Respiratory Research最新文献

{"title":"All-cause and cause-specific mortality in respiratory symptom clusters: a population-based multicohort study.","authors":"Daniil Lisik, Helena Backman, Hannu Kankaanranta, Rani Basna, Linnea Hedman, Linda Ekerljung, Fredrik Nyberg, Anne Lindberg, Göran Wennergren, Eva Rönmark, Bright Nwaru, Lowie Vanfleteren","doi":"10.1186/s12931-025-03224-7","DOIUrl":"https://doi.org/10.1186/s12931-025-03224-7","url":null,"abstract":"<p><strong>Background: </strong>Respiratory symptoms are common in the general adult population. Increased burden of respiratory symptoms may increase the risk of mortality. We assessed the association between respiratory symptom clusters and mortality.</p><p><strong>Methods: </strong>Participants were derived from two population-based Swedish adult cohorts (N = 63,060). Cluster analysis was performed with Locality Sensitive Hashing (LSH)-k-prototypes in subjects with ≥ 1 self-reported respiratory symptom. Linked mortality register data (up to 21 years of follow-up, > 600,000 person-years) were used. Associations between clusters and all-cause/cause-specific mortality were assessed using asymptomatic subjects as reference.</p><p><strong>Results: </strong>Over 60% reported ≥ 1 respiratory symptom and ~ 30% reported ≥ 5 respiratory symptoms. Five clusters were identified, partly overlapping with established respiratory disease phenotypes but many individuals were undiagnosed: (1) \"low-symptomatic\" (30.3%); (2) \"allergic nasal symptoms\" (10.7%); (3) \"allergic nasal symptoms, wheezing, and dyspnea attacks\" (4.7%); (4) \"wheezing and dyspnea attacks\" (6.6%); (5) \"recurrent productive cough and wheezing\" (4.1%). All but Cluster 2 were associated with all-cause mortality, highest risk for Cluster 3 (hazard ratio 1.4, 95% confidence interval 1.13-1.73) and Cluster 5 (1.4, 1.22-1.61). Comparable associations were seen for cardiovascular mortality. For respiratory mortality, Cluster 4 (2.02, 1.18-3.46) and Cluster 5 (1.89, 1.1-3.25) were most strongly associated.</p><p><strong>Conclusions: </strong>Respiratory symptoms are common in the general adult population, with identifiable clusters. These clusters have clinical relevancy as they are differentially associated with mortality and relatively weakly correlated with diagnosed respiratory disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"150"},"PeriodicalIF":5.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association and impact of radiographic, pathological emphysema and spirometric airway obstruction on patients with resectable lung adenocarcinoma.","authors":"Yixiao Zhang, Lu Lang, Xiaojuan Guo, Kewu Huang, Jiawen Yi, Yuan Yuan, Min Zhu, Shu Zhang, Bin Hu, Xue Li, Yuhui Zhang","doi":"10.1186/s12931-025-03225-6","DOIUrl":"https://doi.org/10.1186/s12931-025-03225-6","url":null,"abstract":"<p><strong>Background: </strong>Destruction of alveoli structure and lung function are interrelated, however, their correlation and clinical significance have been not well defined in patients with lung cancer. Thus, this study aimed to examine the association among radiographic, pathological emphysema and spirometric airway obstruction in patients with resectable lung cancer as well as explore their impact on postoperative pulmonary complications (PPCs) and long-term prognosis.</p><p><strong>Methods: </strong>Lung adenocarcinoma (LUAD) patients who performed chest CT, spirometry, and curative resection were included from a prospective three-institution database. CT-defined emphysema at baseline was assessed visually and quantitatively, pathological emphysema was reviewed on postoperative specimen. Multivariable regression models, propensity score matching, stratified analysis, and subgroup analysis were adopted to reduce selection bias.</p><p><strong>Results: </strong>Our cohort included 902 patients, with a median follow-up of 5.6 years. CT-defined emphysema was present in 163 patients (18.1%) and most of them (86.5%) were validated with pathological evidence. 