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.BK virus nephropathy after allogeneic hematopoietic stem cell transplantation: a case report and literature review
Wenli ZHANG ; Yingling ZU ; Zhenghua HUANG ; Zhen LI ; Ruirui GUI ; Juan WANG ; Xianjing WANG ; Huili WANG ; Xinxin FAN ; Yongping SONG ; Baijun FANG ; Jian ZHOU
Chinese Journal of Hematology 2025;46(3):273-275
A 20-year-old male patient with T-lymphoblastic lymphoma/leukemia received 9/10 human leukocyte antigen-compatible unrelated peripheral blood stem cell transplantation. He was transplanted with 5.91×10 8 mononuclear cells/kg and 2.88×10 6 CD34 + cells/kg, and neutrophil engraftment was obtained at +11 days and platelet engraftment at +9 days. After transplantation, he presented with repeatedly increased serum creatinine levels, BK virus (BKV) -associated hemorrhagic cystitis, and BKV viremia. BK virus nephropathy was diagnosed based on renal biopsy and metagenomic next-generation sequencing. After adjusting the immunosuppressant, intravenous immunoglobulin, and donor lymphocyte infusion treatment, the patient’s renal function deteriorated progressively, and he eventually died of multiple organ failure at +289 days.
3.Analysis of inpatient death cases in a tertiary hospital in Sichuan province from 2019 to 2023
Yongping DENG ; Gang HUANG ; Li TANG ; Hang QU ; Fan YANG
Modern Hospital 2025;25(9):1433-1437
Objective To analyze the characteristics of death cases in a certain tertiary hospital,providing references for hospital management decisions and the evaluation of the effectiveness of medical services.Methods The information of death ca-ses of inpatients in the hospital from 2019 to 2023 was extracted through the inpatient medical records information system,and the medical records of inpatients were retrospectively analyzed by clinical epidemiological methods.Results The cumulative number of inpatients admitted to the hospital from 2019-2023 was 459 821,with 3 250 deaths and a case-fatality rate of 0.71%.There was a decreasing trend in the case fatality rate from 0.71%in 2019 to 0.63%in 2023,but the difference was not statistically significant(APC=-3.17,P>0.05).The case fatality rate was 0.97%for males and 0.45%for females,with males having a higher case fatality rate than females(x2=435.206,P<0.05).The mean age of the deceased cases was(69.59±17.70)years,and the case fatality rate increased gradually with age,and the highest case fatality rate was 2.98%in the age group of ≥80 years.The difference in case fatality rate between patients of different age groups was statistically significant(x2=3 502.991,P<0.05).The top 5 causes of death of hospitalized patients were tumor,circulatory diseases,respiratory diseases,some infec-tious and parasitic diseases and injuries,poisoning and external causes,accounting for 87.33%of the total deaths.The main causes of death in neoplasms were bronchial and pulmonary malignancies,hepatic and intrahepatic biliary malignancies,and gas-tric malignancies;in the circulatory diseases,cerebral infarction,acute myocardial infarction,and intracerebral haemorrhage;and in the respiratory diseases,pathogens unspecified pneumonias,bacterial pneumonias,and other chronic obstructive pulmona-ry diseases.Conclusion The case fatality rate of male and ≥80 years old patients in this hospital is higher.Tumor,circulatory diseases and respiratory diseases are the main causes of death.The hospital should allocate medical resources in a scientific and reasonable way according to the age,gender and disease characteristics of the patients;strengthen the prevention and treatment of tumors,circulatory diseases and respiratory diseases according to the cause of death and their distribution,improve the diagnosis and treatment level,and reduce the inpatient morbidity and fatality rate.
