Respiratory Research最新文献

{"title":"Current smoking and COPD are associated with differentiation-dependent secretory and inflammatory programs in airway basal cells.","authors":"Felix Ritzmann, Michelle Brand, Gilles Gasparoni, Xuan Zhang, Frank Langer, Christian Herr, Yiwen Yao, Migdat Mustafi, Daniela Yildiz, Jörn Walter, Robert Bals, Christoph Beisswenger","doi":"10.1186/s12931-026-03847-4","DOIUrl":"https://doi.org/10.1186/s12931-026-03847-4","url":null,"abstract":"<p><strong>Background: </strong>Persistent airway epithelial abnormalities contribute to chronic obstructive pulmonary disease (COPD), but it remains unclear whether smoking- and COPD-associated epithelial remodeling is retained in airway basal cells and transmitted during differentiation. We determined whether current smoking and COPD are associated with methylation-linked regulatory programs in airway basal cells that shape epithelial differentiation in patient-derived bronchial organoids.</p><p><strong>Methods: </strong>We integrated DNA methylation profiling and bulk transcriptomics in patient-derived airway basal cells and matched three-dimensional bronchial organoids. Methylation-defined gene sets were mapped to organoid epithelial cell states using single-cell RNA-seq and contextualized with publicly available airway epithelial datasets.</p><p><strong>Results: </strong>In this exploratory cohort, current smoking was associated with a predominant shift toward promoter hypomethylation in airway basal cells and matched organoids. Hypomethylated promoters were enriched for genes preferentially expressed in secretory epithelial cells, including BPIFB1, BPIFA2, MSMB and GALNT6. These genes showed little smoking-associated expression difference in basal-cell culture but were upregulated after organoid differentiation, indicating a differentiation-dependent epithelial memory of smoking. In COPD-derived basal cells, promoter methylation changes involved reduced xenobiotic metabolism and enhanced immune- and infection-related programs. Consistently, COPD-derived organoids showed reduced expression of detoxification-associated pathways and increased lysosomal, endocytic and host-defense programs.</p><p><strong>Conclusions: </strong>Current smoking and COPD are associated with persistent methylation-linked regulatory alterations in airway basal cells that become functionally apparent during epithelial differentiation. These findings support a model in which airway basal-cell memory contributes to secretory, inflammatory and host-defense remodeling in chronic airway disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alarmins differentially modulate airway contraction and relaxation of human small airways.","authors":"Joshua L Kennedy, Dana N Frederick, Reynold A Panettieri, Cynthia J Koziol-White","doi":"10.1186/s12931-026-03869-y","DOIUrl":"10.1186/s12931-026-03869-y","url":null,"abstract":"<p><p>Alarmins, including Thymic Stromal Lymphopoietin (TSLP) and Interleukins 33 and 25 (IL-33 and IL-25), contribute to the pathophysiology of allergic and nonallergic asthma by evoking exacerbations in response to allergens, viruses, and environmental irritants (as reviewed in [1]). Current evidence shows that inhibiting alarmins reduces symptoms and exacerbations in obstructive lung diseases, including asthma [1]. Preclinical work has largely focused on alarmins' role in modulating airway inflammation, but far less is known about how alarmins regulate airway tone (contraction and relaxation). We posit that IL-33, TSLP, and IL-25 exert distinct effects on airway contraction and relaxation in airways from non-diseased subjects and those with asthma.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851834","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":"Response to \"Respiratory outcomes in Korean COPD patients using e-cigarettes: methodological and interpretive limitations\".","authors":"Taeyun Kim, Danbee Kang, Hye Yun Park","doi":"10.1186/s12931-026-03823-y","DOIUrl":"10.1186/s12931-026-03823-y","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800438","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":"Respiratory outcomes in Korean COPD patients using e-cigarettes: methodological and interpretive limitations.","authors":"Davide Campagna, Francesca Cucuzza, Lucia Spicuzza","doi":"10.1186/s12931-026-03653-y","DOIUrl":"https://doi.org/10.1186/s12931-026-03653-y","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800510","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":"Genome-wide association study of image-based emphysema scoring in the Swedish CArdioPulmonary bioImage Study (SCAPIS) suggests two new risk loci in smokers.","authors":"Fredrik Nyberg, Per Lundmark, Anders Blomberg, Koen Dekkers, Arne Egesten, Jonas Eriksson Ström, Bruna Gigante, Anders Gummesson, Cecilia Gunnarsson, Christer Janson, Andrei Malinovschi, Anna-Carin Olin, Marju Orho-Melander, Hans Lennart Persson, Ida Pesonen, Magnus Sköld, Stefan Söderberg, Hanan Tanash, Lowie E G W Vanfleteren, Tove Fall","doi":"10.1186/s12931-026-03853-6","DOIUrl":"10.1186/s12931-026-03853-6","url":null,"abstract":"<p><strong>Background: </strong>Despite the high prevalence and clinical significance of emphysema, few genetic risk loci have been consistently replicated. We conducted a genome-wide association study (GWAS) of CT-based emphysema, with a particular focus on non-smoking-related genetic determinants.