1.WTAP-mediated m6A modification of ACSL3 inhibits ferroptosis and cisplatin resistance in lung cancer
Yuanyuan XIE ; Xin LV ; Jing ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):937-946
Objective To investigate the role and mechanisms of acyl-CoA synthetase long-chain family member 3(ACSL3)m6A modification in suppressing ferroptosis during cisplatin resistance in non-small cell lung cancer.Methods In vitro,cisplatin-resistant human lung adenocarcinoma A549/DDP cells were subjected to the following interventions:transduction with lentiviral vectors expressing ACSL3 short hairpin RNA,transfection with Wilms'tumor 1-associating protein(WTAP)small interfering RNA(siRNA)plasmids,or co-transfection with WTAP siRNA plasmids and ACSL3 overexpression plasmids.After 48 hours,all the groups were replaced with complete medium containing 1 μg/mL cisplatin and continued to culture for 24 h.A549(or A549/DDP)cells infected with ACSL3 short hairpin RNA lentivirus were subcutaneously inoculated into the backs of nude mice to establish a subcutaneous xenograft model.Immunofluorescence assay was performed to detect ACSL3 protein expression in cisplatin-treated or normally cultured A549 and A549/DDP cells.Cisplatin sensitivity was evaluated using colony formation assays.FerroOrange staining and total iron assay kits were used to measure intracellular and tissue iron levels.Lipid peroxidation was detected using the BODIPY 581/591 C11 probe.ACSL3 m6A methylation was analyzed by MeRIP-qPCR,while RNA decay assays evaluated ACSL3 mRNA stability.qRT-PCR and Western blotting were used to measure mRNA and protein expressions of ACSL3 and WTAP.Ferritin and COX2 levels were measured by immunohistochemistry.Results After cisplatin treatment,the decrease in ACSL3 expression was significantly smaller in A549/DDP cells[(48.70±3.81)%]than in A549 cells[(65.62±2.53)%].ACSL3 knockdown significantly reduced the colony formation capacity of A549/DDP cells,but increased FerroOrange intensity,total iron levels and lipid peroxidation levels(P<0.05).Cisplatin reduced ACSL3 m6A methylation in A549/DDP cells,with a less decline than in A549 cells(P<0.05).WTAP knockdown accelerated ACSL3 mRNA decay and reduced m6A enrichment of ACSL3.Compared to A549/DDP cells with only WTAP knockdown,those with combined si-WTAP knockdown and ACSL3 overexpression showed increased colony formation capacity,but decreased FerroOrange intensity,total iron levels,and lipid peroxidation levels.In vivo,ACSL3 knockdown upregulated COX2 and ferritin levels,increased Fe2+and ROS levels in tumor tissues,and suppressed tumor growth.Conclusion WTAP suppresses ferroptosis and reduces cisplatin sensitivity in A549 cells by mediating m6A modification of ACSL3 mRNA,thereby regulating the progression of lung cancer.
2.Alterations in white matter free water in anti-N-methyl-D-aspartate receptor encephalitis
Jie Hu ; Xin Wang ; Yuanyuan Guo ; Xinyi Lv ; Siyu Fan ; Yanghua Tian
Acta Universitatis Medicinalis Anhui 2025;60(7):1225-1230
Objective :
To analyze the distribution characteristics of free water ( FW) and FW-corrected fractional anisotropy (FAt) in the white matter of the brain in patients with anti-N-methyl-D-aspartate receptor ( NMDAR) encephalitis and to explore their correlation with cognitive function.
Methods :
A total of 38 patients with anti- NMDAR encephalitis and 30 controls were recruited from three hospitals in Hefei.Diffusion tensor imaging data and neuropsychological assessment results were collected.Tract-Based Spatial Statistics was applied to compare group differences in FW and FAt across the whole brain white matter.Correlation analyses were further performed to ex- amine the relationships between FW/ FAt metrics and cognitive function.
Results :
Compared to the control group, patients with anti-NMDAR encephalitis showed significantly lower scores on the montreal cognitive assessment,im- mediate recall,delayed recall,and the verbal fluency test (all P<0. 05) ,as well as significantly longer comple- tion times for color naming and word reading tasks in the stroop color word test (all P<0. 05) .Diffusion tensor im- aging analysis revealed significantly elevated FW and reduced FAt in widespread white matter regions in the patient group (all P<0. 000 1) .Further correlation analysis showed that increased FW was positively associated with the completion time of the color-switching condition in the color digital trail making test (P = 0. 044 ) and with the difference between color-switching and number sequencing conditions ( P = 0. 016 ) ,while negatively correlated with semantic fluency scores (P = 0. 002) .Additionally,FAt was positively associated with delayed recall perform- ance (P = 0. 012) ,and negatively correlated with the completion times for color naming (P = 0. 018 ) and word reading (P = 0. 046) tasks in the SCWT.
