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Biomedical and Environmental Sciences 2024年第4期37卷 423-427页

作者： ZHANG Sai CHEN Zhi Xian ZHANG Mo DU Yan ZHOU Jia Yi WU Jing YU Yin Hua CAO Qi ZHAO Hong Bo Obstetrics and Gynecology Hospital Fudan UniversityShanghai 200011China shanghai key laboratory of female reproductive endocrine related diseases Shanghai 200011China

Placental site trophoblastic tumor(PSTT),a rare gestational trophoblastic neoplasm(GTN),exhibits slow growth,late-onset metastasis,and chemotherapy insensitivity[1,2].The invasive capacity of trophoblasts induces angiogenesis in PSTT,yet the specific mechanism remains unclear[3].PSTT is typically resistant to chemotherapy and hysterectomy stands as the primary therapeutic choice for patients with an overall cure rate of approximately 75%-80%[4,5].Therefore,investigating the precise emergence and progression of PSTT is crucial,aiming to identify novel targets for diagnosis and therapy.

关键词： chemotherapy diagnosis metastasis

PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives

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Frontiers of Medicine 2019年第4期13卷 438-450页

作者： Yumeng Wang Guiling Li shanghai key laboratory of female reproductive endocrine related diseases Fudan University Shanghai 200011 China Department of Integration of Western and Traditional Medicine Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011 China

Cervical cancer (CC) is the fourth most commonly diagnosed female malignancy and a leading cause of cancer-related mortality worldwide, especially in developing countries. Despite the use of advanced screening and preventive vaccines, more than half of all CC cases are diagnosed at advanced stages, when therapeutic options are extremely limited and side effects are severe. Given these circumstances, new and effective treatments are needed. In recent years, exciting progress has been made in immunotherapies, including the rapid development of immune checkpoint inhibitors. Checkpoint blockades targeting the PD-1/PD-L1 axis have achieved effective clinical responses with acceptable toxicity by suppressing tumor progression and improving survival in several tumor types. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway, including the expression patterns of PD-1/PD-L1 and potential PD-l/PD-Ll-related therapeutic strategies for CC.

关键词： PD-1 PD-L1 immune checkpoint blockade antibody immunotherapy cervical cancer

Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse

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World Journal of Stem Cells 2024年第6期16卷 708-727页

作者： Lei-Mei Xu Xin-Xin Yu Ning Zhang Yi-Song Chen Department of Gynecology Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China Department of Gynecology Shanghai Key Laboratory of Female Reproductive Endocrine-related DiseasesShanghai 200011China

BACKGROUND Pelvic organ prolapse(POP)involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity,and vaginal structure is an essential *** POP,the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and *** intricate etiology of POP and the prohibition of trans-vaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy *** umbilical cord mesenchymal stromal cells(hucMSCs)present limitations,but their exosomes(hucMSC-Exo)are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix *** inflammation in POP group fibroblasts,stimulated primary fibroblast growth,and elevated collagen I(Col1)production in ***-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11(MMP11)*** HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in *** miRNAs in hucMSC-Exo targeted and downregulated MMP11 ***-Exo-based therapy may be ideal for safely and effectively treating POP.

关键词： Pelvic organ prolapse Exosomes Fibroblasts Human umbilical cord mesenchymal stromal cells Extracellular matrix Collagen I

Trophoblast-derived CXCL16 induces M2 macrophage polarization that in turn inactivates NK cells at the maternal–fetal interface

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Cellular & Molecular Immunology 2018年第12期15卷 1038-1046页

作者： Xiao-Qiu Wang Wen-Jie Zhou Xin-Xin Hou Qiang Fu Da-Jin Li laboratory for reproductive Immunology Key Laboratory of Reproduction Regulation of NPFPCSIPPRShanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesHospital and Institute of Obstetrics and GynecologyIRDFudan UniversityShanghai Medical CollegeShanghaiChina College of Basic Medicine Binzhou Medical UniversityYantaiShandongChina

Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy have not beencompletely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in themaintenance of maternal–fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces thepolarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, whichfacilitates the inactivation of NK cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2 MΦ. The data shown inthe present study provide evidence to support the hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involvedin decidual M2 MΦ polarization, which in turn regulates the killing ability of NK cells, thereby contributing to the homeostatic andimmune-tolerant milieu required for successful fetal development.

