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Introducción: El cáncer de endometrio ocupa el sexto lugar en incidencia del cáncer en mujeres. La caracterización molecular de este cáncer permite optimizar la estratificación de riesgo para mejorar el tratamiento de las pacientes. Objetivo: Determinar el perfil molecular TCGA de pacientes con cáncer de endometrio en Bogotá, D.C., Colombia. Método: Estudio descriptivo en una cohorte de pacientes con cáncer de endometrio. Las mutaciones en los exones 9 a 14 del gen POLE fueron identificadas mediante amplificación por reacción en cadena de la polimerasa, seguida de secuenciación Sanger y análisis bioinformático. La expresión de las proteínas MMR y p53 se identificó mediante inmunohistoquímica. Resultados: Se incluyeron 40 pacientes con una mediana de edad de 66 años. El 15% presentaron mutaciones en el dominio exonucleasa de POLE. El 32% de las pacientes que no presentaron mutaciones manifestaron deficiencia en el sistema MMR. El 43,47% de las pacientes sin mutaciones en POLE ni alteración del sistema MMR presentaron alteración de la proteína p53. Conclusiones: La población de cáncer de endometrio analizada presenta un perfil molecular TCGA similar a lo reportado para otras poblaciones.
Introduction: Endometrial cancer ranks sixth in cancer incidence among women. Its molecular characterization allows for a more precise risk stratification with the aim of improving patient treatment. Objective: To determine the TCGA molecular profile of patients with endometrial cancer in Bogota, Colombia. Method: A descriptive study of a cohort of patients with endometrial cancer. The expression of MMR proteins and p53 was identified through immunohistochemistry. Mutations in exons 9 to 14 of the POLE gene were identified through polymerase chain reaction amplification, followed by Sanger sequencing and bioinformatic analysis. Results: Forty patients were included in the study, with a median age of 66 years, 15% of them exhibited mutations in the exonuclease domain of POLE, while 32% of patients without mutations showed deficiency in the MMR system. Forty three percent of patients without mutations in POLE or MMR alterations showed aberrant p53 protein expression. Conclusions: The analyzed population of endometrial cancer presents a TCGA molecular profile similar to that reported for other populations.
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Humans , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/therapy , Prognosis , Tumor Suppressor Protein p53/genetics , ColombiaABSTRACT
AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.
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Objective To investigate the biological function and main molecular mechanism of long noncoding RNA RMRP(lncRNA RMRP)in endometrial carcinoma.Methods The specimens of carcinoma tissues and adjacent tissues of 30 patients with endometrial carcinoma who received surgical treatment in our hospital were collected.RT-qPCR was used to detect the expression of lncRNA RMRP in endometrial carcinoma tissues and adjacent tissues,and HESC cells and HEC-1-A cells.The endometrial carcinoma cell line HEC-1-A was cultured in vitro,and the Vector,pcDNA-RMRP,NC-siRNA,RMRP-siRNA,NC mimic,miR-580-3p mimic,pcDNA-RMRP+NC mimic,pcDNA-RMRP+ miR-580-3p mimic,RMRP-siRNA+Vector,RMRP-siRNA+pcDNA-JAK2,NC inhibitor,and miR-580-3p inhibitor were transfected into HEC-1-A cells as the Vector group,the pcDNA-RMRP group,the NC-siRNA group,the RMRP-siRNA group,the NC mimic group,the miR-580-3p mimic group,the pcDNA-RMRP+NC mimic group,the pcDNA-RMRP+miR-580-3p mimic group,the RMRP siRNA+Vector group,the RMRP-siRNA+pcDNA-JAK2 group,the NC inhibitor group,and the miR-580-3p inhibitor group respectively.RT-qPCR was used to detect the expression of lncRNA RMRP and miR-580-3p in cells.CCK-8 was used to detect cell proliferation rate.The apoptosis rate was detected by flow cytometry analysis.Bioinformatics software and dual luciferase reporter gene experiment were used to predict and verify the targeted relationships between miR-580-3p and lncRNA RMRP,as well as miR-580-3p and JAK2.Western blot was used to detect the protein expression of JAK/STAT signaling pathway.Results Compared with adjacent tissues,lncRNA RMRP was highly expressed in endometrial carcinoma tissues(P<0.05).Compared with HESC cells,the expression of lncRNA RMRP in HEC-1-A cells was significantly increased(P<0.05).pcDNA-RMRP significantly promoted cell proliferation and inhibited cell apoptosis,while RMRP-siRNA significantly inhibited cell proliferation and promoted cell apoptosis,with statistically