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 Cesarean scar pregnancy （CSP） is a very rare but life-threatening entity and there is no optimal management strategy.Here we report a successfully conservative treatment of CSP.Methods We retrospectively ...Background Cesarean scar pregnancy （CSP） is a very rare but life-threatening entity and there is no optimal management strategy.Here we report a successfully conservative treatment of CSP.Methods We retrospectively analyzed the clinical data of 54 women with CSP,who underwent uterine artery embolization between January 2007 and September 2012 at the Peking University People＇s Hospital.We evaluated the clinical outcomes,the technique and the complications of uterine artery embolization.Results Of the 54 patients,2 patients with hemorrhage after induced abortion received bilateral uterine artery embolization treatment alone,and 52 patients underwent suction curettage after bilateral uterine artery embolization.All 54 women were successfully cured,without any severe complications,and uterine function was restored.During the follow-up,one patient had accidental normal interuterine pregnancy and received induced abortion during the first trimester.Conclution Uterine artery embolization combined with suction curettage is an effective and safe conservative treatment for cesarean scar pregnancy.展开更多
Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe ...Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.展开更多
Objective To evaluate the possibility of vaginal hysterectomy for patients with moderately enlarged uterus of benign lesions. Methods One hundred and seventeen women with benign uterine diseases underwent vaginal hyst...Objective To evaluate the possibility of vaginal hysterectomy for patients with moderately enlarged uterus of benign lesions. Methods One hundred and seventeen women with benign uterine diseases underwent vaginal hysterectomy. These patients were divided into two groups according to uterine weight. Group Ⅰ contained 60 patients with uterine enlargement to a weight of 200 to 750 g, and group Ⅱ contained 57 patients with uterine weight of less than 200 g. Uterine morcellation was performed in some cases. The peri-operative data in both groups were analyzed. Results In group Ⅰ, 59 cases underwent transvaginal hysterectomy successfully, except 1 case con-verted to abdominal operation and the uterine morcellation was performed in 21 women. In group Ⅱ, all patients successfully underwent transvaginal hysterectomy without any assistance of special technique. The mean uterine weight of group Ⅰ was significantly heavier than that of group Ⅱ(280.18 ± 100.40 g vs 146.48 ± 35.19 g). The mean operating time was significantly longer for group Ⅰ than that for group Ⅱ(83.93 ± 26.26 minutes vs 35.22 ± 20.55 minutes). There were no significant differences in blood loss and complications between groupⅠ and group Ⅱ. There was no injury of urinary bladder or rectum, and no vaginal vault infection. Conclusions Vaginal hysterectomy of moderately enlarged uterus can be safely and effectively performed by experienced operators. In some cases, in order to reduce the uterine volume, uterine mor-cellation should be used to shorten operative time, reduce the bleeding, and lower the postoperative complications.展开更多
The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea(PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on ut...The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea(PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction(GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F_2 alpha(PGF_(2α)) and Ca^(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF_(2α) and Ca^(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.展开更多
Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregn...Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites.In species with invasive hemochorial placentation,these uterine natural killer(uNK)cells,via secretion of cytokines,chemokines,mucins,enzymes and angiogenic growth factors,contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis.In humans,uNK cells have the phenotype CD56^(bright) CD16^(dim) and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy.Gene expression studies indicate that CD56^(bright) CD16^(dim) uterine and circulating cells are functionally distinct.In humans but not mice or other species with post-implantation decidualization,uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility.Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function,achieved via interferon(IFN)-c secretion.During spiral arterial modification,branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict.The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance,high-volume channels.Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women.Here we briefly review key information concerning uNK cell functions from studies in rodents,summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized,pregnant mouse model for in vivo investigations of human 展开更多
Objective:To study the effect of estrogen on anovulatory dysfunctional uterine bleeding(ADUB).Methods:Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolylic activity of gelalinase was d...Objective:To study the effect of estrogen on anovulatory dysfunctional uterine bleeding(ADUB).Methods:Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolylic activity of gelalinase was determined by gelatin zymography analysis.Cellular mRNA and protein synthesis was blocked respectively to determine whether the increased expression of MMP-2/9 was induced by estrogen.The expression of VEGF was blocked by siRNA.After treatment with various factors.MMP-9,VEGF,total Erk and phosphorylated Erk expression in primary uterine epithelial cells was detected by Western blotting analysis.Cell MMP-2/9mRNA levels was measured by real-time RT-PCR.Results:The activity and expression of MMP2/9 was inereased in the endometrium of patients with ADUB.Estrogen could up-regulate the expression of VEGF and activate Erk 1/2-Elk1 signal path.After interference by siRNA,ERK1/2 pathway was blocked in cells,and the expression of MMP-2/9 was down-regulated.ERK1/2 specific blocker U0126 blocked ERK phosphorylation,and it could down-regulate the expression of MMP-2/9.Conclusions:The results showed that the estrogen can increase the expression of VEGF,and thus activate ERK1/2 pathway to induce MMP-2/9 expression.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
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 Cesarean scar pregnancy （CSP） is a very rare but life-threatening entity and there is no optimal management strategy.Here we report a successfully conservative treatment of CSP.Methods We retrospectively analyzed the clinical data of 54 women with CSP,who underwent uterine artery embolization between January 2007 and September 2012 at the Peking University People＇s Hospital.We evaluated the clinical outcomes,the technique and the complications of uterine artery embolization.Results Of the 54 patients,2 patients with hemorrhage after induced abortion received bilateral uterine artery embolization treatment alone,and 52 patients underwent suction curettage after bilateral uterine artery embolization.All 54 women were successfully cured,without any severe complications,and uterine function was restored.During the follow-up,one patient had accidental normal interuterine pregnancy and received induced abortion during the first trimester.Conclution Uterine artery embolization combined with suction curettage is an effective and safe conservative treatment for cesarean scar pregnancy.
