1.Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.
Dan FENG ; Jian ZHANG ; Huanmin NIU ; Xiaoxue ZHENG ; Mengqi JIA ; Qiqi LU ; Jing WANG ; Wenxue GUO ; Qi SUN ; Huiqing YUAN ; Hongxiang LOU
Acta Pharmaceutica Sinica B 2025;15(4):2095-2113
The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe2+ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe2+, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.
2.Expression Profiling of Circular RNA Associated with Lymph Node Metastasis in Cervical Cancer
Rui LI ; Yilin GUO ; Lu WANG ; Xingyue XU ; Fuhua LU ; Mengqi LI ; Hu ZHAO
Journal of Practical Obstetrics and Gynecology 2025;41(3):223-229
Objective:To screen differentially expressed circular RNAs(circRNA)associated with lymph node metastasis in cervical cancer and investigate their molecular mechanism and biological function.Methods:Cancer tissue samples were collected from 40 cervical cancer patients(20 with lymph node metastasis and 20 without lymph node metastasis).Three specimens were randomly selected from each group,and the circRNA expression profile was analyzed using high-throughput sequencing technology,and perform KEGG and GO enrichment analy-sis was performed on the differentially expressed circRNA derived mother genes.Real-time fluorescence quantita-tive PCR(qRT-PCR)technology was used to validate four significantly upregulated circRNAs with high differential multiples,and a ceRNA network was constructed for database prediction.The relationship between circRNA with the most significant differential expression and clinical pathological features was analyzed.Transfect circRNA small interfering RNA(siRNA)into cervical cancer cell lines.Cell lines were divided into circRNA knockdown group and negative control(si-NC)group.The proliferation of SiHa cells and HeLa cells in cervical cancer was detected by Cell Counting Kit-8(CCK-8).Results:①A total of 2039 differentially expressed circRNAs were detec-ted.The differentially expressed circRNA derived mother genes are mainly enriched in ubiquitin mediated protein hydrolysis,MAPK signaling pathway,endocytosis,apoptosis and other signaling pathways.②Four significantly up-regulated circRNAs with high differential multiples in the transfer group were selected,which are hsa_circ_0067492,hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718.qRT-PCR showed that hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718 were all highly expressed in cervical cancer tissues with lymph node metas-tasis(P<0.01).Hsa_circ_0004904 could interact with microRNAs(miRNAs)such as hsa-miR-3916.Hsa_circ_0085465 could interact with miRNAs such as hsa-miR-4659b-3p,and hsa_circ_0007718 could interact with miRNAs such as hsa-miR-127-5p.③The high and low expression groups of hsa_circ_0004904 showed statistically signigi-cant differences in lymph node metastasis and lymphovascular invasion status(P<0.05).Compared with the si-NC group,the proliferation ability of SiHa cells and HeLa cells was significantly reduced after transfection with hsa_circ_0004904 at 24,48,and 72 hours(P<0.05).Conclusions:Differentially expressed circRNAs were identi-fied in cervical cancer patients with lymph node metastasis.Silencing these circRNAs significantly inhibited the proliferation of cervical cancer cells,suggesting their potential involvement in the progression of lymph node me-tastasis.These circRNAs may serve as specific biomarkers for predicting lymph node metastasis.
3.A study on the practical effect of critical value management based on the goal and key result approach
Qing GUO ; Jie ZHOU ; Xiaoshuang YU ; Mingyang YANG ; Mengqi HAN ; Xin SONG ; Jing LI ; Jiaoqian YING
Modern Hospital 2025;25(6):865-868
Objective To explore the effectiveness of the OKR method in improving the efficiency of the whole process of critical value management,and to provide new ideas for the implementation of medical quality improvement in other medical insti-tutions.Methods A hospital in Tianjin was selected as the study object,which used the OKR method to reform the management of critical value since January 2024.The core goal of"improving the effectiveness of critical value management"was set,and the goal was broken down into quantitative key results such as"the rate of receiving the critical value system is over 95%"and"the rate of completing the standardised writing of medical records is up to 85%".Results After the reform,several quantitative key results,such as the completion rate of critical care medical record writing,the rate of standardised medical record writing,and the rate of overtime acceptance,were all better than before.Conclusion Through the OKR method to unify the whole hospital's strategic objectives,and the dynamic adjustment of the program based on data review,the hospital's critical value management efficiency has been significantly improved,effectively guaranteeing the safety of patients,and providing new perspectives and methods for the management of critical value in other medical institutions.
4.A study on the practical effect of critical value management based on the goal and key result approach
Qing GUO ; Jie ZHOU ; Xiaoshuang YU ; Mingyang YANG ; Mengqi HAN ; Xin SONG ; Jing LI ; Jiaoqian YING
Modern Hospital 2025;25(6):865-868
Objective To explore the effectiveness of the OKR method in improving the efficiency of the whole process of critical value management,and to provide new ideas for the implementation of medical quality improvement in other medical insti-tutions.Methods A hospital in Tianjin was selected as the study object,which used the OKR method to reform the management of critical value since January 2024.The core goal of"improving the effectiveness of critical value management"was set,and the goal was broken down into quantitative key results such as"the rate of receiving the critical value system is over 95%"and"the rate of completing the standardised writing of medical records is up to 85%".Results After the reform,several quantitative key results,such as the completion rate of critical care medical record writing,the rate of standardised medical record writing,and the rate of overtime acceptance,were all better than before.Conclusion Through the OKR method to unify the whole hospital's strategic objectives,and the dynamic adjustment of the program based on data review,the hospital's critical value management efficiency has been significantly improved,effectively guaranteeing the safety of patients,and providing new perspectives and methods for the management of critical value in other medical institutions.
