This article reports the clinical features and gene mutation types of a large family with Nascimento form of syndromic X-linked intellectual developmental disorder (MRXSN), involving 9 individuals across 3 generations, and a literature review was conducted. In this family, 9 individuals had similar manifestations including mental retardation and unusual facies, and 4 of them had passed away. Genetic testing showed that the proband had the deletion of exons 2-3 of the UBE2A gene, which was inherited from the mother. Fluorescent quantitative polymerase chain reaction showed that the proband and his uncle had the deletion of exons 2-3 of the UBE2A gene; the proband's mother, grandmother, and great-aunt had a heterozygous deletion of exons 2-3 of the UBE2A gene; the proband's father, sister, and aunt had a normal copy number of exons 2-3 of the UBE2A gene. The 34 patients reported in the literature had diverse clinical phenotypes, and UBE2A gene mutations (22/34, 65%) and large fragment deletions (12/34, 35%) were the main mutation types. Moderate to severe mental retardation (34/34, 100%), speech and language impairment (33/34, 97%), and unusual facies (32/34, 94%) were the main clinical manifestations of MRXSN patients. The disease has obvious phenotypic heterogeneity, and early diagnosis facilitates optimal prenatal and postnatal management to improve reproductive outcomes.
Humans ; Male ; Ubiquitin-Conjugating Enzymes/genetics* ; Female ; X-Linked Intellectual Disability/genetics* ; Gene Deletion ; Child ; Pedigree ; Child, Preschool ; Adult

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of elderly patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of elderly DLBCL patients diagnosed pathologically between 2010 and 2015 were extracted from the SEER database. Cox proportional hazards model was used for multivariate analysis, and Kaplan-Meier survival curves were plotted to explore the prognostic factors affecting overall survival (OS). RESULTS: A total of 11 523 elderly DLBCL patients were included, of whom 58.6% had stage Ⅲ/Ⅳ disease, and 28.8% exhibited extranodal involvement. Besides lymph nodes (68.5%), common primary extranodal sites included the gastrointestinal tract (9.8%) and lip, mouth, and pharynx (4.1%). The median survival time for the entire cohort was 47 months, with a 3-year survival rate of 52.0%, and a 5-year survival rate of 47.8%. Multivariate Cox regression analysis revealed that age, sex, race, Ann Arbor stage, primary site, B symptoms, treatment modality, treatment sequence, and whether DLBCL was the first malignant primary indicator were independent prognostic factors affecting OS in elderly DLBCL patients (all P <0.05). CONCLUSION Age≥70 years, male, black race, advanced Ann Arbor stage, primary sites in the lungs, liver, or kidney, presence of B symptoms, and preoperative systemic therapy were independent risk factors for poor prognosis in elderly DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Prognosis ; Aged ; Male ; Female ; Survival Rate ; Proportional Hazards Models ; Aged, 80 and over ; Kaplan-Meier Estimate ; Neoplasm Staging

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with intellectual development disorder and seizures due to a variant of AP2M1 gene. METHODS: Clinical data of a child with intellectual development disorder and epilepsy who was admitted to the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in January 2021 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected for whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The three-dimensional structure of the AP2M1 protein was visualized using Chimera v1.10.1 software. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants from the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). With "AP2M1 gene" "epilepsy" "intellectual disability" as the keywords, relevant cases were searched from CNKI, Wanfang Data knowledge service platform and PubMed databases with the search time spanning from the establishment of the database to September 2024. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2020-57). RESULTS: The child was a 8-years-and-6-months-old boy, who could raise his head at 3 months and sit alone at 8 months old. He could not walk alone at 1 year old and underwent 2 months' rehabilitation treatment, and could walk alone and call his parents at 1-and-a-half-years-old. At 4-years-and-10-months-old, he started to have frequent seizures, manifesting as low level of consciousness, body shaking, accompanied by blinking, lasting about a few seconds several times a day and could be relieved. With the treatment of sodium valproate combined with lamotrigine, the convulsions were controlled, but his movement and cognition were lagged behind. DNA sequencing revealed that he has harbored a novel variant of the AP2M1 gene (NM_004068.3) c.508C>T (p.Arg170Trp). Sanger sequencing confirmed that both of his parents were of the wild-type. According to the guidelines from the American College for Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PS2+PS4+PM1+PM2+PP2+PP3). The difference between the wild-type and mutant AP2M1 proteins can be clearly viewed through its three-dimensional structure. Two previous reports have included 5 cases due to the same variant. Common manifestations have included seizures (100%, 5/5), motor retardation (100%, 5/5), intellectual impairment (100%, 5/5), autism spectrum disorder (60%, 3/5), ataxia (100%, 5/5), and special facial features (20%, 1/5). CONCLUSION The c.508C>T (p.Arg170Trp) variant of the AP2M1 gene may underlie the intellectual retardation and seizure in this child.
Humans ; Male ; Child ; Intellectual Disability/genetics* ; Seizures/genetics* ; Exome Sequencing ; Mutation