文摘Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.
文摘Objective To evaluate the possibility of vaginal hysterectomy for patients with moderately enlarged uterus of benign lesions. Methods One hundred and seventeen women with benign uterine diseases underwent vaginal hysterectomy. These patients were divided into two groups according to uterine weight. Group Ⅰ contained 60 patients with uterine enlargement to a weight of 200 to 750 g, and group Ⅱ contained 57 patients with uterine weight of less than 200 g. Uterine morcellation was performed in some cases. The peri-operative data in both groups were analyzed. Results In group Ⅰ, 59 cases underwent transvaginal hysterectomy successfully, except 1 case con-verted to abdominal operation and the uterine morcellation was performed in 21 women. In group Ⅱ, all patients successfully underwent transvaginal hysterectomy without any assistance of special technique. The mean uterine weight of group Ⅰ was significantly heavier than that of group Ⅱ(280.18 ± 100.40 g vs 146.48 ± 35.19 g). The mean operating time was significantly longer for group Ⅰ than that for group Ⅱ(83.93 ± 26.26 minutes vs 35.22 ± 20.55 minutes). There were no significant differences in blood loss and complications between groupⅠ and group Ⅱ. There was no injury of urinary bladder or rectum, and no vaginal vault infection. Conclusions Vaginal hysterectomy of moderately enlarged uterus can be safely and effectively performed by experienced operators. In some cases, in order to reduce the uterine volume, uterine mor-cellation should be used to shorten operative time, reduce the bleeding, and lower the postoperative complications.
基金supported by a grant from Ministry of Education,the New Teachers’Fund for Ph.D Stations(Program No.20110096120011)2011’Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education
文摘The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea(PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction(GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F_2 alpha(PGF_(2α)) and Ca^(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF_(2α) and Ca^(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.
基金These studies were supported by awards from the Natural Sciences and Engineering Research Council,Canada,the Canadian Institutes of Health Research and the Canada Research Chairs Program to BAC and a Province of Ontario/Queen’s Postdoctoral Fellowship award to JHZ.
文摘Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites.In species with invasive hemochorial placentation,these uterine natural killer(uNK)cells,via secretion of cytokines,chemokines,mucins,enzymes and angiogenic growth factors,contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis.In humans,uNK cells have the phenotype CD56^(bright) CD16^(dim) and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy.Gene expression studies indicate that CD56^(bright) CD16^(dim) uterine and circulating cells are functionally distinct.In humans but not mice or other species with post-implantation decidualization,uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility.Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function,achieved via interferon(IFN)-c secretion.During spiral arterial modification,branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict.The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance,high-volume channels.Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women.Here we briefly review key information concerning uNK cell functions from studies in rodents,summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized,pregnant mouse model for in vivo investigations of human
基金supported by Natural Science Foundation of Hainan Province(No.812148)
文摘Objective:To study the effect of estrogen on anovulatory dysfunctional uterine bleeding(ADUB).Methods:Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolylic activity of gelalinase was determined by gelatin zymography analysis.Cellular mRNA and protein synthesis was blocked respectively to determine whether the increased expression of MMP-2/9 was induced by estrogen.The expression of VEGF was blocked by siRNA.After treatment with various factors.MMP-9,VEGF,total Erk and phosphorylated Erk expression in primary uterine epithelial cells was detected by Western blotting analysis.Cell MMP-2/9mRNA levels was measured by real-time RT-PCR.Results:The activity and expression of MMP2/9 was inereased in the endometrium of patients with ADUB.Estrogen could up-regulate the expression of VEGF and activate Erk 1/2-Elk1 signal path.After interference by siRNA,ERK1/2 pathway was blocked in cells,and the expression of MMP-2/9 was down-regulated.ERK1/2 specific blocker U0126 blocked ERK phosphorylation,and it could down-regulate the expression of MMP-2/9.Conclusions:The results showed that the estrogen can increase the expression of VEGF,and thus activate ERK1/2 pathway to induce MMP-2/9 expression.
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.
