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Conditioned Medium from Human Umbilical Vein Endothelial Cells Promotes Proliferation,Migration,Invasion and Angiogenesis of Adipose Derived Stem Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2018年第1期38卷 124-130页

作者：骆名恋刘小平王芳刘晓夏刘维芳吴迪陶惠王绒莉赵茵朱剑文邹丽 Department of obstetrics and gynecology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of obstetrics and gynecology Wuhan First Hospital

Preeclampsia（PE） is a pregnancy-specific hypertensive complication,closely related to endothelial dysfunction.Adipose derived stem cells（ADSCs） have the capacity to differentiate into endothelial cells for vascular repair.Therefore,we hypothesized that induced endothelial differentiation of ADSCs might hold great potential for the treatment of PE.In this study,the primary ADSCs and human umbilical vein endothelial cells（HUVECs） were isolated by the collagenase digestion method.The supernatant of HUVECs was collected from the first generation of cells.Then,ADSCs were divided into two groups：ADSCs alone group and induced ADSCs（i ADSCs） group.In i ADSCs group,ADSCs were induced by HUVECs conditioned medium and ADSCs special culture medium at a ratio of 1：1 over a two-week period.In order to identify the endothelial characteristics of i ADSCs,CD31 and CD34 were examined by flow cytometry.The proliferation,migration,invasion and angiogenesis assays were employed to compare the bioactivity of i ADSCs and ADSCs.Furthermore,The levels of angiogenic related factors including vascular endothelial growth factor（VEGF） and placenta growth factor（Pl GF） were detected by RT-PCR and Western blotting.Results showed conditioned medium from HUVECs promoted ADSCs proliferation,migration,invasion and angiogenesis.In addition,the levels of VEGF and Pl GF were significantly enhanced in i ADSCs group.This study uncovered the i ADSCs application potential in the therapy and intervention of PE.

关键词： adipose derived stem cells endothelial differentiation angiogenesis preeclampsia

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Regulation of angiogenesis by microRNAs and long non-coding RNAs in endometriosis

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Reproductive and Developmental Medicine 2022年第3期6卷 133-137页

作者： Rui-Hui Lu Jing-Wen Zhu Fang-Yuan Li Qing Xue Department of obstetrics and gynecology Peking University First HospitalBeijingChina

Endometriosis(EM)is a benign gynecological disease that affects the fertility and health of women of reproductive age;it is characterized by the presence of endometrial glands and stroma outside the uterine cavity.Although several hypotheses have been proposed to explain the underlying cause of EM,its pathogenesis remains obscure.Recently,non-coding RNAs were reported to be involved in the occurrence and development of EM.MicroRNAs and long non-coding RNAs are the main members of the non-coding RNA family that contribute to EM progression in various aspects,such as cell proliferation,apoptosis,invasion,and angiogenesis.Angiogenesis plays a pivotal role in the initiation and development of EM and provides a substantial background for the invasion,proliferation,and long-term growth of endometriotic implants.This review aimed to investigate the role of microRNAs and long non-coding RNAs in regulating angiogenesis in EM and discuss how this mechanism can be used for diagnostic and therapeutic purposes in EM.

关键词： MicroRNAs Long non-coding RNAs Endometriosis Angiogenesis Pathogenesis

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Clinicopathological Evaluation of Ovarian Juvenile Granulosa Cell Tumor: Is Fertility-Sparing Surgery Safe?

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Reproductive and Developmental Medicine 2019年第1期3卷 24-29页

作者： Lu Guo Xiao-Cheng Liu Xiu-Ying Chen Xi-Rong Xiao Yu-Qing Qu Bin Li Department of obstetrics and gynecology Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Department of obstetrics and gynecology of Shanghai Medical School Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China

Objective:To retrospectively investigate the clinicopathological characteristics of ovarian juvenile granulosa cell tumors(JGCTs)and to evaluate the safety of fertility-sparing surgery.Methods:In this study,surgically treated patients with JGCTs diagnosed between January 2004 and October 2018 in our center were identified.Clinicopathological data,survival outcomes,and recurrence rates were examined in these patients.Results:A total of 8 patients were included.All patients were premenarchal girls or young women(age range,9-32 years).Irregular vaginal bleeding was the most common presenting symptom.Of them,seven patients were classified with Stage I JGCTs,and they underwent fertility-sparing surgery.One patient who had Stage IIIC JGCT and had completed childbearing underwent complete surgery.Seven patients received adjuvant chemotherapy.The median follow-up duration in the total cohort was 64 months(range,2-117 months).The overall survival rate in the fertility-sparing group was 100%,whereas the patient with Stage IIIC JGCT died 1 month after the treatment.Conclusions:Fertility-sparing surgery might not show a negative impact on oncologic outcomes.Fertility sparing could be considered a modified option for patients with Stage I JGCTs.However,due to the limited number of patients,the conclusion must be interpreted with caution,and larger or multicenter studies are needed before conclusions can be drawn.

