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A bifactor model with a general (p) factor reflecting shared variance and specific factors reflecting additional variance in individual symptoms has been introduced to explain common co-occurrence among anxiety, depression and schizotypy. However, longitudinal evidence is lacking and the validity of bifactor modeling is debatable. The current study aimed to examine the presence of the p factor together with specific factors in accounting for relationships between anxiety, depression and schizotypy both cross-sectionally and longitudinally, and to investigate the relationship between these factors and rumination. A validated sample of university students were surveyed on levels of anxiety, depression, schizotypy and rumination at baseline (N = 2291), one year (N = 1833) and two years (N = 1656). Models were estimated using exploratory structural equation modeling (ESEM) and compared at each time point. Longitudinal invariance of the best-fitting model was examined and all potential within- and between-factor stability pathways were tested in an SEM framework. A bifactor model with a p factor and four specific factors (representing residual information of composite anxiety and depression, cognitive-perceptual, interpersonal and disorganized schizotypy respectively) consistently outperformed a correlated-factors model. The bifactor structure appeared longitudinally stable. Within-factor stabilities were moderate, and between-factor pathways reflected a few significant interactions, mostly involving the p factor. Rumination was independently associated with p and four specific factors at each time point. Therefore, there is a p factor accounting for concurrent and sequential co-occurrence of anxiety, depression and schizotypy. Rumination explained partly the p and specific factors. Transdiagnostic interventions should target rumination.

Simple Summary There is limited information about genomic markers, especially for cervical adenocarcinoma treatment decisions. In this prospective study, it was found that nonsynonymous PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. It is the first indication of the predictive power of PIK3CA aberration in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for the prolonged strategy of surveillance and indicates the possibility of tailoring management of this particular women’s cancer. Abstract Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.

Endometrioid endometrial carcinoma (EEC) is one of the common causes of cancer-related mortality in women. Mounting evidences suggest that long noncoding RNAs (lncRNAs) function in multiple cancers. In this study, we discovered that HAND2-AS1, a lncRNA transcribed antisense adjacent to Heart and Neural Crest Derivatives Expressed 2 (HAND2) in chromosome 4q33-34, is significantly down-regulated in EEC. HAND2-AS1 and HAND2 were frequently down-regulated in EEC tissues, especially in poor differentiated tumor tissues. Down-regulation of HAND2-AS1 and HAND2 was correlated with tumor grade, lymph node metastasis and recurrence of EEC patients. HAND2-AS1 and HAND2 were co-downregulated by promoter DNA hypermethylation in EEC. Overexpression of HAND2-AS1 in EEC cells demonstrated that HAND2-AS1 suppressed migration and invasion of EEC cells. Similarly, overexpression of HAND2 also inhibited migration and invasion EEC cells indicating that HAND2-AS1 and HAND2 had a concordant role in the progression of EEC. However, HAND2 was not regulated by HAND2-AS1 in EEC. Furthermore, the anti-tumorigenic effect of HAND2-AS1 was mediated by down-regulating NMU, which has an oncogenic role in EEC. Our findings therefore provide the first evidence that HAND2-AS1 is a critical tumor suppressor in EEC.

