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

The traditional theory of "the spleen governs the dispersion of essence" refers to the spleen's pivotal role in distributing refined nutrients throughout the body. In traditional Chinese medicine （TCM）， lipids are categorized under "gaozhi （膏脂）"， and their transportation and metabolism via apolipoproteins are believed to be closely related to the spleen's dispersing function. The liver， which synthesizes apolipoproteins， is functionally linked to the spleen system in TCM. Impaired dispersion of essence by the spleen and disrupted transportation of gaozhi constitute the pathological mechanism of dyslipidemia due to spleen deficiency. Strengthening the spleen and resolving dampness is the core therapeutic principle. From the perspective of modern medicine， this may involve promoting hepatic functional recovery related to lipid metabolism， thereby enhancing lipid processing and reducing the levels of abnormally accumulated lipids in the bloodstream.

Objective:To analyze the clinical features and diagnostic process of ring chromosome syndrome.Methods:Clinical data of 9 children with ring chromosome syndrome who were treated at the Children′s Medical Center of Peking University First Hospital from September 2009 to May 2025, were summarized and analyzed in a case series study. The data included clinical manifestations, types of epileptic seizures, genetic testing, treatment outcomes, and follow-up results, et al.Results:Among the 9 children with ring chromosome syndrome, there were 6 girls and 3 boys, including 4 children with ring chromosome 20 syndrome, 3 children with ring chromosome 14 syndrome, and 1 child each with ring chromosome 13 and 17 syndrome. All 9 children had de novo chromosomal variations. Among them, 3 children of ring chromosome 20 syndrome were mosaic, and the remaining 6 children were non-mosaic. All 9 children exhibited diverse clinical features, especially those with ring chromosome 20 syndrome, which presented with specific manifestations. The 4 children with ring chromosome 20 syndrome all had acute epileptic seizures as the initial symptom, with onset ages of 67, 39, 17, and 96 months, and all had focal seizures. One child with ring chromosome 20 syndrome had non-convulsive status epilepticus. Development of all 4 children with ring chromosome 20 syndrome was normal before seizure onset, but 3 children showed regression after onset. No physical deformities were observed in 4 children with ring chromosome 20 syndrome, and 2 children were misdiagnosed, 3 children underwent whole exome sequencing and copy number variation analysis in their families, with no abnormalities detected. All 4 children with ring chromosome 20 syndrome were diagnosed through chromosomal karyotype analysis, the intervals between onset and diagnosis were 2, 81, 19 and 13 months, respectively. Follow-up showed that epileptic seizures were not controlled in all 4 children with ring chromosome 20 syndrome. The other 5 children were characterized by developmental delay as the initial symptom, followed by epileptic seizures between 3 and 24 months of age. Developmental regression of the other 5 children did not occur after onset, 2 of them had microcephaly, and 3 had wide-set eyes. No misdiagnoses were reported in these 5 children, and the intervals between onset and diagnosis were 7, 3, 55, 3, and 106 months, respectively. Follow-up showed that epileptic seizures were controlled in these 5 children. Conclusions:Ring chromosome 20 syndrome typically manifest with epilepsy as the initial symptom and are refractory to drug treatment, their early development is entirely normal. Ring chromosome 13, 14, and 17 syndrome are characterized by developmental delay from an early age, followed by the onset of epileptic seizures, which are easily controlled. Conventional whole exome sequencing and copy number variation analysis in families rarely detect ring chromosome abnormalities. Early chromosomal karyotype analysis is essential for the diagnosis of ring chromosome syndrome.

Objective:To explore the genetic and clinical characteristics of epilepsy related with ATP6V1A gene heterozygous variants.Methods:A case series study was conducted. The clinical data of 10 children of epilepsy associated with ATP6V1A gene variants who were admitted to the Children′s Medical Center, Peking University First Hospital from January 2019 to December 2024 was collected. The characteristics of children′ gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among the 10 children, there were 4 boys and 6 girls. All 10 children with ATP6V1A gene variants were de novo heterozygous variants, including 1 case of mosaic variant. A total of 9 different variants were identified and 7 variants have not been reported previously. The age at epilepsy onset was 28 (9, 48) months. Five children experienced their first seizure as a fever induction. The types of epileptic seizures included focal seizures in 6 children, epileptic spasms in 5 children, tonic spasms and atonic seizures in 1 child respectively. Three children had 2 seizure types. Global developmental delays were exhibited in 8 children, 2 of whom manifested autism spectrum disorder phenotypes. Two children showed normal development. Electroencephalography revealed slowed background activity in 5 children. Interictal epileptiform discharges were recorded in 9 cases, including hypsarrhythmia, focal, multifocal or generalized discharges. Clinical seizures were captured in 4 children. Brain magnetic resonance imaging abnormalities were found in 4 children, including frontotemporal cortical dysplasia, prominent sulci, delayed myelination of white matter, dysplasia of the corpus callosum, bilateral ventricular enlargement, and cerebral atrophy. Five children were diagnosed with developmental and epileptic encephalopathy (DEE), and 4 of them were diagnosed with infantile epileptic spasms syndrome. At the last follow-up, the age was 78 (25, 120) months. Seizures were controlled in 6 children, while 4 children had uncontrolled seizures despite treatment with ≥3 anti-seizure medications. Conclusions:All children with ATP6V1A gene related epilepsy harbored de novo heterozygous missense variants, with few showing mosaic variants. Seizure onset age ranged widely from the neonatal period to childhood. The predominant seizure types were focal seizures and epileptic spasms. The phenotypic spectrum may exhibit DEE, while a minority maintain normal development.

