1.Regulatory Mechanism of Extracellular Vesicles in The Tumor Immune Microenvironment and Its Application in Diagnosis and Treatment
Zi-Qi WANG ; Jing WANG ; Yuan-Yu HUANG ; Mei LU
Progress in Biochemistry and Biophysics 2026;53(4):968-981
Extracellular vesicles (EVs) are pivotal mediators of intercellular communication within the tumor immune microenvironment (TME). They are broadly categorized into exosomes, microvesicles, and apoptotic bodies based on their distinct biogenesis pathways. Exosomes originate from the endosomal system via multivesicular body fusion, microvesicles bud directly from the plasma membrane, and apoptotic bodies are released during programmed cell death. By shuttling diverse bioactive cargoes—including proteins, lipids, and nucleic acids such as mRNA, miRNA, and DNA—EVs exert dual modulatory effects on tumor initiation, progression, and immune evasion. Importantly, EVs exhibit remarkable compositional heterogeneity that is intrinsically linked to their cellular origin. Tumor-derived EVs (TDEVs) are typically enriched with immunosuppressive molecules like PD-L1, TGF‑β, and miR-21, which promote tumor immune escape and metastasis. In contrast, EVs derived from immune cells, such as dendritic cells or cytotoxic T lymphocytes, often carry immunostimulatory components including antigens, co-stimulatory molecules, and granzymes, thereby potentiating anti-tumor immunity. This review systematically delineates the biogenesis and molecular composition of EVs, with a particular emphasis on their dynamic regulatory functions within the TME. Specifically, we discuss how EVs mediate intricate crosstalk between immune and tumor cells, facilitating signal transfer that reshapes immune surveillance. For instance, TDEVs can induce macrophage polarization toward an M2-like pro-tumor phenotype, while also suppressing natural killer cell cytotoxicity and dendritic cell maturation. The clinical utility of EV-associated biomarkers in liquid biopsy is increasingly recognized. Circulating EVs carry tumor-specific molecular signatures that mirror the genetic and proteomic alterations of primary tumors, enabling non-invasive early diagnosis, molecular subtyping, and real-time monitoring of therapeutic responses. Their natural biocompatibility, low immunogenicity, and intrinsic ability to traverse biological barriers make them ideal candidates for drug delivery systems. This review explores cutting-edge applications, including the use of EVs in immune checkpoint blockade therapy—for instance, engineered EVs displaying anti-PD-1 antibodies or carrying siRNA to silence immunosuppressive genes. Moreover, EV-based tumor vaccines are being developed, leveraging dendritic cell-derived EVs loaded with tumor antigens to elicit potent T cell responses. The feasibility of loading EVs with therapeutic molecules such as chemotherapeutic agents, oncolytic viruses, or CRISPR-Cas9 components is also under active investigation. The advent of engineered EVs has further expanded their therapeutic potential. Through surface modification or cargo encapsulation, EVs can be tailored for targeted delivery and controlled release, enhancing precision immunotherapy. However, several hurdles impede clinical translation. Current isolation and purification methods, such as ultracentrifugation and size-exclusion chromatography, suffer from low yield and purity. Distinguishing EV subpopulations remains technically challenging due to overlapping size and marker expression. Moreover, the lack of standardized protocols for EV production, characterization, and quality control poses significant barriers to regulatory approval and clinical adoption. Looking forward, the convergence of multi-omics technologies with artificial intelligence offers a powerful approach to decipher EV heterogeneity and identify robust diagnostic signatures. Machine learning algorithms can integrate proteomic, transcriptomic, and lipidomic data from large patient cohorts to construct predictive models for cancer diagnosis and prognosis. Concurrently, advances in bioengineering are enabling the design of next-generation EVs with enhanced targeting specificity, on-demand drug release, and reduced off-target effects. Future efforts should also focus on establishing good manufacturing practice (GMP)‑compliant production processes and conducting rigorous preclinical and clinical evaluations. In summary, this review provides a comprehensive overview of EV biology, their multifaceted roles in the TME, and their transformative potential in cancer diagnostics and therapeutics. By addressing current challenges and leveraging emerging technologies, EV-based strategies are poised to revolutionize precision oncology.
