International journal of stem cells最新文献

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Guidelines for Packaging, Transport, and Storage of Source Cells for Organoids. 有机体源细胞的包装、运输和储存指南。
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-05-30 Epub Date: 2024-05-13 DOI: 10.15283/ijsc24042
Sungin Lee, Dayeon Kwon, Han Byeol Lee, Sooyeon Jeon, Chihye Park, Tae Sung Kim, Jin Hee Lee, Il Ung Oh, Sun-Ju Ahn
{"title":"Guidelines for Packaging, Transport, and Storage of Source Cells for Organoids.","authors":"Sungin Lee, Dayeon Kwon, Han Byeol Lee, Sooyeon Jeon, Chihye Park, Tae Sung Kim, Jin Hee Lee, Il Ung Oh, Sun-Ju Ahn","doi":"10.15283/ijsc24042","DOIUrl":"10.15283/ijsc24042","url":null,"abstract":"<p><p>This paper presents guidelines for the systematic management of packaging, storage, transportation, and traceability of source cells used for organoid research. Given the important role of source cells in organoid studies, it is important to ensure the preservation of their quality and integrity throughout transportation and distribution processes. The proposed guidelines, therefore, call for a cohesive strategy through these stages to minimize the risks of contamination, deterioration, and loss-threats that significantly compromise the safety, efficacy, and efficiency of source cells. Central to these guidelines is the quality control measures that include roles and responsibilities across the entire supply chain, with recommendations specific to packaging materials, transportation facilities, and storage management. Furthermore, the need for an integrated management system is emphasized, spanning from source cell collection to the final application. This system is crucial for maintaining the traceability and accountability of source cells, facilitating the sharing, distribution, and utilization on a global scale, and supporting to advance organoid research and development.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"113-119"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Guidelines for Manufacturing and Application of Organoids: Liver. 有机体制造和应用指南》:肝脏
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-05-30 Epub Date: 2024-05-22 DOI: 10.15283/ijsc24044
Hye-Ran Moon, Seon Ju Mun, Tae Hun Kim, Hyemin Kim, Dukjin Kang, Suran Kim, Ji Hyun Shin, Dongho Choi, Sun-Ju Ahn, Myung Jin Son
{"title":"Guidelines for Manufacturing and Application of Organoids: Liver.","authors":"Hye-Ran Moon, Seon Ju Mun, Tae Hun Kim, Hyemin Kim, Dukjin Kang, Suran Kim, Ji Hyun Shin, Dongho Choi, Sun-Ju Ahn, Myung Jin Son","doi":"10.15283/ijsc24044","DOIUrl":"10.15283/ijsc24044","url":null,"abstract":"<p><p>Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"120-129"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Standards for Organoids. 有机体标准
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-05-30 Epub Date: 2024-05-27 DOI: 10.15283/ijsc24043
Sun-Ju Ahn
{"title":"Standards for Organoids.","authors":"Sun-Ju Ahn","doi":"10.15283/ijsc24043","DOIUrl":"10.15283/ijsc24043","url":null,"abstract":"","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"99-101"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Guidelines for Manufacturing and Application of Organoids: Brain. 有机体制造和应用指南》:脑。
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-05-30 Epub Date: 2024-05-23 DOI: 10.15283/ijsc24056
Taehwan Kwak, Si-Hyung Park, Siyoung Lee, Yujeong Shin, Ki-Jun Yoon, Seung-Woo Cho, Jong-Chan Park, Seung-Ho Yang, Heeyeong Cho, Heh-In Im, Sun-Ju Ahn, Woong Sun, Ji Hun Yang
{"title":"Guidelines for Manufacturing and Application of Organoids: Brain.","authors":"Taehwan Kwak, Si-Hyung Park, Siyoung Lee, Yujeong Shin, Ki-Jun Yoon, Seung-Woo Cho, Jong-Chan Park, Seung-Ho Yang, Heeyeong Cho, Heh-In Im, Sun-Ju Ahn, Woong Sun, Ji Hun Yang","doi":"10.15283/ijsc24056","DOIUrl":"10.15283/ijsc24056","url":null,"abstract":"<p><p>This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"158-181"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application. 胃有机体--胃干细胞稳态和治疗应用的前景模型
