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摘要 ：
Pancreatic cancer (PC) is assumed to be an intimidating and deadly malignancy due to being the leading cause of cancer-led mortality, predominantly affecting males of older age. The overall (5 years) survival rate of PC is less than 9% and is anticipated to be aggravated in the future due to the lack of molecular acquaintance and diagnostic tools for its early detection. Multiple factors are involved in the course of PC development, including genetics, cigarette smoking, alcohol, family history, and aberrant epigenetic signatures of the epigenome. In this review, we will mainly focus on the genetic mutations and epigenetic signature of PC. Multiple tumor suppressor and oncogene mutations are involved in PC initiation, including K-RAS, p53, CDKN2A, and SMAD4. The mutational frequency of these genes ranges from 50 to 98% in PC. The nature of mutation diagnosis is mostly homozygous deletion, point mutation, and aberrant methylation. In addition to genetic modification, epigenetic alterations particularly aberrant hypermethylation and hypomethylation also predispose patients to PC. Hypermethylation is mostly involved in the downregulation of tumor suppressor genes and leads to PC, while multiple genes also represent a hypomethylation status in PC. Several renewable drugs and detection tools have been developed to cope with this aggressive malady, but all are futile, and surgical resection remains the only choice for prolonged survival if diagnosed before metastasis. However, the available therapeutic development is insufficient to cure PC. Therefore, novel approaches are a prerequisite to elucidating the genetic and epigenetic mechanisms underlying PC progression for healthier lifelong survival.
关键词 ：
Aberrant epigenetic signature Aberrant epigenetic signature Aberrant hypermethylation Aberrant hypermethylation CDKN2A CDKN2A KRAS KRAS p53 p53 Pancreatic cancer Pancreatic cancer SMAD4 SMAD4
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| GB/T 7714 | Khan Aamir Ali , Liu Xinhui , Yan Xinlong et al. An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression. [J]. | Cancer metastasis reviews , 2021 , 40 (1) : 245-272 . |
| MLA | Khan Aamir Ali et al. "An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression." . | Cancer metastasis reviews 40 . 1 (2021) : 245-272 . |
| APA | Khan Aamir Ali , Liu Xinhui , Yan Xinlong , Tahir Muhammad , Ali Sakhawat , Huang Hua . An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression. . | Cancer metastasis reviews , 2021 , 40 (1) , 245-272 . |
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摘要 ：
肿瘤组织是由恶性上皮细胞及其周围的基质细胞微环境形成的复杂混合体。在肿瘤的发生发展过程中,肿瘤细胞与肿瘤微环境相互作用相互影响,其中癌相关成纤维细胞(CAF)是肿瘤微环境的重要组成部分。CAF不仅促进肿瘤细胞的增殖与转移、肿瘤微血管生成以及耐药性产生,还能抑制机体的抗肿瘤免疫,从而促进肿瘤的恶性进展。本文简要综述癌相关成纤维细胞的特性及其在调控肿瘤发生发展中的作用。
关键词 ：
癌相关成纤维细胞 癌相关成纤维细胞 靶向治疗 靶向治疗 肿瘤微环境 肿瘤微环境
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| GB/T 7714 | 万令飞 , 杨慧 , 葛晨 et al. 癌相关成纤维细胞的特性及其调控肿瘤进程的研究进展 [J]. | 生物技术通讯 , 2020 , 31 (01) : 75-82 . |
| MLA | 万令飞 et al. "癌相关成纤维细胞的特性及其调控肿瘤进程的研究进展" . | 生物技术通讯 31 . 01 (2020) : 75-82 . |
| APA | 万令飞 , 杨慧 , 葛晨 , 刘蕴慧 , 岳文 , 裴雪涛 et al. 癌相关成纤维细胞的特性及其调控肿瘤进程的研究进展 . | 生物技术通讯 , 2020 , 31 (01) , 75-82 . |
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摘要 ：
