American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Macrophage CCL18 promotes lung inflammation in checkpoint inhibitor pneumonitis.","authors":"Mohammad I Ghanbar, Andres Villabona-Rueda, Nicolas Philip, Romy Rodriguez Ortega, Shannon Fonti, Arabellis Wally, Haiyang Jiang, Rulin Wang, Wilhelm Berger, Jeffrey Thiboutot, Hans Lee, Patrick Forde, Jarushka Naidoo, Julie Brahmer, Sang Taek Kim, Naval Daver, Mehmet Altan, Ajay Sheshadri, Pierre Van Mol, Els Wauters, Francois-Xavier Danlos, Jerome Le Pavec, Ariane Laparra, Rachel Damico, Srinivasan Yegnasubramanian, Sonye K Danoff, Franco D'alessio, Karthik Suresh","doi":"10.1165/rcmb.2025-0405OC","DOIUrl":"10.1165/rcmb.2025-0405OC","url":null,"abstract":"<p><strong>Background: </strong>Checkpoint inhibitor pneumonitis (CIP) is a highly morbid complication of immune checkpoint immunotherapy, characterized by acute lung injury leading, in severe cases, to hypoxic respiratory failure and death. CIP incidence in lung cancer is high (10%-15%). Yet, the pathophysiology of CIP is poorly understood.</p><p><strong>Objective/methods: </strong>To investigate the mechanisms underlying alveolar inflammation in patients with CIP, human bronchoalveolar lavage fluid (BALF) samples from control patients and patients with CIP were analyzed using flow cytometry, single-cell RNA sequencing (scRNA-seq), and ELISA. Findings were validated using multiple external cohorts. In vitro experiments and in vivo rodent models were employed to investigate the mechanisms driving alveolar inflammation in CIP.</p><p><strong>Results: </strong>Analysis of scRNA-seq and flow cytometry data demonstrated increased macrophages in patients with CIP compared to controls. Several distinct proinflammatory alveolar macrophage subsets were increased in CIP. CIP macrophages expressed increased CCL18 at the transcript (scRNA-seq), cellular (flow cytometry) and secreted protein (BALF ELISA) levels. BALF CCL18 levels were associated with clinical CIP severity. CCL18 overexpression in mice promoted lung inflammation that phenocopied human CIP, including upregulation of proinflammatory macrophage subsets.</p><p><strong>Conclusion: </strong>These findings suggest that BALF macrophages and CCL18 protein levels are increased in patients with CIP and associate with greater CIP severity. Additionally, CCL18 promotes lung inflammation in mice that mimics human CIP, suggesting a causal role for CCL18 in CIP.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"454-465"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273675","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":"Alteration of oxidized phospholipids profile in bronchoalveolar lavage fluid collected from atopic individuals co-exposed to air pollution and allergen.","authors":"Angela A Zhang, Min Hyung Ryu, Aruni Jha, Christopher Pascoe, Amir Ravandi, Andrew J Halayko, Chris Carlsten","doi":"10.1165/rcmb.2025-0303LE","DOIUrl":"10.1165/rcmb.2025-0303LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"563-566"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273691","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":"Enter the matrix: fibroblast transcriptome and matrisome alterations direct fibrotic transitions in influenza-mediated lung injury.","authors":"Jeffrey R Koenitzer","doi":"10.1165/rcmb.2025-0559ED","DOIUrl":"10.1165/rcmb.2025-0559ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"425-426"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297957","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":"Single cell omics identify an anti-inflammatory niche in macrophages of mild to moderate chronic obstructive pulmonary disease.","authors":"Baihui Lv, Mengmeng Jiang, Guofei Zhang, Dongyu Guo, Jinkang Yu, Xing Fang, Haoyu Tang, Huaqi Guo, Yinling Han, Yanqi Guo, Huiyu Sun, Yun Zhao, Zheng Wang, Songmin Ying, Wen Li, Zhouyang Li, Zhihua Chen","doi":"10.1165/rcmb.2025-0134OC","DOIUrl":"10.1165/rcmb.2025-0134OC","url":null,"abstract":"<p><strong>Rationale: </strong>Chronic obstructive pulmonary disease (COPD) is a major contributor to global mortality rates, yet the cell-specific mechanisms underlying its pathobiology remain poorly understood, particularly in mild disease stages.</p><p><strong>Objectives: </strong>To investigate the cooperative anti-inflammatory roles of macrophages and secretory cells in mild and moderate COPD.</p><p><strong>Methods: </strong>Single-cell profiles of lung tissues from individuals with mild to moderate COPD or control lungs were analyzed using Microwell-seq. Transcriptomic findings were validated using microfluidic single-cell RNA sequencing of murine lungs, high-throughput single-nucleus total RNA sequencing (snHH-seq) of human lung tissues from severe COPD, spatial transcriptomics, functional in vitro models, and immunostaining of human lung samples.