF), and NT5DC2 was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR), whereas their protein expression was assessed using a western blotting assay. Cell proliferation was determined using a cell counting kit-8 (CCK-8) assay. Cell apoptosis, CD11b expression, and CD206 expression were analyzed using flow cytometry. Tube formation was assessed through a tube formation assay. Glucose consumption, lactate production, and ATP levels were measured using colorimetric methods. The effect of NT5DC2 on the malignant progression of LUSC cells was analyzed using a xenograft mouse model assay. The levels of transforming growth factor-beta 1 (TGF-β1) and interleukin-10 (IL-10) were detected using enzyme-linked immunosorbent assays. The associations among IGF2BP3, CTCF and NT5DC2 were identified using dual-luciferase reporter assay, RNA immunoprecipitation assay and m6A RNA immunoprecipitation assay.</p> </section> <section> <h3> Results</h3> <p>The expression of NT5DC2 was found to be upregulated in LUSC tissues and cells when compared with normal lung tissues and normal human bronchial epithelial cells. Silencing of NT5DC2 inhibited LUSC cell proliferation, tube formation, glycolysis, M2 macrophage polarization, and tumor formation while inducing cell apoptosis. In addition, CTCF was found to transcriptionally activate NT5DC2 in LUSC cells. IGF2BP3 stabilized the mRNA expression of CTCF through m6A methylation. Further, overexpression of CTCF or NT5DC2 attenuated the effects of IGF2BP3 silencing in both NCI-520 and SK-MES-1 cells.</p> </section> <section> <h3> Conclusion</h3> <p>The IGF2BP3/CTCF axis–dependent NT5DC2 promotes M2 macrophage polarization, thereby enhancing the malignant progression of LUSC. This study was the first to reveal the role of NT5DC2 in LUSC and the underlying mechanism. The result suggests that targeting the IGF2BP3/CTCF/NT5DC2 axis may have clinical significance in the treatment of LUSC.</p>

背景：肺鳞状细胞癌（LUSC）是一种发生在鳞状细胞中的肺癌。众所周知，肺鳞状细胞癌是由各种信号通路的激活和关键调控分子的失调引起的。5'-nucleotidase domain containing 2 (NT5DC2)就是这样一种分子，它已被确定为包括肺癌在内的各种癌症的关键调节因子。然而，目前还没有关于它在肺癌中作用的数据：方法：使用实时定量聚合酶链反应（qRT-PCR）分析胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）、CCCTC 结合因子（CTCF）和 NT5DC2 的 mRNA 表达，并使用 Western 印迹分析评估它们的蛋白表达。细胞增殖用细胞计数试剂盒-8（CCK-8）测定。使用流式细胞术分析细胞凋亡、CD11b 表达和 CD206 表达。通过试管形成试验评估试管形成情况。使用比色法测量葡萄糖消耗、乳酸生成和 ATP 水平。利用异种移植小鼠模型试验分析了 NT5DC2 对 LUSC 细胞恶性进展的影响。使用酶联免疫吸附试验检测了转化生长因子-β1（TGF-β1）和白细胞介素-10（IL-10）的水平。利用双荧光素酶报告实验、RNA免疫沉淀实验和 m6A RNA 免疫沉淀实验确定了 IGF2BP3、CTCF 和 NT5DC2 之间的关联：结果：与正常肺组织和正常人支气管上皮细胞相比，NT5DC2在LUSC组织和细胞中表达上调。沉默 NT5DC2 可抑制 LUSC 细胞增殖、管形成、糖酵解、M2 巨噬细胞极化和肿瘤形成，同时诱导细胞凋亡。此外，研究还发现 CTCF 能转录激活 LUSC 细胞中的 NT5DC2。IGF2BP3 通过 m6A 甲基化稳定了 CTCF 的 mRNA 表达。此外，在 NCI-520 和 SK-MES-1 细胞中，过表达 CTCF 或 NT5DC2 可减弱 IGF2BP3 沉默的效果：结论：依赖于IGF2BP3/CTCF轴的NT5DC2促进了M2巨噬细胞的极化，从而增强了LUSC的恶性进展。该研究首次揭示了NT5DC2在LUSC中的作用及其内在机制。结果表明，靶向IGF2BP3/CTCF/NT5DC2轴可能对治疗LUSC具有临床意义。