Background & Aims: Intrahepatic cholangiocarcinoma (ICC) is the second most common liver malignancy. ICC typically features remarkable cellular heterogeneity and a dense stromal reaction. Therefore, a comprehensive understanding of cellular diversity and the interplay between malignant cells and niche cells is essential to elucidate the mechanisms driving ICC progression and to develop therapeutic approaches. Methods: Herein, we performed single-cell RNA sequencing (scRNA-seq) analysis on unselected viable cells from 8 human ICCs and adjacent samples to elucidate the comprehensive transcriptomic landscape and intercellular communication network. Additionally, we applied a negative selection strategy to enrich fibroblast populations in 2 other ICC samples to investigate fibroblast diversity. The results of the analyses were validated using multiplex immunofluorescence staining, bulk transcriptomic datasets, and functional in vitro and in vivo experiments. Results: We sequenced a total of 56,871 single cells derived from human ICC and adjacent tissues and identified diverse tumor, immune, and stromal cells. Malignant cells displayed a high degree of inter-tumor heterogeneity. Moreover, tumor-infiltrating CD4 regulatory T cells exhibited highly immunosuppressive characteristics. We identified 6 distinct fibroblast subsets, of which the majority were CD146-positive vascular cancer-associated fibroblasts (vCAFs), with highly expressed microvasculature signatures and high levels of interleukin (IL)-6. Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations in ICC cells, particularly upregulating enhancer of zeste homolog 2 (EZH2) and thereby enhancing malignancy. Furthermore, ICC cell-derived exosomal miR-9-5p elicited high expression of IL-6 in vCAFs to promote tumor progression. Conclusions: Our single-cell transcriptomic dataset delineates the inter-tumor heterogeneity of human ICCs, underlining the importance of intercellular crosstalk between ICC cells and vCAFs, and revealing potential therapeutic targets. Lay summary: Intrahepatic cholangiocarcinoma is an aggressive and chemoresistant malignancy. Better understanding the complex transcriptional architecture and intercellular crosstalk of these tumors will help in the development of more effective therapies. Herein, we have identified important interactions between cancer cells and cancer-associated fibroblasts in the tumor stroma, which could have therapeutic implications. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.
关键词 ：
Cancer-associated fibroblasts Cancer-associated fibroblasts CD146 CD146 Intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma Single-cell RNA sequencing Single-cell RNA sequencing Tumor heterogeneity Tumor heterogeneity
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| GB/T 7714 | Zhang, Min , Yang, Hui , Wan, Lingfei et al. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma [J]. | JOURNAL OF HEPATOLOGY , 2020 , 73 (5) : 1118-1130 . |
| MLA | Zhang, Min et al. "Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma" . | JOURNAL OF HEPATOLOGY 73 . 5 (2020) : 1118-1130 . |
| APA | Zhang, Min , Yang, Hui , Wan, Lingfei , Wang, Zhaohai , Wang, Haiyang , Ge, Chen et al. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma . | JOURNAL OF HEPATOLOGY , 2020 , 73 (5) , 1118-1130 . |
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摘要 ：
目的探讨β-拉帕醌以及联合帕博西尼对肝内胆管细胞癌(ICC)细胞、肿瘤干细胞球的抑制作用及其作用机制。方法首先,利用CCK-8和克隆形成实验检测β-拉帕醌单药及与帕博西尼联用对人ICC HuCCT1和QBC939细胞系增殖的影响;其次利用肿瘤干细胞球形成实验检测β-拉帕醌单药,帕博西尼单药及联合用药对人ICC细胞中肿瘤干细胞球形成的影响;进一步应用qRT-PCR和Western印迹检测β-拉帕醌处理组与对照组的肿瘤干性相关基因mRNA和蛋白表达水平的影响。结果β-拉帕醌单药及与帕博西尼联用对人ICC肿瘤干细胞球的形成具有显著的抑制作用,且协同效果更加显著。结论β-拉帕醌联合帕博西尼能够显著抑制...
关键词 ：
β-拉帕醌 β-拉帕醌 肝内胆管细胞癌 肝内胆管细胞癌 肿瘤干细胞球 肿瘤干细胞球 帕博西尼 帕博西尼
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| GB/T 7714 | 杨慧 , 韩瑞刚 , 万令飞 et al. β-拉帕醌联合帕博西尼抑制肝内胆管细胞癌细胞及肿瘤干细胞球的增殖 [J]. | 军事医学 , 2019 , 43 (10) : 761-766 . |
| MLA | 杨慧 et al. "β-拉帕醌联合帕博西尼抑制肝内胆管细胞癌细胞及肿瘤干细胞球的增殖" . | 军事医学 43 . 10 (2019) : 761-766 . |
| APA | 杨慧 , 韩瑞刚 , 万令飞 , 葛晨 , 刘蕴慧 , 王海洋 et al. β-拉帕醌联合帕博西尼抑制肝内胆管细胞癌细胞及肿瘤干细胞球的增殖 . | 军事医学 , 2019 , 43 (10) , 761-766 . |
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摘要 ：
我国“双一流”建设目标的实现以高素质的高校教师队伍为基础,更需合理的激励制度进行维护与保障.教师职称晋升作为高校教师评聘环节中最为重要的激励制度,对教师发展有明确的导向作用.本研究梳理了教师发展的内涵、理念与作用,建立了教师发展视域下的政策分析框架与标准,并采用案例法对北京市两所一流学科建设院校的教师职称评审政策文本从完整度、清晰度和适切性上进行了理念与使命、结构与内容、方法与程序、反馈与改进四个方面的分析,并提出了相应的问题与政策建议.
