Association between pelvic floor muscle strength and sexual function based on PISQ-12—an analysis of data from a multicenter cross-sectional study on 735 nulliparae during pregnancy

BackgroundPelvic floor muscle strength is well-known to be associated with female sexual function. However, there were a few studies that reported on the relationship between pelvic floor muscle strength and female sexual function in pregnant women, and the presented results were inconsistent. Nulliparae represent a specific cohort with simplicity to exclude confounding factors that are caused by parity. The present study aimed to explore the association of pelvic floor muscle strength and sexual function based on the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) of nulliparae during pregnancy.MethodsThis is the second analysis of the baseline data from a randomized controlled trial (RCT), which aimed to study the protective efficacy of pelvic floor muscle training on stress urinary incontinence at 6th week postpartum (registration number: ChiCTR2000029618). Nulliparae aged 20–40 years with singleton pregnancy before 16 weeks of gestation were enrolled in this study, and data, including participants' demographic information, the Modified Oxford Scale (MOS), and PISQ-12, were collected. Eligible nulliparae were divided into two groups: Group MOS > 3 and Group MOS ≤ 3. Demographic information of the two groups was compared. Sexual function based on the PISQ-12 scores of the two groups was compared. A comparison of the PISQ-12 scores between the two groups was calculated by the Mann–Whitney U-test using SPSS version 23.0.ResultsA total of 735 eligible nulliparae were enrolled in this study. Along with MOS grading up, PISQ-12 scores tended to get lower. Of the 735 nulliparae, there were 378 and 357 participants included in Group MOS > 3 and Group MOS ≤ 3, respectively. The PISQ-12 scores of Group MOS > 3 were significantly lower than those of Group MOS ≤ 3 (11 vs. 12, p < 0.001). The scores of the frequency of feeling sexual desire, orgasm achievement, sexual excitement, sexual activity satisfaction, sexual intercourse pain, fear of urinary incontinence, and negative emotion reactions with the sexual intercourse of Group MOS > 3 were lower than those of Group MOS ≤ 3 (p < 0.05).ConclusionPelvic floor muscle strength was positively associated with sexual function based on the questionnaire of young nulliparae during their first trimester. Up to half of the nulliparae during the first trimester were suffering from weak pelvic floor muscle strength and nearly a quarter of the nulliparae were facing this weakness combined with sexual dysfunction.Trial registrationThis study has been registered at http://www.chictr.org.cn (registration number: ChiCTR2000029618)

Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium

Objectives It is essential to understand the molecular basis of ovarian cancer etiology and tumor development to provide more effective preventive and therapeutic approaches to reduce mortality. Particularly, the molecular targets and pathways involved in early malignant transformation are still not clear. Pro-inflammatory lipids and pathways have been reported to play significant roles in ovarian cancer progression and metastasis. The major objective of this study was to explore and determine whether platelet activating factor (PAF) and receptor associated networking pathways might significantly induce malignant potential in BRCA1-mutant at-risk epithelial cells. Methods BRCA1-mutant ovarian epithelial cell lines including (HOSE-636, HOSE-642), BRCA1-mutant ovarian cancer cell (UWB1.289), wild type normal ovarian epithelial cell (HOSE-E6E7) and cancerous cell line (OVCA429), and the non-malignant BRCA1-mutant distal fallopian tube (fimbria) tissue specimens were used in this study. Mutation analysis, kinase microarray, western blot, immune staining, co-immune precipitation, cell cycle, apoptosis, proliferation and bioinformatic pathway analysis were applied. Results We found that PAF, as a potent pro-inflammatory mediator, induced significant anti-apoptotic effect in BRCA1-mutant ovarian surface epithelial cells, but not in wild type HOSE cells. With kinase microarray technology and the specific immune approaches, we found that phosphor-STAT1 was activated by 100 nM PAF treatment only in BRCA1-mutant associated at-risk ovarian epithelial cells and ovarian cancer cells, but not in BRCA1-wild type normal (HOSE-E6E7) or malignant (OVCA429) ovarian epithelial cells. Co-immune precipitation revealed that elevated PAFR expression is associated with protein-protein interactions of PAFR-FAK and FAK-STAT1 in BRCA1-mutant ovarian epithelial cells, but not in the wild-type control cells. Conclusion Previous studies showed that potent inflammatory lipid mediators such as PAF and its receptor (PAFR) significantly contribute to cancer progression and metastasis. Our findings suggest that these potent inflammatory lipids and receptor pathways are significantly involved in the early malignant transformation through PAFR-FAK-STAT1 networking and to block apoptosis pathway in BRCA1 dysfunctional at-risk ovarian epithelium

The ratio of neutrophil to lymphocyte is a predictor in endometrial cancer

Objective: The aim of our study was to assess the prognostic value of the ratio of neutrophil to lymphocyte (NLR) for patients with surgically treated endometrial cancer (EC). Methods: We retrospectively reviewed 510 EC patients who were surgically treated between January 2010 and December 2016. We used receiver-operating characteristic (ROC) curve analysis to identify an optimal cut-off for NLR in predicting overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Nonparametric tests were used to determine the associations between NLR and clinicopathologic characteristics. The Kaplan–Meier method and Cox proportional-hazards regression were used for survival analysis. Results: With a cut-off of 2.47, the 510 patients were divided into low NLR (NLR <2.47) and high NLR (NLR ≥2.47). Elevated NLR was associated with advanced stage (P=0.039), increased histology grade (P=0.005) and lymph node metastasis (P=0.041). Multivariable analysis suggested that NLR was an independent prognostic marker for OS (hazard ratio [HR] 4.7; 95% confidence interval [CI], 1.5-14.1; P =0.006), CSS (HR 3.6; 95% CI, 1.1-11.5; P =0.028) and DFS (HR 2.3; 95% CI, 1.0-5.2; P =0.044). Conclusion: NLR may be an independent prognostic indicator for OS, CSS and DFS. It could help clinicians with preoperative risk stratification and treatment strategy tailoring