4.Analysis of inpatient death cases in a tertiary hospital in Sichuan province from 2019 to 2023
Yongping DENG ; Gang HUANG ; Li TANG ; Hang QU ; Fan YANG
Modern Hospital 2025;25(9):1433-1437
Objective To analyze the characteristics of death cases in a certain tertiary hospital,providing references for hospital management decisions and the evaluation of the effectiveness of medical services.Methods The information of death ca-ses of inpatients in the hospital from 2019 to 2023 was extracted through the inpatient medical records information system,and the medical records of inpatients were retrospectively analyzed by clinical epidemiological methods.Results The cumulative number of inpatients admitted to the hospital from 2019-2023 was 459 821,with 3 250 deaths and a case-fatality rate of 0.71%.There was a decreasing trend in the case fatality rate from 0.71%in 2019 to 0.63%in 2023,but the difference was not statistically significant(APC=-3.17,P>0.05).The case fatality rate was 0.97%for males and 0.45%for females,with males having a higher case fatality rate than females(x2=435.206,P<0.05).The mean age of the deceased cases was(69.59±17.70)years,and the case fatality rate increased gradually with age,and the highest case fatality rate was 2.98%in the age group of ≥80 years.The difference in case fatality rate between patients of different age groups was statistically significant(x2=3 502.991,P<0.05).The top 5 causes of death of hospitalized patients were tumor,circulatory diseases,respiratory diseases,some infec-tious and parasitic diseases and injuries,poisoning and external causes,accounting for 87.33%of the total deaths.The main causes of death in neoplasms were bronchial and pulmonary malignancies,hepatic and intrahepatic biliary malignancies,and gas-tric malignancies;in the circulatory diseases,cerebral infarction,acute myocardial infarction,and intracerebral haemorrhage;and in the respiratory diseases,pathogens unspecified pneumonias,bacterial pneumonias,and other chronic obstructive pulmona-ry diseases.Conclusion The case fatality rate of male and ≥80 years old patients in this hospital is higher.Tumor,circulatory diseases and respiratory diseases are the main causes of death.The hospital should allocate medical resources in a scientific and reasonable way according to the age,gender and disease characteristics of the patients;strengthen the prevention and treatment of tumors,circulatory diseases and respiratory diseases according to the cause of death and their distribution,improve the diagnosis and treatment level,and reduce the inpatient morbidity and fatality rate.
5.BK virus nephropathy after allogeneic hematopoietic stem cell transplantation: a case report and literature review
Wenli ZHANG ; Yingling ZU ; Zhenghua HUANG ; Zhen LI ; Ruirui GUI ; Juan WANG ; Xianjing WANG ; Huili WANG ; Xinxin FAN ; Yongping SONG ; Baijun FANG ; Jian ZHOU
Chinese Journal of Hematology 2025;46(3):273-275
A 20-year-old male patient with T-lymphoblastic lymphoma/leukemia received 9/10 human leukocyte antigen-compatible unrelated peripheral blood stem cell transplantation. He was transplanted with 5.91×10 8 mononuclear cells/kg and 2.88×10 6 CD34 + cells/kg, and neutrophil engraftment was obtained at +11 days and platelet engraftment at +9 days. After transplantation, he presented with repeatedly increased serum creatinine levels, BK virus (BKV) -associated hemorrhagic cystitis, and BKV viremia. BK virus nephropathy was diagnosed based on renal biopsy and metagenomic next-generation sequencing. After adjusting the immunosuppressant, intravenous immunoglobulin, and donor lymphocyte infusion treatment, the patient’s renal function deteriorated progressively, and he eventually died of multiple organ failure at +289 days.
6.Noninvasive assessment of the risk of esophageal variceal bleeding from noncirrhotic portal hypertension
Hangfei XU ; Yu WANG ; Fuliang HE ; Zhenhua FAN ; Hui LIU ; Yongping YANG ; Jidong JIA ; Fuquan LIU ; Huiguo DING
Chinese Journal of Hepatology 2022;30(10):1092-1099
Objective:To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH).Methods:111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results:Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively ( P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 ( P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups ( P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively ( P<0.05). Conclusion:Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.
7.Application of quantitative detection of multiple-source cytomegalovirus DNA in diagnosis of cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation
Haoyu CHENG ; Fan YANG ; Yixin YANG ; Shuqin ZHANG ; Yongping ZHANG ; Weijie ZHANG ; Xinhong FEI ; Yuming YIN ; Jiangying GU ; Jingbo WANG
Organ Transplantation 2021;12(1):96-
