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.Tianxiang Pills Alleviates Myocardial Cell Pyroptosis in Rat Model of Myocardial Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress via ROS/Caspase-1/GSDMD Signaling Pathway
Fei ZENG ; Hao HUANG ; Yu CAO ; Yaoming XI ; Jing LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):143-150
ObjectiveTo investigate the mechanism by which Tianxiang pills (TXP) alleviates myocardial cell pyroptosis in the rat model of myocardial ischemia/reperfusion (I/R) injury through modulating the reactive oxygen species (ROS)/cysteinyl aspartate-specific proteinase-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway. MethodsA total of 54 SPF-grade adult male Sprague-Dawley rats were randomized into six groups (n=9): sham (thoracotomy only without ligation), I/R (left anterior descending coronary artery ligation for 30 min followed by reperfusion), NAC (positive control, N-acetylcysteine, 150 mg·kg-1, by gavage), low-dose Tianxiang pills (TXP-L, 2.5 g·kg-1, by gavage)], medium-dose Tianxiang pills (TXP-M, 5 g·kg-1, by gavage), and high-dose Tianxiang pills (TXP-H, 10 g·kg-1, by gavage). The fluorescent probe method was employed to measure the ROS level. Biochemical assay kits were employed to determine the Caspase-1 activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity. Myocardial infarct size was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western blot analysis was performed to evaluate the expression levels of proteins in the ROS/Caspase-1/GSDMD pathway, including GSDMD, cleaved Caspase-1/Caspase-1 ratio, the N-terminal domain of GSDMD (GSDMD-N), and the p22-phox subunit of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Enzyme-linked immunosorbent assay (ELISA) was utilized to determine the concentration of interleukin-1β (IL-1β). Transmission electron microscopy (TEM) was employed to observe mitochondrial structure and to score the degree of mitochondrial swelling. ResultsCompared with the Sham group, the I/R group exhibited elevated the levels of ROS, Caspase-1 activity, GSDMD expression, IL-1β concentration, MDA content, infarct area, mitochondrial swelling score, cleaved Caspase-1/Caspase-1, GSDMD-N, and p22phox and decreased activities of SOD and GSH-Px (P<0.05). Compared with the I/R group, NAC and different doses of TXP significantly reduced the ROS level, Caspase-1 activity, GSDMD expression, IL-1β concentration, MDA content, infarct area, and mitochondrial swelling score. Moreover, they downregulated the expression of cleaved Caspase-1/Caspase-1, GSDMD-N, and p22phox and increased the activities of SOD and GSH-Px (P<0.05). Furthermore, TXP exerted effects on ROS, MDA, SOD, GSH-Px, Caspase-1 activity, GSDMD expression, IL-1β concentration, cleaved Caspase-1/Caspase-1, GSDMD-N, p22phox, infarct area, and mitochondrial swelling score in a dose-dependent manner (P<0.05). ConclusionTianxiang pills alleviates myocardial I/R injury by mitigating oxidative stress and cell pyroptosis through the inhibition of the ROS/Caspase-1/GSDMD signaling pathway.
3.Shengmai Yin alleviates myocardial ischemia/reperfusion injury via inhibiting Calpains expression
Rong MIAO ; Jing-wen GUO ; Ming HUANG ; Hai-shuo REN ; Rui LIU ; Xiao-yu SUN ; Opoku Bonsu FRANCIS ; Qi-long WANG ; Shi-ming FANG ; Ling LENG
Chinese Pharmacological Bulletin 2025;41(8):1569-1577
Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.
4.Therapeutic effects of virtual reality-based accommodation training device on accommodative excess asthenopia
Ziting HUANG ; Jing ZHONG ; Jijing LI ; Jing MA ; Yu LIU ; Wei CHEN ; Yiming LUO ; Jin YUAN
Chinese Journal of Experimental Ophthalmology 2025;43(2):121-129
Objective:To analyze the therapeutic effect of a virtual reality (VR)-based accommodation training device on accommodative excess visual fatigue.Methods:A case-control study was conducted.A total of 20 normal subjects (20 eyes) and 20 patients with accommodative excess visual fatigue (20 eyes) were recruited at Zhongshan Ophthalmic Center, Sun Yat-sen University between January and December 2022.The study consisted of two phases.In the first phase, the effect of watching videos with VR glass on the subjects' subjective and objective visual function was evaluated.Normal subjects wore VR device to watch a 2D video for 30 minutes, and assessments were performed before and after viewing.These assessments included binocular accommodation/convergence function (accommodation response, accommodative convergence to accommodation ratio [AC/A]), tear film function (first tear film break-up time), subjective symptoms (visual fatigue score), and basic visual health parameters including best corrected visual acuity (BCVA) and intraocular pressure (IOP).In the second phase, the improvement in subjective and objective visual fatigue metrics with the VR-based accommodation training device was investigated.Patients with visual fatigue were divided into a traditional training group using traditional flipper lenses and a VR training group using the VR accommodation training device, with 10 eyes in each group.The effects of the VR accommodation training device on indicators such as accommodative sensitivity, accommodation response, convergence function, visual fatigue score, acceptability score, system usability score, BCVA, and IOP were evaluated and compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.IIT2021007).Written informed consent was obtained from each subject.Results:In normal subjects, there was no statistically significant difference in first tear film break-up time, distance phoria, near phoria, AC/A, accommodative response, BCVA, or IOP before and after 30 minutes of continuous viewing of 2D video using VR glass ( t=1.155, 1.360, 4.479, 1.979, -1.249, -3.017, 2.211; all P>0.05).The visual fatigue score remained unchanged at (1.00±0.00) points before and after viewing.Among the subjects with visual fatigue, there were statistically significant differences in binocular accommodative sensitivity, dominant eye accommodative sensitivity, and BCVA before and after using the VR accommodation training device ( F=8.693, 4.078, 4.942; all P<0.05).Ocular accommodation sensitivity at 8 weeks after training was improved compared with 1 week after training, and BCVA at 4 weeks after training was improved compared with before training, and the differences were statistically significant (both P<0.05).In the VR training group, the average tear film break-up time, first tear film break-up time, and BCVA increased and the visual fatigue score decreased compared with before training, the differences were statistically significant (all P<0.05).In the traditional training group, the accommodation sensitivity of the dominant eye increased after training compared with before training, with a statistically significant difference ( P<0.05). Conclusions:Watching 2D videos with VR glass for 30 minutes does not induce subjective or objective symptoms of visual fatigue.The VR-based accommodation training paradigm effectively improves accommodative sensitivity and alleviates subjective symptoms of visual fatigue in individuals with accommodative excess visual fatigue.