169 had spirometric airway obstruction, while only 29.6% patients overlapped with CT-defined emphysema. Multivariable logistic regression models showed CT-defined emphysema, not airway obstruction, was associated with an increased risk of PPCs (adjusted odds ratio, 2.35; 95% CI, 1.40-3.93; P = 0.001). After adjusting for age, sex, body mass index, smoking history, tumour stage, vascular invasion, pleural invasion, multivariate cox analysis identified CT-defined emphysema, not airway obstruction, as an independent prognostic factor for OS (adjusted hazard ratio, 1.44; 95%CI, 1.05-1.97; P = 0.022). Patients with both radiographic and pathological emphysema experienced worse OS (log-rank P < 0.001). In the propensity score-matched cohort, stratified analysis, and never-smokers subgroup analysis, CT-defined emphysema remained a strong and statistically significant factor related to poor survival.</p><p><strong>Conclusions: </strong>The presence of radiological and pathological emphysema in resectable LUAD was associated with frequent PPCs and decreased survival.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"151"},"PeriodicalIF":5.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances and applications of biosensors in pulmonary hypertension.","authors":"Zhi Liu, Zhuojun Bai, Xiang Chen, Yajie Chen, Zhu Chen, Li Wang, Yi He, Yuan Guo","doi":"10.1186/s12931-025-03221-w","DOIUrl":"https://doi.org/10.1186/s12931-025-03221-w","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a serious disease characterized by elevated pulmonary artery pressure, with its prevalence and incidence continuously increasing, posing a threat to the lives of many patients worldwide. Due to the complex etiology of PH and the lack of specificity in clinical manifestations, there is currently a lack of effective and specific methods for early diagnosis in clinical practice. Biosensors hold significant promise for the early detection, therapeutic monitoring, prognostic evaluation, and personalized treatment of PH, owing to their rapid, sensitive, and highly selective characteristics. The rapid development of various types of biosensors, such as electrochemical biosensors, optical biosensors, microfluidic biosensors, and wireless biosensors, combined with the use of nanomaterials, makes the rapid and accurate detection of PH-related biomarkers possible. Despite the broad application prospects of biosensors in the field of PH, challenges remain in terms of sensitivity, selectivity, stability, and regulation. This article reviews the main pathophysiological mechanisms and commonly used biomarkers of PH, the types and principles of biosensors, and summarizes the progress of biosensors in PH research as well as the current challenges, in order to promote further in-depth research and the development of biosensor technology, thereby improving the diagnosis and treatment effects of PH. Clinical trial number: Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"147"},"PeriodicalIF":5.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered maturation and activation state of circulating monocytes is associated with their enhanced recruitment in pulmonary arterial hypertension.","authors":"Rebecca L Harper, Xin Zhou, David P Marciano, Aiqin Cao, Lingli Wang, Guibin Chen, Mir S Adil, Wenyu Zhou, Peter Maguire, Shanthi Deivanayagam, Quan Yu, Vignesh Viswanathan, Dan Yang, Marcy Martin, Sarasa Isobe, Shoichiro Otsuki, Jordan Burgess, Audrey Inglis, Devon Kelley, Patricia A Del Rosario, Andrew Hsi, Francois Haddad, Roham T Zamanian, Manfred Boehm, Michael P Snyder, Marlene Rabinovitch","doi":"10.1186/s12931-025-03182-0","DOIUrl":"https://doi.org/10.1186/s12931-025-03182-0","url":null,"abstract":"<p><strong>Background: </strong>It is well-established that patients with pulmonary arterial hypertension (PAH) exhibit increased recruitment of circulating monocytes to their pulmonary arteries. However, it remains unclear whether these monocytes have intrinsic abnormalities that contribute to their recruitment and to PAH pathogenesis. This study aimed to characterize the gene expression profiles of circulating classical, intermediate, and non-classical monocytes and assess their maturation trajectory in patients with idiopathic (I) PAH compared to control subjects. Additionally, it sought to explore the relationship between the observed IPAH abnormalities and deficiencies in bone morphogenetic receptor 2 (BMPR2), the most frequently mutated gene in PAH, and to assess adhesion and transendothelial migration, key processes in monocyte infiltration of pulmonary arteries.