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 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.

The incidence rate of Parkinson's disease ranks the second among degenerative diseases of the nervous system,only lower than Alzheimer's disease.Early-onset Parkinson's disease(EPOD)refers to Parkinson's disease with initial symptoms appearing before the age of 50.EOPD is associated with certain genetic mutations and has distinct clinical features.This study reports a case of EOPD with mutations in both the PRKN and the APOB genes.The patient presented with the initial symptom of unstable walking at the age of 28,followed by bradykinesia,limb tremors,masked face,shuffling gait,and cogwheel rigidity in both upper limbs.The blood lipid test showed total cholesterol of 6.48 mmol/L and low-density lipoprotein cholesterol of 4.13 mmol/L.Genetic testing showed a deletion in exon 5 and a point mutation[c.850G＞C(p.Gly284Arg)]in exon 7 of the PRKN gene,as well as a point mutation[c.10579C＞T(p.Arg3527Trp)]in exon 26 of the APOB gene.Based on these clinical manifestations and examination results,the patient was diagnosed with EOPD.The compound heterozygous mutations in the PRKN gene,as well as the combined mutations in the PRKN and APOB genes,are both reported for the first time,expanding the spectrum of genetic mutations associated with EOPD.

BackgroundMost of the researches on continuous nursing education is from the perspective of patients， and there is a lack of studies on the impact of continuous nursing education on patient caregivers， and the care quality of caregivers is closely related to postoperative rehabilitation status of the patients. ObjectiveTo investigate the effect of continuous nursing education on anxiety relief of caregivers of patients with all-robot coronary artery bypass surgery， and to provide references for improving caregivers' anxiety and promoting patients' recovery. MethodsA total of 120 caregivers of patients with all-robot coronary artery bypass surgery at the First and Sixth Center of 301 Chinese PLA General Hospital were included from January 1， 2021 to December 31， 2022. The caregivers were randomly divided into study group and control group with 60 cases in each group by systematic random sampling method. Before the patient discharge from the hospital， all caregivers received routine nursing education. The study group received continuous nursing education for 4 weeks after patient discharged. Self-rating Anxiety Scale （SAS） was used to evaluate the two groups before and one month after discharge. ResultsOne month after discharge， SAS score in the study group was significantly lower than that in the control group ［（57.77±14.08） vs. （70.19±13.60）， t=-4.913， P<0.01］， and the proportion of SAS score above 60 in the study group was significantly lower than that in the control group （41.67% vs. 75.00%， χ²=-13.714， P<0.01）. ConclusionContinuous nursing education may help reduce the level of anxiety in caregivers of patients with all-robot coronary artery bypass surgery.

Objective To investigate the characteristics of gut microbiota in patients with schizophrenia. Methods The composition of the fecal microbiota in 16 schizophrenia patients and 20 healthy controls was analyzed by 16S rRNA sequencing. Results At the phylum level, TM7 was increased in the patients (P<0.05). At the class level, the abundance of Peptostreptococcaceae, Lactobacillaceae and Actinomycetaceae in the patients increased (P<0.05), whereas the abundance of Tissierellaceae decreased relative to health controls (P<0.05). At the genus level, Actinomyces, Scardovia, Atopobium, Moryella, G07 and Lactobacillus were increased in the patients relative to healthy controls (P<0.05). Prediction of functional properties of bacterial flora showed that the metabolic pathways of fatty acids and pyruvate were different between the patients and healthy controls (P<0.05). Conclusion The present study reveals an alteration in the characteristics of gut microbiota in schizophrenia patients which may be an auxiliary diagnosis marker for clinical diagnosis of schizophrenia.