Extracellular vesicle-mediated transfer of the lncRNA-TC0101441 promotes endometriosis migration/invasion.

Extracellular vesicular long noncoding RNAs (lncRNAs) to influence recipient cells is emerging as a novel mechanism for disease progression. TC0101441 is a newly identified metastasis-related lncRNA involved in cancer. Since endometriosis exhibits prometastasis behavior similar to those observed in cancer, we aimed to investigate whether TC0101441 is involved in endometriosis and, if so, whether extracellular vesicular TC0101441 contributes to the migration/invasion of endometriotic cyst stromal cells (ECSCs). Clinically, we found that TC0101441 was highly expressed in ectopic endometria than in the eutopic and normal endometria. Serum extracellular vesicular TC0101441 levels were substantially increased in patients at stage III/IV endometriosis in comparison with stage I/II endometriosis and controls. In vitro, using TC0101441-high-expression ECSCs (ECSCs-H) as extracellular vesicles (EVs)-generating cells and TC0101441-low-expression ECSCs (ECSCs-L) as recipient cells, we observed that the PKH67-labeled ECSCs-H-derived EVs were effectively internalized by ECSCs-L. ECSCs-H-derived EVs shuttling TC0101441 were transferred to ECSCs-L, modulating their migratory/invasive abilities partially by regulating certain metastasis-related proteins, which eventually facilitated endometriosis migration/invasion. This study elucidates a potential crosstalk between ECSCs via EVs in endometriotic milieus, suggests a novel mechanism for endometriosis migration/invasion from the perspective of the "extracellular vesicular transfer of lncRNAs" and highlights the potential of circulating extracellular vesicular TC0101441 as a biomarker for endometriosis.

Long noncoding RNA TC0101441 induces epithelial-mesenchymal transition in epithelial ovarian cancer metastasis by downregulating KiSS1.

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC.

Genipin improves reproductive health problems caused by circadian disruption in male mice.

BACKGROUND: Circadian rhythm disruption impacts a wide range of physiological processes, including fertility. However, the effect of circadian disruption on male spermatogenesis and fertility, and treatments for these effects have been largely unexplored at the molecular level. METHODS: In this study, we examined the effects of genipin on improving the reproductive health problems caused by circadian disruption. Three groups of animals were fed under different conditions: control group (normal T cycle with saline), group of shortened T cycles (Light/Dark = 4 hours/4 hours) with saline, and a group of shortened T cycles with genipin by oral gavage. The male fertility was evaluated by fertility study and pups parameters analysis after successful sexual behavior and mating with female mice. We sacrificed the treated animals after 5 or 10 weeks and collected the testis, sperm and serum for histological analysis, sperm motility assay, and serum hormone detection, respectively. Furthermore, the effect of genipin was assessed by detection of progesterone secretion and steroidogenic key proteins expression, including StAR and CYP11A1, in mouse Leydig tumor MLTC-1 cells. RESULTS: Male mice exposed to shortened light-dark cycles, much shorter than 24 hours, had reduced fertility with decreased sperm concentrations and sperm motility. Male mice under circadian disruption have reduced testis size and abnormal morphology, leading to lower fertility rates, reduced litter size and pup body weight. Treatment with exogenous genipin, a natural plant-derived compound, alleviated circadian disruption-induced damage to fertility and spermatogenesis and normalized testosterone, dihydrotestosterone (DHT), and androstenedione (ASD) levels in the male mice. The levels of key proteins involved in steroidogenesis, StAR and CYP11A1, were reduced in mouse testes after the circadian disruption, but genipin treatment restored the reduction. The mRNA expression of SRD5A1, which encodes an androgen synthesis enzyme, was also upregulated by genipin treatment. Furthermore, genipin treatment showed a positive effect on steroidogenesis in MLTC-1 cells, resulting in an increase in hormone secretion and the upregulation of StAR and CYP11A1. CONCLUSIONS: Our results showed an association between circadian disruption and reproductive health problems in male mice and indicated that treatments with genipin have positive effects on the reproductive health of male mice with circadian rhythm disorders.

Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-ß and Ku70.

