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TGF-β-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer

Oncology Research 2024年第2期32卷 373-391页

作者： JIANFA WU QIANYI LIAO LI ZHANG SUQIN WU ZHOU LIU department of gynecology Shanghai University of Medicine&Health Sciences Affiliated Zhoupu HospitalShanghaiChina department of gynecology Shanghai University of Medicine&Health SciencesShanghaiChina department of gynecology Gongshan People’s HospitalNujiang Lisu Autonomous PrefectureChina

The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP

关键词： Chemoresistance Cisplatin Iron Ovarian neoplasms TGF-β

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Curcumin modulates oxidative stress to inhibit pyroptosis and improve the inflammatory microenvironment to treat endometriosis

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Genes & Diseases 2024年第3期11卷 102-105页

作者： Jie Ding Shanshan Mei Kaili Wang Wen Cheng Shuai Sun Zhexin Ni Xiaoqiu Wang Chaoqin Yu department of gynecology of Traditional Chinese Medicine Changhai Hospital Affiliated to Naval Medical UniversityShanghai 200433China Obstetrics and gynecology department The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouZhejiang 310006China department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Obstetrics and gynecology Hospital of Fudan University Shanghai 200433China

Endometriosis(EM)is a common disease that affects approximately 10%-15%of women of childbearing age.The pathogenesis of EM is unclear,but studies have shown a strong association between EM and inflammation,as well as oxidative stress.^(1) Pyroptosis is also called inflammatory cell death.When pyroptosis occurs,it activates a strong inflammatory response.Pyroptosis is associated with oxidative stress,and Ros act as intermediate triggers to activate pyroptosi.

关键词： inflammatory death oxidative

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Perinatal outcomes of re-recurrent gestational diabetes mellitus and their prognostic factors:A retrospective cohort study in China

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Chinese Medical Journal 2024年第4期137卷 499-501页

作者： Xia Xu Yanni Guo Tingting Liao Huale Zhang Rumeng Jiang Shuyao Huang Jianying Yan department of Obstetrics and gynecology Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian 350001China

To the Editor:Gestational diabetes mellitus(GDM)is a pathologic condition in which glucose intolerance and insulin resistance develop to different degrees during pregnancy.Women with GDM have higher odds of adverse maternal and fetal outcomes.Patients with a history of GDM were at a significantly increased risk for recurrence of GDM in subsequent pregnancies.Our previous and some other studies found an increased incidence of adverse perinatal outcomes in pregnant with recurrent GDM.^([1])So far,women with a prior history of GDM are not recommended to refrain from subsequent pregnancy in light of the limited available data.What about those women with a history of recurrent GDM?Should women with recurrent GDM be recommended to avoid further pregnancy?Currently,studies on perinatal outcomes of women with re-recurrent GDM and their prognostic factors are very rare.Therefore,this retrospective cohort study was performed to explore perinatal outcomes of pregnant woman with re-recurrent GDM and their prognostic factors.

关键词： mellitus pregnancy diabetes

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Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

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BIOCELL 2024年第4期48卷 571-580页

作者： JIA SHAO CAN ZHANG YAONAN TANG AIQIN HE WEIPEI ZHU department of Obstetrics and gynecology The Second Affiliated Hospital of Soochow UniversitySuzhou215004China department of gynecology Oncology Affiliated Tumor Hospital of Nantong UniversityNantong226361China

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell growth.However,the expression,clinical signiﬁcance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain unclear.Methods:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent tissues.The expression of circRNA_001896 was detected in 72 CC patients usingﬂuorescence quantitative PCR.Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis.The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis assays.Results:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC tissues.Fluorescence quantitative PCR conﬁrmed circRNA_001896 as a circular RNA.High expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC patients.Proportional hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’prognosis.Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming ability.In vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells.Conclusion:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and survival period in patients.Moreover,downregulating cir

关键词： Uterine cervical neoplasms RNA Circular Cell proliferation Cancer stem cells

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Development of immature ovarian teratoma after mature teratoma in a girl with familial ovarian teratoma:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1442-1447页

作者： U Chul Ju Woo Dae Kang Seok Mo Kim department of Obstetrics and gynecology Chonnam National University Medical SchoolGwangju 61469South Korea

BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.

关键词： Familial ovarian teratomas Adolescent female Immature ovarian teratoma Management Case report

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Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma

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World Journal of Clinical Cases 2024年第6期12卷 1111-1119页

作者： Xiao-Yu Xing Wei Zhang Li-Ya Liu Li-Ping Han department of gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000Henan ProvinceChina

BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare.AIM To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the ovary.METHODS A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary,analyzing clinicopathological characteristics,treatment modalities,and survival status.RESULTS The median age at diagnosis was 34.5 years(range:20 to 62 years).Among the 12 cases,9 were small cell carcinoma of the ovary and 3 were large cell NEC.Five cases were stage I tumors,one case was stage IV,and six cases were stage III.Eleven patients underwent surgery as part of their treatment.All patients received adjuvant chemotherapy.Among the 12 patients,one patient received radiotherapy,and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy.The median progression-free survival was 13 months,and the median overall survival was 19.5 months.Four cases remained disease-free,while eight cases experienced tumor recurrence,including three cases that resulted in death due to disease recurrence.CONCLUSION NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes.Surgical resection remains the mainstay of treatment,with some patients benefiting from adjuvant chemoradiation therapy.