Objectives To evaluate the morphological outcome of levator ani muscle (LAM) avulsion 3-5 years after a first delivery and to assess the effect of a second delivery on this condition. The impact of LAM avulsion on pelvic floor disorders was also studied. Methods Six hundred and sixty-six women who had been assessed for LAM avulsion 8 weeks after their first delivery were invited for a follow-up examination 3-5 years later. Women completed the Pelvic Floor Distress Inventory including the Urinary Distress Inventory (UDI) and Pelvic Organ Prolapse Distress Inventory (POPDI) questionnaires to explore symptoms of pelvic floor disorders, and the pelvic floor was examined using three-dimensional translabial ultrasound and assessed using the pelvic organ prolapse quantification system. Results Three hundred and ninety-nine women completed the study, of whom 151 were multiparous. Mean interval between first delivery and follow-up was 42.3 ± 7.6 months. Among 69 women who had LAM avulsion 8 weeks after their first delivery, nine (13.0%) had no LAM avulsion at follow-up. One (0.9%) woman had a new LAM avulsion after her second vaginal delivery. A greater proportion of women with LAM avulsion reported symptoms of stress urinary incontinence (SUI) (adjusted odds ratio, 2.09 (95% CI, 1.18-3.70); P = 0.01) and symptoms of prolapse than did women without avulsion; however, this difference did not reach statistical significance (P = 0.61). Women with LAM avulsion had higher UDI and POPDI scores than did women without avulsion (median UDI score, 17.7 (interquartile range (IQR), 5.0-32.4) vs 9.2 (IQR, 0.0-22.1); P = 0.045 and median POPDI score, 20.8 (IQR, 8.8-40.5) vs 10.7 (IQR, 0.0-32.8); P = 0.021). Conclusions The risk of developing new LAM avulsion after a second vaginal delivery is low (0.9%). Healing of LAM avulsion was observed in 13% of women who had at least one vaginal delivery. At 3-5 years after delivery, women with LAM avulsion reported symptoms of SUI more often than did those without, and had higher UDI and POPDI scores, implying more bothersome symptoms. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

This study aimed to determine the prevalence of urinary incontinence (UI), fecal incontinence (FI), and pelvic organ prolapse (POP) 3–5 years after the first pregnancy and their associated risk factors. We assessed 506 women using the Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire (PFIQ). Maternal characteristics and obstetric data were analyzed using descriptive analysis, independent sample t test, chi-squared test, and logistic regression. The prevalence of UI, FI, and POP, respectively, at a mean of 43 months after first delivery was 40.8, 6.6, and 10.2% following vaginal delivery (VD) and 22.7, 4.5, and 4.5% following cesarean section (CS). Stress urinary incontinence (SUI) was reported by more women following VD than CS (38.7 vs 22.4%, P = 0.010). Compared with 8 weeks’ postpartum, more women reported SUI at this later follow-up visit (40.1 vs 19.5%, P

Objective To evaluate the relationship between antenatal pelvic floor biometry and levator ani muscle (LAM) injury in Chinese women. Methods Three-dimensional transperineal ultrasound was performed in nulliparous Chinese women with a singleton pregnancy at 9–12 weeks, 26–28 weeks and 36–38 weeks of gestation and again at 12 months after delivery. Hiatal anteroposterior (AP) diameter, transverse diameter and area were measured on the antenatal ultrasound volumes obtained at rest, on Valsalva maneuver and during pelvic floor muscle contraction (PFMC). LAM injury was evaluated using ultrasound volumes obtained during PFMC at 12 months after delivery. Results In total, 328 women completed the study. At 12 months after delivery, 38 (14.8% of those who delivered vaginally) women had LAM injury; 28 were unilateral (14 right- and 14 left-sided) and 10 were bilateral. In all three trimesters there was smaller hiatal AP diameter and hiatal area in women with LAM injury when compared with women without injury. On multivariable analysis of the three factors, hiatal AP diameter at rest, hiatal area at rest and operative vaginal delivery, only hiatal AP diameter at rest in all three trimesters was an independent factor of LAM injury. A larger hiatal AP diameter at rest in the first, second and third trimesters reduced the likelihood of LAM injury with odds ratios of 0.21, 0.15 and 0.21, respectively. Conclusions A smaller antenatal hiatal AP diameter at rest is a risk factor for LAM injury. The hiatal AP diameter is relatively simple to measure and the error in measurement is relatively small. A prospective study to confirm this relationship and to explore whether this measurement, performed in the midsagittal plane, is repeatable should be performed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Background A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. Objectives To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. Study design Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. Results The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 μL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. Conclusions HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.

