Dietary interventions such as fasting are gaining increasing attention for their synergistic effects in anti-tumor therapy, yet the precise underlying mechanisms remain incompletely understood. Recent research has unveiled a novel mode of cell death named “mitoxyperilysis”, providing a fresh perspective on the molecular mechanisms by which fasting may interfere with tumor treatment. This form of death is primarily triggered by the synergy between metabolic dysfunction and innate immune activation. Its mechanism involves the mTORC2 signaling pathway mediating prolonged abnormal contact between damaged mitochondria and the plasma membrane. This leads to massive local release of reactive oxygen species (ROS), which further induces lipid peroxidation of the plasma membrane, ultimately resulting in the physical rupture and death of the cell. The most significant distinction between mitoxyperilysis and classical cell death pathways lies in its independence from caspases and GSDMD. This comment aims to systematically elucidate the process, molecular mechanisms, and differences from other classical cell death pathways of mitoxyperilysis, while also exploring its potential for clinical translation in oncological diseases. Targeting induction of mitoxyperilysis may enhance the efficacy of existing anti-tumor drugs and overcome chemotherapy resistance. However, intervention protocols require further optimization to achieve an optimal balance between safety and therapeutic effectiveness in clinical application.

Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

Objective:To investigate the correlation between pathological features at the positive margins and biochemical re-currence after radical prostatectomy for prostate cancer.Methods:From June 2014 to December 2019,a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching(1:1).One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study.All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0.BCR-free survival was estimated using the Kaplan-Meier method.An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis(CART).Cox proportional hazards regression model was used to assess the association between variables and BCR-free surviv-al.Results:A total of 200 patients were included in this study,and 177 patients with pT2 stage were pathological after operation.The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months.A total of 28 cases of biochemi-cal recurrence were found through PSA follow-up after surgery,including 6 cases(6.0％)in the negative margin group and 22 cases(22.0％)in the positive margin group.The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group(log rank x2=9.336,P=0.003).It was found that the length of positive margin≥1 mm in the positive margin group was positively correlated with postoperative biochemical re-currence.Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of pos-itive ≥ 1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin.Conclusion:The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

Objective To explore the regulatory effect of methyltransferase-like 3(METTL3)on m6A methylation of Sigma-1 receptor(Sigma-1R)mRNA and mitophagy in cerebral microvascular endothelial cells of sepsis mice.Methods Twelve adult male C57BL/6J mice were randomly divided into the Sham group(without cecal ligation or puncture)and the sepsis group(received cecal ligation and puncture),with 6 mice in each group.m6A methylation levels,and relative expression of METTL3 and Sigma-1R mRNA and protein in cerebral micro-vascular tissues were detected by m6A Dot blot,RT-qPCR,and Western blot,respectively.The bEnd.3 cells were cultured in vitro and divided into the control group(normal culture),model group[lipopolysaccharide(LPS)-induced in vitro sepsis],si-NC group(LPS treat-ment combined with si-NC transfection),and si-METTL3 group(LPS treatment combined with si-METTL3 transfection).m6A Dot blot was used to detect m6A methylation levels of cells in each group;RT-qPCR was used to detect the mRNA expression of METTL3 and Sigma-1R;and Western blot was used to detect the expression of METTL3,Sigma-1R,and autophagy-related proteins of Bnip3,LC3B,and Beclin1.m6A chromatin immunoprecipitation-qPCR was used to detect m6A methylation level of Sigma-1R of cells in each group.JC-1 probe was used to detect the mitochondrial membrane potential,and the ATP assay kit was used to detect the mitochondrial ATP content.Results Compared with the Sham group,the sepsis group showed increased m6A methylation level and METTL3 expression(P<0.05),and decreased Sigma-1R expression in cerebral microvascular tissues(P<0.05).Compared with the control group,m6A methylation level,METTL3 expression and m6A methylation level of Sigma-1R mRNA increased,the expression of Sigma-1R,the normal rate and increase rate of mitochondrial membrane potential,and the ATP content decreased,and the protein expression of Bnip3,LC3B and Beclin1 downregulated in the model group and the si-NC group,with statistically significant differences(P<0.05).Compared with the si-NC group,m6A methylation level,METTL3 expression and m6A methylation level of Sigma-1R mRNA decreased,the expression of Sigma-1R,the normal rate and increase rate of mitochondrial membrane potential elevated,the ATP content increased,and the protein expression of Bnip3,LC3B and Beclin1 upregulated in the si-METTL3 group,with statistically significant differences(P<0.05).Conclusion Silencing METTL3 can inhibit m6A methylation of Sigma-1R mRNA and promote the mitophagy in cerebral microvascular endothelial cells of septic mice.