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Per- and polyfluoroalkyl substances (PFAS) exposure is a potential risk factor for thyroid cancer and may be a contributor to the increasing thyroid cancer incidence rates. A systematic review and meta-analysis was performed to summarize all human studies to date investigating the association between PFAS exposure and thyroid cancer. A search of the National Library of Medicine and National Institutes of Health PubMed and Scopus databases was done to identify relevant articles published in English through January 2024. Studies reporting the association between PFAS exposure and thyroid cancer using odds ratios (OR) were included in the meta-analysis with summary estimate calculated using a random effects model (n=5). Perfluorooctanoic acid (PFOA) was the most investigated PFAS. Results of the included studies varied, ranging from significant positive to significant negative associations with thyroid cancer incidence for different PFAS. Meta-analyses of PFOA, Perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS) were not significant. This comprehensive review of the current literature highlights the limited knowledge and inconsistent results of this association. Large longitudinal cohort studies with varying time between sample collection and thyroid cancer diagnosis are needed to better understand the role of PFAS exposure on thyroid carcinogenesis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maaike van Gerwen reports financial support was provided by National Institutes of Health. Lauren Petrick reports financial support was provided by National Institutes of Health. Angela Leung reports a relationship with United States Environmental Protection Agency that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mesenchymal stem cells (MSCs) are one of the few stem cell types used in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair, due to their unique paracrine capacity, multiple differentiation potential, active components in exosomes, and effective mitochondria donation. At present, MSCs derived from tissues such as bone marrow and umbilical cord are widely applied in preclinical and clinical studies. Nevertheless, there remain challenges to the maintenance of consistently good quality MSCs derived from different donors or tissues, directly impacting their application as advanced therapy products. In this review, we discuss the promises, problems, and prospects associated with translation of MSC research into a pharmaceutical product. We review the hurdles encountered in translation of MSCs and MSC-exosomes from the research bench to an advanced therapy product compliant with good manufacturing practice (GMP). These difficulties include how to set up GMP-compliant protocols, what factors affect raw material selection, cell expansion to product formulation, establishment of quality control (QC) parameters, and quality assurance to comply with GMP standards. To avoid human error and reduce the risk of contamination, an automatic, closed system that allows real-time monitoring of QC should be considered. We also highlight potential advantages of pluripotent stem cells as an alternative source for MSC and exosomes generation and manufacture., (© 2023 Wiley Periodicals LLC.)

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.

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., (Copyright © 2019. Published by Elsevier B.V.)

Introduction and Hypothesis: Levator ani muscle (LAM) avulsion is associated with pelvic organ prolapse (POP). There is limited information on the prevalence of LAM avulsion in Chinese women with POP. This study evaluated the prevalence of LAM avulsion in women presenting with POP and the effects on their quality of life (QoL)., Methods: This prospective study was conducted in a tertiary urogynecology center. Chinese women presenting with POP were recruited and completed standardized questionnaires exploring their symptoms and QoL and underwent gynecological examination to assess the stage of POP and involved compartments. Four-dimensional translabial ultrasound (US) was performed on all women, and evaluation of LAM avulsion was done offline., Results: Three hundred and ninety-eight women completed the study. The prevalence of LAM avulsion was 38.9% [95% confidence interval (CI) 34.1-43.7%]; 31 (7.8%), 26 (6.5%), and 98 (24.6%) had left, right, and bilateral LAM avulsion, respectively. LAM avulsion was associated with a more advanced stage of prolapse (P < 0.005) and prolapse of stage ≥II of all three compartments. Bilateral LAM avulsion was associated with a more severe stage of prolapse. More women with LAM avulsion reported bothersome symptoms of prolapse and had higher Pelvic Organ Prolapse Distress Inventory (POPDI) and Urinary Incontinence Questionnaire (UIQ) scores, implying more impairment in QoL. However, after multivariate linear regression analysis, POP stage remained a significant predictor of POPDI and UDI scores (P ≤ 0.006); LAM avulsion was not a predictor (P = 0.2 and 0.27, respectively)., Conclusions: LAM avulsion was detected in 39% of Chinese women with POP. It was associated with a more advanced POP stage, and these women had more impairment of QoL. However, LAM avulsion was not an independent factor influencing the QoL of these women.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: This study was conducted to explore chromosomal copy number variations (CNV) and transcript expression and to examine pathways in cervical pathogenesis using genome-wide high resolution microarrays., Methods: Genome-wide chromosomal CNVs were investigated in 6 cervical cancer cell lines by Human Genome CGH Microarray Kit (4x44K). Gene expression profiles in cervical cancer cell lines, primary cervical carcinoma and normal cervical epithelium tissues were also studied using the Whole Human Genome Microarray Kit (4x44K)., Results: Fifty common chromosomal CNVs were identified in the cervical cancer cell lines. Correlation analysis revealed that gene up-regulation or down-regulation is significantly correlated with genomic amplification ( P =0.009) or deletion ( P =0.006) events. Expression profiles were identified through cluster analysis. Gene annotation analysis pinpointed cell cycle pathways was significantly ( P =1.15E-08) affected in cervical cancer. Common CNVs were associated with cervical cancer., Conclusion: Chromosomal CNVs may contribute to their transcript expression in cervical cancer., Competing Interests: CONFLICTS OF INTEREST None of the authors of this manuscript report conflicts of interest regarding the performance of this study or its publication.

Introduction and Hypothesis: 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., Methods: 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., Results: 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 < 0.001), but fewer reported FI. More women who had an instrumental delivery reported symptoms of POP compared with those who had a normal VD. Higher body weight and weight gain from first trimester were risk factors of SUI [odds ratio (OR) 1.03] and urge urinary incontinence (UUI) (OR 1.18), respectively. Women who delivered vaginally had higher PFDI subscales scores., Conclusions: VD increased UI risk. Higher body weight and weight gain from first trimester were risk factors for SUI and UUI, respectively. More women reported symptoms of POP following an instrumental delivery than those who had a normal VD.

