BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

OBJECTIVE: Uterine carcinosarcoma (UCS) shared the same staging system with endometrial carcinoma in the International Federation of Gynecology and Obstetrics 2009. The aim of the present study was to compare the clinicopathological and prognostic characteristics between UCS and grade 3 endometrioid endometrial carcinoma (G3EC). METHODS: A retrospective analysis of 60 UCS and 115 G3EC patients with initial treatment at the Department of Gynecology in the Fudan University Shanghai Cancer Center between February 2006 and August 2013. Chi-square analysis was used to compare differences between variables. Prognostic factors were determined using univariate/multivariate analysis, and the survival rates were assessed using the Kaplan-Meier method. The Cox regression model was used to assess the independent prognostic factor. RESULTS: UCS had significantly worse overall survival (OS) compared with G3EC. Carcinosarcoma subtype was an independent factor (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.0 to 5.8; p=0.039), stratified based on stage. Compared with G3EC, UCS patients had a greater incidence of ascites fluid (55.0% vs. 15.7%, p<0.001) and adnexal involvement (20.0% vs. 8.7%, p=0.048) and larger median tumor volume (4.6 cm vs. 4.0 cm, p=0.046). Subgroup analysis of the prognostic factors revealed that UCS patients exhibited worse OS than G3EC patients in such specific subgroups as patients at younger ages, with postmenopausal status, without ascites fluid, with early stage diseases, without vagina invasion, without lymph node metastases and receiving adjuvant chemo/radiotherapy. Adjuvant radiotherapy with chemotherapy was predictive of better survival in UCS patients compared with chemotherapy or radiotherapy alone (5-year OS, 71.0% vs. 35.8%, p=0.028). Multivariate Cox regression revealed that tumor mesenchymal component (HR, 4.6; 95% CI, 1.4 to 15.8; p=0.014) was an independent prognostic factor for UCS, whereas advanced stages (HR, 5.9; 95% CI, 1.0 to 33.9; p=0.046) and ascites fluid (HR, 5.1; 95% CI, 1.1 to 22.7; p=0.032) were independently correlated with poor prognosis for G3EC patients. CONCLUSION: The distinctions in both clinicopathological and prognostic characteristics between UCS and G3EC suggest that this subtype should be treated separately from high-risk epithelial endometrial carcinoma.
Adnexa Uteri/pathology ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aorta ; Ascites/etiology ; Carcinoma, Endometrioid/*secondary/*therapy ; Carcinosarcoma/*secondary/*therapy ; Chemotherapy, Adjuvant ; Cytoreduction Surgical Procedures ; Endometrial Neoplasms/*pathology/*therapy ; Female ; Humans ; Hysterectomy ; *Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Pelvis ; Postmenopause ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Tumor Burden ; Vagina/pathology

PURPOSE: This study was done to determine whether muscle strength training programs have an impact on improving symptoms of urinary incontinence (UI) and physical function among elderly women with UI who reside in long-term care facilities. METHODS: A randomized controlled trial was conducted. Participants had to be over 65 years, score over 15 score on the mini-mental state examination, and be able to walk alone or with an assistant. Seventy residents were randomly allocated to either the training group (n=35) or control group (n=35). The program consisted of 50 minutes, twice a week for 8 weeks, and included Kegel's exercise, Thera-band training and indoor walking. Main outcomes were UI symptoms, peak vaginal pressure and physical functions measured with timed up and go test (TUG), one leg standing test (OLST), activities of daily living (ADL) and grip strength. Changes in outcome measurements were calculated from baseline to 4 weeks and to 8 weeks using repeated measures ANOVA. RESULTS: There were significant differences in peak vaginal pressure (p<.001), TUG (p<.001), OLST (p=.012) and grip strength (p<.001) in the interaction between groups and time. CONCLUSION: Future studies are suggested to confirm the effect of muscle strength training in long-term care facilities where elderly women with UI reside.
Aged ; Aged, 80 and over ; Female ; Hand Strength ; Humans ; Long-Term Care ; Muscle Strength/*physiology ; Resistance Training ; Urinary Incontinence/pathology/*therapy ; Vagina/physiology ; Walking

OBJECTIVETo investigate the risk factors of vaginal dilators by 567 adverse event reports, and to provide a reference for the reasonable use.