Development and Validation of a Nomogram Based on Metabolic Risk Score for Assessing Lymphovascular Space Invasion in Patients with Endometrial Cancer

Objective: This study assessed the predictive value of the metabolic risk score (MRS) for lymphovascular space invasion (LVSI) in endometrial cancer (EC) patients. Methods: We included 1076 patients who were diagnosed with EC between January 2006 and December 2020 in Peking University People’s Hospital. All patients were randomly divided into the training and validation cohorts in a ratio of 2:1. Data on clinicopathological indicators were collected. Univariable and multivariable logistic regression analysis was used to define candidate factors for LVSI. A backward stepwise selection was then used to select variables for inclusion in a nomogram. The performance of the nomogram was evaluated by discrimination, calibration, and clinical usefulness. Results: Independent predictors of LVSI included differentiation grades (G2: OR = 1.800, 95% CI: 1.050–3.070, p = 0.032) (G3: OR = 3.49, 95% CI: 1.870–6.520, p p = 0.004), MI (OR = 4.286, 95% CI: 2.663–6.896, p p p = 0.0376 and p = 0.0386 in the training and validation cohort, respectively). Subsequently, the calibration plot showed a favorable consistency in both groups. Moreover, we conducted a decision curve analysis, showing the great clinical benefit obtained from the application of our nomogram. However, our study faced several limitations. Further external validation and a larger sample size are needed in future studies. Conclusion: MRS-based nomograms are useful for predicting LVSI in patients with EC and may facilitate better clinical decision-making

Prediction of complete regression in fertility-sparing patients with endometrial cancer and apical hyperplasia: the GLOBAL model in a large Chinese cohort

Abstract Background Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. Methods We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. Results Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828–0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). Conclusion We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment

Sentinel Lymph Node Biopsy Is Feasible in Cervical Cancer Laparoscopic Surgery: A Single-Center Retrospective Cohort Study

Background and Objective. Sentinel lymph node (SLN) biopsy efficiency has been confirmed in various solid tumors. This study aimed to assess SLN biopsy feasibility in clinical application and explore how to improve its detection rates and diagnostic accuracy in cervical cancer laparoscopic surgery. Methods. A total of 100 cervical cancer patients undergoing laparoscopic surgery with SLN biopsy were included. Indocyanine green, carbon nanoparticles (CNPs), and a combination of both were used during surgeries. Detection rates, sensitivity, negative predictive value (NPV) of SLN biopsy, and related factors were analyzed. Results. The overall and bilateral SLN detection rates were 92% (92/100) and 74% (74/100), respectively. Combined tracers had higher bilateral SLN detection rates than CNPs alone (p=0.005). Menopause and lymph node metastasis were associated with lower overall and bilateral SLN detection rates (p<0.05). SLN biopsy sensitivity and NPV for lymph node metastasis in patients with at least one detected SLN were 81.8% (9/11) and 97.3% (72/74), respectively. Among those with bilateral detected SLNs, higher sensitivity and NPV of 87.5% (7/8) and 98.3% (57/58) were observed, respectively. SLN algorithm can ensure that all patients with lymph node metastasis are detected by SLN biopsy. Conclusion. SLN biopsy appears to be safe and effective for specific cervical cancer patients with high detection rates and NPV in laparoscopic surgery, especially for those with detected bilateral SLNs and undergoing the SLN algorithm. Selecting suitable patients for SLN mapping has prospects for clinical application

Calcium-Related Genes Predicting Outcomes and Serving as Therapeutic Targets in Endometrial Cancer

Endometrial cancer (EC) is the most common gynecologic cancer with increasing incidence. The dysregulation of intracellular calcium plays a crucial role in cancer progression. However, the relationship between calcium-related genes and prognosis remains unclear. In this study, we aimed to establish a risk model based on calcium-related genes for prognosis prediction in patients with EC. The TCGA-total set was divided into a training set and a testing set (1:1). The four-gene prognostic signature (CACNA2D1, SLC8A1, TRPM4 and CCL2) was established and classified all EC patients into a low-risk or high-risk group. This model was validated in both the testing dataset and the total set. The EC patients with high RiskScores showed significantly shorter overall survival than those with low RiskScores, and this trend was consistent among most subgroups. Moreover, an enrichment analysis confirmed that calcium-related and estrogen-response signalings were significantly enriched in the high-risk group. The knockdown of CACNA2D1 by siRNA or its blocker, amlodipine (AM) inhibited cell proliferation and induced cycle arrest in vitro. The calcium channel blocker AM inhibited cell proliferation and induced cycle arrest in vitro. AM also showed marked tumor inhibition effects in vivo. In summary, the prognostic model constructed by four calcium-related genes can reliably predict the outcomes of EC patients, and a calcium channel blocker, AM, has significant potential for EC treatment