1.Elevated SLC3A2 Expression Promotes the Progression of Gliomas and Enhances Ferroptosis Resistance through the AKT/NRF2/GPX4 Axis
Yuqian ZHENG ; Shaolong ZHOU ; Yiran TAO ; Zimin SHI ; Xiang LI ; Xudong FU ; Jian MA ; Weihua HU ; Wulong LIANG ; Xinjun WANG
Cancer Research and Treatment 2026;58(1):71-94
Purpose:
The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity.
Materials and Methods:
The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells.
Results:
Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis.
Conclusion
Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.
2.Extracellular vesicles deliver thioredoxin to rescue stem cells from senescence and intervertebral disc degeneration via a feed-forward circuit of the NRF2/AP-1 composite pathway.
Xuanzuo CHEN ; Sheng LIU ; Huiwen WANG ; Yiran LIU ; Yan XIAO ; Kanglu LI ; Feifei NI ; Wei WU ; Hui LIN ; Xiangcheng QING ; Feifei PU ; Baichuan WANG ; Zengwu SHAO ; Yizhong PENG
Acta Pharmaceutica Sinica B 2025;15(2):1007-1022
Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.
3.Therapeutic mechanism of hederagenin, an active component in Guizhi Fuling Pellets, against cervical cancer in nude mice.
Yinfu ZHU ; Yiran LI ; Yi WANG ; Yinger HUANG ; Kunxiang GONG ; Wenbo HAO ; Lingling SUN
Journal of Southern Medical University 2025;45(7):1423-1433
OBJECTIVES:
To explore the therapeutic mechanism of Guizhi Fuling (GZFL) Pellets against cervical cancer.
METHODS:
Publicly available databases were used to identify the targets of GZFL Pellets and cervical cancer to construct the protein-protein interaction (PPI) network, followed by GO biological process and KEGG pathway enrichment analysis of the hub genes. The "Traditional Chinese Medicine-Active Ingredients-Targets-Pathways" network for GZFL Pellets in cervical cancer treatment was generated using Cytoscape v10.0.0, and molecular docking of the drug and potential targets was performed to predict the specific targets of active components in Guizhi Fuling Pellets. The inhibitory effects of hederagenin, an active ingredient in GZFL Pellets, was tested in cultured cervical cancer cells and in nude mice bearing cervical cancer xenografts.
RESULTS:
GZFL Pellets contain 338 active components targeting 247 action sites. A total of 10127 cervical cancer-related targets were obtained, and among them 195 were identified as potential therapeutic targets of GZFL Pellets for cervical cancer treatment, including the key targets of GABRA1, PTK2, JAK2, HTR3A, GSR, and IL-17. Molecular docking study showed low binding energies of the active components such as hederagenin, campesterol, and stigmasterol for protein-molecule interaction. GO enrichment analysis suggested that GZFL Pellets inhibited cervical cancer primarily by regulating responses to steroid hormones, oxidative stress, and lipopolysaccharides. Among the active components of GZFL Pellets, hederagenin was found to inhibit cervical cancer cells in vitro and significantly reduced STAT3 phosphorylation level in the cancer cells. In nude mice bearing cervical cancer xenografts, hederagenin effectively inhibited tumor growth rate without causing obvious adverse effects.
CONCLUSIONS
GZFL Pellets inhibit cervical cancer cell growth through its multiple active components that target different pathways. Among these components, hederagenin inhibits tumor cell growth possibly by directly binding to JAK2 protein to inhibit STAT3 phosphorylation.
Female
;
Animals
;
Uterine Cervical Neoplasms/pathology*
;
Mice, Nude
;
Humans
;
Mice
;
Oleanolic Acid/therapeutic use*
;
Drugs, Chinese Herbal/therapeutic use*
;
Molecular Docking Simulation
;
Xenograft Model Antitumor Assays
;
Cell Line, Tumor
;
STAT3 Transcription Factor/metabolism*
;
Protein Interaction Maps
;
Janus Kinase 2/metabolism*
4.Effects of class presentations on intercultural sensitivity of students in a TCM university under the framework of community of practice
International Journal of Traditional Chinese Medicine 2025;47(6):872-876
A total of 62 students of grade 2022 from Beijing University of Chinese Medicine who took the course of Comparative Study on Chinese and Western Cultures were selected. Based on the theory of community of practice (CoP), a community of learning and practice of Chinese and Western cultures was constructed through classroom presentations. Through the pre-test and post-test of the Intercultural Communication Sensitivity Scale (ISS) and the reflection sheets at the end of the semester, the influence of this community on students' intercultural sensitivity was explored. The data of pre-test and post-test were input SPSS 26.0 software for statistical analysis, and the reflection sheets were under thematic analysis based on the six elements of intercultural sensitivity. The results of ISS pre-test and post-test showed that classroom presentations could significantly improve interactive confidence in majors related to TCM ( t=2.32, P<0.05) and interactive focus in majors of nursing ( t=2.13, P<0.05), management and law ( t=2.87, P<0.05); The analysis results of the reflection sheets showed that class presentations could help students establish identity confidence and form a sense of cultural belonging; the introduction of intercultural theories could enhance the element of "self-monitoring"; the level of intercultural knowledge could promote the degree of "open-mindedness"; intercultural experiences could promote the element of "empathy"; the combination of intercultural theories and intercultural phenomena could improve the element of "suspending judgement". The community of learning and practice of Chinese and Western cultures constructed in this study has a positive impact on the development of intercultural sensitivity of students in TCM colleges and universities.
