Zinc Finger Protein 90 Knockdown Promotes Cisplatin Sensitivity via Nrf2/HO-1 Pathway in Ovarian Cancer Cell.

Our study discussed the role of Zfp90 in ovarian cancer (OC) cell lines' sensitivity to cisplatin. We used two OC cell lines, SK-OV-3 and ES-2, to evaluate their role in cisplatin sensitization. The protein levels of p-Akt, ERK, caspase 3, Bcl-2, Bax, E-cadherin, MMP-2, MMP-9 and other drug resistance-related molecules, including Nrf2/HO-1, were discovered in the SK-OV-3 and ES-2 cells. We also used a human ovarian surface epithelial cell to compare the effect of Zfp90. Our outcomes indicated that cisplatin treatment generates reactive oxygen species (ROS) that modulate apoptotic protein expression. The anti-oxidative signal was also stimulated, which could hinder cell migration. The intervention of Zfp90 could greatly improve the apoptosis pathway and block the migrative pathway to regulate the cisplatin sensitivity in the OC cells. This study implies that the loss of function of Zfp90 might promote cisplatin sensitization in OC cells via regulating the Nrf2/HO-1 pathway to enhance cell apoptosis and inhibit the migrative effect in both SK-OV-3 and ES-2 cells.

Clinical Risk Factors for Uterine Cervical Elongation among Women with Pelvic Organ Prolapse.

BACKGROUND: Cervical elongation is commonly associated with pelvic organ prolapse (POP). It was an identified risk for recurrent prolapse after hysteropexy, requiring additional surgeries. The aim of the study is to investigate the risk factors for uterine cervical elongation among women with POP. METHODS: In this single-center retrospective cohort study, women who underwent vaginal total hysterectomy for POP between 2014 and 2016 were collected. The cervical and total uterine lengths were measured by pathologists, while the ratio of cervical length to total uterine length were calculated. The cervical elongation is defined as corpus/cervix ratio ≤ 1.5. RESULTS: A total of 133 patients were enrolled in this study. Among these patients, 43 women had cervical elongation and 90 women had normal length of uterine cervix. We found that age > 65 years old (67.4% vs. 42.2%, p = 0.007), total vaginal length ≥ 9.5 cm (65.1% vs. 45.6%, p = 0.035), uterine weight < 51 gm (72.1% vs. 52.2%, p = 0.03), and Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6) ≥ 12 (30.2% vs. 14.4%, p = 0.032) were associated with the risk of cervical elongation. There were no significant differences on preoperative urodynamic parameters in the two groups. CONCLUSION: The patient age > 65 years old, the total vaginal length of POP-Q system ≥ 9.5 cm, uterine weight < 51 g, and POPDI-6 ≥ 12 are independent risk factors of cervical elongation in women with POP. For women scheduled for pelvic reconstructive hysteropexy, concomitant cervical amputation should be considered.

Impact of COVID-19 on Pregnancy.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an emerging disease. There has been a rapid increase in cases and deaths since it was identified in Wuhan, China, in early December 2019, with over 4,000,000 cases of COVID-19 including at least 250,000 deaths worldwide as of May 2020. However, limited data about the clinical characteristics of pregnant women with COVID-19 have been reported. Given the maternal physiologic and immune function changes during pregnancy, pregnant women may be at a higher risk of being infected with SARS-CoV-2 and developing more complicated clinical events. Information on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) may provide insights into the effects of COVID-19's during pregnancy. Even though SARS and MERS have been associated with miscarriage, intrauterine death, fetal growth restriction and high case fatality rates, the clinical course of COVID-19 pneumonia in pregnant women has been reported to be similar to that in non-pregnant women. In addition, pregnant women do not appear to be at a higher risk of catching COVID-19 or suffering from more severe disease than other adults of similar age. Moreover, there is currently no evidence that the virus can be transmitted to the fetus during pregnancy or during childbirth. Babies and young children are also known to only experience mild forms of COVID-19. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during pregnancy.

Laparoscopic Long Mesh Surgery with Augmented Round Ligaments: A Novel Uterine Preservation Procedure For Apical Pelvic Organ Prolapse.

