Abstract:Objective To investigate the causal relationship between gut microbiota and functional dyspepsia(FD)and the potential mediating effects of blood metabolites using Mendelian randomization(MR).Methods Summary-level data were obtained from publicly available genome-wide association studies(GWAS)databases.Genetic instruments were extracted for 473 gut microbial taxa and 233 blood metabolites,and FD GWAS data were sourced from a Finnish database.Two-sample MR was performed to assess the potential associations of gut microbiota and blood metabolites with FD.Sensitivity analyses were conducted to evaluate the robustness of the MR results.Mediation MR was used to explore the potential mediating effects of blood metabolites.Results A total of 29 gut microbial taxa and 2 blood metabolites showed reliable causal relationships with FD(P<0.05).Mediation analysis indicated that the proportion of total cholesterol in high-density lipoprotein(HDL)mediated the causal relationship between Lawsonibacter and FD risk.Conclusion Lawsonibacter was positively correlated with FD,and the proportion of total cholesterol in HDL played a mediating role in this relationship.

Abstract:Objective To systematically review risk prediction models for malnutrition in patients with chronic heart failure(CHF),and to provide evidence for model optimization and clinical practice.Methods Databases including PubMed,The Cochrane Library,Embase,Web of Science,CNKI,Wanfang,VIP,and SinoMed were searched from inception to March 2025 for studies on malnutrition risk prediction models in CHF patients.Model quality was assessed using the PROBAST tool,and Meta-analysis of predictors was performed using R version 4.4.1.Results Nine studies reporting nine models were included.All models were rated as having high risk of bias and good applicability.The area under the receiver operating characteristic curve(AUC)of the models ranged from 0.730 to 0.996.The pooled AUC was 0.84[95%CI(0.79,0.90)].Meta-analysis identified the following independent predictors of malnutrition risk in CHF patients:age,smoking,edema,and C-reactive protein(P<0.05).Conclusion Malnutrition risk prediction models for CHF patients require further development.Healthcare professionals should pay particular attention to older patients,smokers,those with edema,and individuals with elevated C-reactive protein,implementing targeted preventive measures accordingly.

Abstract:Objective To systematically evaluate the impact of preoperative biliary drainage(PBD)on postoperative complications in patients with malignant obstructive jaundice undergoing pancreaticoduodenectomy(PD),thereby providing evidence for clinical decision-making.Methods A comprehensive search of PubMed,Embase,Web of Science,The Cochrane Library,CNKI,VIP,Wanfang,and CBM databases was conducted for studies published between January 1,2014 and February 10,2026.Literature screening,quality assessment,and data extraction were performed according to predefined inclusion/exclusion criteria.Statistical analyses of postoperative complications were conducted using RevMan 5.4 and Stata 17.0.Results A total of 42 studies were included,involving 19,036 patients,with 12,156 patients in the PBD group and 6,880 in the non-PBD(NPBD)group.Meta-analysis revealed that the incidence of postoperative hemorrhage was lower in the PBD group than in the NPBD group[OR=0.80,95%CI(0.66,0.96),P=0.02];the incidence of wound infection was higher in the PBD group than in the NPBD group[OR=1.92,95%CI(1.54,2.39),P<0.001].No statistically significant differences were observed between the two groups in the incidence of overall complications,pancreatic fistula,bile leakage,intra-abdominal infection,delayed gastric emptying,or perioperative mortality(P>0.05).Conclusion Preoperative biliary drainage significantly reduces the risk of postoperative bleeding but may increase the incidence of wound infection.Current evidence is insufficient to support that PBD can comprehensively improve prognosis.Future multicenter randomized controlled trials are warranted to identify optimal candidates and standardize procedural protocols for PBD.

