medRxiv - Respiratory Medicine最新文献

{"title":"Insulin-AKT1-YBX1 Regulation of ANGPTL8 Promote Lipogenesis in OSA-Associated Dyslipidemia","authors":"Feng Liu, Yuenan Liu, Haolin Yuan, Anzhao Wang, Shengming Wang, Xu Xu, Junhui Hu, Jinhong Shen, Yiming Hu, Xinyi Li, Niannian Li, Zhenfei Gao, Xiaoxu Zhang, Xiaoman Zhang, Yupu Liu, Huajun Xu, Hongliang Yi, Jian Guan, Zhiqiang Li, Yongxu Zhao, Shankai Yin","doi":"10.1101/2024.06.23.24309370","DOIUrl":"https://doi.org/10.1101/2024.06.23.24309370","url":null,"abstract":"Dyslipidemia is a hallmark of obstructive sleep apnea (OSA)-induced metabolic syndrome, yet the mechanisms remain poorly understood. We conducted a genome-wide association study on lipid traits in the OSA cohorts, identifying the SNP rs3745683 in ANGPTL8, significantly associated with reductions in multiple lipid traits. ANGPTL8, an essential lipogenic hormone and potential therapeutic target for metabolic syndrome, showed elevated expression in OSA patients compared to healthy controls, strongly correlated with increased insulin levels. Notably, ANGPTL8 expression can be upregulated by insulin stimulation, indicating it as an insulin-responsive hormone regulating dyslipidemia in OSA. Mechanistically, SNP rs3745683 attenuated ANGPTL8 transcription by inhibiting its binding to transcription factor YBX1. Insulin prompted AKT1 to phosphorylate YBX1 at Ser102, facilitating YBX1's nuclear translocation and subsequent regulation of ANGPTL8 expression and lipid synthesis. Specific knockdown of YBX1 in mouse liver confirmed its necessity for ANGPTL8 expression and hepatic lipid synthesis in vivo. Our findings highlight ANGPTL8 as a critical regulator of dyslipidemia in OSA patients, offering a promising therapeutic avenue for managing metabolic syndrome in OSA.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigated ultrasound bronchoscopy with integrated positron emission tomography - A human feasibility study","authors":"Arne Kildahl-Andersen, Erlend Fagertun Hofstad, Ole-Vegard Solberg, Hanne Sorger, Tore Amundsen, Thomas Langø, Håkon Olav Leira","doi":"10.1101/2024.06.18.24308570","DOIUrl":"https://doi.org/10.1101/2024.06.18.24308570","url":null,"abstract":"Background and objective: Patients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data.\u0000Methods: The proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope's tip. Navigation accuracy was measured postoperatively using ultrasound recordings.\u0000Results: The study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm.\u0000Conclusion: Our study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Neutrophil Elastase Inhibitor (Sivelestat Sodium) on Oxygenation in Patients with Sepsis Induced Acute Respiratory Distress Syndrome","authors":"Tiejun Wu, Tao Wang, Jinjiao Jiang, Yue Tang, Lina Zhang, Zhiming Jiang, Fen Liu, Guiqing Kong, Tingfa Zhou, Ruijin Liu, Haipeng Guo, Jie Xiao, Wenqing Sun, Yuye Li, Yingying Zhu, Quan Liu, Weifeng Xie, Yan Qu, Xiaozhi Wang","doi":"10.1101/2024.05.30.24308242","DOIUrl":"https://doi.org/10.1101/2024.05.30.24308242","url":null,"abstract":"<strong>Objectives</strong> Neutrophil elastase (NE) plays an important role in the development of acute respiratory distress syndrome (ARDS). Sivelestat sodium, as a selective NE inhibitor, may improve the outcomes of patients with sepsis-induced ARDS in previous studies, but there is a lack of solid evidence. This trial aimed to evaluate the effect of sivelestat sodium on oxygenation in patients with sepsis-induced ARDS.