Introduction Mesh-related complications from reconstructive surgery for pelvic organ prolapse are of international concern. The present study aimed to review the incidence, management, and surgical outcomes of mesh-related complications in a Chinese population compared with existing studies involving Western populations. Methods This was an analysis of a prospectively collected cohort. Laparoscopic sacrocolpopexy, laparoscopic hystercolposacropexy, or transvaginal mesh surgery were offered with or without concomitant vaginal hysterectomy or continence surgery. Patients were followed up and mesh-related complications were noted. Results Overall, 276 Chinese women who received mesh surgery were included for data analysis. There were 22 mesh-related complications found during a mean follow-up period of 40 months. Mesh exposure accounted for 20 these complications; significantly more occurred after transvaginal than after abdominal mesh surgery (16 vs 4; P=0.01). Median duration from primary operation to the time of mesh exposure detection was 12 months (interquartile range=4.8-32.8 months). Ten patients required surgical excisions of exposed mesh. The re-operation rate after mesh complications was 6.7% (9/134) for transvaginal mesh surgery and 1.4% (2/142) for laparoscopic sacrocolpopexy (P=0.03). All excisions were performed transvaginally and 95% remained well after surgery. Occurrence of mesh exposure was higher in transvaginal mesh surgery (adjusted odds ratio=6.1; P=0.008), in sexually active patients (adjusted odds ratio=5.4; P=0.002), and in obese patients (adjusted odds ratio=3.7; P=0.046). Over 90% were satisfied with the outcome, regardless of mesh complications. Conclusions The rates of mesh exposure and re-operation were consistent with those reported in the literature, suggesting no significant differences in outcome between Chinese and Western patients for this type of surgery.

