1.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
2.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.
3.Efficacy of stereotactic body radiotherapy combined with sintilimab and bevacizumab in treatment of unresectable hepatocellular carcinoma
Teng ZHANG ; Quan WANG ; Wengang LI ; Xuezhang DUAN
Journal of Clinical Hepatology 2025;41(1):69-74
ObjectiveTo investigate the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with sintilimab and bevacizumab in the treatment of patients with unresectable hepatocellular carcinoma (uHCC) and related prognostic factors. MethodsA total of 42 patients with uHCC who underwent SBRT combined with sintilimab and bevacizumab in Department of Radiation Oncology, The Fifth Medical Centre of PLA General Hospital, from March to December 2022 were enrolled. The prescribed dose of planning target volume was 36 — 50 Gy in 5 — 6 fractions for continuous irradiation, followed by the regimen of sintilimab and bevacizumab. Each course of treatment was 3 weeks until the presence of tumor progression or serious adverse events. The Kaplan-Meier method was used to calculate overall survival (OS) rate and progression-free survival (PFS) rate, and the log-rank test was used for comparison between groups; the Cox proportional hazards model was used to investigate the influencing factors for prognosis. ResultsThe median follow-up time was 21.6 months, with an objective response rate of 69%, a disease control rate of 85.7%, a median PFS of 10.0 months (95% confidence interval [CI]: 6.7 — 13.0), and a median OS of 23.3 months (95%CI: 14.7 — 31.8). Most adverse events were grade 1 — 2 events, and there were no fatal adverse events. At 6 — 8 weeks after treatment, the AFP response group had a significantly better OS than the non-AFP response group (not reached vs 11.8 months, P=0.007). The multivariate analysis showed that AFP response was associated with the good prognosis of patients (hazard ratio=0.31, 95%CI: 0.13 — 0.75, P=0.009). ConclusionFor patients with uHCC, SBRT combined with sintilimab and bevacizumab can improve survival with a manageable safety profile, and a >50% reduction in AFP at 6 — 8 weeks after treatment can be used as a potential prognostic indicator.
4.Application of machine learning in the diagnosis and treatment of chronic hepatitis C
Hua HAN ; Zhongping DUAN ; Yang WANG
Journal of Clinical Hepatology 2025;41(1):141-144
With the development of artificial intelligence, machine learning has shown great potential in the field of medical health. Machine learning conducts a comprehensive analysis of patient data including clinical features, blood tests, and imaging examinations and establishes corresponding mathematical models to achieve the diagnosis and treatment of diseases and the prediction of disease conditions, thereby guiding disease management. With reference to the latest research findings, this article reviews the application of machine learning in chronic hepatitis C and related research advances.
5.Research progress on the influencing factors of psychological distress in patients with coronary heart disease
Xiaotian DUAN ; Hongshi CAO ; Taiyu BI ; Haiyan WANG ; Songyu WANG ; Quantong ZHAO ; Ran WANG ; Chunjing WU
Sichuan Mental Health 2025;38(1):89-96
Coronary heart disease is a chronic and lifelong disease, which places a dual burden on the physiological and psychological well-being of patients, and can easily lead to psychological distress and affect their prognosis and quality of life. This article provides a systematic review, in which the current status, evaluation tools, influencing factors and intervention methods of psychological distress in patients with coronary heart disease are explored, aiming to provide key information beneficial for identifying and preventing psychological distress, and to improve the overall management and treatment effectiveness of coronary heart disease patients. In this paper, 18 articles were included, and the demographic, physiological, psychological and social factors affecting the psychological distress of patients with coronary heart disease were systematically analyzed, thus to provide a deeper understanding of psychological distress and offering references for formulating targeted intervention strategies.