5.Mental health literacy and its relationship with symptoms of depression,anxiety,and insomnia in young adults
Yuqing YANG ; Jing HUANG ; Zixin LIN ; Tong YU ; Xiyuan CHEN ; Ning YANG ; Shaoling ZHONG ; Liang ZHOU
Chinese Mental Health Journal 2025;39(4):344-349
Objective:To explore the level of mental health literacy and its relationship with symptoms of de-pression,anxiety,and insomnia in young adults.Methods:A total of 10 273 young adults aged 18-23 in Guang-zhou were selected and assessed with the National Mental Health Literacy Questionnaire,Patient Health Question-naire-9(PHQ-9),General Anxiety Disorder 7-Item Scale(GAD-7)and Insomnia Severity Index(ISI).Results:Totally 1 137(11.1%)participants met the criteria for adequate mental health literacy,2 758(26.8%)participants were with symptoms of depression,1 355(13.2%)with symptoms of anxiety and 4 936(48.0%)experiencing symptoms of insomnia.Logistic regression analyses showed that after adjusting for other factors,substandard mental health literacy was an independent risk factor for symptoms of depression,anxiety and insomnia(OR=2.08,1.93,1.49;95%CI:1.74-2.48,1.52-2.46,1.31-1.70).Conclusion:The level of mental health literacy in young a-dults is insufficient,and the lack of mental health literacy is significantly associated with the symptoms of depres-sion,anxiety and insomnia.
6.Effects of palatal scar contraction force on the displacement of maxillary alveolar bone with cleft palate:A finite element analysis
Yifei LIU ; Guanyue CHEN ; Yu WANG ; Jing LIU ; Hongbao GENG ; Wei HUANG
Journal of Practical Stomatology 2025;41(4):468-472
Objective:To simulate and compare the impact of scar contraction force on maxillary alveolar bone displacement after cleft palate surgery in different regions of the palate.Methods:The same scar contraction force was applied to the grouping hard pal-ate area on the original finite element model of the maxilla with cleft palate,and calculations were performed in ANSYS 17.0.Divid-ed into four groups based on the applied force area:anterior half(group 1),posterior half(group 2),lateral half(group 3),and me-dial half(group 4).Nodes in the alveolar bone of the cleft and non-cleft sides were selected as observation points.The three-dimen-sional displacement of observation points was recorded and compared between groups.Results:The displacement of group 1>group 3,4>group 2(P<0.01).Conclusion:Scars from different parts of the hard palate can lead to a decrease in the length,width,and height of the maxillary alveolar bone.Among them,the anterior scar has the most severe impact,followed by the medial and lateral scars,and the posterior scar has the smallest impact.
