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Evaluation of intestinal biopsy tissue preservation methods to facilitate large-scale mucosal microbiota research. 评估肠道活检组织保存方法,促进大规模粘膜微生物群研究。
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2024-12-31 DOI: 10.1016/j.ebiom.2024.105550
Nicola J Wyatt, Hannah Watson, Gregory R Young, Mary Doona, Ned Tilling, Dean Allerton, Andrea C Masi, Tariq Ahmad, Jennifer A Doyle, Katherine Frith, Ailsa Hart, Victoria Hildreth, Peter M Irving, Claire Jones, Nicholas A Kennedy, Sarah Lawrence, Charlie W Lees, Robert Lees, Trevor Liddle, James O Lindsay, Julian R Marchesi, Miles Parkes, Nick Powell, Natalie J Prescott, Tim Raine, Jack Satsangi, Kevin Whelan, Ruth Wood, Andrew King, Luke Jostins-Dean, R Alexander Speight, Naomi McGregor, Christopher J Stewart, Christopher A Lamb
{"title":"Evaluation of intestinal biopsy tissue preservation methods to facilitate large-scale mucosal microbiota research.","authors":"Nicola J Wyatt, Hannah Watson, Gregory R Young, Mary Doona, Ned Tilling, Dean Allerton, Andrea C Masi, Tariq Ahmad, Jennifer A Doyle, Katherine Frith, Ailsa Hart, Victoria Hildreth, Peter M Irving, Claire Jones, Nicholas A Kennedy, Sarah Lawrence, Charlie W Lees, Robert Lees, Trevor Liddle, James O Lindsay, Julian R Marchesi, Miles Parkes, Nick Powell, Natalie J Prescott, Tim Raine, Jack Satsangi, Kevin Whelan, Ruth Wood, Andrew King, Luke Jostins-Dean, R Alexander Speight, Naomi McGregor, Christopher J Stewart, Christopher A Lamb","doi":"10.1016/j.ebiom.2024.105550","DOIUrl":"10.1016/j.ebiom.2024.105550","url":null,"abstract":"<p><strong>Background: </strong>Large-scale multicentre studies are needed to understand complex relationships between the gut microbiota, health and disease. Interrogating the mucosal microbiota may identify important biology not captured by stool analysis. Gold standard tissue cryopreservation ('flash freezing') limits large-scale study feasibility. We aimed to compare gut microbiota in gold standard and pragmatic mucosal biopsy storage conditions.</p><p><strong>Methods: </strong>We collected endoscopic recto-sigmoid biopsies from 20 adults with inflammatory bowel disease. Biopsies were preserved using three methods: (i) flash freezing (most proximal and distal biopsy sites); (ii) nucleic acid preservative reagents (QIAGEN Allprotect®, Invitrogen RNAlater™, and Zymo DNA/RNA Shield™); and (iii) formalin fixation with paraffin embedding (FFPE), which is used to preserve tissue for clinical histopathology within healthcare settings. Microbiota were sequenced on the MiSeq platform (V4 region, 16S rRNA gene).</p><p><strong>Findings: </strong>Tissue microbiota were consistent between most proximal and distal tissue suggesting any within-patient variation observed reflected storage condition, not biopsy location. There was no significant difference in alpha-diversity or microbial community profiles of reagent-preserved versus gold standard tissue. FFPE community structure was significantly dissimilar to other tissue samples, driven by differential relative abundance of obligate gut anaerobes; Faecalibacterium, Anaerostipes and Lachnospiraceae. Despite these differences, tissue microbiota grouped by participant regardless of preservation and storage conditions.</p><p><strong>Interpretation: </strong>Preservative reagents offer a convenient alternative to flash freezing tissue in prospective large-scale mucosal microbiota studies. Whilst less comparable, FFPE provides potential for retrospective microbiota studies using historical samples.</p><p><strong>Funding: </strong>Medical Research Council (MR/T032162/1) and The Leona M. and Harry B. Helmsley Charitable Trust (G-2002-04255).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105550"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wildfires, smog, and the persistent threat of air pollution to human health.
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 DOI: 10.1016/j.ebiom.2025.105602
eBioMedicine
{"title":"Wildfires, smog, and the persistent threat of air pollution to human health.","authors":"eBioMedicine","doi":"10.1016/j.ebiom.2025.105602","DOIUrl":"10.1016/j.ebiom.2025.105602","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105602"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic insights into psychotic major depressive disorder: bridging the mood-psychotic disorder spectrum.