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引用次数: 0

SIRT3 Inhibits Cell Proliferation of Nonsmall Cell Lung Carcinoma by Inducing ROS Production SIRT3 通过诱导 ROS 生成抑制非小细胞肺癌细胞增殖

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-11-05 DOI: 10.1111/crj.70033

Ze Yu, Hongtao Liao, Guanhuai Wu, Ying Liu, Guoqiang Zhang, Liang Xiao, Shuibo Yang, Jia Liu, Guocai Yang

Background

Sirtuin 3 (SIRT3) is located in the mitochondrial matrix, regulating acetylation levels of metabolic enzymes. As an oncogene or a tumor suppressor gene, SIRT3 plays an important role in the commencement and progression of certain cancers. In this research, we investigated the role of SIRT3 in the progression of nonsmall cell lung carcinoma (NSCLC).

Methods

In this study, bioinformatics was used to analyze the differential expression of SIRT3 in NSCLC tissue and normal tissues, prognosis, single-cell analysis, and related signaling pathways. The Lentiviral overexpressing SIRT3 was constructed, and CCK8 and colony formation assay were used to evaluate the NSCLC cells proliferation, ROS production was detected by flow cytometry, and the sea-horse test was used to measure cellular oxygen consumption (OCR).

Results

SIRT3 expression was significantly decreased in NSCLC, and low expression of SIRT3 was closely related to the poor prognosis. Besides, on the whole, upregulation of SIRT3 suppressed cell proliferation in A549 and SK-MES-1 cells via increasing oxidative phosphorylation (OXPHOS) and ROS production.

Conclusions

Overall, our findings suggested that SIRT3 functions as a tumor suppressor that can suppress the progression of NSCLC via stimulating ROS production.

背景：Sirtuin 3（SIRT3）位于线粒体基质中，调节代谢酶的乙酰化水平。作为癌基因或抑癌基因，SIRT3 在某些癌症的发生和发展过程中发挥着重要作用。本研究探讨了 SIRT3 在非小细胞肺癌（NSCLC）进展过程中的作用：本研究采用生物信息学方法分析了SIRT3在NSCLC组织和正常组织中的差异表达、预后、单细胞分析以及相关信号通路。构建了过表达SIRT3的慢病毒，用CCK8和集落形成试验评估NSCLC细胞的增殖，用流式细胞术检测ROS的产生，用海马试验测量细胞耗氧量（OCR）：结果：SIRT3在NSCLC中的表达明显下降，而SIRT3的低表达与预后不良密切相关。此外，从整体上看，SIRT3的上调通过增加氧化磷酸化（OXPHOS）和ROS的产生抑制了A549和SK-MES-1细胞的增殖：总之，我们的研究结果表明，SIRT3 是一种肿瘤抑制因子，可通过刺激 ROS 生成抑制 NSCLC 的进展。

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引用次数: 0

Clinical Benefits of new Systemic Therapy for Small-Cell Lung Cancer Over Two Decades: A Cross-Sectional Study 二十年来小细胞肺癌新系统疗法的临床疗效：一项横断面研究

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-10-30 DOI: 10.1111/crj.70032

Yuejing Chen, Honghong Liu, Shaohua Bai, Xuejiao Han, Fei Jin, Bo Cui

Introduction

Small cell lung cancer (SCLC) is one of the most lethal malignancies worldwide. This study aimed to examine the clinical benefits of new systemic therapies derived from randomized controlled trials (RCTs) published from 2002 to 2023 based on the magnitude of clinical benefit scale developed by the European Society for Medical Oncology (ESMO-MCBS).

