EMP1 correlated with cancer progression and immune characteristics in pan-cancer and ovarian cancer.

This study examines the prognostic role and immunological relevance of EMP1 (epithelial membrane protein-1) in a pan-cancer analysis, with a focus on ovarian cancer. Utilizing data from TCGA, CCLE, and GTEx databases, we assessed EMP1 mRNA expression and its correlation with tumor progression, prognosis, and immune microenvironment across various cancers. Our results indicate that EMP1 expression is significantly associated with poor prognosis in multiple cancer types, including ovarian, bladder, testicular, pancreatic, breast, brain, and uveal melanoma. Immune-related analyses reveal a positive correlation between EMP1 and immune cell infiltration, particularly neutrophils, macrophages, and dendritic cells, as well as high expression of immune checkpoint such as CD274, HAVCR2, IL10, PDCD1LG2, and TGFB1 in most tumors. In vivo experiments confirm that EMP1 promotes ovarian cancer cell proliferation, metastasis, and invasion. In conclusion, EMP1 emerges as a potential prognostic biomarker and therapeutic target in various cancers, particularly ovarian cancer, due to its influence on tumor progression and immune cell dynamics. Further research is warranted to elucidate the precise mechanisms of EMP1 in cancer biology and to translate these findings into clinical applications.

Role of CircCHD2 in the pathogenesis of gestational diabetes mellitus by regulating autophagy via miR-33b-3p/ULK1 axis.

Gestational diabetes mellitus (GDM) is a common pregnancy complication with a high incidence in women; however, its pathophysiology remains unknown. Our previous study suggested that the circCHD2/miR-33b-3p/ULK1 axis may be involved in GDM pathogenesis. However, the mechanism through which circCHD2 regulates GDM development requires further investigation. We found that high-glucose (HG, 25 mmol/L) significantly induced the expression of circCHD2, increased autophagy and apoptosis, and decreased cell viability in human placental trophoblast HTR-8/SVneo cells. In contrast, the downregulation of circCHD2 significantly attenuated the effects of HG on HTR-8/SVneo cells. MiR-33b-3p downregulated in the placenta of GDM patients was reduced by HG and detected as a target of circCHD2 using bioinformatics analysis, a dual-luciferase reporter assay, and qRT-PCR assay. Further studies showed that the inhibition of miR-33b-3p significantly blocked the effects of circCHD2 downregulation on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. ULK1 is a target of miR-33b-3p, based on bioinformatics analysis, a dual-luciferase reporter assay, qRT-PCR assay, and Western blot analysis. Compared to miR-33b-3p, ULK1 is upregulated in the placenta of GDM patients. ULK1 overexpression notably blocked the effects of miR-33b-3p mimics on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. These findings suggested that circCHD2 acts as an autophagy promoter via the miR-33b-3p/ULK1 axis to induce apoptosis in HTR-8/SVneo cells, suggesting that circCHD2 is a potential diagnostic and therapeutic target for GDM.

Interactions between ultrasonographic cervical length and placenta accreta spectrum on severe postpartum hemorrhage in women with placenta previa.

OBJECTIVE: To explore the interactions between cervical length (CL) and placenta accreta spectrum (PAS) on severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: A retrospective case-control study was conducted at four medical centers in China, and 588 patients with placenta previa were included. The logistic regression analysis and restricted cubic splines (RCS) were used to evaluate the association between CL and SPPH. Furthermore, the joint effect of CL and PAS on SPPH was assessed, and the additive and multiplicative interactions were calculated. RESULTS: After adjusting for potential confounders, the negative linear dose-response relationship was confirmed by RCS, and the change of odds ratio (OR) was more significant when CL was 2.5 cm or less. The risk of SPPH was significantly higher when CL of 2.5 cm or less co-existed with placenta increta/percreta than when CL of 2.5 cm less, or placenta increta/percreta existed alone (adjusted OR [aOR]CL ≤2.5cm&placenta accreta/non-PAS 3.40, 95% confidence interval [CI] 1.37-8.45; aORplacenta increta/percreta&CL >2.5cm 4.75, 95% CI 3.03-7.47; aORCL ≤2.5cm&placenta increta/percreta 14.51, 95% CI 6.08-34.64), and there might be additive interaction between CL and placenta increta/percreta on SPPH (attributable proportion due to interaction 50.7%, 95% CI 6.1%-95.3%). CONCLUSION: If CL was routinely performed during PAS evaluation, the increased OR of short CL and PAS could allow better patient preparation through counseling.

