STEM CELLS最新文献

{"title":"Impact of pro-inflammatory cytokine preconditioning on metabolism and extracellular vesicles in feline mesenchymal stromal cells: a preliminary study.","authors":"Maria Soltero-Rivera, Boaz Arzi, Lynda Bourebaba, Krzysztof Marycz","doi":"10.1093/stmcls/sxaf014","DOIUrl":"10.1093/stmcls/sxaf014","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) derived from mesenchymal stem cells have shown promise in treating inflammation. This study investigates whether preconditioning feline adipose-derived stem cells (FeASCs) with inflammatory cytokines, specifically IFN-γ and TNF-α, enhances the anti-inflammatory efficacy of MSC-derived EVs.</p><p><strong>Objective: </strong>We hypothesize that cytokine-primed FeASCs will produce EVs with improved anti-inflammatory properties and that this preconditioning will affect mitochondrial dynamics to enhance EV therapy effectiveness.</p><p><strong>Methods: </strong>FeASCs were exposed to a TNF-α/IFN-γ combination to mimic a pro-inflammatory milieu favoring ASCs' immunosuppressive phenotype. We analyzed morphological, metabolic, and immunomodulatory characteristics of native and cytokine-primed FeASCs. EVs were assessed for anti-inflammatory and mitochondrial-related markers. We also evaluated mitochondrial function and apoptosis markers in cytokine-primed cells.</p><p><strong>Results: </strong>Cytokine priming led to significant morphological changes in FeASCs, including enhanced cell projections and increased apoptosis. EVs from cytokine-primed FeASCs exhibited a heightened immunomodulatory profile, with increased expression of both pro-inflammatory and anti-inflammatory mediators. Transcriptomic analysis of these EVs revealed the upregulation of genes associated with cell proliferation, survival, and apoptosis. Mitochondrial function was impaired in cytokine-primed cells, but mitochondrial morphology remained unchanged. EVs from these cells contained higher levels of mitochondrial-related transcripts, indicating a compensatory response.</p><p><strong>Conclusions: </strong>Cytokine-primed FeASCs generate EVs with enhanced immunomodulatory potential, highlighting their therapeutic promise. However, further research is needed to validate their efficacy and safety and refine preconditioning strategies to optimize EV-based therapies for inflammatory conditions. These advancements could pave the way for broader applications in regenerative medicine.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rabbit induced pluripotent stem cells-derived mesenchymal stem cells for enhanced wound healing.","authors":"Hsing-Yi Yu, Yang-Zhe Huang, Edward Chern","doi":"10.1093/stmcls/sxaf028","DOIUrl":"10.1093/stmcls/sxaf028","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine, particularly for their efficacy in tissue repair. However, sourcing high-quality MSCs presents challenges due to limited availability and compromised function. Induced pluripotent stem cells (iPSCs) offer a promising alternative for generating MSCs through specific differentiation protocols. In this study, we employed rabbit iPSCs to explore their capacity for differentiation into MSCs, facilitated by the use of SB431542, a TGF-β signaling inhibitor. Upon treatment with SB431542, rabbit iPSCs underwent embryoid body (EB) formation, leading to successful differentiation into the mesenchymal lineage. Our results demonstrated significant upregulation of mesodermal markers while reduced expression of ectodermal and endodermal markers, confirming effective MSC differentiation. Additionally, in a mouse wound healing model, rabbit iPSC-derived MSCs significantly enhanced wound closure compared to controls. These findings highlight the potential of SB431542 in generating functional iPSC-derived MSCs, offering valuable applications in regenerative medicine across species.