6.Role of alkaloid compounds in regulating chronic liver diseases
Yihui ZHENG ; Jiahui WANG ; Tiejian ZHAO ; Xuelin DUAN ; Lei WANG ; Yang ZHENG ; Shiquan YANG
Journal of Clinical Hepatology 2025;41(2):375-382
Chronic liver diseases with common causes including viral infections, alcohol abuse, and autoimmune diseases. Alkaloids, as a class of plant-derived compounds, have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis, inflammatory response, oxidative stress, and cell apoptosis, and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways, thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases, in order to provide new ideas and directions for the treatment of chronic liver diseases.
7.Inverse distance weight interpolation method for missing data of PM2.5 spatiotemporal series
Yurou LIANG ; Hongling WU ; Weipeng WANG ; Feng CHENG ; Ping DUAN
Journal of Environmental and Occupational Medicine 2025;42(2):171-178
Background Fine particulate matter (PM2.5) monitoring stations may generate missing data for a certain period of time due to various factors. This data loss will adversely affect air quality assessment and pollution control decision-making. Objective To propose an inverse distance weighted (IDW) spatiotemporal interpolation method based on particle swarm optimization (PSO) to interpolate and fill missing PM2.5 spatiotemporal sequence data and increase interpolation accuracy. Methods An interpolation experiment was designed into two parts. The first part used hourly PM2.5 observational data from four moments on January 1, 2017 in the Yangtze River Delta region. The second part employed daily PM2.5 observational data from the first 10 d of January 2017 in the Beijing-Tianjin-Hebei region. Interpolation accuracy was evaluated using four metrics: root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and mean relative error (MRE). Results IDW spatiotemporal interpolation method optimized with PSO significantly improved the accuracy of filling missing PM2.5 spatiotemporal sequence data. In the hourly-scale experiment conducted in the Yangtze River Delta region, compared to a distance index of 2, the accuracy metrics RMSE, MAE, MAPE, and MRE generated by the proposed method improved on average by 0.17 μg·m−3, 0.27 μg·m−3, 0.17%, and 0.01%, respectively. The PM2.5 spatial field maps generated for four moments based on this method clearly illustrated the spatiotemporal distribution characteristics of hourly PM2.5 concentrations in the Yangtze River Delta region. In the daily-scale experiment conducted in the Beijing-Tianjin-Hebei region, the PSO-optimized distance index outperformed the traditional method, with interpolation accuracy improvements of approximately 0.215 μg·m−3, 0.283 μg·m−3, 0.174%, and 0.014%, respectively. Furthermore, the seasonal PM2.5 spatial field maps generated by this method revealed the spatiotemporal distribution characteristics of PM2.5 concentrations in the Beijing-Tianjin-Hebei region across different seasons, further validating the effectiveness and applicability of this method. Conclusion The IDW spatiotemporal interpolation method optimized with PSO is highly accurate and reliable for interpolating the missing data in the Yangtze River Delta region and the Beijing-Tianjin-Hebei region, providing valuable insights for air pollution control and public health protection.
8.Inhibitory effect of hydroxy safflower yellow A on neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment
Zeqian WANG ; Yanzhe DUAN ; Yige WU ; Dong MA ; Jianjun HUANG ; Yuqing YAN ; Lijuan SONG
Chinese Journal of Tissue Engineering Research 2025;29(19):4044-4051
BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.
9.BIRC5 Is a Potential Biomarker Associated with Immune System Infiltration in Glioma
Xitong YANG ; Yuanyuan ZHANG ; Fuhui DUAN ; Siying LI ; Guangming WANG
Journal of Korean Neurosurgical Society 2025;68(2):184-201
Objective:
: Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood.
Methods:
: The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases.
Results:
: Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues.
Conclusion
: BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.
10.BIRC5 Is a Potential Biomarker Associated with Immune System Infiltration in Glioma
Xitong YANG ; Yuanyuan ZHANG ; Fuhui DUAN ; Siying LI ; Guangming WANG
Journal of Korean Neurosurgical Society 2025;68(2):184-201
Objective:
: Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood.
Methods:
: The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases.
Results:
: Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues.
Conclusion
: BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.

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