ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula（YHJF） on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated， model， low-dose YHJF（4.1 g·kg^-1）， and high-dose YHJF（8.2 g·kg^-1） groups. Except for the sham-operated group， a cecal ligation and puncture（CLP） procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses， while the sham-operated and model groups received an equal volume of physiological saline. After the intervention， the 7-day survival rate of each group was recorded， and spleen samples were collected 72 h post-intervention， and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL） staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay（ELISA） was performed to measure the levels of interleukin（IL）-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes（DEGs） and differential metabolites in the spleen， followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction（Real-time PCR）， flow cytometry， and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice（P0.05）. Compared with the sham-operated group， the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling， with markedly elevated peripheral serum IL-4 and IL-10 levels（P0.01）. Compared with the model group， the high-dose YHJF group showed a reduction in apoptosis of spleen cells， an increase in the spleen index， and a significant decrease in peripheral serum IL-4 and IL-10 levels（P0.05）. Spleen transcriptomics identified 255 DEGs between groups， potentially serving as intervention targets for YHJF. Gene Ontology（GO） enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer（NK） cell-mediated positive immune regulation， cell killing， cytokine production， positive regulation of innate immune cells， and interferon production. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions， viral protein interactions with cytokines and cytokine receptors， chemokine signaling pathway， and nuclear transcription factor-κB（NF-κB） signaling pathway. Protein-protein interaction（PPI） network analysis identified CD160， granzyme B（GZMB）， and chemokine ligand 4（CCL4） as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention， and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism， arachidonic acid metabolism， glycosylphosphatidylinositol（GPI） anchor biosynthesis， linoleic acid metabolism， and α-linolenic acid metabolism pathways. Verification results showed that， compared with the sham-operated group， the model group exhibited significantly elevated CD160 mRNA expression level in the spleen， along with markedly decreased CCL4 and GZMB mRNA expression， and had a significant increase in CD160 expression on the surface of natural killer T（NKT） cells in the spleen（P0.01）. Compared with the model group， the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen， a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group， CD160 expression on the surface of splenic NKT cells in the model group was significantly increased（P0.01）， while high-dose YHJF intervention significantly reduced CD160 expression（P0.01）. ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160， and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.

ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula（YHJF） on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated， model， low-dose YHJF（4.1 g·kg^-1）， and high-dose YHJF（8.2 g·kg^-1） groups. Except for the sham-operated group， a cecal ligation and puncture（CLP） procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses， while the sham-operated and model groups received an equal volume of physiological saline. After the intervention， the 7-day survival rate of each group was recorded， and spleen samples were collected 72 h post-intervention， and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL） staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay（ELISA） was performed to measure the levels of interleukin（IL）-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes（DEGs） and differential metabolites in the spleen， followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction（Real-time PCR）， flow cytometry， and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice（P0.05）. Compared with the sham-operated group， the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling， with markedly elevated peripheral serum IL-4 and IL-10 levels（P0.01）. Compared with the model group， the high-dose YHJF group showed a reduction in apoptosis of spleen cells， an increase in the spleen index， and a significant decrease in peripheral serum IL-4 and IL-10 levels（P0.05）. Spleen transcriptomics identified 255 DEGs between groups， potentially serving as intervention targets for YHJF. Gene Ontology（GO） enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer（NK） cell-mediated positive immune regulation， cell killing， cytokine production， positive regulation of innate immune cells， and interferon production. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions， viral protein interactions with cytokines and cytokine receptors， chemokine signaling pathway， and nuclear transcription factor-κB（NF-κB） signaling pathway. Protein-protein interaction（PPI） network analysis identified CD160， granzyme B（GZMB）， and chemokine ligand 4（CCL4） as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention， and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism， arachidonic acid metabolism， glycosylphosphatidylinositol（GPI） anchor biosynthesis， linoleic acid metabolism， and α-linolenic acid metabolism pathways. Verification results showed that， compared with the sham-operated group， the model group exhibited significantly elevated CD160 mRNA expression level in the spleen， along with markedly decreased CCL4 and GZMB mRNA expression， and had a significant increase in CD160 expression on the surface of natural killer T（NKT） cells in the spleen（P0.01）. Compared with the model group， the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen， a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group， CD160 expression on the surface of splenic NKT cells in the model group was significantly increased（P0.01）， while high-dose YHJF intervention significantly reduced CD160 expression（P0.01）. ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160， and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.