We aim to assess the surgical outcomes of our novel hysteropexy procedure, laparoscopic long mesh surgery (LLMS) with augmented round ligaments. Twenty-five consecutive women with stage II or greater main uterine prolapse defined by the POP quantification staging system were referred for LLMS. Long mesh is a synthetic T-shaped mesh, with the body fixed at the uterine cervix and the two arms fixed along the bilateral round ligaments. The clinical evaluations performed before and 6 months after surgery included pelvic examinations, urodynamic studies, and questionnaires for urinary and sexual symptoms. After a follow-up time of 12 to 24 months, the anatomical reduction rate was 92% (23/25) for the apical compartment. The average operative time was 65.4 ± 28.8 minutes. No major complications were recognized during LLMS. The lower urinary tract symptoms and scores on the questionnaires improved significantly after the surgery, except urgency urinary incontinence and nocturia. Neither voiding nor storage dysfunction was observed after the operations. All of the domains and total Female Sexual Function Index (FSFI) scores of the 15 sexually active women did not differ significantly after LLMS. The results of our study suggest that LLMS is an effective, safe, and time-saving hysteropexy surgery for the treatment of apical prolapse.

CD47 promotes cell growth and motility in epithelial ovarian cancer.

Endometriosis is considered a high risk factor for the development of ovarian carcinoma, including clear cell and endometrioid malignancies. The mechanism by which endometriosis-associated ovarian cancer (EAOC) avoids anti-tumor immune surveillance by macrophages remains unclear, but CD47 is a very important immune checkpoint for macrophage phagocytosis. Therefore, we collected 36 clinical ovarian samples and detected the protein profile of CD47 by immunohistochemistry and analyzed the correlation with clinical pathological features using statistical software. We found that CD47 expression was relatively higher in patients with EAOC compared with the normal group. High CD47 expression was positively and significantly correlated with histology (P = 0.007) and tumor grade (P = 0.002). We also found that CD47 overexpression promotes cancer cell growth and motility in the TOV-112D and TOV-21G cell lines. Silencing CD47 and anti-CD47 mAb inhibit cancer cell growth and motility in cancer cell lines. Together, these results demonstrate that CD47 in EAOC may be a useful surface marker and offer a novel therapeutic option by targeting CD47 in ovarian cancer.

Estradiol induces cell proliferation in MCF­7 mammospheres through HER2/COX­2.

Cluster of differentiation (CD)44+/CD24- breast cancer cells have stem cell­like characteristics and are potent initiators of tumorigenesis. Mammosphere cells can partially initiate breast tumorigenesis by inducing estradiol (E2)­dependent breast cancer cells. However, the mechanisms by which E2 mediates cancer formation in MCF­7 mammosphere (MS) cells have remained elusive. In the present study, MS cells were isolated by sphere culture. It was possible to maintain these MS cells in culture for long periods of time, while retaining the CD44+/CD24- stem cell marker status. The CD44+/CD24- status was confirmed by flow cytometry. Furthermore, the stem­cell markers Musashi­1, cytokeratin (CK)7 and CK19 were identified by immunofluorescence microscopy. It was revealed that treatment of MS cells with E2 increased the expression of CD44, whereas decreased the expression of CD24 on MS cells. In addition, treatment with E2 increased colony formation by MS cells. E2 also induced cyclooxygenase­2 (COX­2) expression in MS cells, which promoted their proliferation through the estrogen receptor/human epidermal growth factor receptor 2 (HER2)/mitogen­activated protein kinase/phosphoinositide­3 kinase signaling pathway. The results suggested a tumorigenic mechanism by which E2 promotes tumor cell proliferation via HER2/COX­2 signaling. The present study provided evidence for the molecular impact of E2 on breast tumorigenesis, and suggested possible strategies for preventing and treating human breast cancer.

Laparoscopic Organopexy with Non-mesh Genital (LONG) Suspension: A Novel Uterine Preservation Procedure for the Treatment of Apical Prolapse.

