BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

Objective:To analyze the influencing factors of hospitalization costs in patients with ischemic stroke,design a diagnosis related groups(DRG)subgrouping scheme,providing references for refined DRG subgrouping.Methods:Ischemic stroke patients discharged from a tertiary comprehensive hospital in Bengbu,Anhui Province from Jan 2021 to Dec 2023 were included.Through the rank-sum test and multiple linear regression analysis,the main factors influencing the hospitalization cost were analyzed.The E-CHAID algorithm was applied to construct a DRG subgrouping scheme,and the variance reduction and coefficient of variation were used to validate subgroup rationality.Results:The length of hospital stay,presence of surgical procedures,severity,and admission route were included in the decision tree model,generating 12 DRG subgroups.Both variance reduction and coefficient of variation confirmed high subgroup validity.Conclusion:The E-CHAID-based DRG subgrouping scheme for ischemic stroke inpatients is scientific and reasonable,supporting future adjustments in treatment-related grouping,hierarchical medical practices,and the fine hospital management.

Objective To explore the trajectory of disability acceptance and the factors influencing it in first stroke patients.Methods A total of 202 first-ever stroke patients admitted to Wenzhou Central Hospital from December 2022 to December 2023 were selected,low acceptance group(n=38),medium acceptance group(n=96),and high acceptance group(n=68)based on the trajectory of disability acceptance after discharge.Multivariate Logistic regression was applied to explore the factors affecting disability acceptance in first-episode stroke patients.Results The total score of acceptance of disability scale-revised(ADS-R)in stroke patients was(89.93±13.51)points.There were differences between three groups in terms of age,education level,family income,caregiver or no caregiver,severity of illness,medical social support scale(MOS-SSS)scores,herth hope index(HHI)scores,and patient health questionnaire depression scale-9 scores(P＜0.05).Multivariate Logistic regression analysis reveled that age(OR=12.419,95％CI:3.967-38.882),absence of caregiver(OR=5.793,95％CI:1.989-16.875),severity of the condition(OR=5.724,95％CI:1.927-16.999)were risk factors affecting disability acceptance in first-episode stroke patients(P＜0.05),while educational level(OR=0.207,95％CI:0.069-0.624),household income(OR=0.238,95％CI:0.079-0.712),and MOS-SSS score(OR=0.502,95％CI:0.303-0.832)were protective factors(P＜0.05).Conclusion There are three different trajectories of disability acceptance in first-episode stroke patients.Age,presence or absence of caregivers,severity of the condition,education level,household income,and MOS-SSS score are influencing factors of disability acceptance in first-episode stroke patients and can be used as predictive factors for disability acceptance trajectories.

Lactylation, a newly discovered post-translational modification, has been reported to be involved in various physiological and pathological processes. Recent studies have found that lactylation is potentially linked to the pathological processes and repair mechanisms of ischemic stroke. This article explores the impact and role of lactylation after the occurrence of ischemic stroke on neuroinflammation, energy metabolism regulation, oxidative stress, signaling pathway modulation, and angiogenesis. It may serve as a bridge connecting lactylation and ischemic stroke, offering insights and guidance for future research and clinical strategies in ischemic stroke.

Objective:To analyze the influencing factors of hospitalization costs in patients with ischemic stroke,design a diagnosis related groups(DRG)subgrouping scheme,providing references for refined DRG subgrouping.Methods:Ischemic stroke patients discharged from a tertiary comprehensive hospital in Bengbu,Anhui Province from Jan 2021 to Dec 2023 were included.Through the rank-sum test and multiple linear regression analysis,the main factors influencing the hospitalization cost were analyzed.The E-CHAID algorithm was applied to construct a DRG subgrouping scheme,and the variance reduction and coefficient of variation were used to validate subgroup rationality.Results:The length of hospital stay,presence of surgical procedures,severity,and admission route were included in the decision tree model,generating 12 DRG subgroups.Both variance reduction and coefficient of variation confirmed high subgroup validity.Conclusion:The E-CHAID-based DRG subgrouping scheme for ischemic stroke inpatients is scientific and reasonable,supporting future adjustments in treatment-related grouping,hierarchical medical practices,and the fine hospital management.