Background Pyrethroid pesticides (PYRs) can cross the placental barrier to cause intrauterine fetal exposure, which may lead to developmental immunotoxicity (DIT). However, the specific effect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. Objective To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. Methods A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites, including 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid (cis-DBCA), in the urine of pregnant women during the first trimester (gestational weeks 6-12), the second trimester (gestational weeks 21-24), and the third trimester (gestational weeks 33-36). Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry. Exposure levels of PYRs metabolites in each trimester were divided into low, moderate, and high exposure groups based on the 25th (P₂₅) and 75th (P₇₅) percentiles. Meanwhile, participants were classified as having repeated high or low exposure if their metabolite levels were > P₇₅ or <P₂₅ in at least two trimesters, respectively, while all others were categorized as having repeated moderate exposure. Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell (WBC) and lymphocyte counts in children aged 1 year. Results A total of 336 mother-child pairs were included in this study. For the pregnant women, the total detection rates of maternal urinary 3PBA, 4F3PBA, and cis-DBCA across the three trimesters of pregnancy were 80.5%, 100.0%, and 81.3%, respectively; and median creatinine-corrected concentrations were 0.24, 0.36, and 0.42 μg·g⁻¹, respectively. In children aged 1 year, the mean WBC and lymphocyte counts in peripheral blood were (8.9±2.0)×10⁹·L⁻¹ and (5.7±1.6)×10⁹·L⁻¹, respectively. The results of the generalized linear model analysis indicated that compared to the low exposure group, the high cis-DBCA exposure group during the third trimester of pregnancy had significantly lower peripheral blood WBC count (β=−0.87, 95%CI: −1.51, −0.23) and lymphocyte count (β=−0.64, 95%CI: −1.15, −0.13); and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count (β=−1.34, 95%CI: −2.34, −0.34) and lymphocyte count (β=−0.80, 95%CI: −1.60, −0.01) than the repeated low exposure group. Similarly, the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count (β=−0.83, 95%CI: −1.59, −0.07) than the repeated low exposure group. Conclusion High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year, and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring. The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during pregnancy.

Objective: To examine the association of physical activity with cognitive function and mental health among primary school students based on latent subgroup identification and dose response modeling, and to clarify cognitive-psychological profiles and the protective role of physical exercise, so as to provide evidence based support for physical exercise promoting mental health among primary school students. Methods: A study was conducted among 546 primary school students aged 8-12 years old from a primary school in Shanghai from March to June 2025. Physical fitness indicators, including vital capacity, 50 m sprint, sit and reach, and 1 min rope skipping were measured. Physical exercise was assessed by using the Physical Activity Rating Scale-3 (PARS-3), and mental health was assessed by using the Revised Child Anxiety and Depression Scale, 47-item version (RCADS-47). Cognitive function was assessed by using Stroop, N-back, and task-switching tasks. Latent profile analysis (LPA) was performed for cognitive-psychological health of primary school students based on seven cognitive indicators and six psychological indicators. Multivariable Logistic regression, trend test, and restricted cubic spline (RCS) analysis were used to examine associations between physical exercise and psychological highrisk status. Results: Five cognitive psychological health subgroups were identified:high symptom and impaired cognition group ( n =40, 7.3%), low cognition and low symptom group ( n =108, 19.8% ), and high cognition and high symptom group ( n =110, 20.2%), cognitive advantage and psychologically healthy group ( n = 272, 49.8%), and extremely high symptom and cognitively vulnerable group ( n =16, 2.9%). Among them, the high symptom and impaired-cognition group and extremely high symptom and cognitively vulnerable group were classified as psychologically high risk types. Significant differences were observed across subgroups in psychological symptoms, cognitive function, some physical fitness indicators and physical exercise level, except for body weight, body mass index, and sit and reach ( F =2.64-297.53, all P < 0.05). The results of the multivariate Logistic regression analysis indicated that high level sports, including high total volume of physical exercise, single session duration >30 min, high intensity, and frequency ≥3 times/week, was associated with lower psychological high risk status ( OR =0.20, 0.36, 0.33, 0.40, all P <0.05). Trend analysis showed that total volume of physical exercise and single session exercise duration were negatively associated with psychological high risk status among primary school students ( OR =0.98, 0.79, both P trend <0.05). RCS analysis showed no statistically significant overall or nonlinear association between total volume of physical exercise and psychological high risk status ( χ 2=2.92, 0.01, both P >0.05). Conclusions Cognitive-psychological health among primary school students is heterogeneous. Physical exercise is associated with psychological health improvement and may show a threshold effect, with total volume of physical exercise and single session exercise duration being the key dimensions.

