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Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis

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World Journal of Gastroenterology 2019年第32期25卷 4715-4726页

作者： Ran-Xu Zhu alfred sze lok cheng Henry Lik Yuen Chan Dong-Ye Yang Wai-Kay Seto Department of Gastroenterology and Hepatology The University of Hong Kong–Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell ***2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor ***,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully *** To investigate the function and mechanism of GAS2 in *** GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western *** proliferation was analyzed by counting,MTS,and colony formation *** cycle analysis was performed by flow *** apoptosis was investigated by Annexin V apoptosis assay and western *** GAS2 protein expression was lower in HCC than in normal *** of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(P<0.05).Furthermore,GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells,particularly the elevation of sub G1(P<0.01).Apoptosis induced by GAS2 was dependent on p53,which was increased by etoposide *** expression of p53 and apoptosis markers was further enhanced when GAS2 was upregulated,but became diminished upon downregulation of *** the clinic specimen,GAS2 was downregulated in more than 60%of *** average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(P<0.05).CONCLUSION GAS2 plays a vital role in HCC cell proliferation and apoptosis,possibly by regulating the cell cycle and p53-dependent apoptosis pathway.

关键词： Growth arrest-specific gene 2 Cell cycle Apoptosis Hepatocellular carcinoma p53-dependent signaling pathway

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang alfred sze-lok cheng School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive *** an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)*** of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,***,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic ***,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer T cell

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Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing

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Research 2024年第1期2023卷 763-778页

作者： Qing Liu Qiaoyun Long Jiayu Zhao Wenjie Wu Zexin Lin Wei Sun Ping Gu Tuo Deng Kerry Martin Loomes Donghai Wu Alice P.S.Kong Jingying Zhou alfred S.cheng Hannah Xiaoyan Hui School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Guangzhou Institute of Biomedicine and Health Chinese Academy of SciencesGuangzhouChina China-New Zealand Joint Laboratory on Biomedicine and Health Chinese Academy of SciencesGuangzhouChina Department of Endocrinology Jinling HospitalNanjing UniversitySchool of MedicineNanjingChina National Clinical Research Center for Metabolic Diseases and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina Key Laboratory of Diabetes Immunology Ministry of Educationand Metabolic Syndrome Research CenterThe Second Xiangya Hospital of Central South UniversityChangshaChina Clinical Immunology Center The Second Xiangya Hospital of Central South UniversityChangshaChina School of Biological Sciences and Maurice Wilkins Centre University of AucklandAucklandNew Zealand Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Hong Kong Institute of Diabetes and Obesity The Chinese University of Hong KongPrince of Wales HospitalShatinHong KongChina Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongPrince of Wales HospitalShatinHong KongChina

Adipose browning has demonstrated therapeutic potentials in several ***,by conducting transcriptomic profiling at the single-cell and single-nucleus resolution,we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue(iWAT)at thermoneutrality or chronic cold *** major nonimmune cells within the iWAT,including adipose stem and progenitor cells(ASPCs),mature adipocytes,endothelial cells,Schwann cells,and smooth muscle cells,were recovered,allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown *** findings also unravel the existence of subpopulations in mature adipocytes,ASPCs,and endothelial cells,as well as new insights on their interconversion and reprogramming in response to *** adipocyte subpopulation competent of major histocompatibility complex class Ⅱ(MHCⅡ)antigen presentation is ***,a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCⅡ^(+)*** adipocytes are transdifferented from preexisting lipid generating adipocytes,which exhibit developmental trajectory from de novo differentiation of amphiregulin cells(Aregs).Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to *** data reveal fundamental changes during cold-evoked adipose browning.

关键词： evoked programming generating

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煤系高岭石热活化及其对水泥净浆长期强度的影响研究

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太原理工大学学报 2024年第2期55卷 325-330页

作者：王林浩程寅高树峰闫晓彦 alfred Attoh 杨宏太原理工大学土木工程学院太原030024 山西省交通科技研发有限公司太原030021 交通运输部科学研究院北京100029 吕梁学院建筑系山西吕梁033001 中铁二十局集团市政工程有限公司兰州730046

【目的】煤矸石的高值化利用是目前研究的热点,煤矸石中高岭石的活化及作用对煤矸石的高值化利用意义重大。【方法】首先采用正交试验方法进行了煤系高岭石的热活化参数优化设计研究,再以最优条件形成的煤系偏高岭土替代部分水泥,对净... 详细信息