Abstract:Premature ovarian failure(POF)is a pathological condition characterised by the decline of ovarian function in women under the age of 40.It is closely associated with decreased fertility,elevated risks of osteoporosis and cardiovascular diseases,and has emerged as a significant clinical issue affecting women's reproductive health and quality of life.Current research indicates that granulosa cell(GC),as key components of the follicular microenvironment,can accelerate follicular atresia through abnormal apoptosis,thereby contributing to the onset and progression of POF.In recent years,advances in molecular biology and omics technologies have facilitated deeper investigation into the mechanisms of GC apoptosis.Studies have revealed that its regulation involves multi-level factors:at the protein level,the BCL-2 family and the Caspase cascade constitute the core module of apoptosis execution;at the signaling pathway level,pathways such as Wnt/β-catenin,death receptor signaling,Hippo,and PI3K/AKT/mTOR interact through crosstalk to coordinately regulate GC apoptosis.In addition,epigenetic modifications,oxidative stress,hormonal imbalances,and inflammatory microenvironments collectively contribute to the initiation and progression of GC apoptosis.Hence,this review systematically summaries the signaling pathways,key proteins,and underlying regulatory mechanisms related to GC apoptosis,to elucidate its role in the pathogenesis of POF.This work seeks to provide novel theoretical perspectives on the pathological mechanisms of POF and to offer a reference for developing targeted intervention strategies aimed at regulating GC apoptosis.

Abstract:Primary culture of bladder smooth muscle cells is challenged by issues such as proneness to dedifferentiation,susceptibility to impurity contamination,and operational complexity.This article summarizes the isolation methods(tissue explant culture method,enzymatic digestion method),purification techniques(differential adhesion method,selective medium method,differential centrifugation,mesh filtration separation),biophysical stimulation(mechanical stretch,intravesical pressure,basic fibroblast growth factor,collagen matrix,hypoxic stimulation),identification methods(histological observation,immunofluorescence staining),and key operational considerations.By comparing the advantages and disadvantages of different approaches,this review aims to provide references for subsequent related research.

Abstract:Objective To investigate the effect of Dexmedetomidine(Dex)on osteosarcoma(OS)cells and its underlying mechanism.Methods The optimal exposure concentrations of Dex,α2-adrenergic receptor(α2-AR)antagonist,PKA inhibitor,and ERK1/2 inhibitor were determined by MTT assay.Genes positively correlated with ERK1/2 expression in OS samples and potentially mediating its tumor-promoting effect were extracted from the GEPIA database,and their expression levels in OS cells were verified by qRT-PCR and Western blot.After silencing candidate genes with siRNA,MTT assay,flow cytometry,Transwell assay,and colony formation assay were performed to evaluate the role of ERK1/2 pathway genes in the processes by which Dex affects OS cell proliferation,apoptosis,invasion,and colony formation ability.Results 25 nM Dex was the optimal concentration for promoting OS cell viability.The ERK1/2 inhibitor(Ravoxertinib)significantly antagonized the enhancement of OS cell viability induced by low-concentration Dex,whereas inhibition of α2-AR or PKA exerted weaker effects.Bioinformatics analysis identified that TRIO,PKN2,CKAP5,and NEK4 were highly associated with the oncogenic function of ERK1/2 in OS.Western blot demonstrated that Ravoxertinib blocked the upregulation of TRIO,PKN2,CKAP5,and NEK4 induced by Dex.Silencing TRIO,PKN2,or CKAP5 effectively suppressed Dex-induced increases in OS cell viability,invasion capacity,and colony formation,while attenuating the inhibitory effect of Dex on cell apoptosis.Conclusion Low-concentration Dex upregulates the expression of TRIO,PKN2,and CKAP5 in an ERK1/2-dependent manner,thereby promoting the malignant biological potential of OS cells.

Abstract:Objective To systematically assess the non-linear and lag effects of daily mean temperature on varicella incidence in Weifang using a distributed lag non-linear model(DLNM).Methods Surveillance data on varicella cases and concurrent meteorological data in the Weifang area from January 2014 to December 2023 were collected.A DLNM was applied to analyze the exposure-response relationship between daily mean temperature and varicella incidence in Weifang area.Results A total of 7,871 varicella cases were reported in Weifang area during the study period.Daily mean temperature correlated negatively with case counts(rs=-0.235,P<0.001).With the median of daily mean temperature(15.69℃)as the reference value,the relative risk(RR)value was higher under low temperature conditions,and the influence of low temperature appeared in the early lag period(0～9 d),while the effect of hightemperature showed a two-stage characteristic.Inthe earlylag(0～7days),it was a weak riskfactor,but inthe later lag(e.g.,14 days),it may turnintoa protective factor.Subgroup analysis revealed that varicella incidence had significant seasonal heterogeneity and age differences,and the incidence risk of the 3～6 years old group in winter was 1.9 times that in summer,showing an obvious seasonal fluctuation pattern.Sensitivity analysis confirmed model robustness.Conclusion Temperature nonlinearly influences varicella incidence in Weifang,with low temperatures posing sustained risks and high temperatures exhibiting a mild and biphasic lag pattern.Prevention and control measures should be strengthened in crowded places such as schools and childcare institutions.