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI: 10.1016/j.ebiom.2025.105576
Thuy-Dung Nguyen, Joeri J Meijsen, Robert Sigström, Ralf Kuja-Halkola, Ying Xiong, Arvid Harder, Kaarina Kowalec, Joëlle A Pasman, Carolina Scarpa, Elin Hörbeck, Lina Jonsson, Sara Hägg, Niamh Mullins, Kevin S O'Connell, Christina Dalman, Dorte Helenius, Richard Zetterberg, Henrik Larsson, Paul Lichtenstein, Ole A Andreassen, Thomas Werge, Alfonso Buil, Mikael Landén, Patrick F Sullivan, Yi Lu
{"title":"Genetic insights into psychotic major depressive disorder: bridging the mood-psychotic disorder spectrum.","authors":"Thuy-Dung Nguyen, Joeri J Meijsen, Robert Sigström, Ralf Kuja-Halkola, Ying Xiong, Arvid Harder, Kaarina Kowalec, Joëlle A Pasman, Carolina Scarpa, Elin Hörbeck, Lina Jonsson, Sara Hägg, Niamh Mullins, Kevin S O'Connell, Christina Dalman, Dorte Helenius, Richard Zetterberg, Henrik Larsson, Paul Lichtenstein, Ole A Andreassen, Thomas Werge, Alfonso Buil, Mikael Landén, Patrick F Sullivan, Yi Lu","doi":"10.1016/j.ebiom.2025.105576","DOIUrl":"10.1016/j.ebiom.2025.105576","url":null,"abstract":"<p><strong>Background: </strong>Psychotic major depressive disorder (MDD), a subtype of MDD characterised by psychotic symptoms that occur exclusively during mood episode, is clinically significant yet underexplored genetically due to its rarity. This study comprehensively examines the genetic basis of psychotic MDD and elucidates its position within the mood-psychotic spectrum.</p><p><strong>Methods: </strong>This population-based cohort study used Swedish and Danish registry data for over 5.1 M individuals born between 1958 and 1993/1996. Specialist-diagnosed psychotic MDD was defined using ICD-10 sub-codes of MDD, F32.2/F32.3. We estimated familial aggregation/coaggregation using generalised estimating equations, heritability and genetic correlations using structural equation modelling. We also analysed ∼30,000 genotyped MDD cases from the UK Biobank and a Swedish cohort to explore which polygenic risk score (PRS) may predispose individuals to psychotic MDD.</p><p><strong>Findings: </strong>With over 10,000 psychotic MDD identified from the two nationwide patient registers, this study highlights the familial aggregation of psychotic MDD, co-aggregation with mood and psychotic disorders, and its stronger genetic correlation with schizophrenia compared to non-psychotic MDD. The familial risks increased with closer biological relatedness, suggesting genetic influence. Pedigree-heritability of psychotic MDD was 30.17% (95% CI 23.53-36.80%). While the genetic correlation between psychotic and non-psychotic MDD was high (0.82, 95% CI 0.73-0.92), the psychotic subgroup showed a higher genetic correlation with schizophrenia than non-psychotic MDD (0.67 vs 0.46, p-value 7.55∗10<sup>-4</sup>). Within 30,000 genotyped MDD cases, individuals with psychotic MDD had higher mean PRS for schizophrenia and BD but a lower MDD PRS than non-psychotic MDD. PRS for BD type-I was associated with increased odds of psychotic MDD, while BD type-II PRS showed no significant association with psychotic MDD.</p><p><strong>Interpretation: </strong>This study provides evidence for the genetic basis of psychotic MDD, underscoring its unique position bridging the spectrum of mood and psychotic disorders. These findings advance our understanding of the aetiology of psychotic MDD and contribute to the limited body of evidence on this phenotype by utilising large-scale population-based data.</p><p><strong>Funding: </strong>European Research Council; US National Institutes of Mental Health; European Union Horizon 2020 Program; Swedish Research Council; Research Council of Norway; Swedish Foundation for Strategic Research; Hjärnfonden.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105576"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New questions and avenues for research regarding interpretation of the significance of respiratory viruses adrift in the air. 关于解释空气中漂浮的呼吸道病毒的意义的新问题和研究途径。
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1016/j.ebiom.2024.105524
John A Lednicky
{"title":"New questions and avenues for research regarding interpretation of the significance of respiratory viruses adrift in the air.","authors":"John A Lednicky","doi":"10.1016/j.ebiom.2024.105524","DOIUrl":"10.1016/j.ebiom.2024.105524","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105524"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liver regeneration in fatty liver disease: can metabolomics shed light on the contribution of the gut microbiome? 脂肪性肝病的肝脏再生:代谢组学能否揭示肠道微生物组的贡献?