Objective To evaluate the diagnostic value of quantitative detection of cytomegalovirus (CMV) DNA from different sources [plasma, sputum and bronchoalveolar lavage fluid(BALF)] for CMV pneumonia after allogeneic hematopoietic stem cell transplantation. Methods Clinical data of 405 recipients undergoing allogeneic hematopoietic stem cell transplantation were retrospectively analyzed. Among them, 19 recipients diagnosed with CMV pneumonia were assigned into the CMV pneumonia group, and 229 recipients with CMV viremia alone, 11 recipients without CMV pneumonia who received fiberoptic bronchoscopy and 16 recipients diagnosed with bacterial or fungal pneumonia based on pathogenic evidence receiving sputum culture were assigned into the control A, B and C groups, respectively. The incidence of CMV pneumonia was summarized. The CMV DNA load of specimens from different sources (plasma, sputum and BALF) of recipients with CMV pneumonia was analyzed. The clinical prognosis of recipients with CMV pneumonia was evaluated. Results Among 405 recipients undergoing allogeneic hematopoietic stem cell transplantation, 19 cases developed CMV pneumonia, and the overall incidence of CMV pneumonia was 4.7%(19/405). The CMV DNA load in the plasma, sputum and BALF of recipients with CMV pneumonia was higher than those in the control A, B and C groups (all
8.Construction of formative evaluation system for practical teaching of medical laboratory
Lin YU ; Zhongmin LIU ; Yongping LIN ; Tingting FAN ; Lidong LIU ; Hongguang XIAO
Chinese Journal of Medical Education Research 2021;20(10):1148-1152
Objective:To establish a reasonable and effective formative evaluation system based on the characteristics of practical teaching of medical laboratory to evaluate the effect of practical teaching and improve the quality and level of teaching.Methods:A survey and research method was used to screen the elements needed for the formative evaluation system, so as to construct the framework and evaluation indicators of the practice teaching of this specialty. The students from Batch 2016 were scored before and after implementing formative evaluation, and the results were statistically analyzed by paired t test with SPSS 20.0 software. Results:The survey results of a total of 30 teachers (experts) and 121 students in this major were counted. According to the practical characteristics of this major, the evaluation system included two first-level indicators, five second-level indicators, and corresponding third-level and fourth-level indicators. After statistical analysis, students' learning interest, practical ability, self-learning ability, team assistance ability and knowledge development ability were all significantly improved after the implementation of formative evaluation ( P<0.01- P<0.05), and students' enthusiasm for class also increased ( P<0.05). Conclusion:It proves that the constructed formative evaluation system conforms to the characteristics of practical teaching of medical laboratory, which helps to improve the effect of practical teaching and lays a foundation for its application in the practical teaching of this professional course.
9.Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon α-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study
Runan WEI ; Nanhong ZHENG ; Xiangao JIANG ; Chunlian MA ; Xiaowei XU ; Shourong LIU ; Yongping CHEN ; Kaijin XU ; Hainv GAO ; Jiansheng ZHU ; Qiang SHU ; Jifang SHENG ; Xiaoqiang ZHANG ; Minghui LI ; Yan ZHANG ; Mengjie MA ; Xuan ZHANG ; Shibo LI ; Qiujing WANG ; Lingjun YING ; Yongjun ZHANG ; Yunzhen SHI ; Lingyan FAN ; Wanjun YU ; Huaying WANG ; Dandan SUN ; Xiaodong WANG ; Jichan SHI ; Yinghu CHEN ; Xinsheng XIE ; Yunqing CHEN ; Weihong WANG ; Zhaowei TONG ; Lingling TANG ; Mengfei ZHU ; Lingjian ZHANG ; Lanjuan LI
Chinese Journal of Clinical Infectious Diseases 2020;13(1):9-15
Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.
10.Clonal heterogeneity and its prognostic significance in acute lymphoblastic leukemia
Xiaodong LYU ; Zhen GUO ; Yangwei LI ; Jieying HU ; Ruihua FAN ; Yongping SONG
Chinese Journal of Internal Medicine 2020;59(8):629-633
Objective:To explore the characteristics and clinical significance of clonal heterogeneity in patients with acute lymphoblastic leukemia(ALL).Methods:From January 2016 to June 2019, 170 newly diagnosed ALL patients were enrolled in the Department of Hematology, Henan Cancer Hospital, including 93 males and 77 females, with a median age of 17 (2-80) years. Fifty-two ALL-related genes were detected by high-throughput sequencing technique. The clonal heterogeneity of mutations was analyzed according to the variant allele frequency (VAF) and the results of flow cytometry. The prognostic value of mutations was also evaluated.Results:Gene mutations were detected in 121 (71.2%, 121/170) patients, of which 2 or more clones were detected in 18 (52.9%, 18/34) T-cell acute lymphoblastic leukemia patients, while only 23 (16.9%, 23/136) B-cell acute lymphoblastic leukemia patients were positive of multiple mutations ( P<0.01).Gene mutation-related clonal heterogeneity analysis showed that 2 or more clones were frequent in patients with NOTCH1 mutations (13/19 patients) ( P<0.01). Event free survival (EFS) in patients with 3 or more clones was significantly lower than other patients (χ 2=10.330, P=0.016). Child ALL patients had similar result, that multiple clones predicted lower overall survival (OS) and EFS (OS: χ 2=7.974, P=0.047; EFS: χ 2=10.860, P=0.013). Conclusion:Clonal heterogeneity in ALL patients is closely related to the different origin of lymphocyte lineages and the age of onset, which may reveal the nature of the disease and predict the clinical outcome.

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