OBJECTIVE Ethnicity has been suggested to be a significant risk factor for pelvic organ prolapse (POP); yet, pelvic organ descent in different ethnic groups, especially in Asian populations, is not well studied. The aim of this study was to compare prolapse stages, pelvic organ descent and hiatal dimensions between East Asian and Caucasian women presenting with symptoms of POP. METHODS This was a prospective observational study of East Asian and Caucasian women presenting with symptoms of POP to a tertiary urogynecology clinic in, respectively, Hong Kong and Sydney. Demographic data, prolapse symptoms and prolapse stage were assessed. Physical examination was performed using the pelvic organ prolapse quantification (POP-Q) system. All women underwent transperineal ultrasound using Voluson systems. Offline analysis of four-dimensional ultrasound volume data was performed at a later date, by one operator blinded to all clinical data, to ascertain pelvic organ descent and hiatal dimensions on Valsalva maneuver. Levator muscle avulsion was assessed in volumes obtained on pelvic floor muscle contraction. Multiple logistic regression analysis was performed to assess factors associated with prolapse on clinical and ultrasound examinations. RESULTS A total of 225 East Asian women were included between July 2012 and February 2014 from the Hong Kong clinic and 206 Caucasian women between January 2015 and July 2016 from the Sydney clinic. There was no significant difference in the overall staging of prolapse. However, in East Asian women, compared with Caucasians, apical compartment prolapse was more common (99.6% vs 71.8%, P < 0.001) and posterior compartment prolapse less common (16.9% vs 48.5%, P < 0.001) on POP-Q examination. On Valsalva maneuver, the position of the uterus was lower in East Asian than in Caucasian women (-11.3 vs 1.35 mm, P < 0.001), while the rectal ampulla position was lower in Caucasians than in East Asians (-10.6 vs - 4.1 mm, P < 0.001). On multiple regression analysis, Caucasian ethnicity was a significant factor for lower risk of apical compartment prolapse on clinical assessment (odds ratio (OR), 0.01; P < 0.001) and on ultrasound (OR, 0.13; P < 0.001), and for a higher risk of posterior compartment prolapse on clinical assessment (OR, 4.36; P < 0.001) and of true rectocele on ultrasound (OR, 8.14; P < 0.001). CONCLUSIONS East Asian women present more commonly with uterine prolapse while Caucasians show more often posterior compartment prolapse. Ethnicity was a significant predictor of type of prolapse on multivariate analysis. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Objectives Levator ani muscle (LAM) injury is common after first vaginal delivery, and a higher incidence is associated with instrumental delivery. This study was conducted to compare the incidence of LAM injury after forceps or ventouse extraction in primiparous Chinese women, and to study their subsequent health-related quality of life. Methods This prospective observational study was conducted between 1 September 2011 and 31 May 2012 in a tertiary obstetric unit. All eligible primiparous women who had undergone instrumental delivery were recruited 1 to 3 days following delivery. The subjects completed the Pelvic Floor Distress Inventory questionnaire and Pelvic Floor Impact Questionnaire, and translabial ultrasound was performed 8 weeks' postpartum to determine whether the subjects had suffered LAM injury. Results Among the 289 women who completed the study, 247 (85.5%) had ventouse extraction and 42 (14.5%) had forceps delivery. Subsequent translabial ultrasound identified a total of 58 women with LAM injury. The prevalence of LAM injury after ventouse extraction and forceps delivery was 16.6% (95% CI, 12.0–21.2%) (41/247) and 40.5% (95% CI, 25.6–55.4%) (17/42), respectively (P = 0.001). Forceps delivery was identified as a risk factor for LAM injury, with an odds ratio of 3.54. No statistically significant differences were observed between the quality of life in women who underwent ventouse extraction and those with forceps delivery or between the quality of life in women with a unilateral or bilateral LAM injury. Conclusions In our cohort of primiparous Chinese women, 20.1% (58/289) had LAM injury after instrumental delivery, and forceps delivery was identified as the only risk factor. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Objective To compare the differences in levator ani muscle biometry and hiatal dimensions between pregnant nulliparous Caucasian and East Asian women. Methods Offline analysis of three/four-dimensional ultrasound volume data obtained from two groups of pregnant nulliparous women, Caucasian and East Asian, was performed. Volume acquisition was performed in the late third trimester using the same method in both groups, in the context of two prospective observational studies with identical entry criteria. Pelvic organ descent and levator hiatal dimensions were assessed using the volumes acquired on Valsalva maneuver, and pubovisceral muscle thickness was measured from the volumes obtained on pelvic floor muscle contraction (PFMC). Results Datasets of 200 East Asian and 168 Caucasian women were analyzed. Compared with Caucasian women, East Asian women had a significantly lower body mass index. All indices of pelvic organ descent were significantly higher in the Caucasian group than in the East Asian group. The difference, expressed as a percentage, in levator hiatal area on both Valsalva maneuver and PFMC was markedly greater in Caucasian (32% vs 19%; P < 0.001) than in East Asian (24% vs 20%; P = 0.01) women. After controlling for potential confounders using multivariate regression analysis, racial origin remained the only significant factor associated with differences in pelvic organ descent and hiatal dimensions. The thickness and area of pubovisceral muscle were significantly higher in the East Asian group. Conclusions Pregnant women of East Asian racial origin have a thicker pubovisceral muscle, smaller hiatus and less mobility of pelvic organs than do pregnant Caucasian women. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Objectives To identify clinical risk factors for dislodgment of vaginal pessary within one year in women with symptomatic pelvic organ prolapse. Study design This was a prospective observational study which recruited consecutive women with symptomatic pelvic organ prolapse in a tertiary urogynecology center. Basic demographics, clinical symptoms and staging of pelvic organ prolapse were assessed. A vaginal pessary was offered where appropriate. Main outcome measures Demographics and clinical parameters were compared between women who were able to use a vaginal pessary for one year and those whose pessaries were dislodged within one year. Results A total of 779 women were recruited and had a vaginal pessary inserted. Of them, 528 women, with a mean age of 64.7 (SD 10.1) years, returned for one-year follow-up; 177 (33.5%) had their pessary dislodged within one year and 351 (66.5%) had been able to retain the pessary. Stage III or IV prolapse (OR 1.76), prolapse predominant at the apical compartment (OR 2.14) and larger genital hiatus (OR 1.63) were factors associated with dislodgment of the vaginal pessary. Age, body mass index, previous hysterectomy and short vagina were not associated with dislodgment. Nevertheless, 47.6% of women with stage III/IV prolapse could still keep the pessary for one year. Conclusion Higher staging of prolapse, larger genital hiatus and apical compartment prolapse are clinical predictors for dislodgment of a vaginal pessary. Despite this, nearly half of women with stage III/IV prolapse were able to use a vaginal pessary for one year. Therefore, a vaginal pessary should be offered despite their staging of prolapse.