significant diferences(P<0.05).miR-580-3p was the downstream target miRNA of lncRNA RMRP,and lncRNA RMRP could negatively regulate the expression of miR-580-3p.JAK2 was the downstream target gene of miR-580-3p,and miR-580-3p could negatively regulate the expression of JAK2 protein.pcDNA-RMRP significantly increased the protein levels of JAK2,p-JAK2 and p-STAT3 in the cells,while co-transfection of pcDNA-RMRP and miR-580-3p mimic significantly decreased the protein levels of JAK2,p-JAK2 and p-STAT3,with statistically significant diferences(P<0.05).RMRP-siRNA could signifi-cantly reduce the protein levels of JAK2,p-JAK2 and p-STAT3 in cells.After co-transfection of RMRP-siRNA and pcDNA-JAK2,the protein levels of JAK2,p-JAK2 and p-STAT3 were significantly increased,with statistically significant diferences(P<0.05).In addition,co-transfection of RMRP-siRNA and pcDNA-JAK2 increased cell proliferation and decreased cell apoptosis,with statistically significant diferences(P<0.05).Conclusion Knockdown of lncRNA RMRP could inhibit endometrial carcinoma cell proliferation and promote cell apoptosis by regulating JAK2/STAT3 signaling pathway,which might be a potential therapeutic target for endometrial carcinoma.
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Objective To observe the value of combined synthetic MRI and multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)for differentiating benign and malignant endometrial lesions.Methods Data of 112 patients with benign or malignant endometrial lesion confirmed by pathology were retrospectively analyzed.According to pathologic diagnosis,the patients were divided into malignant group(n=72)and benign group(n=40).Synthetic MRI and MUSE-DWI quantitative parameters,including T1,T2,proton density(PD)and apparent diffusion coefficient(ADC)of all lesions were acquired.The clinical data as well as ADC,T1,T2 and PD values of lesions were compared between groups,and those being significantly different between groups were included in univariate and multivariate logistic regression.Then the univariate and combined models were established for differentiating benign and malignant endometrial lesions.The receiver operating characteristic curves were drawn,and areas under the curves(AUC)were calculated to evaluated the diagnostic efficacy of the models,which were compared with DeLong test.Results Patients'age in malignant group were higher than that in benign group(P＜0.05).The length of the maximum diameter was larger,ADC,T2 and PD values were lower in malignant lesions than those in benign ones(all P＜0.05),while no significant difference of T1 value was found between groups(P=0.074).The AUC of ADC univariate model was 0.966,and there was no significant difference in AUC(0.970)between the combined ADC+T2+PD model(adjusted P＞0.05),but both higher than AUC of T2 univariate model(0.618),PD univariate model(0.664)and the combined T2+PD model(0.668)(all adjusted P＜0.05).Conclusion ADC univariate model and combined model with other parameters of combined synthetic MRI and MUSE-DWI could be used to effectively differentiate benign and malignant endometrial lesions.
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In recent years,significant progress has been made in the study of endometrial epitheli-al organoids in the field of reproduction.Traditional two-dimensional cell culture models and animal ex-periments fail to accurately replicate the three-di-mensional structure and physiological functions of the endometrium,limiting the in-depth exploration of its normal physiological mechanisms and related disease mechanisms.Emerging organoid technolo-gies have provided new avenues for research.These organoids,formed by self-organization of stem cells or progenitor cells in a three-dimensional culture system,faithfully recapitulate the character-istics of endometrial glands in situ.Not only can these organoid models mimic the changes in the endometrium at different stages of the menstrual cycle,but they can also simulate the interaction be-tween the fertilized embryo and the endometrium.Moreover,organoid systems have become essential tools for fundamental research in the field of repro-duction and for disease research,including studies related to reproductive biology,drug screening and development,disease mechanism exploration,drug action mechanisms,drug combination therapies,and targeted therapies.These studies have provid-ed novel insights and methods for a deeper under-standing of the biological properties of the endome-trium,its disease mechanisms,and the develop-ment of therapeutic strategies for related disorders.
