{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:58:06Z","timestamp":1784901486543,"version":"3.55.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Scientific Research Fund of Zhejiang Provincial Education Department","award":["Y202148325"],"award-info":[{"award-number":["Y202148325"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81827804"],"award-info":[{"award-number":["81827804"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802330"],"award-info":[{"award-number":["81802330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein\u2013protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-022-03394-8","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T13:08:12Z","timestamp":1651151292000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification of invasion-metastasis associated MiRNAs in gallbladder cancer by bioinformatics and experimental validation"],"prefix":"10.1186","volume":"20","author":[{"given":"Jiasheng","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijiang","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarun","family":"Jeungpanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Win","family":"Topatana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujun","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"3394_CR1","first-page":"99","volume":"6","author":"R Hundal","year":"2014","unstructured":"Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol. 2014;6:99\u2013109.","journal-title":"Clin Epidemiol"},{"key":"3394_CR2","first-page":"221","volume":"3","author":"M Raki\u0107","year":"2014","unstructured":"Raki\u0107 M, Patrlj L, Kopljar M, Kli\u010dek R, Kolovrat M, Loncar B, et al. Gallbladder cancer hepatobiliary. Surg Nutr. 2014;3:221\u20136.","journal-title":"Surg Nutr"},{"key":"3394_CR3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21654","volume":"71","author":"RL Siegel","year":"2021","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7\u201333.","journal-title":"CA Cancer J Clin"},{"key":"3394_CR4","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/S0140-6736(21)00153-7","volume":"397","author":"JW Valle","year":"2021","unstructured":"Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021;397:428\u201344.","journal-title":"Lancet"},{"key":"3394_CR5","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1245\/s10434-017-6025-x","volume":"25","author":"YS Chun","year":"2018","unstructured":"Chun YS, Pawlik TM, Vauthey JN. 8th Edition of the AJCC cancer staging manual: pancreas and hepatobiliary cancers. Ann Surg Oncol. 2018;25:845\u20137.","journal-title":"Ann Surg Oncol"},{"key":"3394_CR6","doi-asserted-by":"crossref","unstructured":"Mantripragada KC, Hamid F, Shafqat H, Olszewski AJ. Adjuvant therapy for resected gallbladder cancer: analysis of the national cancer data base. J Natl Cancer Inst. 2017;109.","DOI":"10.1093\/jnci\/djw202"},{"key":"3394_CR7","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000098","volume":"10","author":"M Chen","year":"2019","unstructured":"Chen M, Cao J, Bai Y, Tong C, Lin J, Jindal V, et al. Development and validation of a nomogram for early detection of malignant gallbladder lesions. Clin Transl Gastroenterol. 2019;10: e00098.","journal-title":"Clin Transl Gastroenterol"},{"key":"3394_CR8","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature25492","volume":"554","author":"DVF Tauriello","year":"2018","unstructured":"Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, Iglesias M, et al. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018;554:538\u201343.","journal-title":"Nature"},{"issue":"993\u20131002","key":"3394_CR9","volume":"29","author":"MJ Wu","year":"2019","unstructured":"Wu MJ, Chen YS, Kim MR, Chang CC, Gampala S, Zhang Y, et al. Epithelial\u2013mesenchymal transition directs stem cell polarity via regulation of mitofusin. Cell Metab. 2019;29(993\u20131002): e6.","journal-title":"Cell Metab"},{"key":"3394_CR10","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41419-018-0399-y","volume":"9","author":"L Zheng","year":"2018","unstructured":"Zheng L, Xu M, Xu J, Wu K, Fang Q, Liang Y, et al. ELF3 promotes epithelial-mesenchymal transition by protecting ZEB1 from miR-141-3p-mediated silencing in hepatocellular carcinoma. Cell Death Dis. 2018;9:387.","journal-title":"Cell Death Dis"},{"issue":"303\u201318","key":"3394_CR11","volume":"30","author":"G Civenni","year":"2019","unstructured":"Civenni G, Bosotti R, Timpanaro A, Vazquez R, Merulla J, Pandit S, et al. Epigenetic control of mitochondrial fission enables self-renewal of stem-like tumor cells in human prostate cancer. Cell Metab. 