</p><p><strong>Methods: </strong>We analyzed 25,639 individuals of European ancestry from the SCAPIS national cohort, aged 50-65 years, of which 51% were never-smokers. Emphysema was assessed through semi-quantitative visual scoring of CT scans. GWAS was performed in the whole sample and stratified on smoking status. We also examined the association of previously reported emphysema- and lung function-related variants with emphysema in our dataset.</p><p><strong>Results: </strong>Emphysema criteria were fulfilled for 1,479 participants (5.6%), with higher prevalence among current (N = 576, 18.2%) and former smokers (N = 612, 6.5%) compared to never-smokers (N = 263, 2.0%). We identified three independent genetic loci for emphysema in smokers and no signals in never-smokers. The strongest signal was observed in the well-established nicotinic acetylcholine receptor cluster (CHRNA5-A3-B4) locus on chromosome 15. Additionally, we discovered novel associations near the dysferlin (DYSF) gene on chromosome 2 and in an intergenic region on chromosome 3. By assessing previously lung phenotype-associated variants we also found evidence supporting association with emphysema in smokers for variants in the EFEMP1/MIR217HG/PNPT1 locus on chromosome 2, previously linked to reduced FEV₁/FVC ratio.</p><p><strong>Conclusion: </strong>This study, based on the largest unselected population sample to date, provides novel insights into the genetic architecture of emphysema. However, no signals were detected in never-smokers despite the large sample-size, likely due to the low prevalence of emphysema in that group. The proposed genetic risk loci require external replication.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809433","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":"Utility of mouse precision cut lung slices as an in vitro model for interrogating the lung immune response against bacterial pathogens in the context of immunomodulatory therapeutics.","authors":"Guanghui Liu, Susann Busch, Taylor S Cohen, Linnea Särén, Johanna Sagemark, Eva Lamm Bergström, Xiao-Hong Zhou, Per Åberg, Anna Ollerstam, Jorrit J Hornberg, David H Dockrell, Catherine J Betts, Kinga Balogh Sivars","doi":"10.1186/s12931-026-03856-3","DOIUrl":"10.1186/s12931-026-03856-3","url":null,"abstract":"<p><p>High rates of respiratory infections have been observed in patients following treatment with immunomodulatory therapeutics, yet preclinical assessment and mechanistic understanding of drug-associated infection risk remains a challenge. Here, an ex vivo infection model of mouse precision-cut lung slices (PCLS) is described to address this gap. Naïve mouse PCLS were pre-treated with immunomodulatory drugs previously reported to exacerbate clinical infection risk (Idelalisib, Anakinra and Tofacitinib), followed by incubation with the lung pathogen Streptococcus pneumoniae. Bacterial uptake by the PCLS and cytokine release was measured to assess innate responses. Both Anakinra and Tofacitinib increased intracellular accumulation of bacteria within epithelial cells and reduced inflammatory cytokine release in a dose-dependent manner. Idelalisib also increased bacterial uptake with an inverse dose-response relationship, while the inhibitory effects on cytokine release were dose-dependent. These effects were confirmed in normal human bronchial epithelial cells (NHBE), suggesting that low concentrations of Idelalisib might negatively impact essential innate immune pathways. RNA-Seq analysis of the lung slices revealed the activation of key pathways linked to the innate immune response following infection, including PI3K signaling, oxidative stress response, cytoskeletal reorganization and autophagy. Notably, these pathways were modulated in the presence of Idelalisib and translation of the involvement of these pathways in the response to S. pneumoniae was confirmed in NHBE. In conclusion, the PCLS model offers potential to inform early risk assessment whilst aiding mechanistic understanding of the immunomodulatory impact of drug candidates on the lung.