Objective To explore the trajectory of disability acceptance and the factors influencing it in first stroke patients.Methods A total of 202 first-ever stroke patients admitted to Wenzhou Central Hospital from December 2022 to December 2023 were selected,low acceptance group(n=38),medium acceptance group(n=96),and high acceptance group(n=68)based on the trajectory of disability acceptance after discharge.Multivariate Logistic regression was applied to explore the factors affecting disability acceptance in first-episode stroke patients.Results The total score of acceptance of disability scale-revised(ADS-R)in stroke patients was(89.93±13.51)points.There were differences between three groups in terms of age,education level,family income,caregiver or no caregiver,severity of illness,medical social support scale(MOS-SSS)scores,herth hope index(HHI)scores,and patient health questionnaire depression scale-9 scores(P＜0.05).Multivariate Logistic regression analysis reveled that age(OR=12.419,95％CI:3.967-38.882),absence of caregiver(OR=5.793,95％CI:1.989-16.875),severity of the condition(OR=5.724,95％CI:1.927-16.999)were risk factors affecting disability acceptance in first-episode stroke patients(P＜0.05),while educational level(OR=0.207,95％CI:0.069-0.624),household income(OR=0.238,95％CI:0.079-0.712),and MOS-SSS score(OR=0.502,95％CI:0.303-0.832)were protective factors(P＜0.05).Conclusion There are three different trajectories of disability acceptance in first-episode stroke patients.Age,presence or absence of caregivers,severity of the condition,education level,household income,and MOS-SSS score are influencing factors of disability acceptance in first-episode stroke patients and can be used as predictive factors for disability acceptance trajectories.

Lactylation, a newly discovered post-translational modification, has been reported to be involved in various physiological and pathological processes. Recent studies have found that lactylation is potentially linked to the pathological processes and repair mechanisms of ischemic stroke. This article explores the impact and role of lactylation after the occurrence of ischemic stroke on neuroinflammation, energy metabolism regulation, oxidative stress, signaling pathway modulation, and angiogenesis. It may serve as a bridge connecting lactylation and ischemic stroke, offering insights and guidance for future research and clinical strategies in ischemic stroke.

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective To compare the efficacy of intravenous thrombolysis combined with intravascular therapy for patients with acute ischemic stroke(AIS)from different treatment opportunities and its impact on prognosis.Methods A total of 180 AIS patients admitted to Wenzhou Central Hospital from July 2021 to September 2023 were selected as study objects,and divided into group A(thrombolysis within 2h),Group B(thrombolysis within 2-3h),group C(thrombolysis within 3-4.5h),group D(thrombolysis within 4.5-6h)and group E(thrombolysis within 6-9h)according to different thrombolysis times after owset.There were 36 cases in each group.All patients received alteplase intravenous thrombolysis combined with intravascular therapy.Vascular recanalization,neurological function,prognosis,ability of daily living and complications were compared among all groups.Results Vascular recanalization rate of five groups had statistical significance(χ2=11.500,P=0.022).Vascular recanalization rate of group E was significantly lower than that of other four groups(P<0.05),and vascular recanalization rate of group D was significantly lower than that of groups A,B and C(P<0.05).After thrombolysis,National Institutes of Health stroke scale(NIHSS)score and modified Rankin scale(mRS)score of patients in all groups were significantly decreased with the extension of time(P<0.05).At different time after thrombolysis,NIHSS score and mRS score in group E were significantly higher than those in other four groups,and NIHSS score and mRS score in group D were significantly higher than those in groups A,B and C(P<0.05).After thrombolysis,Barthel index(BI)of all groups increased significantly with the extension of time(P<0.05).At different time after thrombolysis,BI score of group E were significantly lower than those of other four groups,and BI score of group D were significantly lower than those of groups A,B and C(P<0.05).Within 90 days after thrombolysis,there was no significant difference in the incidence of intracranial hemorrhage,oral hemorrhage,nosocomial infection and cerebral hernia among five groups(χ2=1.356,P=0.852).Conclusion Alteplase intravenous thrombolysis combined with intravascular therapy in AIS patients within 4.5h has better clinical efficacy and better prognosis.

Ischemic stroke has a high rate of disability and mortality and is often accompanied by white matter injury(WMI).WMI patients often have cognitive disorders,emotional disorders,sensorimotor disorders,urinary incontinence and other symptoms,which seriously affect daily life.WMI can be detected early through imaging techniques,but there is a lack of appropriate intervention and specific treatment.Studying the pathological mechanism of WMI after ischemic stroke is helpful to prevent the occurrence of WMI,delay its progression,and contribute to the development of effective drugs or specific treatments.This article reviewed the research progress of WMI mechanism after ischemic stroke in order to provide scientific basis for clinical prevention and treatment.