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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. [ABSTRACT FROM AUTHOR]

Self‐directed learning is recognised as a key goal of higher education. To facilitate self‐directed learning, emotional intelligence (EI), which encompasses the ability to regulate one's own emotions and to generate positive emotions, is important. The present study aimed to examine the effects of EI on self‐directed learning and how EI and self‐directed learning contribute to key learning outcomes in higher education, including grade point average (GPA), generic learning outcomes (including social, cognitive and self‐growth outcomes) and students' satisfaction with their university experience. The study adopted a prospective longitudinal design with 560 first‐year undergraduate students completing different measures at the beginning and end of the academic year. Results of the structural equation modelling showed that EI had a strong effect on self‐directed learning, which in turn was positively associated with GPA and various generic learning outcomes that are related to students' satisfaction with the university experience. To better delineate the relationship between EI and self‐directed learning, multiple regression was performed. Results indicated that three key emotional abilities—emotional regulation of the self (ERS), appraisal of emotions in the self (AES) and emotional regulation of others (ERO)—were positively associated with self‐directed learning. This study provided empirical evidence that students who are more emotionally intelligent are more self‐directed, leading to higher achievement in both academic and generic development, which in turn results in higher university satisfaction. Implications of the findings are discussed. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate pelvic floor biometry of women 3-5 years after their first delivery. The effect of a subsequent delivery and the mode of delivery on pelvic floor biometry were also studied.Methods: Three-hundred and twenty-eight women who had been examined by translabial ultrasound during their first singleton pregnancy and at 8 weeks and 1 year postpartum, were invited for a follow-up 3-5 years later. The positions of the bladder neck, cervix, anorectal junction and hiatal area (HA) were evaluated using translabial ultrasound. The effects of parity, mode of delivery and levator ani muscle avulsion were studied.Results: A total of 240 women completed the study. Of these, 179 had one or more vaginal deliveries (VD) (VD-only group), 52 had one or more Cesarean sections (CS) (CS-only group) and nine had both VD and CS at follow-up. The mean interval between the first delivery and follow-up was 3.8 years. A significantly lower bladder neck and anorectal junction on Valsalva, a lower cervix at rest, on Valsalva and pelvic floor muscle contraction, and a greater HA were observed in the VD-only group at follow-up, compared with findings at 1 year of follow-up or in the first pregnancy. The findings were similar in the CS-only group, except without a lower anorectal junction on Valsalva. Compared with the primiparous VD-only group, a greater HA at rest was observed in the multiparous VD-only group (P = 0.027). The VD-only group had a greater HA than the CS-only group.Conclusions: At 3-5 years after first delivery, a lower bladder neck, cervix and anorectal junction, and a greater HA were observed compared with findings in the first trimester and at 1 year of follow-up, regardless of parity or mode of delivery. Women with two or more VDs had a greater HA compared with those who had only one VD, and women with at least one VD had a greater HA compared with those who delivered by CS only. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Women suffering from urinary incontinence have impaired quality of life ( Qo L). 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 Qo L 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 Qo L 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 Qo L of women presenting with urinary incontinence. Future studies on long-term effectiveness and cost-effectiveness are also required. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. To assess health care professionals' and patients' attitudes towards the psychological impact of miscarriage. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Aims and objectives. To examine the validity and reliability of the short form of the Childbirth Self-Efficacy Inventory in a clinical Chinese pregnant population. Background. Childbirth self-efficacy has become an important psychological construct for both childbirth educators and researchers because pregnant women's perception may influence the meaning and consequences of childbirth. Assessment done by the original Childbirth Self-Efficacy Inventory limits the scientific rigor for generating additional research into the construct, as its items were repetitive and its structure is lengthy. Methods. This prospective study investigated 293 Chinese pregnant women in their third trimester of pregnancy. The women completed the short form of the Childbirth Self-Efficacy Inventory, the Chinese Self-efficacy Scale and the socio-demographic questionnaire in an interview room of the study hospital. The re-testing of the scale on the participants was carried out two weeks later in the same clinic. Results. Factor analysis and item-subscale correlations supported the conceptual dimensions of the short form of the Chinese Childbirth Self-Efficacy Inventory. The Cronbach's alpha coefficients for both subscales were over 0·9. The convergent validity with the Chinese Self-Efficacy Scale was reflected by a moderate correlation for the two subscales. The efficacy expectancy subscale differentiated primigravid from multigravid women ( t = 2·83, P < 0·01, CI = −2·33 to 2·34). Conclusions. The reliability and validity information presented in this paper supports the use of the short form of the Childbirth Self-Efficacy Inventory as a research instrument in measuring the childbirth self-efficacy among the Chinese population. Further validation of the measure is warranted. Relevance to clinical practice. The reliable short form of the Childbirth Self-Efficacy Inventory could be used in routine clinical practice in maternity care services to provide a point of reference for future research and development in both childbirth education and clinical practice. [ABSTRACT FROM AUTHOR]

