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 investigate the efficacy and safety of ketogenic diet (KD) therapy in the epilepsy of infancy with migrating focal seizures (EIMFS) associated with TBC1D24 gene mutation.Methods:Clinical data of two children with TBC1D24 gene-related EIMFS were collected retrospectively, who were admitted to Department of Pediatrics, Fujian Medical University Union Hospital from 2019 to 2020. Their clinical characteristics and the efficacy and safety of KD therapy were analyzed, and literature review was conducted.Results:Seizures were onset before six months old in the two children with TBC1D24 gene-related EIMFS. Multifocal myoclonic seizures were manifested and happened frequently, lasting for more than 30 minutes sometimes. Developmental retardation was obvious in the two children. A small amount of focal sharp, spike, sharp-slow complex, and spike-slow complex waves were showed in the interictal electroencephalography (EEG). TBC1D24 gene mutations were found in the two children, one with a compound heterozygous mutation (c.1025C>T, p.S342L; c.229_c.240delATCGTGGGCAAG,p.I77_K80del), and the other with a homozygous mutation [c.119G>A,p.R40H(Arg40His)]. Both of those were potentially pathogenic. A variety of anti-epileptic drugs showed poor outcome for the two children. The epilepsy was drug-refractory one. After four to 17 months of KD therapy, the epilepsy in the two children was controlled effectively. There was not obvious adverse reactions. Among six children with TBC1D24 gene-related EIMFS in the literature review, four cases were effective or partially effective for KD therapy, one was discontinued due to insufficient ketogenic ratio, and one was discontinued without effect. There were no obvious adverse reactions in the six children.Conclusions:TBC1D24 gene-related EIMFS is mostly drug-refractory epilepsy. Early KD therapy may help to control seizures.

BACKGROUND: Specific gene expression at specific injury sites enhances cell regeneration. OBJECTIVE: To summarize the concept of gene therapy, to review the strategies of gene therapy and the mechanism of gene therapy for osteoarthritis, and to introduce the research direction of gene therapy. METHODS: Extensive consulted the literature on osteoarthritis gene therapy and related content in foreign databases such as PubMed and Science Direct. The key words were “Gene therapy, Cartilage, Cartilage repair, Osteoarthritis, Expression vectors, miRNA”. Above data were analyzed and summarized. RESULTS AND CONCLUSION: Gene therapy for osteoarthritis can be applied to all aspects of the pathogenesis of osteoarthritis and affect the metabolism of related substances. The target gene is delivered to the target cells through viral or non-viral vectors. At present, the focus of gene therapy is to accelerate cell repair and reduce inflammatory response. At the same time, multiple choices of gene vectors and target genes provide better individualized treatment options. The specific mechanism of gene therapy for osteoarthritis in clinic is not clear, and there is the possibility of gene mutation, which needs to be further studied to verify the safety.

Objective Articular cartilage injury is one of the most common orthopedic diseases with high morbidity and morbidity,especially in the elderly. Articular cartilage injury causes degenerative changes of articular cartilage, such as osteoarthritis, which can lead to disability, pain during joint movement and deformation of bone and joint. The prevalence of osteoarthritis accounts for 10% ～12% of the total population in the world. It is a common disease. The prevalence of osteoarthritis has increased to 49. 7% for the elderly aged over 65 years old ( Statistics of the World Health Organization ( who) in 2010 show that with the development of social aging and obesity and other adverse factors,these figures will continue to rise. It is known that osteoarthritis is related to aging,trauma,genetic susceptibility,obesity and inflammation,but the specific cause of osteoarthritis has not been fully identified, which leads to many obstacles in clinical treatment of osteoarthritis. At present,most of the clinical and research work in this field is focused on the restoration of cartilage trauma. In this review, we summarize and discuss the methods of cartilage defect repair,as well as the hot spots and directions of future research work.

Objective To analyze the influencing factors for fungal infection in hospitalized patients with acquired immunodeficiency syndrome(AIDS),and provide basis for taking preventive and control measures.Methods Clini-cal data of 112 inpatients with AIDS in a tertiary first-class hospital from January 2010 to October 2015 were ana-lyzed retrospectively,related risk factors were analyzed in patients with fungal infection,univariate analysis was performed byχ2 or t test,and multivariate analysis was performed by logistic regression analysis.Results Among 112 AIDS inpatients,41 (36.61%)had fungal infection.Candida albicans was the main pathogen (n=52, 76.74%)and was mainly isolated from lower respiratory tract (n=29,42.65%).Univariate analysis showed that invasive procedures,duration of antimicrobial use,combined antimicrobial use,and decreased CD4+ T lymphocyte count in peripheral blood were risk factors for fungal infection in AIDS inpatients(all P<0.05),while oral cleaning care and systemic antiviral therapy were protective factors for fungal infection(all P<0.05);multivariate analysis showed that decreased CD4+ T lymphocyte count in peripheral blood(OR,1.017[95% CI,1.009-1.025])and combined antimicrobial use(OR,3.975[95%CI,1.093-14.448])were independent risk factors for fungal infection in AIDS inpatients,while systemic antiviral therapy was independent protective factor for fungal infection (OR, 0.288[95%CI,0.099-0.841]).Conclusion There are many factors influencing fungal infection in AIDS patients, rational use of antimicrobial agents,systemic antiviral therapy,and increasing serum albumin concentration are main methods to prevent fungal infection,avoid unnecessary invasive procedures and application of preventive antifungal therapy for high-risk patients are also effective to prevent fungal infection.