</p><p><strong>Methods: </strong>Differentially expressed genes and maturation trajectories of circulating monocytes from patients with IPAH vs. control subjects were compared using single cell RNA sequencing (scRNAseq), followed by FACS analysis. Observations from IPAH and control cells were related to reduced BMPR2 using a THP1 monocyte cell line with BMPR2 reduced by siRNA as well as induced pluripotent stem cell (iPSC) derived monocytes (iMono) from hereditary (H) PAH patients with a BMPR2 mutation and monocytes from mice with Bmpr2 deleted (MON-Bmpr2^-/-).</p><p><strong>Results: </strong>Classical IPAH monocytes have decreased CD14 mRNA leading to a deviation in their maturation trajectory and early terminal fate, which is not rescued by cytokine treatment. Monocytes that evade early cell death show elevated STAT1, PPDPF and HLA-B, and an interferon (IFN) signature indicative of an altered activation state. A strong link between decreased BMPR2 and CD14 was observed in THP1 cells and in HPAH iMono with a BMPR2 mutation associated with STAT1 and IFN related genes, and in monocytes from MON-Bmpr2^-/- mice. Increased adhesion to iPSC-derived endothelial cells (iECs) in HPAH-BMPR2 mutant iMono was associated with elevated ICAM1 expression. Enhanced transendothelial migration of these cells was associated with the reduction in endothelial VE-cadherin (CDH5).</p><p><strong>Conclusions: </strong>IPAH monocytes exhibit an altered activation state associated with reduced BMPR2 and CD14, along with elevated STAT1-IFN expression. These changes are linked to intrinsic functional abnormalities that contribute to the monocytes' increased propensity to invade the pulmonary circulation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"148"},"PeriodicalIF":5.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prevalence of pathogenic variants in the BMPR2 gene in patients with the idiopathic pulmonary arterial hypertension in the Russian population: sequencing data and meta-analysis.","authors":"Galina Okhrimenko, Irina Borovikova, Elena Dankovtseva, Vladimir Zamyatin, Dmitry Nikulin, Ekaterina Zobova, Anna Lyzhenkova, Anna Danilova, Natalia Osipova, Larisa Minushkina, Dmitry Zateyshchikov, Maria Poptsova","doi":"10.1186/s12931-025-03214-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03214-9","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary arterial hypertension (IPAH) is a rare and severe form of pulmonary hypertension, with a genetic basis most commonly associated with mutations in the BMPR2 gene. However, no genetic testing has been reported for IPAH patients in the Russian population, nor have systematic studies been conducted to assess the frequency of pathogenic variants in this group.</p><p><strong>Methods: </strong>The study cohort included 105 IPAH patients, consisting of 23 males and 82 females, who were managed at the PH care center in Moscow, Russia, from 2014 to 2024. Genetic testing was performed using whole-genome sequencing. Variant identification and annotation were conducted using GATK, DeepVariant, VEP, sv-callers and AnnotSV. A meta-analysis, performed with MOOSE, included 24 studies involving 3124 IPAH patients and 470 P/LP variants. Pathogenicity reassessment was carried out using InterVar, which incorporates ACMG criteria.</p><p><strong>Results: </strong>Analysis of 105 adult IPAH patients in Russia revealed 11 patients (10.48%) as carriers of pathogenic or likely pathogenetic (P/LP) BMPR2 variants. As the result of reassessment, the number of P/LP BMPR2 variants raised from 394 (59%) to 445 (67%) with 80 pathogenic variants became of uncertain significance, and 152 unclassified variants became P/LP. The meta-analysis of these reevaluated pathogenic variants showed that while the frequency of P/LP variants in our cohort (10.48%) is lower than the overall average of 17.75% from the meta-analysis, the difference is not statistically significant (p = 0.062). Additionally, we report three P/LP BMPR2 variants, not reported in literature, with one being structural, and four P/LP variants in TBX4, ATP13A3 and AQP1 genes from 27 IPAH genes in 3 patients.</p><p><strong>Conclusions: </strong>For the first time, we present the results of genetic testing in IPAH patients from the Russian population. Despite the considerable heterogeneity in the world-wide data, the prevalence of pathogenic BMPR2 mutations in IPAH patients from the Russian population does not significantly differ from the overall average in the meta-analysis. It is crucial to periodically reassess the pathogenicity of published variants, as half of the pathogenic BMPR2 IPAH variants were reclassified as LP or of uncertain significance.