Kaihong Xu

Methotrexate therapy for cesarean section scar pregnancy with and without suction curettage

OBJECTIVE To compare the clinical effects in women with cesarean scar pregnancy (CSP) who were treated with either methotrexate (MTX) regimen only or MTX regimen followed by dilation and curettage (D&C). DESIGN Prospective consecutive clinical cohort study. SETTING University hospital for obstetrics, gynecology, and reproductive medicine. SUBJECT(S) Seventy-one cases of CSP. INTERVENTION(S) The subjects were treated with either MTX only (MTX group, 21 cases) or MTX followed by D&C (combined therapy group, 50 cases). MAIN OUTCOME MEASURE(S) Success rates, hysterectomy rates, and time to resolution of serum beta-hCG and the CSP mass were compared between the two groups. RESULT(S) Compared with the MTX group, the combined therapy group had a shorter time to resolution of the CSP mass and serum beta-hCG. There was no significant difference between the MTX and combined therapy groups regarding success rates (76.2% vs. 90.0%, respectively) and hysterectomy rates (19.0% vs. 8.0%, respectively). CONCLUSION(S) Both therapies could treat the majority of CSP patients successfully, but the combined therapy resulted in a shorter time of therapy and indicated a more favorable effect.

Immunohistochemical detection of aquaporin expression in eutopic and ectopic endometria from women with endometriomas

OBJECTIVE To investigate the expression of aquaporin (AQP) in eutopic and ectopic endometrial tissues from women with endometriomas. DESIGN Controlled laboratory research. SETTING Hospital-based unit for gynecology and obstetrics and research laboratories. PATIENT(S) Premenopausal women undergoing laparoscopy for endometriomas. INTERVENTION(S) Endometrial biopsy samples obtained from 70 women with endometriomas. MAIN OUTCOME MEASURE(S) Semiquantitative analysis by immunohistochemistry. RESULT(S) Aquaporins 2, 5, and 8 were mainly located in luminal and glandular epithelia. The frequency of positive immunostaining for aquaporins 2, 5, and 8 decreased in ectopic compared with eutopic endometria. Aquaporins 2, 5, and 8 were found at a low frequency in the endometria in early proliferative phases but at a higher frequency in late proliferative and secretory phases. There were no significant differences in the menstrual cycle of the proliferative phase and secretory phase in the two groups. CONCLUSION(S) Aquaporins 2, 5, and 8 were expressed with greater frequency in eutopic endometrial cells than inectopic endometrial cells, suggesting that eutopic endometrial cells have stronger migration activity than ectopic endometrial cells in women with endometriosis.

Increased steroid receptor RNA activator protein (SRAP) accompanied by decreased estrogen receptor-beta (ER-β) levels during the malignant transformation of endometriosis associated ovarian clear cell carcinoma.

The modulating attributes of steroid receptor RNA activator protein (SRAP) on steroid receptors have been shown in some types of tumor cells. There is compelling evidence to suggest that this molecule may play a critical role in the development of the tumor. However, little has been reported on its expression in endometriosis associated ovarian clear cell carcinoma (EAOCCC). In order to investigate the role of SRAP and estrogen receptors (ERs) in EAOCCC, we have analyzed the distribution of these proteins in the malignant transformation tissues and endometrioma tissues by immunohistochemistry. Our results revealed that the positive ratio of ER-β expression was gradually reduced during the malignant transformation from endometriosis to atypical endometriosis to clear cell carcinoma. Conversely, during the process, a gradual increase in SRAP expression was observed. Furthermore, there is a negative relationship between the expressions of these two molecules. Overall an increase in SRAP and a reduction in ER-β expression might be associated with malignant transformation of EAOCCC.

Phosphatase of regenerating liver-3: a novel and promising marker in human endometriosis

OBJECTIVE To investigate the expression of phosphatase of regenerating liver-3 (PRL-3) in ectopic, eutopic, and normal endometria and explore its relationship with endometriosis. DESIGN A clinical retrospective and molecular study. SETTING Department of obstetrics, gynecology, and reproductive medicine. PATIENT(S) One hundred and five women with histopathologically confirmed endometriosis, and 50 women with histopathologically assessed normal endometria. INTERVENTION(S) Immunohistochemical staining and Western blot analysis. MAIN OUTCOME MEASURE(S) Expression of PRL-3 protein. RESULT(S) As shown by the immunohistochemical analysis, PRL-3 was mainly located in the cytoplasm and membrane. The cells that tested positive for PRL-3 were detected in endometriotic tissues that did not occur in eutopic and normal endometria. Statistical analysis indicated that the expression of PRL-3 was closely associated with the clinical stages and recurrence of endometriosis. CONCLUSION(S) Expression of PRL-3 is related to the clinical stages and recurrence of endometriosis, which provides use with a novel marker and promising target in the treatment of human endometriosis.

