{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:24:20Z","timestamp":1764937460667,"version":"build-2065373602"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammation"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>\n                        <jats:italic>Abstract<\/jats:italic>\n                     <\/jats:title><jats:p>A cytokine storm (CS) is an out-of-control inflammatory response closely associated with the progression of diseases, such as multiple organ failure (MOF), severe sepsis, and severe or critical COVID-19. However, there is currently a lack of reliable diagnostic markers to distinguish CS from normal inflammatory responses. Tumor necrosis factor-\u03b1 (TNF-\u03b1) includes transmembrane TNF-\u03b1 (tmTNF-\u03b1) and secreted TNF-\u03b1 (sTNF-\u03b1). The MOF mouse model in this study showed that the tmTNF-\u03b1 expression changes in the neutrophils differed from the serum TNF-\u03b1 and serum IL-18, INF-\u03b3, IL-4, and IL-6. Furthermore, tmTNF-\u03b1, instead of serum TNF-\u03b1, IL-18, INF-\u03b3, IL-4, and IL-6, reflected liver and kidney tissue damage and increased with the aggravation of these injuries. Analysis of the ROC results showed that tmTNF-\u03b1 effectively distinguished between inflammatory responses and CS and efficiently differentiated between surviving and dead mice. It also significantly improved the diagnostic value of the traditional CRP marker for CS. These results indicated that the tmTNF-\u03b1 expressed in the neutrophils could be used to diagnose CS in MOF mice, providing an experimental basis to further develop tmTNF-\u03b1 for diagnosing CS patients.<\/jats:p>","DOI":"10.1007\/s10753-022-01738-6","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T18:02:53Z","timestamp":1663178573000},"page":"359-369","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Transmembrane TNF-\u03b1 as a Novel Biomarker for the Diagnosis of Cytokine Storms in a Mouse Model of Multiple Organ Failure"],"prefix":"10.1007","volume":"46","author":[{"given":"Peng","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongsheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"issue":"8","key":"1738_CR1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.it.2021.06.001","volume":"42","author":"R Karki","year":"2021","unstructured":"Karki, R., and T.D. Kanneganti. 2021. The \u2018cytokine storm\u2019: Molecular mechanisms and therapeutic prospects. Trends in Immunology 42 (8): 681\u2013705.","journal-title":"Trends in Immunology"},{"issue":"Pt B","key":"1738_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107087","volume":"89","author":"V Kumar","year":"2020","unstructured":"Kumar, V. 2020. Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets. IntImmunopharmacol 89 (Pt B): 107087.","journal-title":"IntImmunopharmacol"},{"issue":"23","key":"1738_CR3","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","volume":"383","author":"DC Fajgenbaum","year":"2020","unstructured":"Fajgenbaum, D.C., and C.H. June. 2020. Cytokine storm. New England Journal of Medicine 383 (23): 2255\u20132273.","journal-title":"New England Journal of Medicine"},{"issue":"8","key":"1738_CR4","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1093\/infdis\/jiab065","volume":"223","author":"NAF Janssen","year":"2021","unstructured":"Janssen, N.A.F., I. Grondman, A.H. de Nooijer, C.K. Boahen, V.A.C.M. Koeken, V. Matzaraki, V. Kumar, X. He, M. Kox, H.J.P.M. Koenen, R.L. Smeets, I. Joosten, R.J.M. Br\u00fcggemann, I.J.E. Kouijzer, H.G. van der Hoeven, J.A. Schouten, T. Frenzel, M.H.E. Reijers, W. Hoefsloot, A.S.M. Dofferhoff, M.J. van Apeldoorn, M.J.T. Blaauw, K. Veerman, C. Maas, A.H. Schoneveld, I.E. Hoefer, L.P.G. Derde, M. van Deuren, J.W.M. van der Meer, R. van Crevel, E.J. Giamarellos-Bourboulis, L.A.B. Joosten, M.M. van den Heuvel, J. Hoogerwerf, Q. de Mast, P. Pickkers, M.G. Netea, and F.L. van de Veerdonk. 