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Objective:To investigate the dosimetry effect of rotational errors of multi-channel cylinder vaginal applicator of intravaginal irradiation after surgery of endometrial cancer.Methods:A total of 18 patients who underwent surgery of endometrial cancer at Peking Union Medical College Hospital from June to December 2022 were selected.The plans of patients who adopted the treatment of multi-channel cylinder applicator of vagina were retrospectively analyzed,which maintained the same retained mode with clinical plan.The applicator was rotated clockwise by 22.5? and 45.0?,respectively,simulating the rotational errors that occurred in placing the applicator among clinical inter-fractions.And then,the changes of dosimetry of target area and organs at risk(OAR)under two kinds of rotation amplitudes were further analyzed.Results:When the applicator was rotated as 22.5?,the minimum doses to 90%volumes of CTV by 2.03%than that of clinical plan,which was significantly different(t=5.86,P<0.05),and the maximal doses to 2cc of OARs of bladder and rectum respectively increased 2.35%and 2.71%,and the differences of them were statistically significant(t=-3.49,-2.40,P<0.05),respectively.When the applicator was rotated as 45?,the D90 of the target area decreased by 5.75%than that of clinical plan,which was statistically significant(t=14.07,P<0.05).The D2cc values of the bladder and rectum increased respectively by 6.50%and 9.49%than that of clinical plan,which were statistically significant(t=-7.72,-6.9,P<0.05).The differences of the exposed doses of sigmoid colon and small intestine after the applicator was rotated by 22.5? and 45.0? between the plan and original plan were respectively less,which were not statistical significance.Conclusion:The multi-channel cylinder applicator can provide individualized dose distribution in intravaginal irradiation.However,attention should be paid to the placement of the applicator when patients undergo inter-fractional treatment,in order to avoid deviations in the angular alignment from the original plan.This can impact the dosages of the target area and OARs.
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Objective:To explore the predictive value of deep learning based on three dimensional deep residual network(3D Res-Unet)model for the dose accuracy of postoperative volume modulated arc therapy(VMAT)plan of endometrial carcinoma.Methods:A retrospective collection of 154 VMAT radiotherapy plans for endometrial carcinoma from The First People's Hospital of Neijiang was conducted.The data set was divided into one training set with 108 cases,one validation set with 15 cases and one test set with 31 cases as the ratio of 7:1:2 through randomly sampling.The approved dose of clinical application was used as"gold standard"to compare the difference between predictive radiotherapy dose of 3D Res-UNet and clinically radiotherapy dose.Results:There were statistical differences in the conformity index(CI)of target area and average dose(Dmean)between deep learning and clinical gold standard(t=-3.115,-0.124,P<0.05),and the difference of bladder V40 of organ at risk(OAR)between them was significant(t=0.510,P<0.05),and the difference of rectum V50 between them was significant(t=-2.121,P<0.05).The predictive dose of the left femoral head V30 was significantly lower than that of clinical dose(t=0.415,P<0.05).The predictive dose of the right femoral head V30 was significantly lower than that of clinical dose(t=-3.102,P<0.05).The predictive dose of pelvic Dmean was significantly higher than that of clinical dose(t=1.224,P<0.05).The predictive dose of small intestine V40 was significantly higher than that of clinical dose(t=0.461,P<0.05).There were no statistically significant difference in other indicators(P>0.05).The difference plot of dose showed that there was few difference between predictive results and clinical results,and the dose volume histogram of prediction basically coincided with that of clinical application.Conclusion:The 3DRes-UNet model can effectively predict the three-dimensionally spatial dose of VMAT plan after surgery for endometrial carcinoma,which can guide clinical radiotherapy work.