Abstract:Objective To analyze and predict the changing trends of cardiovascular disease(CVD)burden attributable to high low-density lipoprotein cholesterol(LDL-C)in China from 1990 to 2021.Methods Based on the Global Burden of Disease 2021 database,Joinpoint regression analysis was used to analyze the changing trends of CVD attributable to high LDL-C.An age-period-cohort model was used to explore the effects of age,period,and cohort.An ARIMA model was used to predict the CVD burden trend attributable to high LDL-C from 2022 to 2031.Results In 2021,the disability-adjusted life year(DALY)of CVD attributable to high LDL-C was 18,407,700 person-years,with 832,800 deaths.From 1990 to 2021,there was no significant trend in the age-standardized DALYs rate(ASDR)of CVD attributable to high LDL-C[AAPC=-0.15%,95%CI(-0.35%,0.05%)].There was no significant trend in ASDR in the ischemic heart disease subgroup[AAPC=0.06%,95%CI(-0.18%,0.30%)].The ASDR in the ischemic stroke subgroup showed a decreasing trend[AAPC=-0.46%,95%CI(-0.63%,-0.29%)].Age-standardized mortality rate(ASMR)attributable to high LDL-C CVD showed no clear trend from 1990 to 2021[AAPC=0.11%,95%CI(-0.19%,0.42%)].The ASMR in the ischemic heart disease subgroup showed an increasing trend[AAPC=0.47%,95%CI(0.18%,0.76%)],while the ASMR in the ischemic stroke subgroup showed a decreasing trend[AAPC=-0.42%,95%CI(-0.66%,-0.18%)].In 2021,the CVD burden attributable to high LDL-C increased exponentially with age.The disease burden was higher in men than in women.The age effect showed that the rates of DALYs and mortality from CVD attributable to high LDL-C,ischemic heart disease,and ischemic stroke,increased with age.The period effect showed that the risks of DALYs and mortality from CVD,ischemic heart disease,and ischemic stroke attributable to high LDL-C all initially increased and then decreased.The cohort effect showed that later birth cohorts had lower risks of DALYs and mortality.The ARIMA model predicts that the overall CVD burden attributable to high LDL-C will increase from 2022 to 2031,but that of ischemic stroke will decrease.Conclusion From 1990 to 2021,the overall CVD disease burden attributable to high LDL-C in China showed no significant trend,while the disease burden trends differed between ischemic heart disease and ischemic stroke subgroups.The burden increased with age,and the disease burden was higher in males than in females.The ARIMA model predicts that from 2022 to 2031,the overall CVD disease burden attributable to high LDL-C will increase,mainly driven by ischemic heart disease,while the ischemic stroke burden will continue to decline.

Abstract:Objective To analyze the association between the triglyceride-glucose(TyG)index and osteoarthritis(OA).Methods Using data from the National Health and Nutrition Examination Survey of the United States from 2009 to 2020,multivariable Logistic regression and restricted cubic spline(RCS)were used to evaluate the relationship between the TyG index and OA,with threshold-effect analyses performed.Results Among 10,986 participants(1,484 with OA),multivariable Logistic regression showed a significant positive association between the TyG index and OA.After adjustment for age,sex,race,body-mass index,C-reactive protein,and other relevant covariates,each one-unit increase in the TyG index was associated with a 53%higher odds of OA[OR=1.53,95%CI(1.38,1.69)].RCS analysis revealed a non-linear relationship(P<0.001),when TyG index increased and approached 8.5,the risk intensity of OA increased significantly[OR=1.87,95%CI(1.43,2.44)].However,when TyG index≥8.5,the impact of elevated TyG index on OA slowed down[OR=1.18,95%CI(1.03,1.35)].Conclusion The TyG index may serve as a potential biomarker for assessing OA risk.When the TyG index is<8.5,its increase is positively correlated with an elevated risk of OA.Future interventions targeting the TyG index could contribute to lowering OA prevalence.

