1.Treatment of Idiopathic Pulmonary Fibrosis from Impediment
Siyu CHEN ; Zhenghua CAO ; Rong XU ; Qingrong LI ; Yanze BI ; Boyi SHANG ; Shaodan HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):254-264
Idiopathic pulmonary fibrosis (IPF) is a chronic and fibrotic lethal interstitial lung disease with poor prognosis. It is mainly treated by organ transplantation and administration of chemical drugs, which have poor efficacy and induce side effects, failing to meet the clinical needs. Therefore, it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that TCM has remarkable therapeutic effects on IPF and thus demonstrate broad application prospects. Modern medical research shows that the pathogenesis of IPF can be discussed from inflammation (macrophage polarization), oxidative stress, epithelial-mesenchymal transition (EMT), autophagy inhibition and other related signaling pathways, while few studies systematically explain the relationship between the signaling pathways and TCM theory. According to the theory of TCM, lung collateral obstruction is the basic pathogenesis of IPF. Therefore, according to the principle of dredging and replenishing lung collaterals, IPF can be treated with the methods of reinforcing healthy qi and eliminating pathogen, replenishing qi and activating blood, and detoxifying and dredging collaterals, which demonstrate definite curative effect and can effectively relieve clinical symptoms, restore the lung function and blood oxygen partial pressure, improve the quality of life of patients, and reduce adverse reactions. Experimental studies have found that dredging and replenishing lung collaterals have significant effects on IPF inflammation (macrophage polarization), oxidative stress, EMT, autophagy inhibition and other signaling pathways. Therefore, from the perspective of impediment, this article reviews pathogenesis of IPF, the research progress in TCM treatment of IPF, and the treatment of IPF from active components, single herbs, and compound prescriptions of TCM, with the aim of revealing the scientific connotation of the treatment of IPF from impediment and providing a new theoretical basis for enriching the TCM methods of treating IPF.
2.Mechanisms and treatments of cognitive decline induced by cranial radiation
Yifan HU ; Wenjing YANG ; Shufang CUI ; Xiaoying BI
Chinese Journal of Radiological Health 2026;35(1):128-135
While cranial radiotherapy effectively kills tumor cells and significantly prolongs patient survival, it often leads to progressive cognitive decline. To date, the specific mechanisms underlying radiation-induced cognitive decline have not been fully elucidated, which greatly limits the development of related therapeutic strategies. Therefore, this article provides a comprehensive analysis of post-radiation changes in neurogenesis, neuronal synaptic plasticity, myelin injury plasticity, and parenchymal cells such as microglia in the brain, systematically elucidates the potential mechanisms of radiation-induced cognitive decline, and summarizes feasible therapeutic approaches. These findings provide a solid foundation for developing novel strategies to mitigate radiation-induced cognitive decline.
3.Relationship between physical development and onset and progression of myopia among children and adolescents
MA Xiaohui, GONG Yizhuo, QIU Tingting, LIU Zheng, HUO Huanhuan, HU Yuanyuan, BI Hongsheng
Chinese Journal of School Health 2026;47(5):723-727
Objective:
To investigate the relationship between physical development indicators and the onset and progression of myopia among children and adolescents, so as to provide theoretical support for coordinated vision and physical health management.
Methods:
A prospective cohort study was conducted. In September 2022, 3 102 students from grade one in primary school to grade three in junior high school (five year primary school and four year junior high school) from six schools in Huantai County, Shandong Province, were selected using multistage cluster random sampling method to participate in an epidemiological survey on myopia, with follow up completed in September 2023. Follow up value minus baseline value( d ) was used to assess changes in physical development and vision indicators. Multivariate Logistic regression analysis was used to examine the relationship between physical development indicators and the incidence of myopia. Generalized linear models were established to analyze the relationship between physical development indicators and changes in d spherical equivalent (SE) and d axial length (AL) .