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Inflammation is a key player in various pathophysiological processes and diseases, especially throughout the gestational cycle, and inflammation plays an important role in ovulation, embryo implantation, placental formation, and all stages of pregnancy maintenance. However, excessive inflammatory activity can impair endometrial receptivity, which can lead to clinical problems such as infertility, recurrent implantation failure, and recurrent miscarriage, which in turn can negatively impact women's reproductive health and pregnancy outcomes. Studies have shown that about two-thirds of embryo implantation failures are associated with inadequate endometrial receptivity. Therefore, the precise regulation of inflammatory states is of great significance for increasing pregnancy rates and improving pregnancy outcomes.
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Objective To observe the effect of Shoutai Pills on endometrial decidualization of mice with recurrent spontaneous abortion(RSA);To explore its possible mechanism in the treatment of RSA based on histone modification.Methods Totally 40 female CBA/J mice were divided into normal group,model group,Shoutai Pills low-dosage group(7.5 g/kg),Shoutai Pills high-dosage group(15 g/kg)and dydrogesterone group(3 mg/kg).The normal group were co housed with BALB/C male mice,while the other groups were co housed with DBA/2 male mice to establish an RSA mouse model.After modeling,the administration groups were given corresponding medication solution by gavage,while the normal group and model group were given equal volume of pure water by gavage for 10 consecutive days.The embryo condition was observed and the embryo loss rate was calculated,ELISA was used to detect serum prolactin(PRL)content,HE staining was used to observe the morphological changes of decidual tissue,RT-PCR was used to detect PRL mRNA expression in decidual tissue,Western blot was used to detect the protein expressions of H4ac,H3K27ac,H3K27me3.Results Compared with the normal group,the model group mice showed a significant increase in embryo loss rate,a significant decrease in serum PRL content,disordered arrangement of decidual cells,and extensive bleeding and necrosis;the expression of PRL mRNA and protein in decidual tissue significantly decreased,the protein expressions of H4ac and H3K27ac significantly decreased,while the expression of H3K27me3 protein significantly increased,with statistical significance(P<0.05).Compared with the model group,the embryo loss rate of Shoutai Pills low-and high-dosage groups and the dexamethasone group significantly decreased,the serum PRL content significantly increased,tightly arranged decidual cells,reduced necrosis,and intact glands;the expression of PRL mRNA and protein in decidual tissue of mice in Shoutai Pills high-dosage group and the dexamethasone group significantly increased,the protein expressions of H4ac and H3K27ac significantly increased,the expression of H3K27me3 protein significantly decreased,with statistical significance(P<0.05).Conclusion Shoutai Pills can promote endometrial decidualization in RSA mice,which is related to the changes of histone modification in endometrial stromal cells.
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This paper reported the clinical characteristics, diagnosis, and treatment of a case of recurrent endometrial stromal sarcoma with term pregnancy. The patient had undergone laparoscopic surgery to remove hysteromyoma before conception in 2017, which was pathologically diagnosed as low-grade endometrial stromal sarcoma after surgery. Due to her strong reproductive willingness, the patient attempted to conceive in light of her stable condition and no evidence of recurrence and was closely followed up with an informed choice. She conceived successfully in 2020 and underwent regular pregnancy examinations. Ultrasound examination at 37 +4 weeks of gestation revealed a slightly hypoechoic mass of about 6.3 cm×4.5 cm size in the pelvic cavity. After admission, a pelvic MRI indicated multiple solid nodules in the right adnexa uteri and beside the iliac vessels in the left pelvic wall and anterior pelvic wall with the larger one being about 58 mm×28 mm. Diffusion-weighted imaging showed multiple pelvic nodules and masses with significant diffusion restriction. The patient was diagnosed as having multiple solid nodules and masses in the pelvic cavity, and the recurrence of sarcoma was highly suspected. Brain CT and lung CT showed no obvious metastatic lesions. A consultation involving the Department of Gynecological Tumor Chemoradiotherapy was held and the sarcoma recurrence during pregnancy was prenatally diagnosed. After ruling out the contraindications for surgery, a cesarean section was performed in the lower segment of uterus under general anesthesia and a live female baby was delivered at 38 ＋3 weeks. The excised mass was confirmed as recurrent uterine stromal sarcoma by rapid freezing pathology during cesarean section. A combination surgery was performed subsequently, including total extra-fascial hysterectomy, bilateral oophorectomy, bilateral salpingectomy, appendectomy, greater omentum resection, pelvic lesion resection (right side), and pelvic adhesiolysis. Recurrent low-grade uterine stromal sarcoma was reconfirmed by postoperative pathology. The patient was discharged after recovery. After two years of follow-up, no distant metastasis recurrences were found.
