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Abstract Background Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis. Methods The activation model of ESCs was constructed by TGF-β1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis. Results We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes. Conclusion Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.

AimThe aim of this study was to assess the risk factors for coexisting deep endometriosis (DE) in patients with recurrent ovarian endometrioma (OE).MethodsWe retrospectively reviewed 151 recurrent OE patients who had been diagnosed of OE but not DE at the time of their first surgery and then received a second surgery for recurrent endometriosis with or without DE. Their clinical characteristics at the time of the first and second surgeries were collected. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors for coexisting DE in patients with recurrent OE.ResultsAmong the 151 recurrent OE patients, 46 were diagnosed of DE during the recurrent surgery and included in the DE group, while the remaining 105 patients were included in the non-DE group. In univariate analysis, there were significant differences in terms of uterine retroversion during the primary surgery and the follow-up time after the primary surgery between the DE and non-DE groups. The multivariate analysis also showed that both uterine retroversion and the follow-up time (≥5 years) were associated with the coexistence of DE during the recurrent surgery. The odds ratio (OR) for uterine retroversion was 3.72 [95% confidence interval (CI) 1.62–8.53], and the OR for follow-up time (≥5 years) was 5.03 (95% CI 2.29–11.02).ConclusionsOur study suggested that for recurrent OE patients, uterine retroversion during the first surgery and a follow-up time of at least 5 years are risk factors for the coexistence of DE in recurrent surgery, early prevention and full preparation before the recurrent surgery should be emphasized in these conditions.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. The novel sensitive biomarkers and therapeutic targets are urgently needed for the early diagnosis of HCC and improvement of clinical outcomes. Glia maturation factor-β (GMFB) is a growth and differentiation factor for both glia and neurons and has been found to be tightly involved in inflammation and neurodegeneration conditions. In our study, the expression level of GMFB was significantly up-regulated in patients with HCC and positively co-expression with tumor node metastases (TNM) stage and histopathological grade of HCC. The high expression level of GMFB was remarkably associated with poor overall survival, which mainly occurred in males rather than females. Multivariate analysis revealed GMFB to be an independent prognostic factor for overall survival in patients with HCC. Results of Gene Ontology (GO) and KEGG pathways analysis showed that down-regulation of pathways related to protein translation and mitochondria function were enriched. Protein-protein interaction analysis revealed the central role of mitochondria protein in HCC. The downregulation of genes involved in glycolysis and gluconeogenesis was observed among the co-expression genes of GMFB. Knockdown of GMFB in Hep3B significantly inhibited proliferation, migration, and invasion of Hep3B cells, and also downregulated the expression levels of some of metal matrix proteinase (MMP), increased mtDNA copy number and loss of mitochondrial transmembrane potential. GMFB influences the malignancy rate of HCC possibly through regulation of the expression of MMPs, mtDNA function and glycolysis. We proposed that GMFB was a promising HCC diagnostic and prognostic biomarker and therapeutic target in HCC.

Objective This study was performed to assess the predictive value of the anti-Müllerian hormone (AMH) serum level for spontaneous pregnancy in women after endometriosis surgery. Methods In total, 124 patients with suspected ovarian endometrioma planning to undergo laparoscopic ovarian cystectomy were divided into a high AMH group (AMH > 2 ng/mL) and low AMH group (AMH ≤ 2 ng/mL) according to their preoperative AMH levels. The postoperative AMH levels were also measured, and pregnancy outcomes were followed up. Results Twenty-one patients were excluded, and 52 pregnancies were registered in the remaining 103 patients diagnosed with endometriosis. The pregnancy rate was significantly greater in the high than low AMH group. Receiver operator characteristics analysis of preoperative AMH, postoperative AMH, and the AMH decline rate showed that preoperative AMH was associated with the greatest area under the curve. Kaplan–Meier curves showed that women in the high AMH group had a significantly higher cumulative pregnancy rate than those in the low AMH group. Conclusion The preoperative AMH level might be a useful marker to predict the occurrence of natural pregnancy and could be offered as part of the fertility strategy to women who desire pregnancy after endometriosis surgery.

