Stem Cells Translational Medicine最新文献

{"title":"In vivo bioengineered tooth formation using decellularized tooth bud extracellular matrix scaffolds.","authors":"Weibo Zhang, Pamela C Yelick","doi":"10.1093/stcltm/szae076","DOIUrl":"10.1093/stcltm/szae076","url":null,"abstract":"<p><p>The use of dental implants to replace lost or damaged teeth has become increasingly widespread due to their reported high survival and success rates. In reality, the long-term survival of dental implants remains a health concern, based on their short-term predicted survival of ~15 years, significant potential for jawbone resorption, and risk of peri-implantitis. The ability to create functional bioengineered teeth, composed of living tissues with properties similar to those of natural teeth, would be a significant improvement over currently used synthetic titanium implants. To address this possibility, our research has focused on creating biological tooth substitutes. The study presented here validates a potentially clinically relevant bioengineered tooth replacement therapy for eventual use in humans. We created bioengineered tooth buds by seeding decellularized tooth bud (dTB) extracellular matrix (ECM) scaffolds with human dental pulp cells, porcine tooth bud-derived dental epithelial cells, and human umbilical vein endothelial cells. The resulting bioengineered tooth bud constructs were implanted in the mandibles of adult Yucatan minipigs and grown for 2 or 4 months. We observed the formation of tooth-like tissues, including tooth-supporting periodontal ligament tissues, in cell-seeded dTB ECM constructs. This preclinical translational study validates this approach as a potential clinically relevant alternative to currently used dental implants.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898300","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":"Targeting chromatin modifying complexes in acute myeloid leukemia.","authors":"Alexandra Schurer, Shira G Glushakow-Smith, Kira Gritsman","doi":"10.1093/stcltm/szae089","DOIUrl":"10.1093/stcltm/szae089","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a devastating hematologic malignancy with high rates of relapse, which can, in part, be attributed to the dysregulation of chromatin modifications. These epigenetic modifications can affect the capacity of hematopoietic cells to self-renew or differentiate, which can lead to transformation. Aberrant histone modifications contribute to the derepression of self-renewal genes such as HOXA/B and MEIS1 in committed hematopoietic progenitors, which is considered a key mechanism of leukemogenesis in MLL-rearranged (MLL-r) and NPM1-mutated AML. As regulators of some of the key histone modifications in this disease, the menin-KMT2A and polycomb repressive (PRC1/2) complexes have been identified as promising targets for the treatment of AML. This review explores recent discoveries of how leukemic cells hijack these complexes and their interactions with other chromatin regulators to promote disease progression. We also discuss inhibitors targeting these complexes that have demonstrated therapeutic efficacy in preclinical and clinical studies and propose novel therapeutic combinations targeting the KMT2A and PRC1/2 broader interacting networks to overcome issues of resistance to existing monotherapies.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751719","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":"Exosomes containing miR-148a-3p derived from mesenchymal stem cells suppress epithelial-mesenchymal transition in lens epithelial cells.","authors":"Jingyu Ma, Qihang Sun, Yijia Chen, Jinyan Li, Shuyi Chen, Lixia Luo","doi":"10.1093/stcltm/szae091","DOIUrl":"10.1093/stcltm/szae091","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is responsible for the development of fibrotic cataracts, which contribute to severe visual impairment. Recent evidence has shown that mesenchymal stem cell-derived exosomes (MSC-Exo) can attenuate EMT in several tissues. However, the effect of MSC-Exo on EMT in LECs (LECs-EMT) has not been determined. In this study, we isolated exosomes from human umbilical cord MSCs (hucMSC-Exo) and evaluated their effect on LECs-EMT both in vitro and in vivo. HucMSC-Exo application significantly suppressed the expression of mesenchymal cell-associated genes while increasing the expression of epithelial cell-associated genes. Cell proliferation and migration of LECs undergoing EMT were inhibited after hucMSC-Exo treatment. The volume of EMT plaques in mice with injury-induced anterior subcapsular cataract (ASC) was significantly reduced in the hucMSC-Exo-treated group. Furthermore, miR-148a-3p was abundant in hucMSC-Exo. After transfection with miR-148a-3p inhibitor, the anti-fibrotic effect of hucMSC-Exo was attenuated in LECs-EMT. A dual-luciferase reporter assay identified PRNP as a direct target gene of miR-148a-3p. Furthermore, we verified that hucMSC-Exo inhibited LECs-EMT through the miR-148a-3p/PRNP axis and the potential downstream ERK signaling pathway. Taken together, our work reveals the inhibitory effect of hucMSC-Exo on LECs-EMT and the underlying mechanism involved, which may provide potential therapeutic options for fibrotic cataracts.