5.Chest computed tomography-based artificial intelligence-aided latent class analysis for diagnosis of severe pneumonia.
Caiting CHU ; Yiran GUO ; Zhenghai LU ; Ting GUI ; Shuhui ZHAO ; Xuee CUI ; Siwei LU ; Meijiao JIANG ; Wenhua LI ; Chengjin GAO
Chinese Medical Journal 2025;138(18):2316-2323
BACKGROUND:
There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA).
METHODS:
This retrospective study included 413 patients hospitalized at Xinhua Hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods.
RESULTS:
The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections ( P <0.001) than patients with subphenotype-2 and had lower 30-day ( P <0.001) and 90-day ( P <0.001) mortality, and lower in-hospital ( P = 0.001) and 2-year ( P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes ( P <0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment.
CONCLUSIONS
A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.
Humans
;
Tomography, X-Ray Computed/methods*
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Artificial Intelligence
;
Aged
;
Pneumonia/diagnosis*
;
Latent Class Analysis
;
Adult
6.The 510th case: fever of unknown origin, acute kidney injury
Yiran SHOU ; Yulin MAI ; Fuping GUO ; Hua ZHENG ; Congwei JIA ; Xiaoyuan LI ; Zhengyin LIU ; Taisheng LI
Chinese Journal of Internal Medicine 2025;64(1):83-87
A 65-year-old male was admitted to Peking Union Medical College Hospital. The patient had intermittent fever for 2 months with a maximum body temperature of 39.3 ℃ and elevated serum creatinine levels for 1 week. He had no other suggestive symptoms or positive signs. Laboratory test results suggested acute kidney injury and a sharp elevation in serum lactic dehydrogenase levels. Abdominal enhanced computed tomography (CT) revealed multiple low-density lesions, and further biopsy pathology demonstrated chronic inflammation. Thereafter, positron emission tomography (PET)/CT showed abnormally elevated uptake value for the bones throughout the entire body, in addition to the liver and brain. Repeated bone marrow biopsy finally confirmed metastatic bone cancer, which possibly originated from the kidney according to immunohistochemical staining. In this rare case of fever of unknown origin, the primary lesion was a renal tumor with bone, liver, and brain metastases. Enhanced CT and PET/CT provided negative results, and the diagnosis was eventually confirmed by repeated bone marrow pathology.
7.Interpretation of the "Guidelines for public health adaptation actions to climate change"
Jie BAN ; Qing WANG ; Yiran MA ; Yiran LYU ; Haiqiong LU ; Yi ZHANG ; Tianji LIN ; Min MENG ; Tiantian LI
Chinese Journal of Preventive Medicine 2025;59(10):1620-1623
In recent years, the situation of climate change has intensified, posing a threat to public health. There is an urgent need to promote public health adaptation actions to climate change. In January 2025, the National Disease Control and Prevention Administration issued the "Guidelines for Public Health Adaptation Actions to Climate Change" (hereinafter referred to as the "Guidelines"). The Guidelines put forward 20 items of guidance on six categories of public health adaptation actions, including understanding basic concepts, comprehending important policies, learning core knowledge, paying attention to key populations, practicing a low-carbon lifestyle, and mastering protection skills. It elaborates on the key concepts and the latest policies that the public needs to understand, and also provides the behavioral concepts and protection skills that should be mastered to adapt to climate change. This article provides a systematic interpretation of the Guidelines, introducing the background, ideas, connotations, and applications of their compilation, with the aim of enhancing society′s cognitive understanding of the Guidelines.
