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 prenatal ultrasound diagnostic features and prognosis of congenital megalourethra (CM).Methods:A retrospective analysis was conducted on the clinical data and prenatal ultrasound features of two fetuses with CM diagnosed and treated at the Affiliated Hospital of Jining Medical College from July to December 2023. Literature related to the prenatal diagnosis of fetal CM was searched using the Chinese keywords "megalourethra" and "congenital megalourethra" in CNKI, Wanfang, Yiigle, and VIP Chinese Journal Database; and the same keywords in English were used for the retrieval in PubMed, Embase, and Web of Science databases, with the search period from January 1, 1955, to December 31, 2023. Descriptive methods were used to analyze and summarize the prenatal ultrasound features, outcomes, and prognosis of all included cases.Results:(1) Cases from our hospital: Case 1, at 19 weeks of gestation, an ultrasound revealed the symptoms of penile urethral dilation and urinary tract obstruction, with the distal urethral opening visible. Case 2, at 17 weeks of gestation, an ultrasound showed the entire urethra of the fetus was dilated, particularly the penile urethra, with the urethral opening visible at the front end, and bilateral mild pyelectasis. Both cases were considered as fetal CM. The first case decided to terminate the pregnancy after examination at a higher-level hospital; the second case was re-examined two weeks later, showing linear separation of the penile urethra and significant relief in bilateral pyelectasis. Subsequent ultrasound examinations showed no significant changes, and a male infant was delivered by cesarean section at 37 weeks of gestation, with normal urination. (2) Literature review: A total of 54 fetal CM cases were retrieved, plus two cases from our hospital, making a total of 56 cases. Among the 56 cases, 49 cases (88%) were detected in the second trimester; penile urethral dilation was observed in all cases, with 54 cases (96%) being complicated by urinary system abnormalities, and 30 cases (54%) having other system abnormalities; 24 cases (43%) had oligohydramnios or no amniotic fluid. Eighteen cases (32%) resulted in the termination of pregnancy, one case (2%) involved intrauterine fetal death, and 37 cases (66%) resulted in live births, among which, six neonatal deaths occurred (all with oligohydramnios, three with renal dysplasia, two with increased renal parenchymal echogenicity, and one with impaired renal function). Among the 31 surviving cases, six experienced spontaneous resolution of fetal megalourethra in utero, with a favorable prognosis. Of the 20 cases with increased renal parenchymal echogenicity or renal dysplasia, nine (45%) resulted in termination of pregnancy, five (25%) in neonatal death, and among the six (30%) surviving infants, four underwent renal function tests, all showing renal impairment. Among the four cases detected in early pregnancy, two resulted in termination of pregnancy, one in neonatal death, and one infant developed end-stage renal disease.Conclusions:Fetal CM ultrasound images are characterized by dilatation of the penile urethra. Early detection, increased renal echogenicity or renal dysplasia, and oligohydramnios may be associated with adverse outcomes such as neonatal death or renal impairment.

Objective:To explore the prenatal ultrasound diagnostic features and prognosis of congenital megalourethra (CM).Methods:A retrospective analysis was conducted on the clinical data and prenatal ultrasound features of two fetuses with CM diagnosed and treated at the Affiliated Hospital of Jining Medical College from July to December 2023. Literature related to the prenatal diagnosis of fetal CM was searched using the Chinese keywords "megalourethra" and "congenital megalourethra" in CNKI, Wanfang, Yiigle, and VIP Chinese Journal Database; and the same keywords in English were used for the retrieval in PubMed, Embase, and Web of Science databases, with the search period from January 1, 1955, to December 31, 2023. Descriptive methods were used to analyze and summarize the prenatal ultrasound features, outcomes, and prognosis of all included cases.Results:(1) Cases from our hospital: Case 1, at 19 weeks of gestation, an ultrasound revealed the symptoms of penile urethral dilation and urinary tract obstruction, with the distal urethral opening visible. Case 2, at 17 weeks of gestation, an ultrasound showed the entire urethra of the fetus was dilated, particularly the penile urethra, with the urethral opening visible at the front end, and bilateral mild pyelectasis. Both cases were considered as fetal CM. The first case decided to terminate the pregnancy after examination at a higher-level hospital; the second case was re-examined two weeks later, showing linear separation of the penile urethra and significant relief in bilateral pyelectasis. Subsequent ultrasound examinations showed no significant changes, and a male infant was delivered by cesarean section at 37 weeks of gestation, with normal urination. (2) Literature review: A total of 54 fetal CM cases were retrieved, plus two cases from our hospital, making a total of 56 cases. Among the 56 cases, 49 cases (88%) were detected in the second trimester; penile urethral dilation was observed in all cases, with 54 cases (96%) being complicated by urinary system abnormalities, and 30 cases (54%) having other system abnormalities; 24 cases (43%) had oligohydramnios or no amniotic fluid. Eighteen cases (32%) resulted in the termination of pregnancy, one case (2%) involved intrauterine fetal death, and 37 cases (66%) resulted in live births, among which, six neonatal deaths occurred (all with oligohydramnios, three with renal dysplasia, two with increased renal parenchymal echogenicity, and one with impaired renal function). Among the 31 surviving cases, six experienced spontaneous resolution of fetal megalourethra in utero, with a favorable prognosis. Of the 20 cases with increased renal parenchymal echogenicity or renal dysplasia, nine (45%) resulted in termination of pregnancy, five (25%) in neonatal death, and among the six (30%) surviving infants, four underwent renal function tests, all showing renal impairment. Among the four cases detected in early pregnancy, two resulted in termination of pregnancy, one in neonatal death, and one infant developed end-stage renal disease.Conclusions:Fetal CM ultrasound images are characterized by dilatation of the penile urethra. Early detection, increased renal echogenicity or renal dysplasia, and oligohydramnios may be associated with adverse outcomes such as neonatal death or renal impairment.

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 systematic review the clinical value of urine derived prostate cancer gene 3 (PCA3) scores for predicting the result of prostate biopsy during diagnosing the prostate cancer.Methods Articles related to the value of urine derived PCA3 score for forecasting the result of prostate biopsy during diagnosing the prostate cancer,published from inception to November 2013,were retrieved in the databanks including PubMed (1966-2013),CNKI (1979-2013),EMBASE(1988-2013),and Cochrane liberary.Meta-Disc 1.4 software was used to analyze data.According to the inclusion and exclusion criteria,the literatures were screened.And the quality of included literatures were evaluated.The pooled sensitivity,specificity,the likelihood ratio(LR) were calculated and summary receiver operating characteristic curve(SROC curve) was made.Results A total of 22 articles with 3 060 prostate cancer cases and 5 307 normal or BPH cases were included.Since there was heterogeneity between the studies,the data was calculated by the random effect model.The pooled sensitivity of PCA3 score was 63％ (95％CI:0.61-0.65) and the pooled specificity was 70％ (95％CI:0.69-0.72),respectively.The positive (P-LR) and negative likelihood ratio (N-LR) were 2.38 (95％CI:2.05-2.77) and 0.51 (95％CI:0.46-0.58),respectively.The diagnosis odds ratio (DOR) was 4.88 (95％ CI:3.83-6.21).Summary receiver operating characteristic curve area under curve (SROC AUC) was 0.7445,Q* index was 0.689,respectively.Conclusions The performance of urine derived PCA3 score has higher accuracy of detection than other method in the diagnosis of prostate cancer.It can be a novel and optional non-invasive test and an important adjunct test for predicting the result of prostate biopsy.