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 2","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557938","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":"Autophagy modulates tenogenic differentiation of cartilage-derived stem cells in response to mechanical tension via FGF signaling.","authors":"Rui Zuo, Haoke Li, Chenhui Cai, Wen Xia, Jiabin Liu, Jie Li, Yuan Xu, Yi Zhang, Changqing Li, Yuzhang Wu, Chao Zhang","doi":"10.1093/stcltm/szae085","DOIUrl":"10.1093/stcltm/szae085","url":null,"abstract":"<p><strong>Background: </strong>In our previous study, we demonstrated that cartilage-derived stem cells (CDSCs) possess multi-differentiation potential, enabling direct bone-to-tendon structure regeneration after transplantation in a rat model. Therefore, the objective of this study is to investigate whether CDSCs are a suitable candidate for achieving biological regeneration of tendon injuries.</p><p><strong>Methods: </strong>Tenogenic differentiation was evaluated through cell morphology observation, PCR, and Western blot (WB) analysis. Autophagic flux, transmission electron microscopy, and WB analysis were employed to elucidate the role of autophagy during CDSC tenogenic differentiation. Cell survival and tenogenesis of transplanted CDSCs were assessed using fluorescence detection of gross and frozen section images. Heterotopic ossification and quality of tendon healing were evaluated by immunofluorescence, hematoxylin-eosin (H&E), and Safrinin O/Fast Green stains.</p><p><strong>Results: </strong>We found autophagy is activated in CDSCs when treated with cyclic tensile stress, which facilitates the preservation of their chondrogenic potential while impeding tenogenic differentiation. Inhibiting autophagy with chloroquine promoted tenogenic differentiation of CDSCs in response to cyclic tensile stress through activation of the Fgf2/Fgfr2 signaling pathway. This mechanism was further validated by 2 mouse transplantation models, revealed that autophagy inhibition could enhance the tendon regeneration efficacy of transplanted CDSCs at the patellar tendon resection site.</p><p><strong>Conclusion: </strong>Our findings provide insights into CDSC transplantation for achieving biological regeneration of tendon injuries, and demonstrate how modulation of autophagy in CDSCs can promote tenogenic differentiation in response to tensile stress both in vivo and in vitro.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823465","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":"Investigational New Drug-enabling studies to use genetically modified mesenchymal stromal cells in patients with critical limb ischemia.","authors":"Amin Cressman, Bryan Le, David Morales, Won-Shin Yen, Fang-Ju Wu, Nicholas H Perotti, Brian Fury, Jan A Nolta, Fernando A Fierro","doi":"10.1093/stcltm/szae094","DOIUrl":"10.1093/stcltm/szae094","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have been tested in multiple clinical trials to treat peripheral artery disease, especially the more severe form called critical limb ischemia. However, MSCs have often not met the expected efficacy endpoints. We developed a more potent therapeutic by genetically modifying MSCs to overexpress Vascular Endothelial Growth Factor (VEGF-A165). Here, we report preclinical studies submitted to the Food and Drug Administration (FDA) as part of our Investigational New Drug submission package. In vitro studies included the characterization of cell banks, transcriptome and secretome analysis, and in vitro potency assays. In vivo studies using immune-deficient NSG mice include dose-finding efficacy studies using a Matrigel plug model, cell retention studies, measurements of circulating VEGF, and toxicology studies to rule out severe adverse events. Our results suggest both the safety and efficacy of MSC/VEGF and support a first-in-human clinical trial to test this new combined cell/gene therapy.