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<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05)., 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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., Clinical Trial Registration: Centre for Clinical Research and Biostatistics-Clinical Trials Registry, https://www2.ccrb.cuhk.edu.hk/web/?page&#95;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). Although most pregnant women may not recognise a miscarriage until uterine bleeding and cramping occur, a repeat miscarriage after one or more pregnancy loss and the chance of having a successful pregnancy varies. 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. Many clinical studies have reported that Chinese herbal medicines can improve pregnancy outcomes for pregnant women who had previously suffered recurrent miscarriage. 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.

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., (© 2015 UICC.)

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<0.01) and 80.3% versus 85.7% (P=0.58), respectively., Conclusions: Transobturator tension-free vaginal tape is an effective treatment for urinary stress incontinence in women who received it alone or with concomitant pelvic floor repair surgery for pelvic organ prolapse, providing high subjective and objective efficacy for up to 5 years after operation. Transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery achieved similar, if not better, long-term outcome compared with transobturator tension-free vaginal tape alone.

Background: Fatigue is common in stroke survivors. Lesion location may influence the risk of poststroke fatigue (PSF) but it is uncertain whether location has an impact on the prognosis of PSF. This study examined the association between PSF outcome and infarct location., Methods: The study sample comprised 435 Chinese patients with acute ischemic stroke admitted to the acute stroke unit of a university affiliated regional hospital in Hong Kong. Three and fifteen months after the onset of the index stroke a research assistant administered the Fatigue Severity Scale (FSS). PSF was defined as a FSS score of 4.0 or above. Of the 139 patients with PSF three months poststroke, 97 (69.8%) attended the 15-month follow-up, when 50 (51.5%) patients still had PSF ('non-remitters') and 47 (48.5%) did not report fatigue ('remitters'). The presence and location of infarcts were evaluated with magnetic resonance imaging., Results: In comparison with the remitters, the non-remitters were more likely to have subcortical white matter infarcts (40.0% vs 21.3%, p = 0.046). These infarcts remained an independent predictor of non-remission of PSF in the multivariate analysis, with an odds ratio of 4.208 (p = 0.011)., Conclusions: The results suggest that subcortical white matter infarcts may influence the outcome of PSF. Further investigations are needed to explore whether infarcts have any impact on the response of PSF to pharmacological or psychological interventions.

Introduction and Hypothesis: To evaluate the effect of levator ani muscle (LAM) injury on pelvic floor disorders and health-related quality of life in Chinese primiparous women during the first year after delivery., Methods: At 8 weeks and 12 months after delivery, 328 women were assessed for symptoms of pelvic floor disorders and quality of life using the standardised questionnaire, POP-Q; and translabial ultrasound to detect LAM injury. Descriptive analysis, independent sample t test, non-parametric testing, Chi-squared test and two-sided Fisher's exact test were used., Results: At 8 weeks after delivery, 48 (19.0% [95% CI, 14.2-23.8%]) women with vaginal delivery had LAM injury; 38 women (79.2%) had persistent LAM injury at 12 months. At 8 weeks, LAM injury was associated with prolapse symptoms, descent at Pelvic Organ Prolapse Quantification (POP-Q) Aa and Ba points and a higher Pelvic Organ Prolapse Distress Inventory (POPDI) general and Urinary Distress Inventory (UDI) Obstructive subscale score. At 12 months, it was not associated with prolapse symptoms, Pelvic Floor Distress Inventory (PFDI) or Pelvic Floor Impact Questionnaire (PFIQ). There was also no association between stress urinary incontinence (SUI), urge urinary incontinence (UUI), mixed urinary incontinence (UI), faecal incontinence (FI) with LAM injury at both time points., Conclusions: Seventy-nine per cent of women who had LAM injury at 8 weeks after vaginal delivery had persistent LAM injury at 12 months. LAM injury was associated with prolapse symptoms, lower POP-Q Aa and Ba points at 8 weeks after delivery and a higher POPDI general and UDI Obstructive subscale scoring. However, we are not able to confirm the association between LAM injury and SUI, UUI, mixed UI, FI at 8 weeks or 12 months after delivery; or prolapse symptoms, PFDI or PFIQ scores at 12 months after delivery.

Objective: To investigate the effects of 4-month treatment of medroxyprogesterone acetate (MPA) and Diane-35 on the clinical and biochemical features of hyperandrogenism and quality of life of adolescent girls with polycystic ovarian syndrome (PCOS)., Design: A prospective, randomized, cross-over study., Setting: An accredited pediatric and adolescent gynecology clinic of a university-affiliated tertiary hospital., Participants: 76 adolescents girls aged 14 to 19 years old with PCOS were recruited from July 2007 to July 2010., Interventions: Girls were randomized into 2 groups. Group 1 received oral MPA for 4 months, followed by a washout period of 4 months, and then Diane-35 for another 4 months. Group 2 received the same combination but in the reverse order., Main Outcome Measures: Clinical and biochemical features of hyperandrogenism and quality of life were assessed., Results: There was no significant difference between the 2 groups at baseline. No significant difference was found in the clinical and biochemical parameters of hyperandrogenism before and after treatment with MPA. Significant reduction of the acne score, LH/FSH ratio, and testosterone level was seen after taking Diane-35. Hirsutism was also improved but it did not reach statistical significant. When comparing post-MPA and post-Diane-35, the post-Diane-35 group had significantly improved acne score and LH/FSH ratio. No significant difference was found on quality of life between both groups after treatment., Conclusion: Diane-35 may be a more suitable treatment option in adolescent girls diagnosed with PCOS when compared to MPA., (Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Each year, ∼25 000 women are newly diagnosed with ovarian cancer in the USA. The vast majority (>90%) of cases are of epithelial origin. This highly lethal cancer carries a mortality rate of >50% and a high risk of recurrence after conventional, first-line chemotherapy. Müllerian-inhibiting substance (MIS) is a gonadal hormone that causes regression of the Müllerian ducts. A series of studies have demonstrated that MIS also has multiple extra-Müllerian functions including inhibition of epithelial ovarian cancer cells in vitro and in vivo. Accumulating evidence has shown that many human cancers are organized hierarchically and contain a small population of cancer stem cells (CSCs) that are inherently resistant to common chemotherapy and radiation therapy. The effect of MIS on ovarian CSC seems to be particularly useful in rescuing ovarian cancer patients with resistance to conventional treatment. Based on recent studies evaluating MIS, this review updates our current understanding of the molecular genetic aspects of MIS, its pathophysiology, as well as its potential to treat chemoresistant epithelial ovarian cancer.

