Clinical Respiratory Journal最新文献

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Prediction of Optimal Positive Airway Pressure in Chinese Patients With Obstructive Sleep Apnea.
IF 1.9 4区 医学
Clinical Respiratory Journal Pub Date : 2024-12-01 DOI: 10.1111/crj.70047
Feng Pang, Wenmin Deng, Jingyan Huang, Yu Guo, Minmin Lin, Xiangmin Zhang, Jie Liu
{"title":"Prediction of Optimal Positive Airway Pressure in Chinese Patients With Obstructive Sleep Apnea.","authors":"Feng Pang, Wenmin Deng, Jingyan Huang, Yu Guo, Minmin Lin, Xiangmin Zhang, Jie Liu","doi":"10.1111/crj.70047","DOIUrl":"10.1111/crj.70047","url":null,"abstract":"<p><strong>Purpose: </strong>Positive airway pressure (PAP) is the primary treatment for obstructive sleep apnea (OSA). This study aims to predict the optimal PAP pressure in Chinese OSA patients by their polysomnography (PSG) variables and demographic characteristics.</p><p><strong>Methods: </strong>Patients with an apnea-hypopnea index (AHI) ≥ 15 times/h who received PAP therapy (residual AHI < 5 times/h) and underwent PSG were included in this study. Sex, age, body mass index (BMI), Epworth Sleepiness Scale (ESS), AHI, supine AHI, lowest oxygen saturation (LSaO<sub>2</sub>), percentage of total sleep time spent with SaO<sub>2</sub> < 90% (CT90), and PAP pressure were recorded. PAP pressure and other variables were analyzed using univariate correlation and multivariate linear stepwise regression analysis.</p><p><strong>Results: </strong>A total of 167 patients were enrolled, with 122 in the study group and 45 in the validation group. Univariate correlation analysis revealed a significant correlation between PAP pressure and age, BMI, ESS, AHI, supine AHI, LSaO<sub>2</sub>, and CT90. The multivariate linear regression analysis showed that PAP pressure was correlated with gender (b = 1.142, p = 0.032), age (b = -0.039, p = 0.005), AHI (b = 0.047, p = 0.000), and CT90 (b = 0.037, p = 0.000). The final PAP pressure prediction equation was PAPpre (cmH<sub>2</sub>O) = 8.548 + 1.142 × sex -0.039 × age + 0.047 × AHI + 0.037 × CT90 (R<sup>2</sup> = 0.553) (male is defined as 0 and female as 1). This model accounts for 55.3% of the optimal pressure variance, and the area under the ROC curve of PAP prediction pressure is 0.7419.</p><p><strong>Conclusion: </strong>PSG variables can be used to predict PAP pressure in Chinese OSA patients, but for some individuals, the prediction model is not very good. PAP is correlated with age, BMI, ESS, AHI, supine AHI, LSaO<sub>2</sub>, and percentage of total sleep time spent with SaO<sub>2</sub> < 90% (CT90), which can be used to predict the optimal PAP pressure.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 12","pages":"e70047"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883675","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
A Nomogram for Predicting Recurrence in Stage I Non-Small Cell Lung Cancer 预测 I 期非小细胞肺癌复发的提名图
IF 1.9 4区 医学
Clinical Respiratory Journal Pub Date : 2024-11-24 DOI: 10.1111/crj.70022
Rongrong Bian, Feng Zhao, Bo Peng, Jin Zhang, Qixing Mao, Lin Wang, Qiang Chen
{"title":"A Nomogram for Predicting Recurrence in Stage I Non-Small Cell Lung Cancer","authors":"Rongrong Bian,&nbsp;Feng Zhao,&nbsp;Bo Peng,&nbsp;Jin Zhang,&nbsp;Qixing Mao,&nbsp;Lin Wang,&nbsp;Qiang Chen","doi":"10.1111/crj.70022","DOIUrl":"https://doi.org/10.1111/crj.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early-stage non–small cell lung cancer (NSCLC) is being diagnosed increasingly, and in 30% of diagnosed patients, recurrence will develop within 5 years. Thus, it is urgent to identify recurrence-related markers to optimize the management of patient-tailored therapeutics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The eligible datasets were downloaded from TCGA and GEO. In the discovery phase, two algorithms, least absolute shrinkage and selector operation and support vector machine-recursive feature elimination, were used to identify candidate genes. The recurrence-associated signature was developed by penalized Cox regression. The nomogram was constructed and further tested via other independent cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this retrospective study, 14 eligible datasets and 7 published signatures were included. A 13-gene based signature was generated by penalized Cox regression categorized training cohort into high-risk and low-risk subgroups (HR = 8.873, 95% CI: 4.228–18.480 <i>p</i> &lt; 0.001). Furthermore, a nomogram integrating the recurrence-related signature, age, and histology was developed to predict the recurrence-free survival in the training cohort, which performed well in the two external validation cohorts (concordance index: 0.737, 95% CI: 0.732–0.742, <i>p</i> &lt; 0.001; 0.666, 95% CI: 0.650–0.682, <i>p</i> &lt; 0.001; 0.651, 95% CI: 0.637–0.665, <i>p</i> &lt; 0.001, respectively). The nomogram was further performed well in the Jiangsu cohort enrolled 163 patients (HR = 2.723, 95% CI: 1.526–4.859, <i>p</i> = 0.001). Post-operative adjuvant therapy achieved evaluated disease-free survival in high and intermediate risk groups (HR = 4.791, 95% CI: 1.081–21.231, <i>p</i> = 0.039).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed nomogram is a promising tool for estimating recurrence-free survival in stage I NSCLC, which might have tremendous value in management of early stage NSCLC and guiding adjuvant therapy strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142707982","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