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 2","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557951","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":"Correction to: Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes.","authors":"","doi":"10.1093/stcltm/szaf003","DOIUrl":"10.1093/stcltm/szaf003","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 2","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415357","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":"Cell-based therapies in preclinical models of necrotizing enterocolitis: a systematic review and meta-analysis.","authors":"Camille Maltais-Bilodeau, Ewa Henckel, Marc-Olivier Deguise, Flore Lesage, Kelly D Cobey, Nadera Ahmadzai, Becky Skidmore, Emanuela Ferretti, Bernard Thébaud","doi":"10.1093/stcltm/szae102","DOIUrl":"10.1093/stcltm/szae102","url":null,"abstract":"<p><p>Necrotizing enterocolitis (NEC) remains an incurable gut complication of prematurity with significant morbidity and mortality. Cell therapies, including mesenchymal stromal cells (MSCs), may be a promising treatment given their anti-inflammatory and regenerative potential. We assessed the effect of MSCs and other cell therapies (not classified as MSCs) on incidence, severity, and mortality in preclinical models of NEC. Bibliographic and gray literature searches yielded 17 371 records with 107 full-text articles assessed and ultimately 16 studies were included. These studies featured only rodents NEC models via combination of hyperosmolar feeds, hypoxia, hypothermia, or lipopolysaccharides. Ten studies used interventions with MSCs. Only 2 met the minimal criteria to define MSCs proposed by the International Society for Cell & Gene Therapy (ISCT). The overall risk of bias was assessed as high partly due to paucity of data with important gaps in reporting, reinforcing the importance of rigorous research framework, appropriate cell-therapy and outcome reporting in preclinical research. A reduction in the incidence of NEC (odds ratio [OR] 0.32, 95% CI [0.17, 0.62]), severe NEC (OR 0.30, 95% CI [0.18, 0.50]), and mortality (OR 0.30, 95% CI [0.16, 0.55]) was noted with MSCs treatment, seemingly more pronounced for ISCT-defined (ISCT+) MSCs. Amniotic fluid stem cells, neural stem cells, and placenta stem cells also showed a reduction in these measures. Given their accessibility (ie, umbilical cord) and proven safety profile in extremely preterm infants, our analysis provides a foundation for considering MSCs as promising candidate that requires further evaluation for the treatment of NEC.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 2","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557935","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":"LncRNA NR_045147 modulates osteogenic differentiation and migration in PDLSCs via ITGB3BP degradation and mitochondrial dysfunction.","authors":"Lujue Long, Chen Zhang, Zhengquan He, Ousheng Liu, Haoqing Yang, Zhipeng Fan","doi":"10.1093/stcltm/szae088","DOIUrl":"10.1093/stcltm/szae088","url":null,"abstract":"<p><p>Periodontitis is an inflammation of the alveolar bone and soft tissue surrounding the teeth. Although mesenchymal stem cells (MSCs) have been implicated in periodontal regeneration, the mechanisms by which they promote osteogenesis remain unclear. We examined whether epigenetic modifications mediated by the long-noncoding RNA (lncRNA) NR_045147, which plays a crucial role in cancer, influence the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Alkaline phosphatase staining, alizarin red staining, and western blotting were used to detect the effects of NR_045147 on PDLSC osteogenic differentiation. Scratch migration and transwell chemotaxis assays were used to evaluate the effects of NR_045147 on PDLSC migration. Mitochondrial function was evaluated via Seahorse XF analysis to measure changes in cellular respiration upon manipulation of NR_045147 expression. Ubiquitination assays were performed to examine the protein stability and degradation pathways affected by the NR_045147-MDM2 interaction. An in vivo nude rat calvarial defect model was established and gene-edited PDLSCs were re-implanted to examine the osteogenic effects of NR_045147. NR_045147 significantly reduced PDLSC osteogenic differentiation and migration ability both in vitro and in vivo. Under inflammatory conditions, the loss of NR_045147 rescued osteogenesis. NR_045147 significantly blocked the expression of integrin beta3-binding protein (ITGB3BP). Mechanistically, NR_045147 promoted the ITGB3BP-MDM2 interaction, thus increasing ITGB3BP ubiquitination and degradation. NR_045147 regulated PDLSC mitochondrial respiration and ITGB3BP upregulation efficiently promoted their osteogenic differentiation and migration ability. Concluding, NR_045147 downregulation enhances PDLSC osteogenic differentiation and migration, connects changes in cellular metabolism to functional outcomes via mitochondrial respiration, and promotes ITGB3BP degradation by mediating its interaction with MDM2.