2021. Dysregulated innate and adaptive immune responses discriminate disease severity in COVID-19. Journal of Infectious Diseases 223 (8): 1322\u20131333.","journal-title":"Journal of Infectious Diseases"},{"issue":"1","key":"1738_CR5","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1080\/22221751.2021.1884503","volume":"10","author":"X Yongzhi","year":"2021","unstructured":"Yongzhi, X. 2021. COVID-19-associated cytokine storm syndrome and diagnostic principles: An old and new Issue. Emerg Microbes Infect 10 (1): 266\u2013276.","journal-title":"Emerg Microbes Infect"},{"key":"1738_CR6","doi-asserted-by":"crossref","unstructured":"Kim J.S., J.Y Lee, J.W Yang, K.H Lee, M Effenberger, W Szpirt, A and Kronbichler J.I Shin. 2021. Immunopathogenesis and treatment of cytokine storm in COVID-19. Theranostics\u00a011(1): 316\u2013329.","DOI":"10.7150\/thno.49713"},{"issue":"3","key":"1738_CR7","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.jaci.2020.07.001","volume":"146","author":"A Copaescu","year":"2020","unstructured":"Copaescu, A., O. Smibert, A. Gibson, E.J. Phillips, and J.A. Trubiano. 2020. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. The Journal of Allergy and Clinical Immunology 146 (3): 518-534.e1.","journal-title":"The Journal of Allergy and Clinical Immunology"},{"key":"1738_CR8","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/969875","volume":"2013","author":"L Su","year":"2013","unstructured":"Su, L., L. Feng, Q. Song, H. Kang, X. Zhang, Z. Liang, Y. Jia, D. Feng, C. Liu, and L. Xie. 2013. Diagnostic value of dynamics serum sCD163, sTREM-1, PCT, and CRP in differentiating sepsis, severity assessment, and prognostic prediction. Mediators of Inflammation 2013: 969875.","journal-title":"Mediators of Inflammation"},{"issue":"2","key":"1738_CR9","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1515\/cclm-2015-0277","volume":"54","author":"AP Yang","year":"2016","unstructured":"Yang, A.P., J. Liu, L.H. Yue, H.Q. Wang, W.J. Yang, and G.H. Yang. 2016. Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis. Clinical Chemistry and Laboratory Medicine 54 (2): 345\u2013351.","journal-title":"Clinical Chemistry and Laboratory Medicine"},{"issue":"7","key":"1738_CR10","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/rheumatology\/keq031","volume":"49","author":"T Horiuchi","year":"2010","unstructured":"Horiuchi, T., H. Mitoma, S. Harashima, H. Tsukamoto, and T. Shimoda. 2010. Transmembrane TNF-alpha: Structure, function and interaction with anti-TNF agents. Rheumatology (Oxford) 49 (7): 1215\u20131228.","journal-title":"Rheumatology (Oxford)"},{"issue":"12","key":"1738_CR11","doi-asserted-by":"publisher","first-page":"3881","DOI":"10.4049\/jimmunol.149.12.3881","volume":"149","author":"CF Ware","year":"1992","unstructured":"Ware, C.F., P.D. Crowe, M.H. Grayson, M.J. Androlewicz, and J.L. Browning. 1992. Expression of surface lymphotoxin and tumor necrosis factor on activated T, B, and natural killer cells. The Journal of Immunology 149 (12): 3881\u20133888.","journal-title":"The Journal of Immunology"},{"issue":"3","key":"1738_CR12","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1136\/ard.2010.138065","volume":"70","author":"HL Wright","year":"2011","unstructured":"Wright, H.L., B. Chikura, R.C. Bucknall, R.J. Moots, and S.W. Edwards. 