1.Epidemiological Characteristics and Disease Burden of Malignant Tumors in Shijiazhuang, 2021
Jing DANG ; Xinyan MA ; Yufan DUAN
Cancer Research on Prevention and Treatment 2026;53(2):133-141
Objective To analyze the epidemiological characteristics and disease burden of malignant tumors in Shijiazhuang in 2021. Methods Based on data from the Shijiazhuang City Cancer Registry, incidence and mortality indicators for malignant tumors were calculated, including crude rates, age-standardized rates (using Chinese and world standard populations), and the cumulative rate (0−74 years old), to describe the epidemiological profile. The disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) were calculated to estimate the disease burden of malignant tumors. Results In 2021, a total of
2.Risk factors for 90-day mortality in patients with acute-on-chronic liver failure and establishment of a predictive model
Jing SUN ; Tingji WANG ; Zhijiao DUAN ; Li ZHANG ; Yanmei LI
Journal of Clinical Hepatology 2026;42(1):151-159
ObjectiveTo investigate the independent predictive factors for 90-day mortality in patients with acute-on-chronic liver failure (ACLF), to establish a risk predictive model, and to assess its predictive efficacy in comparison with MELD, MELD-Na, MELD 3.0, and COSSH-ACLF Ⅱ. MethodsA retrospective analysis was performed for the clinical data of 394 patients with ACLF who were admitted to The Affiliated Hospital of Inner Mongolia Medical University and Hohhot Second Hospital from July 2018 to July 2024, and general information and laboratory markers on admission were collected from all patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of quantitative data between two groups, and the chi-square test or the adjusted chi-square test was used for comparison of qualitative data between two groups. The LASSO regression analysis was used to identify related variables, and the multivariate logistic regression analysis was used to establish a predictive model and generate a nomogram. The receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), calibration curve, and clinical decision curve were used to assess the performance of the model. ResultsA total of 394 patients with ACLF were included in this study, with 136 patients in the training set, 58 in the internal validation set, and 200 in the external validation set. The cohort had a mean age of 52.9±11.7 years, among whom male patients accounted for 72.84% (287/394), the patients with HBV infection accounted for 22.33% (88/394), the patients with alcohol-related causes accounted for 45.94% (181/394), and the patients with other causes (including drug-induced and autoimmune diseases) accounted for 31.73% (125/394). The overall 90-day mortality rate was 27.41% (108/394). The multivariate logistic regression analysis showed that diabetes (odds ratio [OR]= 5.831, 95% confidence interval [CI]: 1.587 — 21.424, P=0.008), cystatin C (Cys-C) (OR=2.984, 95%CI: 1.501 — 5.933, P=0.002), and spontaneous peritonitis (SBP) (OR=5.692, 95%CI: 2.150 — 15.071, P<0.001) were independent risk factors, and a nomogram was generated based on these factors. This model had an AUC of 0.836 in the training set, 0.881 in the internal validation set, and 0.878 in the external validation set, showing a good discriminatory ability. The calibration curve showed a good degree of fitting, with a relatively high net clinical benefit. The subgroup analysis based on etiology showed that the model had an AUC of 0.850 in the patients with HBV infection, 0.858 in the patients with alcohol-induced ACLF, and 0.908 in the patients with other etiologies, indicating that the model had a good discriminatory ability across the populations with different etiologies. Compared with traditional scores, the model (AUC=0.836) had a significantly better predictive value than MELD (AUC=0.619, Z=3.197, P=0.001), MELD-Na (AUC=0.651, Z=2.998, P=0.003), MELD 3.0 (AUC=0.601, Z=3.682, P<0.001), and COSSH-ACLF Ⅱ (AUC=0.719, Z=2.396, P=0.017) alone. ConclusionDiabetes, SBP, and Cys-C are independent risk factors for 90-day mortality in patients with ACLF. Compared with MELD, MELD-Na, MELD 3.0, and COSSH-ACLF Ⅱ scores, this model has a higher predictive value for 90-day prognosis in patients with ACLF and is suitable for patients with ACLF caused by various etiologies.