【目的】煤矸石的高值化利用是目前研究的热点,煤矸石中高岭石的活化及作用对煤矸石的高值化利用意义重大。【方法】首先采用正交试验方法进行了煤系高岭石的热活化参数优化设计研究,再以最优条件形成的煤系偏高岭土替代部分水泥,对净浆的抗压强度、物相组成及微观结构进行了分析。【结果】试验结果表明,煤系高岭石最佳热活化条件为煅烧温度800℃,保温时间2 h,粉磨细度2.82μm.煅烧温度对煤系偏高岭土活性影响最大,粉磨细度次之,保温时间最小;采用煤系偏高岭土替代20%(质量分数)水泥,可加快水泥的水化反应速率,有效提升净浆在各养护龄期的抗压强度,其中早期强度提升最显著;微观机理分析发现,煤系偏高岭土发生火山灰反应消耗了大量氢氧化钙,形成了结构更致密的低钙硅比水化硅酸钙。

关键词：煤系高岭石正交试验水泥净浆抗压强度煤矸石

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The FAST all sky HI survey(FASHI):The first release of catalog

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Science China(Physics,Mechanics & Astronomy) 2024年第1期67卷 112-133页

作者： Chuan-Peng Zhang Ming Zhu Peng Jiang cheng cheng Jing Wang Jie Wang Jin-Long Xu Xiao-Lan Liu Nai-Ping Yu Lei Qian Haiyang Yu Mei Ai Yingjie Jing Chen Xu Ziming Liu Xin Guan Chun Sun Qingliang Yang Menglin Huang Qiaoli Hao FAST Collaboration Guizhou Radio Astronomical Observatory Guizhou UniversityGuiyang 550000China National Astronomical Observatories Chinese Academy of Sciences(CAS)Beijing 100101China Chinese Academy of Sciences South America Center for Astronomy National Astronomical ObservatoriesCASBeijing 100101China Kavli Institute for Astronomy and Astrophysics Peking UniversityBeijing 100871China

The FAST All Sky HI survey(FASHI)was designed to cover the entire sky observable by the Five-hundred-meter Aperture Spherical radio Telescope(FAST),spanning approximately 22000 square degrees of declination between-14°and+66°,and in the frequency range of 1050-1450 MHz,with the expectation of eventually detecting more than 100000 HI *** August 2020 and June 2023,FASHI had covered more than 7600 square degrees,which is approximately 35%of the total sky observable by *** has a median detection sensitivity of around 0.76 m Jy beam-1and a spectral line velocity resolution of~6.4 km s-1at a frequency of~1.4 *** of now,a total of 41741 extragalactic HI sources have been detected in the frequency range 1305.5-1419.5 MHz,corresponding to a redshift limit of z■*** cross-matching FASHI sources with the Siena Galaxy Atlas(SGA)and the Sloan Digital Sky Survey(SDSS)catalogs,we found that 16972(40.7%)sources have spectroscopic redshifts and 10975(26.3%)sources have only photometric *** of the remaining 13794(33.0%)HI sources are located in the direction of the Galactic plane,making their optical counterparts difficult to identify due to high extinction or high contamination of Galactic stellar *** on current survey results,the FASHI survey is an unprecedented blind extragalactic H I *** has higher spectral and spatial resolution and broader coverage than the Arecibo Legacy Fast ALFA Survey(ALFALFA).When completed,FASHI will provide the largest extragalactic HI catalog and an objective view of HI content and large-scale structure in the local universe.

关键词： surveys redshifts galaxies telescope radio lines HI line

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女性性功能障碍与性激素相关性的多中心横断面研究

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中华生殖与避孕杂志 2024年第3期44卷 278-284页

作者：鞠蕊阮祥燕代荫梅杨瑜许新程姣姣白勇涛施琰红杨幸子孙艳华李瑞玲 alfred O.Mueck 首都医科大学附属北京妇产医院、北京妇幼保健院药物临床试验机构办公室北京100026 首都医科大学附属北京妇产医院、北京妇幼保健院内分泌科北京100026 北京市朝阳区太阳宫社区卫生服务中心妇科北京100028 北京市朝阳区妇幼保健院妇科北京100022 德国图宾根大学妇产医院妇女健康部与妇女健康研究中心图宾根D-72076

目的探讨内源性性激素与女性性功能的相关性。方法本研究是一项队列研究的基线数据,纳入2020年4月至2021年3月期间在首都医科大学附属北京妇产医院、北京市朝阳区妇幼保健院、北京市朝阳区太阳宫社区卫生服务中心就诊符合标准的711例女... 详细信息