To assess whether our novel uterus-sparing procedure- laparoscopic organopexy with non-mesh genital(LONG) suspension is an effective, safe, and timesaving surgery for the treatment of apical prolapse. Forty consecutive women with main uterine prolapse stage II or greater defined by the POP quantification(POP-Q) staging system were referred for LONG procedures at our hospitals. Clinical evaluations before and 6 months after surgery included pelvic examination, urodynamic study, and a personal interview to evaluate urinary and sexual symptoms with overactive bladder symptom score(OABSS), the short forms of Urogenital Distress Inventory(UDI-6) and Incontinence Impact Questionnaire(IIQ-7), and the Female Sexual Function Index(FSFI). After follow-up time of 12 to 30 months, anatomical cure rate was 85%(34/40), and the success rates for apical, anterior, and posterior vaginal prolapse were 95%(38/40), 85%(34/40), and 97.5%(39/40), respectively. Six recurrences of anterior vaginal wall all suffered from significant cystocele (stage3; Ba>+1) preoperatively. The average operative time was 73.1 ± 30.8 minutes. One bladder injury occurred and was recognized during surgery. The dyspareunia domain and total FSFI scores of the twelve sexually-active premenopausal women improved postoperatively in a significant manner (P < 0.05). The results of our study suggest that LONG suspension is an effective and safe uterus-sparing surgery for the treatment of apical prolapse.

LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells.

The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the underlying mechanisms were not fully understood. In this study, HPV16 positive CaSki and SiHa cells were used as in vitro cell model. Knockdown of HPV16 E7 significantly inhibited PVT1 and restored miR-195 expression. PVT1 directly interacts with EZH2 and the complex anchors in the promoter region of miR-195. PVT1 overexpression resulted in increased H3K27me3 levels in the miR-195 promoter region, while PVT1 knockdown decreased H3K27me3 levels in the promoter region. In addition, PVT1 could competitively bind with miR-195. MiR-195 overexpression suppressed PVT1 expression in the cancer cells. Both PVT1 and miR-195 could inhibit paclitaxel (PTX) induced epithelial-to-mesenchymal transition (EMT) and also sensitize CaSki cells to PTX. Based on these findings, we infer that PVT1 could decrease miR-195 expression via enhancing histone H3K27me3 in the miR-195 promoter region and also via direct sponging of miR-195. In addition, the PVT1/miR-195 axis can modulate responses of the cancer cells to PTX via regulating EMT.

Factors Associated with Types and Intensity of Postoperative Pain following Gynecological Laparoscopic Surgery: A Cross-Sectional Study.

OBJECTIVE: To evaluate influences of various factors on the types and intensity of postoperative pain following gynecologic laparoscopic surgery. STUDY DESIGN: Cross-sectional questionnaire and chart review. RESULTS: A total of 84 questionnaires were distributed and returned. The types of postlaparoscopic pain are different in multiparous women and nulliparous ones (71.43% surgical wound pain versus 63.64% nonsurgical wound pain, p = 0.0033) and those with striae gravidarum and without striae gravidarum (93.94% surgical wound pain versus 52.94% nonsurgical wound pain, p < 0.0001). On postoperative day 1, the average VAS score is higher in nonsurgical wound pain than in surgical wound pain (5.62 ± 1.50 versus 3.51 ± 1.68, p < 0.0001). The CO2 removal procedure has a significant negative correlation with the VAS of nonsurgical wound pain (coefficient: -0.4339, p = 0.0187). CONCLUSION: Our study suggests that women with abdominal rigidity (nulliparous, no striae gravidarum) experience mainly nonsurgical wound pain, while women with abdominal wall laxity mostly experience surgical wound pain. The VAS score of nonsurgical wound pain is greater than surgical wound pain on postoperative day 1. The CO2 removal procedure has negative correlation to the VAS score of nonsurgical wound pain on postoperative day 1.

Clinical effects of transobturator tape procedure with porcine small intestine submucosa for female stress urinary incontinence.