8.Effects of a virtual reality rehabilitation support system on discharge readiness among caregivers of post-laryngectomy patients
Li LI ; Yongling LIU ; Yang ZHANG ; Meng LIAN ; Yuehong WANG ; Shunli LU ; Chen YANG ; Tingting LI ; Yiran HE ; Xiaoting JIN ; Feilong XU ; Zirong TIAN
Chinese Journal of Nursing 2025;60(20):2451-2457
Objective To develop a virtual reality rehabilitation support system and evaluate its effects on improving discharge readiness in caregivers of laryngectomy patients.Methods The system is equipped with a virtual reality-based home nursing skills guidance module for post-laryngectomy patients and an evidence-based artificial intelligence Q&A module.A convenience sampling method was adopted to select 64 caregivers of patients who underwent laryngectomy for the first time in the otorhinolaryngology head and neck surgery department of a tertiary A hospital in Beijing from July 2024 to January 2025 for a systematic study on application effects.To avoid cross-contamination between an experimental group and a control group,ward-based grouping was applied.A coin toss was used to assign Ward 1 to an experimental group and Ward 2 to a control group,with 32 cases in each group.The experimental group received discharge guidance based on the virtual reality technology,while the control group was provided with conventional verbal and written discharge instructions.The readiness for hospital discharge and the quality of discharge teaching scores of caregivers were compared between the 2 groups after the intervention.Results No sample detachment.After the intervention,the patient caregivers in the experimental group scored significantly higher than those in the control group in terms of discharge readiness and quality of discharge guidance,with a statistically significant difference(P<0.001).Conclusion This study developed the virtual reality rehabilitation system for laryngeal cancer patients demonstrated good feasibility and effectiveness.The application of this system for discharge education significantly improved discharge readiness of caregivers and quality of discharge guidance for post-laryngectomy patients.It also helped with the optimization of health education models,enhancement of nursing resource utilization efficiency,and improvement of transitional care.
9.Pathogens isolated from cervical cancer patients with postoperative urinary catheter-associated urinary tract infection and predictive values of serum HMGB1,TLR4 and NF-κB
Li REN ; Xiyan MENG ; Yiran ZHANG ; Li JI ; Jingjing GUO
Chinese Journal of Nosocomiology 2025;35(6):885-889
OBJECTIVE To explore the distribution of pathogens isolated from the cervical cancer(CC)patients with postoperative urinary catheter-associated urinary tract infection(UTI)and analyze the predictive values of se-rum high mobility group protein B1(HMGB1),Toll-like receptor 4(TLR4)and nuclear factor kappa B(NF-κB).METHODS Totally 116 patients with CC who underwent radical resection in the First Affiliated Hospital of Henan University of Science and Technology from Jan.2021 to Jan.2024 were enrolled in the study and were divided into the infection group with 31 cases and the non-infection group with 85 cases according to the status of complication with UTI after urinary catheterization.The midstream urine specimens were collected by aseptic method,the pathogens were isolated and identified.The serum HMGB1 level was detected by means of enzyme-linked immu-nosorbent assay,the relative expression levels of peripheral blood TLR4 and NF-κB proteins were detected by Western blot.The efficiencies of serum HMGB1,TLR4 and NF-κB in prediction of postoperative urinary catheter-associated UTI in the CC patients were analyzed by means of receiver operating characteristic(ROC)curves.RESULTS Totally 49 strains of pathogens were isolated from 31 CC patients with postoperative urinary catheter-associated UTI,and the patients who had infection of single species were dominant.Gram-negative bacteria were the most common pathogens,accounting for 61.22%.There were significant differences in the age,complication with diabetes mellitus,duration of urinary catheter indwelling,postoperative uroschesis and previous history of UTI between the infection group and the non-infection group(P<0.05);there were significant differences in the levels of serum HMGB1,TLR4 and NF-κB between the two groups(P<0.05).The area under the curve(AUC)of the joint detection of serum HMGB1,TLR4 and NF-κB was 0.906 in prediction of the postoperative urinary catheter-associated UTI in the CC patients,with the sensitivity 83.87%;the predictive efficiencies of the joint de-tection of the indexes were better than those of the single detection(P<0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the CC patients with postoperative urinary catheter-asso-ciated UTI.The joint detection of the serum HMGB1,TLR4 and NF-κB has the highest value in prediction of postoperative urinary catheter-associated UTI in the CC patients.
10.Research progress of transcranial magnetic stimulation in treating different symptom groups of depression
Xiaoyu ZHANG ; Dan QIAO ; Gaizhi LI ; Yiran LI ; Zhifen LIU
Chinese Journal of Psychiatry 2025;58(1):59-68
Depressive disorder is one of the common mental diseases, which seriously affects the daily work and life of patients. In recent years, transcranial magnetic stimulation (TMS) treatment has shown satisfactory effects in the clinical application of depression. However, depressive disorder involves complex symptoms, including functional impairment in different dimensions such as emotion, cognition, body and behavior, which leads to significant individual differences in the efficacy of TMS intervention. Therefore, with different symptoms as the starting point, this article systematically reviewed the clinical studies of TMS treatment for different symptom groups of depressive disorder, in order to provide scientific reference for individualized treatment of depressive disorder using TMS treatment.

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