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advantages of cell proliferation and immune regulation in CD146+NESTIN+ HUMSCs: insights from single-cell RNA sequencing.","authors":"Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma","doi":"10.1093/stmcls/sxae063","DOIUrl":"10.1093/stmcls/sxae063","url":null,"abstract":"<p><p>The heterogeneity of stem cells is a significant factor inhibiting their clinical application, as different cell subpopulations may exhibit substantial differences in biological functions. We performed single-cell sequencing on human umbilical cord mesenchymal stem cells (HUMSCs) from 3 donors of different gestational ages (22 + 5, 28, and 39 weeks). We also compared the data with single-cell sequencing data from BMSCs from 2 public databases. The content of CD146+Nestin+ MSCs in preterm HUMSCs (22 + 5W: 30.2%, 28W: 25.8%) was higher than that in full-term HUMSCs (39W: 0.5%) and BMSCs (BMSC1: 0, BMSC2: 0.9%). Cell cycle analysis indicated a higher proportion of cells in the proliferative G2M phase in CD146+Nestin+ MSCs (40.8%) compared to CD146+Nestin- MSCs (20%) and CD146-Nestin- MSCs (12.5%). The degree of differentiation assessment suggested that CD146+Nestin+ MSCs exhibited lower differentiation than other cell subpopulations. Differential gene analysis revealed that CD146+Nestin+ MSCs overexpressed immune regulation-related factors. GO and KEGG enrichment analysis of modules identified by weighted gene co-expression network analysis suggested enrichment in pathways related to cellular immune regulation, antimicrobial activity, and proliferation. Immune-related gene analysis indicated that CD146+Nestin+ MSCs exhibited expression of multiple immune-related genes associated with \"antimicrobials,\" \"cytokines,\" and \"cytokine receptors.\" Gene regulatory network analysis revealed high expression of immune-related regulators RELB, GAPB1, and EHF in CD146+Nestin+ MSCs. Our study provides a single-cell atlas of preterm HUMSCs, demonstrating the expression of CD146+Nestin+ MSCs across different tissues and confirming their advantages in cellular proliferation, antimicrobial activity, immune regulation, and low differentiation at the RNA level. This contributes valuable insights for the clinical application of HUMSCs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E3 ligase Trim63 promotes the chondrogenic differentiation of mesenchymal stem cells by catalyzing K27-linked cysteine ubiquitination of Myh11.","authors":"Shanyu Ye, Yanqing Wang, Ziwei Luo, Aijun Liu, Xican Li, Jiasong Guo, Wei Zhao, Dongfeng Chen, Lin Yang, Helu Liu","doi":"10.1093/stmcls/sxaf017","DOIUrl":"10.1093/stmcls/sxaf017","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are multipotent stem cells that have a chondrogenic differentiation capacity. However, the molecular mechanism underlying the chondrogenic differentiation of MSCs has not been fully elucidated, which hinders further development of MSC-based cell therapies for cartilage repair in the clinic. Here, we showed that the E3 ubiquitin ligase Trim63 positively regulates the chondrogenic differentiation of MSCs by catalyzing the K27-linked cysteine ubiquitination of Myh11. Trim63 directly interacts with Myh11 and catalyzes K27-linked ubiquitination of cys382. Mutation of cys382 diminishes Trim63-catalyzed K27-linked ubiquitination and chondrogenic differentiation of MSCs. A deficiency in Trim63 significantly impairs the chondrogenic differentiation of MSCs. Trim63 enhances the repair of articular cartilage defects in vivo. Taken together, the results of our study demonstrated that Trim63 promotes the chondrogenic differentiation of MSCs by catalyzing K27-linked cysteine ubiquitination of Myh11, which provides an alternative therapeutic target for cartilage regeneration and repair.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids.","authors":"Mathilde Colinet, Ioana Chiver, Antonela Bonafina, Gérald Masset, Daniel Almansa, Emmanuel Di Valentin, Jean-Claude Twizere, Laurent Nguyen, Ira Espuny-Camacho","doi":"10.1093/stmcls/sxaf010","DOIUrl":"10.1093/stmcls/sxaf010","url":null,"abstract":"<p><p>SARS-CoV2, severe acute respiratory syndrome coronavirus 2, is frequently associated with neurological manifestations. Despite the presence of mild to severe CNS-related symptoms in a cohort of patients, there is no consensus whether the virus can infect directly brain tissue or if the symptoms in patients are a consequence of peripheral infectivity of the virus. Here, we use long-term human stem cell-derived cortical organoids to assess SARS-CoV2 infectivity of brain cells and unravel the cell-type tropism and its downstream pathological effects. Our results show consistent and