The aim of this study was to evaluate the efficacy of the transobturator tape (TOT) procedure using porcine small intestine submucosa (SIS) for the treatment of female stress urinary incontinence (SUI). Forty-two consecutive patients with SUI who underwent the TOT procedure with porcine SIS were enrolled. The surgical outcomes, and data of urodynamic study and a questionnaire prior to and after surgery were collected and analyzed retrospectively. SUI was reported subjectively cured in 34 of the 42 patients (81.0%) 1 year after surgery, and declined to the rate of 66.7% at 5 years postoperatively. The subjective symptoms of frequency and nocturia also improved significantly (p < 0.01). Graft-versus-host disease (GVHD) developed in four patients, but without major complications. Despite the bladder volume at first desire to void increased significantly after surgery (p < 0.01), the remaining urodynamic parameters did not differ in a significant manner. In conclusion, the long-term cure rate of the TOT procedure with SIS is lower than with synthetic materials, but with relatively lower morbidity.

Suppression of IL-8-Src signalling axis by 17ß-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.

Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17ß -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17ß-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17ß-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.

Comparison of clinical outcomes using "elevate anterior" versus "Perigee" system devices for the treatment of pelvic organ prolapse.

OBJECTIVE: This study aims to compare clinical outcomes using the Perigee versus Elevate anterior devices for the treatment of pelvic organ prolapse (POP). STUDY DESIGN: One hundred and forty-one women with POP stages II to IV were scheduled for either Perigee (n = 91) or Elevate anterior device (n = 50). Preoperative and postoperative assessments included pelvic examination, urodynamic study, and a personal interview about quality of life and urinary symptoms. RESULTS: Despite postoperative point C of Elevate group being significantly deeper than the Perigee group (median: -7.5 versus -6; P < 0.01), the 1-year success rates for two groups were comparable (P > 0.05). Apart from urgency incontinence, women with advanced POP experienced significant resolution of irritating and obstructive symptoms after both procedures (P < 0.05), generating the improvement in postoperative scores of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) (P < 0.01). On urodynamics, only the residual urine decreased significantly following these two procedures (P < 0.05). Women undergoing Perigee mesh experienced significantly higher visual analogue scale (VAS) scores and vaginal extrusion rates compared with the Elevate anterior procedure (P < 0.05). CONCLUSIONS: With comparable success rates, the Elevate procedure has advantages over the Perigee surgery with lower extrusion rate and postoperative day 1 VAS scores.

Comparison of low urinary tract symptoms during pregnancy between primiparous and multiparous women.

BACKGROUND AND PURPOSE: Low urinary tract symptoms (LUTS) are a common problem during pregnancy. This study aimed to compare changes in the prevalence of LUTS during pregnancy between primiparous and multiparous women. METHODS: A chart review of consecutive pregnant women who attended our antenatal clinic from March 2002 to January 2006 was performed. All of the women were asked to respond to a LUTS questionnaire in either of the three trimesters. RESULTS: Of the 270 women included, 164 were nullipara and 106 were multipara. The most common LUTS during pregnancy were frequency (77%), followed by nocturia (75.6%), stress urinary incontinence (SUI) (51.1%), incomplete emptying (43.7%), dysuria (17.8%), and urgency incontinence (10.4%). There was a significantly higher prevalence of SUI (P<0.001) and urgency incontinence (P=0.005) in the multiparous compared to the nulliparous women. Increasing prevalence rates of frequency, nocturia, SUI, and incomplete emptying were reported with gestational age in both the nulliparous and multiparous women. CONCLUSIONS: Frequency and nocturia were the two most common LUTS during pregnancy. The prevalence rates of all LUTS increased with increasing gestational age except for frequency in the nulliparous women during the second trimester. In addition, multipara was a predictor of SUI during pregnancy.

Modified prepubic TVT-obturator tape procedure versus the conventional method: a preliminary study.