7.Clinicopathological analysis of 495 cases of gastrointestinal mesenchymal tumors resected via endoscopy
Shuaixia YU ; Yao HUANG ; Xiao HU ; Jing FU ; Huajun SUN ; Baijie TANG ; Qian TANG ; Ying XU ; Xudan YANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(7):897-903
Purpose To characterize the clinicopathological features of gastrointestinal mesenchymal tumors(GMTs)resected via endoscopic techniques.Methods A retrospective analysis was conducted on 495 cases of endo-scopically resected GMTs.Clinical information,histomorphological findings,immunohistochemical profiles,and mo-lecular characteristics were reviewed.Results The cohort included 495 patients aged 20-78 years(median:53 years).The majority of tumors were located in the stomach(58.8%)and esophagus(36.8%).Histologically,most tumors consisted of spindle cells,with a minority composed of epithelioid cells;fibrocollagenous or myxoid stroma was occasionally observed.Immunohistochemically,leiomyomas showed diffuse positivity for α-SMA(98.8%)and desmin(99.3%),gastrointestinal stromal tumors(GISTs)expressed CD117(99.4%),DOG1(97.6%),and CD34(97.0%),and schwannomas were positive for S-100(93.7%).The predominant tumor types were leiomyomas(54.1%)and GISTs(33.7%),while the remaining 12.2%comprised other rare types.Various endoscopic resection techniques were employed based on the tumors' anatomical depth,including endoscopic submucosal dissection(ESD,40.5%),submucosal tunneling endoscopic resection(STER,17.1%),endoscopic mucosal resection(EMR,16.5%),endoscopic full-thickness resection(EFTR,13.9%),and endoscopic submucosal excavation(ESE,12.0%).EMR and ESD were primarily used for superficial lesions,while deeper tumors with were more often treated with STER,EFTR,and ESE.The rate of negative resection margins was lower in GISTs(72.2%)and other tumors with indistinct margins,compared to leiomyomas(92.6%)and those with well-defined boundaries.Conclusion Leiomyomas and GISTs are the most common gastrointestinal mesenchymal tumors resected via endoscopy.A variety of resection techniques are applicable depending on tumor location and depth.Accurate pathological diagnosis should be based on HE morphology,supplemented by endoscopic findings,margin status,immunohistochemistry,and necessary molecular tests.
8.Isolation,identification,and biological characterization of enterotoxigenic Escherichia coli from a South China tiger
Jing-ru XU ; Zhi-hao ZHU ; Yu-qi LI ; Si-si FAN ; Ya-li KANG ; Yu-bin ZHUO ; Ling-shan HUANG ; Shu-qi QIU ; XUE-YUXI ; Xiao-ping WU ; Yu-ting LIAO ; Wei-ye LIN ; Xiao-ziyi XIAO ; Xue-jin LI ; Teng-teng CHEN ; Xi-pan LIN ; Kai-xiong LIN ; Ke-wei FAN
Chinese Journal of Zoonoses 2025;41(6):567-573
This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.
9.Real experience of perimenopausal women participating in group public welfare exercise program: a qualitative research
Jialing YANG ; Yingzhu HUANG ; Jing ZHOU ; Xun LEI ; Lili YU
Chinese Journal of Modern Nursing 2025;31(3):314-320
Objective:To explore the real experience of perimenopausal women participating in a group public welfare exercise program, so as to inform the optimization of the program, and to provide recommendations for the development and implementation of perimenopausal exercise prescriptions.Methods:This study was a qualitative study. Twenty-five perimenopausal women who participated in a group perimenopausal public welfare exercise program were selected for face-to-face semi-structured interviews from December 2023 to February 2024 using purposive sampling method. Data were organized and analyzed using Colaizzi phenomenological analysis and MAXQDA 2022 software.Results:A total of 12 secondary themes were distilled from four primary themes of positive physical experience, positive psychological experience, positive social experience, and motivation and resistance.Conclusions:Group exercise intervention can improve the physical health, mental health, and social experience of perimenopausal women. Based on the motivation and resistance of participants to participate in the program, corresponding measures can be taken to further optimize the exercise program and provide health assistance for perimenopausal women.
10.Coverage of National Immunization Program vaccines and vaccination information consistency rate among children born during 2020-2021 in 3 provinces in China
Wenqi HUANG ; Miao XU ; Xiaohua QI ; Qing WANG ; Jing CHEN ; Ming GUANG ; Yu LIU ; Xu CHEN ; Fangfang ZENG ; Dan LIU ; Xiaofeng LIANG
Chinese Journal of Epidemiology 2025;46(8):1393-1399
Objective:To understand the coverage and information consistency rate of National Immunization Program (NIP) vaccines among children born during 2020-2021 in Zhejiang Province, Chongqing City, and Shanxi Province (3 provinces) of China .Methods:A simple random sampling method was used to randomly select 3 counties (districts) from each of the 3 provinces, 5 townships from each county (district), and 5 villages from each township. Vaccination information for seven NIP vaccines was collected for children born between 2020 and 2021 in each village. The vaccination coverage, timely coverage, and consistency rates between the survey data and the Immunization Planning Information System data were analyzed.Results:A total of 1 117 children were investigated. The vaccination coverage for each dose of NIP vaccine ranged from 99.10% to 100.00%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 99.19% to 100.00%, 98.92% to 100.00%, and 99.20% to 100.00%, respectively. The timely coverage of each dose of NIP vaccine ranged from 89.79% to 99.82%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 94.09% to 99.73%, 89.52% to 99.73%, and 78.55% to 100.00%, respectively. The consistency rate of information on each dose of NIP vaccine ranged from 94.36% to 99.91%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 97.85% to 99.73%, 98.92% to 100.00%, and 86.06% to 100.00%, respectively.Conclusions:Coverage of NIP vaccines was generally high among children born during 2020-2021 in the 3 provinces of China, but there were regional differences in the timely coverage of some vaccine doses and the vaccination information consistency rate. It is necessary to strengthen the timely vaccination of children's vaccine booster doses and optimize the management of vaccination services.

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