Background:Low-grade endometrial stromal sarcoma(LG-ESS)is a rare tumor that lacks a prognostic prediction model.Our study aimed to develop a nomogram to predict overall survival of LG-ESS patients.Methods:A total of ...Background:Low-grade endometrial stromal sarcoma(LG-ESS)is a rare tumor that lacks a prognostic prediction model.Our study aimed to develop a nomogram to predict overall survival of LG-ESS patients.Methods:A total of 1172 patients confirmed to have LG-ESS between 1988 and 2015 were selected from the Surveillance,Epidemiology and End Results(SEER)database.They were further divided into a training cohort and a validation cohort.The Akaike information criterion was used to select variables for the nomogram.The discrimination and calibration of the nomogram were evaluated using concordance index(C-index),area under time-dependent receiver operating characteristic curve(time-dependent AUC),and calibration plots.The net benefits of the nomogram at different threshold probabilities were quantified and compared with those of the International Federation of Gynecology and Obstetrics(FIGO)criteria-based tumor staging using decision curve analysis(DCA).Net reclassification index(NRI)and integrated discrimination improvement(IDI)were also used to compare the nomogram’s clinical utilitywith that of the FIGO criteria-based tumor staging.The risk stratifications of the nomogram and the FIGO criteria-based tumor staging were compared.Results:Seven variables were selected to establish the nomogram for LG-ESS.The C-index(0.814 for the training cohort and 0.837 for the validation cohort)and the time-dependent AUC(>0.7)indicated satisfactory discriminative ability of the nomogram.The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations in both the training and validation cohorts.The NRI values(training cohort:0.271 for 5-year and 0.433 for 10-year OS prediction;validation cohort:0.310 for 5-year and 0.383 for 10-year OS prediction)and IDI(training cohort:0.146 for 5-year and 0.185 for 10-year OS prediction;validation cohort:0.177 for 5-year and 0.191 for 10-year OS prediction)indicated that the established nomogram performed significantly better than the FIGO criteria-based 展开更多
Objective： Intrauterine adhesion （IUA） is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there ...Objective： Intrauterine adhesion （IUA） is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-β （TGF-β） signaling pathways to form an intricate network governing the development of fibrosis. Data Sources： Original research articles in English that were published until July 2017 were collected from the PubMed database. Study Selection： Literature search was conducted using the search terms ＂endometrial fibrosis OR fibrosis AND or OR intrauterine adhesion OR Asherman syndrome OR IUA,＂ ＂Hippo AND or OR Hippo/TAZ,＂ ＂TGF-β,＂ and ＂Wnt.＂ Related original research articles were included in the comprehensive analysis. Results： Endometrial fibrosis is recognized as a key pathological event in the development of IUA, which is characterized by epithelial/fibroblast-myofibroblast transition. Myofibroblasts play crucial roles in the pathogenesis of fibrous scarring, and myofibroblast differentiation can be triggered by multiple signaling pathways. H ippo signaling is a critical regulator of the epithelial/fibroblast-myofibroblast transition and α-smooth muscle actin, which exhibits a specific spatiotemporal expression in the endometrium. Conclusions： Hippo signaling plays a critical role in fibrous diseases and participates in cross talks with Wnt and TGF-β signaling. Our findings not only contributed to knowledge on the pathogenesis of endometrial fibrosis, but can also serve as a useful resource for developing specific molecular inhibitors for IUA treatment and prevention.展开更多
Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the...Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.展开更多
Background Endometrial carcinoma is one of the most common gynecological malignancies among women.Early diagnosis and correct preoperative evaluation of myometrial invasion are necessary to improve the prognosis.This ...Background Endometrial carcinoma is one of the most common gynecological malignancies among women.Early diagnosis and correct preoperative evaluation of myometrial invasion are necessary to improve the prognosis.This study aimed to determine whether features and time-intensity curves （TIC） of transvaginal contrast-enhanced ultrasound （CEUS） differ from those of conventional ultrasound for endometrial carcinoma,and to further explore the clinical role of transvaginal CEUS in the early diagnosis of endometrial carcinoma.Methods Forty women with a normal uterus and seventy-nine patients with endometrial carcinoma were examinedby the transvaginal CEUS with SonoVue （Bracco,Imaging B.V,Switzerland）.The enhancement patterns and TIC of lesions were analyzed.The results of CEUS were compared with those of conventional ultrasound and pathology.Results In the early and late enhanced stages,the intensity of enhancement of the normal endometrium was always lower than that in the myometrium,and the boundary between normal endometrium and myometrium was clear.A total of 65.8% （52/79） of lesions presented with inhomogeneous enhancement,34.2% （27/79） presented