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141258917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-time breath metabolomics to assess early response to CFTR modulators in adults with cystic fibrosis: an open-label proof-of-concept study","authors":"Emmanuelle Bardin, Hélène Salvator, Camille Roquencourt, Elodie Lamy, Nicolas Hunzinger, Isabelle Sermet-Gaudelus, Sandra De Miranda, Dominique Grenet, Philippe Devillier, Stanislas Grassin-Delyle","doi":"10.1101/2024.05.29.24308131","DOIUrl":"https://doi.org/10.1101/2024.05.29.24308131","url":null,"abstract":"<strong>Background</strong> The combination of CFTR modulators ivacaftor/tezacaftor/elexacaftor (ETI) achieves unprecedented improvements in clinical symptoms and respiratory function of people with cystic fibrosis. Yet, evaluation is difficult in people with high baseline lung function and the sweat test may vary depending on the type of CFTR mutation. Exhaled breath is a non-invasive sample, rich in personalised metabolic information and breathomics has emerged as a promising tool to monitor and assess therapeutic response. We hypothesised that ETI induces alterations in the breath composition and that these changes may correlate with clinical readouts.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease","authors":"Linh T. Ngo, Michaella J. Rekowski, Devin C. Koestler, Takafumi Yorozuya, Atsushi Saito, Imaan Azeem, Alexis Harrison, M. Kristen Demoruelle, Jonathan Boomer, Bryant R. England, Paul Wolters, Philip L. Molyneaux, Mario Castro, Joyce S. Lee, Joshua J. Solomon, Koji Koronuma, Michael P. Washburn, Scott M. Matson","doi":"10.1101/2024.05.30.24308215","DOIUrl":"https://doi.org/10.1101/2024.05.30.24308215","url":null,"abstract":"<strong>Background</strong> Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF).","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Respiratory Diseases using Peak Energy Analysis of Acoustic Cough","authors":"Sujith Thomas Chandy, Balamugesh Thangakunam, Gowrisree Rudraraju, Narayana Rao Sripada, Jayanthy Govindaraj, Charishma Gottipulla, Baswaraj Mamidgi, Shubha Deepti Palreddy, Nikhil kumar Reddy Bhoge, Harsha Vardhan Reddy Narreddy, Prasanna Samuel P, Devasahayam Jesudas Christopher, Venkat Yechuri","doi":"10.1101/2024.05.29.24308077","DOIUrl":"https://doi.org/10.1101/2024.05.29.24308077","url":null,"abstract":"<strong>Background and Objectives</strong> Cough is a common symptom of respiratory diseases and change in the cough sound can reflect a pathological condition in the lungs. Recent advancement on the analysis of the cough sound has suggested that it has the potential to be used as a non-invasive marker for screening respiratory conditions, such as Asthma, Chronic Pulmonary Obstructive Disease (COPD), Interstitial Lung Disease (ILD) and Bronchiectasis. The energy envelope is distinguishable for normal subjects versus subjects with respiratory conditions. Peak analysis of the energy envelope helps in quantifying the feature variation for these conditions.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral etiology of respiratory infections among patients at Adama Hospital Medical College, a facility-based surveillance site in Oromia, Ethiopia","authors":"Bedado Dulo, Gamachu Hinsene, Ephrem Mannekulih","doi":"10.1101/2024.05.31.24308236","DOIUrl":"https://doi.org/10.1101/2024.05.31.24308236","url":null,"abstract":"<strong>Background</strong> Acute viral origins account for around 80% of respiratory illnesses globally. The influenza virus, respiratory syncytial virus, coronavirus, adenovirus, and rhinovirus are the main viruses that cause these illnesses. All ages are susceptible to severe acute respiratory infections, which have a high rate of morbidity and mortality.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141258997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis","authors":"Yunli Zhao, Ya Gao, Gordon Guyatt, Timothy M. Uyeki, Ping Liu, Ming Liu, Yanjiao Shen, Xiaoyan Chen, Shuyue Luo, Xingsheng Li, Rongzhong Huang, Qiukui Hao","doi":"10.1101/2024.05.28.24307995","DOIUrl":"https://doi.org/10.1101/2024.05.28.24307995","url":null,"abstract":"<strong>Background</strong> To support an update of WHO influenza guidelines, we performed a systematic review and network meta-analysis of the evidence on antiviral drugs for prophylaxis of influenza.