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.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
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Artificial Intelligence
;
Aged
;
Pneumonia/diagnosis*
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Latent Class Analysis
;
Adult
3.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
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Anterior Cruciate Ligament Reconstruction/methods*
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Biomechanical Phenomena
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Anterior Cruciate Ligament/surgery*
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Anterior Cruciate Ligament Injuries/surgery*
;
Suture Techniques
;
Sutures
;
Tendons/transplantation*
;
Joint Instability/prevention & control*
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Knee Joint/surgery*
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.Exploring the mechanism of electroacupuncture to improve cognitiveimpairment in alzheimer's disease model rats based on NF-κB/NLRP3/Caspase-1 signaling pathway
Rongxin LI ; Li HUANG ; Yueyang ZENG ; Shuhui ZHANG ; Yiran CHEN ; Yuli LIU ; Tieming MA
The Journal of Practical Medicine 2025;41(3):322-329
Objective To investigate the effects of electroacupuncture(EA)at"Baihui(GV 20),""Pishu(BL 20),"and"Zusanli(ST 36)"on the learning and memory functions of rats with Alzheimer's disease(AD)induced by Aβ1-42.Additionally,the mechanism of EA in treating AD was explored from the perspective of the inflammatory cascade mediated by the NF-κ B/NLRP3/Caspase-1 signaling pathway.Methods A rat model of Alzheimer's disease was established by bilateral injection of Aβ1-42 solution into the C1 region of the hippocampus.According to the random number table method,32 male SPF-grade rats were divided into four groups(n=8 per group):a sham-operated group,a model group,an electroacupuncture(EA)group,and a Western medicine group(donepezil hydrochloride).The EA group received electroacupuncture at the"Baihui","Pishu",and"Zusanli"acu-points;the Western medicine group received donepezil hydrochloride via gavage.After the treatment period,Morris water maze experiments were conducted to evaluate learning and memory abilities.Hematoxylin and eosin(HE)staining was used to examine morphological changes in hippocampal tissues.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum levels of TNF-α and IL-1β.Western blotting and immunofluorescence staining were utilized to assess the co-expression levels of NF-κB p65,NLRP3,and Caspase-1 proteins in the hippocampal region.Results Compared with the sham-operated group,rats in the post-modeling group exhibited significantly prolonged escape latency(P<0.05),reduced crossings of the original platform location,and decreased time spent in the target quadrant(P<0.05).Additionally,nuclear morphology was altered,neurons surrounding the hippocampus displayed necrosis,vacuolar degeneration,and chromatin marginalization.Serum levels of TNF-α and IL-1β were elevated(P<0.05),and protein expression levels as well as fluorescent positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were increased(P<0.05).Compared with the model group,rats in both the EA and Western medicine groups showed a trend toward shorter escape latency(P<0.05),increased crossings of the original platform location and time spent in the target quadrant(P<0.05).Cell structures were largely intact,with only a few nuclei showing slight irregularities and some chromatin accumulation at the edges.Serum levels of TNF-α and IL-1β were reduced(P<0.05),and protein expression levels and fluorescence positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were also decreased(P<0.05).Conclusion EA enhances the learning and memory capabilities of AD rats,potentially by downregulating the NF-κ B/NLRP3/Caspase-1+signaling+pathway and decreasing the release of neuroinflammatory factors,thereby alleviating cognitive dysfunction in AD rats.
7.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.
8.One case of pulmonary infection in a patient with polymyalgia rheumatica caused by Legionella marssiliensis
Yiran HU ; Sisi ZHANG ; Anhua WU ; Chunhui LI
Chinese Journal of Infection Control 2025;24(3):422-425
A 70-year-old male patient was admitted to a hospital on March 1,2024 due to"muscle soreness in his extremities for over a month".Diagnosis consideration:polymyalgia rheumatica(with a high likelihood,the possi-bility of a tumor needs to be excluded).The patient was treated with methylprednisolone.After discharge from the hospital,the patient's symptoms worsened due to self-withdrawal of medication(methylprednisolone treatment for 20 days),and developed fever and cough.He then revisited the hospital and was confirmed to have Legionella mar-ssiliensis infection through metagenomic sequencing of bronchoalveolar lavage fluid(nucleic acid of all microorga-nisms were extracted from the specimens and compared in the PMDB database to obtain species information of the suspected pathogenic microorganisms).Subsequently,the patient was treated with a combination of 0.75 g levo-floxacin intravenous infusion qd+0.1 g doxycycline enteric-coated capsules orally bid for anti-infective therapy.The patient's symptoms,such as cough and muscle pain,improved significantly after anti-inflammatory and anti-in-fective treatment,and he was discharged on March 18.As the first reported case of Legionella marssiliensis pulmo-nary infection in China,this case highlights that among the multiple species of Legionella,there is another bacte-rium that can infect the human body and cause disease.This case report is beneficial for improving medical staff's understanding on Legionella marssiliensis and providing reference for the diagnosis and treatment of future cases of Legionella marssiliensis infection.
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.Association between the overuse of short-form video,inattention and school refusal behavior among junior high school students
Youdong LI ; Jianqiang WANG ; Ziyan WANG ; Jiuying LIU ; Jing LYU ; Yiran GE ; Yuru DU
Chinese Mental Health Journal 2025;39(1):49-56
Objective:To explore the prominent manifestations and internal associations of the overuse of short-form videos,inattention,and school refusal behavior in junior high school students.Methods:A survey was conducted among 1 106 junior high school students,utilizing the Short-form Video APP Overuse Scale,the Inatten-tion subscale of the Swanson,Nolan,and Pelham Rating Scale(SNAP-Ⅳ),and the School Refusal Behavior Ques-tionnaire to assess the extent of short-form video overuse,inattention,and school refusal behavior.By using the R language for network analysis,the core nodes of individual networks and the bridge nodes connecting the combined networks were analyzed,and the structural differences in networks across genders and grades were compared.Re-sults:The core nodes of the network pertaining to overuse of short-form video,inattention,and school refusal behav-ior were"Using short videos enhances connection with others"(expected influence value=1.03),"easily distract-ed"(expected influence value=1.99),and"school alienation"(expected influence value=0.83).The bridge nodes in the combined network were"defiant behavior"(bridge expected influence value=0.69)and"difficulty sustaining mental activities"(bridge expected influence value=0.47).Analysis of network structure differences i-dentified that the core nodes within the combined networks of the first,second,and third grades of junior high school students were respectively"prioritizing short videos over other activities","defiant behavior",and"academic aptitude".Conclusion:Junior high school students exhibiting overuse of short videos,inattention,or school refusal behavior are characterized by enhanced social connectivity through platforms such as short video apps,a propensity for distraction,and feelings of school alienation,respectively.When these three behaviors coexist,the most salient related factor is oppositional behavior,coupled with difficulties in sustaining cognitive tasks and maintaining con-centration.

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