During recent decades there have been remarkable advances in biology, in which one of the most important discoveries is RNA interference (RNAi). RNAi is a specific post-transcriptional regulatory pathway that can result in silencing gene functions. Efforts have been done to translate this new discovery into clinical applications for disease treatment. However, technical difficulties restrict the development of RNAi, including stability, off-target effects, immunostimulation and delivery problems. Researchers have attempted to surmount these barriers and improve the bioavailability and safety of RNAi-based therapeutics by optimizing the chemistry and structure of these molecules. This paper aimed to describe the principles of RNA interference, review the therapeutic potential in various diseases and discuss the new strategies for in vivo delivery of RNAi to overcome the challenges., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To compare the 1-year and 5-year outcomes of transobturator tension-free vaginal tape with outside-in and inside-out approaches in women with urinary stress incontinence, and to identify risk factors for treatment failure at 5 years., Method: A prospective observational study was carried out for women with urinary stress incontinence who underwent transobturator tension-free vaginal tape from September 2004 to March 2008 in a tertiary urogynecology center. Women (n = 213) had either an outside-in (n = 124) or inside-out (n = 89) procedure. They were followed up annually until 5 years after the operation. Subjective cure was defined as women not experiencing any urine loss on physical activity. Objective cure was defined as no urine leak at cough during a standard urodynamic study., Results: At a mean follow up of 59.2 months, the subjective cure rates were 81.7% and 84.1%; the objective cure rate were 82.6% and 82.5% for the outside-in and inside-out approach, respectively. There was no statistically significant difference between the procedures. De novo overactive bladder syndrome (10.6% in outside-in and 14.6% in inside-out approach; P = 0.40) and de novo detrusor overactivity (5.8% in outside-in and 15% in inside-out approach; P = 0.11) was also comparable between the two groups. Complications at the fifth year were low and not significantly different among both methods., Conclusion: The outside-in approach and inside-out approach are both safe and effective in treating women with urinary stress incontinence up to 5 years., (© 2013 The Japanese Urological Association.)

We have investigated the role of cytokine lymphotoxin in tumour-stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other hand, our co-culture studies demonstrated that the cancer cell-derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF-κB signalling. Amongst the chemokines being produced, we found that fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer., (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background. Miscarriage is a very common complication during early pregnancy. So far, clinical therapies have limitation in preventing the early pregnancy loss. Chinese Medicine, regarded as gentle, effective, and safe, has become popular and common as a complementary and alternative treatment for miscarriages. However, the evidence to support its therapeutic efficacy and safety is still very limited. Objectives and Methods. To summarize the clinical application of Chinese Medicine for pregnancy and provide scientific evidence on the efficacy and safety of Chinese medicines for miscarriage, we located all the relevant pieces of literature on the clinical applications of Chinese Medicine for miscarriage and worked out this systematic review. Results. 339,792 pieces of literature were identified, but no placebo was included and only few studies were selected for systematic review and conducted for meta-analysis. A combination of Chinese medicines and Western medicines was more effective than Chinese medicines alone. No specific safety problem was reported, but potential adverse events by certain medicines were identified. Conclusions. Studies vary considerably in design, interventions, and outcome measures; therefore conclusive results remain elusive. Large scales of randomized controlled trials and more scientific evidences are still necessary to confirm the efficacy and safety of Chinese medicines during early pregnancy.

Objective: To assess perioperative and short-term outcomes after tension-free vaginal mesh repair of pelvic organ prolapse in local Chinese women., Design: Case series., Setting: The urogynaecology unit of a university teaching hospital in Hong Kong., Patients: All women with stage III or more pelvic organ prolapse who underwent tension-free vaginal mesh repair with or without vaginal hysterectomy from May 2007 to June 2011., Main Outcome Measures: Perioperative and short-term outcomes., Results: In all, 47 women underwent the procedure during the study period. The mean operating time was 94 minutes, the mean estimated blood loss was 163 mL, and the mean hospital stay was 4 days. Four patients had visceral injuries, all of which were identified and repaired during the operation; all four patients recovered uneventfully. The mean duration of follow-up was 25 (standard deviation, 13) months. Pelvic organ prolapse quantification improved significantly; nine (19%) of the patients had recurrent stage II prolapse but only one was symptomatic, six (13%) had postoperative mesh exposure, three of whom underwent mesh excision. There were five (11%) who had de-novo urodynamic stress incontinence, which was mostly mild and managed conservatively. Overall 91% (43/47) were satisfied with their operative outcome., Conclusions: The success rate of tension-free vaginal mesh repair for the treatment of pelvic organ prolapse in local Chinese women was comparable to rates reported internationally. There was a high degree of subjective satisfaction with the procedure. There were low rates of mesh exposure and de-novo stress incontinence that was mostly asymptomatic or mild.

Introduction and Hypothesis: This study evaluated factors and their prevalence associated with urinary (UI) and fecal (FI) incontinence during and after a woman's first pregnancy., Methods: Nulliparous Chinese women with no UI or FI before pregnancy were studied with a standardized questionnaire for UI and FI from early pregnancy until 12 months after childbirth. Maternal characteristics and obstetric data were analyzed using descriptive analysis, independent sample t test, chi-square test, and logistic regression., Results: Three hundred and twenty-eight (74.2 %) women completed the study. The prevalence of antenatal UI increased with gestation. Overall, 192 (58.5 %), 60 (18.3 %), and 76 (23.1 %) had normal vaginal delivery, instrumental delivery, and cesarean section, respectively. Twelve months after delivery, prevalence of stress urinary incontinence (SUI) and urge urinary incontinence (UUI) was 25.9 % [95 % confidence interval (CI) 21.5-30.6] and 8.2 % (95 % CI 5.2-11.2), respectively. In those who delivered vaginally, the prevalence was 29.7 % and 9.1 %, respectively. Prevalence of FI was 4.0 % (95 % CI 1.9-6.1). On logistic regression, vaginal delivery [odds ratio (OR) 3.6], antenatal SUI (OR 2.8), and UUI (OR 2.4) were associated with SUI. Antenatal UUI (OR 6.4) and increasing maternal body mass index (BMI) at the first trimester (OR 1.2) were associated with UUI. Antenatal FI was associated with FI (OR 6.1)., Conclusions: The prevalence of SUI, UUI, and FI were 25.9 %, 8.2 %, and 4.0 %, respectively, 12 months after delivery. Vaginal delivery, antenatal SUI, and UUI were associated with SUI; antenatal UUI and increasing maternal BMI at the first trimester were associated with UUI. Antenatal FI was associated with FI. Pregnancy, regardless of route of delivery and obstetric practice, had an effect on UI and FI.