关键词： CXCL16 trophoblasts macrophage polarization NK cells maternal-fetal interface

Altered vaginal eukaryotic virome is associated with different cervical disease status

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Virologica Sinica 2023年第2期38卷 184-197页

作者： Yanpeng Li Le Cao Xiao Han Yingying Ma Yanmei Liu Shujun Gao Chiyu Zhang shanghai Public Health Clinical Center Fudan UniversityShanghai201508China Center of Diagnosis and Treatment for Cervical diseases Obstetrics and Gynecology Hospital of Fudan UniversityShanghai200080China shanghai key laboratory of female reproductive endocrine-related disease Fudan UniversityShanghai200080China

Viruses are important components of the human *** evidence suggests that they are engaged in the physiology and disease status of the *** though the vaginal microbiome is involved in human papillomavirus(HPV)infection and cervical cancer(CC)progression,little is known about the role of the vaginal *** this pilot exploratory study,using unbiased viral metagenomics,we aim to investigate the vaginal eukaryotic virome in women with different levels of cervical lesions,and examine their associations with different cervical disease *** altered eukaryotic virome was observed in women with different levels of lesions and Lactobacillus *** and papillomaviruses are the most commonly detected eukaryotic viruses of the vaginal *** abundance and richness of anelloviruses and papillomaviruses were associated with lowgrade squamous intraepithelial lesion(LSIL)and ***,higher anellovirus abundance was also associated with lactobacillus-depleted microbiome profiles and bacterial community state(CST)type ***,increased correlations between Anelloviridae and Papillomaviridae occurred in the women with increased cervical disease severity level from LSIL to *** data suggest underlying interactions between different microbes as well as the host *** abundance and diversity of both anelloviruses and papillomaviruses shared by LSIL and CC suggest that anellovirus may be used as a potential adjunct biomarker to predict the risk of HPV persistent infection and/or *** studies need to focus on the clinical relevance of anellovirus abundance with cervical disease status,and the evaluation of their potential as a new adjunct biomarker for the prediction and prognoses of CC.

关键词： Vaginal virome Cervical cancer Anellovirus Papillomavirus

TIM-3: a crucial regulator of NK cells in pregnancy

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Cellular & Molecular Immunology 2017年第11期14卷 948-950页

作者： Yanhong Li Dajin Li Meirong Du laboratory for reproductive Immunology Hospital of Obstetrics and GynecologyFudan University Shanghai Medical CollegeShanghaiChina key laboratory of Reproduction Regulation of NPFPC SIPPRIRDFudan UniversityShanghaiChina shanghai key laboratory of female reproductive endocrine related diseases ShanghaiChina

In pregnancy,the maternal immune system(including innate and adaptive immunity)makes elaborate adjustments to endure the embryo’s expression of paternal antigens and to protect the embryo from attacks by invading pathogens such as bacteria or viruses.1 As the predominant innate immune cells during gestation,natural killer(NK)cells have been proven to mediate the establishment of maternal-fetal immune tolerance and to initiate appropriate defenses against infections.2 Tim-3,a member of the T-cell immunoglobulin and mucin domain proteins,has emerged as a key molecule in both innate and adaptive responses and represents a promising novel therapeutic target.

关键词： pregnancy immunity predominant

Interactions of Indoleamine 2,3-dioxygenase-expressing LAMP3^(+) dendritic cells with CD4^(+) regulatory T cells and CD8^(+) exhausted T cells:synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications

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Cancer Communications 2023年第11期43卷 1207-1228页

作者： Xinyu Qu Yumeng Wang Qian Jiang Tingting Ren Chenyan Guo Keqin Hua Junjun Qiu Department of Gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghaiP. R. China shanghai key laboratory of female reproductive endocrine-related diseases ShanghaiP. R. China

Background Cervical cancer(CC)is the fourth most common cancer in women *** immunotherapy has been applied in clinical practice,its therapeutic efficacy remains far from satisfactory,necessitating further investigation of the mechanism of CC immune remodeling and exploration of novel treatment *** study aimed to investigate the mechanism of CC immune remodeling and explore potential therapeutic *** We conducted single-cell RNA sequencing on a total of 17 clinical specimens,including normal cervical tissues,high-grade squamous intraepithelial lesions,and CC *** validate our findings,we conducted multicolor immunohistochemical staining of CC tissues and constructed a subcutaneous tumorigenesis model in C57BL/6 mice using murine CC cell lines(TC1)to evaluate the effectiveness of combination therapy involving indoleamine 2,3-dioxygenase 1(IDO1)inhibition and immune checkpoint blockade(ICB).We used the unpaired two-tailed Student's t-test,Mann-Whitney test,or Kruskal-Wallis test to compare continuous data between two groups and one-way ANOVA with Tukey's post hoc test to compare data between multiple *** Malignant cervical epithelial cells did not manifest noticeable signs of tumor escape,whereas lysosomal-associated membrane protein 3-positive(LAMP3^(+))dendritic cells(DCs)in a mature state with immunoregulatory roles were found to express IDO1 and affect tryptophan *** cells interacted with both tumor-reactive exhausted CD8^(+)T cells and CD4^(+) regulatory T cells,synergistically forming a vicious immunosuppressive cycle and mediating CC immune *** validation through multicolor immunohistochemical staining showed co-localization of neoantigen-reactive T cells(CD3^(+),CD4^(+)/CD8^(+),and PD-1^(+))and LAMP3+DCs(CD80^(+) and PD-L1^(+)).Additionally,a combination of the IDO1 inhibitor with an ICB agent significantly reduced tumor volume in the mouse model of CC compared with an ICB agent alone.C