Highly Sensitive and Specific Panels of Plasma Exosomal microRNAs for Identification of Malignant Pulmonary Nodules 用于鉴定恶性肺结节的高灵敏度和特异性血浆外泌体 microRNA 小组。
IF 1.9 4区 医学
Clinical Respiratory Journal Pub Date : 2024-11-15 DOI: 10.1111/crj.70034
Rui Tao, Dandan Wang, Wenjing Pei, Yanfei Liu, Pengcheng Liu, Renming Li, Jiegou Xu, Jing Ye, Dahai Zhao
{"title":"Highly Sensitive and Specific Panels of Plasma Exosomal microRNAs for Identification of Malignant Pulmonary Nodules","authors":"Rui Tao,&nbsp;Dandan Wang,&nbsp;Wenjing Pei,&nbsp;Yanfei Liu,&nbsp;Pengcheng Liu,&nbsp;Renming Li,&nbsp;Jiegou Xu,&nbsp;Jing Ye,&nbsp;Dahai Zhao","doi":"10.1111/crj.70034","DOIUrl":"10.1111/crj.70034","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;With wide application of computed tomography (CT) in early lung cancer screening, solitary pulmonary nodules (SPNs) are frequently detected. Due to their high etiological diversity and potential for malignancy, rapid and accurate identification and malignant SPNs are crucial in the clinical management. In the present study, plasma exosomal microRNAs were identified and evaluated as sensitive and specific indicators for malignant SPNs.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Exosomal miRNAs isolated from the plasmas of pathologically confirmed patients with SPN (four malignant and four benign, designated as the screening set) were subjected for high throughput sequencing and eight candidate miRNAs were selected. The pre-operation plasma levels of the candidate miRNAs in 77 patients with SPN (48 malignant and 29 benign, designated as the identification set) were detected by quantitative PCR, five miRNAs were identified as potential biomarkers for malignant SPNs, and the diagnostic values of the five miRNAs each alone or combined were then analyzed by AUROC analysis. The prediction values of the identified miRNAs were further evaluated in 95 patients with SPN (double blind, 74 malignant and 21 benign, designated as the validation set).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;High-throughput sequencing identified 45 miRNAs with statistical differences between benign and malignant SPNs. Among the eight candidate miRNAs in the identification set, miR-1-3p alone had the best diagnostic value, with the sensitivities and specificities of 89.6% and 100% for malignant SPNs. Unexpectedly, when miR-1-3p was combined with miR-99a-5p, both the sensitivity and specificity reached 100% for malignant SPNs. miR-1-3p+miR-125b-5p and miR-1-3p+miR-218-5p were also good indicators of malignant SPNs with sensitivities of 95.8% and 97.9%, specificities of 100% and 96.6%. Further analysis of these microRNA combinations in the validation set indicated that the PPV were 91.4%, 97.4%, and 93.5% and the NPV were 100%, 100%, and 88.9% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, with the sensitivities were 100%, 100%, and 97.3% and the specificities were 66.7%, 90.5%, and 76.2% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, respectively.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Through high throughput sequencing, qPCR determination of plasma microRNAs and AUROC analysis, miR-1-3p combined with miR-99a-5p, miR-125b-5p, or miR-218-5p have been found to be ","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645232","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
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
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
{"title":"A Novel Scale for Diagnosis of Pulmonary Ground-Glass Nodules: A Multicenter and Ambispective Cohort Study","authors":"Minhao Yu,&nbsp;Yalin Cheng,&nbsp;Tao Wen,&nbsp;Liming Zhang,&nbsp;Xiubo Wei,&nbsp;Yonghong Wang,&nbsp;Jiang Du,&nbsp;GuangKe Xie,&nbsp;Lei Bi","doi":"10.1111/crj.70027","DOIUrl":"10.1111/crj.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A screening tool was devised to aid the diagnosis and treatment of ground-glass nodules (GGNs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>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 (<i>p</i> = 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 (<i>p</i> = 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%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The GGN screening scale has high sensitivity and accuracy, making it suitable for diagnosis of GGNs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633056","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