2011. Changes in expression of membrane TNF, NF-{kappa}B activation and neutrophil apoptosis during active and resolved inflammation. Annals of the Rheumatic Diseases 70 (3): 537\u2013543.","journal-title":"Annals of the Rheumatic Diseases"},{"issue":"13","key":"1738_CR13","doi-asserted-by":"publisher","first-page":"3938","DOI":"10.1158\/0008-5472.CAN-13-0002","volume":"73","author":"S Ardestani","year":"2013","unstructured":"Ardestani, S., B. Li, D.L. Deskins, H. Wu, P.P. Massion, and P.P. Young. 2013. Membrane versus soluble isoforms of TNF-\u03b1 exert opposing effects on tumor growth and survival of tumor-associated myeloid cells. Cancer Research 73 (13): 3938\u20133950.","journal-title":"Cancer Research"},{"issue":"13","key":"1738_CR14","doi-asserted-by":"publisher","first-page":"4061","DOI":"10.1158\/0008-5472.CAN-12-3946","volume":"73","author":"M Yu","year":"2013","unstructured":"Yu, M., X. Zhou, L. Niu, G. Lin, J. Huang, W. Zhou, H. Gan, J. Wang, X. Jiang, B. Yin, and Z. Li. 2013. Targeting transmembrane TNF-\u03b1 suppresses breast cancer growth. Cancer Research 73 (13): 4061\u20134074.","journal-title":"Cancer Research"},{"issue":"4","key":"1738_CR15","doi-asserted-by":"publisher","first-page":"801","DOI":"10.3390\/jcm10040801","volume":"10","author":"S Yokota","year":"2021","unstructured":"Yokota, S., T. Miyamae, Y. Kuroiwa, and K. Nishioka. 2021. Novel coronavirus disease 2019 (COVID-19) and cytokine storms for more effective treatments from an inflammatory pathophysiology. Journal of Clinical Medicine 10 (4): 801.","journal-title":"Journal of Clinical Medicine"},{"key":"1738_CR16","doi-asserted-by":"publisher","first-page":"5928078","DOI":"10.1155\/2017\/5928078","volume":"2017","author":"R Yang","year":"2017","unstructured":"Yang, R., X. Zou, J. Tenhunen, and T.I. T\u00f8nnessen. 2017. HMGB1 and extracellular histones significantly contribute to systemic inflammation and multiple organ failure in acute liver failure. Mediators of Inflammation 2017: 5928078.","journal-title":"Mediators of Inflammation"},{"issue":"6","key":"1738_CR17","doi-asserted-by":"publisher","first-page":"512","DOI":"10.4049\/immunohorizons.2000104","volume":"5","author":"KG Greenfield","year":"2021","unstructured":"Greenfield, K.G., V.P. Badovinac, T.S. Griffith, and K.A. Knoop. 2021. Sepsis, cytokine storms, and immunopathology: The divide between neonates and adults. Immunohorizons 5 (6): 512\u2013522.","journal-title":"Immunohorizons"},{"key":"1738_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.659419","volume":"12","author":"S Yuan","year":"2021","unstructured":"Yuan, S., S.C. Jiang, Z.W. Zhang, Y.F. Fu, J. Hu, and Z.L. Li. 2021. Quantification of cytokine storms during virus infections. Frontiers in Immunology 12: 659419.","journal-title":"Frontiers in Immunology"},{"key":"1738_CR19","doi-asserted-by":"crossref","unstructured":"Morris G., C.C., Bortolasci, B.K Puri, W Marx, A O'Neil, E Athan, K Walder, M Berk, L Olive, A.F Carvalho and M Maes. 2021. The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all? Cytokine 144:155593.","DOI":"10.1016\/j.cyto.2021.155593"},{"key":"1738_CR20","doi-asserted-by":"crossref","unstructured":"Bernardi, M., R. Moreau, P. Angeli, B. Schnabl and V. Arroyo. 2015. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. Journal of Hepatology 63 (5): 1272\u20131284.","DOI":"10.1016\/j.jhep.2015.07.004"},{"key":"1738_CR21","doi-asserted-by":"crossref","unstructured":"Cl\u00e0ria J., R. EStauber, M.J Coenraad, R. Moreau, R. Jalan, M. Pavesi, \u00c0. Amor\u00f3s, E. Titos, J. Alcaraz-Quiles, K. Oettl, M. Morales-Ruiz, P. Angeli, M. Domenicali, C. Alessandria, A. Gerbes, J. Wendon, F. Nevens, J.T. Rebicka, W. Laleman, F. Saliba, T.M. Welzel, A. Albillos, T. Gustot, D. Benten, F. Durand, P. Gin\u00e8s, M. Bernardi and V. Arroyo. 