METHODSWith retrospective case study, analyzed 567 reports induced by vaginal dilators by National Adverse Drug Reaction Monitoring Center in 2012.

RESULTSExpected treatment of disease might be relevant with severity of adverse events, while age was not the related factor; the influencing factor of consequences of grading was the classification of the cause of adverse events.

CONCLUSIONMonitoring should be strengthen in order to reduce or avoid the vaginal dilator adverse events.

Adverse Drug Reaction Reporting Systems ; Dilatation ; adverse effects ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; Female ; Humans ; Retrospective Studies ; Risk Factors ; Vagina ; pathology

We would like to report a case of leiomyoma of the ovaries in a dog. Leiomyoma is commonly seen in the vagina in dogs. However, it is a very rare neoplasm in the ovaries. As there have only been a few reported cases, this report provides valuable information on veterinary medicine and pathology. Masses found in the ovaries need to be differentiated from other ovarian tumors. Therefore, we describe the gross, histopathological, and immunohistochemical features of a case of ovarian leiomyoma in a 10-year-old female Yorkshire Terrier dog. The mass on the right of the uterus was found accidentally by pelvic ultrasonography. Laparatomy revealed a large multi-nodulated ovarian mass. Grossly, cut surfaces of the mass showed multiple firm whitish nodules in the cortex and bloody loose connective tissue in the medulla. Histopathologically, the cortex of the mass was composed of spindle cells forming interlacing fascicles. The cells had elongated, blunt-ended nuclei and eosinophilic cytoplasm as detected by hematoxylin and eosin staining. Immunohistochemical stained sections were immunoreactive for alpha-smooth muscle actin and desmin but negative for vimentin and S-100. Therefore, differential diagnosis confirmed leiomyoma based on morphology and positive staining for alpha-smooth muscle actin and desmin.
Actins ; Animals ; Child ; Connective Tissue ; Cytoplasm ; Desmin ; Diagnosis, Differential ; Dogs* ; Eosine Yellowish-(YS) ; Eosinophils ; Female ; Hematoxylin ; Humans ; Leiomyoma* ; Ovary* ; Pathology ; Ultrasonography ; Uterus ; Vagina ; Veterinary Medicine ; Vimentin

INTRODUCTIONWe aimed to evaluate the local incidences of hydronephrosis and renal impairment in the presence of severe uterovaginal or vault prolapse, and determine whether treatment by surgery or ring pessary resulted in the resolution of hydronephrosis in these patients.

METHODSThis was a retrospective case study of 121 patients who presented with severe uterovaginal or vault prolapse. All patients who had fourth degree uterovaginal or vault prolapse, and underwent renal ultrasonography and renal function blood tests were included in the study. Follow-up imaging for hydronephrosis was performed to determine the outcome after patients received treatment.

RESULTSThe mean age of the study population was 66.1 years. The overall incidence of hydronephrosis was 20.6%. The incidence of hydronephrosis in patients with severe vault prolapse was 7.1%, while that in patients with severe uterovaginal prolapse was 22.4%. Of the 25 patients with hydronephrosis, 16 (64.0%) had complete resolution of hydronephrosis after treatment, 5 (20.0%) had residual but smaller degrees of hydronephrosis, and 4 (16.0%) were lost to follow-up. The incidence of renal impairment was 3.3%.

CONCLUSIONThe local incidence of hydronephrosis in patients with severe uterovaginal or vault prolapse was 20.6% in our study. We established that 3.3% of women with severe uterovaginal or vault prolapse had mild renal impairment. Treatment by vaginal surgery for severe uterovaginal or vault prolapse appears to result in either complete resolution or improvement of hydronephrosis in the majority of patients.