目的探讨内源性性激素与女性性功能的相关性。方法本研究是一项队列研究的基线数据,纳入2020年4月至2021年3月期间在首都医科大学附属北京妇产医院、北京市朝阳区妇幼保健院、北京市朝阳区太阳宫社区卫生服务中心就诊符合标准的711例女性,收集社会人口学资料(根据学历分为高中及以上、高中以下;根据婚姻关系分为满意、一般、不满意)和检测血清性激素水平。采用女性性功能指数(female sexual function index,FSFI)量表评估女性性功能。根据生殖衰老研讨会+10(Stages of Reproductive Aging Workshop+10,STRAW+10)分期系统标准将研究对象分为生育期(R)组、绝经过渡期(T)组,绝经后期(P)组。Spearman秩相关分析和多元线性回归分析确定FSFI及其各维度分数与血清性激素水平之间的相关性。结果多元线性回归分析显示,FSFI总分与绝经后期、高中以下学历、婚姻关系一般、婚姻关系不满意呈显著负相关(均P<0.01)。除疼痛评分外,高中以下学历、婚姻关系一般或不满意与FSFI中其他5个维度得分均呈负相关(均P<0.05);绝经后期与阴道润滑、性满意度和性交疼痛呈负相关(均P<0.05)。内源性性激素中的卵泡刺激素与所有FSFI得分均呈负相关(均P<0.05);除性高潮和性满意度外,雌二醇与FSFI中其他4个维度得分呈正相关(均P<0.05);总睾酮与FSFI总分和性欲得分呈正相关(均P<0.05);游离睾酮与性高潮得分呈正相关(P<0.05)。结论雌二醇和总睾酮是女性性功能的保护因素。

关键词：绝经性激素女性性功能障碍性功能指数生殖衰老分期

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N-乙酰半胱氨酸对冻融人卵巢组织的保护作用

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首都医科大学学报 2024年第4期45卷 573-582页

作者：李扬璐阮祥燕李妍秋谷牧青杜娟王泽铖程姣姣金凤羽蒋玲玲杨瑜 alfred O.Mueck 首都医科大学附属北京妇产医院/北京妇幼保健院内分泌科北京100026 德国图宾根大学妇产医院妇女健康部与妇女健康研究中心图宾根D-72076

目的以首都医科大学附属北京妇产医院生育力保护中心现有冻存复苏方案为基础,以雌性去势裸鼠为模型,通过人冻融卵巢组织异种移植探讨抗氧化剂N-乙酰半胱氨酸(N-Acetyl-L-Cysteine,NAC)对人卵巢组织的保护作用。方法将4例患者的卵巢组织... 详细信息

目的以首都医科大学附属北京妇产医院生育力保护中心现有冻存复苏方案为基础,以雌性去势裸鼠为模型,通过人冻融卵巢组织异种移植探讨抗氧化剂N-乙酰半胱氨酸(N-Acetyl-L-Cysteine,NAC)对人卵巢组织的保护作用。方法将4例患者的卵巢组织按照原有冻融方案和改良方案(加入NAC)进行冻融,所有患者取材后留取新鲜卵巢组织进行钙黄绿素AM(Calcein acetoxymethyl ester,Calcein-AM)和苏木精-伊红(hematoxylin-eosin staining,HE)染色评估卵泡活性并计数。将36只雌性去势裸鼠随机分为4组,将复苏后的卵巢组织移植于双侧裸鼠肾被膜下,按照移植卵巢组织的冻融方案分为原有冻融方案组(control group),改良方案组(NAC group),卵巢去势组(ovariectomy group)和正常对照组(normal group,不进行手术)。分别在移植第3天、第7天、第21天处死裸鼠,取血清及卵巢组织移植物。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测血清雌二醇(estradiol,E2)、卵泡刺激素(follicle stimulating hormone,FSH)和抗苗勒管激素(anti-mullerian hormone,AMH)水平,取卵巢组织移植物1片用于HE染色观察卵泡发育情况,1片用于总抗氧化能力(total antioxidant capability,TAC)的检测。结果移植后各时间点两移植组卵泡发育分级差异无统计学意义(P>0.05)。NAC组总抗氧化能力显著高于control组(P0.05)。移植第3天control组裸鼠血清中E2水平显著高于卵巢去势组(P0.05)。移植后第3天和第21天两移植组裸鼠血清中FSH水平低于卵巢去势组(P0.05)。移植后第3天control组AMH显著高于卵巢去势组(P0.05),移植第7天两移植组AMH水平下降,显著低于正常对照组(P0.05)。结论原有冻存方案及改良冻存方案均能有效恢复卵巢组织的内分泌功能。与原有冻存方案相比,NAC改良方案能够提高移植卵巢组织的抗氧化能力,并减少移植初期原始卵泡的激活,保存更多的原始卵泡数量。

关键词： N-乙酰半胱氨酸原始卵泡卵泡激活卵泡丢失卵巢储备

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Melting mechanisms of Pt-based multimetallic spherical nanoparticles by molecular dynamics simulation

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稀有金属：英文版 2023年第2期42卷 406-417页

作者： Chun-Yu cheng Yuan-Yuan Guo Yi-Ming Zou Amanda Jiamin Ong alfred ling Yoong Tok Shuzhou Li School of Materials Science and Engineering Nanyang Technological UniversitySingapore639798Singapore