Objective This study was performed to assess whether prophylactic uterine artery embolization (UAE) is beneficial for second-trimester abortion with complete placenta previa (CPP). Methods Patients with CPP who underwent second-trimester pregnancy termination by labor induction with or without UAE from January 2010 to January 2018 were retrospectively reviewed. In total, 25 patients were eligible for analysis. The primary outcomes were the abortion success rate and bleeding volume, and the secondary outcomes were the induction-to-abortion time, length of hospital stay, and complications. Results CPP occurred in all 25 patients. Fifteen patients underwent prophylactic UAE (UAE group) and 10 did not (control group). Abortion was successful in 13 of 15 (86.7%) women in the UAE group and in 9 of 10 (90.0%) women in the control group. There was no significant difference in the bleeding volume or induction-to-abortion time between the two groups. The hospital stay was longer and pyrexia was more common in the UAE than control group. Conclusion Prophylactic UAE did not markedly improve the outcomes of second-trimester abortion in patients with CPP. Conversely, it may increase the risk of complications and prolong the hospital stay.

Articular cartilage is not a physiologically self‐renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocyte‐based tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte‐derived progenitor cells (CDPCs). The stem cell‐like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low‐density, low‐glucose 2‐dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL‐cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6–13 cm2) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte‐based therapies. Significance Injury of cartilage, a non‐self‐repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue‐derived stem cells have been shown to contribute to tissue renewal and homeostasis, the derivation, biological function, and application potential of stem/progenitor cells found in adult human articular cartilage are incompletely understood. This study reports the derivation of a population of cartilage stem/progenitor cells from fully differentiated chondrocytes under specific culture conditions, which have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. These findings support the possibility of using in vitro amplified chondrocyte‐derived progenitor cells for joint cartilage repair.

ObjectiveThis study sought to uncover the relationship between physical education courses integrated with civic education (PECICE) and prosocial behavior among university students. Additionally, we aimed to decipher the mediating roles of cultural confidence and self-esteem within this relationship.MethodsEmploying a questionnaire-based approach, we assessed the relationship among PECICE, cultural confidence, self-esteem, and prosocial behavior in university students. The instrument comprised four distinct scales: the Perceived Effectiveness Scale for PECICE, the Cultural Confidence Scale, the Self-Esteem Scale, and the Prosocial Behavior Scale. Our sample encompassed 293 Chinese college students, consisting of 137 men and 156 women, with an average age of 21.39 years (SD = 2.1).ResultsPECICE demonstrated significant positive associations with cultural confidence (r = 0.29, p < 0.001), self-esteem (r = 0.35, p < 0.001), and prosocial behavior (r = 0.40, p < 0.001). The influence of PECICE on prosocial behavior among university students was mediated through three channels: solely via cultural confidence (mediating effect value: 0.14), solely via self-esteem (mediating effect value: 0.22), and through the combined influence of both cultural confidence and self-esteem (mediating effect value: 0.2).ConclusionThe intertwined mediating roles of cultural confidence and self-esteem highlight their pivotal significance in enhancing the efficacy of PECICE. These insights offer a valuable reference for both educators and policymakers striving to augment prosocial behavior in university students.