2.Advances in the application of antiplatelet therapy in intravenous thrombolysis for acute ischemic stroke patients
Xiaohui ZI ; Xue XIA ; Jing LI ; Xiaoli ZHANG ; Quan ZHOU ; Anxin WANG ; Yilong WANG
Journal of Capital Medical University 2025;46(2):234-242
Acute ischemic stroke(AIS)is associated with high mortality and disability rates,presenting a substantial challenge to global public health challenge.Intravenous thrombolysis(IVT)is recognized as a cornerstone of early AIS treatment and is recommended as the standard therapeutic approach by both national and international guidelines.However,the clinical efficacy of IVT remains suboptimal due to several limitations,including a narrow therapeutic time window and the inevitable activation of the coagulation system and platelet aggregagation during thrombolysis.These factors may contribute to adverse outcomes such as early neurological deterioration(END)and vascular re-occlusion.Antiplatelet therapy(APT),which inhibits platelet aggregations,reduces microthrombus formation,and stabilizes the vascular endothelium with multifaceted mechanisms,has emerged as a promising adjunctive strategy to IVT,offering potential synergistic effects.This review summarized the latest evidence from both domestic and international studies,focusing on the mechanisms of APT,recent clinical advancements in IVT combined with APT,and the safety and efficacy of APT administration at different time windows relative to IVT.Emphasis is placed on the influence of various antiplatelet agents,dosing regimens,and initiation timing on therapeutic outcomes,alongside a comprehensive evaluation in the context of current guideline recommendations and clinical practice.Current guidelines recommend initiating APT 24 h after IVT,following imaging confirmation to exclude the risk of intracranial hemorrhage.However,the efficacy and safety of earlier APT initiation remain inconclusive.Individualized treatment strategies,such as early administration of low-dose,short-acting APT or combination therapy in specific patient subgroups,may effectively balance therapeutic benefits and risks.The adjunctive use of APT in IVT holds promise for enhancing efficacy and improving clinical outcomes,but precise stratification of safety and efficacy is essential.Future research should focus on optimizing combination IVT and APT strategies through individualized patient profiling,appropriate drug selection,and dynamic imaging monitoring to achieve precision management in AIS treatment.
3.Comparison of active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms
Yan-ran HE ; Jing WANG ; Jia-qiang XU ; Zhao-zhao XIA ; Ying-jiao LIU ; Zi-shu DONG ; Liang-shan MING ; Hong-ning LIU ; Qi-meng FAN
Chinese Traditional Patent Medicine 2025;47(2):357-364
AIM To compare total sugar,total protein,total phenol,total flavonoid,calycosin-7-O-β-D-glucoside,liquiritin,lobetyolin,quercetin,isoferulic acid,hesperidin,glycyrrhizic acid contents and their antioxidant activities,hypoglycemic activities of big honey pill,small honey pill,water pill,concentrated pill,granule,mixture and decoction of Buzhong Yiqi Recipe.METHODS Anthraquinone-sulfuric acid method,Coomassie brilliant blue method,Folin-phenol colorimetry method,sodium nitrite-aluminum nitrate method and HPLC were adopted in the content determination of total sugar,total protein,total phenol,total flavonoid and seven constituents,respectively,after which the scavenging capacities,reducing powers on DPPH·free radical,ABTS+free radical,hydroxyl free radical,and inhibition capacity on α-glucosidase activity were detected.Subsequently,correlation analysis was performed.RESULTS Total sugar,total protein,total phenol and total flavonoid contents demonstrated significant differences among different dosage forms(P<0.05,P<0.01).Calycosin-7-O-β-D-glucoside,glycyrrhizin,codonoside and quercetin displayed the highest contents in the decoction,while those of isoferulic acid,hesperidin and glycyrrhizin were observable in the mixture.The water pill exhibited the strongest antioxidant activity,while those of the concentrated pill and mixture were weak;the big honey pill exhibited the strongest hypoglycemic activity,while that of the decoction was the weakest.Total protein,total phenol,total flavonoid and liquiritin contents displayed significant positive correlations between antioxidant activity(P<0.05,P<0.01),while hesperidin content displayed significant negative correlation between the latter(P<0.05);total protein,calycosin-7-O-β-D-glucoside,codonoside and quercetin contents displayed significant negative correlations between hypoglycemic activity(P<0.05,P<0.01).CONCLUSION Active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms exist differences,total sugar,total protein,total flavonoids,calycosin-7-O-β-D-glucoside,licorice glycoside,hesperidin,codonoside and quercetin can be taken as quality control indices for this prescription.
4.Eplerenone alleviates rheumatoid arthritis in mice by inhibiting macrophage M1 polarization through Kv1.3/Bcl-2/NF-κB pathway
Chi XIAO ; Jing CAI ; Zi-hang WANG ; Yong-zheng ZHANG ; Jing YANG ; Lu-feng CHENG
Chinese Pharmacological Bulletin 2025;41(4):726-737
Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P<0.05,P<0.01),and the high-dose EPL group reduced the serum RF in mice(P<0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P>0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P<0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P<0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P<0.01).EPL significantly increased the pro-tein expression of Bcl-2(P<0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P<0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.