Identification of human placenta-derived circular RNAs and autophagy related circRNA-miRNA-mRNA regulatory network in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a metabolic and reproductive disease with serious risks and adverse health effects. However, the pathophysiological mechanism of GDM, especially the roles of circRNAs in its pathogenesis, is largely unknown. The objective of this study was to identify and investigate the roles of circRNAs in GDM. In the current study, placental circRNA expression profiles of normal controls and GDM patients were analyzed using high-throughput sequencing. Bioinformatics analysis identified a total of 4,955 circRNAs, of which 37 circRNAs were significantly deregulated in GDM placentas compared with NC placentas. GO and KEGG enrichment analyses demonstrated that metabolic process-associated terms and metabolic pathways that may be related to GDM were significantly enriched. The biological characteristics of placenta-derived circRNAs, such as their stability and RNase R resistance, were also validated Bioinformatics prediction. Moreover, we constructed the autophagy related circRNA-miRNA-mRNA regulatory network and further functional analysis revealed that the circCDH2-miR-33b-3p-ULK1 axis may be associated with autophagy in the placentas of GDM patients. Our study indicates that aberrant expression of circRNAs may play roles in autophagy in GDM placentas, providing new insights into GDM.

Systematic external evaluation of four preoperative risk prediction models for severe postpartum hemorrhage in patients with placenta previa: A multicenter retrospective study.

AIM: To compare and evaluate the validity of the existing risk prediction models for severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: We conducted a systematic literature review to collect the existing risk prediction models for SPPH in patients with placenta previa, and recruited patients with placenta previa who underwent cesarean section in Tongji Hospital (Wuhan, China) and 4 cooperative hospitals from January 2018 to June 2021. We defined SPPH as total blood loss ≥1500 mL or transfusion packed red blood cell ≥4 U. The risk of SPPH of each patient was predicted by the collected models, respectively. Then we calculated the sensitivity, specificity, coincidence rate (CCR), positive predictive value (PPV), negative predictive value (NPV) and drawn the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve of each model. RESULTS: This external cohort contained 1172 patients of whom 284 patients (24.23%) experienced SPPH, and 4 risk prediction models were collected in this study. After evaluated by this external cohort, the area under the ROC curve (AUC), sensitivity, specificity, CCR, PPV and NPV of the four models ranged from 0.644 to 0.755, 38.38% to 86.31%, 42.75% to 86.49%, 56.23% to 74.83%, 38.68% to 47.60%, 81.15% to 87.45%, respectively. The model established by Kim JW et al. had the highest sensitivity, NPV, AUC and net benefit, the model established by Lee JY et al. had the highest specificity, CCR and PPV. CONCLUSIONS: The four prediction models showed moderate predictive performance, the discrimination indicators and benefit indicators of each model were not simultaneously ideal in this population. The prediction models should be further optimized to improve the discrimination ability and benefit, and prospective external validation studies should also be carried out before they are applied to clinical practice.

Developing and Validating Nomogram to Predict Severe Postpartum Hemorrhage in Women With Placenta Previa Undergoing Cesarean Delivery: A Multicenter Retrospective Case-Control Study.

