1.Upregulation of NR2F1 Induces Dormancy in Ovarian Cancer Cells and Promotes Their Resistance to Chemotherapeutic Agents
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(5):794-805
ObjectiveTo explore the molecular mechanism of the chemo-resistance in NR2F1-mediated dormant ovarian cancer(OC) cells. MethodsThe expression of the NR2F1 molecule in OC patients and its relationship with the overall survival of patients were analyzed using the GEPIA database. Nuclear receptor subfamily 2 group F member 1(NR2F1) overexpressed OC cell and control cell were constructed by lentivirus in vitro transfection. The proliferation of OC cells was analyzed by CCK-8 method. Real-time fluorescent quantitative PCR(qRT-PCR) was used to analyze the mRNA expression of dormancy-related molecular genes in OC cells. Western blot was performed to analyze the protein expression levels of related molecules. The viability of OC cells treated with different chemotherapy drugs was analyzed by trypan blue exclusion method. Annexin V-FITC/PI double-staining assay was used to detect the apoptosis of OC cells treated by different chemotherapy drugs. Transcriptome sequencing technology was used to analyze the differentially expressed genes in NR2F1 overexpressed SKOV3 cell line, and the relevant signaling pathways were screened through KEGG enrichment analysis. qRT-PCR was performed to verified the mRNA expression level of drug resistance-related molecules in OC cells. The GEPIA database was used to further verify the correlation between the expression of NR2F1 and the drug resistance-related genes. ResultsThe NR2F1 expression is low in the tumor tissues and the high expression of NR2F1 correlates with poor overall survival in the OC patients. Compared with the control group, the proliferation ability of the NR2F1 overexpressed OC cell lines was significantly reduced. The expression of dormancy-related molecules, cyclin-dependent kinase inhibitor 1B(p27), differentiated embryonic cartilage gene-2(DEC2) and transforming growth factor-β2(TGF-β2), increased significantly in the NR2F1 overexpressed OC cell lines, and anti-apoptotic molecule B-cell lymphoma gene-2(BCL-2) also increased. In contrast, the expression of the proliferation-related molecule KI67 was decreased. In addition, the NR2F1 overexpressed OC cell lines significantly enhanced the resistance to chemotherapy drugs. Transcriptome sequencing and KEGG enrichment analysis showed that the upregulated genes in NR2F1 overexpressed OC cells were enriched in phosphatidylinositol-3-kinase-protein kinase(PI3K-Akt) signaling pathway, focal adhesion pathway, extracellular matrix-receptor interactions and signaling pathways regulating pluripotency of stem cells, and the downregulated genes in NR2F1 overexpressed OC cells were mainly enriched in cell cycle pathway. The results of qRT-PCR verification showed that drug resistance-related molecules kinesin family member 26B(KIF26B), secreted protein acidic and rich in cysteine(SPARC), collagen type Ⅵ alpha 1(COL6A1), collagen type Ⅴ alpha 2 chain(COL5A2), frizzled homolog 1(FZD1) and inhibin subunit beta A gene(INHBA) were up-regulated in NR2F1 overexpressed OC cells. GEPIA database analysis showed that the expression of NR2F1 in OC tumor tissues was positively correlated with the expression of drug resistance-related genes KIF26B, SPARC, COL6A1, COL5A2, FZD1 and INHBA. ConclusionsThis study shows that upregulation of NR2F1 may induce dormancy in OC cells and enhance their resistance to chemo-drugs. The NR2F1-mediated drug resistance of dormant OC cells might be associated with the PI3K-Akt signaling pathway and signaling pathways regulating pluripotency of stem cells, and closely related to the upregulation of KIF26B, SPARC, COL6A1, COL5A2, FZD1 and INHBA.
2.Effect of new labor process on early postpartum pelvic floor muscle strength
Yu WANG ; Xinnan HOU ; Lei ZHANG ; Songwen NIAN ; Ruilin GUO ; Bingbing XIAO ; Xiaoqing WANG ; Xiaoxiao WANG ; Ye LU
Chinese Journal of Perinatal Medicine 2024;27(6):499-503
Objective:To explore the changes in early postpartum pelvic floor muscle strength following the implementation of the new labor process.Methods:This retrospective cohort study selected 1 834 primiparous women with singleton, full-term pregnancies who delivered at Peking University First Hospital from February 2011 to March 2016 and had a pelvic floor re-examination 6-8 weeks postpartum. Out of these, 738 cases who followed the old labor process before 2014 were categorized as the old process group, and 1 096 cases who followed the new labor process after 2014 were categorized as the new process group. Basic data, childbirth information, and postpartum pelvic floor muscle strength of the two groups were compared. Data were statistically analyzed using t-test, Chi-square test, Mann-Whitney U test, Wilcoxon rank-sum test, and ordered multicategory logistic regression to assess the impact of the new and old labor process and other factors on pelvic floor muscle strength. Results:The total duration of labor, as well as the duration of the first, second, and third stages of labor, were longer in the new process group than in the old process group [549.0 min (360.0-768.0 min) vs. 482.5 min (328.0-635.0 min), 465.0 min (297.5-672.5 min) vs. 420.0 min (285.0-555.0 min), 42.0 min (24.0-74.0 min) vs. 27.0 min (18.0-45.0 min), with Z-value of-5.72,-3.95, and-9.28, all P<0.05). The rates of vaginal delivery and labor analgesia were higher in the new process group [72.1% (790/1 096) vs. 67.2% (496/738), χ2=7.41; 67.4% (739/1 096) vs. 53.4% (394/738), χ2=36.82; both P<0.05]. There were no statistically significant differences in the comparison of Class Ⅰ and Class Ⅱ muscle strength grades between the two groups (all P>0.05). Conclusion:There was no significant decline in early postpartum pelvic floor muscle strength following the implementation of the new labor process standards.
3.Application of Mini Nutritional Assessment in patients with chronic obstructive pulmonary disease and its correlation with BODE indexes.
Jia SUN ; Jingjing ZHENG ; Songwen GUO ; Zhe ZHU ; Xin CHEN
Journal of Southern Medical University 2013;33(8):1217-1220
OBJECTIVETo evaluate the value of Mini Nutritional Assessment (MNA) in geratic patients with chronic obstructive pulmonary disease (COPD) and analyze the correlation of MNA scores with BODE indexes.
METHODSA total of 139 geratic outpatients with stable COPD admitted from April 2012 to October 2012 were enrolled. The nutritional statuses of the patients were assessed using MNA and the patients were subsequently classified into well-nourished group, risk of malnutrition group and malnutrition group. For all the patients, the anthropometric parameters, pulmonary function and 6-minute-walk distance (6MWD) were examined, and functional dyspnea was evaluated using Modified Medical Research Council Scale (MMRC). The BODE indexes were calculated and analyzed for their correlation with the MNA scores.
RESULTSThe 3 groups showed no significant differences in gender distribution (P>0.05), but their age, anthropometric parameters and BODE indexes (BMI, MMRC, 6MWD, FEV1%pred) differed significantly (P<0.001). In all the patients, MNA scores showed a significant inverse correlation with BODE index (r=-0.602; P<0.001).
CONCLUSIONMNA scores are strongly correlated with the anthropometrical parameters and BODE indexes to allow screening of the nutritional status in patients with COPD. Nutrition is an important factor affecting the disease symptoms, and nutritional improvement is one of the effective measures to relieve the symptoms of COPD.
Aged ; Female ; Humans ; Male ; Middle Aged ; Nutrition Assessment ; Nutritional Status ; Outpatients ; Pulmonary Disease, Chronic Obstructive ; physiopathology ; Severity of Illness Index

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