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Brain metastasis is an uncommon complication that occurs in the advanced stage of gynecologic malignancies. Brain metastasis tends to be one of the major factors contributing to the poor prognosis of patients. There have been more reports about brain metastasis in cervical, ovarian and endometrial cancers in recent years due to the growth of large databases and improved diagnostic methods. Great attention has been paid to the selection of appropriate therapeutic options to improve the survival of gynecologic malignancies patients with brain metastasis. This article reviews the research progress of brain metastasis in cervical, ovarian and endometrial cancers, aiming to provide better options for treatment of patients with common advanced gynecologic malignancies.
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This paper summarized professor LIU Ruifen's clinical experience in treating endometrial hyperplasia. It is believed that the core pathogenesis of endometrial hyperplasia is internal obstruction of uterus and intrauterine collaterals by latent stasis. Based on the clinical manifestations， the menstrual cycle is divided into three stages， that is menstrual period， menstrual leakage period， and clear menstrual period， and the method of “three-staged stasis dispelling” is proposed. During the menstrual period， it is appropriate to move qi and invigorate blood， dissolve stasis and disperse concretions， with self-made Gongqing Formula （宫清方）. For menstrual leakage period， it is suggested to boost qi and clear heat， dispel stasis and stanch bleeding， with self-made Tongyong Zhixue Formula （通用止血方）. In terms of clear menstrual period， the method of dissolving phlegm and dissipating masses， moving qi and dispelling stasis is advised， and self-made Zhitong Tiaoxue Formula （止痛调血方） can be used. Simultaneously， attention should be paid to the combination of syndrome differentiation and disease differentiation， as well as collaborative diagnosis and treatment with traditional Chinese and Western medicine.
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【Objective】 To explore the effectiveness of an image recognition system based on artificial intelligence (AI) in diagnosing benign and malignant endometrial cell clumps. 【Methods】 We selected endometrial cytological specimens from The First Affiliated Hospital of Xi’an Jiaotong University and Xi’an Daxing Hospital from August 2021 to February 2023; histopathology was used as the gold standard. We compared and analyzed the sensitivity, specificity, positive predictive value, negative predictive value, accuracy and diagnostic time of AI image recognition system (AI diagnosis) and professional pathologists’ manual diagnosis (manual diagnosis) of benign and malignant endometrial cell clumps. 【Results】 Among the 126 patients included in the analysis, the overall coincidence rate of AI diagnosis and histological diagnosis was 92.1% (116/126), which was highly consistent with histopathological results (Kappa=0.841). The overall coincidence rate of manual diagnosis and histological diagnosis was 94.4% (119/126), which was highly consistent with histopathological results (Kappa=0.889). There was no statistically significant difference between AI diagnosis and manual diagnosis methods (χ2=0.568, P=0.451). The sensitivity, specificity, positive predictive value, and negative predictive value of AI diagnosis were 91.8%, 92.3%, 91.8%, and 92.3%, respectively. There were 126 cytology sections, each of which required 6.67 minutes for manual diagnosis and 5.00 minutes for AI diagnosis. 【Conclusion】 The AI image recognition system has high diagnostic accuracy, sensitivity and specificity, which is equivalent to the manual diagnosis level of professional pathologists. Therefore, this system has application value in the diagnosis of benign and malignant endometrial cell clumps.
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Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.