OBJECTIVE: To compare the efficacy and safety of the modified prepubic tension-free vaginal tape-obturator (PTVT-O) system procedure with the original TVT-O methods. STUDY DESIGN: One hundred and ninety women with urodynamic stress incontinence (USI) were included in this study (93 cases in the TVT-O group and 97 in the PTVT-O group). Clinical assessments before and one year after surgery included urinalyses, 1-h pad tests, urodynamic studies, and a personal interview with the overactive bladder symptom score (OABSS) questionnaire. RESULTS: There were no differences between the two groups in mean age, parity, menopausal status, mean operative time and subjective cure rates (P>0.05), but the efficacy of surgery (cure and improvement) in the PTVT-O group was significantly higher than that in the TVT-O group (P=0.038). Complication rates and visual analog scale (VAS) scores were found to be similar (P>0.05). OABSS decreased significantly after surgery in both groups (P<0.05) although all urodynamic parameters revealed no significant difference after both procedures (P>0.05). CONCLUSION: Our modified procedure is a safe and effective treatment for female USI. It has an advantage over the original TVT-O with better surgical efficacy and comparable postoperative pain, although the follow-up times in this study are different.

Clinical and urodynamic effects of tolterodine in women with an overactive bladder.

OBJECTIVE: The aim of this study was to compare the changes in urinary symptoms and urodynamic parameters after administration of tolterodine in women with an overactive bladder (OAB). MATERIALS AND METHODS: Thirty-eight women diagnosed with OAB and treated with tolterodine were reviewed. Urinalysis, pelvic examination, 3-day bladder diary, urodynamic study, and a personal interview to identify urinary symptoms prior to and 3 months after treatment were recorded and interpreted. RESULTS: Most of our patients were menopausal (76.3%; mean age 55.7 years) and multiparous (mean parity 3.3) women. Urinary symptoms such as urinary frequency, urgency, urge incontinence, and nocturia were decreased significantly (p < 0.05). All urodynamic parameters did not change significantly except for the maximum cystometric capacity (p < 0.05), showing a significant increase after 3 months of medication. CONCLUSIONS: Tolterodine, at a recommended dose, improves the symptoms of OAB syndrome without causing urine retention, as proved by the changes of urodynamic parameters.

Risk factors of surgical failure following transvaginal mesh repair for the treatment of pelvic organ prolapse.

OBJECTIVE: To identify the factors associated with pelvic organ prolapse (POP) recurrence after transvaginal mesh (TVM) repair. STUDY DESIGN: One hundred and thirteen women with symptomatic POP stage II to IV were scheduled for TVM procedures. All subjects underwent urinalyses and pelvic examination using the POP quantification (POP-Q) staging system before and after surgery. RESULTS: Seven (6.2%) of 113 women reported POP recurrence after a mean follow-up time of 30 months. We performed a univariate analysis of patients' characteristics to identify the predictors of surgical failure after TVM. There was no difference between two groups as to body mass index, POP stage, mesh type, and preoperative urinary symptoms and urodynamic parameters (P>0.05). However, we found that uterine prolapse (P=0.016) and surgical experience (P=0.043) were two significant predictors of surgical failure. Multivariate logistic regression showed similar results. CONCLUSION: Advanced uterine prolapse and lack of surgical experience were two significant predictors of failure following TVM. POP recurrence after mesh repair appears to be unlikely beyond the learning curve.

Three-year outcome of transvaginal mesh repair for the treatment of pelvic organ prolapse.

OBJECTIVE: To evaluate the clinical and urodynamic outcomes of transvaginal mesh repair (TVM) for the treatment of pelvic organ prolapse (POP). STUDY DESIGN: One hundred and twenty-four women with POP stage II to IV were scheduled for a TVM procedure. Preoperative and postoperative assessments included pelvic examination, urodynamic testing, and a personal interview about urinary symptoms using a standard questionnaire. RESULTS: We found a significant improvement at points Aa, Ba, C, Ap, and Bp (P<0.001) except for total vaginal length (P=0.08), and the overall success rate was 93.5% (116/124). Various urinary symptoms improved significantly following TVM (P<0.01). In addition, residual urine, functional urethral length, and the rate of detrusor overactivity, improved significantly after surgery (P<0.05). Apart from vaginal erosion (14/124; 11.3%), the rates of other surgical complications were acceptably low. CONCLUSION: TVM is an effective procedure for the treatment of POP and urinary symptoms, this being possibly related to postoperative release of urethral obstruction. Vaginal erosion is less likely to occur beyond the learning curve.