A new fertility-preserving surgery for interstitial pregnancy involving hysteroscopic removal under laparoscopic guidance

Interstitial pregnancy is a rare form of tubal ectopic pregnancy, accounting for 2%–4% of all such pregnancies [1]. Although medical treatment can successfully resolve the pregnancy when detected early enough, the standard treatment is cornual resection [2]. However, surgical treatmentmay result in aweakened uterinewall, leading to reduced fertility and a risk of uterine rupture in subsequent pregnancies. Successful transcervical evacuation of interstitial pregnancy under laparoscopic guidance has been reported [2]. However, owing to the characteristics of interstitial pregnancy and potential difficulties encountered during surgery, the placenta may be left behind—necessitating further treatment [3]. Hysteroscopic removal, when possible, reduces the incidence rate of this complication. In 2013, a 26-year-old nulliparous woman presented with an interstitial pregnancy. She wanted to preserve an intact uterus, so hysteroscopic removal was carried out using a technique similar to that performed for intrauterine evacuation. Hegar dilators were used for dilation of the cervical canal and the ostium of the fallopian tube; the dilators were used to reach the uterine cornu and to carefully establish a passage to the gestational site under laparoscopic guidance. A 6-mm suction catheter was then inserted into the uterus and introduced into the gestational site. The products of conception were evacuated at a negative pressure of 180 mm Hg. The hysteroscope was then introduced into the interstitial cavity because a more dilated pathologic tubal ostium was observed. Graspers were used to remove residual tissue from the interstitial cavity, leaving it empty (Fig. 1). Had uterine perforation occurred, cornual resection and salpingectomy would have been performed via laparoscopy. Thewomanwas discharged 2 days later; her serum β-human chorionic gonadotropin levels were undetectable by the second postoperative week. Ultrasound examination 4 weeks postoperatively showed that the cornual region had a normal appearance. When there is a possibility of interstitial pregnancy that is a relatively short distance from the cornual end and is associated with an unruptured mass and hemodynamic stability, hysteroscopic removal under laparoscopic guidance—rather than cornual resection—is a feasible treatment option. Furthermore, this new treatment can prevent a large amount of blood loss; however, when there is a high risk of tubal scarring, recurrent interstitial pregnancy may occur.

Silencing of SRA1 Regulates ER Expression and Attenuates the Growth of Stromal Cells in Ovarian Endometriosis

Estradiol and its nuclear receptors, estrogen receptor (ER) α and ER-β, have important functions in endometriosis, and the transcriptional activity of these receptors is modulated by coactivators and corepressors. The steroid receptor RNA activator 1 (SRA1) produces SRA long noncoding RNA (lncRNA) and SRA protein (SRAP), which regulate ER expression at the RNA and protein levels in some hormone-dependent tumors via an alternative splicing event. However, only a few are reported on their expressions in endometriosis. Here, we observed that low expression levels of SRA lncRNA and ER-α but relatively high expression levels of SRAP and ER-β were detected in ovarian endometriotic tissues versus normal endometrial tissues. Steroid receptor RNA activator I-small interfering RNA treatment significantly increased ER-α levels but reduced ER-β levels in endometriotic stromal cells (ESCs). Furthermore, the treatment can also attenuate the proliferation and promote early apoptosis in these cells. Our results indicate that the regulation of ER via SRA in ovarian endometriosis may play a significant role in the growth of ESCs.Estradiol and its nuclear receptors, estrogen receptor (ER) α and ER-β, have important functions in endometriosis, and the transcriptional activity of these receptors is modulated by coactivators and corepressors. The steroid receptor RNA activator 1 (SRA1) produces SRA long noncoding RNA (lncRNA) and SRA protein (SRAP), which regulate ER expression at the RNA and protein levels in some hormone-dependent tumors via an alternative splicing event. However, only a few are reported on their expressions in endometriosis. Here, we observed that low expression levels of SRA lncRNA and ER-α but relatively high expression levels of SRAP and ER-β were detected in ovarian endometriotic tissues versus normal endometrial tissues. Steroid receptor RNA activator 1–small interfering RNA treatment significantly increased ER-α levels but reduced ER-β levels in endometriotic stromal cells (ESCs). Furthermore, the treatment can also attenuate the proliferation and promote early apoptosis in these cells. Our results indicate that the regulation of ER via SRA in ovarian endometriosis may play a significant role in the growth of ESCs.

Analysis of long non-coding RNA expression profiles using RNA sequencing in ovarian endometriosis

Endometriosis is a common gynecological condition with unclear pathogenesis. Although a dysregulated lncRNA expression profile has been speculated, very few studies have addressed this hypothesis. We determined the differential lncRNA and mRNA expression patterns between endometriosis and control tissues, and between eutopic and normal endometrium in the proliferative phase, using RNA sequencing. The potential targets of lncRNA were predicted on the basis of cis and trans action, and lncRNAs were functionally annotated in relation to their co-expressed mRNAs. Dysregulated lncRNAs and mRNAs were screened relative to the biological features of endometriosis, and the five filtered lncRNAs were validated using qRT-PCR. A total of 9924 novel lncRNA transcripts were identified, and 86 lncRNAs and 1228 mRNAs were differentially expressed between the endometriosis and control groups. GO and KEGG pathway analysis showed that the differentially expressed lncRNAs were enriched in the biological processes and signaling pathways involved in endometriosis. A coding-noncoding gene (CNC) co-expression network was constructed using the dysregulated lncRNAs and their co-expressed mRNAs to simulate the complex intergenic interactions. This study is the first to use sequencing technology to elucidate the differentially lncRNA expression profiles of eutopic and normal endometrium in the proliferative phase of endometriosis. The dysregulated lncRNAs can potentially be novel diagnostic biomarkers and therapeutic targets of endometriosis.