The recently described gene, RAB32, is a ras proto-oncogene family member that encodes an A-kinase-anchoring protein. RAB32 has been found to be frequently hypermethylated in microsatellite instability-high (MSI-H) colon cancers. We sought to determine the prevalence of RAB32 hypermethylation in gastric and endometrial adenocarcinomas, the 2 other major tumor types in which MSI-H is common. Moreover, we delineated the association of RAB32 hypermethylation with microsatellite instability (MSI) and hMLH1 hypermethylation. MSI status and hypermethylation of the RAB32 and hMLH1 genes were studied in paired primary normal and tumor tissues from 48 patients with gastric cancer. An additional 80 endometrial cancer patients were studied for RAB32 methylation and MSI status. Thirteen (27%) of 48 gastric cancers demonstrated evidence of RAB32 hypermethylation. MSI status was determined in 46 of the tumors, with 7 (100%) of 7 MSI-H tumors, 1 (33%) of 3 MSI-low (MSI-L) tumors and 4 (11%) of 36 microsatellite-stable (MSS) tumors found to harbor RAB32 hypermethylation. RAB32 methylation was significantly associated with intestinal type histology and concomitant hMLH1 hypermethylation in gastric cancer. In contrast, RAB32 methylation occurred in only 1 of 80 endometrial cancers, including 20 MSI-H, 8 MSI-L and 52 MSS tumors. Hypermethylation of hMLH1 was noted in 16 (20%) of 80 endometrial tumors. We conclude that although RAB32 methylation is rare in endometrial cancers, it is strongly associated with hMLH1 hypermethylation and MSI in gastric adenocarcinomas. Given its similar involvement in colon cancer, RAB32 inactivation may represent a component of the oncogenic pathway of microsatellite-unstable gastrointestinal adenocarcinomas. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

An analysis of gene expression profiles obtained from cervical cancers was performed to find those genes most aberrantly expressed. Total RNA was prepared from 29 samples of cervical squamous cell carcinoma and 18 control samples, and hybridized to Affymetrix oligonucleotide microarrays with probe sets complementary to over 20,000 transcripts. Unsupervised hierarchical clustering of the expression data readily distinguished normal cervix from cancer. Supervised analysis of gene expression data identified 98 and 139 genes that exhibited >2-fold upregulation and >2-fold downregulation, respectively, in cervical cancer compared to normal cervix. Several of the genes that were differentially regulated included SPP1 (Osteopontin), CDKN2A ( p16), RPL39L, Clorf1, MAL, p11, ARS and NICE-1. These were validated by quantitative RT-PCR on an independent set of cancer and control specimens. Gene Ontology analysis showed that the list of differentially expressed genes included ones that were involved in multiple biological processes, including cell proliferation, cell cycle and protein catabolism. Immunohistochemical staining of cancer specimens further confirmed differential expression of SPP1 in cervical cancer cells vs. nontumor cells. In addition, 2 genes, CTGF and RGS1 were found to be upregulated in late stage cancer compared to early stage cancer, suggesting that they might be involved in cancer progression. The pathway analysis of expression data showed that the SPP1, VEGF, CDC2 and CKS2 genes were coordinately differentially regulated between cancer and normal. The present study is promising and provides potential new insights into the extent of expression differences underlying the development and progression of cervical squamous cell cancer. This study has also revealed several genes that may be highly attractive candidate molecular markers/targets for cervical cancer diagnosis, prognosis and therapy. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

