1.Investigation of the impact and mechanism of IRF2BP2 knockdown on the proliferation in acute myeloid leukemia cells
Bi Zhou ; Xiaodong Tang ; Ying Li ; Yongping Zhang ; Shaoyan Hu
Acta Universitatis Medicinalis Anhui 2025;60(9):1682-1688
Objective:
To explore the effect of interferon regulatory factor 2 binding protein 2 ( IRF2BP2) on the proliferation of acute myeloid leukemia ( AML) cells and its molecular mechanism.
Methods:
The CRISPR-Cas9 gene editing technology was used to knock out IRF2BP2 in human AML cell lines Kasumi-1 and U937,and West- ern blot was performed to detect the knockout efficiency of IRF2BP2 protein.Cell morphology was observed using a microscope.Cell phenotypes were analyzed by CCK-8 assay,colony formation experiments,and flow cytometry. RNA-Seq was performed to identify differentially expressed genes between the IRF2BP2 knockout group and the control group in the U937 cell line.Gene Set Enrichment Analysis ( GSEA) was conducted to explore the down- stream molecular mechanisms.Western blot was used to detect the expression of downstream differentially expressed genes.The Cleavage Under Targets and Tagmentation ( CUT&Tag) technique was applied to identify the direct tar- gets of the IRF2BP2 protein,and the corresponding binding signals were visualized using the Integrated Genomics Viewer ( IGV) .
Results:
Compared with the control group,after knocking out IRF2BP2,the CCK-8 experiment showed that AML cell proliferation was inhibited ( P <0. 05) ; the number of colonies in the IRF2BP2 knockout group decreased ( P<0. 05) ,and the proportion of G1 phase was prolonged ( P<0. 05) ; in U937 cell lines,knoc- king out IRF2BP2 resulted in significant enrichment of differential genes in myelocytomatosis oncogene ( MYC) -re- lated signaling pathways,and the protein expression levels of pathway molecules MYC,cyclin-dependent kinase 4 ( CDK4) ,and cyclin - dependent kinase 2 ( CDK2 ) decreased with the downregulation of IRF2BP2; using IRF2BP2 antibodies in U937 cell lines for CUT&Tag experiments,IGV visualization analysis showed a significant increase in signal peaks in the MYC promoter region.
Conclusion
IRF2BP2 protein affects the cell cycle and pro- liferation of AML cells by targeting and regulating MYC.
2.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.
3.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.
4.Study on the mechanistic role of the Fuzheng Huayu formula against cholestatic liver fibrosis in mice
Zheng ZHANG ; Yue LIANG ; Enqi TANG ; Xiaoxi ZHOU ; Yonghong HU ; Gaofeng CHEN ; Wei LIU ; Yongping MU ; Ping LIU ; Jiamei CHEN
Chinese Journal of Hepatology 2025;33(9):889-897
Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2-/ -) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2-/ -mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 -/ - mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 -/ - mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 -/ - mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.
5.Comparison of the efficacy of anatomical resection versus hepatic parenchymal preservation preference in patients with solitary small hepatocellular carcinoma and cirrhosis: a multicenter retrospective study
Liming HUANG ; Yun YANG ; Yuntong LI ; Xianming WANG ; Siming ZHENG ; Qiang LU ; Zisen LAI ; Yongping LAI ; Zongren DING ; Jiahui LYU ; Jiacheng ZHANG ; Xinfeng QIU ; Weiping ZHOU ; Kongying LIN ; Yongyi ZENG
Chinese Journal of Hepatology 2025;33(4):348-358
Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.
6.Research progress of microfibril-associated protein 2 in malignant tumors
Zhijie DING ; Weiming YANG ; Yong YAN ; Miaokang XU ; Minglong HUANG ; Hao WANG ; Yongping ZHOU
Chinese Journal of Hepatobiliary Surgery 2025;31(7):557-560
Microfibrino-associated protein (MFAP) 2 is an extracellular matrix glycoprotein and a member of the MFAP family. It participates in the assembly of extracellular elastic microfibers.Upregulation of MFAP2 can promote the occurrence and development of various tumors and regulate multiple cancer-related signaling pathways and is related to their prognosis, making it a potential target for tumor treatment. This article summarizes the research progress on the pathogenesis, targeted therapy and prognosis of MFAP2 in malignant tumors.
7.Research progress of microfibril-associated protein 2 in malignant tumors
Zhijie DING ; Weiming YANG ; Yong YAN ; Miaokang XU ; Minglong HUANG ; Hao WANG ; Yongping ZHOU
Chinese Journal of Hepatobiliary Surgery 2025;31(7):557-560
Microfibrino-associated protein (MFAP) 2 is an extracellular matrix glycoprotein and a member of the MFAP family. It participates in the assembly of extracellular elastic microfibers.Upregulation of MFAP2 can promote the occurrence and development of various tumors and regulate multiple cancer-related signaling pathways and is related to their prognosis, making it a potential target for tumor treatment. This article summarizes the research progress on the pathogenesis, targeted therapy and prognosis of MFAP2 in malignant tumors.