Abstract:Objective To explore the present situation of emergency medical rescue nursing ability based on compact county-level medical community(hereinafter referred to as"medical community"),and to analyze the training needs of emergency medical rescue nursing for nurses.Methods This study is a cross-sectional investigation.From December 2023 to December 2024,a multi-stage stratified random sampling method was used to select 300 nursing stafffrom 15 township hospitals in the Luzhou region as research subjects.A questionnaire was administered to collect data on general information,such as age and professional title,as well as emergency medical rescue nursing competency and nursing knowledge needs.Principal component analysis(PCA)was applied to reduce the dimensionality of the emergency medical rescue nursing knowledge needs,aiming to identify core demand dimensions.Results A total of 300 electronic questionnaires were distributed in this study,and 292 were valid.The score of emergency medical rescue nursing ability of 292 nurses in this study was(133.60±26.45).The nurses'gender,education level,working years,participation in emergency medical rescue,and emergency medical rescue knowledge training all affected their emergency medical rescue nursing ability(P<0.05).The majority of nursing staff express a strong desire for disaster nursing knowledge training(83.90%)and favor in-person skills instruction as the training method(92.81%).Three principal components were identified:skill and knowledge application capability,multi-scenario treatment adaptability,and dynamic rescue comprehensive capability,with a cumulative contribution rate of 83.06%.Conclusion The emergency medical rescue nursing capabilities of healthcare professionals within medical consortiums have generally reached a good level,but there is still room for improvement.There is an urgent need for nursing staffto improve their skills in hospital-based treatment,emergency care,post-disaster health management,and psychological support.PCA reveals that the core dimensions of current training needs are the application of skills and knowledge,adaptability to multi-scenario rescue scenarios,and comprehensive dynamic rescue capabilities.This highlights the necessity for targeted development of practice-oriented training systems.

Abstract:Objective To analyze the ultrasonic features of cervical lymph nodes and related involved sites in children with histiocytic necrotizing lymphadenitis(HNL).Methods The clinical data of children with HNL admitted to the First Affiliated Hospital of Henan University of Chinese Medicine between May 2022 to May 2025 were retrospectively analyzed,and the ultrasonic features of lymph nodes in abnormal parts were observed and recorded.Results A total of 33 children with HNL were enrolled,all of whom had cervical lymphadenopathy,mainly unilateral involvement(60.61%).Lymph nodes in 69.70%of the children showed an orderly rounded distribution with round-like shape;increased echo of the perinodal tissue was found in 72.73%of the children;homogeneous hypoechogenicity was observed in the internal echo of lymph nodes in 72.73%of the children;30.30%of the children had a tendency toward lymph node fusion.Some children were complicated with lymphadenopathy in other parts as well as hepatosplenomegaly.Color Doppler ultrasonography showed that the blood flow signals of lymph nodes in all children presented a hilar distribution,mainly with abundant blood flow signals(69.70%).Conclusion Ultrasonography is helpful for the early diagnosis and disease assessment of HNL in children,which can provide more effective imaging evidence for clinical practice,optimize the diagnosis and treatment pathway of HNL in children,and guide decisions regarding puncture biopsy and overall clinical management.