with homogeneous enhancement; 60.8% （48/79） presented with hyperechoic enhancement,27.8% （22/79） presented with isoechoic enhancement,and 11.4% （9/79） presented with hypoechoic enhancement.The average arrival time,time to peak,rise time,half-wash out time of lesions were shorter than of normal endometrium （P 〈0.05）.The average peak intensity,relative rise in intensity,half-wash out intensity of lesions were higher than of normal endometrium （P〈0.05）.There were 49 （must be and may be present） cases of endometrial carcinoma by ultrasound （US）; 24 cases were consistent with pathology results,16 cases were underestimated and 9 cases were overestimated.There were 72 （must be and may be present） cases of endometrial carcinoma by CEUS; 53 cases were consistent with pathology results,12 cases were underestimated and 7 cases we展开更多
Background： Thin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endomctrial thickness （EMT）. The aim of this retrospective cohort study was to investigate the factors inf...Background： Thin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endomctrial thickness （EMT）. The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium. Methods： Relevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected. Possible factors influencing the effectiveness of treatment were analyzed retrospectively by logistic regression analysis. Eighty-seven infertile women without thin endometrium who had undergone assisted reproduction served as controls. The cases and controls were matched for age, assisted reproduction method, and number of embryos transferred. Reproductive outcomes of study and control groups were compared using Student＇s t-test and the Chi-square test. Results： At the end of estrogen treatment, EMT was ≥8 mm in 93/101 patients （92.1%）. Effectiveness of treatment was significantly associated with maximal pretreatment EMT （P = 0.017） and treatment duration （P = 0.004）. The outcomes of assisted reproduction were similar in patients whose treatment was successful in increasing EMT to ≥8 mm and the control group. The rate of clinical pregnancy in patients was associated with the number of good-quality embryos transferred in both fresh （P = 0.005） and frozen-thawed （P = 0.000） embryo transfer cycles. Conclusions： Thinner EMT before estrogen treatment requires longer treatment duration and predicts poorer treatment outcomes. The effectiveness of treatment depends on the duration of estrogen administration. Assisted reproductive outcomes of patients whose treatment is successful （i.e., achieves an EMT ≥8 mm） are similar to those of controls. The quality of embryos transferred is an important predictor of assisted reproductive outcomes in patients treated successfully with exogenous estrogen.展开更多
Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked ang...Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2(b FGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of b FGF100 μg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients(2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved.Histological study showed blood vessel density increased obviously. Three patients(3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the b FGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.展开更多
Objective This study aimed to review the available literature on fertility-preserving treatment and pregnancy outcomes in patients with early-stage endometrial carcinoma who desired to preserve their fertility. Data s...Objective This study aimed to review the available literature on fertility-preserving treatment and pregnancy outcomes in patients with early-stage endometrial carcinoma who desired to preserve their fertility. Data sources The PubMed database （1992-2012） was searched for the words ＂conservative ＂OR＂ fertility sparing ＂OR＂ fertility preserving＂ AND ＂endometrial neoplasms＂ （MESH）. All relevant articles in English and the relevant references were collected. Study selection Data from published articles about fertility-preserving treatment of endometrial cancer, including the response and recurrence rate of conservative treatment, strategies of infertility treatment, pregnancy, and obstetric outcomes, were selected. Data were mainly extracted from 41 studies, which are listed in the reference section of this review. Results Hormone therapy was the most common method used for early-stage endometrial carcinoma in patients who wished to preserve fertility. Sixty percent of the patients became pregnant after remission of the carcinoma. The percentage of patients who conceived in the assisted reproductive technology group was higher than that of the natural pregnancy group （80.0% vs. 43.2%, P〈0.01）. A higher rate of preterm labor and multiple pregnancies was observed in the assisted reproductive technology group than that in the natural pregnancy group. The majority of pregnancies （71.4%） in the assisted reproductive technology group were achieved by in vitro fertilization-embryo transfer. The clinical pregnancy rate of transfer cycles in patients with endometrial carcinoma was 34.1%. Conclusions Assisted reproductive technology is a good option in well-selected patients with early-stage endometrial carcinoma who have completed conservative treatment. In vitro fertilization-embryo transfer offers an opportunity to achieve an immediate pregnancy.展开更多