</p><p><strong>Measurements and main results: </strong>An increased subpopulation, termed interstitial COPD-associated macrophages (ICMs), was identified, with transcriptional evidence of anti-inflammatory activity, and reduced the transcription of proteins associated with elastase secretion in mild to moderate COPD. Comprehensive analysis of single-cell datasets revealed enhanced expression of secretoglobin 3A2 (SCGB3A2) and macrophage receptor with collagenous structure (MARCO) across epithelial secretory cells and interstitial macrophages. Transcriptomic data demonstrated that MARCO activation was pivotal for phenotypic changes in interstitial macrophages transitioning to alveolar macrophages. Spi-1 proto-oncogene (SPI1) transcription factor levels aligned with the MARCO transcriptome in ICMs derived from COPD.</p><p><strong>Conclusions: </strong>In mild to moderate COPD, secretory cells play protective roles by regulating ICMs through the SCGB3A2-MARCO pathway. Targeting ICMs for COPD treatment may preserve the anti-inflammatory interstitial environment in patients.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"534-546"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273637","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":"Lung-targeted lipid nanoparticle delivery of a matricellular mRNA promotes fibrotic lung repair.","authors":"Kalpana R Betageri, Jeffrey A Meridew, Brian J Parrett, Rachel M Gilbert, Patrick A Link, Nichole A Schussler, Arnaldo Mercado-Perez, Nunzia Caporarello, Michael A Barry, Daniel J Tschumperlin","doi":"10.1165/rcmb.2025-0247OC","DOIUrl":"10.1165/rcmb.2025-0247OC","url":null,"abstract":"<p><p>Pulmonary fibrosis is increasingly understood to involve dysfunction within and across multiple cellular compartments, with recent attention highlighting the involvement of pulmonary vascular dysfunction in failed repair and progression of fibrosis. Formulation and delivery of lung-targeting lipid nanoparticles (LNPs) may provide a means to selectively target the lung but not systemic vasculature. However, the feasibility and efficacy of such approaches in the fibrotic lung are unknown. We sought to test whether intravenously administered lung-targeting LNPs can safely deliver mRNA to the healthy and fibrotic lung vasculature in young and aged mice and whether delivery of mRNA encoding a matricellular protein could promote fibrosis resolution. We used a selective organ targeting LNP formulation and characterized cell-specificity of delivery after bleomycin-induced lung fibrosis. We then delivered Ccn3 mRNA (encoding cellular communication network factor 3) to aged mice in the setting of established lung fibrosis and evaluated fibrotic regression and vascular repair. The matricellular protein encoded by Ccn3 was previously identified by our group as an important regulator of lung endothelial function. We found that LNP delivery was lung specific and predominantly endothelial targeting in the setting of lung fibrosis. Delivery of Ccn3 mRNA to aged mice via LNPs modestly reduced fibrosis and improved microvascular density in the lungs. Our results support the concept that cell-specific and repair-promoting cargos delivered via lung-targeting LNPs may have utility for treatment of established fibrosis.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"445-453"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290783","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":"FBXW7 ameliorates pulmonary arterial hypertension via reducing SPI1-mediated transcriptional activation of MFAP4.","authors":"Zhenzhu Jiang, Binlan Xiao, Zhe Hu, Yuanmao Li, Hang Zhang, Haiyan Peng","doi":"10.1093/ajrcmb/aanag074","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag074","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the role of the FBXW7/SPI1/MFAP4 axis in pulmonary arterial hypertension (PAH).</p><p><strong>Methods: </strong>An in vivo PAH model was constructed using a hypoxia chamber. The expression levels of FBXW7, SPI1 and MFAP4 were detected by immunofluorescence and Western blotting. Cardiopulmonary function was assessed; pathological changes in lung tissue were examined by HE staining, and inflammatory factors levels were measured using ELISA. For in vitro studies, a PAH model was simulated using hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs). MFAP4-stable knockdown cells were constructed. Cell proliferation was evaluated with CCK8 and EdU assays, and cell migration was assessed using scratch wound and transwell assays. The targeting relationship between SPI1 and MFAP4 was verified by dual-luciferase reporter and ChIP-qPCR assays. Further, co-immunoprecipitation (Co-IP) and protein stability experiments were performed to confirm FBXW7-mediated ubiquitination of SPI1.