8.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.
9.Mediating effect of psychological capital between safety organization and work engagement among Operating Room nurses
Yongping SHI ; Bo ZHANG ; Xiaoling HAO ; Dubiao ZHOU
Chinese Journal of Modern Nursing 2025;31(27):3709-3714
Objective:To explore the direct effect of safety organization on work engagement of Operating Room nurses, as well as the mediating effect of psychological capital between safety organization and work engagement, so as to provide theoretical basis for developing intervention programs to enhance work engagement of Operating Room nurses.Methods:From October to December 2024, convenience sampling was used to select 260 Operating Room nurses from three ClassⅢ Grade A hospitals as research subjects. Psychological Capital Questionnaire, Safety Organizing Scale, and Work Engagement Scale were used to survey Operating Room nurses. AMOS 26.0 software was used to analyze the mediating effect of Operating Room nurses' psychological capital between safety organization and work engagement.Results:A total of 260 questionnaires were distributed and 241 valid questionnaires were recovered, with a valid recovery rate of 92.69%. Among 241 Operating Room nurses, the total scores of Work Engagement Scale, Psychological Capital Questionnaire, and Safety Organizing Scale were (37.35±7.30), (90.10±11.62), and (41.58±10.82), respectively. The total score and scores of each dimension of the Work Engagement Scale were positively correlated with the total score and scores of each dimension of the Psychological Capital Questionnaire and the total score of the Safe Organizing Scale ( P<0.05). The total score and scores of each dimension of the Psychological Capital Questionnaire were positively correlated with the total score of the Safe Organizing Scale ( P<0.05). Mediating effect analysis showed that the direct effect of safety organization on work engagement of Operating Room nurses was established, with an effect value of 0.266 ( P<0.05). Psychological capital played a partially mediating effect between safety organization and work engagement of, with an effect value of 0.275, and the mediating effect accounted for 50.83% of the total effect. Conclusions:Safety organization has a positive impact on work engagement of Operating Room nurses, and psychological capital partially mediates the effect between safety organization and work engagement of Operating Room nurses. Hospital nursing administrators should be aware of the importance of building a safety organization and pay attention to building the psychological capital of Operating Room nurses so as to improve work engagement.
10.Mediating effect of psychological capital between safety organization and work engagement among Operating Room nurses
Yongping SHI ; Bo ZHANG ; Xiaoling HAO ; Dubiao ZHOU
Chinese Journal of Modern Nursing 2025;31(27):3709-3714
Objective:To explore the direct effect of safety organization on work engagement of Operating Room nurses, as well as the mediating effect of psychological capital between safety organization and work engagement, so as to provide theoretical basis for developing intervention programs to enhance work engagement of Operating Room nurses.Methods:From October to December 2024, convenience sampling was used to select 260 Operating Room nurses from three ClassⅢ Grade A hospitals as research subjects. Psychological Capital Questionnaire, Safety Organizing Scale, and Work Engagement Scale were used to survey Operating Room nurses. AMOS 26.0 software was used to analyze the mediating effect of Operating Room nurses' psychological capital between safety organization and work engagement.Results:A total of 260 questionnaires were distributed and 241 valid questionnaires were recovered, with a valid recovery rate of 92.69%. Among 241 Operating Room nurses, the total scores of Work Engagement Scale, Psychological Capital Questionnaire, and Safety Organizing Scale were (37.35±7.30), (90.10±11.62), and (41.58±10.82), respectively. The total score and scores of each dimension of the Work Engagement Scale were positively correlated with the total score and scores of each dimension of the Psychological Capital Questionnaire and the total score of the Safe Organizing Scale ( P<0.05). The total score and scores of each dimension of the Psychological Capital Questionnaire were positively correlated with the total score of the Safe Organizing Scale ( P<0.05). Mediating effect analysis showed that the direct effect of safety organization on work engagement of Operating Room nurses was established, with an effect value of 0.266 ( P<0.05). Psychological capital played a partially mediating effect between safety organization and work engagement of, with an effect value of 0.275, and the mediating effect accounted for 50.83% of the total effect. Conclusions:Safety organization has a positive impact on work engagement of Operating Room nurses, and psychological capital partially mediates the effect between safety organization and work engagement of Operating Room nurses. Hospital nursing administrators should be aware of the importance of building a safety organization and pay attention to building the psychological capital of Operating Room nurses so as to improve work engagement.


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