Conclusion
Patients with anti-NMDAR encephalitis exhibit significantly elevated FW and significantly reduced FAt in white matter tracts,both of which are closely linked to cognitive im- pairment.
3.Long-term efficacy of CMV/EBV bivirus-specific T cells for viral co-reactivation after stem cell transplantation.
Xuying PEI ; Meng LV ; Xiaodong MO ; Yuqian SUN ; Yuhong CHEN ; Chenhua YAN ; Yuanyuan ZHANG ; Lanping XU ; Yu WANG ; Xiaohui ZHANG ; Xiaojun HUANG ; Xiangyu ZHAO
Chinese Medical Journal 2025;138(5):607-609
4.Preemptive immunotherapy for KMT2A rearranged acute leukemias post-allogeneic stem cell transplantation.
Jing LIU ; Shuang FAN ; Xiaohui ZHANG ; Lanping XU ; Yu WANG ; Yifei CHENG ; Chenhua YAN ; Yuhong CHEN ; Yuanyuan ZHANG ; Meng LV ; Yazhen QIN ; Xiaosu ZHAO ; Xiaojun HUANG ; Xiaodong MO
Chinese Medical Journal 2025;138(22):3034-3036
5.WTAP-mediated m6A modification of ACSL3 inhibits ferroptosis and cisplatin resistance in lung cancer
Yuanyuan XIE ; Xin LV ; Jing ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):937-946
Objective To investigate the role and mechanisms of acyl-CoA synthetase long-chain family member 3(ACSL3)m6A modification in suppressing ferroptosis during cisplatin resistance in non-small cell lung cancer.Methods In vitro,cisplatin-resistant human lung adenocarcinoma A549/DDP cells were subjected to the following interventions:transduction with lentiviral vectors expressing ACSL3 short hairpin RNA,transfection with Wilms'tumor 1-associating protein(WTAP)small interfering RNA(siRNA)plasmids,or co-transfection with WTAP siRNA plasmids and ACSL3 overexpression plasmids.After 48 hours,all the groups were replaced with complete medium containing 1 μg/mL cisplatin and continued to culture for 24 h.A549(or A549/DDP)cells infected with ACSL3 short hairpin RNA lentivirus were subcutaneously inoculated into the backs of nude mice to establish a subcutaneous xenograft model.Immunofluorescence assay was performed to detect ACSL3 protein expression in cisplatin-treated or normally cultured A549 and A549/DDP cells.Cisplatin sensitivity was evaluated using colony formation assays.FerroOrange staining and total iron assay kits were used to measure intracellular and tissue iron levels.Lipid peroxidation was detected using the BODIPY 581/591 C11 probe.ACSL3 m6A methylation was analyzed by MeRIP-qPCR,while RNA decay assays evaluated ACSL3 mRNA stability.qRT-PCR and Western blotting were used to measure mRNA and protein expressions of ACSL3 and WTAP.Ferritin and COX2 levels were measured by immunohistochemistry.Results After cisplatin treatment,the decrease in ACSL3 expression was significantly smaller in A549/DDP cells[(48.70±3.81)%]than in A549 cells[(65.62±2.53)%].ACSL3 knockdown significantly reduced the colony formation capacity of A549/DDP cells,but increased FerroOrange intensity,total iron levels and lipid peroxidation levels(P<0.05).Cisplatin reduced ACSL3 m6A methylation in A549/DDP cells,with a less decline than in A549 cells(P<0.05).WTAP knockdown accelerated ACSL3 mRNA decay and reduced m6A enrichment of ACSL3.Compared to A549/DDP cells with only WTAP knockdown,those with combined si-WTAP knockdown and ACSL3 overexpression showed increased colony formation capacity,but decreased FerroOrange intensity,total iron levels,and lipid peroxidation levels.In vivo,ACSL3 knockdown upregulated COX2 and ferritin levels,increased Fe2+and ROS levels in tumor tissues,and suppressed tumor growth.Conclusion WTAP suppresses ferroptosis and reduces cisplatin sensitivity in A549 cells by mediating m6A modification of ACSL3 mRNA,thereby regulating the progression of lung cancer.