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-10 DOI: 10.1016/j.ebiom.2024.105552
Florian Jokisch, Laura Jennifer Marie Geyer, Klaus-Peter Janssen
{"title":"Liver regeneration in fatty liver disease: can metabolomics shed light on the contribution of the gut microbiome?","authors":"Florian Jokisch, Laura Jennifer Marie Geyer, Klaus-Peter Janssen","doi":"10.1016/j.ebiom.2024.105552","DOIUrl":"10.1016/j.ebiom.2024.105552","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105552"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epithelial stem cells from human small bronchi offer a potential for therapy of idiopathic pulmonary fibrosis. 来自人小支气管的上皮干细胞为特发性肺纤维化的治疗提供了潜力。
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1016/j.ebiom.2024.105538
Zeyu Liu, Qi Zheng, Zhoubin Li, Moli Huang, Cheng Zhong, Ruize Yu, Rong Jiang, Haotian Dai, Jingyuan Zhang, Xiaohua Gu, Yongle Xu, Chunwei Li, Shan Shan, Feng Xu, Yue Hong, Tao Ren
{"title":"Epithelial stem cells from human small bronchi offer a potential for therapy of idiopathic pulmonary fibrosis.","authors":"Zeyu Liu, Qi Zheng, Zhoubin Li, Moli Huang, Cheng Zhong, Ruize Yu, Rong Jiang, Haotian Dai, Jingyuan Zhang, Xiaohua Gu, Yongle Xu, Chunwei Li, Shan Shan, Feng Xu, Yue Hong, Tao Ren","doi":"10.1016/j.ebiom.2024.105538","DOIUrl":"10.1016/j.ebiom.2024.105538","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with restrictive ventilation. Recently, the structural and functional defects of small airways have received attention in the early pathogenesis of IPF. This study aimed to elucidate the characteristics of small airway epithelial dysfunction in patients with IPF and explore novel therapeutic interventions to impede IPF progression by targeting the dysfunctional small airways.</p><p><strong>Methods: </strong>Airway trees spanning the proximal-distal axis were harvested from control lungs and explanted lungs with end-stage IPF undergoing transplant. Qualified basal cells (BCs, p63/Krt5/ITGA6/NGFR) were expanded, and their cellular functions, feasibility, safety and efficacy for transplantation therapy in IPF were validated with experiments in vitro and mouse model. Single-cell RNA-sequencing was employed to elucidate the underlying mechanisms governing the BCs based therapy. Based upon these evidences, three patients with advanced IPF and small airway dysfunction received autologous-BCs transplantation. Post-transplantation assessments included lung function, exercise capacity and high resolution computed tomography (HRCT) scans were analyzed to quantify the clinical benefits conferred by the BCs transplantation.</p><p><strong>Findings: </strong>An overall landscape of senescent phenotype in airway epithelial cells and airway stem/progenitor cells along the proximal-distal axis of the airway tree in IPF were outlined. In contrast to the cells situated in distal airways, BCs located in small bronchi in IPF displayed a non-senescent phenotype, with comparable proliferative, differentiative capabilities, and similar transcriptomic profiles to normal controls. In a mouse model of pulmonary fibrosis, BCs exhibited promising protective efficacy and safety for transplantation therapy. Autologous BCs transplantation in three advanced IPF patients with small airway dysfunction yielded significant clinical improvements in pulmonary function, particularly evidence in lung volume and small airway function.</p><p><strong>Interpretation: </strong>Epithelia of small bronchi in IPF contain functional and expandable basal stem cells, which exert therapeutic benefits via bronchoscopic implantation. Our findings offer a potential for IPF treatment by targeting small airways.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (82430001, 81930001, and 81900059), Shanghai Shenkang Hospital Development Center (SHDC2020CR3063B), Department of Science and Technology of Shandong Province (2024HWYQ-058).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105538"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating tumour DNA in predicting and monitoring survival of patients with locally advanced rectal cancer undergoing multimodal treatment: long-term results from a prospective multicenter study. 循环肿瘤DNA预测和监测局部晚期直肠癌多模式治疗患者的生存:一项前瞻性多中心研究的长期结果
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-15 DOI: 10.1016/j.ebiom.2024.105548