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"146"},"PeriodicalIF":5.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A LncRNA panel within EpCAM-specific exosomes for noninvasive early diagnosing non-small cell lung cancer.","authors":"Linyuan Liu, Danlei Li, Amei Zhuo, Jiachun Lu, Jianjun Zou, Guitian Huang, Zhaoting Hu, Zili Zhang, Yibin Deng, Lei Yang","doi":"10.1186/s12931-025-03220-x","DOIUrl":"https://doi.org/10.1186/s12931-025-03220-x","url":null,"abstract":"<p><strong>Background: </strong>Plasma tumor-associated exosomes represent a promising source for cancer biomarkers; however, the role of long non-coding RNAs (lncRNAs) within these exosomes is not well-defined in non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>We identified a panel of NSCLC-specific lncRNAs within plasma EpCAM-specific exosomes (Epexo) through a comparative analysis of lncRNA profiles between plasma Epexo and lung tissues. The panel's diagnostic value was firstly evaluated in a retrospective cohort of 210 NSCLC patients and 245 healthy controls, and validated in a prospective cohort of 192 patients with pulmonary nodules (nodule size < 3 cm in diameter). The evaluation utilized the area under the ROC curve (AUC) based on a random forest model. For precision, repeat testing was conducted with 31 randomly selected samples. Additionally, 39 paired tissue-plasma samples were employed to assess the concordance of lncRNA expression between tissue and plasma within the same individuals.</p><p><strong>Results: </strong>The panel, including linc01125, HNF1A-AS1, MIR100HG, linc01160, and ZNRF3-AS1, demonstrated superior capability in distinguishing early-stage NSCLC patients from controls, achieving AUC values of 0.805 and 0.856 in the discovery and validation set, respectively. The panel also showed potential for differentiating adenocarcinoma and squamous cell carcinoma. Repeat sample testing showed a consistency of 90.3% for this panel. The expression levels of MIR100HG and HNF1A-AS1 showed significant correlations between plasma Epexo and cancerous tissues.</p><p><strong>Conclusions: </strong>The identified lncRNA panel, consisting of linc01125, HNF1A-AS1, MIR100HG, linc01160, and ZNRF3-AS1, presents a promising diagnostic tool for NSCLC.</p><p><strong>Clinical trial number: </strong>not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"144"},"PeriodicalIF":5.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum and exosome WNT5A levels as biomarkers in non-small cell lung cancer.","authors":"Zsofia Torok, Kitti Garai, Judit Bovari-Biri, Zoltan Adam, Judith A Miskei, Bela Kajtar, Veronika Sarosi, Judit E Pongracz","doi":"10.1186/s12931-025-03216-7","DOIUrl":"https://doi.org/10.1186/s12931-025-03216-7","url":null,"abstract":"<p><strong>Background: </strong>Despite significant advances in the treatment of lung cancer (LC), there are no reliable biomarkers to effectively predict therapy response and overall survival (O/S) in non-small cell lung cancer (NSCLC) subtypes. While targeted therapies have improved survival rates in lung adenocarcinoma (LUAD), effective treatment options for lung squamous cell carcinoma (LUSC) are still limited. Recent evidence indicates that exosome-bound WNT5A may significantly contribute to disease progression. Our study assessed the WNT5A protein as a potential biomarker for diagnosing patients and predicting prognosis to assist in therapy selection.</p><p><strong>Methods: </strong>Primary tumor tissue and serum samples were collected from a cohort of 60 patients with histologically confirmed NSCLC before therapy. Healthy serum donors served as controls. Exosomes were isolated, then exosome number and size were measured, and WNT5A protein levels were identified in tissue and in vesicle-free, vesicle-bound fractions of the serum by ELISA.</p><p><strong>Results: </strong>Extensive statistical analysis (ROC, AUC, Cox, etc.) revealed that elevated WNT5A levels on the serum-exosome surface correlated with distant metastasis, advanced disease stage, and lymph node involvement in LUSC but not in LUAD patients. Moreover, a high WNT5A exosome surface expression was associated with a poor response to therapy and shorter O/S in LUSC patients. Additionally, serum-exosome surface + cargo WNT5A content distinguished LUAD and LUSC subtypes.