</p><p><strong>Results: </strong>In vivo, MFAP4 knockdown led to decreases in right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), right ventricular (RV) contraction index, and pulmonary arterial (PA) wall thickness. In vitro, MFAP4 knockdown suppressed PASMC proliferation and migration. SPI1 was identified as an upstream transcription factor of MFAP4. FBXW7 was shown to promote SPI1 ubiquitination and its degradation in vitro. Overexpression of FBXW7 suppressed PAH progression both in vitro and in vivo, while simultaneous overexpression of either SPI1 or MFAP4 counteracted the protective effects of FBXW7 overexpression.</p><p><strong>Conclusion: </strong>Decreased FBXW7 expression in PAH inhibits SPI1 ubiquitination and protein degradation, leading to increased MFAP4 levels, which ultimately promotes PAH progression.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832441","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":"FOXJ1 transcriptional targets in human airway cells and impaired multiciliogenesis in FOXJ1-associated primary ciliary dyskinesia.","authors":"Lucie Thomas, Jacques Serizay, Rahma Mani, Sandrine Couvet, Jean-François Papon, Aline Tamalet, Rana Mitri, Catherine Faucon, Marlene Murris-Espin, Emmanuelle Blanchard, Maud Langeois, Sophie Blesson, Sylvie Tissier, Guy Montantin, Florence Dastot-Le Moal, Romain Levergeois, Bruno Louis, Nicole Beydon, Guillaume Thouvenin, Estelle Escudier, Serge Amselem, Irina Giurgea, Laure-Emmanuelle Zaragosi, Alice Meunier, Marie Legendre","doi":"10.1093/ajrcmb/aanag071","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag071","url":null,"abstract":"<p><p>Fluid mobilization on epithelia is ensured by the motile cilia of differentiated multiciliated cells (MCCs). Key transcriptional regulators of motile ciliogenesis include CCNO, MCIDAS, RFXs, and the transcription factor FOXJ1, whose precise role in humans remains unclear. We show that, unlike CCNO and MCIDAS, FOXJ1 expression persists in well-differentiated human airway epithelial cells (hAECs), suggesting functions beyond cilia initiation. ChIP-seq in hAECs allowed us to refine the consensus target motifs of FOXJ1 and RFXs, as well as their close proximity, which strongly suggests functional cooperation within a transcriptional complex. By combining ChIP-seq in normal cells with RNAseq from patients with FOXJ1-related primary ciliary dyskinesia (PCD), we identified 683 direct FOXJ1 target genes. Among these, 89 MCC-enriched genes-particularly those encoding axonemal proteins such as microtubule-inner proteins (MIPs) and dynein arm docking components-were downregulated in FOXJ1-deficient cells. Collectively, these findings provide new insights into how FOXJ1 contributes to human motile ciliogenesis, and reveal a potential role for FOXJ1 in maintaining MCCs differentiation and ciliary function by sustaining the expression of ciliary proteins, particularly those in direct contact with axonemal tubulin.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832437","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":"MLKL Regulates Intracellular Trafficking of Neutrophil Elastase to Promote Lung Epithelial Cell Senescence.","authors":"Rong Liu, Aifang Zhang, Steven D Shapiro, Dongshi Chen","doi":"10.1093/ajrcmb/aanag072","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag072","url":null,"abstract":"<p><p>Neutrophil elastase (NE) is a key contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD), driving airway inflammation and tissue destruction. While the RIPK3/MLKL-mediated necroptosis has been implicated in cigarette smoke (CS)-induced COPD, its role in NE-mediated lung injury remains undefined. In this study, we demonstrate that NE does not induce necroptosis in lung epithelial cells in vitro. Although genetic deletion of RIPK3 or MLKL did not prevent NE-induced apoptosis, the absence of MLKL significantly reduced NE-induced cellular senescence. Mechanistically, we found that after NE is internalized into endosomes, MLKL facilitates its escape into the cytoplasm and subsequent translocation to the nucleus, where it induces DNA damage and senescence. In contrast, MLKL deficiency retains NE within endosomes, promoting its degradation via lysosomal trafficking. Furthermore, Mlkl knockout mice were protected from porcine pancreatic elastase (PPE)-induced emphysema, highlighting the pathological relevance of this mechanism. Collectively, our findings reveal a novel, necroptosis-independent function of MLKL in regulating intracellular NE trafficking, suggesting a new therapeutic target for protease-driven lung injury in COPD.