关键词： Neuroendocrine carcinoma Ovary Pathology Treatment

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Fertility preservation in patients with gynecologic cancer

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World Journal of Clinical Cases 2024年第14期12卷 2301-2303页

作者： Nicolae Gică department of Obstetrics and gynecology Carol Davila University of Medicine and PharmacyBucharest 775887Romania

In this editorial we comment on the article by Gu et al.We focus and debate the necessity of fertility sparing surgery in young women’s with gynecologic cancers,specifically on those patients with the desire to conceive.This type of individu-alized treatment options is often very difficult,due to the risk of disease evolution and multiple disparities in fertility preservation services among women in di-fferent countries and societies.For this reason national policy interventions are mandatory in order to ensure equitable access this procedures,in women with cancer.

关键词： Fertility sparing surgery Pregnancy Gynecologic cancer Endometrial cancer Ovarian cancer

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Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes: An analysis of 15,124 normal ovarian responders in China

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中华医学杂志(英文版) 2024年第7期137卷 837-845页

作者： Zheng Danlei Wang Yuanyuan Chen Lixue Zeng Lin Li Rong department of Obstetrics and gynecology Center for Reproductive Medicine Peking University Third Hospital Beijing 100191 China Research Center of Clinical Epidemiology

Background: High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth inin vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response.Methods: We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5-15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes.Results: High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682-0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646-0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595-0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533-2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547-3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24 kg/m2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5 yea

关键词： Obesity Body mass index In vitro fertilization Live birth Decision trees Normal ovarian response

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Chinese Population Reference Curves for Ultrasound-Measured Amniotic Fluid Deepest Vertical Pocket in Dichorionic Twin Pregnancies,and Their Associations With Pregnancy Outcomes

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Maternal-Fetal Medicine 2024年第1期6卷 29-36页

作者： Zhengxin Lyu Tianchen Wu Shan Lu Pengbo Yuan Yangyu Zhao Yuan Wei department of Obstetrics and gynecology Peking University Third HospitalBeijing 100191China

Objective:To establish the Chinese population's amniotic fluid deepest vertical pocket(DVP)reference curves for dichorionic twin pregnancies and to investigate DVP links with adverse perinatal outcomes.Methods:This retrospective cohort study,conducted at Peking University Third Hospital from August 2011 to December 2020,used data from 375 women aged 20 to 45 years who had dichorionic twin pregnancies that were confirmed through first-trimester ultrasound.After exclusions,reference curves were developed using 318 women with 3,299 DVP scans,and the data analyzed included maternal demographics,pregnancy outcomes,ultrasound measurements,and neonatal information.DVPs were assessed via ultrasound at regular intervals and grouped by gestational age(GA)for analyses.Linear mixed models were used to create amniotic fluid reference curves.Associations between abnormalities and adverse perinatal outcomes were examined using Chi-squared or Fisher's exact tests.Logistic regression provided both crude and adjusted odds ratios,adjusting for pre-pregnancy weight,age,ethnicity,parity,and conception mode.Significance was set at P<0.05 with 95%confidence intervals(CI),and the analyses were conducted using SPSS ver.26.0(IBM Corp.,Armonk,NY)and SAS ver.9.4(SAS Institute Inc.,Cary,NC,USA)software.Results:DVP increased from the first trimester to a maximum at 26 weeks(95%confidence interval(CI),2.7–8.3 cm for twin 1 and 2.8–7.9 cm for twin 2)and then decreased gradually toward term.Differences between twins 1 and 2 were significant after 26 weeks(95%CI for twin 1:5.3,5.5;95%CI for twin 2:4.4,4.5;P<0.010).Polyhydramnios of twin 1 increased the risk of large for GA.Oligohydramnios of twin 1 increased the risk of small for GA.Polyhydramnios of twin 2 increased the risk of small for GA,premature birth,and neonatal complications.Oligohydramnios of twin 2 increased the risk of preeclampsia,hypertensive disorder complicating pregnancy,and premature rupture of membranes.Conclusion:Reference curves for twin amniotic fluid volumes vary by GA and

关键词： Amniotic fluid Amniotic fluid deepest vertical pocket Reference curve Dichorionic twin Pregnancy outcome Ultrasound examination

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Exploring the molecular mechanisms and potential therapeutic strategies of ferroptosis in ovarian cancer

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BIOCELL 2024年第3期48卷 379-386页

作者： LISHA MA WANQI SHAO WEILI ZHU department of gynecology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingChina department of gynecology Jiaxing University Affiliated Women and Children’s HospitalJiaxingChina

The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and speciﬁc diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identiﬁcation of new therapeutic targets due to the absence of efﬁcient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efﬂux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the mo

关键词： Ovarian cancer Ferroptosis Therapy

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