Introduction Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. Methods One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. Results PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size ( p PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival ( p Conclusions As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.

OBJECTIVE The aim of this study was to investigate whether the presence of levator ani muscle (LAM) avulsion is associated with expulsion within 1 year of a vaginal pessary placed for pelvic organ prolapse (POP). METHODS This was a prospective observational study of consecutive women with symptomatic POP, who had not received treatment for the condition before the consultation and opted for vaginal pessary placement in our center. Volume acquisition was performed before pessary insertion and offline analysis of the 3D/4D transperineal ultrasound volume data was performed. LAM was assessed on maximum pelvic floor muscle contraction (PFMC) and hiatal dimensions were assessed at rest, on PFMC and on maximum Valsalva. Results were compared between women in whom the pessary was retained for 1 year and those in whom the pessary was expelled within 1 year. RESULTS The datasets of 255 women were analyzed including 147 (57.6%) women who had a vaginal pessary continuously in place over 1 year and 108 (42.4%) with pessary expulsion. Mean age was 63.2 (SD, 9.9) years and median parity was 3 (2-4). Eighteen (7.1%) had Stage I, 164 (64.3%) Stage II, 67 (26.3%) Stage III and six (2.4%) Stage IV POP. Women with vaginal pessary expulsion within 1 year had significantly larger hiatal dimensions at rest and on Valsalva, larger hiatal area during rest, PFMC and Valsalva and higher rate of LAM avulsion (53.7% vs 27.2%, P

We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients' plasma: 60-64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.

Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

To compare pelvic floor symptoms, quality of life, and complications in women with symptomatic pelvic organ prolapse (POP) with or without vaginal pessaries in addition to those who do pelvic floor exercises for 12 months.This was a parallel-group, single-blind, randomized controlled trial with 12 months of follow-up. Women with symptomatic stage I to stage III POP were randomized to either pelvic floor exercises training (control group) or pelvic floor exercises training and insertion of a vaginal pessary (pessary group). The primary outcome was the change of prolapse symptoms and quality of life by using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaires. Secondary outcomes included bothersome of prolapse symptoms, desired treatment, and any complications.From December 2011 through November 2014, 311 women were screened and 276 were randomized as follows: 137 to the control and 139 to the pessary group. One hundred thirty-two (95.0%) women in the pessary group and 128 (93.4%) in the control group completed the study. The Pelvic Organ Prolapse Distress Inventory of Pelvic Floor Distress Inventory and the Pelvic Organ Prolapse Impact Questionnaire of Pelvic Floor Impact Questionnaire scores decreased in both groups after 12 months, but the mean score differences were higher in the pessary group (Pelvic Organ Prolapse Distress Inventory: -29.7 compared with -4.7, P.01; Pelvic Organ Prolapse Impact Questionnaire: -29.0 compared with 3.5, P.01). Complication rates were low and similar in both groups.We provided further evidence in nonsurgical treatment for POP. Prolapse symptoms and quality of life were improved in women using a vaginal pessary in addition to pelvic floor exercises.Centre for Clinical Research and Biostatistics-Clinical Trials Registry, https://www2.ccrb.cuhk.edu.hk/web/?page_id=746, ChiCTR-TRC-11001796.

