1.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
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.
2.Correlation between frailty and carotid plaque stability in patients with ischemic stroke
Shuqi SHI ; Yan HE ; Yuchun LIU ; Tingting XU ; Yundi YIN ; Zhiling ZHAO ; Haiya SUN
Chinese Journal of Modern Nursing 2024;30(14):1857-1863
Objective:To explore the correlation between frailty and carotid plaque stability in patients with ischemic stroke.Methods:This study was a cross-sectional study. From May to December 2023, convenience sampling was used to select 360 patients with ischemic stroke in the Department of Neurology of Affiliated Hospital of Jining Medical University and underwent carotid artery color Doppler ultrasound examination as the study subject. Patients were surveyed using the General Information Questionnaire, Barthel Index and the Edmonton Frail Scale. Carotid artery color Doppler ultrasound was used to evaluate the stability of carotid plaques in patients. Multivariate Logistic regression was used to explore the correlation between frailty and carotid plaque stability.Results:A total of 360 questionnaires were distributed, and 352 valid questionnaires were collected, with a valid response rate of 97.78%. The incidence of frailty in 352 ischemic stroke patients was 44.89% (158/352). Multivariate analysis showed that compared to stable plaques, unstable carotid plaques were an independent risk factor for frailty in patients with ischemic stroke ( OR=2.127, 95% confidence interval: 1.247-3.626) . Conclusions:Compared to stable plaques, unstable carotid plaques increase the risk of frailty in patients with ischemic stroke. Strengthening the assessment of carotid plaques in patients with ischemic stroke by nursing staff can early identify high-risk individuals for frailty, and timely carry out personalized interventions, thereby reducing the occurrence of adverse health events in patients.
3.Practice and experience of group therapy in improving the subjective well-being of elderly patients with long-term hospitalization
Min ZHAO ; Ping YE ; Shuqi HU ; Lingna GU ; Jianhong WU ; Dingmei SHI
Chinese Journal of Modern Nursing 2017;23(8):1102-1104
Objective To investigate the application effect of group therapy in improving the subjective well-being (SWB) of elderly patients with long-term hospitalization. Methods Totally 100 cases of elderly patients admitted in geriatric ward of Ningbo First Hospital for long-time were selected. Newfoundland scale of happiness (MUNSH) scale and the negative life events questionnaire were used to investigate elderly inpatients, and patients with MUNSH ≤12 points received group therapy. Patients were divided into several groups to receive the intervention according to the negative life events. One year after intervention,patients receiving group therapy were evaluated again by using MUNSH scale to evaluate the intervention effect. Results Among 100 elderly patients,there were 32 cases of high SWB,3 cases of low SWB,and 65 cases of medium SWB. 53 cases of patients had sleep disorders,and 62.26% of them had low SWB. After intervention,the scores of negative experience and emotion of elderly patients were lower than those before intervention (P<0.05);the scores of positive emotion and positive experience and the total MUNSH score were higher than those before intervention (P < 0.05). Conclusions According to the different influencing factors,group interventions can significantly improve the SWB level of elderly patients with long-term hospitalization,so as to improve their quality of life.

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