2019;30(303\u201318): e6.","journal-title":"Cell Metab"},{"key":"3394_CR12","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","volume":"136","author":"DP Bartel","year":"2009","unstructured":"Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215\u201333.","journal-title":"Cell"},{"key":"3394_CR13","first-page":"83","volume":"3","author":"GC Shukla","year":"2011","unstructured":"Shukla GC, Singh J, Barik S. MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 2011;3:83\u201392.","journal-title":"Mol Cell Pharmacol"},{"key":"3394_CR14","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1053\/j.gastro.2021.10.015","volume":"162","author":"N Liu","year":"2021","unstructured":"Liu N, Chang CW, Steer CJ, Wang XW, Song G. MicroRNA-15a\/16-1 prevents hepatocellular carcinoma by disrupting the communication between Kupffer cells and regulatory T cells. Gastroenterology. 2021;162:575.","journal-title":"Gastroenterology"},{"key":"3394_CR15","doi-asserted-by":"publisher","first-page":"19875","DOI":"10.1002\/jcp.28586","volume":"234","author":"M Zhu","year":"2019","unstructured":"Zhu M, Wei C, Lin J, Dong S, Gao D, Chen J, et al. UHRF1 is regulated by miR-124-3p and promotes cell proliferation in intrahepatic cholangiocarcinoma. J Cell Physiol. 2019;234:19875\u201385.","journal-title":"J Cell Physiol"},{"key":"3394_CR16","doi-asserted-by":"publisher","first-page":"7071","DOI":"10.1002\/jcp.30378","volume":"236","author":"E Roshani Asl","year":"2021","unstructured":"Roshani Asl E, Rasmi Y, Baradaran B. MicroRNA-124-3p suppresses PD-L1 expression and inhibits tumorigenesis of colorectal cancer cells via modulating STAT3 signaling. J Cell Physiol. 2021;236:7071\u201387.","journal-title":"J Cell Physiol"},{"key":"3394_CR17","doi-asserted-by":"publisher","first-page":"D322","DOI":"10.1093\/nar\/gkj021","volume":"34","author":"OC Gene","year":"2006","unstructured":"Gene OC. The Gene Ontology (GO) project in 2006. Nucleic Acids Res. 2006;34:D322\u20136.","journal-title":"Nucleic Acids Res"},{"key":"3394_CR18","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2105-14-128","volume":"14","author":"EY Chen","year":"2013","unstructured":"Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013;14:128.","journal-title":"BMC Bioinformatics"},{"key":"3394_CR19","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607\u201313.","journal-title":"Nucleic Acids Res"},{"key":"3394_CR20","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s00535-015-1145-1","volume":"51","author":"D Mohri","year":"2016","unstructured":"Mohri D, Ijichi H, Miyabayashi K, Takahashi R, Kudo Y, Sasaki T, et al. A potent therapeutics for gallbladder cancer by combinatorial inhibition of the MAPK and mTOR signaling networks. J Gastroenterol. 2016;51:711\u201321.","journal-title":"J Gastroenterol"},{"key":"3394_CR21","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/hep.31304","volume":"73","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Wang H, Chen T, Wang H, Liang X, Zhang Y, et al. C24-ceramide drives gallbladder cancer progression through directly targeting PIP4K2C to facilitate mTOR signaling activation. Hepatology. 2020;73:692.","journal-title":"Hepatology"},{"key":"3394_CR22","doi-asserted-by":"publisher","first-page":"6126","DOI":"10.1158\/1078-0432.CCR-04-0579","volume":"10","author":"T Takahashi","year":"2004","unstructured":"Takahashi T, Shivapurkar N, Riquelme E, Shigematsu H, Reddy J, Suzuki M, et al. Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res. 2004;10:6126\u201333.","journal-title":"Clin Cancer Res"},{"key":"3394_CR23","doi-asserted-by":"publisher","first-page":"6373","DOI":"10.1007\/s13277-014-1841-0","volume":"35","author":"F Wisnieski","year":"2014","unstructured":"Wisnieski F, Calcagno DQ, Leal MF, Chen ES, Gigek CO, Santos LC, et al. Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A. Tumour Biol. 2014;35:6373\u201381.","journal-title":"Tumour Biol"},{"key":"3394_CR24","doi-asserted-by":"publisher","first-page":"687","DOI":"10.4103\/IJPM.IJPM_138_20","volume":"64","author":"P Singh","year":"2021","unstructured":"Singh P, Jain SL, Sakhuja P, Agarwal A. Expression of VEGF-A, HER2\/neu, and KRAS in gall bladder carcinoma and their correlation with clinico-pathological parameters. Indian J Pathol Microbiol. 2021;64:687\u201392.","journal-title":"Indian J Pathol Microbiol"},{"key":"3394_CR25","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1186\/s13046-019-1250-8","volume":"38","author":"H Shen","year":"2019","unstructured":"Shen H, He M, Lin R, Zhan M, Xu S, Huang X, et al. PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR\/CCL2 pathway. J Exp Clin Cancer Res. 2019;38:247.","journal-title":"J Exp Clin Cancer Res"},{"key":"3394_CR26","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.jhep.2013.04.034","volume":"59","author":"Y Chang","year":"2013","unstructured":"Chang Y, Liu C, Yang J, Liu G, Feng F, Tang J, et al. MiR-20a triggers metastasis of gallbladder carcinoma. J Hepatol. 