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Objective To analyze the effects of down-regulation+hormone replacement therapy(HRT)endometrial preparation regimen on the pregnancy outcomes of advanced age women(≥35 years old)undergoing frozen-thawed embryo transfer.Methods The clinical data of 329 patients with frozen-thawed em-bryo transfer in this hospital from June 2020 to June 2022 were analyzed retrospectively.Among them,149 pa-tients receiving gonadotropin-releasing hormone analogue(GnRHa)down-regulation+HRT endometrial preparation were included in the group A,and the other 180 patients with HRT endometrial preparation were included in the group B.The basic situation,endometrial transformation day situation and clinical outcome were compared between the two groups.The group A and group B were further divided into the two sub-groups according to age:group A1(35-＜40 years old,n=101),group A2(≥40 years old,n=48),group B1(35-＜40 years old,n=99)and group B2(≥40 years old,n=81).The effects of two endometrial prepara-tion regimens were compared among the different age groups.Results There were no significant differences in the age,infertility years,BMI,anti-Mullerian hormone level,as well as basal hormones levels such as estra-diol,progesterone,follicle-stimulating hormone,luteinizing hormone(LH),prolactin and testosterone between the two groups(P＞0.05).The levels of estradiol and LH on the endometrial transformation day in the group A were significantly lower than those in the group B(P＜0.05),the endometrial thickness,proportion of the patients with endometrial thickness ≥8 mm and proportion of the patients with type Ⅲ blood intima in the group A were significantly higher than those in the group B(P＜0.05).There was no significant difference in the number of transplanted embryos and the number of transplanted excellent embryos between the two groups(P＞0.05).The clinical pregnancy rate and embryo implantation rate in the group A were significantly higher than those in the group B(46.31％vs.35.56％;33.33％vs.25.18％,P＜0.05),and there was no significant difference in the early miscarriage rate between the two groups(P＞0.05).The further subgroup analysis showed that the clinical pregnancy rate and embryoimplantation rate in the group A2 were significant-ly higher than those in the group B2(35.42％vs.18.52％;21.43％vs.12.40％,P＜0.05),while there was no significant difference between the group A1 and group B1(P＞0.05).Conclusion The advanced age pa-tients undergoing frozen-thawed embryo transfer could select GnRHa down-regulation+HRT regimen to a-chieve better pregnancy outcomes,especially for those age ≥40 years old.
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Objective To investigate the relationship between the expression of miR-141-3p,miR-149-3p and proliferative genes,clinicopathological features and prognosis in endometrial carcinoma tissues.Methods From February 2017 to February 2019,98 patients with endometrial cancer were selected as the study objects.Real-time fluorescence quantitative PCR was used to detect the relative mRNA expression levels of miR-141-3p,miR-149-3p and proliferating genes[proliferating cell nuclear antigen(PCNA),cyclin D1,cyclin dependent kinase 4(CDK4)]in cancer tissues of patients with endometrial cancer.The correlation between the expres-sions of miR-141-3p,miR-149-3p and PCNA,cyclin D1 and CDK4 mRNA in cancer tissues of patients with en-dometrial cancer was analyzed by Pearson correlation analysis.The expression of miR-141-3p and miR-149-3p in cancer tissues of endometrial carcinoma patients with different clinicopathological characteristics was com-pared.Kaplan-Meier curve was used to analyze the influence of miR-141-3p and miR-149-3p expression on prognosis of patients with endometrial carcinoma.Univariate and multivariate Cox regression analysis of prog-nostic factors in patients with endometrial cancer.Results The relative expression levels of miR-141-3p,miR-149-3p,PCNA mRNA,cyclinD1 mRNA and CDK4 mRNA in cancer tissues of patients with endometrial carci-noma were higher than those in adjacent tissues,with statistical significance(P＜0.05).The expressions of miR-141-3p and miR-149-3p were positively correlated with the expressions of PCNA mRNA,cyclinD1 mR-NA and CDK4 mRNA in cancer tissues of patients with endometrial carcinoma(all P＜0.05).The relative ex-pression levels of miR-141-3p and miR-149-3p in cancer tissues of endometrial cancer patients with stage Ⅲand lymph node metastasis according to International Federation of Gynecology and Obstetrics(FIGO)were higher than those of endometrial cancer patients with stage Ⅰ-Ⅱ and no lymph node metastasis,respective-ly,and the difference was statistically significant(P＜0.05).The 3-year overall survival rate of miR-141-3p high expression group was significantly lower than that of miR-141-3p low expression group,and the differ-ence was statistically significant(Log-rank x2=7.043,P=0.008).The 3-year overall survival rate of patients with high miR-149-3p expression group was significantly lower than that of patients with low miR-149-3p ex-pression group,with statistical significance(Log-rank x2=7.094,P=0.007).FIGO stage Ⅲ,lymph node me-tastasis,miR-141-3p elevation and miR-149-3p elevation were independent risk factors for prognosis of pa-tients with endometrial cancer(P＜0.05).Conclusion Detecting the expression of miR-141-3p and miR-149-3p in cancer tissues of patients with endometrial carcinoma is helpful to evaluate the survival and prognosis of patients.