Background Recurrent miscarriage affects 1% to 3% of women of reproductive age and mostly occurs before the 10th week of gestation (and around the same gestational week in subsequent miscarriages). After a miscarriage, the chances of having another miscarriage in a subsequent pregnancy varies. In some cases, recurrent miscarriages have an underlying cause (related to the mother or her baby) and specific treatments targeting these causes may be effective. However, in most cases the underlying causes may not be identified and recurrent miscarriage is unexplained. To date, there is no universally accepted treatment for unexplained recurrent miscarriage. Chinese herbal medicines have been widely used in Asian societies for millennia and have become a popular alternative to Western medicines in recent years. This systematic review evaluated the efficacy of Chinese herbal medicines for recurrent miscarriage. Objectives To assess the effectiveness and safety of Chinese herbal medicines for the treatment of unexplained recurrent miscarriage. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (01 June 2015), Embase (1980 to 01 June 2015); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 01 June 2015); Chinese Biomedical Database (CBM) (1978 to 01 June 2015); China Journal Net (CJN) (1915 to 01 June 2015); China Journals Full-text Database (1915 to 01 June 2015); and WanFang Database (Chinese Ministry of Science & Technology) (1980 to 01 June 2015). We also searched reference lists of relevant trials and reviews. We identified and contacted organisations, individual experts working in the field, and medicinal herb manufacturers. Selection criteria Randomised or quasi-randomised controlled trials, including cluster-randomised trials, with or without full text, comparing Chinese herbal medicines (alone or combined with other intervention or other pharmaceuticals) with placebo, no treatment, other intervention (including bed rest and psychological support), or other pharmaceuticals as treatments for unexplained recurrent miscarriage. Cross-over studies were not eligible for inclusion in this review. Data collection and analysis Two review authors independently assessed all the studies for inclusion in the review, assessed risk of bias and extracted the data. Data were checked for accuracy. Main results We included nine randomised clinical trials (involving 861 women). The trials compared Chinese herbal medicines (various formulations) either alone (one trial), or in combination with other pharmaceuticals (seven trials) versus other pharmaceuticals alone. One study compared Chinese herbal medicines and other pharmaceuticals versus psychotherapy. We did not identify any trials comparing Chinese herbal medicines with placebo or no treatment, including bed rest. Various Chinese herbal medicines were used in the different trials (and some of the classical the formulations were modified in the trials). The Western pharmaceutical medicines included tocolytic drugs such as salbutamol and magnesium sulphate; hormonal supplementation with human chorionic gonadotrophin (HCG), progesterone or dydrogesterone; and supportive supplements such as vitamin E, vitamin K and folic acid. Overall, the methodological quality of the included studies was poor with unclear risk of bias for nearly all the 'Risk of bias' domains assessed. Chinese herbal medicines alone versus other pharmaceuticals alone - the live birth rate was no different between the two groups (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.67 to 1.65; one trial, 80 women). No data were available for the outcome of pregnancy rate (continuation of pregnancy after 20 weeks of gestation). In contrast, the continuing pregnancy rate (RR 1.27 95% CI 1.10 to 1.48, two trials, 189 women) and live birth rate (average RR 1.55; 95% CI 1.14 to 2.10; six trials, 601 women, Tau² = 0.10; I² = 73%) were higher among the group of women who received a combination of Chinese herbal medicines and other pharmaceuticals when compared with women who received other pharmaceuticals alone. For Chinese herbal medicines and psychotherapy versus psychotherapy alone (one study) - there was a higher live birth rate (RR 1.32; 95% CI 1.07 to 1.64; one trial, 90 women) in the group of women who received a combination of Chinese herbal medicines and psychotherapy compared to those women who received psychotherapy alone. No data were available on the continuing pregnancy rate for this comparison. Other primary outcomes (maternal adverse effect and toxicity rate and the perinatal adverse effect and toxicity rate) were not reported in most of the included studies. Two trials (341 women) reported that no maternal adverse effects were found (one trial compared (combined) medicines with other pharmaceuticals, and one trial compared combined Chinese herbal medicine alone versus other pharmaceuticals). One trial (Chinese herbal medicine alone versus other pharmaceuticals alone) reported that there were no abnormal fetuses (ultrasound) or after delivery. There were no data reported for any of this review's secondary outcomes. Authors' conclusions We found limited evidence (from nine studies with small sample sizes and unclear risk of bias) to assess the effectiveness of Chinese herbal medicines for treating unexplained recurrent miscarriage; no data were available to assess the safety of the intervention for the mother or her baby. There were no data relating to any of this review's secondary outcomes. From the limited data we found, a combination of Chinese herbal medicines and other pharmaceuticals (mainly Western medicines) may be more effective than Western medicines alone in terms of the rate of continuing pregnancy and the rate of live births. However, the methodological quality of the included studies was generally poor. A comparison of Chinese herbal medicines alone versus placebo or no treatment (including bed rest) was not possible as no relevant trials were identified. More high-quality studies are needed to further evaluate the effectiveness and safety of Chinese herbal medicines for unexplained recurrent miscarriage. In addition to assessing the effect of Chinese herbal medicines on pregnancy rate and the rate of live births, future studies should also consider safety issues (adverse effects and toxicity for the mother and her baby) as well as the secondary outcomes listed in this review. This review would provide more valuable information if the included studies could overcome the problems in their designs, such as lacking of qualified placebo-controlled trials, applying adequate randomisation methods and avoiding potential bias.