关键词： Adjuvant Chemotherapy Complete Surgery Fertility-Sparing Surgery Ovarian Juvenile Granulosa Cell Tumor

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Value of fasting plasma glucose to screen gestational diabetes mellitus before the 24th gestational week in women with different pre-pregnancy body mass index

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Chinese Medical Journal 2019年第8期132卷 883-888页

作者： Yu-Mei Wei Xin-Yue Liu Chong Shou Xing-Hui Liu Wen-Ying Meng Zi-Lian Wang Yun-Feng Wang Yong-Qing Wang Zhen-Yu Cai Li-Xin Shang Ying Sun Hui-Xia Yang Department of obstetrics and gynecology Peking University First Hospital Beijing 100034 China Department of obstetrics and gynecology General Hospital of Beijing Military Region Beijing 100700 China Department of obstetrics and gynecology Navy General Hospital Beijing 100000 China Department of Pharmaceutical Outcomes and Policy College of Pharmacy University of Florida Gainesville FL 32611 USA Hallmark Health System Medford MA 02155 USA Department of obstetrics and gynecology West China Second University Hospital Chengdu Sichuan 610041 China Department of obstetrics and gynecology Tongzhou Maternal and Child Health Hospital of Beijing Beijing 101101 China Department of obstetrics and gynecology First Affiliated Hospital of Sun Yat-Sen University Guangzhou Guangdong 510080 China Department of obstetrics and gynecology Beijing Miyun Hospital Beijing 101500 China Department of obstetrics and gynecology Peking University Third Hospital Beijing 100191 China Department of obstetrics and gynecology Center Hospital of Aviation Industry Beijing 100012 China

Background:Gestational diabetes mellitus(GDM)is usually diagnosed between 24th and 28th gestational week using the 75-g oral glucose tolerance test(OGTT).It is difficult to predict GDM before 24th gestational week because fast plasma glucose(FPG)decreases as the gestational age increases.It is controversial that if FPG≥5.1 mmol/L before 24th gestational week should be intervened or not.The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy body mass index(BMI).Methods:This was a multi-region retrospective cohort study in China.Women who had a singleton live birth between June 20,2013 and November 30,2014,resided in Beijing,Guangzhou and Chengdu,and received prenatal care in 21 selected hospitals,were included in this study.Pre-pregnancy BMI,FPG before the 24th gestational week,and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical charts and analyzed.The pregnant women were classified into four groups based on pre-pregnancy BMI:Group A(underweight,BMI<18.5 kg/m^2),Group B(normal,BMI 18.5-23.9 kg/m^2),Group C(overweight,BMI 24.0-27.9 kg/m^2)and Group D(obesity,BMI≥28.0 kg/m^2).The trend of FPG before 24th week of gestation was described,and the sensitivity and specificity of using FPG before the 24th gestational week to diagnose GDM among different pre-pregnancy BMI groups were reported.Differences in the means between groups were evaluated using independent sample t-test and analysis of variance.Pearson Chi-square test was used for categorical variables.Results:The prevalence of GDM was 20.0%(6806/34,087)in the study population.FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week.FPG was higher in women with higher pre-pregnancy BMI.FPG before the 24th gestational week and pre-pregnancy BMI could be used to predict GDM.The incidence of GDM in women with FPG≥5.10 mmol/L in the 19th to 24th gestational weeks and pre-

关键词： Body mass index Fasting plasma glucose Gestational diabetes mellitus

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Vitamin D-Binding Protein is Involved in the Pathogenesis of Preeclampsia by Inhibiting the Tyrosine Phosphorylation of Vascular Endothelial Growth Factor Receptor-2 in Endothelial Cells

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Reproductive and Developmental Medicine 2021年第3期5卷 140-147页

作者： Ting-Feng Lu Yun-Zhen Ye Xiao-Tian Li Ying Zhang Department of obstetrics Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200032China

Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls,and aimed to explore the effect of DBP on endothelial cells(ECs)and the underlying mechanism.Methods::DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry.The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA(siRNA)and DBP-expression vector,respectively.The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC(HUVEC)cultures.Angiogenic effects on HUVECs were assessed by tube formation assays,and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer.The expression of vascular endothelial growth factor(VEGF)and VEGF receptor(VEGFR)-2,as well as the phosphorylation of different residues of VEGFR-2 in HUVECs,were determined by western blotting.Results::DBP expression was significantly increased in the placental tissues collected from PE patients.The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs,in addition to their proliferation and migration.Furthermore,treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996,whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951,996,and 1,175.Conclusions::The expression of DBP is increased in the placentas of PE patients.DBP plays potential roles in endothelial dysfunction,which contributes to PE development,by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.

关键词： Angiogenesis Phosphorylation Preeclampsia Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor-2 Vitamin D-Binding Protein

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Ovarian cancer presenting with hypercalcemia:two cases with similar manifestations but different mechanisms

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Cancer Biology & Medicine 2018年第2期15卷 182-187页

作者： Xuegong Ma Yingmei Wang Xuhong Zhang Mengting Dong Wen Yang Fengxia Xue Department of gynecology and obstetrics Tianjin Medical University General Hospital

Hypercalcemia presenting in ovarian cancer is uncommon in the clinic.Here,two cases of ovarian epithelial carcinoma that presented with severe hypercalcemia were reported,with a review of the literature.The laboratory findings and stepwise clinical investigations of these two cases differed,indicating distinct underlying causes of hypercalcemia.In case one,the serum levels and immunostaining for parathyroid hormone-related protein(PTHr P)verified humoral hypercalcemia of malignancy(HHM).In case two,the high level of parathyroid hormone(PTH)and the scintigraphy scan showing parathyroid gland adenoma confirmed primary hyperparathyroidism-induced hypercalcemia.Both patients received optimal cytoreductive operation and adjuvant chemotherapy but showed different outcomes respectively.This article focused on differential diagnosis of ovarian cancerassociated hypercalcemia,by stepwise imaging and laboratory investigation,and the appropriate therapy should be considered based on the different etiologies.

关键词：癌症卵巢案例类似机制调查结果甲状旁腺大小写

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NLRP3 inhibitor dopamine receptors agonist as a potential therapeutic strategy for treatment of overactive immune responses in COVID-19

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Reproductive and Developmental Medicine 2023年第2期7卷 65-67页

作者： Jia-Lei Zhu Jing Jin Jing Tang Department of Pharmacy Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China

Patients infected with coronavirus disease 2019(COVID-19)have high serum levels of proinflammatory cytokines.The"cytokine storm"has become one of the major causes of death for critically ill patients infected by COVID-19.Glucocorticoids,plasma from convalescent patients,blood purification,and tocilizumab are currently recommended for use when the body’s inflammatory response is overactivated.However,there are limitations in terms of medicinal effects,equipment reserves,and treatment expense.These challenges prompted us to assess classical agents with good safety and mature production technology.A recent study showed that nucleotide-binding oligomerization domain(NOD)-,leucine-rich repeat(LRR)-,and pyrin domain-containing protein 3(NLRP3)inflammasomes drive COVID-19 pathology.We speculate that suppression of NLRP3 inflammasome-derived cytokine production may be beneficial in COVID-19-infected patients.Dopamine receptors are present in almost all immune cells and can modulate their activation,proliferation,and cytokine production of immune cells.Previous studies have shown that dopamine receptor agonists can control systemic inflammation through inhibition of the NLRP3 inflammasome.This suggests that dopamine receptor agonists may be a new strategy for the treatment of overactive immune responses in COVID-19 patients.This is worthy of further investigation in clinical practice.