3.Modern Clinical Applications and Mechanism of Zhigancao Tang: A Review
Zhibo CHANG ; Chuhan DUAN ; Xiaoyan WANG ; Jing SHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):361-370
Zhigancao Tang, derived from the Treatise on Cold Damage,is a classic and renowned formula for treating "intermittent and irregular pulse, and palpitations of the heart". It has an exquisite formulation. By replenishing Qi, nourishing Yin, activating Yang, and restoring the pulse, it achieves the dual supplementation of Yin and Yang, and the simultaneous treatment of Qi and blood. With the practical expansion by practitioners over successive dynasties, the application scope of this formula has been continuously expanding, extending from traditional cardiovascular diseases to diseases of multiple systems, fully reflecting the theoretical characteristics of traditional Chinese medicine (TCM) of "treating different diseases with the same method". Modern research shows that Zhigancao Tang not only has a remarkable curative effect on cardiovascular diseases but is also widely applied to diseases of the respiratory, nervous, digestive, endocrine, oncologic, gynecologic, and otorhinolaryngologic systems, demonstrating its interdisciplinary clinical application value. At the same time, research on the mechanism of action of Zhigancao Tang is also continuously deepening. The mechanisms by which it treats diseases involve multiple aspects, including anti-arrhythmic effects, myocardial protection, anti-fibrosis, antioxidative stress and anti‑inflammatory effects, regulation of glucose and lipid metabolism, enhancing hematopoietic function, and improving hemorheology. These mechanisms work synergistically to jointly regulate the physiological functions of the body and play a role in treating diseases. However, there are still some deficiencies in current research. For example, the sample size of some clinical trials is small, most of the mechanism studies are based on animal models or in vitro experiments, there is insufficient high-quality evidence from clinical trials, the composition of the compound formula is complex, and the pharmacodynamic material basis and the rules of compatibility still need to be deeply analyzed. By consulting relevant literature, this article systematically summarizes the modern clinical application and action mechanism of Zhigancao Tang, aiming to provide new ideas for its subsequent in-depth research and clinical application, promote the integrated development of classic TCM formulas and modern medicine, and further explore its great potential in clinical treatment.
4.The Potential and Challenges of Temporal Interference Stimulation in Chronic Pain Management
Hao-Qing DUAN ; Yu-Qi GOU ; Ya-Wen LI ; Li HU ; Xue-Jing LÜ
Progress in Biochemistry and Biophysics 2026;53(2):369-387
Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.
5.The Potential and Challenges of Temporal Interference Stimulation in Chronic Pain Management
Hao-Qing DUAN ; Yu-Qi GOU ; Ya-Wen LI ; Li HU ; Xue-Jing LÜ
Progress in Biochemistry and Biophysics 2026;53(2):369-387
Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.
6.Impact of blood donation scenario difference on donor characteristics and blood quality in Xi'an
Yuanyuan JING ; Yan GUO ; Hanshi GONG ; Yong DUAN ; Wenjuan ZHANG
Chinese Journal of Blood Transfusion 2026;39(4):519-525
Objective: To explore the impact of different blood donation scenarios on population characteristics and blood donation behaviors, and to provide a basis for precise blood donation recruitment. Methods: Eligible voluntary blood donors with complete records from four scenarios in Xi'an: medical institutions, cultural tourism SITES, commercial superstores, and blood centers. After a preliminary analysis of overall donor characteristics across the four scenarios, three core subgroups were defined based on scenarios and donor population differences: the medical subgroup (aged 30-39 years), the blood center subgroup (aged 30-39 years), and the cultural tourism and commercial superstore subgroup (aged 18-29 years). Baseline characteristics, blood donation behaviors, and blood test results were compared among the subgroups. Results: The blood donors in all four scenarios were mainly male, but the proportion of female donors in the medical scenario was the highest (26.4%, 8 878/33 634). In terms of age distribution, the cultural tourism and commercial superstore scenarios were dominated by donors aged 18-29, while the blood center and medical scenarios were dominated by those aged 30-39, with the highest proportion of donors over 40 in the medical scenario. The occupational and educational composition of blood donors in the blood center scenario spanned a wide range, exhibiting a clear bipolar distribution. Significant differences were observed in baseline characteristics, blood donation behaviors, and blood test results among the three core subgroups (P<0.001). The medical subgroup was mainly composed of enterprise/industrial workers and married individuals, with high proportions of first-time blood donors, and the highest unqualified rate of infectious indicators (2.0%, 274/13 509). The cultural tourism and commercial superstore subgroup was mainly unmarried and students, featured high proportions of large-volume donations and evening donations, and had a relatively high unqualified rate for ALT (0.4%, 130/31 443). The blood center subgroup had a complex population structure, a high proportion of repeat blood donors (45.3%, 6449/14 225), and moderate results in all test indicators. Conclusion: There is an inherent correlation between the attributes of blood donation scenarios, population characteristics, and blood donation behaviors. The differences among the three core subgroups provide a clear basis for precise scenario operation. By constructing transformation channels between different scenarios and optimizing scenario-specific strategies, the structure of blood donors can be improved, thereby supporting the sustainable development of voluntary blood donation.