OBJECTIVE: Developing and validating nomogram to predict severe postpartum hemorrhage (SPPH) in women with placenta previa (PP) undergoing cesarean delivery. METHODS: We conducted a multicenter retrospective case-control study in five hospitals. In this study, 865 patients from January, 2018 to June, 2020 were enrolled in the development cohort, and 307 patients from July, 2020 to June, 2021 were enrolled in the validation cohort. Independent risk factors for SPPH were obtained by using the multivariate logistic regression, and preoperative nomogram and intraoperative nomogram were developed, respectively. We compared the discrimination, calibration, and net benefit of the two nomograms in the development cohort and validation cohort. Then, we tested whether the intraoperative nomogram could be used before operation. RESULTS: There were 204 patients (23.58%) in development cohort and 80 patients (26.06%) in validation cohort experienced SPPH. In development cohort, the areas under the receiver operating characteristic (ROC) curve (AUC) of the preoperative nomogram and intraoperative nomogram were 0.831 (95% CI, 0.804, 0.855) and 0.880 (95% CI, 0.854, 0.905), respectively. In validation cohort, the AUC of the preoperative nomogram and intraoperative nomogram were 0.825 (95% CI, 0.772, 0.877) and 0.853 (95% CI, 0.808, 0.898), respectively. In the validation cohort, the AUC was 0.839 (95% CI, 0.789, 0.888) when the intraoperative nomogram was used before operation. CONCLUSION: We developed the preoperative nomogram and intraoperative nomogram to predict the risk of SPPH in women with PP undergoing cesarean delivery. By comparing the discrimination, calibration, and net benefit of the two nomograms in the development cohort and validation cohort, we think that the intraoperative nomogram performed better. Moreover, application of the intraoperative nomogram before operation can still achieve good prediction effect, which can be improved if the severity of placenta accreta spectrum (PAS) can be accurately distinguished preoperatively. We expect to conduct further prospective external validation studies on the intraoperative nomogram to evaluate its application value.

Effect of spindle checkpoint on Akt2-mediated paclitaxel-resistance in A2780 ovarian cancer cells.

Recent evidence has suggested that Akt2 plays an important role in the protection of cells from paclitaxel (PTX)-induced apoptosis and control of the cell cycle. In addition, some scholars suggested that the PTX sensitivity depends on a functional spindle assembly checkpoint. In the present study, we investigated the role of the Akt2/Bub1 cross-talking in apoptosis and cell cycle after exposure of the A2780 ovarian cancer cells to paclitaxel (PTX). Recombinant expression plasmid WT-Akt2 was transfected into A2780 cells by lipofectamine2000, and then the expression level of Akt2 gene was detected by using RT-PCR and Western blotting. Cell apoptosis and cell cycle were detected by flow cytometry and Hoechst 33342 staining after treatment with PTX. Moreover, we compared the expression level of Bub1 in different groups by Western blotting. Our study showed that up-regulation of Akt2 contributed to A2780 ovarian cancer cells overriding PTX-induced G(2)/M arrest, and inhibited Bub1 expression. Our findings might shed light on the molecular mechanism of PTX-induced resistance in ovarian cancer and help develop novel anti-neoplastic strategies.

Effect of Spindle Checkpoint on Akt2-mediated Paclitaxel-resistance in A2780 Ovarian Cancer Cells / 华中科技大学学报（医学）（英德文版）

Recent evidence has suggested that Akt2 plays an important role in the protection of cells from paclitaxel(PTX)-induced apoptosis and control of the cell cycle.In addition,some scholars suggested that the PTX sensitivity depends on a functional spindle assembly checkpoint.In the present study,we investigated the role of the Akt2/Bub1 cross-talking in apoptosis and cell cycle after exposure of the A2780 ovarian cancer cells to paclitaxel(PTX).Recombinant expression plasmid WT-Akt2 was transfected into A2780 cells by lipofectamine2000,and then the expression level of Akt2 gene was detected by using RT-PCR and Western blotting.Cell apoptosis and cell cycle were detected by flow cytometry and Hoechst 33342 staining after treatment with PTX.Moreover,we compared the expression level of Bubl in different groups by Western blotting.Our study showed that up-regulation of Akt2 contributed to A2780 ovarian cancer cells overriding PTX-induced G2/M arrest,and inhibited Bub1 expression.Our findings might shed light on the molecular mechanism of PTX-induced resistance in ovarian cancer and help develop novel anti-neoplastic strategies.