Background: Women suffering from urinary incontinence have impaired quality of life (QoL). Pelvic floor muscle training (PFMT) has been recommended to be the first-line treatment for them., Aims: This study evaluated the role of (PFMT) in women with urinary incontinence., Materials and Methods: All women suffering from urinary incontinence without pelvic organ prolapse who attended the urogynaecology unit of a university hospital from January 2009 to June 2010 were recruited. Urinary symptoms and impact on QoL were assessed using the Chinese validated Urogenital Distress Inventory short form (UDI-6) and Incontinence Impact Questionnaire short form (IIQ-7) before and after PFMT. Urodynamic studies (UDS) were used to differentiate the diagnoses of urinary incontinence., Results: Three hundred and seventy-two women, aged 52.3 ± 10.8 years and practised PFMT for 9.9 ± 7.3 months, completed the study. Over 65% recorded improvement in both UDI-6 and IIQ-7. Stratified for urodynamic diagnosis, stress incontinence group and those who had no UDS abnormality had significant improvement in their urinary symptoms and QoL after PFMT. UDI-6 and IIQ-7 also improved significantly after PFMT in groups where the clinical presentation was stress incontinence, overactive bladder symptoms or mixed urinary incontinence. Age was not associated with a significant difference in the response to PFMT., Conclusions: Pelvic floor muscle training appears to be an effective first-line intervention for improving urinary symptoms and QoL of women presenting with urinary incontinence. Future studies on long-term effectiveness and cost-effectiveness are also required., (© 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: The purposes of this study were to identify aberrantly expressed miRNAs and investigate their pathogenic roles in cervical cancer., Methods: miRNA expression was assessed in cervical cancer cell lines, micro-dissected normal cervical epithelium cells and primary cervical carcinoma by TaqMan RT-PCR. Spatial expression of miR-182 in cervical carcinoma and normal cervix was explored by in situ hybridization. HeLa xenograft mice model was used for evaluation of the effect on tumor growth of miR-182 inhibitor. Western blot, flow cytometry and gene expression analysis were used for identification of the functional role of miR-182 in HeLa cells., Results: Two up-regulated (miR-182 and -183) and nine down-regulated (miR-211, 145, 223, 150, 142-5p, 328, 195, 199b, 142-3p) microRNAs were consistently identified in cervical cancer cell lines. Further investigation confirmed the most up-regulated miRNA (miR-182) was significantly elevated in primary cervical carcinoma and discovered a significant correlation between the increased expression of miR-182 and advanced stages of cervical cancer. In HeLa xenograft mouse model, we demonstrated that inhibition of the miR-182 could exert the effect of tumor growth regression. Western blot, flow cytometry and pathway analysis for the HeLa cells with miR-182 over/down-expression in vitro showed that miR-182 was involved in apoptosis and cell cycle pathways, it also associated with the regulation of FOXO1., Conclusions: Our findings indicated that miR-182 plays an onco-miRNA role in cervical cancer and its alteration is associated with cervical cancer pathogenesis by disrupting cell proliferation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: To evaluate the risk of missing a malignancy in surgical specimens following hysterectomy for uterine prolapse if routine pathological examination is not performed. Additionally, information on the risk of missing an hitherto unsuspected malignancy if uterine preservation is the preferred management option will be provided., Materials and Methods: A retrospective study was performed on all cases of surgery performed for uterine prolapse in a tertiary referral institution from 2003 to 2011. Those with confirmed malignancy before operation were excluded. The study subjects had their clinical history, investigations, the type of operations and histopathology report analysed. They were classified into symptomatic or asymptomatic, depending on whether they reported symptoms that were suggestive of uterine malignancy., Results: A total of 640 women were studied. Three cases of hitherto unsuspected uterine malignancy were found, giving an incidence of 0.47%. Among the 456 asymptomatic women, both pre- and postmenopausal, the risk of incidental malignancy was 0.22%. Within the postmenopausal group, risk of incidental malignancy was 0.26%. Another 3 cases of uterine premalignant conditions were identified, giving an overall risk of premalignant and malignant uterine condition of 0.94%. Five cases of cervical intra-epithelial neoplasia were found, contributing to a risk of 0.78%., Conclusions: The risk of missing an uterine malignancy in patients with uterine prolapse is low if appropriate investigations are carried out prior to surgery. If hysterectomy is to be performed, we recommend that all surgical specimens be subjected to histopathological examination., (© 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: The management of first-trimester miscarriage has been studied extensively in recent years. However, relatively little attention has been focussed on woman's satisfaction and psychological impact from different treatment modalities., Aim: To investigate the clinical and psychological outcomes of surgical, medical and expectant management of first-trimester miscarriage., Materials and Methods: A prospective randomised controlled trial of 180 women suffering miscarriage managed by either surgical evacuation, medical evacuation or expectant management was conducted in a university-affiliated, tertiary referral hospital. The complete miscarriage rate, clinical symptomatology, complications, women's satisfaction and the psychological impact were evaluated., Results: Women in surgical evacuation (98.1%) had a significantly higher complete miscarriage rate when compared with medical evacuation (70%) and expectant management (79.3%). Women who had surgical evacuation had significantly shorter duration of vaginal bleeding, but higher rate of infection. Women who had medical evacuation had significantly more gastrointestinal symptoms. Despite differences in efficacy and complication profile, there was no significant difference in satisfaction among groups. There were no significant differences in terms of psychological well-being, depression scores, anxiety level, fatigue symptoms as measured in General Health Questionnaire-12, Beck Depression Inventory, Spielberger's State Anxiety Inventory and fatigue scale at treatment and four weeks after treatment. However, women with active intervention had greater post-traumatic stress symptoms as measured in Chinese version of Impact of Event Scale-Revised at the time of treatment when compared with women in expectant management., Conclusion: Without substantial differences in the clinical and psychological impact between different treatment modalities, a more conservative approach with expectant management for miscarriage may be an option for women., (© 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Introduction and Hypothesis: This study evaluated the responsiveness and minimal important differences (MID) of the Chinese Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ) in women undergoing urodynamic stress incontinence (USI) and/or pelvic organ prolapse (POP) treatment., Methods: One hundred and fifty-six women were assessed using the PFDI and PFIQ before and after they received continence surgery and or pelvic floor repair (PFR) surgery, or vaginal pessary. Symptom severity was recorded using a visual analog scale (VAS) before and after treatment as was rating of their satisfaction with the treatment they received. Responsiveness of the PFDI and PFIQ were evaluated by effect sizes, standardized response mean, paired samples t test or Wilcoxon Signed Rank Test. MID in the PFDI and PFIQ for different treatments were determined by satisfaction rating, change in VAS scoring, and distribution-based methods., Results: There were significant improvements in the respective subscales of PFDI and PFIQ, demonstrating moderate to great responsiveness after different treatments. The estimation of MID for the Urinary Distress Inventory (UDI) was -30 to -14 and the Urinary Impact Questionnaire (UIQ) was -28 to -14 for women who underwent continence surgery. The MID for the Pelvic Organ Prolapse Distress Inventory (POPDI) was -44 to -21, the Pelvic Organ Prolapse Impact Questionnaire (POPIQ) -40 to -27, the UDI -22 to -16, the UIQ -37 to -31, the Colo-Rectal-Anal Distress Inventory (CRADI) -37 to -14, and the Colo-Rectal-Anal Impact Questionnaire (CRAIQ) -34 to -6 for women who underwent PFR surgery; and estimation of MID for the POPDI was -16, the POPIQ -29, the UDI -28, the UIQ -17, the CRADI -25, and the CRAIQ -31 for women who received a vaginal pessary. The MID of the respective subscales were supported by the distribution-based methods., Conclusions: The Chinese PFDI and PFIQ instruments are responsive to change in women undergoing continence surgery, PFR surgery or vaginal pessary for USI or POP.

