Background: Studies have assessed the effects of menstrual irregularities and menopause on diabetes, but no definitive conclusion has been reached. This study investigated for the first time the relationship between menstrual irregularity and diabetes before and after menopause. Methods: This population-based cross-sectional study included 9043 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) V (2010–2012). Multivariate logistic regression was used to assess the effect of menstrual irregularities on impaired fasting glucose (IFG) and diabetes incidence in women before and after menopause. Results: After adjustment for age and other diabetes-related factors, both menopause (OR = 1.51, 95% CI = 1.101–2.27, p = 0.047) and menstrual irregularities (OR = 1.51, 95% CI = 1.1–2.07, p = 0.011) were found to increase the risk of diabetes. Menstrual irregularities were significantly related to diabetes in the postmenopausal group (OR = 1.65, 95% CI = 1.12–2.42, p = 0.012) but not in the premenopausal group (OR = 1.22, 95% CI = 0.64–2.32, p = 0.555). Conclusions: In this study, menopausal status appeared to independently affect diabetes risk; menstrual irregularities were found to be a risk factor for postmenopausal diabetes. This study emphasizes the need for monitoring and early prevention, along with medical advice on menstrual irregularities, to reduce the prevalence of diabetes and improve the quality of life of postmenopausal women.

Background and Objectives: This study aimed to investigate whether mild fetal tricuspid regurgitation (TR) at 11^+ 0 to 13^+ 6 weeks of gestation affects perinatal outcomes. Since fetal right ventricular load is associated with placental resistance, we hypothesized that fetal mild TR would be associated with perinatal outcomes as a consequence of abnormal placentation. Materials and Methods: We retrospectively evaluated 435 women with first-trimester scan data. Blood flow across the tricuspid valve was examined in singleton pregnancies between 11^+ 0 and 13^+ 6 weeks of gestation. Women were categorized according to the presence or absence of fetal mild TR, and the maternal and pregnancy characteristics and perinatal outcomes were compared. Multiple linear and logistic regression analyses were conducted to identify independent predictors of perinatal outcome. Results: In the group with mild TR, there were more cases of borderline amniotic fluid index, including oligohydramnios (p = 0.031), and gestational age- and sex-specific birth weights were lower (p = 0.012). There were no significant differences in other perinatal outcomes, including preeclampsia, gestational hypertension and small for gestational age. Gestational diabetes (adjusted odds ratio (OR) 0.514, 95% confidence interval (CI) 0.312–0.947) and fetal mild TR (adjusted OR 1.602, 95% CI 1.080–2.384) were identified as factors associated with below borderline amniotic fluid index before birth. The factors that affected gestational age and sex-specific birth weight were also gestational diabetes (adjusted beta coefficient 9.673, p = 0.008) and the presence of fetal mild TR (adjusted beta coefficient −6.593, p = 0.007). Conclusions: Mild fetal TR observed in the first trimester is negatively associated with fetal growth and the amniotic fluid index at term but not with other adverse pregnancy or perinatal outcomes due to abnormal placentation.

Background: The Hippo signaling pathway has a key role in tumorigenesis. This study aimed to evaluate the relationship between the expression of core components of the Hippo signaling pathway and its association with clinicopathological features in endometrial cancer. Materials and Methods: We retrospectively collected endometrioid endometrial cancer specimens from 60 patients between January 2002 and December 2009 at Gyeongsang National University Hospital. Relevant clinicopathological data were obtained through electronic medical records of patients. The expression patterns of six core components (YAP, p-YAP, LATS1/2, MST1/2, KIBRA, and Merlin) were identified by immunohistochemistry on tissue microarray sections. Results: The positive expression ratio was 75.0% for YAP, 73.3% for p-YAP, 26.7% for MST1/2, 16.7% for KIBRA, 15.0% for Merlin, and 15.0% for LATS1/2. YAP expression was negatively correlated with MST 1/2 kinases (p = 0.045) and positively correlated with p-YAP (p = 0.012). Merlin, and MST 1/2 kinases (p = 0.043) showed a positive correlation. A subgroup of patients aged below 60 years (p = 0.004) and with myometrial invasion depth of less than 1/2 (p = 0.041) showed a positive association with YAP expression. p-YAP expression was negatively associated with a subset of patients with primary tumour size ≥4 cm (p = 0.03). Logistic regression analysis showed a significant association between age and YAP expression. The odds ratio of p-YAP expression was significantly lower in the group with tumour size ≥4 cm. Conclusion: Two prognostic factors, age and tumour size, were significantly associated with the expression of YAP and p-YAP in endometrial cancer. Further research should focus on their expression as a marker for prediction of clinicopathological implications in endometrial cancer.