Jiaolin Zhou, Lifeng Li, Yuxin Liu, Wenzhuo Jia, Qian Liu, Xuan Gao, Aiwen Wu, Bin Wu, Zhanlong Shen, Zhenjun Wang, Jiagang Han, Beizhan Niu, Yuhua Gong, Yanfang Guan, Jianfeng Zhou, Huadan Xue, Weixun Zhou, Ke Hu, Junyang Lu, Lai Xu, Xuefeng Xia, Xin Yi, Ling Yang, Guole Lin
{"title":"Circulating tumour DNA in predicting and monitoring survival of patients with locally advanced rectal cancer undergoing multimodal treatment: long-term results from a prospective multicenter study.","authors":"Jiaolin Zhou, Lifeng Li, Yuxin Liu, Wenzhuo Jia, Qian Liu, Xuan Gao, Aiwen Wu, Bin Wu, Zhanlong Shen, Zhenjun Wang, Jiagang Han, Beizhan Niu, Yuhua Gong, Yanfang Guan, Jianfeng Zhou, Huadan Xue, Weixun Zhou, Ke Hu, Junyang Lu, Lai Xu, Xuefeng Xia, Xin Yi, Ling Yang, Guole Lin","doi":"10.1016/j.ebiom.2024.105548","DOIUrl":"10.1016/j.ebiom.2024.105548","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemoradiotherapy (nCRT) is the standard for locally advanced rectal cancer (LARC). However, distant metastasis remains the primary cause of treatment failure. Early identification of high-risk individuals for personalized treatment may offer a solution. Circulating tumour DNA (ctDNA) could assist in this process.</p><p><strong>Methods: </strong>From September 2017 to June 2019, the study prospectively recruited 113 patients with LARC (cT3-4N0M0 or cTanyN + M0) who underwent nCRT followed by radical surgery across 8 tertiary centers. ctDNA was analysed using large-panel targeted sequencing at baseline, during nCRT, pre-surgery, post-surgery, post-adjuvant chemotherapy (ACT), and during annual follow-ups for 3 years.</p><p><strong>Findings: </strong>We analysed 103 tissue and 669 plasma samples from 103 patients. With a median 53-month follow-up, significantly worse progression-free survival (PFS) and overall survival (OS) were observed if median variant allele frequency (mVAF) of baseline ctDNA per patient was ≥0.5% (PFS, HR 4.39, p < 0.001; OS, HR 5.61, p = 0.004) or ctDNA was still detectable two weeks into nCRT (PFS, HR 7.63, p < 0.001; OS, HR 5.08, p < 0.001). Furthermore, when compared to the low-risk (C1) group (characterized by \"ctDNA undetected during nCRT with baseline mVAF <0.5%\" or \"ctDNA undetected during nCRT with TMB (tumour mutational burden) ≥20/Mb\"), the high-risk (C2) group (characterized by \"ctDNA detected during nCRT\" or \"baseline mVAF ≥0.5% with TMB <20/Mb\") showed significantly worse long-term outcomes (3 y-PFS, 55.9% vs. 94.2%; 3 y-OS, 79.4% vs. 100%). The ctDNA clearance during nCRT, baseline mVAF, and TMB may be effective prognostic indicators.</p><p><strong>Interpretation: </strong>Our findings reaffirm the clinical monitoring value of ctDNA and demonstrate the strong prognostic value of baseline ctDNA and its early clearance status in patients with LARC undergoing nCRT. This highlights the potential of dynamic ctDNA monitoring as actionable stratified indicators to guide personalized neoadjuvant treatment strategies.</p><p><strong>Funding: </strong>This work was supported by the Major Grants Program of Beijing Science and Technology Commission (No. D171100002617003) and the National High Level Hospital Clinical Research Funding (2022-PUMCH-C-005).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105548"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A comparative cohort study of post-COVID-19 conditions based on physical examination records in China. 基于体检记录的中国新冠肺炎后状况对比队列研究
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1016/j.ebiom.2024.105549
Zhong Liu, Boqiang Hu, Tao Zeng, Cuiping You, Nan Li, Yongjing Liu, Jie Zhang, Chenbing Liu, Piaopiao Jin, Xiaoxi Feng, Jun Chen, Jinyan Huang
