Background: Integrin beta4 (ITGB4) is a transmembrane receptor that plays a key role in tumorigenesis and tumor development. However, there are no pan-cancer analyses of ITGB4. Methods: This study demonstrates the first potential oncogenic roles of ITGB4 across 33 tumors based on the dataset of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Results: ITGB4 is highly expressed in many cancers, and distinct correlations exist between ITGB4 expression and the prognosis of tumor patients. We also found that the methylation and genetic alteration level of ITGB4 was associated with some cancer prognosis. Furthermore, we found a reduced phosphorylation of ITGB4 at S1457 in several tumors, such as breast and ovarian cancers. Finally, ITGB4 expression was correlated with cancer-associated fibroblasts in liver hepatocellular carcinoma and prostate adenocarcinoma, and the infiltration level of NK cells and neutrophils was observed in other cancers, such as breast invasive carcinoma and lung adenocarcinoma. Moreover, RNA metabolism and protein processing-associated functions are involved in the functional mechanism of ITGB4. Conclusion: Our first pan-cancer study may offer a relatively comprehensive understanding of the oncogenic roles of ITGB4 across different tumors.

Persistent injury and the following improper repair in bronchial epithelial cells are involved in the pathogenesis of airway inflammation and airway remodeling of asthma. E-cadherin (ECAD) has been shown to be involved in airway epithelium injury repair, but its underlying mechanisms to this process is poorly understood. Here, we describe a previously undetected function of ECAD in regulating the balance of EMT and MET during injury repair. Injury in mice and human bronchial epithelial cells (HBECs) was induced by successive ozone stress for 4 days at 30 min per day. ECAD overexpression in HBECs was induced by stable transfection. EMT features, transforming growth factor beta1 (TGF-β1) secretion, transcriptional repressor Snail expression, and β-catenin expression were assayed. Ozone exposure and then removal successfully induced airway epithelium injury repair during which EMT and MET occurred. The levels of TGF-β1 secretion and Snail expression increased in EMT process and decreased in MET process. While ECAD overexpression repressed EMT features; enhanced MET features; and decreased TGF-β1 secretion, Snail mRNA level, and β-catenin protein expression. Moreover, activating β-catenin blocked the effects of ECAD on EMT, MET and TGF-β1 signaling. Our results demonstrate that ECAD regulates the balance between EMT and MET, by preventing β-catenin to inhibit TGFβ1 and its target genes, and finally facilitates airway epithelia repair.

Background: The availability and use of frozen–thawed embryos after controlled ovarian hyperstimulation for assisted reproduction have increased with improvements in vitrification techniques and the rise of gonadotropin-releasing hormone (GnRH) antagonist protocols. Although evidence has shown that frozen–thawed embryo transfers (FETs) result in higher live birth rates than fresh embryo transfers, it is uncertain whether this association exists in cycles employing the GnRH antagonist protocol.Objective: To test the hypothesis that FETs are more likely to result in a live birth than fresh embryo transfers in a GnRH antagonist protocol cycle and to investigate whether frozen blastocyst transfer increases live birth rates compared to fresh blastocyst transfer.Design: A retrospective historical cohort study was conducted using data collected from the Department of Reproductive Medicine of Liuzhou Maternity and Child Healthcare Hospital for 1,437 patients who underwent the GnRH antagonist protocol between 1 January 2015, and 31 December 2020. The primary outcome was the live birth rate, which was compared between fresh embryo transfer and FET, and the secondary outcomes were clinical pregnancy rate and miscarriage rate, which were compared between the two groups. Analyses were adjusted to account for the age of the patient, number of embryo transfers, day of embryo transfer, and type of infertility.Results: Fresh embryo transfers accounted for 1,026 (71.4%) of the 1,437 patients who underwent the GnRH antagonist protocol in our analysis, while FETs accounted for 411 (28.6%). Patients with fresh and frozen–thawed embryos had comparable median body mass index (body mass index; 22.3 [IQR, 24.6–20.0] vs. 22.0 [IQR, 24.5–19.9]). There was a significant difference in the median age of the fresh embryo transfer group (34.0 [IQR, 39.0–30.0]) and the Frozen–thawed embryo transfer group (32.0 [IQR, 37.0–29.0]). Blastocysts were transferred in 14.6% of the fresh embryo transfer cycles and 45.5% of the FET cycles, whereas they account for 10.4% and 13.0% of all patients, respectively. The mean number of embryos transferred was 2 (IQR, 2.0–1.0) for the fresh embryo transfer group and 1 (IQR, 2.0–1.0) for the FET group, with a significant difference in the mean number of embryos transferred. The live birth rate after fresh embryo transfer vs. FET was 28.7% vs. 34.5% (absolute difference, 5.9%; adjusted relative risk [aRR], 1.15 [95% CI, 0.88–1.51]). The clinical pregnancy rates were 39.9% vs. 46.0%, respectively (absolute difference, 6.1%; aRR, 1.10 [95% CI, 0.85–1.43]). The miscarriage rates were 22.5% vs. 23.8%, respectively (absolute difference, 1.3%; aRR, 1.13 [95% CI, 0.75–1.70]).Conclusion: In this retrospective study of women who underwent assisted reproduction using GnRH antagonists, FETs resulted in a higher live birth rates and clinical pregnancy rates than fresh embryo transfers, which parts of these differences were attributable to embryo stage. However, the interpretation of the findings is limited by the possibility of selection and confounding biases.