It is well-known that risk for endometrial adenocarcinoma increases in patients with high level ofestrogen that is unopposed by progestin. And activation of extracellular signal-regulated kinase （ERK） and phosphatid...It is well-known that risk for endometrial adenocarcinoma increases in patients with high level ofestrogen that is unopposed by progestin. And activation of extracellular signal-regulated kinase （ERK） and phosphatidylinositol 3 kinase/protein kinase B （PI3K/PKB） pathway are responsible for hormone-dependent cell growth in endometrial carcinoma. PI3K produces phosphatidylinositol- 3-phosphates by phosphory-lating the D3 hydroxyl of phosphoinositides, leading to membrane translocation of PKB,展开更多
BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that me...BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that menstrual-derived stromal stem cells(MenSCs),with high proliferative capacity and self-renewal ability,have a powerful therapeutic effect in patients with severe IUA.However,safety assessment of MenSCs transplantation is essential for its further application.AIM To evaluate the short-,medium-,and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA,with a focus on toxicity and tumorigenicity.METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model,for 3 d,3 mo,and 6 mo separately,to monitor the corresponding acute,sub-chronic,and chronic effects.Healthy rats of the same age served as negative controls.Toxicity effects were evaluated by body weight,organ weight,histopathology,hematology,and biochemistry tests.Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.RESULTS Compared with the same week-old control group,all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight,mainorgan weight,or blood cell composition during the acute,sub-chronic,and chronic observation periods.At the same time,serum biochemical tests showed no adverse effects on metabolism or liver and kidney function.After 4 wk of subcutaneous injection of Men SCs in Balb/c-nu nude mice,no tumor formation or cell metastasis was observed.Moreover,there was no tumor colony formation of Men SCs during soft agar culture in vitro.CONCLUSION There is no acute,sub-chronic,or chronic poisoning,infection,tumorigenesis,or endometriosis in rats with IUA after Men SC transplantation.The above results suggest that intrauterine transplantation of Men SCs is safe for endometrial treatment.展开更多
Objectives To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-β-estradiol, and to elucidate the role of phosphatase and tensin homol...Objectives To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-β-estradiol, and to elucidate the role of phosphatase and tensin homologue (PTEN) and estrogen receptor (ER) subtype on the activation of ERKs.Methods Western blot was used to examine the expression of PTEN and PTEN (G129E) in Ishikawa cells after stable transfection as well as ERK activation in Ishikawa-EGFP, Ishikawa- PTEN and Ishikawa- PTEN (G129E) stimulated with various doses of 17-β-estradiol for different lengths of time. Western blot was also used for examining the expression of ERα and ERβ in NIH3T3 fibroblasts after transient transfection of pCXN2hERα and pCXN2hERβ. Then, ERK activation was examined after stimulation with 17-β-estradiol. Results 17-β-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-β-estradiol also increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-β-estradiol. The activation of ERK2 was inhibited markedly by PTEN, but not by PTEN (G129E). 17-β-estradiol activated ERK cascades in NIH3T3 fibroblasts after transient transfection of pCXN2hERα.Conclusions 17-β-estradiol activate ERK cascades in Ishikawa cells by integrating with ERα. Lipid phosphatase PTEN has an inhibitory role on the activation of ERK stimulated by 17-β-estradiol in Ishikawa cells.展开更多
Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that h...Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that have been recently proposed to act as miRNA sponges that directly regulate expression of target genes or parental genes.Results: We used Illumina Solexa technology to analyze the expression profiles of circRNAs in the endometrium from three goats at gestational day 5(pre-receptive endometrium,PE) and three goats at gestational day 15(receptive endometrium,RE).Overall,21,813 circRNAs were identified,of which 5,925 circRNAs were specific to the RE and 9,078 were specific to the PE,which suggested high stage-specificity.Further analysis found 334 differentially expressed circRNAs in the RE compared with PE(P < 0.05).The analysis of the circRNA-miRNA interaction network further supported the idea that circRNAs act as miRNA sponges to regulate gene expression.Moreover,some circRNAs were regulated by estrogen(E2)/progesterone(P4) in endometrial epithelium cell lines(EECs) and endometrial stromal cell line(ESCs),and each circRNA molecule exhibited unique regulation characteristics with respect to E2 and P4.Conclusions: These data provide an endometrium circRNA expression atlas corresponding to the biology of the goat receptive endometrium during embryo implantation.展开更多
基金supported by grants no.81670123 and no.81670144 from the National Natural Science Foundation of China(NSFC).