关键词： NLRP3 inflammasome Cytokine storm COVID-19 Dopamine receptors Medication regimen Interleukin

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Two Cases of Intrauterine Adhesions with Rare Hysteroscopic Findings

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Chinese Medical Journal 2018年第20期131卷 2474-2476页

作者： Feng-Xian Fu Hua Duan Sha Wang Yi-Qun Tang Lu Gan Qian Xu Department of gynecology Minimally Invasive Center Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100006 China Department of obstetrics and gynecology Aerospace Central Hospital Beijing 100049 China

An intrauterine adhesion （IUA） is a form of disease that causes the uterine muscle walls to become adhered to each other due to the basal layers of the endometrium being damaged by various factors, thus resulting in... 详细信息

关键词： ULTRASOUND

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The imbalance of T-cell immunoglobulin and ITIM domain and CD226 on regulatory T cell in recurrent spontaneous abortion patients

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Reproductive and Developmental Medicine 2022年第3期6卷 175-180页

作者： Cui Li Chun-Mei Ying Zhong-Liang Duan Department of Clinical Laboratory Obstetrics and Gynecology Hospital of Fudan UniversityShanghaiChina

Objective:To analyze the proportion of peripheral regulatory T cells(Tregs)and the expression of the immune checkpoint molecules T-cell immunoglobulin and ITIM domain(TIGIT)and CD226 on Tregs in patients with recurrent spontaneous abortion(RSA).Methods:The proportion of CD3+CD4+CD25+Foxp3+Tregs and the expression levels of CD226 and TIGIT on Tregs in 30 normal pregnant women and 28 patients with RSA were determined via flow cytometry.Results:The proportion of Tregs in the RSA group(4.41%±1.54%)was significantly lower than that in the control group(5.27%±1.52%,P=0.0374).Compared with the normal pregnant women,patients with RSA showed decreased TIGIT expression(54.75±9.70%vs.63.07±12.48%,P=0.0066)and increased CD226 expression on Tregs(25.59%±8.22%vs.20.46%±6.97%,P=0.0168).The ratio of CD226 to TIGIT in the RSA group(0.48±0.19)was higher than that in the control group(0.34±0.15,P=0.0027).The proportion of TIGIT+CD226+Tregs was significantly lower in patients with RSA(9.30%±4.95%vs.13.43%±4.72%,P=0.0020)than in the controls.Conclusions:Patients with RSA show a reduced proportion of Tregs and an imbalance in the expression of TIGIT and CD226 on Tregs.

关键词： Recurrent spontaneous abortion TIGIT CD226

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Improved Fertility Following Enucleation of Intramural Myomas in Infertile Women

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Chinese Medical Journal 2017年第14期130卷 1648-1653页

作者： Yu-Cui Tian Jian-Hong Wu Hong-Mei Wang Yin-Mei Dai Department of Perinatal Medicine Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China Department of gynecology Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China Department of Minimal Invasive gynecology Center Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China

Background：The relationship between intramural myomas and fertility remains unclear.The main debate rests on whether cavity-distorting intramural lnyomas （CDMs） adversely affect fertility more than non-CDMs.We aimed to compare the effects ofenucleating non-CDMs and CDMs on fertility improvement in females with unexplained infertility.Methods：We prospectively recruited 83 women undergoing myomectomy for unexplained infertility with intramural myomas between June 2008 and November 2012 and classified them into non-CDMs group （n =45） and CDMs group （n =38）.We then compared postoperative infertility rates,spontaneous pregnancy rates,pregnancy outcomes,live birth rates,and obstetric complications.For continuous variables,we calculated the mean ± standard deviation,median and interquartile range,and analyzed the data using Student＇s t-test and the Mann-Whitney U-test.For categorical variables,the Pearson＇s Chi-square test,the continuity correction test,and Fisher＇s exact test were used.Results：Patients＇ demographics and myoma characteristics were comparable between the two groups.The overall spontaneous pregnancy rate increased from 0% to 68.42% following myomectomy.The postoperative infertility rate was significantly higher in the non-CDMs group than that in the CDMs group （50.00% vs.23.53%,t =5.579,P =0.018）,whereas the postoperative spontaneous pregnancy rate was significantly lower in the non-CDMs group than that in the CDMs group （47.62% vs.70.59%,t 4.067,P =0.044）.Compared with the enucleation ofnon-CDM,the enucleation of CDM patients was a protective factor for the fertility restoration （risk ratio [RR] =3.717,95% confidence interval [CI]：1.284-10.753,P =0.015）,although postoperative fertility restoration declined with age （RR =1.141,95% CI：1.005-1.295,P =0.041）.Conclusions：Intramural myomas are associated with impaired fertility.Women experiencing unexplained infertility,and possessing intramural myomas,have a better chance of conception following myomectomy,and these benefits are more obvious for younger patie

关键词： Infertility Myoma Pregnancy Outcome Uterine Myomectomy

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