Results:
Multivariate Logistic regression analysis showed that, after adjusting for factors such as gender, age, and baseline body mass index, the third ( Q 3)and fourth ( Q 4)quartiles of d height showed increased risks of myopia onset within one year compared to the first quartile( Q 1) ( OR =1.85,95% CI =1.18-2.88; OR =1.74,95% CI =1.09-2.78,both P <0.05). Results from the generalized linear model indicated that, after adjusting for confounding factors such as gender, age, and baseline SE, d SE was negatively correlated with d height and d weight in children and adolescents ( β =-0.024, 95% CI =-0.031 to -0.018; β =-0.006, 95% CI =-0.011 to -0.001), d AL was positively correlated with d height and d weight in children and adolescents ( β =0.011, 95% CI =0.008-0.013; β =0.005, 95% CI =0.003-0.007) (all P <0.05).
Conclusions
Physical development indicators in children and adolescents were associated with the onset and progression of myopia. Dynamic monitoring and early intervention of myopia should be strengthened for children and adolescents with rapid height and weight gain to achieve coordinated management of myopia and physical development.
4.CD69 Expression is Negatively Associated With T-Cell Immunity and Predicts Antiviral Therapy Response in Chronic Hepatitis B
Yurong GU ; Yanhua BI ; Zexuan HUANG ; Chunhong LIAO ; Xiaoyan LI ; Hao HU ; Huaping XIE ; Yuehua HUANG
Annals of Laboratory Medicine 2025;45(2):185-198
Background:
The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB.
Methods:
We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy.
Results:
CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P = 0.002).
Conclusions
CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.
5.Construction and validation of a novel prognostic risk scoring table for patients with acute-on-chronic liver failure
Zhanhu BI ; Haifeng HU ; Hong DU ; Linxu WANG ; Xiaofei YANG ; Yidi DING ; Jianqi LIAN
Journal of Clinical Hepatology 2025;41(10):2102-2109
ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure (ACLF), and to construct a risk scoring table that can accurately predict the prognosis of patients in the early stage. MethodsA retrospective analysis was performed for the clinical data of 502 patients with ACLF who were admitted to Tangdu Hospital, Air Force Medical University, from January 1, 2010 to December 31, 2020 (training set), and the influencing factors for 28-day mortality rate were identified. The 69 ACLF patients who were admitted to Tangdu Hospital, Air Force Medical University, from January 1 to December 31, 2021 were enrolled as the validation set. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A univariate Cox regression analysis was used to obtain the early warning indicators associated with the 28-day prognosis of ACLF patients, and variance inflation factors were used to assess multicollinearity among predictors; a multivariate Cox regression analysis was used to construct a risk model for ACLF prognosis (mortality). A risk scoring table for ACLF prognosis (mortality) was developed based on regression coefficients (β) from the model equation and weight assignments in the nomogram. Internal validation and comparison were performed for the risk model for ACLF prognosis (mortality), the scoring table for ACLF prognosis (mortality), and other scoring models (Child-Turcotte-Pugh [CTP] score, Model for End-Stage Liver Disease [MELD] score, MELD combined with serum sodium concentration [MELD-Na] score, and integrated MELD [iMELD] score) in the training set, while external validation and comprehensive evaluation of the scoring table and the other scoring models were performed in the validation set. The Nagelkerke’s R2 test and the Hosmer-Lemeshow test were used to assess the degree of fitting of the risk model for ACLF prognosis (mortality), the scoring table for ACLF prognosis (mortality), and other scoring models, and fitting curves were plotted. C-index was used to assess the discriminatory ability of the scoring table for ACLF prognosis (mortality) and the other scoring models, and the Z-test was used for comparison of C-index between different models. The decision curve analysis was used to compare the clinical benefits of the scoring table for ACLF prognosis (mortality) and the other scoring models. ResultsThe multivariate Cox regression analysis showed that age (hazard ratio [HR]=1.027, 95% confidence interval [CI]: 1.015 — 1.039, P<0.001), hepatic encephalopathy grade (grade 1: HR=2.928, 95%CI: 1.463 — 5.858, P=0.002; grade 2: HR=3.811, 95%CI: 2.078 — 6.988, P<0.001; grade 3: HR=3.916, 95%CI: 1.917 — 8.001, P<0.001; grade 4: HR=6.966, 95%CI: 4.559 — 10.644, P<0.001), an increase in total bilirubin (TBil) by ≥17.1 μmol/L per day (HR=1.771, 95%CI: 1.248 — 2.513, P=0.001), creatinine (HR=1.005, 95%CI: 1.004 — 1.006, P<0.001), neutrophil count (HR=1.092, 95%CI: 1.060 — 1.126, P<0.001), and international normalized ratio (HR=1.298, 95%CI: 1.187 — 1.418, P<0.001) were independent risk factors associated with the 28-day mortality rate of ACLF patients, and a risk scoring table was constructed for ACLF prognosis (mortality). The Nagelkerke’s R2 test showed that the risk scoring table for ACLF prognosis (mortality) had an R2 value of 0.599 in the training set and 0.722 in the validation set, which were higher than the R2 values of CTP, MELD, MELD-Na, and iMELD scores. The Hosmer-Lemeshow test showed that the risk scoring table for ACLF prognosis (mortality) had a P value of 0.280 in the training set and 0.788 in the validation set. The C-index analysis showed that the scoring table had a higher C-index than the other scoring models in the validation set (all P<0.001), as well as a higher C-index than CTP score in the training set (P<0.001). The decision curve analysis showed that the risk scoring table for ACLF prognosis (mortality) had higher clinical net benefits than the other scoring models. ConclusionCompared with other scoring models currently used in clinical practice, the novel risk scoring table for ACLF prognosis (mortality) constructed based on the six predictive factors of age, hepatic encephalopathy grade, an increase in TBil by ≥17.1 μmol/L per day, creatinine, neutrophil count, and international normalized ratio has a relatively high value in predicting the 28-day prognosis of ACLF patients.
6.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
7.A comparative study of allogeneic versus autologous platelet rich plasma gels in repair of bone defects
Min LYU ; Da GUO ; Kesong ZHANG ; Long BI ; Junjun FAN ; Dan LI ; Wenxing YU ; Hu LIANG
Chinese Journal of Orthopaedic Trauma 2025;27(11):994-1001
Objective:To compare the differences in repair of rabbit bone defects between allogeneic platelet rich plasma (PRP) gel and autologous PRP gel.Methods:Thirty-six healthy New Zealand white rabbits were selected and randomly divided into an autologous group, an allogeneic group, and a control group ( n=12). A model of bilateral forelimb bone defects was established in each group. The autologous group was repaired with self-made deproteinized bone scaffold materials + autologous bone marrow mesenchymal stem cells (BMSCs) + autologous PRP gel, the allogeneic group with self-made deproteinized bone scaffold materials + autologous BMSCs + allogeneic PRP gel, and the control group with only self-made deproteinized bone scaffold materials + autologous BMSCs. At postoperative 1, 2, and 3 months, 4 animals were euthanized in each group, respectively, for gross observation, X-ray examination, Micro-CT examination, biomechanical testing and histological analysis (HE staining for tissue morphology) to compare the differences in repair of bone defects. Results:The formation of trabecular bone, cortical reconstruction, and medullary recanalization occurred earlier in the autologous and allogeneic groups than in the control group. Micro-CT analysis at postoperative 2 months showed that bone mineral density [(281.51±33.69) mg/mL and (266.13±37.13) mg/mL], bone volume fraction (23.52%±2.81% and 21.91%±1.94%), and trabecular number [(1.68±0.29) mm -1 and (1.63±0.22) mm -1] in the autologous and allogeneic groups were significantly higher than those in the control group [(197.47±18.61) mg/mL, 16.54%±3.06%, and (1.06±0.11) mm -1] ( P<0.05). No significant differences were found among the 3 groups in trabecular thickness [(0.33±0.09) mm, (0.42±0.16) mm, and (0.28±0.13) mm] or in the maximum compressive load ( P>0.05). HE staining revealed a significantly greater number and earlier formation of chondrocytes and osteoblasts in the autologous and allogeneic groups than in the control group. Conclusion:Since allogeneic PRP exhibits similar efficacy in promoting new bone formation compared with autologous PRP in a rabbit bone defect model, it may serve as a viable substitute for autologous PRP.
8.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
9.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.
10.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.


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