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680729","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":"Blood viscosity is associated with smoking status rather than the presence of chronic obstructive pulmonary disease: findings from the Korea COPD Subgroup Study (KOCOSS).","authors":"Ye Jin Lee, Hye-Rin Kang, Sang Hyuk Kim, Hyun Jung Kim, Jae Seung Lee, Chang-Hoon Lee, Sung Kyoung Kim, Yu-Il Kim, Kwang Ha Yoo, Youlim Kim","doi":"10.1186/s12931-026-03827-8","DOIUrl":"10.1186/s12931-026-03827-8","url":null,"abstract":"<p><strong>Background: </strong>The relationship between smoking and blood viscosity is well established. However, the role of blood viscosity in the development of chronic obstructive pulmonary disease (COPD) and its impact on lung function decline remains unclear. Therefore, we aimed to investigate the association of blood viscosity with COPD and lung function decline, independent of smoking status.</p><p><strong>Methods: </strong>Data from 292 participants in the Korea COPD Subgroup Study (KOCOSS), a multicenter prospective cohort, were analyzed. Subjects were classified into four groups based on smoking history and COPD status. Multiple linear regression analysis was performed to determine the association between baseline viscosity and lung function decline after adjusting for age, sex, smoking status, and COPD status.</p><p><strong>Results: </strong>Of the 292 participants, 93 (31.8%) patients had COPD. Ever smokers with or without COPD were older than never smokers and predominantly male. Never smokers with COPD reported the highest scores for the Modified Medical Research Council Dyspnea Scale. Blood viscosity was significantly higher in ever smokers (with COPD: 9.0 ± 1.4; without COPD 9.2 ± 1.5) than in never smokers (with COPD: 8.7 ± 1.8; without COPD: 8.4 ± 1.5). Viscosity did not differ significantly with the presence of COPD within the same smoking category. Adjusted multiple linear regression revealed that baseline blood viscosity was not associated with 2-year declines in forced expiratory volume in 1 s (p = 0.557), forced vital capacity (p = 0.686), or diffusing capacity of the lung for carbon monoxide (p = 0.947).</p><p><strong>Conclusion: </strong>Blood viscosity appeared to be more closely associated with smoking-related hemorheological changes than with COPD. Its potential as a predictive biomarker for lung function decline appears to be limited, necessitating further long-term investigation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674382","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":"Airway microbial compartmentalization under mechanical ventilation: a randomized pilot study comparing an endotracheal tube with suction and continuous cuff pressure control (Venner PneuX^®) to standard intubation.","authors":"Anna E Pilkowski, Patrick Schaal, Lienhard Leibold, Benjamin Seybold, Judith Schenz, Alexander H Dalpke, Markus A Weigand, Bachar A Cheaib, Sébastien Boutin, Mascha O Fiedler-Kalenka","doi":"10.1186/s12931-026-03849-2","DOIUrl":"10.1186/s12931-026-03849-2","url":null,"abstract":"<p><strong>Objectives: </strong>Ventilator-associated pneumonia (VAP) is driven in part by microaspiration along the endotracheal tube cuff, a process difficult to measure directly in ventilated patients. Because microbial communities differ between airway compartments, changes in their similarity over time may serve as an indirect readout of microaspiration. We assessed whether the Venner PneuX^® Tube (VT) system, combining cuff-pressure monitoring, subglottic suction, and a biofilm-resistant coating, reduces microbial exchange between airway compartments compared with a standard endotracheal tube (ST).</p><p><strong>Methods: </strong>In a prospective, randomized, single-center pilot study, 50 adults with acute respiratory failure received an ST or VT intubation. Microbial communities from five airway niches (throat, tracheal secretions, right upper, right lower, and left lower lung lobes) were sampled by 16 S rRNA sequencing at intubation (T1), after four days of ventilation (T2) and, for the tube tip, at extubation (T3). The primary outcome was the change in beta diversity (Morisita-Horn distances) between tube-associated, upper-airway, and lower-airway communities from T1 to T2.</p><p><strong>Results: </strong>Twenty-one of 50 randomized patients had complete microbiota data sets (9 ST, 12 VT) and were comparable in demographics, comorbidities, severity, and ventilation duration. In the ST group, tube-associated communities became more similar to tracheal and lower-airway communities from T1 to T2 (e.g. TS-Tube Morisita-Horn 0.55 → 0.30, p = 0.001), while lung regions diverged from each other and from the throat (LLL-LRL 0.08 → 0.31, p = 0.003; LLL-Throat 0.30 → 0.61, p < 0.001). None of these distances changed significantly in the VT group. Lower-airway Shannon diversity declined in both groups, more in the VT group.