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832484","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":"Optogenetic vagotomy inhibits reflex bronchoconstriction and cardiac chronotropy.","authors":"Aubrey B Pierce, Alexandra B Pincus, James Kornfield, Becky J Proskocil, Allison D Fryer, David B Jacoby, Matthew G Drake","doi":"10.1093/ajrcmb/aanag064","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag064","url":null,"abstract":"<p><p>Optogenetics involves genetic insertion of light-sensitive ion channels into nerves, such as with cre-based recombination. The recent increase in cre-based mouse lines has expanded our ability to test the roles of peripheral nerves in homeostasis and in disease models. Here, we generated an optogenetic mouse line in which hyperpolarizing inhibitory halorhodopsin channels were inserted into vagal cholinergic (parasympathetic) nerves using choline acetyltransferase (ChAT)-cre, enabling targeted inhibition of parasympathetic nerves. Halorhodopsin expression in parasympathetic neurons was confirmed by RT-PCR and confocal microscopy. Nerve reflex responses were generated with aerosolized serotonin or methacholine, during which mice were exposed to hyperpolarizing 645 nm or control 454 nm and 570 nm light. Inhibition of parasympathetic nerves by halorhodopsin attenuated airway hyperreactivity in house dust mite challenged mice while inhibition of cardiac cholinergic nerves increased heart rate. Our findings demonstrate the utility of halorhodopsin as a tool for testing the roles of parasympathetic nerves in cardiopulmonary function.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832485","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":"mRNA therapy improves the composition and motility in CCDC40-deficient cilia in vitro and in vivo.","authors":"Kai Wohlgemuth, Margarida Rasteiro, Manish Aneja, Catarina Bota, Sandra Cindric, Stefanie Freischem, Sebastian George, Gizem Günes Günsel, Seun Ishola, Julia Koenig, Rebekka Kubisch-Dohmen, Thomas Langenickel, Niki Tomas Loges, Miguel Lopes, Verena Mummert, Heike Olbrich, Petra Pennekamp, Telmo Pereira, Andreia L Pinto, Johanna Raidt, Carsten Rudolph, Adrian Ter Steege, Drishti Valecha, Susana S Lopes, Heymut Omran","doi":"10.1093/ajrcmb/aanag034","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag034","url":null,"abstract":"<p><p>Primary Ciliary Dyskinesia (PCD) is a genetically heterogeneous disorder leading to destructive airway disease with severe bronchiectasis and chronic lung failure in adulthood. Pathogenic variants in CCDC40 are associated with more severe reduction of lung function compared to most other PCD types. Currently, no therapies correcting the underlying disease mechanism are available. Here we investigate the efficacy of lipidoid nanoparticle-formulated mRNA encoding human CCDC40 (LNP-CCDC40-mRNA) as a corrective measure for structural and functional defects in vitro (human cells) and in vivo (zebrafish). Human nasal respiratory epithelial cells cultured at air-liquid-interface from five CCDC40-deficient individuals and a newly generated vertebrate animal model (ccdc40-/- zebrafish) were treated with LNP-CCDC40-mRNA. CCDC40-deficient cells were analyzed by high-speed video microscopy and immunofluorescence microscopy. ccdc40-/- zebrafish olfactory pit cilia were analyzed by high-speed video microscopy and fluid flow assays. Topical application of exogenous LNP-CCDC40-mRNA to CCDC40-deficient cells results in endogenous CCDC40 expression (10-74% of ciliated cells), enabling axonemal integration of CCDC40-associated proteins (CCDC39, GAS8/DRC4, DNALI1). Consistently, ciliary beat frequencies were significantly increased in treated CCDC40-deficient cells and comparable to healthy control cells. Further, we showed improved ciliary transport of fluorescent particles. Injection or topical application of human LNP-CCDC40-mRNA to ccdc40-/- zebrafish significantly increased ciliary motility and established directional flow in olfactory pits. We provide structural and functional evidence in vitro and in vivo for the biological efficacy of LNP-CCDC40-mRNA in CCDC40-deficient respiratory cells and zebrafish. Based on our results, an in vivo human study (Phase 1 trial) is planned in individuals with pathogenic variants in CCDC40.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832471","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}