Multiple DNA repair pathways may be involved in the removal of the same DNA lesion caused by endogenous or exogenous agents. Although distinct DNA repair machinery fulfill overlapping roles in the repair of DNA lesions, the mechanisms coordinating different pathways have not been investigated in detail. Here, we show that Ku70, a core protein of nonhomologous end-joining (NHEJ) repair pathway, can directly interact with DNA polymerase-ß (Pol-ß), a central player in the DNA base excision repair (BER), and this physical complex not only promotes the polymerase activity of Pol-ß and BER efficiency but also enhances the classic NHEJ repair. Moreover, we find that DNA damages caused by methyl methanesulfonate (MMS) or etoposide promote the formation of Ku70-Pol-ß complexes at the repair foci. Furthermore, suppression of endogenous Ku70 expression by small interfering RNA reduces BER efficiency and leads to higher sensitivity to MMS and accumulation of the DNA strand breaks. Similarly, Pol-ß knockdown impairs total-NHEJ capacity but only has a slight influence on alternative NHEJ. These results suggest that Pol-ß and Ku70 coordinate 2-way crosstalk between the BER and NHEJ pathways.-Xia, W., Ci, S., Li, M., Wang, M., Dianov, G. L., Ma, Z., Li, L., Hua, K., Alagamuthu, K. K., Qing, L., Luo, L., Edick, A. M., Liu, L., Hu, Z., He, L., Pan, F., Guo, Z. Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-ß and Ku70.

Analysis of the reproductive outcomes and the size of the unicornuate uterus measured by magnetic resonance imaging and their relationship.

PURPOSE: To evaluate the relationship between the uterine size measured by pelvic magnetic resonance and reproductive outcome in women with a unicornuate uterus. METHODS: This was a retrospective study including 140 patients affiliated with unicornuate uterus diagnosed by the pelvic MR prior to their first pregnancy in the Obstetrics and Gynecology Hospital of Fudan University from April 2010 to December 2017. All the length of the unicornuate uterus were re-measured and recorded by skilled radiologists during the study period. We divided all the 140 participants with complete pelvic MR imaging into four groups by the best reproductive outcomes, which refers to Group 1 (primary infertility, n = 21), Group 2 ( < 24 weeks' gestation, n = 34), Group 3 (preterm delivery, 24-35 weeks' gestation, n = 13), Group 4 ( ≥ 35 weeks' gestation, n = 72), followed them up and then analyzed the data. RESULTS: Measurements of 140 patients with hemi-uteri were retrieved for analysis. The mean length of the uterine was 4.90  ± 0.56 cm. There were no significant differences in the uterine cavity length, cervical length, endometrial thickness and uterine wall thickness between the four groups while the uterine length (P = 0.001) was statistically significant. Women with uterine lengths ≥  4.5 cm were more likely to experience full-term delivery compared with the other group (P = 0.001). Ordinal multiple logistic regression analysis showed that the uterine length [OR = 9.03 (95% CI: 2.90-28.13)] and uterine cavity length [OR = 0.32 (95% CI: 0.06-2.04)] were independent protective factors for better obstetric outcomes CONCLUSION: The uterine length is a reliable prognostic factor for the gestational week of delivery and an appropriate antenatal surveillance factor of women with unicornuate uterus.

The role of oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para-aortic lymphadenectomy.

BACKGROUND AND OBJECTIVES: This study is aimed to investigate the possibility of preoperative oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para-aortic lymphadenectomy. MATERIALS AND METHODS: In this retrospective nonrandomized study, of the 30 patients with gynecological malignancies who had indications for laparoscopic para-aortic lymphadenectomy up to renal vessels, 15 were administered preoperative oral oil (oil a administration) (control group) at our hospital between September 2017 and June 2018. The chylous tube displaying rates, incidences of chylous leakage, and other perioperative data of the two groups were compared. RESULTS: Successful display of chylous tubes was observed in 93.3% (14/15) patients in the oil administration group. The chylous leakage was zero in the oil administration group, and 33.3% (5/15) in the control group. The postoperative drainage duration (4.1 ± 1.0 days vs 7.6 ± 1.4 days, P = 0.000), somatostatin application time (0 day vs 5.9 ± 0.8 days), and postoperative hospital stay (6.0 ± 2.3 days vs 9.1 ± 2.1 days, P = 0.001) were significantly shorter in the oil administration group. The total cost is lower in the oil administration group (4972.52 ± 80.54 dollars vs 6260.80 ± 484.47 dollars, P = 0.000). CONCLUSIONS: Preoperative oil administration is a feasible and effective method to display the chylous tubes and to prevent the chylous leakage in para-aortic lymphadenectomy.