Abstract:Objective This study aims to investigate the role and mechanism of regulator of G-protein signaling 14(RGS14)protein in acute myocardial infarction(AMI).Methods The RGS14 knockout mice were selected to construct AMI model.The cardiac tissue and serum of mice were collected 24 h after modeling,the degree of inflammatory infiltration in the cardiac tissue was analyzed by immunohistochemical analysis,and biochemical analyzer detects serum biochemical indicators.Overexpression and knockdown adenovirus were constructed in vitro and transfected into primary rat cardiomyocytes.RT-qPCR and Western blot were used to detect the expression of RGS14,inflammation and apoptosis related markers mRNA and protein.TUNEL staining was used to analyze the apoptosis of heart tissue.Results The expression of RGS14 in myocardial cells of AMI model mouse was downregulated.Compared with wild-type mice,RGS14 knockout mice exhibited increased AMI induced cardiac dysfunction,inflammatory response,and apoptosis.Conversely,overexpression of RGS14 inhibited cardiomyocyte apoptosis in vitro.The protective effect of RGS14 on AMI injury is closely related to its inhibition of TAK1-JNK/p38 signaling pathway activation.Inhibition of TAK1 alleviates the adverse effects of RGS14 knockdown on AMI in vitro.Conclusion RGS14 exerts a protective function in the process of inflammation and apoptosis after AMI,and alleviates cardiac dysfunction by inhibiting the activation of TAK1,which provides a new potential for the treatment of AMI.

Abstract:Objective To investigate the diagnostic value of diffusion tensor imaging(DTI)technology in tremor-dominant Parkinson's disease(TD-PD).Methods Prospectively included TD-PD patients diagnosed in the Department of Neurology in the Yibin Second People's Hospital from December 2019 to March 2023,along with healthy volunteers as the control group.3D-T1WI and DTI sequences were scanned for both the TD-PD group and the control group.The FSL software was utilized to calculate whole-brain white matter fractional anisotropy(FA),mean diffusivity(MD),axial diffusivity(AD),and radial diffusivity(RD).Group differences in whole-brain white matter FA,MD,AD,and RD were compared using the voxel-based analysis(VBA)method.Furthermore,the correlations between DTI parameters in the TD-PD group and Montreal Cognitive Assessment(MoCA),Hoehn-Yahr staging,and Movement Disorder Society Unified Parkinson's Disease Rating Scale(MDS-UPDRS)scores were analyzed.Results A total of 50 subjects were included,comprising 31 cases in the case group and 19 controls in the control group.Compared with the control group,patients in the TD-PD group exhibited decreased FA in the corpus callosum body(voxel-wise P<0.001,uncorrected,cluster-wise P<0.05,FWE-corrected),while MD,AD,and RD increased in the leftanterior cerebellar lobe,and MD and AD increased in the right frontal lobe(voxel-level P<0.001,cluster-level P<0.05,uncorrected).Correlation analysis revealed a positive association between MD in the left anterior cerebellar lobe and Hoehn-Yahr staging(r=0.417,P=0.020).Conclusion TD-PD patients have more extensive cerebral white matter microstructural changes,in which corpus callosum degeneration may be the pathophysiological basis of TD-PD.The structural changes in the leftcerebellar anterior lobe may contribute to the development of tremor symptoms in PD patients.

Abstract:Objective To summarize the key evidence in the development of drug treatment strategies for type 2 diabetes mellitus(T2DM),and to provide an evidence-based roadmap for tailoring pharmacological strategies in patients with T2DM.Methods A systematic search of domestic and foreign databases,relevant guidelines websites,and T2DM guidelines and expert consensus organized by the society was conducted.The search time limit is from January 1,2010,to April 1,2024,and the update search is until April 1,2025.A series of guidelines with early publication,stable and timely update,clear use process of antihyperglycemic drugs and high clinical applicability of the guidelines were screened.Results Two guideline series compiled by the Chinese Diabetes Society and the American Diabetes Association were selected to summarize the development of drug treatment strategies for T2DM,and to summarize the key evidence.With the version updates,the overall development trend of the two guideline series is consistent:both of them pay more attention to individualized treatment and comprehensive management,from blood glucose oriented to outcome oriented,and the dual benefits of GLP-1RA,SGLT2i and other drugs hypoglycemic+cardiorenal protection are the key to promoting change.However,the two series differ in the timing of addressing cardiac and renal complications and weight management.Differences also exist in the details of first-line agent selection and the prioritization of cardiac and renal complications.Conclusion This study summarizes the key evidence in the development of drug treatment strategies for T2DM,and to promote the rational planning of drug treatment strategies for patients with T2DM by medical staff.