Objective To analyze the application trends and research hotspots of brain-computer interface(BCI)technology in stroke rehabilitation over the past five years.Methods Relevant literatures on the use of BCI in stroke rehabilitation published between January,2021 and August,2025 were retrieved from the Web of Science Core Collection database.CiteSpace 6.4.R1 was used for visualiza-tion analysis.Results A total of 458 papers were included.The annual number of publications remained at a high level.China was the leading country in publication output,with Fudan University and Aalborg University as the top institutions.The most prolific author was Mads R.Jochumsen,while G.Pfurtscheller had the highest citation frequency.The key-words and burst terms with the highest frequency in this field were brain-computer interface,motor imagery,up-per limb and deep learning.Conclusion Over the past five years,research on BCI in stroke rehabilitation has maintained a high publication volume.The research hotspots focus on innovations in BCI algorithm technology and multidimensional validation of neu-ral mechanisms and rehabilitation efficacy.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

Objective To review the damage outcomes of patients in medical damage events and to analyze the influencing factors of medical causality determination in medical damage events in Tianjin city,with a view to reducing the occurrence of medical damage events by avoiding risk factors and standardizing the diagnostic and therapeutic activities of medical personnel.Methods 316 cases of medical damage events handled by the Medical Damage Identification Office of Tianjin Medical Association from 2017 to 2023 were selected as the research object,and descriptive analysis was used to summarize the basic situation of medical damage events,and the medical fault factors affecting the magnitude of the cause force of the medical side of medical damage events were explored through single-factor analysis and the construction of multiomal logistic regression models.Results Medical malpractice(OR=3.140)and incomplete preoperative assessment(OR=6.008)are factors that influence the determination of the liability of the medical institution in medical malpractice events(P＜0.05),and all three regression coefficients were greater than 0,all three were positively correlated with the probability that the medical cause power was judged to be greater than or equal to the equivalent cause.Conclusion The number of medical damage incidents in Tianjin shows a fluctuating downward trend.In Tianjin,the number of medical injury incidents showed a fluctuating downward trend,and the number of medical injury incidents in tertiary public general hospitals was the largest.Therefore,medical institutions should establish and improve multidisciplinary diagnosis and treatment mode to improve the level of diagnosis and treatment.Strengthen preoperative evaluation to avoid surgical risk.

Objective To investigate the effects of Demodex infection on clinical symptoms,signs,and tear MMP-9 levels in patients with meibomian gland dysfunction(MGD).Methods A total of 680 patients with MGD were selected from our hospital,including 162 males and 518 females,with an average age of(45.05±15.41)years old.The patients were divided into two groups based on the presence of Demodex mite infestation:the Demodex positive group(340 cases)and the Demodex negative group(340 cases).All patients underwent evaluations using the OSDI questionnaire,SPEED questionnaire,eyelid margin alteration score,corneal fluorescein staining score,tear MMP-9 measurement,meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,tear film breakup time(BUT),and Schirmer I tear secretion test.The differences in these indicators between the two groups were compared.Results SPEED questionnaire score:Demodex positive group:(7.68±2.80),Demodex negative group:(6.28±1.99).There was a statistically significant difference between the two groups(t=2.582,P=0.012).Eyelid margin alteration score:Demodex positive group:(3.63±1.53),Demodex negative group:(2.85±0.77).A statistically significant difference was observed(t=2.861,P=0.006).Corneal fluorescein staining score:Demodex positive group:(2.25±1.86),Demodex negative group:(1.08±1.33).There was a statistically significant difference(t=3.247,P=0.002).Tear MMP-9 content:Demodex positive group:(30.76±43.14)ng/mL,Demodex negative group:(12.36±12.10)ng/mL.A statistically significant difference was found(t=2.598,P=0.013).No statistically significant differences were observed between the Demodex positive and negative groups in meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,BUT,tear secretion examination,and age comparison(P>0.05).Conclusions Demodex mite infestation in patients with MGD exhibits significant differ-ences across various clinical indicators,notably in SPEED questionnaire scores,eyelid margin alterations,corneal fluorescein staining,and tear MMP-9 levels.These changes are associated with mechanisms including inflammatory responses,cellular damage,and immune dysregulation.Demodex mite infestation may significantly influence the clinical progression of MGD by exacerbating inflammation and symptom severity,potentially playing a crucial role in disease development.

Ventilator-induced lung injury(VILI)is a form of lung injury caused by inappropriate ventilator parameter settings or pre-existing lung pathologies during mechanical ventilation.The pathogenesis of VILI is complex,primarily involving barotrauma,volutrauma,atelectrauma,and biotrauma.To prevent VILI,clinical practice advocates protective lung ventilation strategies and personalized positive end-expiratory pressure(PEEP)settings.Early identification and precise assessment are critical for improving patient outcomes.The rapid advancement of imaging technologies has provided multidimensional perspectives for dynamic monitoring of VILI.This review summarizes the imaging principles,clinical applications in the context of VILI management,and limitations of various imaging modalities,including lung ultrasound(LUS),computed tomography(CT),electrical impedance tomography(EIT),and magnetic resonance imaging(MRI).By offering comprehensive diagnostic information,this review aims to provide a theoretical foundation for the precise assessment of VILI and the optimization of ventilatory support strategies.