Objective: This study is a phase II clinical trial that aims to investigate the dose-response relationship of a Chinese herbal medicine preparation, Dang Gui Buxue Tang (DBT), with short-term menopausal symptoms and quality of life in local postmenopausal women., Methods: A randomized, double-blind, multiple-dose escalation trial was performed in 60 postmenopausal women experiencing severe hot flashes and night sweats. The participants were randomized to receive DBT preparations at 1.5, 3.0, or 6.0 g/day for 12 weeks. The primary outcomes were vasomotor symptoms, Greene Climacteric Scale (GCS) score, and Menopause-Specific Quality of Life (MENQOL) score. Secondary outcomes included serum hormones and lipids., Results: There were between-group differences in psychological/psychosocial (P = 0.015, GCS; P = 0.013, MENQOL) and somatic/physical (P = 0.019, GCS; P = 0.037, MENQOL) domains, and improvement was significantly greatest (P < 0.05) in the 6.0 g/day dose group. The frequency and severity of hot flashes and night sweats were significantly reduced in the 3.0 g/day (14.5%-21.2%, P < 0.05, hot flashes; 28.6%-39.6%, P < 0.05, night sweats) and 6.0 g/day (34.9%-37.4.0%, P < 0.01, hot flashes; 10.1%-12.8%, P < 0.01, night sweats) dose groups. The female hormones follicle-stimulating hormone, luteinizing hormone, and 17β-estradiol, as well as the lipids total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, were not significantly different within groups and between groups., Conclusions: DBT preparations at 6.0 g/day significantly improve physical and psychological scores and significantly reduce vasomotor symptoms from baseline. The treatment was well tolerated, with no serious adverse events noted during the 12-week intervention period. The changes do not affect hormones and lipid profiles.

Grief following miscarriage is a complex psychological response. This study was conducted to examine the psychometric properties of the Chinese version of the Perinatal Grief Scale (PGS). A total of 280 Chinese women completed the PGS immediately following a diagnosis of miscarriage (baseline) and were reassessed at 12 months follow-up. The factor structure of the Chinese PGS was explored. The convergent validity of the PGS was established by examining its correlations with the General Health Questionnaire-12 and Beck Depression Inventory at baseline. The reliability of the Chinese PGS was satisfactory. A two-factor structure accounting for 45% of the variance was identified. The Chinese PGS was positively correlated with General Health Questionnaire-12 and Beck Depression Inventory scores. The Chinese PGS was found to be a reliable and valid tool to measure grief following miscarriage.

Introduction and Hypothesis: We performed an investigation of symptoms, quality of life (QOL), and factors affecting women's treatment choice of pelvic organ prolapse (POP)., Methods: Three hundred and eight women presenting with POP were assessed by Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), Short Form-36 (SF-36), Pelvic Organ Prolapse Quantification (POP-Q) system, and urodynamic studies. Treatment was arranged according to each woman's preference after counseling. Factors affecting treatment choice were evaluated. Descriptive statistics, chi-square or Fisher exact test, analysis of variance (ANOVA) test, and logistic regression analysis were used., Results: Patients had high prevalence of urinary, prolapse, and bowel symptoms. Their QOL was impaired, with Urinary Impact Questionnaire (UIQ) higher than the Pelvic Organ Prolapse Impact Questionnaire (POPIQ) score and lower SF-36 score compared with the population norm. Logistic regression analysis indicated that complication from vaginal pessary, urodynamic stress incontinence (USI), stage of prolapse, and Pelvic Organ Prolapse Distress Inventory (POPDI) scoring were factors for choosing surgical treatment., Conclusions: Women with POP had great symptomatic distress and impaired QOL. Complication from vaginal pessary, USI, stage of prolapse, and POPDI scores were factors increasing the likelihood of the patient choosing surgical treatment.

MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.