7.Clinical Efficacy of Modified Huangqi Chifengtang in Treatment of IgA Nephropathy Patients and Exploration of Dose-effect Relationship of Astragali Radix
Xiujie SHI ; Meiying CHANG ; Yue SHI ; Ziyan ZHANG ; Yifan ZHANG ; Qi ZHANG ; Hangyu DUAN ; Jing LIU ; Mingming ZHAO ; Yuan SI ; Yu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):9-16
ObjectiveTo explore the dose-effect relationship and safety of high, medium, and low doses of raw Astragali Radix in the modified Huangqi Chifengtang (MHCD) for treating proteinuria in immunoglobulin A (IgA) nephropathy, and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy, diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity, were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo, while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix (60, 30, 15 g). Each group contained 30 patients, and the treatment period was 12 weeks. Changes in 24-hour urinary protein (24 hUTP), traditional Chinese medicine (TCM) syndrome scores, effective rate, and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment, 24 hUTP significantly decreased in the high, medium, and low-dose groups, as well as the control group (P<0.05, P<0.01). The TCM syndrome scores in the high, medium, and low-dose groups also significantly decreased (P<0.01). Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium, low-dose, and control groups (P<0.05, P<0.01), and the 24 hUTP in the medium-dose group was significantly lower than in the control group (P<0.05). The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups (P<0.05, P<0.01). The total effective rates for proteinuria in the high, medium, low-dose, and control groups were 92.59% (25/27), 85.19% (23/27), 60.71% (17/28), and 57.14% (16/28), respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups (χ2=13.185, P<0.05, P<0.01). The effective rates for TCM syndrome scores in the high, medium, low-dose, and control groups were 88.89% (24/27), 81.48% (22/27), 71.43% (20/28), and 46.43% (13/28), respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group (χ2=14.053, P<0.01). Compared with pre-treatment values, there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However, eGFR significantly decreased in the low-dose and control groups after treatment (P<0.05), and serum creatinine levels increased significantly in the control group (P<0.05). No statistically significant differences were observed in urea nitrogen, uric acid, albumin, total cholesterol, triglycerides, liver function, and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high, medium, and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.
8.The Impairment Attention Capture by Topological Change in Children With Autism Spectrum Disorder
Hui-Lin XU ; Huan-Jun XI ; Tao DUAN ; Jing LI ; Dan-Dan LI ; Kai WANG ; Chun-Yan ZHU
Progress in Biochemistry and Biophysics 2025;52(1):223-232
ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.
9.Nomogram and machine learning models for predicting in-hospital mortality in sepsis patients with deep vein thrombosis.
Hongwei DUAN ; Huaizheng LIU ; Chuanzheng SUN ; Jing QI
Journal of Central South University(Medical Sciences) 2025;50(6):1013-1029
OBJECTIVES:
Global epidemiological data indicate that 20% to 30% of intensive care unit (ICU) sepsis patients progress to deep vein thrombosis (DVT) due to coagulopathy, with an associated mortality rate of 25% to 40%. Existing prognostic tools have limitations. This study aims to develop and validate nomogram and machine learning models to predict in-hospital mortality in sepsis patients with DVT and assess their clinical applicability.