reproducible low levels of SARS-CoV2 infection of astrocytes, deep projection neurons, upper callosal neurons, and inhibitory neurons in 6 months of human cortical organoids. Interestingly, astrocytes showed the highest infection rate among all infected cell populations which led to changes in their morphology and upregulation of SERPINA3, CD44, and S100A10 astrogliosis markers. Further, transcriptomic analysis revealed overall changes in expression of genes related to cell metabolism, astrogliosis and, inflammation and further, upregulation of cell survival pathways. Thus, local and minor infectivity of SARS-CoV2 in the brain may induce widespread adverse effects and lead to the resilience of dysregulated neurons and astrocytes within an inflammatory environment.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic retinopathy.","authors":"Jun Tong, Yueqin Chen, Xinru Ling, Zhenping Huang, Genhong Yao, Zhenggao Xie","doi":"10.1093/stmcls/sxaf023","DOIUrl":"10.1093/stmcls/sxaf023","url":null,"abstract":"<p><p>Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs on endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential of regionally activated injury/ischemia-induced stem cells for neural regeneration.","authors":"Takayuki Nakagomi","doi":"10.1093/stmcls/sxaf015","DOIUrl":"10.1093/stmcls/sxaf015","url":null,"abstract":"<p><p>In the past, the mammal central nervous system (CNS) was assumed to lack the capacity for neural repair. However, increasing evidence shows that the CNS has repair capacity after injury. The migratory capacity of neural stem/progenitor cells (NSPCs) from subventricular zones (SVZ) is limited, and the precise repair mechanism active after ischemic stroke remains unknown. Consequently, it remains unclear how neural regeneration occurs in regions far from the SVZ, such as the cortex, especially given that these NSPCs can only migrate toward ischemic areas within specific brain regions. Nonetheless, using a mouse model of ischemic stroke with ischemic areas limited to the ipsilateral side of the cortex, we previously identified regionally-derived stem cells, injury/ischemia-induced stem cells (iSCs), within poststroke areas. Moreover, we showed that iSCs, which had the potential to differentiate into electrophysiologically functional neurons, were present within ischemic areas in poststroke human brains. This indicates that ischemic insult can activate locally-derived stem cells, even in nonneurogenic zones, and that iSCs can help achieve neural regeneration after ischemic stroke. However, inflammatory cells typically fill ischemic areas impairing neural regeneration in these areas. Here, we present the origin, characterization, and roles of iSCs based on our recent research. In addition, we discussed the potential of iSC-based therapies to achieve neural regeneration after ischemic stroke.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.","authors":"Taiju Ando, Juntaro Yamasaki, Hideyuki Saya, Osamu Nagano","doi":"10.1093/stmcls/sxaf024","DOIUrl":"10.1093/stmcls/sxaf024","url":null,"abstract":"<p><p>CD44, a multifunctional cell surface protein, has emerged as a pivotal regulator in cancer stem cell (CSC) biology, orchestrating processes such as stemness, metabolic reprogramming, and therapeutic resistance. Recent studies have identified a critical role of CD44 in ferroptosis resistance by stabilizing SLC7A11 (xCT), a key component of the antioxidant defense system, enabling CSCs to evade oxidative stress and sustain tumorigenic potential. Additionally, CD44 regulates intracellular iron metabolism and redox balance, further supporting CSC survival and adaptation to stressful microenvironments. Therapeutic strategies targeting CD44, including ferroptosis inducers and combination therapies, have shown significant potential in preclinical and early clinical settings. Innovations such as CD44-mediated nanocarriers and metabolic inhibitors present novel opportunities to disrupt CSC-associated resistance mechanisms. Furthermore, the dynamic plasticity of CD44 isoforms governed by transcriptional, post-transcriptional, and epigenetic regulation underscores the importance of context-specific therapeutic approaches. This review highlights the multifaceted roles of CD44 in CSC biology, focusing