Ovarian endometriosis: risk factor analysis and prediction of malignant transformation.

INTRODUCTION: For the prediction of endometriosis associated ovarian carcinoma (EAOC), the risk factors for malignant ovarian endometriosis (MOE) were explored. MATERIAL AND METHODS: A group of 104 EAOC patients was compared with a group of 104 ovarian endometrial cyst patients. Using single and multivariate risk analysis of EAOC by calculating the area under the curve (AUC) of receiver-operator characteristics (ROC) curves, risks of MOE transformation were calculated for various burdens of risk factors. RESULTS: The age range of 85 EAOC patients (81.73% of EAOC patients) was from 40 to 60 years old, as menopause occurs most frequently in this age range. From single factor ROC curve analysis, if disease duration/age/menopause/times of pregnancy/multiple foci of endometriosis index AUC were above 0.70, this suggested that the above indicators were predictive of MOE. Times of pregnancy/tumour size/myoma of uterus/multiple foci of endometriosis were taken as the independent risk factors of MOE. Using logistic regression, the AUC of 0.89 (95% confidence interval [CI]: 0.84-0.94) was statistically significant (p < 0.001), illustrating the predictive power of this model. CONCLUSIONS: Times of pregnancy/BMI/irregular vaginal bleeding/thyroid disease/myoma of uterus/tumour serious fixation index indicate higher risk of MOE; age/tumour size/menopause/disease duration/ dysmenorrhea/multiple foci of endometriosis suggest lower risk of MOE. Therefore, in patients with endometriosis, malignant transformation could be predicted early.

Evaluation of two intervention models on contraceptive attitudes and behaviors among nulliparous women in Shanghai, China: a clustered randomized controlled trial.

BACKGROUND: With increasing acceptance of premarital sex among young Chinese women, the rates of unintended pregnancies and induced abortions are becoming alarmingly high, suggesting the needs of educating women with adequate contraceptive knowledge and providing them with accessible contraceptive services. Previous studies have shown that knowledge and attitudes towards contraception could be modified through intervention strategies. This study aimed to evaluate the effects of two community intervention models on modifying contraceptive attitudes and behaviors among nulliparous women. METHODS: In this clustered randomized controlled trial, nulliparous women aged 18-40 years from 18 communities were enrolled and randomized to either the traditional community intervention model (TC model) or the more comprehensive new community-based intervention model (NC model) with a ratio of 1:2. Contraceptive attitudes and behaviors were assessed before and after the interventions. RESULTS: A total of 901 nulliparous women were followed. The most common contraceptive method in both groups was condom (approximately 80%) before or after interventions. The rates of using effective contraceptive methods were very low (<5%) even after the intervention. Comparing the NC with TC group, the adjusted ORs and 95% CIs regarding natural family planning, emergency contraceptive usage and short-acting OCPs were1.53 (95% CI: 1.11-2.13), 2.87 (95% CI: 2.05-4.02), and 2.71 (95% CI: 1.65-4.47), respectively; while the ORs and 95%CIs of gynecological examination and contraceptive use were 2.31 (95% CI: 1.63-3.27) and 2.89 (95% CI: 1.98-4.23), respectively. No statistical significant difference was found for the use of effective contraceptive methods at post-intervention among the two models. CONCLUSIONS: High proportions of nulliparous women held negative attitudes and behaviors towards effective contraceptive methods. The NC model, integrating existing health resources, had more positive influence than the TC model on the favorable contraceptive attitudes and behaviors towards the use of any contraceptive methods, but had limited impact on the use of effective contraceptive methods. Our study suggested the feasibility of applying the NC model in Shanghai. Interventions on contraceptive attitudes and behaviors should base on the existing health service system, synthesize resources and selectively apply to populations with distinct characteristics.

Efficacy of caesarean scar defect repair in improving postmenstrual bleeding and factors associated with poor effect.