The melting mechanisms of Pt-based multimetallic nanoparticles(NPs)are important to help determine their optimal melting *** understand the melting and coalescence behaviors of heterogeneous NPs(Pd-Pt NPs)with various sizes and compositions,molecular dynamics(MD)simulation was *** MD results for larger Pd-Pt NPs with an effective diameter of4.6-7.8 nm show that PtPd alloy can form at Pd/Pt interface before Pd NP melted completely,while for Pt-core/Pdshell NP and Pd-core/Pt-shell NP,PtPd alloy formed only after Pd portion melted *** smaller Pd-Pt NPs with an effective diameter of 2.5-4.0 nm,PdPt alloy is not formed until both Pd and Pt NPs melted ***,the coalescence process of Pd-Pt NPs depends on the melting temperature of Pt NP when Pt composition is higher than 20 at%.Furthermore,the melting mechanisms of Pd/Pt/Ir trimetallic NPs are investigated.A two-step melting process occurs in Pd-Pt-Ir NPs and Ir-core/Ptshell/Pd-shell NP,and the melting sequence of Pd-core/Ptshell/Ir-shell NP and Pt-core/Pd-shell/Ir-shell NP is different from Pd/Pt bimetallic NPs.

关键词： Molecular dynamics(MD) Melting mechanism Pt-based Multimetallic Heterogeneous structure

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Exciton dynamics in luminescent carbon nanodots： Electron-hole exchange interaction

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Nano Research 2016年第2期9卷 549-559页

作者： Bo Peng Xin Lu Shi Chen cheng Hon alfred Huan Qihua Xiong Evren Mutlugun Hilmi Volkan Demir Siu Fung Yu Division of Physics and Applied Physics School of Physical and Mathematical Sciences Nanyang Technological University Singapore 637371 Singapore NOVITAS Nanoelectronics Centre of Excellence School of Electrical and Electronic Engineering Nanyang Technological UniversitySingapore 639798 Singapore LUMINOUS Centre of Excellence for Semiconductor Lighting and Displays School of Electrical and Electronic Engineering NanyangTechnological University Singapore 639798 Singapore Department of Applied Physics the Hong Kong Polytechnic University Hong Hum Hong Kong SAR China

The electron-hole exchange interaction significantly influences the optical properties of excitons and radiative decay. However, exciton dynamics in luminescent carbon dots （Cdots） is still not clear. In this study, we have developed a simple and efficient one-step strategy to synthesize luminescent Cdots using the pyrolysis of oleylamine. The sp^2 clusters of a few aromatic rings are responsible for the observed blue photoluminescence. The size of these clusters can be tuned by controlling the reaction time, and the energy gap between the π-π＊ states of the sp^2 domains decreases as the sp^2 cluster size increases. More importantly, the strong electron-hole exchange interaction results in the splitting of the exciton states of the sp^2 clusters into the singlet-bright and triplet-dark states with an energy difference ΔE, which decreases with increasing sp^2 cluster size owing to the reduction of the confinement energy and the suppression of the electron-hole exchange interaction.

关键词： carbon dots photoluminescence pyrolysis electron-hole exchange interaction energy splitting

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Prevention and treatment of iatrogenic premature ovarian insufficiency:r interpretation of the first Chinese guideline on ovarian tissue cryopreservation and transplantation

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Global Health Journal 2021年第2期5卷 70-73页

作者： Xiangyan Ruan Jiaojiao cheng Juan Du Fengyu Jin Yanglu Li Muqing Gu alfred O.Mueck Department of Gynecological Endocrinology Beying Obstetrics and Gynecology HospitalCapital Medical UniversityYaojiayuan Road 251Beijing 100026China Department of Women’s Health University Hospital TuebingenCalwer Strasse 7Tuebingen 72076Germany

In recent years,with the rapid development of medical research,cancer diagnosis and treatment technology have significantly improved young cancer patient’s survival *** therapy such as chemotherapy,radiotherapy,or hematopoietic stem cell transplantation can lead to premature ovarian *** endocrine and reproductive function of the ovary is critical to women’s physical and mental *** tissue cryopreservation and transplantation can protect not only female fertility but also preserve ovarian endocrine *** paper interprets the guidelines for ovarian tissue cryopreservation and transplantation issued by the Chinese Society of Gynecological Endocrinology affiliated to the International Society of Gynecological *** purpose of this guideline’s interpretation is to promote more medical workers to understand the technology of ovarian tissue cryopreservation and transplantation,which can provide patients with more choices of fertility protection methods and improve their quality of life.

关键词： Guideline interpretation Prevention Ovarian tissue cryopreservation and transplantation Fertility preservation

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