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      Therapeutic mechanisms of mesenchymal stem cells in acute respiratory distress syndrome reveal potentials for Covid-19 treatment

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          Abstract

          The mortality rate of critically ill patients with acute respiratory distress syndrome (ARDS) is 30.9% to 46.1%. The emergence of the coronavirus disease 2019 (Covid-19) has become a global issue with raising dire concerns. Patients with severe Covid-19 may progress toward ARDS. Mesenchymal stem cells (MSCs) can be derived from bone marrow, umbilical cord, adipose tissue and so on. The easy accessibility and low immunogenicity enable MSCs for allogeneic administration, and thus they were widely used in animal and clinical studies. Accumulating evidence suggests that mesenchymal stem cell infusion can ameliorate ARDS. However, the underlying mechanisms of MSCs need to be discussed. Recent studies showed MSCs can modulate immune/inflammatory cells, attenuate endoplasmic reticulum stress, and inhibit pulmonary fibrosis. The paracrine cytokines and exosomes may account for these beneficial effects. In this review, we summarize the therapeutic mechanisms of MSCs in ARDS, analyzed the most recent animal experiments and Covid-19 clinical trial results, discussed the adverse effects and prospects in the recent studies, and highlight the potential roles of MSC therapy for Covid-19 patients with ARDS.

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

            Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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              Acute respiratory distress syndrome: the Berlin Definition.

              The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.
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                Author and article information

                Contributors
                zzghyl@126.com
                ncylxf@126.com
                zhaozhenao@hebeinu.edu.cn
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                10 May 2021
                10 May 2021
                2021
                : 19
                : 198
                Affiliations
                [1 ]GRID grid.412026.3, ISNI 0000 0004 1776 2036, Institute of Microcirculation, , Hebei North University, ; 11 Diamond South-road, Keji Building, Room 213, Zhangjiakou, 075000 Hebei China
                [2 ]GRID grid.412026.3, ISNI 0000 0004 1776 2036, Department of Pathophysiology of Basic Medical College, , Hebei North University, ; Zhangjiakou, 075000 Hebei China
                [3 ]Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, 050017 Hebei China
                [4 ]Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Zhangjiakou, 075000 Hebei China
                [5 ]GRID grid.412026.3, ISNI 0000 0004 1776 2036, Pathophysiology Experimental Teaching Center of Basic Medical College, Hebei North University, ; Zhangjiakou, 075000 Hebei China
                [6 ]GRID grid.263761.7, ISNI 0000 0001 0198 0694, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, State Key Laboratory of Radiation Medicine and Protection, Medical College, , Soochow University, ; Suzhou, 215000 Jiangsu China
                [7 ]GRID grid.256883.2, ISNI 0000 0004 1760 8442, Basic Medical College, Hebei Medical University, ; Shijiazhuang, 050017 Hebei China
                Author information
                http://orcid.org/0000-0002-9868-2534
                Article
                2862
                10.1186/s12967-021-02862-x
                8107778
                33971907
                61bef75e-64ae-4595-b455-9f6168aaa6f8
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 16 February 2021
                : 30 April 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003787, Natural Science Foundation of Hebei Province;
                Award ID: C2020405008
                Award ID: H2020405023
                Award Recipient :
                Funded by: Scientific Research Project for Higher Education in Hebei Province
                Award ID: ZD2021005
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81770492
                Award Recipient :
                Funded by: Basic Research Foundation of Hebei North University
                Award ID: JYT2019002
                Award ID: JYT2019006
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Medicine
                mesenchymal stem cells,covid-19,acute respiratory distress syndrome
                Medicine
                mesenchymal stem cells, covid-19, acute respiratory distress syndrome

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