2013;59:518\u201327.","journal-title":"J Hepatol"},{"key":"3394_CR27","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/jhg.2010.54","volume":"55","author":"K Srivastava","year":"2010","unstructured":"Srivastava K, Srivastava A, Mittal B. Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population. J Hum Genet. 2010;55:495\u20139.","journal-title":"J Hum Genet"},{"key":"3394_CR28","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s00535-019-01627-0","volume":"55","author":"K Lu","year":"2020","unstructured":"Lu K, Feng F, Yang Y, Liu K, Duan J, Liu H, et al. High-throughput screening identified miR-7-2-3p and miR-29c-3p as metastasis suppressors in gallbladder carcinoma. J Gastroenterol. 2020;55:51\u201366.","journal-title":"J Gastroenterol"},{"key":"3394_CR29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.canlet.2018.05.022","volume":"430","author":"Q Ma","year":"2018","unstructured":"Ma Q, Zhang Y, Liang H, Zhang F, Liu F, Chen S, et al. EMP3, which is regulated by miR-663a, suppresses gallbladder cancer progression via interference with the MAPK\/ERK pathway. Cancer Lett. 2018;430:97\u2013108.","journal-title":"Cancer Lett"},{"key":"3394_CR30","doi-asserted-by":"publisher","first-page":"12298","DOI":"10.1038\/s41598-021-91804-0","volume":"11","author":"E Ueta","year":"2021","unstructured":"Ueta E, Tsutsumi K, Kato H, Matsushita H, Shiraha H, Fujii M, et al. Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients. Sci Rep. 2021;11:12298.","journal-title":"Sci Rep"},{"key":"3394_CR31","doi-asserted-by":"publisher","first-page":"724","DOI":"10.3389\/fcell.2020.00724","volume":"8","author":"W Wang","year":"2020","unstructured":"Wang W, Ding B, Lou W, Lin S. Promoter hypomethylation and miR-145-5p downregulation-mediated HDAC11 overexpression promotes sorafenib resistance and metastasis of hepatocellular carcinoma cells. Front Cell Dev Biol. 2020;8:724.","journal-title":"Front Cell Dev Biol"},{"key":"3394_CR32","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1186\/s12935-020-01483-6","volume":"20","author":"K Zhou","year":"2020","unstructured":"Zhou K, Song B, Wei M, Fang J, Xu Y. ANGPT2\/MiR-145-5p suppresses the proliferation, migration and invasion of gastric cancer epithelial cells via the NOD_LIKE_RECEPTOR axis. Cancer Cell Int. 2020;20:416.","journal-title":"Cancer Cell Int"},{"key":"3394_CR33","doi-asserted-by":"publisher","first-page":"7634","DOI":"10.1002\/jcp.27525","volume":"234","author":"T Zhou","year":"2019","unstructured":"Zhou T, Chen S, Mao X. miR-145-5p affects the differentiation of gastric cancer by targeting KLF5 directly. J Cell Physiol. 2019;234:7634\u201344.","journal-title":"J Cell Physiol"},{"key":"3394_CR34","first-page":"5975","volume":"34","author":"W Hsu","year":"2020","unstructured":"Hsu W, Li W, Lee Y, Huang A, Chang L, Lin H, et al. MicroRNA-145 suppresses cell migration and invasion in upper tract urothelial carcinoma by targeting ARF6. FASEB J Off Publ Fed Am Soc Exp Biol. 2020;34:5975\u201392.","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"3394_CR35","first-page":"74","volume":"20","author":"Z Yu","year":"2020","unstructured":"Yu Z, Du Y, Li H, Huang J, Jiang D, Fan J, et al. miR-642 serves as a tumor suppressor in hepatocellular carcinoma by regulating SEMA4C and p38 MAPK signaling pathway. Oncol Lett. 2020;20:74.","journal-title":"Oncol Lett"},{"key":"3394_CR36","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s41419-017-0258-2","volume":"9","author":"YP Jin","year":"2018","unstructured":"Jin YP, Hu YP, Wu XS, Wu YS, Ye YY, Li HF, et al. miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K\/AKT pathway in gallbladder carcinoma. Cell Death Dis. 2018;9:182.","journal-title":"Cell Death Dis"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-022-03394-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-022-03394-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-022-03394-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T13:18:08Z","timestamp":1651151888000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-022-03394-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["3394"],"URL":"https:\/\/doi.org\/10.1186\/s12967-022-03394-8","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,28]]},"assertion":[{"value":"2 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The current study was approved by the institutional ethics review board of Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China (No. 20210625-32) (Additional file : Ethics file). The patients provided their written informed consent to participate in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors deny any conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"188"}}