The purpose of this paper is to evaluate the association of maternal clinical and laboratory features and placental histopathological changes with disease severity in pregnancy-related hypertensive disorders. From January 2021 to December 2021, clinical and laboratory data at the time of delivery and histopathological features of the placenta were collected from pregnant women with pregnancy-related hypertensive disorders at a single institution. The women were classified according to the pregnancy-related hypertensive disorder clinical severity, and each variable was compared accordingly. Gestational age-matched normotensive groups were also compared. Univariate and multivariate regression analyses were used to identify factors influencing pregnancy-related hypertensive disorder severity. Fifty-eight pregnancies were analyzed. Maternal albumin levels before delivery (beta coefficient −0.83, p = 0.043) and increased placental syncytial knots (beta coefficient 0.71, p = 0.026) are important parameters that are closely related to disease severity in women with pregnancy-related hypertensive disorders. The combination of albumin, PAPP-A, total bilirubin, and eGFR levels appears to be optimal for predicting pregnancy-related hypertensive disorder severity.

Background and Objectives: S100A8 regulates inflammatory responses and immune cell activation and is overexpressed in several solid tumors. However, its clinicopathological significance in endometrial carcinoma (EC) remains unclear. This study aimed to evaluate the expression patterns of S100A8 in both tumor and immune cells of EC and examine its association with clinicopathological features. Materials and Methods: Fifty-two formalin-fixed, paraffin-embedded EC specimens were analyzed using tissue microarray-based immunohistochemistry. S100A8 expression was assessed in tumor and immune cells. The tumor proportion score (TPS), tumor staining intensity (TI), and immune proportion score (IPS) were dichotomized into low and high categories (TPS/IPS: ≤30% vs. ≥31%; TI: 0–1+ vs. 2–3+). Correlations with clinicopathological parameters were examined using the chi-square and Fisher’s exact tests. Results: A low TPS, high TI, and high IPS were observed in 51.9%, 63.5%, and 57.7% of patients, respectively. TPS and TI showed no significant correlation with clinicopathological variables, including age, tumor size, invasion depth, histologic grade, T stage, and N stage (all p > 0.05). By contrast, IPS was significantly associated with patients’ age (p = 0.044) and histologic grade (p = 0.012), with older patients and those with higher-grade tumors demonstrating a higher IPS. A positive correlation was observed between TPS and IPS (p = 0.044), whereas TI did not correlate with IPS (p = 0.253). Conclusions: S100A8 expression in immune cells, but not in tumor cells, is associated with age and tumor grade in EC. Therefore, immune-related S100A8 expression may serve as a biomarker of the tumor immune microenvironment, warranting further investigation into its prognostic and therapeutic implications.

Background and Objectives: Metabolic reprogramming and dysregulation of Hippo signaling are recognized features of endometrial carcinogenesis; however, the relationship between regional GLUT1 expression patterns and Hippo pathway-related proteins remains incompletely understood. This exploratory study investigated these associations in endometrioid endometrial carcinoma and evaluated changes in YAP-related protein expression following GLUT1-targeting siRNA treatment in vitro. Materials and Methods: Formalin-fixed, paraffin-embedded tumor specimens from 50 patients with endometrioid endometrial carcinoma were retrospectively analyzed by immunohistochemistry for GLUT1, YAP, phosphorylated YAP (p-YAP, Ser127), MST1/2, and LATS1/2. GLUT1 expression was classified as mosaic, central, or diffuse within the sampled tumor tissue. Associations between GLUT1 patterns and Hippo pathway markers were assessed, including an exploratory analysis restricted to YAP-positive tumors. Complementary experiments were performed in Ishikawa cells using GLUT1-targeting siRNA, followed by semi-quantitative RT-PCR and Western blotting, each based on three independent biological experiments. Results: GLUT1 expression was mosaic in 12.0%, central in 56.0%, and diffuse in 32.0% of tumors. Total YAP expression was not significantly associated with GLUT1 distribution (p = 0.411), whereas diffuse GLUT1 expression showed a nominally significant association with absent cytoplasmic p-YAP immunoreactivity (odds ratio [OR] = 5.8, 95% confidence interval [CI]: 1.22–27.7; unadjusted p = 0.044). This association did not remain statistically significant after a focused two-test Benjamini–Hochberg false discovery rate correction (q = 0.088). The association was also not statistically significant in the YAP-positive subgroup (n = 41; OR = 4.50; p = 0.139). In Ishikawa cells, GLUT1-targeting siRNA significantly reduced GLUT1 mRNA expression (p = 0.0089), whereas GLUT1 protein expression showed a nonsignificant reduction (p = 0.1356). Total YAP and p-YAP levels decreased significantly in unadjusted paired analyses (p = 0.0149 and p = 0.0481, respectively). The normalized p-YAP/total YAP ratio also decreased from 0.803 ± 0.192 to 0.634 ± 0.136, although the difference was not statistically significant (p = 0.1488). Conclusions: Diffuse GLUT1 expression showed a nominally significant association with absent cytoplasmic p-YAP immunoreactivity in endometrioid endometrial carcinoma, but this association did not remain statistically significant after a focused BH-FDR correction. In vitro, GLUT1-targeting siRNA treatment was accompanied by changes in YAP-related protein expression without significant reductions in GLUT1 protein expression or the normalized p-YAP/total YAP ratio. These preliminary findings suggest a potential relationship between GLUT1 expression and Hippo-YAP signaling but do not establish altered YAP phosphorylation or a direct causal mechanism. Further validation is warranted.