Caesarean scar defect (CSD) can cause postmenstrual bleeding. Defect repair is an effective technique to improve this symptom, but there are still a few patients getting little improvement. This retrospective study evaluates the efficacy of scar repair and explores the factors associated with poor effect. In total, 123 patients were involved in the final analysis. All of them complained about menstruation period >7 days due to postmenstrual bleeding. Before surgery, 87.8% of patients had a menstruation period more than 10 days and 20.3% had a period more than 15 days. After surgery, a normal menstruation period (< =7 days) was achieved in 46.3% (95%CI 37.3%-55.6%) of patients and a menstruation period lasting no more than 10 days was achieved in 74.8% (95%CI 66.2%-82.2%). Through multivariate logistic analysis, four factors were found dependently associated with poor effect (defined as menstruation period >10 days after surgery): repeated caesarean section (OR 9.75, 95%CI 2.30-41.36, 0.002) was a risk factor, while defect volume >600 mm3 (OR 0.14, 95%CI 0.03-0.56, 0.006), interval from caesarean section to symptom emerging >3 months (OR 0.25, 95%CI 0.07-0.94, 0.041) and straight or retroflexed uterus (OR 0.19, 95%CI 0.05-0.79, 0.022) were protective factors. Impact statement What is already known on this subject? Caesarean scar defect can cause postmenstrual bleeding. Defect repair can improve this symptom, but there are still a few patients getting little improvement after surgery. What do the results of this study add? Defect volume >600 mm3, interval from caesarean section to symptom emerging >3 months and straight or retroflexed uterus are protective factors of poor effect (defined as menstruation period >10 days after surgery), and repeated caesarean section is a risk factor. What are the implications of these findings for clinical practice and/or further research? These findings may help in counselling the patients and in medical decision. Further researches are needed to explore other factors associated with surgical effect and build prediction models.

Comparison of small intestinal submucosa graft with split-thickness skin graft for cervicovaginal reconstruction of congenital vaginal and cervical aplasia.

STUDY QUESTION: What is the difference in vaginal-length gain and resumption of menstruation following cervicovaginal reconstruction using split-thickness skin (STS) graft versus small intestinal submucosa (SIS) graft for patients with congenital vaginal and cervical aplasia? SUMMARY ANSWER: No difference was found in the number of patients who resumed menstruation between the two groups; however, significantly greater vaginal-length gain was found in the STS group. WHAT IS ALREADY KNOWN: Hysterectomy and vaginoplasty are typically recommended for patients without a cervix or without a sufficient cervix to avoid postoperative re-obstruction. Advances in surgical techniques have enabled the use of autologous tissues or heterologous biological grafts for reconstructive procedures, allowing patients undergoing these procedures to preserve the possibility of conception. STUDY DESIGN, SIZE, DURATION: This was a retrospective study of 26 women who were diagnosed with congenital vaginal and cervical aplasia with a functional endometrial cavity and underwent cervicovaginal reconstruction using STS or SIS grafts between January 2012 and October 2015 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PARTICIPANTS/MATERIALS, SETTING, METHOD: 15 women underwent cervicovaginal reconstruction using SIS graft and 11 underwent cervicovaginal reconstruction using STS graft. Clinical characteristics, perioperative data, resumption of menstruation, vaginal stenosis, length of the neovagina, vaginal-length gain, stricture of the cervix and body image were postoperatively assessed. MAIN RESULTS AND THE ROLE OF CHANCE: At a median follow-up of 21 (2-46) months, all but one of the patients experienced relief of abdominal pain and resumed menstruation. Re-obstruction of the cervix occurred in only one patient in the SIS group. The SIS group reported significantly higher body image scores and cosmetic satisfaction. Although the two groups had a similar vaginal length before surgery, the vaginal-length gain was significantly greater in the STS group (4.9 ± 1.7 cm in the SIS group versus 7.5 ± 0.7 cm in the STS group, P = 0.004) and the neovagina length at 6 months post-operation was significantly shorter in the SIS group (6.5 ± 0.7 cm in SIS the group versus 8.0 ± 0.5 cm in the STS group, P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: Due to a lack of long-term follow-up, patient satisfaction with sex life, pregnancy rates and outcomes after the two approaches require further evaluation. WIDER IMPLICATIONS OF THE FINDINGS: Combined laparoscopic and vaginal cervicovaginal reconstruction using SIS or STS graft is a safe and effective treatment for preserving uterus function in women with congenital vaginal and cervical aplasia. However, SIS graft must still be improved to achieve satisfactory vaginal length. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Chinese National Nature Sciences Foundation (grant number 81471416) and the National Key Clinical Faculty Construction Program of China. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis.