Osteonecrosis of the femoral head (ONFH) is a common but intractable disease. In this study, we investigated the mechanisms regulating alterations in mesenchymal stem cell (MSC) differentiation in ONFH. Five patients who were diagnosed with ONFH were enrolled in this study. Bone MSCs (BMSCs) were isolated from the osteonecrotic zone in the femoral head (FH-pMSCs) and from the normal zone in the pelvis (hMSCs) of the same patient. Morphology, cell proliferation and expression of mediators of the Wnt signalling pathway were evaluated. There were significant differences in cell proliferation and expression of surface markers between the two populations of cells. FH-pMSCs exhibited significantly lower osteogenic differentiation compared with hMSCs (P50.0001). Dissection of the Wnt pathway showed that FH-pMSCs had significantly higher GSK3β expression compared with hMSCs (P50.001). Addition of LiCl, a GSK3β inhibitor, significantly increased osteogenic differentiation in FH-pMSCs, suggesting a relationship between the microenvironment and regulation of stem cell behaviour in ONFH. FH-pMSCs also exhibited significant downregulation of other mediators of the Wnt signalling pathway, including runx2 and b-catenin. Our data suggested that mediators of the Wnt signalling pathway, such as GSK3β could be important therapeutic targets for early-stage ONFH. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the third most common carcinoma and the fourth leading cause of cancer-associated mortality in women. The deregulation of fatty acid metabolism plays a crucial role in the progression of various tumors. This study is aimed at exploring the prognostic values of fatty acid metabolism- (FAM-) related long noncoding RNAs (lncRNAs) in CC. FAM-related differentially expressed genes (DEGs) and lncRNAs were screened in CC specimens based on TCGA datasets. Univariate analysis was carried out on differentially expressed lncRNAs to screen the survival-related lncRNAs. Multivariate assays were performed on the resulting lncRNAs to create a novel risk model. Survival assays were applied to examine the prognostic abilities of our model. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of the new model. The association between risk model and immune responses was analyzed. In this study, we screened 9 differently expressed lncRNAs associated with the clinical outcome of CC patients. A nine-lncRNA signature comprising SCAT1, AC119427.1, AC009097.2, MIR100HG, AC010996.1, AL583856.2, MIAT, AP003774.2, and AC004540.2 was established to predict overall survival of CC. Survival assays revealed that patients’ high risk score showed a shorter overall survival than those with low risk score. Multivariate assays demonstrated that the nine-gene signature was an independent prognostic factor in CC. In addition, we observed that APC_co_stimulation, CCR, and parainflammation were distinctly different between low-risk and high-risk groups. Our group observed a distinct difference in the expressions of CD44, TNFRSF8, CD276, LAG3, TNFRSF14, TMIGD2, VTCN1, TNFRSF25, CD80, NRP1, TNFRSF18, CD70, TNFSF9, and LGALS9 between the two groups of patients. Overall, our findings indicated that the 9 FAM-related lncRNA signature might be a promising prognostic factor for CC and can promote the management of FAM-related therapy in clinical practice.

Ovarian cancer (OC) is the main cause of deaths worldwide in female reproductive system malignancies. Growing studies have indicated that eRNAs could regulate cellular activities in various tumors. Yet the potential roles of eRNAs in OC progression have not been elucidated. Thus, comprehensive assays were needed to screen the critical eRNAs and to explore their possible function in OC. We used Kaplan–Meier methods to identify survival-associated eRNAs in OC based on TCGA datasets. The levels of ZFHX4-AS1 were examined using TCGA datasets. Further exploration was carried out based on the following assays: clinical and survival assays, GO terms, and KEGG assays. TIMER was applied to delve into the relationships between ZFHX4-AS1 and tumor immune infiltration. In this research, we observed 71 survival-related eRNAs in OC patients. ZFHX4-AS1 was highly expressed in OC specimens and predicted a poor prognosis of OC patients. In addition, high ZFHX4-AS1 expression was positively related to the advanced stages of OC specimens. Multivariate assays revealed that ZFHX4-AS1 was an independent prognostic factor for overall survival of OC patients. KEGG analysis indicated that ZFHX4-AS1 may play a regulatory effect on TGF-beta signaling, PI3K-Akt signaling, and proteoglycans in cancer. The pan-cancer validation indicated that ZFHX4-AS1 was related to survival in eight tumors, namely, UCEC, STAD, SARC, OV, ACC, KICH, KIRC, and BLCA. The expression of ZFHX4-AS1 was correlated with the levels of B cells, T cell CD8+, neutrophil, macrophage, and myeloid dendritic cells. Simultaneously, ZFHX4-AS1 may be a prognostic biomarker and a distinctly immunotherapy-related eRNA in OC.