METHODS:
This multicenter retrospective study drew on data from the Medical Information Mart for Intensive Care IV (MIMIC-IV; n=2 235), the eICU Collaborative Research Database (eICU-CRD; n=1 274), and the Patient Admission Dataset from the ICU of Third Xiangya Hospital, Central South University (CSU-XYS-ICU; n=107). MIMIC-IV was split into a training set (n=1 584) and internal validation set (n=651), with the remaining datasets used for external validation. Predictors were selected via least absolute shrinkage and selection operator (LASSO) regression and Bayesian Information Criterion (BIC), and a nomogram model was constructed. An extreme gradient boosting (XGBoost) algorithm was used to build the machine learning model. Model performance was assessed by the concordance index (C-index), calibration curves, Brier score, decision curve analysis (DCA), and net reclassification improvement index (NRI).
RESULTS:
Five key predictors, age [odds ratio (OR)=1.02, 95% CI 1.01 to 1.03, P<0.001], minimum activated partial thromboplastin (APTT; OR=1.09, 95% CI 1.08 to 1.11, P<0.001), maximum APTT (OR=1.01, 95% CI 1.00 to 1.01, P<0.001), maximum lactate (OR=1.56, 95% CI 1.39 to 1.75, P<0.001), and maximum serum creatinine (OR=2.03, 95% CI 1.79 to 2.30, P<0.001), were included in the nomogram. The model showed robust performance in internal validation (C-index=0.845, 95% CI 0.811 to 0.879) and external validation (eICU-CRD: C-index=0.827, 95% CI 0.800 to 0.854; CSU-XYS-ICU: C-index=0.779, 95% CI 0.687 to 0.871). Calibration curves indicated good agreement between predicted and observed outcomes (Brier score<0.25), and DCA confirmed clinical benefit. The XGBoost model achieved an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI 0.969 to 0.985) in the training set, but performance declined in external validation (eICU-CRD, AUC=0.825, 95% CI 0.817 to 0.861; CSU-XYS-ICU, AUC=0.766, 95% CI 0.700 to 0.873), though it remained above clinical thresholds. Net reclassification improvement was slightly lower for XGBoost compared with the nomogram (NRI=0.58).
CONCLUSIONS
Both the nomogram and XGBoost models effectively predict in-hospital mortality in sepsis patients with DVT. However, the nomogram offers superior generalizability and clinical usability. Its visual scoring system provides a quantitative tool for identifying high-risk patients and implementing individualized interventions.
Humans
;
Sepsis/complications*
;
Machine Learning
;
Nomograms
;
Venous Thrombosis/complications*
;
Retrospective Studies
;
Hospital Mortality
;
Male
;
Female
;
Middle Aged
;
Aged
;
Intensive Care Units
;
Prognosis
;
Bayes Theorem
10.Chidamide triggers pyroptosis in T-cell lymphoblastic lymphoma/leukemia via the FOXO1/GSDME axis.
Xinlei LI ; Bangdong LIU ; Dezhi HUANG ; Naya MA ; Jing XIA ; Xianlan ZHAO ; Yishuo DUAN ; Fu LI ; Shijia LIN ; Shuhan TANG ; Qiong LI ; Jun RAO ; Xi ZHANG
Chinese Medical Journal 2025;138(10):1213-1224
BACKGROUND:
T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL.
METHODS:
HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse.
RESULTS:
The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo .
CONCLUSIONS
This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans
;
Pyroptosis/drug effects*
;
Forkhead Box Protein O1/genetics*
;
Aminopyridines/pharmacology*
;
Animals
;
Mice
;
Benzamides/pharmacology*
;
Cell Line, Tumor
;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
;
Phosphate-Binding Proteins/metabolism*
;
Histone Deacetylase Inhibitors/pharmacology*
;
Jurkat Cells
;
Histone Deacetylases/metabolism*
;
Apoptosis/drug effects*
;
Gasdermins

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