: ObjectivesTo study whether proactive educational counselling, in addition to routine clinical care, reduces psychological morbidity and improves quality of life and client satisfaction among women who suffer suboptimal outcomes during childbirth.: DesignA randomised controlled trial.: SettingObstetric unit of a tertiary teaching hospital.: PopulationWomen who had unexpected antenatal, intrapartum or postpartum events leading to suboptimal outcomes during pregnancy and childbirth.: InterventionEducational counselling provided by a trained research nurse in the postnatal ward after delivery. Women in the control group received routine clinical care.: Main outcome measuresThe Hospital Anxiety and Depression Scale, the General Health Questionnaire and the Clinical Global Impression (before and after counselling, at six weeks and six months post-delivery) and the World Health Organisation Quality of Life scale (WHO-QOL) (at six weeks and six months post-delivery).: ResultsThere was no significant difference in psychological morbidity, quality of life or client satisfaction between the counselling group and the control group. Participants who underwent elective caesarean section and who had the educational counselling had significantly lower depression scores [mean 2.6 (SD 2.6)] compared with those receiving routine care [mean 3.9 (SD 3.2)]. On the other hand, educational counselling may have deleterious effect to women''s quality of life in those who had instrumental delivery. Participants allocated to the counselling group had a lower mean score 68 (SD 13) in the physical domain of WHO-QOL than those in the intervention group 74 (SD 13).: ConclusionEducational counselling, given on top of routine clinical care, does not give additional beneficial effects on the psychological wellbeing and quality of life of women who encountered suboptimal outcomes during pregnancy. [Copyright &y& Elsevier]

Background: Postcoital bleeding is a common gynaecological problem that impacts on a woman's quality of life and sexual function. There is little systematic research into its management., Aims: To assess the efficacy and side-effects of cryotherapy as treatment for postcoital bleeding., Methods: A prospective randomised controlled trial was conducted in a tertiary referral hospital in Hong Kong. A total of 85 women who presented with postcoital bleeding were recruited, and randomised to cryotherapy or no treatment. The treatment group received cryotherapy with compressed carbon dioxide through a cryoprobe placed on the cervix, and controls had cryoprobe on the cervix without compressed carbon dioxide flow. All recruited women were followed up two weeks, three months and six months to review their symptoms and response to the treatment., Results: The treatment group had a significantly better long-term cure rate and improvement rate. At six months, the cryotherapy group reported a cure rate of 72.1% while that in the control group the cure rate was 50.0% (P = 0.04). The number needed to treat was 5. The mean improvement rate of the cryotherapy group was 82.88% +/- 35.87 but was only 61.62% +/- 55.30 in the control group (P = 0.04). The results were more significant in women with the defined pathological cervix. Apart from the vaginal discharge at second week follow up in the treatment group, there was no statistical significant difference in side-effects and complications among two groups., Conclusion: Our study demonstrated that cryotherapy is a safe and an effective treatment for postcoital bleeding.

Background: A woman's childbirth experience has an influence on her future preferred mode of delivery. This study aimed to identify determinants for women who changed from preferring a planned vaginal birth to an elective cesarean section after their first childbirth., Methods: This prospective longitudinal observational study involved two units that provide obstetric care in Hong Kong. A mail survey was sent to 259 women 6 months after their first childbirth. These women had participated in a longitudinal cohort study that examined their preference for elective cesarean section in the antenatal period of their first pregnancies. Univariate and multivariate analyses were performed to identify determinants for women who changed from preferring vaginal birth to elective cesarean section., Results: Twenty-four percent (23.8%, 95% CI 18.4-29.3) of women changed from preferring vaginal birth to elective cesarean section after their first childbirth. Determinants found to be positively associated with this change included actual delivery by elective cesarean section (OR 106.3, 95% CI 14.7-767.4) intrauterine growth restriction (OR 19.5, 95% CI 1.1-353.6), actual delivery by emergency cesarean section (OR 8.4, 95% CI 3.4-20.6), higher family income (OR 3.2, 95% CI 1.1-8.8), use of epidural analgesia (OR 2.6, 95% CI 1.0-6.8), and higher trait anxiety score (OR 1.1, 95% CI 1.0-1.3). The most important reason for women who changed from preferring vaginal birth to elective cesarean section was fear of vaginal birth (24.4%)., Conclusions: A significant proportion of women changed their preferred mode of delivery after their first childbirth. Apart from reducing the number of cesarean sections in nulliparous women, prompt provision of education to women who had complications and investigations into fear factors during vaginal birth might help in reducing women's wish to change to elective cesarean section.