关键词 ：
双一流 双一流 政策分析 政策分析 教师发展 教师发展 职称评审 职称评审
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| GB/T 7714 | 阎新龙 , 莫蕾钰 , 张琳 . 教师发展视域下北京一流学科建设高校教师职称评审政策分析——基于两所高校的案例 [J]. | 中国地质教育 , 2019 , 28 (3) : 9-14 . |
| MLA | 阎新龙 et al. "教师发展视域下北京一流学科建设高校教师职称评审政策分析——基于两所高校的案例" . | 中国地质教育 28 . 3 (2019) : 9-14 . |
| APA | 阎新龙 , 莫蕾钰 , 张琳 . 教师发展视域下北京一流学科建设高校教师职称评审政策分析——基于两所高校的案例 . | 中国地质教育 , 2019 , 28 (3) , 9-14 . |
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摘要 ：
BackgroundGlioblastoma (GBM) is the most common type of primary malignant brain tumor. Molecular hydrogen has been considered a preventive and therapeutic medical gas in many diseases including cancer. In our study, we sought to assess the potential role of molecular hydrogen on GBM.MethodsThe in vivo studies were performed using a rat orthotopic glioma model and a mouse subcutaneous xenograft model. Animals inhaled hydrogen gas (67%) 1h two times per day. MR imaging studies were performed to determine the tumor volume. Immunohistochemistry (IHC), immunofluorescence staining, and flow cytometry analysis were conducted to determine the expression of surface markers. Sphere formation assay was performed to assess the cancer stem cell self-renewal capacity. Assays for cell migration, invasion, and colony formation were conducted.ResultsThe in vivo study showed that hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM. IHC and immunofluorescence staining demonstrated that hydrogen treatment markedly downregulated the expression of markers involved in stemness (CD133, Nestin), proliferation (ki67), and angiogenesis (CD34) and also upregulated GFAP expression, a marker of differentiation. Similar results were obtained in the in vitro studies. The sphere-forming ability of glioma cells was also suppressed by hydrogen treatment. Moreover, hydrogen treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells.ConclusionsTogether, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.
关键词 ：
Cancer cell stemness Cancer cell stemness Glioblastoma Glioblastoma Glioma stem-like cell Glioma stem-like cell Molecular hydrogen Molecular hydrogen
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| GB/T 7714 | Liu, Meng-yu , Xie, Fei , Zhang, Yan et al. Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation [J]. | STEM CELL RESEARCH & THERAPY , 2019 , 10 . |
| MLA | Liu, Meng-yu et al. "Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation" . | STEM CELL RESEARCH & THERAPY 10 (2019) . |
| APA | Liu, Meng-yu , Xie, Fei , Zhang, Yan , Wang, Ting-ting , Ma, Sheng-nan , Zhao, Peng-xiang et al. Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation . | STEM CELL RESEARCH & THERAPY , 2019 , 10 . |
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摘要 ：
Cancer stem-like cells (CSCs) are critical for the initiation, progression, chemoresistance and postsurgical recurrence of liver cancer. They are thought to be novel targets for the treatment of liver cancer, however, efficient agents that target liver cancer stem cells (CSCs) have not been identified. MicroRNAs (miRNAs) are small non-coding RNAs that target the 3untranslated region (3UTR) of mRNAs. Their dysregulation has been implicated in several types of cancer including liver cancer, but it still remains unknown if they play a role in targeting liver CSCs. We compared the miRNA profiles between liver cancer samples and adjacent non-tumor tissues using The Cancer Genome Atlas (TCGA) datasets. Several miRNAs including miR-486-5p (miR-486) were found to be significantly downregulated in liver cancer tissues. These differentially expressed miRNAs were screened between CSC-enriched tumor spheres and adherent cells. miR-486 was significantly downregulated in tumor spheres and liver cancer samples. Ectopic expression of miR-486 significantly repressed the self-renewal and invasion of CSCs in vitro and tumorigenesis in vivo. Notably, we found that sirtuin 1 (Sirt1) served as a direct target of miR-486. The high expression of Sirt1 was involved in maintaining the self-renewal and tumorigenic potential of liver CSCs. The results of the present study indicated that the miR-486-Sirt1 axis was involved in suppressing CSC traits and tumor progression.