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824115","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":"A comprehensive evaluation system for ultrasound-guided infusion of human umbilical cord-derived MSCs in liver cirrhosis patients.","authors":"Guo Zhou, Yijuan You, Binghua Wang, Simin Wang, Tianhang Feng, Chunyou Lai, Guangming Xiang, Ke Yang, Yutong Yao","doi":"10.1093/stcltm/szae081","DOIUrl":"10.1093/stcltm/szae081","url":null,"abstract":"<p><strong>Background: </strong>Infusion of mesenchymal stem cells (MSCs) via portal vein is one of the main ways for MSCs transplantation to treat liver cirrhosis (LC). As the tissue of LC showed diffuse fibrosis and thickened Glission sheath, the soft pig-tail catheter, or central venous catheter can not successfully insert the portal vein. Thus, our study used an improved method and performed a relatively comprehensive system to evaluate the effect for human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation.</p><p><strong>Method: </strong>Fifteen patients with hepatitis B-related cirrhosis were enrolled in the study, and we performed hUC-MSCs transplantation via portal vein by using an 16-G needle and 0.035-inch guide wire combined with 7FR \"retentional metal stiffner trocar\" of pig-tail catheter under the guidance of contrast-enhanced ultrasound. Serum liver function, fibrotic indicators, tissue stiffness, coagulation function, and hemodynamics were measured at weeks 4, 12, and 24 after MSCs transplantation. Liver biopsy was performed before and 24 weeks after hUC-MSCs transplantation.</p><p><strong>Result: </strong>After hUC-MSCs transplantation, the prothrombin time was lower than before. The levels of hyaluronic acid and IV-C(Type IV collagen) in fibrotic indicators were significantly reduced, and the Young's modulus was also decreased. Moreover, liver biopsy showed that the lytic necrosis of hepatocyte was decreased. In liver hemodynamics, the portal vein diameter was decreased after hUC-MSCs transplantation.</p><p><strong>Conclusion: </strong>hUC-MSCs transplantation can alleviate liver damage caused by LC. The improved \"retentional metal stiffner trocar\" of pig-tail catheter was safe and effective in the infusion of hUC-MSCs transplantation, which is worth promoting in clinical practice.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628459","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":"Amniotic fluid stem cell extracellular vesicles as a novel fetal therapy for pulmonary hypoplasia: a review on mechanisms and translational potential.","authors":"Fabian Doktor, Lina Antounians, Rebeca Lopes Figueira, Kasra Khalaj, Miriam Duci, Augusto Zani","doi":"10.1093/stcltm/szae095","DOIUrl":"10.1093/stcltm/szae095","url":null,"abstract":"<p><p>Disruption of developmental processes affecting the fetal lung leads to pulmonary hypoplasia. Pulmonary hypoplasia results from several conditions including congenital diaphragmatic hernia (CDH) and oligohydramnios. Both entities have high morbidity and mortality, and no effective therapy that fully restores normal lung development. Hypoplastic lungs have impaired growth (arrested branching morphogenesis), maturation (decreased epithelial/mesenchymal differentiation), and vascularization (endothelial dysfunction and vascular remodeling leading to postnatal pulmonary hypertension). Herein, we discuss the pathogenesis of pulmonary hypoplasia and the role of microRNAs (miRNAs) during normal and pathological lung development. Since multiple cells and pathways are altered, the ideal strategy for hypoplastic lungs is to deliver a therapy that addresses all aspects of abnormal lung development. In this review, we report on a novel regenerative approach based on the administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs). Specifically, we describe the effects of AFSC-EVs in rodent and human models of pulmonary hypoplasia, their mechanism of action via release of their cargo, including miRNAs, and their anti-inflammatory properties. We also compare cargo contents and regenerative effects of EVs from AFSCs and mesenchymal stromal cells (MSCs). Overall, there is compelling evidence that antenatal administration of AFSC-EVs rescues multiple features of fetal lung development in experimental models of pulmonary hypoplasia. Lastly, we discuss the steps that need to be taken to translate this promising EV-based therapy from the bench to the bedside. These include strategies to overcome barriers commonly associated with EV therapeutics and specific challenges related to stem cell-based therapies in fetal medicine.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056039","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}