Objectives: To evaluate the quality of life in women with urinary incontinence (categorised by urodynamic findings)., Design: Prospective cohort study on patients., Setting: Urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS. Female patients presenting to our clinic from July 2008 to December 2009 and having their urinary incontinence categorised by urodynamic study., Main Outcome Measures: Patient's quality of life was assessed using the Medical Outcomes Study Short Form, Urogenital Distress Inventory Short Form, and Incontinence Impact Questionnaire Short Form. Their quality of life was compared according to their urodynamic category and a subgroup analysis was performed on patients having continence surgery for urodynamic stress incontinence., Results: Among the 223 women studied, 46% had urodynamic stress incontinence, 18% had detrusor overactivity, 2% had both urodynamic stress incontinence and detrusor overactivity, and 34% had no urodynamic abnormality. In all, the Medical Outcomes Study Short Form scoring was lower than normal local population. The Medical Outcomes Study Short Form score in detrusor overactivity group was significantly lower than urodynamic stress incontinence group in vitality and mental health domains. Detrusor overactivity group also had higher scores in Incontinence Impact Questionnaire Short Form in travel, social and emotional health subscales and total score (46.3 vs 29.1; P<0.01). Women with urodynamic stress incontinence and required continence surgery had higher scores in Incontinence Impact Questionnaire Short Form., Conclusion: Women with urinary incontinence had impaired quality of life and it was comparable to other chronic medical diseases. Women with detrusor overactivity have more impaired quality of life than women with urodynamic stress incontinence. Severity of urodynamic stress incontinence did not correlate with quality of life. Women who opted for continence surgery had poorer quality of life.

OBJECTIVE. To study the presentations, diagnoses, and outcomes in adolescents with menstrual disorders. DESIGN. Prospective cohort study. SETTING. Paediatric and Adolescent Gynaecology Clinic, Hong Kong. PARTICIPANTS. A total of 577 adolescents aged 14 to 19 years. MAIN OUTCOME MEASURES. The presentations and diagnoses of adolescents with menstrual disorders were reviewed and their menstrual outcomes determined by a telephone survey. RESULTS. In all, 47% presented with menorrhagia, prolonged menstruation, and short menstrual cycles; 27% had secondary amenorrhoea, 12% had dysmenorrhoea, 11% had oligomenorrhoea, and 3% had primary amenorrhoea. Significant diagnoses included congenital genital tract anomalies, premature ovarian failure, anorexia nervosa, and polycystic ovarian syndrome. Polycystic ovarian syndrome was diagnosed in 16% of the cohort. In all, 24% of these 577 patients had abnormal menstrual cycles 4 years later. Direct logistic regression analysis indicated a cycle length of more than 35 days at presentation (adjusted odds ratio=2.8; 95% confidence interval, 1.8-4.5), previous diagnosis of polycystic ovarian syndrome (adjusted odds ratio=2.0; 95% confidence interval, 1.1-3.4), and current body mass index of 23 kg/m(2) or higher (adjusted odds ratio=1.8; 95% confidence interval, 1.0-3.0) were risk factors for persistently long menstrual cycle exceeding 35 days. Adolescents who were screened out with a definitive diagnosis after initial assessment were at low risk of persistently long menstrual cycles at follow-up (adjusted odds ratio=0.3; 95% confidence interval, 0.1-0.8). CONCLUSIONS. Adolescent menstrual disorders should not be ignored. Long cycle, diagnosis of polycystic ovarian syndrome at first consultation, and a current body mass index of 23 kg/m(2) or higher were statistically associated with persistent problems.

Background: The rates of preterm birth in Chinese women and the potential effects of differing environments are poorly understood., Aim: To determine the rate of preterm birth in Chinese women in China, Hong Kong and Western Australia., Methods: The rates of preterm birth were obtained from records of 26,611 pregnancies in Jiangsu Province in mainland China, 48,976 pregnancies in Hong Kong and 185,798 pregnancies in Western Australia., Results: Preterm birth rates increased from 2.6 and 2.9% in urban and rural Jiangsu Province, respectively, and 2.5% in China-born women in Western Australia who required an interpreter; to 4.9% in China-born women in Western Australia who did not require an interpreter; to 5.6% in non-resident Chinese women in Hong Kong; and 7.6% for women resident in Hong Kong. Within Western Australia, the rate of preterm birth was significantly less in women who were born in China and declared themselves to be Chinese (4.4%) than Caucasians (7.8%), other women who declared themselves to be 'Asian' (8.7%) and women of Aboriginal heritage (14.5%)., Conclusions: The rate of preterm birth in China is relatively low but appears to differ in Chinese women in other environments. Differences between traditional Chinese and contemporary Western lifestyles, possibly including smoking and sexual practices, may contribute to the different rates of preterm birth. Further research in this area may provide avenues for the prevention of preterm birth and also help to prevent a possible rise in this complication of pregnancy as Chinese society continues on the path of economic and social reform., (© 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Introduction and Hypothesis: The purpose of this study was to investigate the reliability and validity of the Chinese version of Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ)., Methods: Women who presented for pelvic floor disorders completed the Chinese version of PFDI and PFIQ, SF-36, a 3-day urinary and fecal diary. POP-Q assessment, urodynamic study, anal manometry, and ultrasound were performed where appropriate., Results: Five hundred and ninety-seven women completed the study. The Cronbach's alpha and test-retest reliability of PFDI and PFIQ was 0.92 and 0.98, and 0.77 and 0.79, respectively. Convergent validity was demonstrated with negative correlation of PFDI and PFIQ with SF-36; positive correlation of staging of prolapse, urinary or fecal incontinent episodes with the respective subscales of PFDI and PFIQ., Conclusions: The Chinese version of PFDI and PFIQ are reliable and valid condition-specific health-related quality of life questionnaires for women with pelvic floor disorders.