Objective:To summarize the genotype and clinical phenotype characteristics of children with epilepsy associated with the SCN1B gene encoding the sodium channel β1 subunit. Methods:The genotypes and clinical phenotypes of patients with SCN1B variants among suspected genetic epilepsy cases treated at the Children′s Medical Center of Peking University First Hospital between May 2016 and July 2024 were analyzed. These variants were identified using next-generation sequencing and subsequently validated by Sanger sequencing or quantitative polymerase chain reaction methods. Results:A total of 17 patients were analyzed, including 8 males and 9 females. Ten cases of missense variations (including 2 with the same variations), 4 cases of deletion variations, and 1 case each of nonsense variations, splice site variations, and exons 4-5 deletions were identified. Among them, 6 cases had novel SCN1B variations. The variants in 11 cases were inherited from 1 parent. Eleven types of gene variants have not been reported yet. Onset of epilepsy ranged from 3 months to 5 years and 3 months old (median age: 14 months). Types of seizures included generalized tonic-clonic seizures (GTCS) in 14 cases, focal seizures in 9 cases, myoclonic seizures in 3 cases, atypical absence seizures in 2 cases and epilepsy spasms, tonic seizures and atonic seizures in 1 case each. Eleven cases had diverse seizure types. Fourteen cases (14/17) demonstrated fever sensitivity. Electroencephalography revealed focal discharges in 3 cases, coinciding with focal and generalized discharges in 3 additional cases, and multifocal discharges in 6 cases. Seizures were identified in 4 cases: 1 case of myoclonic seizures, 1 case of GTCS, 1 case of atypical absence seizures, and 1 case exhibiting both myoclonic and tonic seizures. Nine cases (9/17) were diagnosed with genetic epilepsy with febrile seizures plus, 1 case diagnosed with myoclonic epilepsy in infancy and 1 diagnosed with infant epileptic spasms syndrome. There were 2 cases of nonspecific developmental epileptic encephalopathy, while the remaining 4 cases could not be diagnosed with a specific epileptic syndrome. Effective antiseizure medications (ASMs) included valproate in 8 cases, levetiracetam in 5 cases, topiramate in 3 cases, clobazam in 2 cases, clonazepam and vigabatrin in 1 case each. Sodium channel blockers exacerbated seizures in 3 cases, specifically oxcarbazepine in 2 cases and lamotrigine in 1 case. At the last follow-up, seizures were controlled for at least 6 months in 14 patients (14/17), while seizures remained uncontrolled in 3 patients despite trialing 2 or more ASMs. Thirteen patients exhibited normal development, while 4 experienced developmental delays. Conclusions:The heterozygous variants in children with SCN1B gene-related epilepsy include missense, deletion, nonsense, splice site variants, and exon deletions. The correlation between different genetic variants and clinical phenotypes remains unclear. These variants are associated with epilepsy onset from infancy to early childhood, presenting with various seizure types, with GTCS being the most common. Phenotypic manifestations can vary significantly in severity, ranging from benign febrile seizures or febrile seizures plus to developmental epileptic encephalopathy. Valproic acid demonstrates the highest effectiveness rate, while the use of sodium channel blockers may worsen seizures in certain patients, necessitating cautious administration.