关键词 ：
cancer stem cells cancer stem cells liver cancer liver cancer miR-486 miR-486 Sirt1 Sirt1
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| GB/T 7714 | Yan, Xinlong , Liu, Xinhui , Wang, Zhaohai et al. MicroRNA-486-5p functions as a tumor suppressor of proliferation and cancer stem-like cell properties by targeting Sirt1 in liver cancer [J]. | ONCOLOGY REPORTS , 2019 , 41 (3) : 1938-1948 . |
| MLA | Yan, Xinlong et al. "MicroRNA-486-5p functions as a tumor suppressor of proliferation and cancer stem-like cell properties by targeting Sirt1 in liver cancer" . | ONCOLOGY REPORTS 41 . 3 (2019) : 1938-1948 . |
| APA | Yan, Xinlong , Liu, Xinhui , Wang, Zhaohai , Cheng, Qian , Ji, Guanghong , Yang, Hui et al. MicroRNA-486-5p functions as a tumor suppressor of proliferation and cancer stem-like cell properties by targeting Sirt1 in liver cancer . | ONCOLOGY REPORTS , 2019 , 41 (3) , 1938-1948 . |
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摘要 ：
本发明提出了新的靶向肿瘤微环境与肺癌干细胞相互作用的miRNA的检测及应用，并提出了试剂在制备药物中的用途。该药物用于下列的至少之一：预防或治疗癌症，抑制癌症干细胞球的形成或增殖，抑制体内癌症的形成或增殖，该药物用于预防或治疗癌症，所述试剂用于过表达核酸，所述核酸具有下列的核苷酸序列：1)SEQ ID NO：1所示的核苷酸序列；2)具有与SEQ ID NO：1所示的核苷酸序列至少70％、至少75％、至少80％、至少85％、至少90％、至少95％、至少99％同一性；或3)3)与1)相比具有一个或者多个核苷酸的突变。
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| GB/T 7714 | 阎新龙 , 岳文 , 裴雪涛 et al. 新的靶向肿瘤微环境与肺癌干细胞相互作用的miRNA的检测及应用 : CN201810388252.4[P]. | 2018-04-26 . |
| MLA | 阎新龙 et al. "新的靶向肿瘤微环境与肺癌干细胞相互作用的miRNA的检测及应用" : CN201810388252.4. | 2018-04-26 . |
| APA | 阎新龙 , 岳文 , 裴雪涛 , 刘馨慧 , 杨慧 , 万令飞 et al. 新的靶向肿瘤微环境与肺癌干细胞相互作用的miRNA的检测及应用 : CN201810388252.4. | 2018-04-26 . |
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摘要 ：
Background: Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for the treatment of ischemic disease or injury and may be an alternative treatment for cell therapy. This aim of the study was to evaluate whether exosomes derived from adipose mesenchymal stem cell (ADSC) can protect the skin flap during ischemia-reperfusion (I/R) injury and induce neovascularization. Methods: To investigate the effects of exosomes in the I/R injury of flap transplantation in vivo, flaps were subjected to 6 h of ischemia by ligating the left superficial inferior epigastric vessels (SIEA) followed by blood perfusion. Exosomes derived from normal ADSC (ADSC-exos) and exosomes derived from ADSC preconditioned with H2O2 (H2O2-ADSC-exos) were injected into the flaps. Then, the blood perfusion unit (BPU) of the flaps was measured by Laser Doppler Perfusion Imaging (LDPI) and microvessel density was determined by the endothelial with cell marker CD31 with Immunohistochemistry (IHC) staining. Inflammatory cell infiltration of the skin flap and apoptosis were detected by hematoxylin & eosin staining (H&E) and the TdT-mediated biotinylated dUTP nick end-labeling (TUNEL) technique. Results: In vivo, exosomes significantly increased flap survival and capillary density compared to I/R on postoperative day 5, and decreased the inflammatory reaction and apoptosis in the skin flap (P < 0.05). Furthermore, H2O2-ADSC-exos had better outcomes compared to normal exosomes (P < 0.05). ADSC-exos could significantly increase human umbilical vein endothelial cell (HUVEC) proliferation (P < 0.05), but no statistic difference was found in exosomes derived from different microenvironments (P > 0.05). HUVEC co-cultured with H2O2-ADSC-exos increased the migration ratio and generated more cord-like structures compared to ADSC-exos and the control group (P < 0.05). Conclusion: ADSC-exos can enhance skin flap survival, promote neovascularization and alleviate the inflammation reaction and apoptosis in the skin flap after I/R injury. The use of a specific microenvironment for in vitro stem cell culture, such as one containing a low concentration of H2O2, will facilitate the development of customized exosomes for cell-free therapeutic applications in skin flap transplantation. (C) 2018 Elsevier Inc. All rights reserved.