2016. CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure (EF-CLIF). Systemic inflammation in decompensated cirrhosis: characterization and role in acute-on-chronic liver failure. Hepatology\u00a064(4): 1249\u201364.","DOI":"10.1002\/hep.28740"},{"key":"1738_CR22","doi-asserted-by":"crossref","unstructured":"Durand, F., I. Graupera, P. Gin\u00e8s, J. COlson and M. K. Nadim. 2016. Pathogenesis of hepatorenal syndrome: Implications for therapy. American Journal of Kidney Diseases 67 (2): 318\u2013328.","DOI":"10.1053\/j.ajkd.2015.09.013"},{"key":"1738_CR23","doi-asserted-by":"crossref","unstructured":"Shakil, A.O., and DKramer, G.V. Mazariegos, J.J. Fung and J. Rakela. 2000. Acute liver failure: Clinical features, outcome analysis, and applicability of prognostic criteria. Liver Transplantation 6 (2): 163\u2013169.","DOI":"10.1016\/S1527-6465(00)80005-2"},{"issue":"6","key":"1738_CR24","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/s41591-018-0036-4","volume":"24","author":"NorelliM., B Camisa, G Barbiera, L","year":"2018","unstructured":"NorelliM., B Camisa, G Barbiera, L Falcone, A Purevdorj, M Genua, F Sanvito, M Ponzoni, C Doglioni, P Cristofori, C Traversari, C Bordignon, F Ciceri, R Ostuni, C Bonini, M Casucci, and A Bondanza. 2018. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nature Medicine 24 (6): 739\u2013748.","journal-title":"Nature Medicine"},{"issue":"1","key":"1738_CR25","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1080\/22221751.2020.1770129","volume":"9","author":"H Han","year":"2020","unstructured":"Han, H., Q. Ma, C. Li, R. Liu, L. Zhao, W. Wang, P. Zhang, X. Liu, G. Gao, F. Liu, Y. Jiang, X. Cheng, C. Zhu, and Y. Xia. 2020. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect 9 (1): 1123\u20131130.","journal-title":"Emerg Microbes Infect"},{"issue":"1","key":"1738_CR26","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1080\/07853890.2020.1840621","volume":"53","author":"N Broman","year":"2021","unstructured":"Broman, N., K. Rantas\u00e4rkk\u00e4, T. Feuth, M. Valtonen, M. Waris, U. Hohenthal, E. Rintala, A. Karlsson, H. Marttila, V. Peltola, T. Vuorinen, and J. Oksi. 2021. IL-6 and other biomarkers as predictors of severity in COVID-19. Annals of Medicine 53 (1): 410\u2013412.","journal-title":"Annals of Medicine"},{"issue":"1","key":"1738_CR27","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cell.2020.11.025","volume":"184","author":"R Karki","year":"2021","unstructured":"Karki, R., B.R. Sharma, S. Tuladhar, E.P. Williams, L. Zalduondo, P. Samir, M. Zheng, B. Sundaram, B. Banoth, R.K.S. Malireddi, P. Schreiner, G. Neale, P. Vogel, R. Webby, C.B. Jonsson, and T.D. Kanneganti. 2021. Synergism of TNF-\u03b1 and IFN-\u03b3 triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell 184 (1): 149-168.e17.","journal-title":"Cell"},{"issue":"6","key":"1738_CR28","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1128\/CVI.00147-15","volume":"22","author":"M Michels","year":"2015","unstructured":"Michels, M., Q. de Mast, M.G. Netea, L.A. Joosten, C.A. Dinarello, P.I. Rudiman, S. Sinarta, R. Wisaksana, B. Alisjahbana, and A.J. van der Ven. 2015. Normal free interleukin-18 (IL-18) plasma levels in dengue virus infection and the need to measure both total IL-18 and IL-18 binding protein levels. Clinical and Vaccine Immunology 22 (6): 650\u2013655.","journal-title":"Clinical and Vaccine Immunology"},{"issue":"9","key":"1738_CR29","first-page":"1315","volume":"5","author":"JN Mandrekar","year":"2010","unstructured":"Mandrekar, J.N. 2010. Receiver operating characteristic curve in diagnostic test assessment. J ThoracOncol 5 (9): 1315\u20131316.","journal-title":"J ThoracOncol"},{"key":"1738_CR30","doi-asserted-by":"crossref","unstructured":"Obuchowski N.A and J.A Bullen. 