6.Development and Verification of a Surgical Prognostic Nomogram for Patients with Cervical Cancer:Based on a Real World Cohort Study
Yuanyuan HE ; Ru JING ; Yanhong LV ; Junli GE ; Biliang CHEN ; Hong YANG ; Jia LI
Journal of Practical Obstetrics and Gynecology 2024;40(1):42-48
Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.
7.Feasibility of a Clinical-Radiomics Model to Predict the Outcomes of Acute Ischemic Stroke
Yiran ZHOU ; Di WU ; Su YAN ; Yan XIE ; Shun ZHANG ; Wenzhi LV ; Yuanyuan QIN ; Yufei LIU ; Chengxia LIU ; Jun LU ; Jia LI ; Hongquan ZHU ; Weiyin Vivian LIU ; Huan LIU ; Guiling ZHANG ; Wenzhen ZHU
Korean Journal of Radiology 2022;23(8):811-820
Objective:
To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes.
Materials and Methods:
Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses.
Results:
Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness.
Conclusion
The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.
8.Relationship between social support and mental health among nurses in China:a Meta- analysis
Shanshan QIAO ; Meixia SHI ; Yuanyuan YAN ; Lifang LV ; Qiannan GUO ; Heng LI
Chinese Journal of Practical Nursing 2018;34(32):2548-2553
Objective To explore the overall relationship between social support and mental health among Chinese nurses and analyze potential moderators and provide a theoretical basis for improving nurses' mental health level. Methods The CNKI database, CQVIP, WAN-FANG DATA and China Outstanding Dissertations Database were searched for literature, in which the social support rating scale (SSRS, measured social support) and self-rating symptom scale (SCL-90, measured mental health) was used to investigate the correlation of social support and mental health in Chinese nurses. A total of 25 articles (including 25 independent samples, 4747 nurses) met the inclusion criteria and were analyzed by meta-analysis and meta-regression. Results The overall mean effect size calculation showed a significant negative correlation between social support and depression among Chinese nurses ( r=-0.17, 95% CI=-0. 24~-0.09, p<0.01). In the following analysis, the objective support, compared with subjective support and utilization degree, was more strongly correlated with SCL-90 (r =-0.20,-0.15,-0.13, Q =13.45, p < 0.01). In addition, the relationship could be influenced by factors such as age, publishing type, publishing age and region. Conclusions The social support is closely related to mental health in Chinese nurses, and the relationship could be influenced by the related factors. At the same time, the relationship between objective support and mental health is more closely related than subjective support and support utilization.
9.Anti-VEGF therapy and subretinal fibrosis
Recent Advances in Ophthalmology 2017;37(6):583-586
Subretinal fibrosis contributes to the loss of vision associated with agerelated macular degeneration.Anti-vascular endothelial growth factor therapy is the current standard treatment for exudative age-related macular degeneration.In this review,many risk factors of subretinal fibrosis are discussed,the relationship between anti-vascular endothelial growth factor therapy and subretinal fibrosis,some potential novel therapeutic methods to suppresses subretinal fibrosis are also revealed.
10.A study on the dimensional error of 3D printing maxilla models
Jun LV ; Yuanyuan LIAO ; Po WU ; Ping XU ; Lanyuan YAN ; Yan LI ; Gang ZHANG
Chongqing Medicine 2017;46(6):799-801,804
Objective To measure the dimensional error of three dimensional printing maxilla models for the clinical application to oral and maxillofacial surgery.Methods The FDM 3D printing was employed to make standard geometric shape models and maxillary models.After the surface finish of both models being observed,the contour data and fineness of geometric models,as well as the distance error of bony markers between maxillary models and jaw bones specimen were measured.Results Within the 3D printing standard geometric model,the fiber arrange horizontally in X-Z,Y-Z surface and crosswise in X-Y surface,and the accuracy errors range from-1.67% to 1.47%.Moreover,the maximum resolution was 0.25 mm in X and Y axis,and 0.50 mm in Z axis.Within the maxillary model,the distance error of bony markers range from-0.08 % to 1.96 %,and the mean errors were 1.59 %,0.86%,0.42% in X,Y and Z axis respectively.The mean error in X axis was significantly larger than that in Y or Z axis (P<0.05).Conclusion 3D printing maxilla models may possess high accuracy and apply to clinical practice.


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