5.Study on the Genotoxicity of Graphene Artificial Nerve Sheath Conduit
Ling-xiao SUN ; Bing-bing SUN ; Yue QIN ; Guo-wei WANG ; Luan-luan WANG ; Zi-yi YANG ; Zi-ye WANG ; Xiao-tian ZHAO ; Xiao-jing LI ; Cheng-hu LIU
Progress in Modern Biomedicine 2025;25(14):2250-2258
Objective:The genotoxicity risk of graphene artificial nerve sheath conduit was systematically evaluated to provide scientific evidence for their clinical safety and to establish methodological references for the genotoxicity assessment of nanomaterial medical devices.Methods:The potential effects of graphene artificial nerve sheath conduit on genetic and chromosomal endpoints were analyzed by integrating bacterial reverse mutation assays,in vitro chromosome aberration assays,mouse lymphoma cell TK gene mutation tests,and mammalian erythrocyte Pig-a gene mutation assays.Results:In the bacterial reverse mutation assay,all plates showed good background growth.There was no significant difference in the average number of revertant colonies between the test group and the negative control group,with a ratio around 1.0.In the in vitro chromosome aberration assay,the chromosomal aberration rate in the test group was less than 5%,showing no significant increase compared to the negative control group.In the mouse lymphoma cell TK gene mutation assay,the mutation frequency in the test group was less than twice that of the negative control group,with no significant difference.In the mammalian erythrocyte Pig-a gene mutation assay,the mutation frequencies of erythrocytes and reticulocytes in the test group were both less than 3× 10-6,showing no significant difference compared to the negative control group.Conclusions:Graphene artificial nerve sheath conduit exhibited no detectable genotoxicity under the tested conditions,the research results can provide reference and guidance for the genotoxicity evaluation of nanomaterial medical devices.
6.Design of intelligent airborne soldier physical training system based on human body composition analysis
Lin YANG ; Zheng LIU ; Yu-shan YE ; Jian-fei PANG ; Jing HE ; Xuan-zi ZHOU ; Qiong WANG ; Xin-sheng CAO ; Tao LIU
Chinese Medical Equipment Journal 2025;46(2):16-23
Objective To design an intelligent airborne soldier physical training system based on human body composition analysis to solve the problems in diversity of training mode,targeted training plan and high incidence of military training-related injuries.Methods The intelligent airborne military physical training system was designed with B/S architecture and developed with Python language,which was composed of four functional modules for airborne soldier information acquisition,trainee physical fitness state assessment,physical fitness training program recommendation and airborne soldier physical fitness training program evaluation.The airborne soldier information acquisition module collected and analyzed the trainee physiological parameter information with a human body composition analyzer,clarified the parameter characteristics related to physical training with considerations on military physical training requirements and constructed a trainee physical fitness assessment parameter model;the trainee physical fitness state assessment module established an evaluation model based on machine learning to realize stage-by-stage physical fitness evaluation for airborne soldiers;the physical fitness training program recommendation module was constructed based on the physical training feature similarity algorithm and graph embedding theory to provide decision making assistance for program development of airborne military physical training;the airborne soldier physical fitness training program evaluation module compared the physical fitness and evaluation results before and after training by means of list and chart,and updated the training program based on the evaluation results by calling the physical training program recommendation module.Results The intelligent airborne soldier physical training system contributed to forming an individualized physical fitness training recommendation mechanism after trainee body evaluation,modifying training program based on comparison and feedback for stage-by-stage training evaluation,so as to decrease the incidence of military training-related injuries while increasing the training efficiency.Conclusion The system developed improves airborne soldier physical training in rationality and reliability,and provides references for intelligent military training of the PLA.[Chinese Medical Equipment Journal,2025,46(2):16-23]
7.Application of ultrasound-guided needling assisted the motor evoked potentials and electromyography monitoring in spinal surgery
Jing HU ; Hai-lin LI ; Zhi-qiang WU ; Jia-cheng LU ; Zi-xuan YUAN ; Yu-xi SUN ; Hui-bo WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(11):960-964
Objective To explore the effect and predictive value of ultrasound-guided needling assisted motor evoked potentials(MEP)and electromyography(EMG)monitoring on neurological recovery in spinal surgery.Methods A retrospective analysis was conducted on the clinical data of 80 patients who underwent spinal surgery at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2024.A total of 41 patients in the observation group received ultrasound-guided needling assisted MEP and EMG monitoring,and 39 patients in the control group received conventional method for MEP and EMG monitoring.The operative time,intraoperative blood loss,and the proportions of intraoperative MEP and EMG warnings were compared between the two groups,and the sensitivity and specificity of intraoperative MEP monitoring were compared between the two groups.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to analyze the efficiency of MEP warning in predicting the dysfunction of postoperative spinal cord.Results There were no significant differences in the operative time,intraoperative blood loss,or the proportions of intraoperative MEP and EMG warnings(P>0.05).The sensitivity,specificity and AUC of intraoperative MEP monitoring in the observation group were significantly higher than those in the control group,with statistically significant differences(P<0.05).The sensitivity,specificity,and AUC of postoperative MEP warning in predicting the dysfunction of spinal cord in the observation group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Ultrasound-guided needling assisted MEP and EMG monitoring can effectively enhance the intraoperative neural monitoring accuracy,and postoperative MEP warning demonstrates superior predictive value for postoperative neurological dysfunction.