</p><p><strong>Conclusions: </strong>WNT5A, particularly its serum exosome-bound form, may serve as a valuable biomarker after further validation for differentiating NSCLC subtypes and predicting disease progression. Importantly, the information can become available from a simple serum sample at the time of diagnosis.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"141"},"PeriodicalIF":5.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative eQTL and Mendelian randomization analysis reveals key genetic markers in mesothelioma.","authors":"Jinsong Li, Xingmeng Wang, Yaru Lin, Zhengliang Li, Wei Xiong","doi":"10.1186/s12931-025-03219-4","DOIUrl":"https://doi.org/10.1186/s12931-025-03219-4","url":null,"abstract":"<p><strong>Background: </strong>Mesothelioma is a rare cancer that originates from the pleura and peritoneum, with its incidence increasing due to asbestos exposure. Patients are frequently diagnosed at advanced stages, resulting in poor survival rates. Therefore, the identification of molecular markers for early detection and diagnosis is essential.</p><p><strong>Methods: </strong>Three mesothelioma datasets were downloaded from the GEO database for differential gene expression analysis. Instrumental variables (IVs) were identified based on expression quantitative trait locus (eQTL) data for Mendelian randomization (MR) analysis using mesothelioma Genome-Wide Association Study (GWAS) data from the FINNGEN database. The intersecting genes from MR-identified risk genes and differentially expressed genes were identified as key co-expressed genes for mesothelioma. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), as well as immune cell correlation analysis, were performed to elucidate the roles of key genes in mesothelioma. Additionally, the differential expression of key genes in mesothelioma was validated in independent GEO datasets and TCGA datasets. This integrative research combining multiple databases and analytical methods established a robust model for identifying mesothelioma risk genes.</p><p><strong>Results: </strong>The research conducted in our study identified 1608 genes that were expressed differentially in mesothelioma GEO datasets. By combining these genes with 192 genes from MR analysis, we identified 14 key genes. Notably, MPZL1, SOAT1, TACC3, and CYBRD1 are linked to a high risk of mesothelioma, while TGFBR3, NDRG2, EPAS1, CPA3, MNDA, PRKCD, MTUS1, ALOX15, LRRN3, and ITGAM are associated with a lower risk. These genes were found to be enriched in pathways associated with superoxide metabolism, cell cycle regulation, and proteasome function, all of which are linked to the development of mesothelioma. Noteworthy observations included a significant infiltration of M1 macrophages and CD4 + T cells in mesothelioma, with genes SOAT1, MNDA, and ITGAM showing a positive correlation with the level of M1 macrophage infiltration. Furthermore, the differential expression analyses conducted on the GEO validation set and TCGA data confirmed the significance of the identified key genes.</p><p><strong>Conclusion: </strong>This integrative eQTL and Mendelian randomization analysis provides evidence of a positive causal association between 14 key co-expressed genes and mesothelioma genetically. These disease critical genes are implicated in correlations with biological processes and infiltrated immune cells related to mesothelioma. Moreover, our study lays a theoretical foundation for further research into the mechanisms of mesothelioma and potential clinical applications.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"140"},"PeriodicalIF":5.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of tumor cell proliferation (Ki-67) and cell cycle regulator proteins in lung adenocarcinoma with different radiological subtypes.","authors":"Rirong Qu, Yang Zhang, Shenghui Qin, Jing Xiong, Xiangning Fu, Lequn Li, Dehao Tu, Yixin Cai","doi":"10.1186/s12931-025-03217-6","DOIUrl":"https://doi.org/10.1186/s12931-025-03217-6","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of ground glass opacity featured lung adenocarcinomas (GGO-LUAD) is significantly better than that of solid nodule featured lung adenocarcinomas (SN-LUAD), but the underlying reasons remain unclear. Ki-67 and cell cycle regulator proteins are highly expressed in many cancers and linked to prognosis. This study aims to investigate their differential expression in LUAD with different radiological subtypes.