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-05-03 DOI: 10.15283/ijsc23075
Subin Lee, Jang-Hyun Choi, So-Yeon Park, Jihoon Kim
{"title":"Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application.","authors":"Subin Lee, Jang-Hyun Choi, So-Yeon Park, Jihoon Kim","doi":"10.15283/ijsc23075","DOIUrl":"https://doi.org/10.15283/ijsc23075","url":null,"abstract":"The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic <i>in vivo</i> conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"82 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140828890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impaired Osteogenesis in Human Induced Pluripotent Stem Cells with Acetaldehyde Dehydrogenase 2 Mutations. 乙醛脱氢酶 2 基因突变的人类诱导多能干细胞成骨功能受损
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-04-12 DOI: 10.15283/ijsc23151
Jooyoung Lim, Heeju Han, Se In Jung, Yeri Alice Rim, Ji Hyeon Ju
{"title":"Impaired Osteogenesis in Human Induced Pluripotent Stem Cells with Acetaldehyde Dehydrogenase 2 Mutations.","authors":"Jooyoung Lim, Heeju Han, Se In Jung, Yeri Alice Rim, Ji Hyeon Ju","doi":"10.15283/ijsc23151","DOIUrl":"https://doi.org/10.15283/ijsc23151","url":null,"abstract":"Acetaldehyde dehydrogenase 2 (ALDH2) is the second enzyme involved in the breakdown of acetaldehyde into acetic acid during the process of alcohol metabolism. Roughly 40% of East Asians carry one or two ALDH2*2 alleles, and the presence of <i>ALDH2</i> genetic mutations in individuals may affect the bone remodeling cycle owing to accumulation of acetaldehyde in the body. In this study, we investigated the effects of ALDH2 mutations on bone remodeling. In this study, we examined the effects of <i>ALDH2</i> polymorphisms on <i>in vitro</i> osteogensis using human induced pluripotent stem cells (hiPSCs). We differentiated wild-type (ALDH2*1/*1-) and ALDH2*1/*2-genotyped hiPSCs into osteoblasts (OBs) and confirmed their OB characteristics. Acetaldehyde was administered to confirm the impact caused by the mutation during OB differentiation. Calcium deposits formed during osteogenesis were significantly decreased in ALDH2*1/*2 OBs. The expression of osteogenic markers were also decreased in acetaldehyde-treated OBs differentiated from the ALDH2*1/*2 hiPSCs. Furthermore, the impact of <i>ALDH2</i> polymorphism and acetaldehyde-induced stress on inflammatory factors such as 4-hydroxynonenal and tumor necrosis factor <i>α</i> was confirmed. Our findings suggest that individuals with ALDH2 deficiency may face challenges in acetaldehyde breakdown, rendering them susceptible to disturbances in normal bone remodeling therefore, caution should be exercised regarding alcohol consumption. In this proof-of-concept study, we were able to suggest these findings as a result of a disease-in-a-dish concept using hiPSCs derived from individuals bearing a certain mutation. This study also shows the potential of patient-derived hiPSCs for disease modeling with a specific condition.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"104 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition. 通过抑制 LRRK2 抑制胶质母细胞瘤干细胞的潜能和肿瘤生长
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-04-08 DOI: 10.15283/ijsc24032
Saewhan Park, Kyung-Hee Kim, Yun-Hee Bae, Young Taek Oh, Hyemi Shin, Hyung Joon Kwon, Chan Il Kim, Sung Soo Kim, Hwan-Geun Choi, Jong Bae Park, Byoung Dae Lee