Methods

We searched PubMed for Phase 3 RCTs on systemic therapy for SCLC published between January 2002 and December 2023. Therapeutic benefit was graded from 5 to 1 according to the ESMO-MCBS framework, with a score of 4 or 5 representing a meaningful clinical benefit. The statistical power of the trial design was also assessed using ESMO-MCBS.

Results

Sixty-four RCTs with 23 683 participants were eligible for inclusion. The number of RCTs related to molecular targeted therapy or immunotherapy has increased over the years. Among the 62 RCTs for which statistical power could be evaluated, 38 (61.3%) were designed to identify an effect size that would meet the ESMO-MCBS benefit threshold and were less likely to investigate second- or subsequent-line treatment (15.8% vs. 50.0%, p = 0.004), have noninferiority design (0% vs. 25.0%, p = 0.002) and set PFS (0% vs. 16.7%) or response rate (0% vs. 16.7%) as the only primary endpoint (p = 0.002). The ESMO-MCBS framework was applied in 29 RCTs reporting positive results, and only 8 (27.6%) met the threshold for a clinical benefit. The RCTs designed to detect differences that would meet the thresholds were more likely to demonstrate meaningful clinical benefit (87.5% vs. 50.0%, p = 0.099).

Conclusion

Most positive SCLC-RCTs did not meet the ESMO-MCBS threshold for meaningful clinical benefits. Strict power calculations should be adopted in the design of future RCTs.

简介小细胞肺癌（SCLC）是全球致死率最高的恶性肿瘤之一。本研究旨在根据欧洲肿瘤内科学会（ESMO-MCBS）制定的临床获益量表，研究2002年至2023年期间发表的随机对照试验（RCT）中新系统疗法的临床获益：我们在 PubMed 上检索了 2002 年 1 月至 2023 年 12 月间发表的有关 SCLC 全身疗法的 3 期 RCT。根据ESMO-MCBS框架，治疗获益从5分到1分不等，4分或5分代表有意义的临床获益。此外，还使用ESMO-MCBS评估了试验设计的统计能力：结果：64 项研究性试验、23 683 名参与者符合纳入条件。近年来，与分子靶向治疗或免疫疗法相关的研究性试验数量有所增加。在可评估统计能力的62项RCT中，有38项（61.3%）的设计旨在确定符合ESMO-MCBS获益阈值的效应大小，较少研究二线或后续治疗（15.8% vs. 50.0%，p = 0.004）、非劣效设计（0% vs. 25.0%，p = 0.002）以及将PFS（0% vs. 16.7%）或反应率（0% vs. 16.7%）作为唯一的主要终点（p = 0.002）。ESMO-MCBS框架被应用于29项报告阳性结果的研究中，只有8项（27.6%）达到了临床获益的阈值。旨在检测符合阈值的差异的 RCT 更有可能显示出有意义的临床获益（87.5% 对 50.0%，P = 0.099）：大多数SCLC-RCT阳性研究未达到ESMO-MCBS的有意义临床获益阈值。未来的 RCT 设计应采用严格的功率计算。

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引用次数: 0

Activation of Automatic Tube Compensation Mode Attenuates Auto-PEEP in Chronic Obstructive Pulmonary Disease Patients 激活自动导管补偿模式可减轻慢性阻塞性肺病患者的自动早搏。

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-10-22 DOI: 10.1111/crj.70028

Omid Moradi Moghaddam, Shahab Mohammadi, Mohsen Sedighi, Alireza Amanollahi, Behrooz Zaman, Mahzad Alimian, Mansoor Soltani, Mohammad Niakan Lahiji

Introduction

Dynamic hyperinflation in chronic obstructive pulmonary disease (COPD) results in intrinsic positive end-expiratory pressure (auto-PEEP). Automatic tube compensation (ATC) is used to increase airway pressure in COPD and overcome endotracheal tube (ETT)–imposed respiratory workload. We aim to investigate effects of ATC activation on auto-PEEP decrease in COPD.