Objective: To determine if placental location in the second trimester of pregnancy is associated with adverse pregnancy outcomes., Methods: We performed a retrospective study on 16 236 patients having ultrasound examination at 14 to 23 weeks of gestation between 2000 and 2007. The placental location was classified into one of four groups: 'central', 'fundal', 'lateral' and 'covering Os'. Obstetric outcomes of non-central placenta were compared to those with 'central' placenta., Results: Women with a 'fundal' placenta were at increased risk of developing pre-eclampsia (PET) (odds ratios (OR) = 2.27; 95% confidence intervals (CI), 1.31-3.93), a preterm delivery before 34 weeks (OR = 2.23; 95% CI, 1.18-4.22), a non-vertex presentation (OR = 3.48; 95% CI, 2.49-4.86), undergoing a manual removal of placenta (MROP) following a vaginal delivery (OR = 7.1; 95% CI, 4.24-11.85) and small for gestational age (SGA) (OR = 1.35; 95% CI, 1.03-1.79). Women with a 'lateral' placenta were at increased risk of developing PET (OR = 2.04; 95% CI, 1.28-3.25), spontaneous preterm delivery before 34 weeks (OR = 2.04; 95% CI, 1.04-3.98), MROP (OR = 6.75; 95% CI, 4.4-10.33) and SGA (OR = 1.82; 95% CI, 1.48-2.23). Five women with a 'cover Os' placenta had an increased risk of postpartum haemorrhage (>1000 mL) (OR = 6.18; 95% CI 2.29-16.65) if they had a vaginal delivery., Conclusion: Non-central placental location in the second trimester is associated with an increase risk of adverse obstetric outcome., (Copyright © 2011 John Wiley & Sons, Ltd.)

The numerically observed approximate functional forms for the transverse and longitudinal-momentum proportional (LP) Gram-Schmidt Lyapunov modes have been studied for some time. We construct a field theory for a system where the number of particles is large enough so the Lyapunov mode contributions from each particle can be considered to change continuously with particle position, whose solution gives the observed functional forms for all modes. The wave equations obtained as solutions of the field theory are derived either phenomenologically or from the exact dynamics of two-dimensional hard particles. The wave speed of the LP modes is predicted to reasonable accuracy for a range of densities and system sizes.

Background: The CHD5 gene located on 1p36 encodes a protein-chromodomain helicase DNA-binding protein 5. CHD5 has been shown to be a tumor suppressor gene candidate. This study investigated the involvement of CHD5 in ovarian cancer and its clinicopathological significance., Methods: CHD5 expression in ovarian cancer and its counterpart were determined by quantitative RT-PCR. The correlation of CHD5 expression to clinicopathological features of the tumor was analyzed., Results: CHD5 expression was downregulated by at least twofold in 32 of 72 (41%) invasive epithelial ovarian carcinomas when compared to 12 controls in Hong Kong Chinese women. CHD5 downregulation was correlated to clinical status (p < 0.05), but not to patient age, tumor type and grade, recurrence and clinical stage (p > 0.05). Survival analysis showed that patients with CHD5 downregulation in their tumors were associated with shorter disease-free and total survival times compared to those without CHD5 downregulation (p < 0.05). Cox proportional-hazards regression analysis indicated that downregulation of CHD5 is an independent adverse prognostic factor in ovarian cancer., Conclusion: This study shows that CHD5 is downregulated in a certain number of ovarian cancers and appears to be an adverse predictor candidate of ovarian cancer disease-free and total survival., (Copyright © 2011 S. Karger AG, Basel.)

Postnatal depression affects both men and women. The detection of postnatal depression is important, yet there are few validated screening tools on Chinese men. The goals of the present study were to compare the psychometric properties of the Edinburgh Postnatal Depression Scale (EPDS), the Beck Depression Inventory (BDI), and the Patient Health Questionnaire - Depression Module (PHQ-9) in screening for postnatal depression among Chinese fathers in Hong Kong. The prevalence of depression at 8 weeks postpartum was also estimated. A prospective cohort of 551 men completed the EPDS, BDI, and PHQ-9 at 8 weeks postpartum. Clinical diagnosis of depression was established with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), non-patient version (SCID-NP). The criterion validity of the instruments was evaluated against this clinical diagnosis. The EPDS was significantly more accurate than the BDI and PHQ-9 in detecting postnatal depression among Chinese men. With a cut-off score of 10 or more, the EPDS has a sensitivity of 91%, specificity of 97%, positive predictive value of 57%, and negative predictive value of 99%. Approximately 3.1% men met the DSM-IV criteria for depression at 8 weeks postpartum. The prevalence rate of postnatal depression in Chinese men is comparable to their Western counterparts. The Chinese EPDS is a valid instrument for detecting postnatal depression in men. It could be applied as a supplementary assessment tool in Chinese fathers who may be reluctant to disclose their depressive symptoms in face-to-face interviews., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Background: Miscarriage is common and may result in significant psychological morbidity for women. Recent research has revealed that health care professionals often tend to neglect this factor. This negligence may lead to delayed diagnosis and appropriate care., Aims: To assess health care professionals' and patients' attitudes towards the psychological impact of miscarriage., Methods: A prospective, cross-sectional survey of nearly 3000 subjects was conducted. Of these, 1269 were health care professionals and 1519 were pregnant women or their spouses. Their perceptions of the psychological impact of miscarriage, in comparison with postnatal depression were studied. RESULTS Health care professionals were less aware of the psychological impact of miscarriage compared with postnatal depression (91.9 vs 98.4%, P = 0.02). Furthermore, they believed that the psychological impact of miscarriage was less than that of postnatal depression (79.9 vs 88.9%, P < 0.001). However, more patients believed that psychological impact after miscarriage can seriously affect women (59.0 vs for health care professionals 38.3%, P < 0.001). A higher proportion of patients compared with health care professionals (85.2 vs 74.3%, P < 0.001) believed that routine psychological support should be provided after miscarriage, but few agreed that primary health professionals were the most suitable people to provide this care although most health care professionals thought this to be appropriate (9.1 vs 59.7%, P < 0.001)., Conclusion: Health care professionals should be more aware of the psychological morbidity associated with miscarriage and also be sensitive to a currently unmet need for psychological care., (© 2010 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2010 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: This randomised trial was designed to study the psychological status and morbidity during and after delivery among women with a previous cesarean section (CS) who were randomised to planned vaginal birth (VBAC) or planned CS., Methods: Two hundred and ninety-eight women with one previous lower segment CS were randomised to either planned VBAC or planned CS. Women were asked to complete psychometric scales during their pregnancy till 6 months after confinement. The primary outcome studied was the differences in psychometric scores between the two study groups., Results: There were no differences in anxiety, depression, psychological well-being or satisfaction scores between the two groups. Significantly more women in planned VBAC (27/123) requested to change to elective CS, compared to those who were randomised to planned CS (15/135) initially requested to change to planned VBAC (OR: 2.25; 95% CI: 1.13-4.47). Subgroup analyses showed that women who changed from planned CS to VBAC had lower satisfaction at delivery [Client Satisfaction Score: 24.0 (23.0-24.3), 23.0 (22.0-24.0); p=0.009] compared to women who did not change their plan for elective CS., Conclusions: The planned mode of delivery, either elective CS or VBAC, in pregnant women who had one previous CS did not influence the psychological dynamic during the course of or after the pregnancy. VBAC was not associated with higher psychological morbidity and therefore should be encouraged.