on its contribution to ferroptosis resistance, iron metabolism, and redox regulation. Targeting CD44 offers a promising avenue for overcoming therapeutic resistance and improving the outcomes of refractory cancers. Future studies are needed to refine these strategies and enable their clinical translation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZIC1 transcription factor overexpression in segmental bone defects is associated with brown adipogenic and osteogenic differentiation.","authors":"Neelima Thottappillil, Zhao Li, Xin Xing, Shreya Arondekar, Manyu Zhu, Masnsen Cherief, Qizhi Qin, Myles Zhou, Mary Archer, Kristen Broderick, Bruno Pèault, Min Lee, Aaron W James","doi":"10.1093/stmcls/sxaf013","DOIUrl":"10.1093/stmcls/sxaf013","url":null,"abstract":"<p><p>Transcriptional factor regulation is central to the lineage commitment of stem/ progenitor cells. ZIC1 (ZIC family member 1) is a C2H2-type zinc finger transcription factor expressed during development, brown fat, and certain cancers. Previously, we observed that overexpression of ZIC1 induces osteogenic differentiation at the expense of white adipogenic differentiation. In the present study, the feasibility of ZIC1 overexpressed human progenitor cells in critical-sized bone defects was studied. To achieve this, human adipose stem/stromal cells with other without lentiviral ZIC1 overexpression were implanted in a femoral segmental defect model in NOD-SCIDγ mice. Results showed that ZIC1 overexpressed cells induced osteogenic differentiation by protein markers in a critical-sized femoral segment defect compared to empty lentiviral control, although bone union was not observed. The immunohistochemical evaluation showed that implantation of ZIC1 overexpression cells led to an increase in osteoblast antigen expression (RUNX2, OCN), activation of Hedgehog signaling (Patched1), and an increase in brown adipogenesis markers (ZIC1, EBF2). In contrast, no change in bone defect-associated vasculature was observed (CD31, Endomucin). Together, these data suggest that overexpression of the ZIC1 transcription factor in progenitor cells is associated with differentiation towards osteoblastic and brown adipogenic cell fates.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular therapies for the prevention and treatment of acute graft-versus-host disease.","authors":"Daniel Peltier, Van Anh Do-Thi, Timothy Devos, Bruce R Blazar, Tomomi Toubai","doi":"10.1093/stmcls/sxaf009","DOIUrl":"10.1093/stmcls/sxaf009","url":null,"abstract":"<p><p>Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) that is caused by donor immune cells attacking and damaging host tissues. Immune suppressive small molecule and protein-based therapeutics targeting donor anti-host immune cells are currently used for GVHD prophylaxis and treatment. Even with these therapies, aGVHD progresses to life-threatening steroid-refractory aGVHD (SR-aGVHD) in up to 50% of cases and is a risk factor for the subsequent development of debilitating chronic GVHD. To improve aGVHD-related outcomes, donor graft engineering techniques and adoptive transfer of immune modulatory cells have been explored. Highly rigorous donor graft T-cell depletion approaches have revealed that mitigation of aGVHD can be accompanied by slow immune recovery post-allo-HCT and reduction in anti-microbial and anti-leukemia responses resulting in increased relapse and infection rates, respectively. Recent T-cell separation techniques allowing for precision graft engineering by selectively eliminating aGVHD-causing T-cells (eg, naïve T-cells) without loss of T-cells with beneficial functions and retaining and/or enriching immune regulatory populations (eg, regulatory T-cells (Tregs) or myeloid-derived suppressor cells) have been tested and will continue to improve. Clinical cell-based regulatory therapies have been employed for targeting SR-aGVHD, particularly mesenchymal stem cells (MSCs) and more recently, Tregs. In this review, we summarize aGVHD pathophysiology, highlight newly discovered aGVHD mechanisms, and discuss current and emerging cellular and graft manipulation approaches for aGVHD prevention and treatment.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12111709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}