Abstract:Objective Based on Meleis'transition theory,this study explored the experiences and perceptions of patients undergoing robot-assisted radical prostatectomy(RARP)in participating in discharge preparation services,aiming to provide more humanized and targeted nursing recommendations for clinical practice.Methods A descriptive qualitative study was conducted.Using purposive sampling,patients who underwent RARP at Nanjing Drum Tower Hospital between August 2023 and January 2024 were selected for semi-structured face-to-face interviews.Interviews were conducted within 24 hours before discharge and during the first follow-up two weeks after discharge.For patients unable to return for follow-up,telephone interviews were conducted.Thematic analysis was performed using directed content analysis.Results A total of 20 patients were included.The experiences of patients participating in discharge preparation services were summarized into three main themes and nine sub-themes:awareness of discharge transition(ambivalence toward discharge decisions,uncertainty about the disease,active participation in the discharge process);multifaceted challenges during discharge transition(changes in physiological function,psychological and emotional distress,difficulties in social reintegration,challenges in accessing information);expectations for postoperative recovery(regaining a sense of control,actively adapting to the patient role).Conclusion Future healthcare and social services should place greater emphasis on addressing patients'physiological,psychological,social,and informational challenges.Through more personalized care,community services tailored to patients'needs,and clear health guidance,patients can be better supported in coping with postoperative challenges.

Abstract:Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation.By modulating iron metabolism,lipid peroxidation,and antioxidant defense systems,ferroptosis can effectively induce tumor cell death and suppress tumor proliferation and metastasis.Emerging research indicates that head and neck cancer(HNC)cells can evade ferroptosis by upregulating the expression of SLC7A11.Consequently,researchers have developed various ferroptosis inducers and explored their therapeutic potential in HNC.Notably,combining these inducers with chemotherapeutic agents or immune checkpoint inhibitors has been shown to significantly enhance antitumor efficacy.However,the specific regulatory mechanisms of ferroptosis across different HNC subtypes and their clinical applications require further investigation.This article reviews recent advances in the molecular mechanisms,regulatory networks,and clinical applications of ferroptosis in HNC,to provide insights for future research and accelerate its clinical translation.

Abstract:Objective To identify risk factors for preoperative lower limb deep vein thrombosis(DVT)in elderly patients with hip fractures and to develop a predictive nomogram model.Methods Elderly patients with hip fractures admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2021 to June 2024 was enrolled.Clinical data were collected and analyzed.Independent influencing factors for preoperative DVT were screened using Lasso regression and multivariate Logistic regression.A nomogram model was developed and validated internally and externally.Model performance was evaluated using Bootstrap resampling,calibration curves,receiver operating characteristic(ROC)curves with area under the curve(AUC),and decision curve analysis(DCA)to assess discrimination,calibration,and clinical utility.Results A total of 644 patients were included,with 451 in the training set and 193 in the validation set.Multivariate Logistic regression revealed that elevated D-dimer levels[OR=1.927,95％CI(1.675,2.257)],prolonged time from injury to admission[OR=1.023,95％CI(1.012,1.034)],increased fibrinogen[OR=1.348,95％CI(1.076,1.703)],higher total cholesterol[OR=1.256,95％CI(1.053,1.504)],and hypoalbuminemia[OR=0.936,95％CI(0.909,0.965)]were independent predictors of preoperative DVT.The AUCs were 0.871[95％CI(0.816,0.925)]for the training set and 0.879[95％CI(0.805,0.953)]for the validation set.Calibration curves showed that the predicted probabilities were consistent with the actuality.DCA demonstrated that the model yielded a higher net benefit than traditional strategies across a risk threshold range of 10％to 70％.Conclusion The nomogram-based predictive model developed in this study enables intuitive and accurate preoperative risk stratification for DVT in elderly patients with hip fractures.It serves as a robust scientific tool to guide early clinical screening and targeted interventions for thromboprophylaxis.