文摘Background:Low-grade endometrial stromal sarcoma(LG-ESS)is a rare tumor that lacks a prognostic prediction model.Our study aimed to develop a nomogram to predict overall survival of LG-ESS patients.Methods:A total of 1172 patients confirmed to have LG-ESS between 1988 and 2015 were selected from the Surveillance,Epidemiology and End Results(SEER)database.They were further divided into a training cohort and a validation cohort.The Akaike information criterion was used to select variables for the nomogram.The discrimination and calibration of the nomogram were evaluated using concordance index(C-index),area under time-dependent receiver operating characteristic curve(time-dependent AUC),and calibration plots.The net benefits of the nomogram at different threshold probabilities were quantified and compared with those of the International Federation of Gynecology and Obstetrics(FIGO)criteria-based tumor staging using decision curve analysis(DCA).Net reclassification index(NRI)and integrated discrimination improvement(IDI)were also used to compare the nomogram’s clinical utilitywith that of the FIGO criteria-based tumor staging.The risk stratifications of the nomogram and the FIGO criteria-based tumor staging were compared.Results:Seven variables were selected to establish the nomogram for LG-ESS.The C-index(0.814 for the training cohort and 0.837 for the validation cohort)and the time-dependent AUC(>0.7)indicated satisfactory discriminative ability of the nomogram.The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations in both the training and validation cohorts.The NRI values(training cohort:0.271 for 5-year and 0.433 for 10-year OS prediction;validation cohort:0.310 for 5-year and 0.383 for 10-year OS prediction)and IDI(training cohort:0.146 for 5-year and 0.185 for 10-year OS prediction;validation cohort:0.177 for 5-year and 0.191 for 10-year OS prediction)indicated that the established nomogram performed significantly better than the FIGO criteria-based
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81601236 and No. 81471505）.
文摘Objective： Intrauterine adhesion （IUA） is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-β （TGF-β） signaling pathways to form an intricate network governing the development of fibrosis. Data Sources： Original research articles in English that were published until July 2017 were collected from the PubMed database. Study Selection： Literature search was conducted using the search terms ＂endometrial fibrosis OR fibrosis AND or OR intrauterine adhesion OR Asherman syndrome OR IUA,＂ ＂Hippo AND or OR Hippo/TAZ,＂ ＂TGF-β,＂ and ＂Wnt.＂ Related original research articles were included in the comprehensive analysis. Results： Endometrial fibrosis is recognized as a key pathological event in the development of IUA, which is characterized by epithelial/fibroblast-myofibroblast transition. Myofibroblasts play crucial roles in the pathogenesis of fibrous scarring, and myofibroblast differentiation can be triggered by multiple signaling pathways. H ippo signaling is a critical regulator of the epithelial/fibroblast-myofibroblast transition and α-smooth muscle actin, which exhibits a specific spatiotemporal expression in the endometrium. Conclusions： Hippo signaling plays a critical role in fibrous diseases and participates in cross talks with Wnt and TGF-β signaling. Our findings not only contributed to knowledge on the pathogenesis of endometrial fibrosis, but can also serve as a useful resource for developing specific molecular inhibitors for IUA treatment and prevention.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030505)Key research and development program of Jiangsu province (BE2016612), Jiangsu Biobank of Clinical Resources (BM2015004)+1 种基金the Key Laboratory for Maternal-Fetal Medicine from the Health Department of Jiangsu Province, China (XK201102)Project of Nanjing clinical medicine center and the National Natural Science Foundation of China (81401223)
文摘Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.