2018. Receiver operating characteristic (ROC) curves: review of methods with applications in diagnostic medicine. Physics in Medicine & Biology 63(7): 07TR01.","DOI":"10.1088\/1361-6560\/aab4b1"},{"key":"1738_CR31","volume":"127","author":"F Liu","year":"2020","unstructured":"Liu, F., L. Li, M. Xu, J. Wu, D. Luo, Y. Zhu, B. Li, X. Song, and X. Zhou. 2020. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J ClinVirol 127: 104370.","journal-title":"J ClinVirol"},{"issue":"6","key":"1738_CR32","first-page":"2265","volume":"34","author":"Alam J Mahmood","year":"2021","unstructured":"Mahmood, Alam J., S.S. Asghar, H. Ali, S.R. Mahmood, and M.A. Ansari. 2021. REPORT- Varying pattern of blood gases, ferritin, procalcitonin, C-reactive protein, interleukin 6 and lactate dehydrogenase in Covid-19 patients suffering from diverse co-morbid, suspected cytokine storm and periodic effects of antiviral and steroidal treatments. Pakistan Journal of Pharmaceutical Sciences 34 (6): 2265\u20132271.","journal-title":"Pakistan Journal of Pharmaceutical Sciences"},{"issue":"2","key":"1738_CR33","doi-asserted-by":"publisher","first-page":"561","DOI":"10.4269\/ajtmh.20-0473","volume":"103","author":"LA Potempa","year":"2020","unstructured":"Potempa, L.A., I.M. Rajab, P.C. Hart, J. Bordon, and R. Fernandez-Botran. 2020. Insights into the use of C-reactive protein as a diagnostic index of disease severity in COVID-19 infections. American Journal of Tropical Medicine and Hygiene 103 (2): 561\u2013563.","journal-title":"American Journal of Tropical Medicine and Hygiene"},{"issue":"1","key":"1738_CR34","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1002\/jmv.26156","volume":"93","author":"W Luo","year":"2021","unstructured":"Luo, W., J.W. Zhang, W. Zhang, Y.L. Lin, and Q. Wang. 2021. Circulating levels of IL-2, IL-4, TNF-\u03b1, IFN-\u03b3, and C-reactive protein are not associated with severity of COVID-19 symptoms. Journal of Medical Virology 93 (1): 89\u201391.","journal-title":"Journal of Medical Virology"}],"container-title":["Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-022-01738-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10753-022-01738-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-022-01738-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T06:15:47Z","timestamp":1677478547000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10753-022-01738-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,14]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["1738"],"URL":"https:\/\/doi.org\/10.1007\/s10753-022-01738-6","relation":{},"ISSN":["0360-3997","1573-2576"],"issn-type":[{"type":"print","value":"0360-3997"},{"type":"electronic","value":"1573-2576"}],"subject":[],"published":{"date-parts":[[2022,9,14]]},"assertion":[{"value":"15 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was authorized by the Ethics Committee of Guizhou University of Traditional Chinese Medicine (20210074). This study was performed in line with the guidelines of the Laboratory Protocol of Animal Handling, Clinical Laboratory of the Second Affiliated Hospital. All animals were housed under specific pathogen-free conditions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}