Abstract:Objective To systematically synthesize qualitative evidence on the inner experiences and care needs of Chinese breast cancer patients during radiotherapy and chemotherapy.Methods A systematic search was conducted in databases including PubMed,Web of Science,Embase,Cochrane Library,CNKI,VIP,WanFang and Chinese Medical Journal Network for qualitative studies published from inception to July 30,2025.Study quality was assessed using the JBI critical appaisal checklistfor qualitative research,and results were integrated via Meta-synthesis using the JBI thematic synthesis approach.Results A total of 21 studies involving 335 patients were included.The overall quality of the included studies was moderate to high.Five core themes were identified:treatment-induced negative emotional responses;multidimensional physical discomfort;dual burden of economic and psychological stress;individualized symptom coping styles;and diverse support needs.Conclusion The inner experiences of Chinese breast cancer patients during radiotherapy and chemotherapy are characterized by specificity in negative emotions,chain effects of physical symptoms,interwoven economic and psychological stressors,differentiated coping styles,and diverse support needs.

Abstract:Objective To investigate the role and mechanism of sex-determining region Y-box protein 9(SOX9)in the progression of ovarian cancer.Methods The ovarian cancer cell lines with stable knockdown of SOX9 were constructed.The effects of SOX9 knockdown on the proliferation,invasion and migration abilities of ovarian cancer cell lines were detected by CCK-8 assay,Transwell assay,and cell scratch assay,respectively.The effects of SOX9 knockdown on ferroptosis in ovarian cancer cell lines were evaluated by the level of Fe2+,glutathione(GSH),malondialdehyde(MDA),and Western blot analysis.The effects of SOX9 knockdown on the lipid peroxidation level of ovarian cancer cell lines were observed by confocal fluorescence microscopy.Chromatin immunoprecipitation followed by quantitative PCR(ChIP-qPCR)was performed to examine the binding of SOX9 to its downstream target gene,SLC7A11.Results Knockdown of SOX9 significantly inhibits the proliferation,invasion and migration abilities of ovarian cancer cells.Meanwhile,SOX9 transcriptionally regulates SLC7A11 and activates ferroptosis via the SLC7A11/GPX4 signaling axis.Conclusion SOX9 promotes ferroptosis in ovarian cancer cells by regulating the SLC7A11/GPX4 signaling pathway,ultimately inhibiting ovarian cancer progression.

Abstract:Objective To investigate the impact of Aurora kinase A(AURKA)on Temozolomide(TMZ)resistance in glioma cells and its regulatory role in ferroptosis.Methods The expression profile of AURKA in glioma and its correlation with prognosis were explored using the GEPIA2 database.U87MG/TMZ and LN229/TMZ drug-resistant cell lines were established,and the mRNA and protein expression levels of AURKA were detected by qRT-PCR and Western blot,respectively.AURKA was silenced using siRNA,and dynamic monitoring of lipid peroxidation levels,intracellular iron content,and glutathione peroxidase 4(GPX4)expression was conducted using BODIPY-C11 staining,FerroOrange iron probe,and immunofluorescence,respectively.Cell viability and IC50 were assessed by the CCK-8 assay,and cell apoptosis was detected by TUNEL staining.Following STAT3 activator treatment,JAK2/STAT3 pathway activity was detected by Western blot,and the molecular association between AURKA and ferroptosis regulation was evaluated.Results AURKA was highly expressed in glioma tissues,which was significantly associated with poor prognosis of patients.AURKA expression was significantly upregulated in U87MG/TMZ and LN229/TMZ resistant cells compared to parental cells.After AURKA silencing,lipid peroxidation products and free iron levels increased,while GPX4 protein expression decreased in U87MG/TMZ and LN229/TMZ cells.Ferroptosis inhibitor partially reversed the decrease in cell viability and TMZ resistance induced by AURKA knockdown.AURKA silencing significantly inhibited JAK2/STAT3 pathway activation;exogenous activation of STAT3(Colivelin)partially restored cell viability and attenuated the promotion of ferroptosis by AURKA knockdown.Conclusion AURKA enhances TMZ resistance in glioma cells by inhibiting ferroptosis through the activation of the JAK2/STAT3 pathway.