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Objective To investigate the relationship between the expression of long non-coding RNA HOXA-AS2(lncRNA HOXA-AS2),long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1),and long non-coding RNA CRNDE(lncRNA CRNDE)in endometrial carcinoma and the clinical pathological character-istics and prognosis of patients.Methods Collect samples of endometrial carcinoma cancer tissues and adja-cent tissues excised during surgery from 119 endometrial carcinoma patients admitted to a hospital from Octo-ber 2017 to February 2020.The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in tissues were retrospectively analyzed,as well as their relationship with clinicopathological features and 3-year survival rate of patients.Results The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were higher than those in adjacent tissues,with statistical signifi-cance(P＜0.05).The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were positively correlated(rHOXA-As2 vs.FOXD2-AS1=0.384,P=0.001;rHoXA-AS2 vs.CRNDE=0.576,P＜0.001;rFoXD2-AS1 vs.CRNDE=0.326,P=0.003).In the HOXA-AS2,FOXD2-AS1 and CRNDE high expression group,the proportion of patients with international federation of gynecology and ob-stetrics(FIGO)stage Ⅲ+Ⅳ,lymph node metastasis,deep infiltration and low differentiation was higher than that in the low expression group,with statistical significance(P＜0.05).The 3-year survival rate of low HOXA-AS2 expression group in endometrial cancer patients(52/60,86.67％)was higher than that of high HOXA-AS2 expression group(40/59,67.79％),the difference was statistically significant(x2=6.039,P＜0.05).The 3-year survival rate of patients with endometrial cancer with low FOXD2-AS1 expression group(53/59,89.83％)was higher than that of patients with endometrial cancer with high FOXD2-AS1 expression group(39/60,65.00％),and the difference was statistically significant(x2=10.456,P＜0.05).The 3-year sur-vival rate of low CRNDE expression group in endometrial cancer patients(51/60,85.00％)was higher than that of high CRNDE expression group(41/59,69.49％),and the difference was statistically significant(x2=4.079,P＜0.05).HOXA-AS2,FOXD2-AS1,and CRNDE were risk factors for death in endometrial carcinoma patients(P＜0.05).Conclusion The expression of HOXA-AS2,FOXD2-AS1,and CRNDE in endometrial carcinoma cancer tissue is closely related to the clinical pathological characteristics and prognosis of patients.
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Objective To explore the influence and mechanism of lentiviral vector-mediated steroidogenic factor-1(SF-1)silence on decidual process of human endometrial stromal cells(hESCs).Methods The endometrial tissues of patients with endometriosis(EM)and normal pregnant women were collected,and the differential expression of SF-1 was detected by Real-time PCR and immunohistochemical staining.hESCs were isolated from the endometrial tissue of normal pregnancy and identified,hESCs were divided into control group,estradiol(E2)+progesterone(P4)group,short hairpin RAN(shRNA,sh)-normal control(NC)+E2+P4 group,sh-SF-1+E2+P4 group,after the corresponding processing,the morphological changes of hESCs were observed under an inverted microscope.Real-time PCR and Western blotting were used to detect the mRNA expression levels and protein levels of human insulin-like growth factor-binding protein-1(IGFBP-1)and prolactin(PRL)in cells,respectively,flow cytometry was used to determine the cycle distribution of the cells,immunofluorescence staining was used to observe the expression of the intracellular auto-bid microtubule-associated protein light chain 3(LC3),Western blotting was used to determine the protein level of intracellular autophagy-related proteins LC3-Ⅱ,LC3-Ⅰ and Beclin-1.Results The relative expression of SF-1 mRNA and the positive rate of SF-1 protein in endometrial tissue of EM patients were higher than those of normal pregnancy endometrial tissue(P<0.05).Compared with the sh-NC+E2+P4 group,the cells in the sh-SF-1+E2+P4 group were mostly long-spindle,and there was no obvious decidualization.The relative mRNA expression and protein expression of IGFBP1 and PRL were significantly down-regulated(P<0.05),the proportion of cells in G0/G1 phase was significantly decreased,the proportion of cells in S phase was significantly increased(P<0.05),the ratio of LC3-Ⅱ/LC3-Ⅰwas significantly increased,and the relative expression of Beclin-1 protein was also significantly up-regulated(P<0.05).Conclusion The expression of SF-1 in the endometrial tissue of EM patients is increased,and SF-1 silencing mediated by lentiviral vector can inhibit the decidualization process of hESCs,which may be related to regulating the level of autophagy.