{"title":"A comparative cohort study of post-COVID-19 conditions based on physical examination records in China.","authors":"Zhong Liu, Boqiang Hu, Tao Zeng, Cuiping You, Nan Li, Yongjing Liu, Jie Zhang, Chenbing Liu, Piaopiao Jin, Xiaoxi Feng, Jun Chen, Jinyan Huang","doi":"10.1016/j.ebiom.2024.105549","DOIUrl":"10.1016/j.ebiom.2024.105549","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2 virus infection, is characterized as a multisystem disease, potentially yielding multifaceted consequences on various organs at multiple levels. At the end of 2022, over 90% of the Chinese population was infected by SARS-CoV-2 within 35 days because of adjustments to epidemic prevention and control policies. This short-term change provides an unprecedented opportunity for comparative studies on COVID-19 infection among large populations.</p><p><strong>Methods: </strong>In this study, the physical examination data of 136,713 people in the past three consecutive years was employed to study the impact of COVID-19. Standard physical examination data, comprising evaluations of nearly a hundred indicators, were investigated for a comprehensive assessment of COVID-19's effect on human health.</p><p><strong>Findings: </strong>The results suggested that most indicators remained stable or changed within a permissible range after the COVID-19 outbreak in December 2022, but several specific indicators presented abnormal patterns of varying durations. There was an observed increase in the fraction of T-wave abnormalities during the outbreak, especially in people with chronic diseases such as hypertension, liver steatosis, and hyperglycemia.</p><p><strong>Interpretation: </strong>These findings highlighted the impact of COVID-19 on cardiovascular health and its potential interaction with chronic diseases.</p><p><strong>Funding: </strong>This work was supported by the National Key Research and Development Program of China (2019YFE0108100), the National Natural Science Foundation of China General Program (82270159, 82070147).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105549"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intracalvariosseous injection: an approach for central nervous system drug delivery through skull bone marrow with a preclinical research in stroke.
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI: 10.1016/j.ebiom.2025.105568
Wenqian Liu, Mo Yang, Nanxing Wang, Xiangrong Liu, Chaoyu Wang, Kaibin Shi, Fu-Dong Shi, Yuesong Pan, Mingjun Zhang, Zhiwei Sun, Yongjun Wang, Yilong Wang
{"title":"Intracalvariosseous injection: an approach for central nervous system drug delivery through skull bone marrow with a preclinical research in stroke.","authors":"Wenqian Liu, Mo Yang, Nanxing Wang, Xiangrong Liu, Chaoyu Wang, Kaibin Shi, Fu-Dong Shi, Yuesong Pan, Mingjun Zhang, Zhiwei Sun, Yongjun Wang, Yilong Wang","doi":"10.1016/j.ebiom.2025.105568","DOIUrl":"10.1016/j.ebiom.2025.105568","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Central nervous system (CNS) accessibility constitutes a major hurdle for drug development to treat neurological diseases. Existing drug delivery methods rely on breaking the blood-brain barrier (BBB) for drugs to penetrate the CNS. Researchers have discovered natural microchannels between the skull bone marrow and the dura mater, providing a pathway for drug delivery through the skull bone marrow. However, there has been no research on the feasibility, safety, and efficacy of this delivery method for drug treatment of stroke.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used a microporous method for intracalvariosseous (ICO) injection to deliver drugs directly into brain parenchyma through skull bone marrow. Safety of ICO was assessed by monitoring changes in skull and peripheral blood neutrophil counts, and FITC-dextran extravasation across the BBB. Drug delivery pathways were observed through transparent skull-dura mater-brain tissue. In a rodent stroke model, NA-1 or Y-3 neuroprotective agents were administered via ICO to evaluate safety and efficacy by assessing neurological deficits, infarct size, neuroinflammatory factors, neuronal apoptosis, and liver/kidney function. Drug concentration in tissues was measured using fluorescence tracing and high-performance liquid chromatography to gauge ICO delivery efficiency.