OBJECTIVES To compare the 5-year subjective and objective outcomes of transobturator tension-free vaginal tape alone versus the same procedure with concomitant pelvic floor repair surgery for pelvic organ prolapse in women with urinary stress incontinence. DESIGN Prospective cohort study. SETTING Urogynaecology unit at a university hospital in Hong Kong. PATIENTS Of 218 women, 96 (44%) received transobturator tension-free vaginal tape alone and 122 (56%) received transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery from September 2004 to December 2009. The women were followed up annually for up to 5 years after the operation. MAIN OUTCOME MEASURES The 5-year subjective and objective cure rates were assessed. Subjective cure was defined as no urine loss during physical activity and objective cure was defined as no urine leakage on coughing during urodynamic study. RESULTS Overall, 88 women receiving transobturator tension-free vaginal tape alone and 101 women receiving transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery were followed up for 5 years after operation. The subjective and objective cure rates of the two groups were 70.5% versus 94.1% (P

Background Endometrioid endometrial carcinoma (EEC) is one of the common cause of cancer-related mortality in women. Despite progress in diagnostics and treatment of EEC, its prognosis remains poor. Mounting evidence suggest that long noncoding RNAs (lncRNAs) function in mutiple human cancers. Aberrant lncRNA expression may predict tumor outcome of patients and have served as diagnostic or prognostic markers. In this study, we investigated the expression levels and functions of lncRNAs in EEC. Methods Differentially expressed lncRNAs involved in EEC were identified by using publically available RNA-Seq data. The expression of 18 dysregulated lncRNA candidates was verified in 5 NE tissues, 5 EEC tissues and 5 EEC cell lines (HEC1-A, HEC1-B, AN3CA, KLE and RL95-2) by real-time polymerase chain reaction (PCR). Further, we selected the most misexpressed lncRNA and confirmed the expression level of the lncRNA in 59 EEC tissues and 24 NE tissues by real-time PCR and correlated the lncRNA expression levels with the clinical pathological characteristics. The promoter methylation assay was used to analyze the methylation level of the lncRNA in EEC. The lncRNA methylation status was confirmed by bisulfite genomic sequencing. Cell proliferation assays, wound healing assays, and invasion and migration assays were performed to determine the biological functions of the lncRNA in EEC cells. To discover the direct targets of the lncRNA in EEC, we performed RNA-sequence analysis in EEC cells overexpressed with the lncRNA and target genes were further studied by functional studies in vitro (knockdown assay and overexpression rescue assay). Results We discovered that HAND2-AS1, a lncRNA transcribed antisense adjacent to Heart and Neural Crest Derivatives Expressed 2 (HAND2), was significantly downregulated lncRNA in EEC. HAND2-AS1 and HAND2 was frequently downregulated in EEC tissues, especially in poor differentiated tumor tissues. Downregulation of HAND2-AS1 and HAND2 was correlated with tumor grade, lymph node metastasis and recurrence of EEC patients. HAND2-AS1 and HAND2 was co-downregulated by promoter hypermethylation in EEC. HAND2-AS1 suppressed EEC cell migration and invasion but not cell growth. Similarly, HAND2 also inhibited EEC cell migration and invasion indicating that HAND2-AS1 and HAND2 have a concordant role in the progression of EEC. Moreover, the anti-tumorigenic effect of HAND2-AS1 was mediated by downregulating NMU, which had an oncogenic role in EEC. Conclusions Our findings provide the first evidence that HAND2-AS1 is a critical tumor suppressor in EEC and may constitute a prognostic biomarker in EEC. Note: This abstract was not presented at the meeting. Citation Format: Xueying Yang, Yu Zhao, Kun Sun, Yuying Li, Jiajian Zhou, Jianzhang Wang, Hao Sun, Chi Chiu Wang, Joseph Kwong, Huating Wang, Tony Kwok Hung Chung. LncRNA HAND2-AS1 inactivates neuromedin U (NMU) and inhibits tumor invasion and metastasis in endometrioid endometrial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3448. doi:10.1158/1538-7445.AM2017-3448