Upregulation of S100A6 in patients with endometriosis and its role in ectopic endometrial stromal cells

Abstract S100 calcium-binding protein A6 (S100A6) is up-regulated in many malignancies and overexpression of S100A6 has been identified associated with proliferation, migration and invasion phenotype in several cancer cells. In the present study, we explored whether S100A6 plays a role in the development of endometriosis. Significantly higher levels of mRNA and protein expression of S100A6 were observed in ectopic endometrial tissues compared to eutopic and normal endometrial tissues. Silencing of S100A6 in ectopic endometrial stromal cells (ESCs) significantly inhibited cell viability, migration and invasion. Moreover, knockdown of S100A6 suppressed p38/MAPK activity in ectopic ESCs, which can be partially attenuated by CacyBP/SIP phosphorylation inhibitor. In conclusion, our results suggest that the abnormal expression of S100A6 may contribute to the pathogenesis of endometriosis and the S100A6/CacyBP/p38 signaling may provide as a promising treatment target.

Correlation of polypeptide N-acetylgalactosamine transferases-3 and -6 to different stages of endometriosis

PurposeTo investigate the expression patterns of N-acetyl galactosamine transferases (GalNAc-Ts)-3 and GalNAc-T6 in clinicopathologically characterized endometriosis (EMS), and to explore their clinical significance.MethodsEctopic and eutopic endometrial tissue samples were obtained and confirmed with CD-10 immunohistochemistry in patients with EMS (n = 12), whereas normal control endometrium was obtained from patients with uterine septum (n = 12). The mRNA and protein levels of GalNAc-T3 and GalNAc-T6 were detected in these samples using quantitative real-time PCR, immunohistochemistry, and western blotting.ResultsGalNAc-T3 and GalNAc-T6 were expressed in the endometrium of all groups, with no significant changes observed during the menstrual cycle. The expression of GalNAc-T3 and GalNAc-T6 in ectopic endometrium was significantly lower than that in eutopic (P < 0.05) or control endometrium (P < 0.05), whereas there were no significant differences (P > 0.05) between eutopic and control endometria. Furthermore, the expression of GalNAc-T3 and GalNAc-T6 was significantly lower in patients with stage III/IV EMS compared to patients with stage I/II (P < 0.05).ConclusionsBoth GalNAc-T3 and GalNAc-T6 expression levels were downregulated in ectopic endometrium, which may increase the adhesion and invasion of endometrial cells and contribute to the development of EMS. Moreover, we found a strong correlation between the expression of GalNAc-T3 and GalNAc-T6 and different stages of EMS.

O422 Immunohistochemical detection of aquaporin expression in eutopic and ectopic endometrial from women with endometriomas

fact that the follow-up survey wanted to monitor the post training performance of newly trained doctors, trainees who intended to return to his/her site to perform uterine evacuations and agreed to take part in the follow-up survey were included in the survey. Ipas has established two training centres during 2004 at the state capital named Ranchi to improve the number of legal providers on safe abortion services. During 2006 established another four training centres in the districts named Dhanbad, Hazaribag, Palamu and Chaibasa and during 2007 another district was added named Lohardaga. To sustain the programme Ipas has built the training capacity of the senior Gyneocologist of the districts. These doctors have imparted the capacity to the doctors who are posted in the rural areas. Observations and Results: During the last five years (Feb. 2004 – Dec. 2008) a total of 449 (146 certified and 303 certification) medical doctors have been trained in CAC in Jharkhand. Comprehensive Abortion Care service is one of the basic services needs to be available at the primary health care settings. Ipas always wants to facilitate training of the doctors based in the primary level so that it becomes easily accessible for the rural women. Of the total 449 doctors trained, 229 (51%) are posted either in Primary Health Centres (PHC) or in the Addl. Primary Health Centres (APHC), i.e. in the rural areas of Jharkhand. Another 77 (17%) are posted in Referral Hospitals and Sub Dist. Hospitals which are generally based in the semi – urban locations. The rest of the 113 (29%) trained doctors are posted in Dist. Hospitals and Medical Colleges and based in urban areas. Most of the 30 (7%) private doctors who received CAC training are also based in urban areas. Trained providers who successfully completed the follow-up survey represent nine districts comprising 3 regions. While four districts Dhanbad (35), East Singbhum (14), West Singbhum (16) and Ranchi (28) accounted around 79% of these trainees, the remaining 21% included from Lohardaga (12), Bokaro (5), Ramgarh (3) and Koderma & Hazaribag (2 each). It is experienced from the intervention as the number of trained providers has increased the number of women who were seeking abortion services increased.