</p><p><strong>Conclusions: </strong>Standard intubation produced progressive microbial convergence between airway compartments, while the VT system did not. The findings provide biological plausibility for previously reported VAP reductions with the VT system and show that microbiota sampling can detect device-related differences in airway community structure, warranting further investigation as an endpoint for evaluating airway devices.</p><p><strong>Trial registration: </strong>The study is registered in the German Clinical Trials Register (DRKS- Deutsches Register für klinische Studien) under the clinical trial number: DRKS00029176. The Date of Trial Registration was 07.07.2022.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698228","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":"Irisin maintains ER homeostasis and activates AMPK via integrin αVβ5 to attenuate CSE + LPS-induced emphysema and inflammation.","authors":"Zina Bai, Tongxinwei Sun, Zelin Chen, Siqin Han, Jingwen Li, Xiaopeng Zhang, Cuiqing Ma, Yahong Chen, Ping Jiang, Xixin Yan, Aihong Meng","doi":"10.1186/s12931-026-03850-9","DOIUrl":"10.1186/s12931-026-03850-9","url":null,"abstract":"<p><strong>Background: </strong>AECOPD adversely affects patient survival rates and overall quality of life. Irisin is being increasingly recognized for its therapeutic potential in attenuating pulmonary injury, but its underlying mechanism remains unclear.</p><p><strong>Methods: </strong>Human lung tissue samples were subjected to IHC analysis for irisin, integrin αVβ5, and GRP78 expression. CSE+LPS-induced mouse and cell models were used to investigate whether irisin protects against emphysema and inflammation by regulating ER homeostasis and AMPK activity via integrin αVβ5.</p><p><strong>Results: </strong>In COPD patients, irisin levels are decreased, whereas integrin αVβ5 and GRP78 levels are elevated. Irisin improved lung function and attenuated emphysema and inflammation in mice, and these effects were abolished by cilengitide. Irisin directly bound to integrin αVβ5, maintained ER homeostasis via the PERK/ATF4/CHOP pathway, and activated AMPK. These protective effects were lost upon integrin αVβ5 knockdown.</p><p><strong>Conclusion: </strong>These findings suggest that through integrin αVβ5, irisin concurrently maintains ER homeostasis and activates AMPK, thereby alleviating CSE+LPS-induced emphysema and inflammation, suggesting a novel therapeutic direction for the management of AECOPD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867284","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 SNP altering the MUC5AC mucin structure is increased in idiopathic pulmonary fibrosis together with the MUC5B SNP.","authors":"Sergio Trillo-Muyo, Anna Ermund, Brendan Dolan, Levent M Akyürek, Jesper M Magnusson, Gunnar C Hansson","doi":"10.1186/s12931-026-03833-w","DOIUrl":"10.1186/s12931-026-03833-w","url":null,"abstract":"<p><strong>Background: </strong>The gel-forming mucins MUC5B and MUC5AC constitute the main structural components of mucus in the respiratory system where MUC5AC is known to form nets. The MUC5B (rs35705950) Single Nucleotide Polymorphism (SNP) has been shown to increase the risk for Idiopathic Pulmonary Fibrosis (IPF). The MUC5AC SNP rs878913005, common in European populations, results in an Arg1201Trp substitution, resulting in more stabilized secreted mucin nets. Here we investigate the association of rs878913005 with the development of IPF and the presence of the two mucins in IPF diagnostic honeycomb cysts.</p><p><strong>Methods: </strong>We compared patient groups using whole genome sequences from the UK-Biobank for the SNPs in MUC5AC and MUC5B mucin genes. Lung tissue from IPF patients were immunostained for these mucins.</p><p><strong>Results: </strong>The MUC5AC SNP shows a significant 1.49x increased frequency in IPF patients relative to controls (p < 0.0001) and an odds ratio of 2.09. The well-known IPF-associated SNP in the MUC5B promoter (rs35705950) has a stronger linkage to IPF when combined with the MUC5AC SNP. These two SNPs are located on the same chromosome and are in linkage disequilibrium (r² = 0.10 in controls and up to r² = 0.17 in IPF). Microscopic honeycomb cysts, typical for IPF, are filled with both the MUC5B and MUC5AC mucins with MUC5AC associated to the cysts' epithelial surface.</p><p><strong>Conclusion: </strong>A genetic variant with more stable MUC5AC nets in peripheral thin airways may increase the risk of IPF.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698193","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}