Methods

ATC was activated three times a day (1 min duration) in the morning, evening, and night shift. Auto-PEEP was measured for the 1 min period (every 6 s) following ATC activation. Linear mixed model (LMM) was used to measure changes in auto-PEEP and compare with baseline value. Age, gender, and COPD types were inserted in model as covariates and analyzed using SPSS.

Results

A total of 60 patients including COPD (n = 40) and COPD with exacerbation (n = 20) were included. Compared with exacerbated COPD, baseline auto-PEEP in COPD was significantly lower in morning (p = 0.011), evening (p = 0.043), and night shift (p = 0.007). After ATC activation, auto-PEEP decreased significantly in COPD in morning, evening, and night (p = 0.001), but magnitude of this decrease was notably larger in COPD than in exacerbated COPD (p = 0.001). Moreover, there was a significant relationship between COPD exacerbation and changes in auto-PEEP in morning (β = −0.27, p = 0.001), evening (β = −0.16, p = 0.001), and night (β = −0.26, p = 0.001).

Conclusion

The activation of ATC mode in COPD patients under mechanical ventilation could decrease the value of auto-PEEP. Nevertheless, COPD patients with an exacerbation appear to benefit less from ATC activation.

简介：慢性阻塞性肺病（COPD）的动态过度充气会导致内在呼气末正压（auto-PEEP）。自动导管补偿（ATC）用于增加慢性阻塞性肺病患者的气道压力，克服气管导管（ETT）造成的呼吸负荷。我们的目的是研究 ATC 激活对慢性阻塞性肺病患者自动气道压力下降的影响：方法：每天早班、晚班和夜班三次启动 ATC（持续时间为 1 分钟）。在 ATC 启动后的 1 分钟内（每 6 秒）测量自动肺活量。采用线性混合模型（LMM）来测量自动肺活量的变化，并与基线值进行比较。将年龄、性别和慢性阻塞性肺病类型作为协变量加入模型，并使用 SPSS 进行分析：结果：共纳入 60 名患者，包括慢性阻塞性肺疾病（40 人）和慢性阻塞性肺疾病加重（20 人）。与病情加重的慢性阻塞性肺病患者相比，慢性阻塞性肺病患者的基线自动肺活量在早班（p = 0.011）、晚班（p = 0.043）和夜班（p = 0.007）明显较低。激活 ATC 后，慢性阻塞性肺病患者在早、晚和夜班时的自动肺活量明显下降（p = 0.001），但慢性阻塞性肺病患者的下降幅度明显大于慢性阻塞性肺病加重患者（p = 0.001）。此外，慢性阻塞性肺病加重与自动肺活量变化之间存在明显的关系：早晨（β = -0.27，p = 0.001）、傍晚（β = -0.16，p = 0.001）和夜间（β = -0.26，p = 0.001）：结论：接受机械通气的慢性阻塞性肺病患者启动 ATC 模式会降低自动肺活量（auto-PEEP）的值。然而，病情加重的慢性阻塞性肺病患者似乎从 ATC 激活中获益较少。

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引用次数: 0

Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database 根据第八版 TNM 分类法，手术在潜在可切除小细胞肺癌中的作用：美国 SEER 数据库人口研究》。

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-10-21 DOI: 10.1111/crj.70024

Xiaokang Guo, Bin Wang, Jian Sun, Ji Li, Wenxiao Jia, Hui Zhu, Hongbo Guo

Background

This study aimed to identify a specific SCLC population that would benefit from surgery.

Methods

This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan–Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer–specific survival (LCSS), respectively.

Outcomes

Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35–63 months vs. 27 months; 95% CI: 21–33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411–0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466–1.040, p = 0.078) compared with sublobar resection after PSM.

Conclusion

Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.

