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.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.
3.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.
4.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.
5.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*
6.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
7.Research progress of suture augmentation in anterior cruciate ligament reconstruction.
Jiaxin LIU ; Hongyu LI ; Meng WANG ; Yiran WANG ; Guanxin GUO ; Hangzhou ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(4):504-510
OBJECTIVE:
To summarize the research progress of suture augmentation (SA) in anterior cruciate ligament (ACL) reconstruction.
METHODS:
A comprehensive review of recent literature about SA in ACL reconstruction at home and abroad was conducted. The efficacy of SA in ACL reconstruction was evaluated by examining the definition, biomechanics, and histological studies of SA, along with its clinical application status in ACL reconstruction.
RESULTS:
SA demonstrates significant advantages in enhancing the biomechanical stability of ACL grafts, reducing the risk of re-rupture, and accelerating postoperative recovery. Specifically, SA improves graft stiffness, ultimate failure strength, and cyclic stability, thereby diminishing the risk of early postoperative failure and joint instability. Histologically, it fosters remodeling and tendon-bone integration through early load-sharing mechanisms; however, stress shielding may interfere with natural remodeling processes, warranting further attention. Clinically, SA reduces graft failure rates and the need for revision surgeries, markedly improving knee joint stability and functional recovery in young patients. Nevertheless, its impact on graft maturation and potential complications remains controversial.
CONCLUSION
Despite the many advantages of SA in ACL reconstruction, future endeavors should focus on optimizing tensioning techniques, developing bioactive materials, and conducting large-scale randomized controlled trials to further elucidate its clinical value and scope of applicability, providing a more reliable solution for ACL reconstruction.
Humans
;
Anterior Cruciate Ligament Reconstruction/methods*
;
Biomechanical Phenomena
;
Anterior Cruciate Ligament/surgery*
;
Anterior Cruciate Ligament Injuries/surgery*
;
Suture Techniques
;
Sutures
;
Tendons/transplantation*
;
Joint Instability/prevention & control*
;
Knee Joint/surgery*
8.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.
9.Galangin Inhibits the Migration and Invasion of Cervical Cancer Hela Cells Through Hippo/YAP Pathway
Yiran YAN ; Chengwan SHEN ; Xiangyu SHANG ; Chan FENG ; Jinqiu LI ; Hasim AXIANGU
Journal of Kunming Medical University 2025;46(1):36-42
Objective To investigate the effects of galangin on the migration and invasion abilities of cervical cancer Hela cells and its potential mechanisms.Methods Hela cells were treated with different concentrations of galangin(0,5,10,20,40,60,80,100 μmol/L)for 48 hours,and CCK-8 assay was used to assess the impact of galangin on cell viability and to determine the half-maximal lethal concentration(IC50)of galangin.Hela cells were divided into a control group(0 μmol/L)and a galangin group(40 μmol/L treatment).Scratch wound healing assays and Transwell chamber assays were conducted to evaluate the migration and invasion abilities of the cells in each group.Western Blot was used to detect the protein expression of E-cadherin and N-cadherin.DIA quantitative proteomics technology was used to detect and screen the differentially expressed proteins between the two groups.Biological function enrichment analysis of the differential genes was performed using the KEGG Pathway and Gene Set Enrichment Analysis(GSEA)methods.Western Blot was used to verify the expression levels of Hippo/YAP signaling pathway-related proteins YAP and p-YAP.Results Compared to the control group,galangin(40 μmol/L)significantly inhibited the viability of Hela cells in a concentration-dependent manner(P<0.001).Compared with the control group,the scratch healing ability and invasion ability of cervical cancer Hela cells treated with galangin(40 μmol/L)were significantly reduced(P<0.001).The expression of E-cadherin protein was increased(P<0.05)and the expression of N-cadherin protein was decreased(P<0.001)in the galangin group(40 μmol/L)compared to the control group.KEGG and GSEA enrichment results indicated that the inhibition of malignant progression in cervical cancer by galangin was significantly associated with the Hippo/YAP signaling pathway.Western Blot confirmed that the expression level of the hallmark protein p-YAP in the Hippo signaling pathway was increased(P<0.01),while the expression level of YAP protein was decreased(P<0.05).Conclusion Galangin inhibits the proliferation,migration and invasion abilities of Hela cells in a dose-dependent manner.The underlying mechanism might be associated with the activation of the Hippo/YAP signaling pathway.
10.Value of ultra-high-resolution photon-counting detector CT in improving neurovascular image quality
Guang YAO ; Jun LI ; Junli REN ; Xing LIU ; Lichen REN ; Yiran WANG ; Xiaolei ZHANG ; Jiawei LIU ; Jianbo GAO ; Yonggao ZHANG
Chinese Journal of Radiology 2025;59(12):1353-1360
Methods:This study was a cross-sectional study. A prospective cohort study enrolled 42 patients with clinically suspected acute cerebrovascular disease and those undergoing follow-up examinations after intracranial vascular stenting at the First Affiliated Hospital of Zhengzhou University from June 2024 to May 2025. All patients underwent UHR PCD-CT examinations of the head and neck. Reconstructions were performed based on raw data, yielding conventional standard resolution (SR group) reconstructions and UHR images reconstructed using four distinct convolution kernels (Hv40, Hv48, Hv56, Hv64) in separate groups (Hv40 UHR group, Hv48 UHR group, Hv56 UHR group, Hv64 UHR group). Regions of interest were selected in the anterior cerebral artery, middle cerebral artery, posterior cerebral artery, posterior communicating artery, and anterior communicating artery. CT values and standard deviation (SD) values were measured for each artery, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Additionally, the sharpness of the vessel edges and the full-width-half-maximum (FWHM) of each artery were measured. One-way analysis of variance or the nonparametric Kruskal-Wallis test was used to compare the subjective and objective image quality metrics across the five groups. Pairwise comparisons were performed using the LSD test or Dunn method.Results:Statistically significant differences were observed in the overall comparison of vascular imaging SD, SNR, CNR, vascular edge sharpness, and FWHM among the SR group, Hv40 UHR group, Hv48 UHR group, Hv56 UHR group, and Hv64 UHR group ( P<0.05). No statistically significant differences in CT values were found ( P>0.05). Pairwise comparisons revealed statistically significant differences between all groups ( P<0.05), except that no significant differences were observed in image SD, SNR, CNR, vascular edge sharpness, or FWHM between the Hv56 UHR and Hv64 UHR groups ( P>0.05). Conclusions:UHR PCD-CT provides better image quality for neurovascular imaging. For the display of small intracranial vessels, the Hv64 provides sharper vessel walls and better subjective image quality compared to the less sharp convolutional cores.Objective:To explore the value of ultra-high resolution (UHR) photon-counting detector CT (PCD-CT) to improve the quality of neurovascular images.

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