Aged ; Female ; Humans ; Hydronephrosis ; epidemiology ; pathology ; therapy ; Incidence ; Kidney ; diagnostic imaging ; Kidney Diseases ; complications ; Kidney Function Tests ; Middle Aged ; Pessaries ; Retrospective Studies ; Treatment Outcome ; Ultrasonography ; Uterine Prolapse ; complications ; epidemiology ; therapy ; Uterus ; surgery ; Vagina ; surgery

We present a case of vaginal ectopic ureter with ipsilateral partial duplication of the upper ureter (Y-type ureter), ipsilateral hypoplastic pelvic kidney and bicornuate uterus in a 20-year-old woman who presented with mild urinary incontinence since infancy. Ultrasonography, computed tomography and intravenous pyelography examination showed a left kidney with no evidence of a right kidney. Cystourethroscopy showed absence of the right hemitrigone. Magnetic resonance (MR) urography demonstrated the presence of a bicornuate uterus, an ectopic dysplastic right kidney in the pelvic cavity, and a right ureter that terminates in the vaginae fornix. The patient underwent right nephroureterectomy and urinary continence was restored completely. Although congenital malformations of the urinary tract are frequently associated with genital tract abnormalities, to best our knowledge, this is the first report of the coexistence of all of these anomalies in an individual. Our report also highlights the importance of MR urography in the diagnosis of such rare and complex anomalies.
Female ; Humans ; Kidney ; abnormalities ; pathology ; Kidney Diseases ; diagnosis ; pathology ; Magnetic Resonance Imaging ; Ureter ; abnormalities ; pathology ; Urinary Incontinence ; etiology ; Uterus ; abnormalities ; pathology ; Vagina ; abnormalities ; pathology ; Young Adult

OBJECTIVE: To analyze magnetic resonance imaging (MRI) findings of Mullerian remnants in young females clinically suspected of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome in a primary amenorrhea workup. MATERIALS AND METHODS: Fifteen young females underwent multiplanar T2- and transverse T1-weighted MRI at either a 1.5T or 3.0T MR imager. Two gynecologic radiologists reached consensus decisions for the evaluation of Mullerian remnants, vagina, ovaries, and associated findings. RESULTS: All cases had bilateral uterine buds in the pelvic cavity, with unilateral cavitation in two cases. The buds had an average long-axis diameter of 2.64 +/- 0.65 cm. In all cases, bilateral buds were connected with fibrous band-like structures. In 13 cases, the band-like structures converged at the midline or a paramedian triangular soft tissue lying above the bladder dome. The lower one-third of the vagina was identified in 14 cases. Fourteen cases showed bilateral normal ovaries near the uterine buds. One unilateral pelvic kidney, one unilateral renal agenesis, one mild scoliosis, and three lumbar sacralization cases were found as associated findings. CONCLUSION: Typical Mullerian remnants in MRKH syndrome consist of bilateral uterine buds connected by the fibrous band-like structures, which converge at the midline triangular soft tissue lying above the bladder dome.
Abnormalities, Multiple/*pathology ; Adolescent ; Adult ; Female ; Humans ; Kidney/abnormalities/pathology ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Mullerian Ducts/abnormalities/pathology ; Retrospective Studies ; Somites/abnormalities/pathology ; Spine/abnormalities/pathology ; Uterus/abnormalities/pathology ; Vagina/abnormalities/pathology

BACKGROUNDTo effectively block the invasion of human immunodeficiency virus (HIV)-1 on mucosal surface, vaginal anti-HIV-1 microbicides should avoid inflammatory responses and disruption of mucosa integrity because these will facilitate transepithelial viral penetration and replication. However, existing models fail to predict and evaluate vaginal mucosal toxicity induced by microbicides, and most importantly, they are unable to identify subtle or subclinical inflammatory reactions. This study was designed to develop a cost-effective in vivo model to evaluate microbicide safety in a preclinical study which can recapitulate the mucosal topical reaction.