背景本研究旨在确定可从手术中获益的特定SCLC人群：本研究利用了从监测、流行病学和最终结果（SEER）数据库中获取的患者数据，时间跨度为2010年至2017年。为减少临床偏倚，采用了倾向得分匹配（PSM）技术。根据 AJCC 第 8 版 TNM 分类，使用 PSM 对不同队列进行了配对。采用卡普兰-梅耶法和竞争风险模型分别评估总生存期（OS）和肺癌特异性生存期（LCSS）：研究共纳入3394例可能切除的SCLC患者，其中3062例接受了放化疗，332例接受了辅助化疗的手术治疗。手术治疗与较好的生存期有关（中位生存期：49个月；95% CI：6个月）：49 个月；95% CI：35-63 个月 vs. 27 个月；95% CI：21-33 个月，P 结论：手术治疗与辅助化疗的疗效更佳：手术配合辅助化疗可明显改善早期SCLC患者的生存预后。然而，对于 II/III 期患者，应慎重考虑手术治疗。肺叶切除术在肿瘤学上等同于肺叶下切除术。

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引用次数: 0

The Relationship of Vitamin A and Neonatal Respiratory Diseases: A Meta-Analysis 维生素 A 与新生儿呼吸道疾病的关系：一项 Meta 分析。

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-10-21 DOI: 10.1111/crj.70030

Yuanyuan Li, Ruoyu Zhang, Zhongliang Li, Qingfeng Zhai

This study systematically analyzes the relationship of vitamin A on the neonatal respiratory diseases. An extensive literature search for relevant studies was conducted on PubMed, Web of Science, and so on. After screening in strict accordance with the inclusion and exclusion criteria, 12 articles on vitamin A deficiency and 12 articles on vitamin A supplementation were included. Stata 17.0 software was used to perform meta-analysis, heterogeneity test, and sensitivity analysis, and the corresponding mathematical model was used to merge the data. The meta-analysis results of the relationship between vitamin A deficiency and neonatal respiratory diseases indicated that compared with the neonates with normal vitamin A, the neonates with vitamin A deficiency had adverse health outcomes of neonatal respiratory diseases (OR = 4.86, 95% CI: 2.68–8.84), of which neonatal respiratory distress syndrome (NRDS) (OR = 4.10, 95% CI: 2.32–7.23) and neonatal pneumonia (OR = 3.22, 95% CI: 2.18–4.77) were analyzed by subgroup analysis. The meta-analysis of the relationship between vitamin A supplementation therapy and neonatal respiratory diseases showed that vitamin A supplementation was an effective therapeutic measure for neonatal respiratory diseases (RR = 1.06, 95% CI: 1.04–1.07): NRDS (RR = 1.03, 95% CI: 1.02–1.05) and NBPD (RR = 1.08, 95% CI: 1.01–1.15). The funnel chart method results show that there was publication bias in studies on vitamin A deficiency induced to and vitamin A supplementation therapy for neonatal respiratory diseases. The sensitivity analysis results showed that excluding some special article had some effect on the final pooled effect. But generally speaking, the result of meta-analysis was stable. There is a statistical correlation of vitamin A on the neonatal respiratory diseases from two aspects of etiological exploration and effect evaluation of treatment.