关键词： cervical cancer dendritic cell immune checkpoint blockade immune escape indoleamine 2,3-dioxygenase 1 single-cell analysis T cell

Current Updates on Salpingectomy for the Prevention of Ovarian Cancer and Its Practice Patterns Worldwide

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Chinese Medical Sciences Journal 2017年第3期32卷 185-192页

作者： Sweta Dhakal Yunxi Zheng Xiaofang Yi Department of Gynecology Obstetrics and Gynecology Hospital of Fudan University Department of Obstetrics and Gynecology Shanghai Medical College Fudan University shanghai key laboratory of female reproductive endocrine related diseases

A paradigm shift of the origin of ovarian cancer to fallopian tube has brought more focus on bilateral salpingectomy as a preventive method for ovarian cancer. Bilateral salpingectomy has shown a dramatic reduction in the risk of ovarian cancer. Bilateral salpingo-oophorectomy has been a long-used practice to prevent ovarian cancer, but it brings surgical menopause and an increased mortality rate to women undergoing such a surgery at the age of related to opportunistic salpingectomy worldwide.

关键词： ovarian cancer salpingectomy prevention clinician opinion

Congenital Vaginal Atresia:A Report of 39 Cases in a Regional Obstetrics and Gynecology Hospital

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2017年第6期37卷 928-932页

作者：张萌张明星李桂玲徐丛剑 Obstetrics and Gynecology Hospital Fudan UniversityShanghai 200011China Department of Obstetrics and Gynecology of shanghai Medical School Fudan University Shanghai 200032China shanghai key laboratory of female reproductive endocrine related diseases Shanghai 200011China

To investigate the clinical course and management of congenital vaginal atresia. This retrospective analysis included patients with congenital vaginal atresia treated from March 2004 to August 2014 at the Obstetrics and Gynecology Hospital of Fudan University. Thirty-nine patients were included in this study. Their average age was 16.87±2.2 years when they came to our hospital. Totally, 51% of the patients had isolated congenital vaginal atresia with a normal cervix, whereas the others had either cervical atresia or imperforate hymen. The primary presenting signs and symptoms included primary amenorrhea（71.8%）, periodic abdominalgia（41.0%）, abdominal pain（36.0%）, dyspareunia（10.3%）, menstrual disorders（5.1%）, and pelvic mass（5.1%）. Ultrasound and magnetic resonance imaging（MRI） were effective inspection methods for the screening of urogenital tract-associated anomalies. Vaginoplasty mainly included simple vagina reconstruction with insertion of a mold（n=22） and split-thickness skin grafting（n=4）. In 64% of surgical patients, normal menstrual bleeding was achieved. Four of the patients subsequently became pregnant and delivered at term. Primary amenorrhea, periodic abdominalgia and abdominal pain are the main reasons for the post pubertal patients to visit doctors. Surgical methods can successfully provide these patients an opportunity for subsequent conservative management, can result in normal menstrual bleeding, resolve cyclic pelvic pain, and provide some potential for fertility.

关键词： congenital vaginal atresia diagnosis treatment

A novel homozygous loss-of-function mutation in RAD51AP2 induces male infertility with nonobstructive azoospermia

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Asian Journal of Andrology 2023年第3期25卷 435-437页

作者： Liu Liu Shu-Yan Tang Feng Zhang Feng Jiang Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China shanghai key laboratory of female reproductive endocrine related diseases Shanghai 200011China shanghai JIAI Genetics and IVF Institute-China USA Center Shanghai 200011China

Dear Editor,The most severe type of male infertility,nonobstructive azoospermia(NOA),is characterized by clinical heterogeneity,implying the involvement of different acquired and genetic ***,the cause of NOA is unidentified in a substantial number of patients after the exclusion of all-known acquired factors and routine genetic testing,such as karyotype and Y chromosome microdeletion analysis.1 With the recent rapid development of whole-exome sequencing(WES),an increasing number of novel monogenic causes have been ***,RAD51-associated protein 2(RAD51AP2)was reported to be a novel causative gene of NOA in a monogenic recessive manner in two sporadic patients.2 Here,we studied the WES data for a family with two NOA patients and found that both carried a novel homozygous loss-of-function(LoF)mutation in RAD51AP2.

关键词： RAD51 routine infertility