Objective:To summarize the clinical phenotype and genetic features of patients with relapsing encephalopathy with cerebellar ataxia (RECA) caused by ATP1A3 gene R756 variants. Methods:A retrospective analysis was performed on patients carrying the ATP1A3 gene R756 variants, identified by whole-exome sequencing of family members, at Capital Center for Children′s Health, Capital Medical University and Children's Medical Center, Peking University First Hospital from August 2005 to February 2024. Their clinical, laboratory, neuroimaging, electrophysiological and genetic characteristics were summarized. Results:A total of 13 RECA patients were enrolled in this study, including 8 males and 5 females. The age of onset was 8 months to 5 years, with a median age of onset of 18 months. All of 13 patients presented paroxysmal episodes of neurological decompensations triggered by fever and residual symptoms following the acute phase. During acute attack stage, ataxia was observed in all 13 cases, muscle weakness in 12 cases, dysarthria in 12 cases, altered consciousness in 10 cases, dysphagia in 10 cases, dystonic episodes in 4 cases, abnormal eye movement in 2 cases, choreoathetosis in 2 cases, and epileptic seizures in 1 case. All 13 patients had residual symptoms during the nonparoxysmal period, of whom 9 patients had ataxia, 9 patients had dysarthria, 4 patients had dystonia, 3 patients had cognitive disorders, and 1 patient had epileptic seizures. All 13 cases had ATP1A3 missense variants, and variant c.2266C>T/p.R756C was found in 6 cases, c.2267G>A/p.R756H in 5 cases, and c.2267G>T/p.R756L in 2 cases. Nine cases carried de novo variants, 4 with inherited variants. Conclusions:RECA caused by variants of ATP1A3 in residue 756 typically presents with an acute onset during infancy or early childhood, precipitated by febrile episodes and characterized by recurrent episodes of ataxia, with bulbar paralysis, muscle weakness and altered consciousness. Recurrence is common, and the most common persistent symptoms are cerebellar ataxia and dysarthria. A few patients have cognitive impairment. Three types of ATP1A3 gene variants R756C, R756H and R756L are related with RECA, and R756C is the most common variant.

Objective:Against the backdrop of population aging and air pollution,this study examined the re-gional distribution of depressive symptoms among middle-aged and elderly people in China and explores the influ-ence of patrticulate matter 2.5(PM2.5)concentration on these symptoms.This study examined the regional distri-bution of depressive symptoms in middle-aged and elderly people in China and explores the influence of PM2.5 concentration and related factors on these symptoms.Methods:Middle-aged and elderly people aged 45 years and above in CHARLS database in 2013,2015 and 2018 were selected as research objects,and the Center for Epidemio-logic Studies Depression Scale(CESD-10)to obtain the detection rate of depressive symptoms.The PM2.5 concen-tration data were derived from the annual data of the China Environmental Monitoring Station.t-test,x2 test and DID model were used to analyze the related factors of depressive symptoms.Stata17.0 and Arc GIS10.8 were used for spatial autocorrelation analysis to explore the regional distribution and relationship of depressive symptoms in mid-dle-aged and elderly people in China.Results:From east to west,the detection rate of depressive symptoms in mid-dle-aged and elderly people in China showed an increasing trend.The regional distribution of PM2.5 mainly showed that the central region was higher than the northern and southern regions and the western region(except Xinjiang)was higher than the eastern region.Conclusion:Both the PM2.5 concentration and depression symptoms exhibit spatial clustering across China.PM2.5 has a negative impact on depression symptoms in middle-aged and elderly people,with other related factors including gender,age,education level,marital status,living area,smoking status.

Objective:To explore the value of blood lactic acid (BLA), procalcitonin (PCT), and total bilirubin (TBil) in the diagnosis and prognosis evaluation of patients with trauma complicated with sepsis.Methods:The clinical data of 151 patients with severe trauma admitted to the Department of Emergency Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2019 to August 2023 were analyzed retrospectively. The patients were divided into the sepsis group (72 cases) and non-sepsis group (79 cases) according to the diagnosis. They were further divided into the death group (37 cases) and non-death group (114 cases) based on clinical outcomes. Clinical data were compared between groups. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the above indicators, and Spearman correlation analysis was applied to evaluate the correlation between the indicators.Results:The levels of BLA, PCT, TBil, and Sequential Organ Failure Assessment (SOFA) score in the sepsis group were higher than those in the non-sepsis group (all P<0.05). The mortality rate of the sepsis group was significantly higher than that of the non-sepsis group, with a statistically significant difference [26/72(36.11%) vs 11/79(13.92%), χ 2=10.024, P=0.002]. The levels of BLA, PCT, TBil, and SOFA score in the death group were higher than those in the non-death group (all P<0.05). ROC curve analysis showed that the areas under the curve (AUC) of BLA, PCT, TBil, and their combination for diagnosing sepsis were 0.745, 0.826, 0.753, and 0.889 respectively; the sensitivity and specificity of the combined diagnosis of sepsis were 87.5% and 72.2%. The AUCs of BLA, PCT, TBil, and their combination for predicting the prognosis of sepsis were 0.644, 0.697, 0.614, and 0.713 respectively; the sensitivity and specificity of the combined prediction of sepsis prognosis were 64.9% and 71.1%. Among the 151 patients, the levels of BLA, PCT, TBil were positively correlated with SOFA score, with statistically significant differences ( r=0.3871, 0.4399, 0.4851, all P<0.001). Conclusions:BLA, PCT, and TBil levels have certain value in the early diagnosis and prognosis evaluation of patients with sepsis. The combined evaluation has the best efficacy and high guiding value in clinical practice.