文摘Background Endometrial carcinoma is one of the most common gynecological malignancies among women.Early diagnosis and correct preoperative evaluation of myometrial invasion are necessary to improve the prognosis.This study aimed to determine whether features and time-intensity curves （TIC） of transvaginal contrast-enhanced ultrasound （CEUS） differ from those of conventional ultrasound for endometrial carcinoma,and to further explore the clinical role of transvaginal CEUS in the early diagnosis of endometrial carcinoma.Methods Forty women with a normal uterus and seventy-nine patients with endometrial carcinoma were examinedby the transvaginal CEUS with SonoVue （Bracco,Imaging B.V,Switzerland）.The enhancement patterns and TIC of lesions were analyzed.The results of CEUS were compared with those of conventional ultrasound and pathology.Results In the early and late enhanced stages,the intensity of enhancement of the normal endometrium was always lower than that in the myometrium,and the boundary between normal endometrium and myometrium was clear.A total of 65.8% （52/79） of lesions presented with inhomogeneous enhancement,34.2% （27/79） presented with homogeneous enhancement; 60.8% （48/79） presented with hyperechoic enhancement,27.8% （22/79） presented with isoechoic enhancement,and 11.4% （9/79） presented with hypoechoic enhancement.The average arrival time,time to peak,rise time,half-wash out time of lesions were shorter than of normal endometrium （P 〈0.05）.The average peak intensity,relative rise in intensity,half-wash out intensity of lesions were higher than of normal endometrium （P〈0.05）.There were 49 （must be and may be present） cases of endometrial carcinoma by ultrasound （US）; 24 cases were consistent with pathology results,16 cases were underestimated and 9 cases were overestimated.There were 72 （must be and may be present） cases of endometrial carcinoma by CEUS; 53 cases were consistent with pathology results,12 cases were underestimated and 7 cases we
文摘Background： Thin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endomctrial thickness （EMT）. The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium. Methods： Relevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected. Possible factors influencing the effectiveness of treatment were analyzed retrospectively by logistic regression analysis. Eighty-seven infertile women without thin endometrium who had undergone assisted reproduction served as controls. The cases and controls were matched for age, assisted reproduction method, and number of embryos transferred. Reproductive outcomes of study and control groups were compared using Student＇s t-test and the Chi-square test. Results： At the end of estrogen treatment, EMT was ≥8 mm in 93/101 patients （92.1%）. Effectiveness of treatment was significantly associated with maximal pretreatment EMT （P = 0.017） and treatment duration （P = 0.004）. The outcomes of assisted reproduction were similar in patients whose treatment was successful in increasing EMT to ≥8 mm and the control group. The rate of clinical pregnancy in patients was associated with the number of good-quality embryos transferred in both fresh （P = 0.005） and frozen-thawed （P = 0.000） embryo transfer cycles. Conclusions： Thinner EMT before estrogen treatment requires longer treatment duration and predicts poorer treatment outcomes. The effectiveness of treatment depends on the duration of estrogen administration. Assisted reproductive outcomes of patients whose treatment is successful （i.e., achieves an EMT ≥8 mm） are similar to those of controls. The quality of embryos transferred is an important predictor of assisted reproductive outcomes in patients treated successfully with exogenous estrogen.
基金supported by The Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030505)Jiangsu Provincial Key Medical Center (YXZXB2016004)+3 种基金Key Research and Development Program of Jiangsu Province (BE2016612)National Natural Science Foundation of China (81771526)Excellent Youth Natural Science Foundation of Jiangsu Province (BK20170051)Six Talent Peaks Projects in Jiangsu Province (WSW-074)
文摘Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2(b FGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of b FGF100 μg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients(2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved.Histological study showed blood vessel density increased obviously. Three patients(3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the b FGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.
文摘Objective This study aimed to review the available literature on fertility-preserving treatment and pregnancy outcomes in patients with early-stage endometrial carcinoma who desired to preserve their fertility. Data sources The PubMed database （1992-2012） was searched for the words ＂conservative ＂OR＂ fertility sparing ＂OR＂ fertility preserving＂ AND ＂endometrial neoplasms＂ （MESH）. All relevant articles in English and the relevant references were collected. Study selection Data from published articles about fertility-preserving treatment of endometrial cancer, including the response and recurrence rate of conservative treatment, strategies of infertility treatment, pregnancy, and obstetric outcomes, were selected. Data were mainly extracted from 41 studies, which are listed in the reference section of this review. Results Hormone therapy was the most common method used for early-stage endometrial carcinoma in patients who wished to preserve fertility. Sixty percent of the patients became pregnant after remission of the carcinoma. The percentage of patients who conceived in the assisted reproductive technology group was higher than that of the natural pregnancy group （80.0% vs. 43.2%, P〈0.01）. A higher rate of preterm labor and multiple pregnancies was observed in the assisted reproductive technology group than that in the natural pregnancy group. The majority of pregnancies （71.4%） in the assisted reproductive technology group were achieved by in vitro fertilization-embryo transfer. The clinical pregnancy rate of transfer cycles in patients with endometrial carcinoma was 34.1%. Conclusions Assisted reproductive technology is a good option in well-selected patients with early-stage endometrial carcinoma who have completed conservative treatment. In vitro fertilization-embryo transfer offers an opportunity to achieve an immediate pregnancy.
基金This study was partially supported by a grant from the Scientific Research Fund for Capital Medicine Development (No.ZD 199911).