HOX transcript antisense RNA (HOTAIR) is a well-known long non-coding RNA (lncRNA) whose dysregulation correlates with poor prognosis and malignant progression in many forms of cancer. Here, we investigate the expression pattern, clinical significance, and biological function of HOTAIR in serous ovarian cancer (SOC). Clinically, we found that HOTAIR levels were overexpressed in SOC tissues compared with normal controls and that HOTAIR overexpression was correlated with an advanced FIGO stage and a high histological grade. Multivariate analysis revealed that HOTAIR is an independent prognostic factor for predicting overall survival in SOC patients. We demonstrated that HOTAIR silencing inhibited A2780 and OVCA429 SOC cell proliferation in vitro and that the anti-proliferative effects of HOTAIR silencing also occurred in vivo. Further investigation into the mechanisms responsible for the growth inhibitory effects by HOTAIR silencing revealed that its knockdown resulted in the induction of cell cycle arrest and apoptosis through certain cell cycle-related and apoptosis-related proteins. Together, these results highlight a critical role of HOTAIR in SOC cell proliferation and contribute to a better understanding of the importance of dysregulated lncRNAs in SOC progression.

Effects of a new community-based reproductive health intervention on knowledge of and attitudes and behaviors toward stress urinary incontinence among young women in Shanghai: a cluster-randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: This study aimed to evaluate the prevalence of stress urinary incontinence (SUI) and to introduce a new community-based reproductive health intervention. We then evaluated the effectiveness of this intervention. METHODS: In this cluster-randomized trial, 2100 participants aged 18-40 years were divided randomly into an intervention group (IG, 1400 women) and a control group (CG, 700 women). The CG received traditional community intervention, cmprising limited reproductive information and education; the IG received the new community-based reproductive health intervention model, comprising self-designed handbooks, health lectures, and free medical consultations, in addition to the traditional community intervention. All participants were surveyed face to face using a self-designed questionnaire before and after the 6-month intervention. RESULTS: In Shanghai, the prevalence rate of SUI was 14.3 %. No difference was observed between groups regarding mean knowledge, attitudes, and practices (KAPs) about SUI and the total score at baseline (P > 0.05). The IG scored significantly higher than the CG on the KAP questions at follow-up, and a significant improvement was observed in the IG after the intervention. Total scores increased with age, educational level, income, and time spent working in Shanghai per year but decreased with gravidity and the number of abortions. Native respondents scored higher than did migrants. CONCLUSIONS: The prevalence of SUI is high in Shanghai, and the new community-based reproductive health intervention model is both effective and easily implemented. This intervention should focus on women with a low income, women with low education levels, young women, migrant women, and women who have had multiple abortions or pregnancies.

Sexual and functional outcomes of vaginoplasty using acellular porcine small intestinal submucosa graft or laparoscopic peritoneal vaginoplasty: a comparative study.