8.Study on the Genotoxicity of Graphene Artificial Nerve Sheath Conduit
Ling-xiao SUN ; Bing-bing SUN ; Yue QIN ; Guo-wei WANG ; Luan-luan WANG ; Zi-yi YANG ; Zi-ye WANG ; Xiao-tian ZHAO ; Xiao-jing LI ; Cheng-hu LIU
Progress in Modern Biomedicine 2025;25(14):2250-2258
Objective:The genotoxicity risk of graphene artificial nerve sheath conduit was systematically evaluated to provide scientific evidence for their clinical safety and to establish methodological references for the genotoxicity assessment of nanomaterial medical devices.Methods:The potential effects of graphene artificial nerve sheath conduit on genetic and chromosomal endpoints were analyzed by integrating bacterial reverse mutation assays,in vitro chromosome aberration assays,mouse lymphoma cell TK gene mutation tests,and mammalian erythrocyte Pig-a gene mutation assays.Results:In the bacterial reverse mutation assay,all plates showed good background growth.There was no significant difference in the average number of revertant colonies between the test group and the negative control group,with a ratio around 1.0.In the in vitro chromosome aberration assay,the chromosomal aberration rate in the test group was less than 5%,showing no significant increase compared to the negative control group.In the mouse lymphoma cell TK gene mutation assay,the mutation frequency in the test group was less than twice that of the negative control group,with no significant difference.In the mammalian erythrocyte Pig-a gene mutation assay,the mutation frequencies of erythrocytes and reticulocytes in the test group were both less than 3× 10-6,showing no significant difference compared to the negative control group.Conclusions:Graphene artificial nerve sheath conduit exhibited no detectable genotoxicity under the tested conditions,the research results can provide reference and guidance for the genotoxicity evaluation of nanomaterial medical devices.
9.Application of ultrasound-guided needling assisted the motor evoked potentials and electromyography monitoring in spinal surgery
Jing HU ; Hai-lin LI ; Zhi-qiang WU ; Jia-cheng LU ; Zi-xuan YUAN ; Yu-xi SUN ; Hui-bo WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(11):960-964
Objective To explore the effect and predictive value of ultrasound-guided needling assisted motor evoked potentials(MEP)and electromyography(EMG)monitoring on neurological recovery in spinal surgery.Methods A retrospective analysis was conducted on the clinical data of 80 patients who underwent spinal surgery at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2024.A total of 41 patients in the observation group received ultrasound-guided needling assisted MEP and EMG monitoring,and 39 patients in the control group received conventional method for MEP and EMG monitoring.The operative time,intraoperative blood loss,and the proportions of intraoperative MEP and EMG warnings were compared between the two groups,and the sensitivity and specificity of intraoperative MEP monitoring were compared between the two groups.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to analyze the efficiency of MEP warning in predicting the dysfunction of postoperative spinal cord.Results There were no significant differences in the operative time,intraoperative blood loss,or the proportions of intraoperative MEP and EMG warnings(P>0.05).The sensitivity,specificity and AUC of intraoperative MEP monitoring in the observation group were significantly higher than those in the control group,with statistically significant differences(P<0.05).The sensitivity,specificity,and AUC of postoperative MEP warning in predicting the dysfunction of spinal cord in the observation group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Ultrasound-guided needling assisted MEP and EMG monitoring can effectively enhance the intraoperative neural monitoring accuracy,and postoperative MEP warning demonstrates superior predictive value for postoperative neurological dysfunction.
10.Assessment of Genotoxicity of Tissue Engineered Materials Based on Improved in vivo Hepatocyte Unscheduled DNA Synthesis(UDS)Assay
Luan-luan WANG ; Li HOU ; Xiang-yu CHU ; Zi-yi YANG ; Ling-xiao SUN ; Xiao-fei WANG ; Qiu-jin QU ; Jing XU ; Zeng-xiang LIU ; Xiao-xia SUN
Progress in Modern Biomedicine 2025;25(17):2740-2748
Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9%sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P<0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P>0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.

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