关键词 ：
Adipose-derived stem cells Adipose-derived stem cells Exosomes Exosomes Hydrogen peroxide Hydrogen peroxide lschemia-reperfusion injury lschemia-reperfusion injury Neovascularization Neovascularization Skin flap transplantation Skin flap transplantation
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| GB/T 7714 | Bai, Yun , Han, Yu-di , Yan, Xin-long et al. Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury [J]. | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS , 2018 , 500 (2) : 310-317 . |
| MLA | Bai, Yun et al. "Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury" . | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 500 . 2 (2018) : 310-317 . |
| APA | Bai, Yun , Han, Yu-di , Yan, Xin-long , Ren, Jing , Zeng, Quan , Li, Xiao-dong et al. Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury . | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS , 2018 , 500 (2) , 310-317 . |
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摘要 ：
Background: Adipose-derived stromal cells (ADSCs)-derived exosomes (ADSC-Exos) account for the proangiogenic potential of stem cell. This study aimed to investigate the effect of ADSC-derived exosomes (ADSC-Exos) on the survival in fat grafting. Methods: A nude mouse model of subcutaneous fat grafting was adopted. Hypoxic preconditioned ADSC-Exos and ADSC-Exos were injected around the grafted tissue. The fat graft sample was weighed and examined by hematoxylin and eosin (H&E) staining and immunohistochemistry. Laser Doppler flowmetry and CD31 immunofluorescence staining were used to analyze neovascularization. Results: ADSC-Exo and hypoxic ADSC-Exo groups had a significantly higher weight of fat graft and more perilipin-positive adipocytes than the control groups from 2 to 8 weeks after grafting, and the hypoxic ADSC-Exo group had better outcomes (all P < 0.05). H&E staining showed that ADSC-Exos attenuated infiltration of inflammatory cells around the fat grafts. Laser Doppler flowmetry showed that the two ADSC-Exo groups had better blood perfusion in the graft tissue than the control groups (all P < 0.05). Immunofluorescence demonstrated that the hypoxic ADSC-Exo group had significantly more CD31-positive cells than the ADSC-Exo group. In vitro study showed that hypoxic ADSC-Exos treatment significantly increased the migration (at 12 and 24 h) and in vitro capillary network formation (at 12 h) in the human umbilical vein endothelial cells (HUVECs) as compared with the ADSC-Exo group and control group (all P < 0.05). Conclusions: Co-transplantation of ADSC-Exos can effectively promote the survival of graft, neovascularization and attenuated inflammation in the fat grafts. Hypoxia treatment can further enhance the beneficial effect of ADSC-Exos. (C) 2018 Elsevier Inc. All rights reserved.
关键词 ：
Adipose-derived stem cells Adipose-derived stem cells Angiogenesis Angiogenesis Exosomes Exosomes Fat grafting Fat grafting Microenvironment Microenvironment
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| GB/T 7714 | Han, Yu-di , Bai, Yun , Yan, Xin-long et al. Co-transplantation of exosomes derived from hypoxia-preconditioned adipose mesenchymal stem cells promotes neovascularization and graft survival in fat grafting [J]. | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS , 2018 , 497 (1) : 305-312 . |
| MLA | Han, Yu-di et al. "Co-transplantation of exosomes derived from hypoxia-preconditioned adipose mesenchymal stem cells promotes neovascularization and graft survival in fat grafting" . | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 497 . 1 (2018) : 305-312 . |
| APA | Han, Yu-di , Bai, Yun , Yan, Xin-long , Ren, Jing , Zeng, Quan , Li, Xiao-dong et al. Co-transplantation of exosomes derived from hypoxia-preconditioned adipose mesenchymal stem cells promotes neovascularization and graft survival in fat grafting . | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS , 2018 , 497 (1) , 305-312 . |
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