STUDY QUESTION: Can vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) be achieved using an acellular porcine small intestinal submucosa (SIS) graft? SUMMARY ANSWER: Vaginoplasty using SIS graft was successfully achieved in women with MRKHS, and the anatomical and functional outcomes of this procedure were comparable to those of laparoscopic peritoneal vaginoplasty. WHAT IS KNOWN ALREADY: There is a great variety of vaginal reconstruction techniques, which suggests there is no single superior surgical technique. STUDY DESIGN, SIZE, DURATION: This prospective observational study included 34 patients with congenital vaginal agenesis who underwent vaginoplasty using SIS graft (the SIS group) between December 2011 and July 2013, and 41 patients with the same disease who underwent laparoscopic peritoneal vaginoplasty (the Davydov group) between January 2008 and July 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patient and surgical data, follow-up information, and the female sexual function index (FSFI) scores in the two groups were analysed and compared. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with the laparoscopic Davydov procedure, the operating time of vaginoplasty using SIS graft was significantly shorter, and the estimated blood loss was significantly less. Patients in the SIS group had an earlier return of bowel activity, and an earlier return to work. However, the total cost in the SIS group was significantly higher than that in the Davydov group due to the cost of the SIS graft ($3525 per graft). Most patients (28/34 in the SIS group and 37/41 in the laparoscopic Davydov group) returned for their follow-up 9 months post-surgery. The mean length of the neovagina in the SIS group seemed slightly shorter than that in the Davydov group (6.8 ± 0.9 cm versus 7.3 ± 1.3 cm, P = 0.081). Thirteen patients (46%) in the SIS group and 11 (29%) in the Davydov group had a neovagina <7 cm long (P = 0.453), whereas 4 patients (14%) in the SIS group and 3 patients (8%) in the Davydov group had a neovagina <6 cm long (P = 0.201). Sixteen patients in the SIS group and 25 in the Davydov group subsequently had a sexual partner and became sexually active. Four patients in the SIS group and six in the Davydov group reported low total FSFI scores (≤23). There was no statistically significant difference in the total FSFI scores and the scores of all six domains of the FSFI between the two groups. The average time of continuous mould wearing in the SIS group was statistically significantly longer than that in the Davydov group (7.8 ± 3.3 months versus 4.8 ± 1.6 months, P = 0.001). In the patients with a neovaginal length of ≥6 cm, the FSFI score of the women (26.6 ± 2.3 versus 21.5 ± 1.5, P < 0.001) and the satisfactory score of their partner (8.6 ± 1.2 versus 6.6 ± 1.2, P < 0.001) were both statistically significantly higher than patients with a neovaginal length of <6 cm. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is that it is non-randomized. Further randomized studies are warranted to compare the effects of these two procedures. WIDER IMPLICATIONS OF THE FINDINGS: Despite the need to wear a mould for longer, vaginoplasty using SIS graft provides an attractive, alternative treatment for women with MRKHS. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Chinese National Nature Sciences Foundation (grant number 81471416) and the National Key Clinical Faculty Construction Program of China. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Acellular porcine small intestinal submucosa graft for cervicovaginal reconstruction in eight patients with malformation of the uterine cervix.

STUDY QUESTION: Can surgical reconstruction of the cervix and vagina in patients be achieved using an acellular porcine small intestinal submucosa (SIS) graft? SUMMARY ANSWER: Our experiences of combined laparoscopic and vaginal cervicovaginal reconstruction using an SIS graft in eight patients were positive, with successful reconstruction and no complications, cervical stenosis or vaginal stenosis. WHAT IS KNOWN ALREADY: In patients with agenesis and dysgenesis of the uterine cervix and vagina, surgical reconstruction of the internal genitalia is a challenging problem for gynecologists. Hysterectomy with the creation of an artificial vagina was the treatment of choice in the 1990s. Recently, conservative management has been gradually adopted to avoid extirpation of the uterus, including the canalization techniques, the uterovaginal anastomosis and the reconstruction of cervical and vaginal agenesis with some autologous tissues. STUDY DESIGN, SIZE, DURATION: This prospective observational study from January 2012 to March 2013 included 8 patients aged 10-18 years with malformation of the cervix (1 with cervical agenesis, 1 with a cervical body consisting of a fibrous band and 6 with obstruction of the cervical os) and vagina (4 with complete vaginal aplasia and 4 with a 1-3 cm long vaginal pouch) diagnosed by physical examination and magnetic resonance imaging. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eight patients underwent combined laparoscopic and vaginal cervicovaginal reconstruction using an SIS graft during the end of menstruation. A T-shaped intrauterine device connected with a 14-French Foley catheter was inserted into the uterine cavity to keep the newly created cervix patent, and then a permanent lower uterine cerclage was placed. Patients were assessed post-operatively at 1, 2, 4, 6, 12 and 15 months, and data on menstruation and the morphology of the neovagina and cervix were recorded. MAIN RESULTS AND THE ROLE OF CHANCE: The mean ± SD age of the patients was 14.5 ± 2.8 (10-18) years. All patients had a history of cyclic abdominal pain, and the average delay in diagnosis was 4.5 ± 4.0 (0-12) months. One patient had a previous history of unsuccessful attempt at canalization and two post-operative hematometra drainages before referral. The mean operating time was 201 ± 67 (120-330) min, with a mean estimated blood loss of 157 ± 154 (30-500) ml. The first case was converted to laparotomy, and the others were successfully completed. None of the patients had a complication or required blood transfusion. All the patients showed resumption of menstruation. The patients were followed for 8 ± 4 (4-15) months, and no cervical or vaginal stenosis occurred in any of the cases. LIMITATIONS, REASONS FOR CAUTION: The sample size of this study was small. A larger study that compared this method with previous techniques regarding the complication and success rates would increase the value of the study. WIDER IMPLICATIONS OF THE FINDINGS: A combined laparoscopic and vaginal cervicovaginal reconstruction with an SIS graft is a potential alternative to the management of congenital agenesis and dysgenesis of uterine cervix and vagina. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by National Key Clinical Faculty Construction Program of China. No competing interests are declared.

Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer.

OBJECTIVES: Although long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in epithelial ovarian cancer (EOC) is just beginning to be studied. In this study, we focused on lncRNA HOX transcript antisense RNA (HOTAIR) and investigated its expression pattern, clinical significance, and biological function in EOC. METHODS: HOTAIR expression in EOC tissues was examined and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of in vitro and in vivo assays were performed to understand the role of HOTAIR in EOC metastasis. RESULTS: HOTAIR expression was elevated in EOC tissues, and HOTAIR levels were highly positively correlated with the FIGO stage, the histological grade of the tumor, lymph node metastasis, and reduced overall survival (OS) and disease-free survival (DFS). A multivariate analysis showed that HOTAIR expression is an independent prognostic factor of OS and DFS in patients with EOC. Additionally, the results of in vitro assays showed that the suppression of HOTAIR expression in the three highly metastatic EOC cell lines (SKOV3.ip1, HO8910-PM, and HEY-A8) significantly reduced cell migration/invasion. The results of in vivo assays further confirmed the pro-metastatic effects of HOTAIR. Moreover, the pro-metastatic effects of HOTAIR were partially mediated by the regulation of certain matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT)-related genes. CONCLUSIONS: Our data suggest that HOTAIR plays a vital role in EOC metastasis and could represent a novel prognostic marker and potential therapeutic target in patients with EOC.

Self-esteem, depression, anxiety and sexual function in Mayer-Rokitansky-Küster-Hauser syndrome with neovagina: A case series.

BACKGROUND: The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare condition with significant psychological implications. However, our understanding of its impact on postoperative sexual function and mental health is still limited. AIM: Evaluate the mental health status and sexual functioning of women with MRKH syndrome after vaginoplasty surgery. METHODS: We enrolled 53 cases with MRKH syndrome who underwent artificial vaginoplasty. The participants were asked to participate in a two-round survey conducted between February 2021 during the covid-19 period and March 2023. The survey included questionnaires to measure depression, anxiety, self-esteem, and sexual functioning. Differences between scores over time were analysed using a paired sample t-test, and we assessed the correlation between mental health and sexual functioning. RESULTS: In the first round, patients' mean ± SD age at surgery was 23.6 ± 4.5 years old, and the mean ± SD time that had elapsed since surgery at the time of the survey was 34.2 ± 20.8 months. None of the patients reported low self-esteem, 45.3 % reported mild-to-moderate depression, and 34.0 % reported mild anxiety. Thirty patients have had vaginal intercourse during the last six months. The mean ± SD Female Sexual Functioning Index score was 24.6 ± 4.4, and 60.0 % had a score of 23.5 or higher, indicating high sexual functioning. The sexual functioning scores were positively correlated with self-esteem scores and negatively correlated with depression or anxiety scores (p < 0.05). There was no significant improvement in patient's mental health status and sexual function between the second round survey (71.3 ± 17.8 months after surgery) and the first round survey (p > 0.05). In contrast, the sexual arousal of FSFI were significantly higher in the second survey round (p < 0.05). CONCLUSION: Most patients undergoing vaginoplasty reported persisting mental health challenges. However, the majority reported good sexual functioning.