</p><p><strong>Methods: </strong>Patients with resected pathological stage 0-III LUAD in our department between July 2019 and March 2022 were retrospectively reviewed. All included patients were divided into four groups based on different consolidation-to-tumour ratio (CTR), we focuses on evaluating the differential expression of Ki-67 and cell cycle regulatory proteins (CCNA2, CCNB1, CCND1, P16, P21, TOP2A, TP53, and pRb) in LUAD with different CTR.</p><p><strong>Results: </strong>A total of 481 patients were included, 108 in the pure ground glass opacity (PGGO, CTR = 0) group, 103 in the GGO-dominant (GGO-D, 0 < CTR ≤ 0.5) group, 74 in the SN-dominant (SN-D, 0.5 < CTR < 1) group, and 196 in the pure solid nodule (SN, CTR = 1) group. The expression of Ki-67 was significantly higher in elderly patients (P < 0.05), former or current smokers (P < 0.0001), males (P < 0.05), poorly differentiated tumors (P < 0.0001), and tumors with spread through air spaces (STAS) (P < 0.0001), and advanced stage tumors (P < 0.0001). Regardless of age, gender, smoking status and epidermal growth factor receptor (EGFR) mutation status, GGO-LUAD demonstrated significantly lower expression of Ki-67 compared to SN-LUAD. The expression of Ki-67 and cell cycle regulatory proteins (except P21) were significantly lower in the PGGO, GGO-D, SN-D than in the SN group. However, there was no significant difference in the expression of Ki-67 and cell cycle regulatory proteins among the PGGO, GGO-D, and SN-D groups.</p><p><strong>Conclusions: </strong>GGO-LUAD demonstrated significantly lower expression of Ki-67 and cell cycle regulatory proteins compared to SN-LUAD, which may explain the reasons behind the excellent prognosis of GGO-LUAD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"138"},"PeriodicalIF":5.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEG spectral analysis of nighttime sleep and daytime MSLTs and neurocognitive evaluations in subjects with co-morbid insomnia and OSA.","authors":"Yuan Shi, Yuru Nie, Fengyi Hao, Xujun Feng, Ye Zhang, Larry D Sanford, Rong Ren, Xiangdong Tang","doi":"10.1186/s12931-025-03193-x","DOIUrl":"https://doi.org/10.1186/s12931-025-03193-x","url":null,"abstract":"<p><strong>Background: </strong>Chronic insomnia and obstructive sleep apnea commonly co-occur. Few studies have explored the neurophysiological and neurocognitive characteristics of COMISA, which could help guide improving treatment diagnostic tools and determining novel therapeutic targets. This study aims to explore the neurophysiological and neurocognitive characteristics of COMISA using electroencephalographic (EEG) spectral analysis and subjective and objective neurocognitive measurements.</p><p><strong>Methods: </strong>Participants were from our community recruited OSA-insomnia-COMISA cohort with 206 included for our current analysis including 74 chronic insomniacs (CIs), 55 OSA patients and 77 COMISA patients. Standard polysomnography (PSG) and multiple sleep latency tests (MSLTs) were recorded and used to obtain relative EEG spectral power in each sleep stage during PSG and each session during MSLTs. A series of subjective and objective neurocognitive tests were conducted to evaluate executive function, attention, retrospective and prospective memory and meta-cognition.</p><p><strong>Results: </strong>In PSG and MSLTs, COMISA patients showed combined EEG power characteristics of both CIs and OSA. Specifically, COMISA patients exhibited similar EEG spectral characteristics to CIs, with decreased delta and increased alpha and beta power in NREM sleep stages, and increased beta power in REM and MSLTs. Similar to the EEG spectral power profile of OSA, COMISA patients showed increased delta power in REM and MSLTs. Compared to OSA patients, COMISA patients exhibited worse subjectively measured attention and meta-cognition related to negative beliefs about uncontrollability and danger of worry (NEG), which were positively associated with ISI scores.</p><p><strong>Conclusions: </strong>The EEG spectral power characteristics of COMISA patients in overnight PSG and daytime MSLT appear to be the manifestation of elements of both CIs and OSA. However, the neurocognitive features of COMISA patients in subjectively measured attention and NEG meta-cognition were primarily affected by chronic insomnia.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"139"},"PeriodicalIF":5.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}