METHODSA murine model was employed with nonoxynol-9 (N-9) as the topical stimulant within the vagina. Different concentrations of N-9 (1%, 3%, and 4%) were topically applied to the vagina for five consecutive days. A panel of inflammatory cytokines including interleukine-2 (IL-2), IL-4, IL-6, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and immuno-regulatory IL-10 were assayed in vaginal lavage. Cytokines were quantified by using cytometric bead array (CBA) and reverse transcript (RT) real-time PCR. Histopathological evaluation of vaginal tissues was conducted on hematoxylin-eosin stained slides and scored with a semi-quantitative system according to the severity of epithelial disruption, leucocyte infiltration, edema, and vascular injection. The association between the cytokines and histopathological scores was assessed by linear regression analysis.

RESULTSAll three concentrations of N-9 induced inflammatory cytokine production. The 4% N-9 application resulted in a consistent production of cytokines in a time-dependent manner. The cytokines reached peak expression on day three with the exception of IL-4 which reached its peak on day one. Histopathological examination of 4% N-9 treated cervicovaginal tissues on day three showed intensive damage in four mice (sores: 10 - 13) and moderate damage in one mouse (score: 8), which were significantly associated with both inflammatory cytokines IL-17A and IL-6 and anti-inflammatory cytokines IL-4 and IL-10. Interestingly, IL-17A showed significant positive association with inflammatory cytokine TNF-α (r = 0.739; P < 0.05), anti-inflammatory cytokines IL-10 (r = 0.804; P < 0.01) and IL-4 (r = 0.668; P < 0.05).

CONCLUSIONSOur data demonstrate that a panel of cytokines (IL-17A, IL-6, IL-4 and IL-10) could be used as surrogate biomarkers to predict the histopathological damage. Th17 may play a central role in orchestrating inflammatory cytokine responses. This Th17 based mouse model is cost-effective and suitable to assess the toxicity of candidate microbicides in preclinical studies.

Animals ; Anti-Infective Agents ; toxicity ; Cost-Benefit Analysis ; Cytokines ; biosynthesis ; Dose-Response Relationship, Drug ; Female ; Linear Models ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Nonoxynol ; toxicity ; Th17 Cells ; physiology ; Vagina ; drug effects ; pathology

The recombined adenovirus DNA was transfected into 293 cells for packing and amplification of replication-deficient Ad-CMV-E6/E7, Ad-K14 -E6/E7 virus was purified by CsCl density gradient centrifugation , recombined adenovirus Ad-CMV-E6/E7, Ad-K14 -E6/E7 were used as experimental group, while pAd-CMV and pAdtrack-K14 were used as control group. Four of them were injected through one main vein of nude mice tail respectively. These mice were then treated with 0.05 mg 17beta-estradiol over 12 weeks. Mice were anaesthesiaed with 2.5% Avertint and the vagina, mammary gland, ovaries and uterus were dissected and fixed in 3.75% paraformaldehyde overnight at 4 degrees C. Paraffin-embedded sections, HE staining and identification of P53 and Bcl-2 protein via immunohistochemistry were performed. The expression of E6/E7 was verified by RT-PCR in different tissue of nude mice. HE staining showed evident hyperplasy in cervix-uterus transformation zone of experimental group 2. The expression of mutant P53 and Bcl-2 were higher than control group via immunohistochemical S-P method in uterus stroma-cell. Western blotting also showed that E6 protein was expressed. The expression of E6/E7 was higher than control group by human cytokeratin promoter 14 and hyperlasy changes were detected in epithelial tissue of cervix-uterus transformation zone.
Adenoviridae ; genetics ; Animals ; Blotting, Western ; Cell Line ; Female ; Genital Diseases, Female ; pathology ; virology ; Genitalia, Female ; pathology ; virology ; Humans ; Immunohistochemistry ; Mammary Glands, Animal ; metabolism ; pathology ; Mice ; Mice, Nude ; Oncogene Proteins, Viral ; genetics ; metabolism ; Ovary ; metabolism ; pathology ; Papillomaviridae ; metabolism ; physiology ; Papillomavirus E7 Proteins ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Protein p53 ; metabolism ; Uterus ; metabolism ; pathology ; Vagina ; metabolism ; pathology