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Purpose To explore the application and clini-copathological significance of molecular classification in endome-trial cancer(EC)of WHO(2020)tumors of the female repro-ductive system.Methods Sixty-two EC patients were collected and categorized into four subgroups,namely POLE mutation type,mismatch repair deficient(MMRd)type,non-specific molecular spectrum(NMSP)type,and p53 mutation type,based on WHO molecular classification tested by PCR and im-munohistochemistry.The correlation among four molecular sub-groups and their clinicopathological features were analyzed.Re-sults The molecular classification was distributed as follows:3(4.8％)cases were POLE-mutated,15(24.2％)cases MMRd,36(58.1％)cases NSMP and 8(12.9％)cases p53 abnormal expression.There were no significant differences a-mong POLE-mutated and infiltration depth,grade,lymph vascu-lar space invasion and other pathological factors such as lymph node metastasis and FIGO stage(P＞0.05).Among 15 patients with MMRd,the proportion of FIGO stage Ⅱ+Ⅲ significantly increased.One case showed abnormal overexpression of p53 pro-tein,while two cases showed complete loss of expression in MMRd subgroup.36 cases of NSMP were associated with low histopathological grade(Grade Ⅰ+Ⅱ)(P＜0.05),and no significant differences were observed among NSMP and other clinicopathological factors(P＞0.05).The p53 abnormal ex-pression in 8 cases was related to high histopathological grade(Grade Ⅲ)(P＜0.05),and the rate of lymph node metastasis and FIGO stage Ⅱ+Ⅲ significantly increased in patients with p53 abnormal expression,and although the difference was not statistically significant(P＞0.05).Conclusion The molecu-lar subgroups of EC have certain clinical application value,the cases with MMRd and p53 abnormal expression may have poor prognosis than these with POLE-mutated and NSMP.
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Objective Differential genes related to prognosis of endometrial carcinoma(EC)were screened and prognostic models were constructed.Methods Gene Expression data of EC and normal control samples were downloaded from The Cancer Genome Atlas(TCGA)database and Gene Expression Omnibus(GEO)dataset GSE63678 to screen out common differential genes.LASSO regression analysis was used to screen out the genes with prognostic significance and construct prognostic characteristics.EC patients with complete information were obtained from the TCGA database and randomly divided into the training group and the validation group in a ratio of 1:1.In the training group,survival curves were constructed based on prognostic characteristics.Functional annotation and pathway enrichment analysis were conducted using gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Combined with prognostic features and clinical risk factors,a calibration curve and C-index were used to evaluate the performance of the histogram.Finally,use a verification group for validation.Results A total of 4800 and 257 differentially expressed genes were screened from TCGA and GEO databases respectively,of which 73 up-regulated genes and 52 down-regulated genes were co-expressed.6 prognostic genes(ORMDL2,BNC2,TTK,MAMLD1,KCTD7 and DCLK2)were screened out by LASSO regression analysis.The survival curve showed that the overall survival of patients in the high-risk group was significantly lower than that in the low-risk group(P<0.01).GO analysis and KEGG results exhibited that prognostic signature was associated with cell cycle.The nomogram showed powerful predictive ability in the training and validation groups.Conclusion We constructed a predictive model based on prognostic genes,which can accurately predict the prognosis of patients with EC and provide new theoretical support for clinical diagnosis and treatment.