本研究系统分析了维生素 A 与新生儿呼吸道疾病的关系。我们在 PubMed、Web of Science 等网站上对相关研究进行了广泛的文献检索。严格按照纳入和排除标准进行筛选后，纳入了 12 篇关于维生素 A 缺乏的文章和 12 篇关于维生素 A 补充的文章。使用Stata 17.0软件进行荟萃分析、异质性检验和敏感性分析，并使用相应的数学模型合并数据。维生素 A 缺乏与新生儿呼吸系统疾病关系的荟萃分析结果表明，与维生素 A 正常的新生儿相比，维生素 A 缺乏的新生儿在新生儿呼吸系统疾病方面有不良的健康结局（OR = 4.86，95% CI：2.68-8.84），其中新生儿呼吸窘迫综合征（NRDS）（OR = 4.10，95% CI：2.32-7.23）和新生儿肺炎（OR = 3.22，95% CI：2.18-4.77）是通过亚组分析得出的。维生素 A 补充疗法与新生儿呼吸系统疾病关系的荟萃分析表明，维生素 A 补充疗法是治疗新生儿呼吸系统疾病的有效措施（RR = 1.06，95% CI：1.04-1.07）：NRDS（RR=1.03，95% CI：1.02-1.05）和NBPD（RR=1.08，95% CI：1.01-1.15）。漏斗图法结果显示，有关维生素 A 缺乏诱发新生儿呼吸系统疾病和维生素 A 补充疗法的研究存在发表偏倚。敏感性分析结果显示，排除一些特殊文章对最终的汇总效应有一定影响。但总体而言，荟萃分析的结果是稳定的。从病因探讨和治疗效果评价两个方面来看，维生素 A 对新生儿呼吸系统疾病的影响存在统计学相关性。

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引用次数: 0

Identification of a Plasma Exosomal lncRNA- and circRNA-Based ceRNA Regulatory Network in Patients With Lung Adenocarcinoma 鉴定肺腺癌患者血浆外泌体 lncRNA 和 circRNA 的 ceRNA 调控网络

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-10-20 DOI: 10.1111/crj.70026

Wangyu Zhu, Huafeng Zhang, Liwei Tang, Kexin Fang, Nawa Lin, Yanyan Huang, Yongkui Zhang, Hanbo Le

Background

Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA- and circRNA-mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive.

Methods and Results

This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA–miRNA–mRNAs/circRNA–miRNA–mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT-qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT-qPCR validated that the expression of circ-0033861, circ-0043273, and circ-0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively).

Conclusion

This study proposed a newly discovered ncRNA–miRNA–mRNA/circRNA–miRNA–mRNA ceRNA network and identified that the expression of circulating circ-0033861, circ-0043273, and circ-0011959 was up-regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.

背景：已证实外泌体富含各种长非编码RNA（lncRNA）和环状RNA（circRNA），可发挥各种生物学效应。然而，从肺腺癌（LUAD）患者血浆中提取的外泌体中，lncRNA和circRNA介导的共表达与内源性RNA（ceRNA）调控网络的竞争仍然难以捉摸：本研究招募了9名肺腺癌患者和3名健康人，利用芯片分析检测了信使RNA（mRNA）、lncRNA和circRNA的差异表达，并通过RNA测序检测了microRNA（miRNA）。此外，还应用生物信息学算法评估了 lncRNA-miRNA-mRNAs/circRNA-miRNA-mRNA 网络。通过定量反转录聚合酶链反应（RT-qPCR）鉴定了差异表达的cicRNA。与健康对照组相比，LUAD 患者血浆外泌体中共有 1016 个 lncRNA、1396 个 circRNA、45 个 miRNA 和 699 个 mRNA 存在差异表达。其中，881个lncRNA上调，135个下调；916个circRNA上调，480个下调；45个miRNA上调，无下调；591个mRNA上调，108个下调（P≤0.05，折合变化≥2）。基因本体（GO）分析和京都基因组百科全书（KEGG）通路分析揭示了差异表达的 RNA 的生物学功能。同时，RNA 网络显示了失调 RNA 之间的调控关系。最后，RT-qPCR验证了与健康对照组相比，circ-0033861、circ-0043273和circ-0011959在LUAD患者血浆外泌体中的表达上调（分别为p = 0.0327、p = 0.0002、p = 0.0437）：该研究提出了一个新发现的ncRNA-miRNA-mRNA/circRNA-miRNA-mRNA ceRNA网络，并确定了循环circ-0033861、circ-0043273和circ-0011959在LUAD患者血浆外泌体中的表达上调，为探索外泌体非编码RNA的潜在功能和确定LUAD的潜在生物标志物提供了有价值的见解。

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引用次数: 0