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141197182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-platform Clinical Proteomics using the Charité Open Standard for Plasma Proteomics (OSPP)","authors":"Ziyue Wang, Vadim Farztdinov, Ludwig Roman Sinn, Pinkus Tober-Lau, Daniela Ludwig, Anja Freiwald, Fatma Amari, Kathrin Textoris-Taube, Agathe Niewienda, Anna Sophie Welter, Alan An Jung Wei, Luise Luckau, Florian Kurth, Matthias Selbach, Johannes Hartl, Michael Mülleder, Markus Ralser","doi":"10.1101/2024.05.10.24307167","DOIUrl":"https://doi.org/10.1101/2024.05.10.24307167","url":null,"abstract":"The role of plasma and serum proteomics in characterizing human disease, identifying biomarkers, and advancing diagnostic technologies is rapidly increasing. However, there is an ongoing need to improve proteomic workflows in terms of accuracy, reproducibility, platform transferability, and cost-effectiveness. Here, we present the Charité <em><span>O</span>pen Peptide <span>S</span>tandard for <span>P</span>lasma <span>P</span>roteomics</em> (OSPP), a panel of 211 extensively pre-selected, stable-isotope labeled peptides combined in an open, versatile, and cost-effective internal standard for targeted and untargeted plasma and serum proteomics studies. The selected peptides show consistent quantification properties in human studies, across platforms and matrices, are well suited for chemical synthesis, and distribute homogeneously over proteomics-typical chromatographic gradients. Being derived from proteins that function in a wide range of biological processes, including several that are routinely used in clinical tests or are targets of FDA-approved drugs, the OSPP quantifies proteins that are important for human disease. On an acute COVID-19 in-patient cohort, we demonstrate the application of the OSPP to i) achieve patient classification and biomarker identification, ii) generate comparable quantitative proteome data with both targeted and untargeted proteomic approaches, and iii) estimate absolute peptide quantities to achieve cross-platform alignment across targeted, data-dependent and data-independent acquisition (DIA) proteomic methods on different instrument platforms. The OSPP adds only cents of cost per proteome sample, thus making the use of an internal standard cost-effective and accessible. In addition to the standards, corresponding spectral libraries and optimized acquisition methods for several platforms are made openly available.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140939501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depicting the regulatory role of JZOL on TRP channels in the treatment of Acute Bronchitis based on the combination of clinical trials, computational analysis and in vivo experiments","authors":"Qinhua Fan, Chongming Wu, Yawei Du, Boyang Wang, Yanming Xie, Zeling Zhang, Wenquan Su, Zizhuo Wang, Changchang Xu, Xueke Li, Ying Ding, Xinjiang An, Jing Chen, Yunying Xiao, Rong Yu, Nan Li, Juan Wang, Yiqun Teng, Hongfen Lv, Nian Yang, Yuling Wen, Xiaoli Huang, Wei Pan, Yufeng Liu, Xueqin Xi, Qianye Zhao, Changshan Liu, Jian Xu, Haitao Zhang, Lie Zhuo, Qiangquan Rong, Yu Xia, Qin Shen, Shao Li, Junhong Wang, Shengxian Wu","doi":"10.1101/2024.05.07.24306993","DOIUrl":"https://doi.org/10.1101/2024.05.07.24306993","url":null,"abstract":"The comparison between traditional Chinese medicine Jinzhen Oral Liquid (JZOL) and western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This head to head randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1 and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels was the key mechanism of action.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140939500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}