AIM:To investigate the prevalence of ocular fundus lesions among active-duty military personnel with high myopia and to analyze the associated influencing factors.

METHODS: A cross-sectional study. Subjects included military personnel with high myopia(≤-6.00 D)and elongated axial length(≥26 mm). A systematic evaluation protocol was implemented, consisting of standardized questionnaires, general physical health examinations, and comprehensive ophthalmic assessments. Optical coherence tomography(OCT)was used to screen for fundus lesions in highly myopic subjects, and the prevalence of related lesions was calculated. Axial length, refractive error, best-corrected visual acuity(BCVA), and macular ganglion cell complex(GCC)thickness were measured. Univariate analysis was performed to compare differences in the above parameters between highly myopic subjects with and without concomitant fundus lesions. Multivariate Logistic regression analysis was further applied to identify risk factors for fundus lesions.

RESULTS:A total of 134 male patients(268 eyes)were enrolled, with the mean age of 24.5±3.2 y. Of the 268 eyes, 123 eyes(45.9%)showed positive signs of fundus lesions. Among these, parapapillary blood flow density reduction was found in 84 eyes(31.3%), GCC thinning in 46 eyes(17.2%), drusen in 8 eyes(3.0%), optic disc edema in 7 eyes(2.6%), retinoschisis in 6 eyes(2.2%), and choroidal excavation in 3 eyes(1.1%). BCVA was significantly lower in highly myopic patients with retinoschisis than in those without retinoschisis(P<0.05).Univariate analysis showed that refractive error, axial length, and posterior scleral expansion were associated with the occurrence of fundus lesions(P<0.05). Multivariate Logistic regression analysis revealed that axial length(OR=2.52, 95%CI: 1.67-3.80, P<0.001)and posterior scleral expansion(OR=3.12, 95%CI: 1.65-5.92, P<0.01)were significant risk factors for fundus lesions in highly myopic military personnel.

CONCLUSION: The prevalence of fundus lesions is relatively high among active-duty military personnel with high myopia. Peripapillary flow density reduction and GCC thinning are the most common manifestations in this population. Increased axial length and posterior scleral ectasia are significant contributing factors. It is recommended that OCT be incorporated into routine ophthalmic examinations for these military personnel, thereby providing a basis for the early detection and intervention of fundus lesions.

AIM:To investigate the role of SET and MYND domain-containing protein 3(SMYD3)-mediated histone H3 lysine 4 trimethylation(H3K4me3)dysregulation in pulmonary vascular remodeling in a rat model of pulmo-nary arterial hypertension associated with atrial septal defect(PAH-ASD).METHODS:The PAH-ASD rat model was created using transseptal puncture and radiofrequency ablation techniques.The rats were randomly assigned to 5 groups:normal,sham,PAH-ASD,PAH-ASD+vehicle(Veh),and PAH-ASD+BCI-121(SMYD3 inhibitor).Four weeks after modeling,lung tissues and pulmonary vessels were harvested for subsequent analysis.Western blot analysis was conducted to evaluate the protein levels of SMYD3,H3K4me3,transforming growth faction-β1(TGF-β1),and collagen type Ⅲ(Col Ⅲ).The mRNA expression of TGF-β1 was quantified using RT-qPCR.Histological assessment of pulmonary vascu-lar fibrosis,vascular wall thickness and smooth muscle proliferation was executed through Masson's trichrome and HE staining.Co-immunoprecipitation(Co-IP)assay was performed to investigate the interactions among SMYD3,H3K4me3,and TGF-β1.Hemodynamic parameters,including mean pulmonary artery pressure(mPAP),were quantified using a computerized physiological signal acquisition system.RESULTS:The Western blot analysis indicated a significant in-crease in the protein levels of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 in the PAH-ASD group compared with the sham group(P<0.05).RT-qPCR corroborated the elevation of TGF-β1 mRNA expression in the PAH-ASD group(P<0.05).Furthermore,Masson's trichrome and HE staining techniques revealed more pronounced pulmonary vascular fibrosis,an augmented vascular wall area,and an elevated vascular area index within the PAH-ASD group(P<0.05).Additionally,the right ventricular hypertrophy index(RVHI)and mPAP were significantly elevated in the PAH-ASD group(P<0.05).The administration of BCI-121 resulted in a significant reduction of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 levels(P<0.05),while also mitigating pulmonary vascular fibrosis,RVHI,mPAP,pulmonary vascular area,and area index(P<0.05).Co-IP confirmed direct interactions among SMYD3,H3K4me3,and TGF-β1.CONCLUSION:Histone methyl-transferase SMYD3-mediated histone H3K4me3 modification plays a role in the pulmonary vascular remodeling of PAH-ASD model rats.The underlying mechanism may involve the regulation of pulmonary vascular proliferation and fibrosis me-diated by the overexpression of TGF-β1 and Col Ⅲ.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