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;ICO injection delivers drugs to the brain parenchyma through microchannels between the skull bone marrow and the dura mater, offering higher delivery efficiency than intravenous injection. After ICO injection, there were no changes in neutrophil counts in the skull bone marrow and peripheral blood, and the amount of FITC-dextran passing through the BBB remained unchanged. This confirmed that ICO injection does not cause skull infection or break BBB, which suggested ICO injection is safe and feasible. In the treatment of stroke with neuroprotective agents, although the drug dosage of ICO injection was lower than intravenous injection, drug accumulation in the brain increased after ICO injection, which helped repair nerve damage, reduce neuronal apoptosis, and decrease the expression of inflammatory factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;ICO injection is a central nervous system drug delivery method that utilizes natural microchannels between the skull and dura mater for efficient drug delivery. Our results assessed the feasibility and safety of ICO injection at the preclinical level and evaluated its efficacy in animal models of stroke. The findings provided a foundation for the clinical translation of ICO injection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This study was supported by The National Natural Science Foundation of China (No. 82425101); Beijing Municipal Science & Technology Commission (No. Z231100004823036); Capital's Funds for Health Improvement and Research (2022-2-2045); National Key Research & Development Program of China (2022YFF1501500, 2022YFF1501501, 2022YF","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105568"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Physio-fUS: a tissue-motion based method for heart and breathing rate assessment in neurofunctional ultrasound imaging.
IF 9.7 1区 医学
EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-31 DOI: 10.1016/j.ebiom.2025.105581
Nicolas Zucker, Samuel Le Meur-Diebolt, Felipe Cybis Pereira, Jérôme Baranger, Isabella Hurvitz, Charlie Demené, Bruno-Félix Osmanski, Nathalie Ialy-Radio, Valérie Biran, Olivier Baud, Sophie Pezet, Thomas Deffieux, Mickael Tanter
{"title":"Physio-fUS: a tissue-motion based method for heart and breathing rate assessment in neurofunctional ultrasound imaging.","authors":"Nicolas Zucker, Samuel Le Meur-Diebolt, Felipe Cybis Pereira, Jérôme Baranger, Isabella Hurvitz, Charlie Demené, Bruno-Félix Osmanski, Nathalie Ialy-Radio, Valérie Biran, Olivier Baud, Sophie Pezet, Thomas Deffieux, Mickael Tanter","doi":"10.1016/j.ebiom.2025.105581","DOIUrl":"10.1016/j.ebiom.2025.105581","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have shown growing evidence that brain function is closely synchronised with global physiological parameters. Heart rate is linked to various cognitive processes and a strong correlation between neuronal activity and breathing has been demonstrated. These findings highlight the significance of monitoring these key physiological parameters during neuroimaging as they provide valuable insights into the overall brain function. Today, in neuroimaging, assessing these parameters requires additional cumbersome devices or implanted electrodes. Here we demonstrate that ultrasonic neurofunctional imaging data alone is sufficient to extract these parameters.</p><p><strong>Methods: </strong>In this work, we performed ultrafast ultrasound imaging in male rodents and human neonates, and we extracted heart and breathing rates from local tissue motion assessed by raw ultrasound data processing. Such \"Physio-fUS\" automatically selects two specific and optimal brain regions with pulsatile tissue signals to monitor such parameters.</p><p><strong>Findings: </strong>We validated the correspondence of these periodic signals with heart and breathing rates assessed using gold-standard electrodes in anaesthetised rodents. We extracted heart and breathing rates in sleeping rats and heart rate in rats moving freely in an arena. We also validated Physio-fUS imaging in sleeping human newborns using conventional ECG.</p><p><strong>Interpretation: </strong>We show the potential of fUS imaging as an integrative tool for simultaneously monitoring physiological parameters during neurofunctional imaging. Beyond the technological improvement, it could enhance our understanding of the link between breathing, heart rate and neurovascular activity in preclinical research and clinical functional ultrasound imaging.</p><p><strong>Funding: </strong>This study was supported by the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement n°311025 and by the Fondation Bettencourt-Schueller under the program \"Physics for Medicine\".</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105581"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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