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
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
{"title":"Prognostic Nomogram for Predicting Survival in Asian Patients With Small-Cell Lung Cancer: A Comprehensive Population-Based Study and External Verification","authors":"Yuanli Xia,&nbsp;Jingjing Qu,&nbsp;Yufang Wang,&nbsp;Yanping Zhu,&nbsp;Jianying Zhou,&nbsp;Jianya Zhou","doi":"10.1111/crj.70021","DOIUrl":"10.1111/crj.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633066","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
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
Clinical Respiratory Journal Pub Date : 2024-11-08 DOI: 10.1111/crj.70020
Bin Bao, Xiaojun Yu, Wujun Zheng, Jiewei Sun
{"title":"Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma","authors":"Bin Bao,&nbsp;Xiaojun Yu,&nbsp;Wujun Zheng,&nbsp;Jiewei Sun","doi":"10.1111/crj.70020","DOIUrl":"10.1111/crj.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633062","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
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
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
{"title":"IGF2BP3/CTCF Axis–Dependent NT5DC2 Promotes M2 Macrophage Polarization to Enhance the Malignant Progression of Lung Squamous Cell Carcinomas","authors":"Jifeng Sun,&nbsp;Hao Wang,&nbsp;Ran Zhang,&nbsp;Xiaoxuan Sun,&nbsp;Zhanbo Wu,&nbsp;Jun Wang,&nbsp;Yuwen Wang","doi":"10.1111/crj.70031","DOIUrl":"10.1111/crj.70031","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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.&lt;/p&gt;\u0000 ","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590977","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
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
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
{"title":"SIRT3 Inhibits Cell Proliferation of Nonsmall Cell Lung Carcinoma by Inducing ROS Production","authors":"Ze Yu,&nbsp;Hongtao Liao,&nbsp;Guanhuai Wu,&nbsp;Ying Liu,&nbsp;Guoqiang Zhang,&nbsp;Liang Xiao,&nbsp;Shuibo Yang,&nbsp;Jia Liu,&nbsp;Guocai Yang","doi":"10.1111/crj.70033","DOIUrl":"10.1111/crj.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, our findings suggested that SIRT3 functions as a tumor suppressor that can suppress the progression of NSCLC via stimulating ROS production.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584939","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
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
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
{"title":"Clinical Benefits of new Systemic Therapy for Small-Cell Lung Cancer Over Two Decades: A Cross-Sectional Study","authors":"Yuejing Chen,&nbsp;Honghong Liu,&nbsp;Shaohua Bai,&nbsp;Xuejiao Han,&nbsp;Fei Jin,&nbsp;Bo Cui","doi":"10.1111/crj.70032","DOIUrl":"10.1111/crj.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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%, <i>p</i> = 0.004), have noninferiority design (0% vs. 25.0%, <i>p</i> = 0.002) and set PFS (0% vs. 16.7%) or response rate (0% vs. 16.7%) as the only primary endpoint (<i>p</i> = 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%, <i>p</i> = 0.099).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 11","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549042","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
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
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
{"title":"Activation of Automatic Tube Compensation Mode Attenuates Auto-PEEP in Chronic Obstructive Pulmonary Disease Patients","authors":"Omid Moradi Moghaddam,&nbsp;Shahab Mohammadi,&nbsp;Mohsen Sedighi,&nbsp;Alireza Amanollahi,&nbsp;Behrooz Zaman,&nbsp;Mahzad Alimian,&nbsp;Mansoor Soltani,&nbsp;Mohammad Niakan Lahiji","doi":"10.1111/crj.70028","DOIUrl":"10.1111/crj.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 60 patients including COPD (<i>n</i> = 40) and COPD with exacerbation (<i>n</i> = 20) were included. Compared with exacerbated COPD, baseline auto-PEEP in COPD was significantly lower in morning (<i>p</i> = 0.011), evening (<i>p</i> = 0.043), and night shift (<i>p</i> = 0.007). After ATC activation, auto-PEEP decreased significantly in COPD in morning, evening, and night (<i>p</i> = 0.001), but magnitude of this decrease was notably larger in COPD than in exacerbated COPD (<i>p</i> = 0.001). Moreover, there was a significant relationship between COPD exacerbation and changes in auto-PEEP in morning (<i>β</i> = −0.27, <i>p</i> = 0.001), evening (<i>β</i> = −0.16, <i>p</i> = 0.001), and night (<i>β</i> = −0.26, <i>p</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513364","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
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