This study investigated sexual drive and satisfaction of Chinese gynecologic cancer survivors. It also examined the extent to which personal mastery, adaptive coping, and perceived spousal support would exert direct and/or indirect influences on sexual outcomes. The cancer survivor group included 134 Chinese women who had received treatment for gynecologic cancer, while the healthy control group included 105 Chinese women who did not have a known history or current diagnosis of cancer. Compared to healthy women, cancer survivors reported lower levels of sexual drive and sexual satisfaction. Among sexually active participants, cancer survivors relative to healthy women engaged in less masturbation, less kissing and caressing, and less sexual fantasy in the past month. Hierarchical multiple regression analyses showed that mastery and spousal support, but not adaptive coping, had a direct influence on sexual outcomes in cancer survivors. Contrary to moderation hypotheses, the three psychological factors did not interact with each other to influence sexual drive and satisfaction. Mediation analyses showed that spousal support fully mediated the influence of mastery on sexual satisfaction. Routine assessment of sexual functioning prior to and following treatment of gynecologic cancer is suggested. Sexual rehabilitation should also aim to enhance personal mastery and spousal support.

Purpose: The aim of the study was to examine the role of neuroticism and mastery in predicting the quality of life (QOL) among Chinese gynecologic cancer survivors., Methods: A total of 184 women participated in this prospective longitudinal study. Participants were to rate their quality of life at baseline (T1) and one year later (T2). Neuroticism as a predictor of QOL was examined by controlling for baseline QOL, sociodemographic, and disease variables using hierarchical linear regression modeling. Mastery as a mediator between the relationship of neuroticism and QOL was also examined., Results: Bivariate correlations showed that the cancer site, time since diagnosis, neuroticism, and mastery at T1 were related to various aspects of QOL at T1 and T2. After controlling for cancer site, time since diagnosis, QOL at T1, high levels of neuroticism at T1 predicted poor physical and emotional QOL at T2, but mastery at T1 did not mediate the relationship between neuroticism at T1 and QOL at T2., Conclusions: Neuroticism is a salient personality variable that predicts poor emotional and physical well-being over time. Gynecologic cancer survivors high on neuroticism should be the target for intervention to reduce negative effects during the course of recovery.

Introduction and Hypothesis: UDI-6 and IIQ-7 are useful disease-specific questionnaires evaluating the impact of urinary incontinence on the QOL of women. We aim at validating them in Chinese language., Methods: Both instruments were translated; 207 urinary incontinent women completed UDI-6 and IIQ-7, SF-36, bladder diary and urodynamic evaluation. The reliability and validity were assessed., Results: There were high internal consistency (Cronbach's alpha for UDI-6 and IIQ-7 was 0.80 and 0.93) and test-retest reliability (Intraclass correlation coefficient was 0.72 and 0.75, P < 0.001). Scoring of UDI-6 and IIQ-7 was negatively correlated with SF-36 (P < 0.001); positively correlated with daytime urinary frequency and incontinent episodes (P < 0.001), and women's VAS (P < 0.001). Subscales of UDI-6 and IIQ-7 could discriminate women with different urodynamic diagnoses., Conclusions: The Chinese UDI-6 and IIQ-7 is reliable and valid. Study on the responsiveness to treatment is in progress. They are useful in assessing impact of the urinary incontinence in Chinese women.

We demonstrate the preservation of the Lyapunov modes in a system of hard disks by the underlying tangent space dynamics. This result is exact for the Zero modes and correct to order ϵ for the Transverse and Longitudinal-Momentum modes, where ϵ is linear in the mode number. For sufficiently large mode numbers, the ϵ terms become significant and the dynamics no longer preserves the mode structure. We propose a modified Gram-Schmidt procedure based on orthogonality with respect to the center zero space that produces the exact numerical mode. This Gram-Schmidt procedure can also exploit the orthogonality between conjugate modes and their symplectic structure in order to find a simple relation that determines the Lyapunov exponent from the Lyapunov mode. This involves a reclassification of the modes into either direction preserving or form preserving. These analytic methods assume a knowledge of the ordering of the modes within the Lyapunov spectrum, but gives both predictive power for the values of the exponents from the modes and describes the modes in greater detail than was previously achievable. Thus the modes and the exponents contain the same information.

Objective: To examine the 1-year longitudinal course of psychological outcomes after miscarriage., Design: Longitudinal observational study., Setting: University-affiliated teaching hospital., Patient(s): 280 miscarrying women and 150 nonpregnant women., Intervention(s): Psychological outcomes were assessed using the 12-item General Health Questionnaire (GHQ-12) and Beck Depression Inventory (BDI) immediately, 3 months, 6 months, and 12 months after miscarriage., Main Outcome Measure(s): Scores on GHQ-12 and BDI., Result(s): Half (55%) of the miscarrying women scored high (>or=4) on the GHQ-12 immediately, 25% at 3 months; 17.8% at 6 months, and 10.8% at 1 year after miscarriage; 26.8% of the patients scored high on the BDI (>or=12) immediately, 18.4% at 3 months, 16.4% at 6 months, and 9.3% at 1 year after miscarriage. Patients who were initially more distressed continued to score higher on both the GHQ-12 and the BDI along the 1-year course when compared with those who were initially less distressed. When compared with the nonpregnant controls, the miscarrying women scored statistically significantly higher on the GHQ-12 and BDI; the differences became not statistically significant only 1 year after miscarriage., Conclusion(s): A statistically significant proportion of patients reported psychological morbidity shortly after miscarriage, but their level of distress reduced over time until they were comparable with the controls 1 year later. Patients who were initially more distressed continued to be throughout the 1-year course., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)