Impact of Personality Trait Interactions on Foraging and Growth in Native and Invasive Turtles.

Animal personalities play a crucial role in invasion dynamics. During the invasion process, the behavioral strategies of native species vary among personalities, just as the invasive species exhibit variations in behavior strategies across personalities. However, the impact of personality interactions between native species and invasive species on behavior and growth are rarely illustrated. The red-eared slider turtle (Trachemys scripta elegans) is one of the worst invasive species in the world, threatening the ecology and fitness of many freshwater turtles globally. The Chinese pond turtle (Mauremys reevesii) is one of the freshwater turtles most threatened by T. scripta elegans in China. In this study, we used T. scripta elegans and M. reevesii to investigate how the personality combinations of native and invasive turtles would impact the foraging strategy and growth of both species during the invasion process. We found that M. reevesii exhibited bolder and more exploratory personalities than T. scripta elegans. The foraging strategy of M. reevesii was mainly affected by the personality of T. scripta elegans, while the foraging strategy of T. scripta elegans was influenced by both their own personality and personalities of M. reevesii. Additionally, we did not find that the personality combination would affect the growth of either T. scripta elegans or M. reevesii. Differences in foraging strategy may be due to the dominance of invasive species and variations in the superficial exploration and thorough exploitation foraging strategies related to personalities. The lack of difference in growth may be due to the energy allocation trade-offs between personalities or be masked by the slow growth rate of turtles. Overall, our results reveal the mechanisms of personality interaction effects on the short-term foraging strategies of both native and invasive species during the invasion process. They provide empirical evidence to understand the effects of personality on invasion dynamics, which is beneficial for enhancing comprehension understanding of the personality effects on ecological interactions and invasion biology.

Factor structure and measurement invariance of the University Demand-Resource Questionnaire: further evidence from Hungarian university students.

Purpose: The present study aimed to further examine the factor structure and measurement invariance of the UDRQ among a sample of Hungarian university students. Methods: Firstly, the factor structure of the UDRQ was examined among 837 Hungarian university students. Specifically, two measurement models (first-order model and second-order model) were constructed and compared. Secondly, the internal consistency reliability of the UDRQ was examined. Thirdly, measurement invariance of the UDRQ was evaluated across genders. Finally, measurement invariance of the UDRQ was evaluated across two different samples. Results: It was found that the first-order model outperformed the second-order model and better represented the factor structure of the UDRQ subscales. Results of Cronbach's alpha and Composite Reliability suggested that the internal consistency reliabilities of the two UDRQ subscales were satisfactory. Measurement invariance analysis revealed that the UDRQ measurement model was strict invariant across genders and samples. Conclusion: The findings of the present study indicated that the UDRQ displayed satisfactory reliability and validity and could be used to assess demands and resources of Hungarian university students.

Prognostic value of centromere protein-A expression in patients with epithelial ovarian cancer.

Altered expression of centromere protein-A (CENP-A) is observed in various types of human cancers. However, the clinical significance and pathological role of CENP-A in epithelial ovarian cancer (EOC) remains unclear. The main objective of this investigation was to clarify the relationships between CENP-A expression and the clinicopathological features of patients with EOC. Real-time quantitative PCR and Western blot were performed to examine CENP-A expression in 20 pairs of fresh-frozen EOC tissues and corresponding noncancerous tissues. Using immunohistochemistry, we performed a retrospective study of the CENP-A expression levels on 120 archival EOC paraffin-embedded samples. Prognostic outcomes correlated with CENP-A were examined using Kaplan-Meier analysis and Cox proportional hazards model. Our results showed that the expression levels of CENP-A mRNA and protein in EOC tissues were both significantly higher than those in noncancerous tissues. By immunohistochemistry, the data revealed that high CENP-A expression was significantly correlated with pathological grade (P = 0.02) and International Federation of Gynecology and Obstetrics stage (P = 0.006). Consistent with these results, we found that high expression of CENP-A was significantly correlated with poor survival in EOC patients (P < 0.001). Furthermore, Cox regression analyses showed that CENP-A expression was an independent predictor of overall survival. Our data suggest that CENP-A could play an important role in EOC and might serve as a valuable prognostic marker and potential target for gene therapy in the treatment of EOC.