Objective:To retrospectively analyze the results of auditory examination,vestibular function examination and laboratory examination of 63 patients diagnosed as vestibular neuritis.Methods:A total of 63 patients diagnosed with vestibular neuritis hospitalized in the Department of Otolaryngology, Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University, from October 2012 to December 2022 were recruited. All patients met the diagnostic criteria for the 2022 Bárány association vestibular neuritis. Clinical data and the results of pure tone audiometry, electrocochleogram, video electronystagmogram, caloric test, cervical vestibuloevoked myogenic potential（cVEMP）, ocular vestibuloevoked myogenic potential（oVEMP）, video head impulse test（vHIT） was collected.A total of 63 age-and sex-matched healthy subjects in the physical examination center were randomly selected as the control group. The differences of blood indexs and lipid metabolism indexes between the two groups were compared. Results:In patients with vestibular neuritis, 50 out of 63 patients presented normal threshold in pure tone audiometry, 8 out of 63 patients had bilateral high-frequency sensorineural hearing loss and 5 out of 63 patients had unilateral mild high-frequency sensorineural hearing loss, 56 out of 63 cases completed the electrocochleogram, of which 3 cases had a binaural-SP/AP amplitude ratio≥0.4, 5 cases had monaural amplitude ratio ≥0.4. Fifty-five out of 63 patients completed the caloric test with CP values greater than 30% in all. The ratio of patients completed cVEMP, oVEMP and vHIT were 46 cases, 22 cases and 30 cases, respectively. 17 out of 63 cases completed all the four vestibular function tests. According to these tests, 49 patients could determine the extent of injury，including 27 cases with unilateral superior vestibular nerve injury, 21 cases with unilateral superior and inferior vestibular nerve injury and 1 case with unilateral inferior vestibular nerve injury. There were significant differences in neutrophil value（P<0.001）, lymphocyte value（P<0.005）, neutrophil/lymphocyte ratio（P<0.001） and apolipoprotein A1（P<0.001） between patient group and control group. Inflammatory markers were risk factors for patients with vestibular neuritis. The OR values of neutrophil value and blood neutrophil/lymphocyte ratio were 1.81（1.38-2.37, P<0.001） and 2.11（1.41-3.16, P<0.001）, respectively. Apolipoprotein A1 was a protective factor for patients with vestibular neuritis, and the OR value was 0.004（0.001-0.042, P<0.001）. Conclusion:Electrocochleogram could be used in vestibular neuritis patients with normal pure tone threshold to test whether there is hidden hearing loss in these patients. Neutrophil value, lymphocyte value, neutrophil/lymphocyte ratio and apolipoprotein A1 were correlated with vestibular neuritis. The Neutrophil value and neutrophil/lymphocyte ratio were risk factors for morbidity.
Humans ; Vestibular Neuronitis/physiopathology* ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone ; Hearing Loss, Sensorineural/physiopathology* ; Middle Aged ; Adult ; Vestibular Function Tests ; Vestibular Evoked Myogenic Potentials ; Aged

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.