{"title":"Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.","authors":"Saewhan Park, Kyung-Hee Kim, Yun-Hee Bae, Young Taek Oh, Hyemi Shin, Hyung Joon Kwon, Chan Il Kim, Sung Soo Kim, Hwan-Geun Choi, Jong Bae Park, Byoung Dae Lee","doi":"10.15283/ijsc24032","DOIUrl":"https://doi.org/10.15283/ijsc24032","url":null,"abstract":"Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in <i>in vitro</i> studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"25 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crosstalk between Signaling Pathways and Energy Metabolism in Pluripotency. 多能性中信号通路与能量代谢之间的相互影响
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-03-18 DOI: 10.15283/ijsc23173
Keun-Tae Kim, Seong-Min Kim, Hyuk-Jin Cha
{"title":"Crosstalk between Signaling Pathways and Energy Metabolism in Pluripotency.","authors":"Keun-Tae Kim, Seong-Min Kim, Hyuk-Jin Cha","doi":"10.15283/ijsc23173","DOIUrl":"https://doi.org/10.15283/ijsc23173","url":null,"abstract":"<p><p>The sequential change from totipotency to multipotency occurs during early mammalian embryo development. However, due to the lack of cellular models to recapitulate the distinct potency of stem cells at each stage, their molecular and cellular characteristics remain ambiguous. The establishment of isogenic naïve and primed pluripotent stem cells to represent the pluripotency in the inner cell mass of the pre-implantation blastocyst and in the epiblast from the post-implantation embryo allows the understanding of the distinctive characteristics of two different states of pluripotent stem cells. This review discusses the prominent disparities between naïve and primed pluripotency, including signaling pathways, metabolism, and epigenetic status, ultimately facilitating a comprehensive understanding of their significance during early mammalian embryonic development.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stem Cell-Based Approaches in Parkinson's Disease Research. 基于干细胞的帕金森病研究方法。
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-03-07 DOI: 10.15283/ijsc23169
Min Seong Kim, Subeen Yoon, Jiwoo Choi, Yong Jun Kim, Gabsang Lee
{"title":"Stem Cell-Based Approaches in Parkinson's Disease Research.","authors":"Min Seong Kim, Subeen Yoon, Jiwoo Choi, Yong Jun Kim, Gabsang Lee","doi":"10.15283/ijsc23169","DOIUrl":"https://doi.org/10.15283/ijsc23169","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of midbrain dopaminergic neurons, leading to motor symptoms. While current treatments provide limited relief, they don't alter disease progression. Stem cell technology, involving patient-specific stem cell-derived neurons, offers a promising avenue for research and personalized regenerative therapies. This article reviews the potential of stem cell-based research in PD, summarizing ongoing efforts, their limitations, and introducing innovative research models. The integration of stem cell technology and advanced models promises to enhance our understanding and treatment strategies for PD.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nervonic Acid Inhibits Replicative Senescence of Human Wharton's Jelly-Derived Mesenchymal Stem Cells. 神经酸抑制人华顿果冻来源的间充质干细胞的复制衰老。
IF 2.3 4区 医学
International journal of stem cells Pub Date : 2024-02-28 Epub Date: 2023-10-12 DOI: 10.15283/ijsc23101
Sun Jeong Kim, Soojin Kwon, Soobeen Chung, Eun Joo Lee, Sang Eon Park, Suk-Joo Choi, Soo-Young Oh, Gyu Ha Ryu, Hong Bae Jeon, Jong Wook Chang
{"title":"Nervonic Acid Inhibits Replicative Senescence of Human Wharton's Jelly-Derived Mesenchymal Stem Cells.","authors":"Sun Jeong Kim, Soojin Kwon, Soobeen Chung, Eun Joo Lee, Sang Eon Park, Suk-Joo Choi, Soo-Young Oh, Gyu Ha Ryu, Hong Bae Jeon, Jong Wook Chang","doi":"10.15283/ijsc23101","DOIUrl":"10.15283/ijsc23101","url":null,"abstract":"<p><p>Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated <i>β</i>-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence. Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"80-90"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41201180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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