Objective:To investigate the effects of psychological state on the setup errors of radiotherapy for breast cancer patients.Methods:A prospective cohort study was conducted. A total of 193 breast cancer patients in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from October 2022 to May 2023 were selected. Radiotherapy was performed after fixation with an integrated multi-functional device for the head, chest and abdomen. Psychological status of patients was assessed by using 9-item health questionnaire (PHQ-9) and generalized anxiety disorder 7 self-rating scale (GAD-7) before first radiotherapy, the 10th radiotherapy and the last radiotherapy. Based on the results of the questionnaires, patients were divided into psychological problem (anxiety or depression) group and non-psychological problem group. The general data and setup errors of radiotherapy in both groups were compared.Results:All the 193 patients were female, with a median age of 47 years. There were 53 patients in psychological problem group and they underwent a total of 507 image-guided procedures, with setup errors [ M ( Q1, Q3)] of 0.18 (0.07, 0.33), 0.20 (0.10, 0.33) and 0.19 (0.09, 0.30) in the left-right (X), superior-inferior (Y), and anterior-posterior (Z) directions, respectively; the remaining 140 patients in non-psychological problem group underwent 1 240 image-guided procedures, with setup errors [ M ( Q1, Q3)]of 0.17 (0.08, 0.30), 0.20 (0.10, 0.30) and 0.18 (0.09, 0.28) in the X, Y, and Z directions, respectively, and the differences were statistically significant ( Z values were -3.78, -2.00; P < 0.001, P = 0.046). Conclusions:Anxiety and depression have an influence on the setup errors of radiotherapy in patients with breast cancer. In the processs of radiotherapy for breast cancer, it is important to pay attention to the psychological status of patients.

Objective To explore the correlation between the expression level of serum fibrinogen-like protein 1(FGL1)and the indexes of metabolism and renal function in patients with diabetic nephropathy(DN)and diabetes mellitus(DM),and provide reference for clinical diagnosis and treatment.Methods From January 2017 to April 2023,30 patients with DM and treated in Jiangsu Province Hospital of Chinese Medicine were selected as the DM group,68 patients with DN were selected as the DN group,and 36 healthy subjects were selected as the control group.The DN group was further divided into the early DN(DN-E)group(n=38)and the late DN(DN-A)group(n=30)according to whether there was a large amount of proteinuria and the severity.Clinical data such as serum albumin(ALB),estimated glomerular filtration rate(eGFR)and albumin-to-creatinine ratio(ACR)were collected.Serum FGL1 level was detected by enzyme-linked immunosorbent assay(ELISA).Pearson linear correlation was used for correlation,the diagnostic value was analyzed by ROC curve.Results Compared with the control group,the levels of ACR,FGL1 in patients with DM group increased,the levels of eGFR decreased,and the differences were statistically significant(t=5.686,4.336,-4.683,all P<0.05).Compated with the DM group,the levels of ACR,FGL1 in patients with DN-E group was increased,and the level of eGFR was decreased,and the differences were statistically significant(t=5.275,3.454,-4.969,all P<0.05).Compared with the DN-E group,the levels of ACR,FGL1 in the DN-A group were increased,the levels of eGFR were decreased,and the differences were statistically significant(t=7.881,7.051,-5.596,all P<0.05).Serum FGL1 level was negatively correlated with ALB and eGFR(r=-0.638,-0.547,all P<0.05),and positively correlated with ACR(r=0.691,P<0.05).The AUC(95%CI),specificity and sensitivity of serum FGL1 level in the diagnosis of DN were 0.947(0.908～0.987),100%and 82.4%,respectively.Conclusion The level of serum FGL1 in DN and DM patients is high,and the level of serum FGL1 is closely related to the common metabolic indexes such as ALB,eGFR and ACR in the diagnosis of DN,which may have certain clinical diagnostic value.