5.Expression Profiling of Circular RNA Associated with Lymph Node Metastasis in Cervical Cancer
Rui LI ; Yilin GUO ; Lu WANG ; Xingyue XU ; Fuhua LU ; Mengqi LI ; Hu ZHAO
Journal of Practical Obstetrics and Gynecology 2025;41(3):223-229
Objective:To screen differentially expressed circular RNAs(circRNA)associated with lymph node metastasis in cervical cancer and investigate their molecular mechanism and biological function.Methods:Cancer tissue samples were collected from 40 cervical cancer patients(20 with lymph node metastasis and 20 without lymph node metastasis).Three specimens were randomly selected from each group,and the circRNA expression profile was analyzed using high-throughput sequencing technology,and perform KEGG and GO enrichment analy-sis was performed on the differentially expressed circRNA derived mother genes.Real-time fluorescence quantita-tive PCR(qRT-PCR)technology was used to validate four significantly upregulated circRNAs with high differential multiples,and a ceRNA network was constructed for database prediction.The relationship between circRNA with the most significant differential expression and clinical pathological features was analyzed.Transfect circRNA small interfering RNA(siRNA)into cervical cancer cell lines.Cell lines were divided into circRNA knockdown group and negative control(si-NC)group.The proliferation of SiHa cells and HeLa cells in cervical cancer was detected by Cell Counting Kit-8(CCK-8).Results:①A total of 2039 differentially expressed circRNAs were detec-ted.The differentially expressed circRNA derived mother genes are mainly enriched in ubiquitin mediated protein hydrolysis,MAPK signaling pathway,endocytosis,apoptosis and other signaling pathways.②Four significantly up-regulated circRNAs with high differential multiples in the transfer group were selected,which are hsa_circ_0067492,hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718.qRT-PCR showed that hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718 were all highly expressed in cervical cancer tissues with lymph node metas-tasis(P<0.01).Hsa_circ_0004904 could interact with microRNAs(miRNAs)such as hsa-miR-3916.Hsa_circ_0085465 could interact with miRNAs such as hsa-miR-4659b-3p,and hsa_circ_0007718 could interact with miRNAs such as hsa-miR-127-5p.③The high and low expression groups of hsa_circ_0004904 showed statistically signigi-cant differences in lymph node metastasis and lymphovascular invasion status(P<0.05).Compared with the si-NC group,the proliferation ability of SiHa cells and HeLa cells was significantly reduced after transfection with hsa_circ_0004904 at 24,48,and 72 hours(P<0.05).Conclusions:Differentially expressed circRNAs were identi-fied in cervical cancer patients with lymph node metastasis.Silencing these circRNAs significantly inhibited the proliferation of cervical cancer cells,suggesting their potential involvement in the progression of lymph node me-tastasis.These circRNAs may serve as specific biomarkers for predicting lymph node metastasis.
6.Construction and Validation of a Nomogram for Predicting Lymph Node Metas-tasis in Cervical Cancer Using Preoperative Inflammatory and Immune Nutri-tional Indicators
Xingyue XU ; Yilin GUO ; Lu WANG ; Mengqi LI ; Rui LI ; Fuhua LU ; Hu ZHAO
Journal of Practical Obstetrics and Gynecology 2024;40(8):645-650
Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P<0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR>1,P<0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.
7.Construction and Validation of a Nomogram for Predicting Lymph Node Metas-tasis in Cervical Cancer Using Preoperative Inflammatory and Immune Nutri-tional Indicators
Xingyue XU ; Yilin GUO ; Lu WANG ; Mengqi LI ; Rui LI ; Fuhua LU ; Hu ZHAO
Journal of Practical Obstetrics and Gynecology 2024;40(8):645-650
Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P<0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR>1,P<0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.
8.Construction and Validation of a Nomogram for Predicting Lymph Node Metas-tasis in Cervical Cancer Using Preoperative Inflammatory and Immune Nutri-tional Indicators
Xingyue XU ; Yilin GUO ; Lu WANG ; Mengqi LI ; Rui LI ; Fuhua LU ; Hu ZHAO
Journal of Practical Obstetrics and Gynecology 2024;40(8):645-650
Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P<0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR>1,P<0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.
9.Construction and Validation of a Nomogram for Predicting Lymph Node Metas-tasis in Cervical Cancer Using Preoperative Inflammatory and Immune Nutri-tional Indicators
Xingyue XU ; Yilin GUO ; Lu WANG ; Mengqi LI ; Rui LI ; Fuhua LU ; Hu ZHAO
Journal of Practical Obstetrics and Gynecology 2024;40(8):645-650
Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P<0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR>1,P<0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.
10.Construction and Validation of a Nomogram for Predicting Lymph Node Metas-tasis in Cervical Cancer Using Preoperative Inflammatory and Immune Nutri-tional Indicators
Xingyue XU ; Yilin GUO ; Lu WANG ; Mengqi LI ; Rui LI ; Fuhua LU ; Hu ZHAO
Journal of Practical Obstetrics and Gynecology 2024;40(8):645-650
Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P<0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR>1,P<0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.

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