文摘It is well-known that risk for endometrial adenocarcinoma increases in patients with high level ofestrogen that is unopposed by progestin. And activation of extracellular signal-regulated kinase （ERK） and phosphatidylinositol 3 kinase/protein kinase B （PI3K/PKB） pathway are responsible for hormone-dependent cell growth in endometrial carcinoma. PI3K produces phosphatidylinositol- 3-phosphates by phosphory-lating the D3 hydroxyl of phosphoinositides, leading to membrane translocation of PKB,
基金Supported by the National Key Research and Development Program,No.2018YFC1002105the Key Research and Development Program of Liaoning Province,No.2018020222the Major Special Construction Plan for Discipline Construction Project of China Medical University,No.3110118033。
文摘BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that menstrual-derived stromal stem cells(MenSCs),with high proliferative capacity and self-renewal ability,have a powerful therapeutic effect in patients with severe IUA.However,safety assessment of MenSCs transplantation is essential for its further application.AIM To evaluate the short-,medium-,and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA,with a focus on toxicity and tumorigenicity.METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model,for 3 d,3 mo,and 6 mo separately,to monitor the corresponding acute,sub-chronic,and chronic effects.Healthy rats of the same age served as negative controls.Toxicity effects were evaluated by body weight,organ weight,histopathology,hematology,and biochemistry tests.Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.RESULTS Compared with the same week-old control group,all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight,mainorgan weight,or blood cell composition during the acute,sub-chronic,and chronic observation periods.At the same time,serum biochemical tests showed no adverse effects on metabolism or liver and kidney function.After 4 wk of subcutaneous injection of Men SCs in Balb/c-nu nude mice,no tumor formation or cell metastasis was observed.Moreover,there was no tumor colony formation of Men SCs during soft agar culture in vitro.CONCLUSION There is no acute,sub-chronic,or chronic poisoning,infection,tumorigenesis,or endometriosis in rats with IUA after Men SC transplantation.The above results suggest that intrauterine transplantation of Men SCs is safe for endometrial treatment.
基金ThisstudywassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 0 0 0 0 178)
文摘Objectives To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-β-estradiol, and to elucidate the role of phosphatase and tensin homologue (PTEN) and estrogen receptor (ER) subtype on the activation of ERKs.Methods Western blot was used to examine the expression of PTEN and PTEN (G129E) in Ishikawa cells after stable transfection as well as ERK activation in Ishikawa-EGFP, Ishikawa- PTEN and Ishikawa- PTEN (G129E) stimulated with various doses of 17-β-estradiol for different lengths of time. Western blot was also used for examining the expression of ERα and ERβ in NIH3T3 fibroblasts after transient transfection of pCXN2hERα and pCXN2hERβ. Then, ERK activation was examined after stimulation with 17-β-estradiol. Results 17-β-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-β-estradiol also increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-β-estradiol. The activation of ERK2 was inhibited markedly by PTEN, but not by PTEN (G129E). 17-β-estradiol activated ERK cascades in NIH3T3 fibroblasts after transient transfection of pCXN2hERα.Conclusions 17-β-estradiol activate ERK cascades in Ishikawa cells by integrating with ERα. Lipid phosphatase PTEN has an inhibitory role on the activation of ERK stimulated by 17-β-estradiol in Ishikawa cells.
基金supported by PhD research startup foundation of Northwest A&F University(00400/Z109021811)National Key Research and Development Program of China(2016YFD0500508)Shaanxi Science and Technology Innovation Project Plan(2015KTCQ03–08)
文摘Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that have been recently proposed to act as miRNA sponges that directly regulate expression of target genes or parental genes.Results: We used Illumina Solexa technology to analyze the expression profiles of circRNAs in the endometrium from three goats at gestational day 5(pre-receptive endometrium,PE) and three goats at gestational day 15(receptive endometrium,RE).Overall,21,813 circRNAs were identified,of which 5,925 circRNAs were specific to the RE and 9,078 were specific to the PE,which suggested high stage-specificity.Further analysis found 334 differentially expressed circRNAs in the RE compared with PE(P < 0.05).The analysis of the circRNA-miRNA interaction network further supported the idea that circRNAs act as miRNA sponges to regulate gene expression.Moreover,some circRNAs were regulated by estrogen(E2)/progesterone(P4) in endometrial epithelium cell lines(EECs) and endometrial stromal cell line(ESCs),and each circRNA molecule exhibited unique regulation characteristics with respect to E2 and P4.Conclusions: These data provide an endometrium circRNA expression atlas corresponding to the biology of the goat receptive endometrium during embryo implantation.