Peritoneum is the commonest site for ovarian cancer metastasis. In peritoneum, stromal fibroblasts are the second most common cell types. In this study, we aimed to investigate the role of tumor-stromal interaction in peritoneal metastasis of ovarian cancer. Using three-dimensional (3D) organoid co-culture model, we found that the interaction between metastatic human ovarian cancer cells and normal human stromal fibroblasts promotes cancer colony formation. Using cytokine antibody array, we identified a group of cytokines are de novo produced in the 3D co-culture. Among them, transforming growth factor alpha (TGF-α) was produced anew from normal stromal fibroblasts in the 3D co-culture. In the co-culture, transcription of TGF-α in normal stromal fibroblasts is activated by tumor necrosis factor alpha (TNF-α) that derived by ovarian cancer cells. By epigenetic studies, we discovered that over-expression of TNF-α in human ovarian cancer cells is due to DNA hypomethylation and chromatin remodeling in TNF-α promoter. TGF-α is a ligand of epidermal growth factor receptor (EGFR), and we confirmed EGFR is over-expressed in a significant portion of human ovarian cancer. When applying EGFR-specific inhibitors (AG1478, Gefitini, and Erlotinib) in our 3D organoid models (3D mono-cultures and 3D co-cultures), we further found that the fibroblast-derived TGF-α promotes colony formation of metastatic ovarian cancer cells in vitro through EGFR activation. In fact, TGF-α activates Hippo/YAP signaling pathway in human ovarian cancer cells via EGFR. In addition, our in vivo experiments showed that normal stromal fibroblasts promote peritoneal metastasis of ovarian cancer through EGFR activation in a xenograft model. Finally, the TNFα-TGFα-EGFR interacting loop was detected in cancer-stroma-cancer compartments of omental metastases of ovarian cancer patients by immunohistochemistry. Based on our experimental results, we proposed a cancer-stroma-cancer interacting loop that promotes peritoneal metastasis of ovarian cancer through TNFα-TGFα-EGFR. The proposed mechanism involves: 1) TNF-α is over-expressed in human ovarian cancer cells by promoter DNA hypomethylation and chromatin remodeling; 2) the ovarian cancer cell-derived TNF-α induces de novo TGF-α production in normal human omental stromal fibroblasts; and 3) the fibroblast-derived TGF-α, in turn, promotes colony formation of metastatic ovarian cancer cells through EGFR-mediated Hippo/YAP signaling pathway. Our results thereby suggest that peritoneal metastasis in the ovarian cancer patients after cytoreductive surgery can be prevented by EGFR-targeted therapy. Citation Format: Tat-San Lau, Loucia Kit-Ying Chan, Chi-Hang Wong, Chi-Wai Man, Tak-Hong Cheung, So-Fan Yim, Jacqueline Ho-Sze Lee, Tony Kwok-Hung Chung, Joseph Kwong. A cancer-stroma-cancer interacting loop promotes peritoneal metastasis of ovarian cancer through TNFα-TGFα-EGFR. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1566.