This study aimed to evaluate the predictive value of relative change in E2 levels during controlled ovarian stimulation (COS) on embryo development and pregnancy outcomes in assisted reproductive technology (ART). We retrospectively analyzed 9,376 patients who underwent their first fresh ART cycle from January 1, 2020, to December 31, 2022. Patients were classified into four groups based on relative change in E2 levels: low response group, moderate response group, moderate-high response group, and high response group. The primary outcomes were blastocyst formation rate, clinical pregnancy rate, and live birth rate, while secondary outcomes included miscarriage rate and ectopic pregnancy rate. Most cycles (96.5%) demonstrated an increase in E2 levels during COS. The blastocyst formation rate significantly increased across the groups (low response group: 0.13, moderate response group: 0.21, moderate-high response group: 0.28, high response group: 0.34; P < 0.001). Multivariable logistic regression showed significantly higher blastocyst formation rates in the moderate response group (adjusted OR = 2.012, 95% CI: 1.687–2.399), moderate-high response group (adjusted OR = 4.613, 95% CI: 3.853–5.523), and high response group (adjusted OR = 11.295, 95% CI: 9.192–13.880) compared to the low response group. Both clinical pregnancy rate and live birth rate were significantly higher in the moderate-high response group and high response group compared to the low response group (clinical pregnancy rate: 54.5% and 61.5% vs. 35.5%, adjusted RR = 1.21 [95% CI: 1.03–1.42] and 1.27 [95% CI: 1.08–1.51]; live birth rate: 44.9% and 52.0% vs. 25.7%, adjusted RR = 1.27 [95% CI: 1.06–1.52] and 1.35 [95% CI: 1.11–1.64]). However, no significant differences were observed in either clinical pregnancy rate or live birth rate between the moderate response group and low response group (clinical pregnancy rate: adjusted RR = 1.07 [95% CI: 0.91–1.25]; live birth rate: adjusted RR = 1.11 [95% CI: 0.92–1.33]). No significant differences in miscarriage rate or ectopic pregnancy rate were observed across the groups. Higher E2 responses were associated with improved embryo development and better pregnancy outcomes.

Background: Thalassemia is a hereditary blood disorder that can impact fertility due to various factors such as iron overload and endocrine disruption. While the effects of iron overload on fertility outcomes in transfusion-dependent thalassemia (TDT) have been well-documented, there is limited data on how NTDT affects assisted reproductive technology (ART) outcomes. This study aims to assess the fertility and pregnancy outcomes of NTDT patients compared to thalassemia carriers (TC) patients in IVF and frozen embryo transfer (FET) cycles.Methods: This retrospective cohort study analyzed 6,911 female patients who underwent autologous IVF treatment at a private reproductive center between January 2013 and December 2022. The study included women who were carriers of thalassemia or diagnosed with NTDT. ART outcomes, including oocyte retrieval rate, embryo development (maturation rate, number of fertilized oocytes and blastocyst formation rate), clinical pregnancy rate, live birth rate, and miscarriage rate, were compared between NTDT and TC patients. Propensity score matching (PSM) and multivariable adjustments for potential confounders were applied in the statistical analyses.Results: NTDT patients had a significantly lower oocyte retrieval rate (0.88 vs. 0.93, p < 0.05) and a longer interval from medication initiation to oocyte retrieval (13.35 days vs. 12.38 days, p < 0.05) compared to TC patients. However, NTDT patients exhibited higher oocyte maturation rates and a greater number of fertilized oocytes. Despite these differences in embryo development metrics, there were no statistically significant differences in clinical pregnancy rates and live birth rates between NTDT and TC patients in both fresh embryo transfer (IVF-ET) and FET cycles (p > 0.05). These findings suggest that while NTDT may affect certain aspects of embryo development, it does not significantly impact overall pregnancy outcomes in ART.Conclusion: This study provides valuable insights into ART outcomes for NTDT patients, showing that, despite challenges in oocyte retrieval, their fertility and pregnancy outcomes are comparable to those of thalassemia carriers. Clinicians should consider individualized treatment plans and provide comprehensive counseling for NTDT patients, focusing on their specific fertility characteristics, to optimize ART outcomes. Further research is needed to explore the underlying mechanisms affecting embryo development in NTDT patients and to confirm these findings in broader populations.

Purpose: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, characterized by intense lung infiltrations of immune cells (macrophages and monocytes). While existing studies have highlighted the crucial role of the competitive endogenous RNA (ceRNA) regulatory network in COPD development, the complexity and characteristics of the ceRNA network in monocytes remain unexplored. Methods: We downloaded messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) microarray data from GSE146560, GSE102915, and GSE71220 in the Gene Expression Omnibus (GEO) database. This data was used to identify differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs). Predicted miRNAs that bind to DElncRNAs were intersected with DEmiRNAs, forming a set of intersecting miRNAs. This set was then used to predict potential binding mRNAs, intersected with DEmRNAs, and underwent functional enrichment analysis using R software and the STRING database. The resulting triple regulatory network and hub genes were constructed using Cytoscape. Comparative Toxicomics Database (CTD) was utilized for disease correlation predictions, and ROC curve analysis assessed diagnostic accuracy. Results: Our study identified 5 lncRNAs, 4 miRNAs, and 149 mRNAs as differentially expressed. A lncRNA-miRNA-mRNA regulatory network was constructed, and hub genes were selected through hub analysis. Enrichment analysis highlighted terms related to cell movement and gene expression regulation. We established a LINC00482-has-miR-6088-PRRC2B ceRNA network with diagnostic relevance for COPD. ROC analysis demonstrated the diagnostic value of these genes. Moreover, a positive correlation between LINC00482 and PRRC2B expression was observed in COPD PBMCs. The CTD database indicated their involvement in inflammatory responses. Conclusion: In summary, our study not only identified pivotal hub genes in peripheral blood mononuclear cells (PBMCs) of COPD but also constructed a ceRNA regulatory network. This contributes to understanding the pathophysiological processes of COPD through bioinformatics analysis, expanding our knowledge of COPD, and providing a foundation for potential diagnostic and therapeutic targets for COPD.