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.

Objective To explore the application value of dual-phase dual-energy CT (DECT) perfusion imaging in preoperative lung function assessment of lung cancer patients. Methods Data were collected from patients with stageⅠA non-small cell lung cancer who underwent surgical treatment in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2022 to June 2024. All patients underwent DECT perfusion imaging and pulmonary function testing (PFT) before surgery. PFT observation indicators included ventilation function indicators such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), 1-second rate (FEV1/FVC), maximal voluntary ventilation (MVV), and diffusion function indicators such as diffusing capacity for carbon monoxide (DLCO) and DLCO per liter of alveolar volume (DLCO/VA). The software eXamine was used to obtain quantitative parameters of DECT perfusion imaging, including volume parameters and perfusion parameters of both lungs and each lung lobe. The correlation between the volume parameters and perfusion parameters of both lungs and the ventilation and diffusion function indicators of the patients, as well as the differences in quantitative parameters of each lung lobe, was analyzed. Results The end-inspiration lung volume and biphasic volume difference were strongly positively correlated with FEV1 and FVC (r=0.636, r=0.682, r=0.614, r=0.624, P<0.001) and moderately positively correlated with MVV and DLCO (r=0.499, r=0.514, r=0.549, r=0.447, P<0.001); the end-expiration lung volume was weakly negatively correlated with DLCO/VA (r=−0.295, P=0.026); the volume ratio was positively correlated with FEV1, FVC, MVV, and MVV% (r=0.424, r=0.399, r=0.415, r=0.310, P<0.05); the end-inspiration iodine content was weakly positively correlated with DLCO/VA% (rs=0.292, P=0.030); the end-expiration iodine content was weakly positively correlated with FEV1, FVC, MVV, DLCO%, and DLCO/VA (r=0.307, r=0.299, r=0.295, r=0.366, r=0.320, P<0.05) and moderately positively correlated with DLCO (r=0.439, P<0.001); the end-inspiration iodine concentration was negatively correlated with FEV1, FVC, MVV, and MVV% (rs=−0.407, rs=−0.426, rs=−0.352, rs=−0.277, P＜0.05); the end-expiratory phase iodine concentration was moderately positively correlated with DLCO/VA (r=0.403, P=0.002); both the iodine concentration difference and the iodine concentration ratio were moderately positively correlated with FEV1, FEV1%, FVC, MVV, MVV% (P<0.05). The lung volume and iodine concentration ratio values were both highest in the left upper lung lobe and lowest in the right middle lung lobe; the differences in lung volume, lung volume ratio, intrapulmonary iodine content, and intrapulmonary iodine concentration were all highest in the lower lobes of both lungs and lowest in the middle lobe of the right lung. Conclusion Dual-phase DECT perfusion imaging can accurately assess overall lung function and quantify regional lung function.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

BACKGROUND:Cellular pyroptosis is an important pathological mechanism of cerebral ischemia/reperfusion injury.Buyang Huanwu Tang is a classic formula for the clinical treatment of ischemic stroke in traditional Chinese medicine,and cellular pyroptosis may be an effective target of Buyang Huanwu Tang in the treatment of cerebral ischemia/reperfusion injury.OBJECTIVE:To observe the effect and mechanism of Buyang Huanwu Tang on pyroptosis in brain tissues of middle cerebral artery occlusion/reperfusion rats.METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,model group,Astragalus membranaceus group and Buyang Huanwu Tang group.Except for the sham operation group,all groups were subjected to middle cerebral artery occlusion for ischemia for 2 hours and reperfusion for 72 hours.The rats in the Astragalus membranaceus group and Buyang Huanwu Tang group were continuously gavaged with the corresponding volume of drugs until ischemia and reperfusion for 72 hours after awakening from the modeling,once in the morning and once in the evening.Zea Longa score was used to observe the neurological deficits of rats.TTC staining was performed to observe cerebral infarct size in rats.Hematoxylin-eosin staining was used to observe the pathological changes of the brain tissue.Immunofluorescence was used to observe the co-expression of Tunel and Cleaved-Caspase-1 in the brain tissue and the expression of the junction protein ASC.Immunohistochemistry and western blot were used to detect the expression of pyroptosis-related proteins in rat brain tissues.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the neurological deficit score of rats was significantly higher in the model group(P<0.01),and compared with the model group,the neurological deficit score of rats was significantly lower in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).(2)Compared with the model group,the volume ratio of cerebral infarction was lower in the Astragalus membranaceus group and Buyang Huanwu Tang group(P<0.01).(3)In the model group,the nuclei of neuronal cells in the brain tissue were deeply stained or lysed,and arrangement of the cells was disorganized.Compared with the model group,the pathologic damage of the brain was less severe in the Buyang Huanwu Tang group and the Astragalus membranaceus group.(4)Compared with the sham operation group,the number of Tunel and Cleaved-Caspase-1 double-positive cells and immunofluorescence intensity of ASC in the brain tissue was significantly increased in the model group,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β was significantly elevated in the model group(P<0.01).Compared with the model group,the number of Cleaved-Caspase-1 and Tunel double-positive cells,immunofluorescence intensity of ASC,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β were all significantly decreased in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).The results indicate that Buyang Huanwu Tang and its monarch drug Astragalus membranaceus can effectively alleviate brain tissue injury in rats with middle cerebral artery occlusion and reperfusion,and its mechanism may be related to the inhibition of neuronal cell pyroptosis.

Objective:To explore the clinical efficacy of coiling dragon needling plus chin tuck against resistance(CTAR)training for post-stroke deglutition disorders and its impact on surface electromyography.Methods:A total of 100 patients with post-stroke deglutition disorders were randomly divided into two groups,with 50 cases in each group.Both groups received the same CTAR training,and the observation group was treated with additional coiling dragon needling.Both groups were treated for 2 weeks.The clinical efficacy,swallowing function,average value of the maximum amplitude of surface electromyography,quality of life,and the difference in adverse reactions were compared between the two groups.Results:The total effective rate of the observation group was higher than that of the control group(P<0.05).After treatment,the standardized swallowing assessment(SSA),aspiration score,and deglutition disorders score of the videofluoroscopic swallowing study(VFSS)in both groups were significantly lower than those before treatment(P<0.05).The average value of the maximum amplitude of surface electromyography in the relaxed state,dry swallowing state,and the state of swallowing water,and the swallowing quality of life questionnaire(SWAL-QOL)score were all significantly higher than those before treatment in the two groups(P<0.05).After treatment,the SSA score,VFSS aspiration score,and VFSS deglutition disorders score in the observation group were lower than those in the control group(P<0.05),and the average value of the maximum amplitude of surface electromyography in the relaxed state,dry swallowing state,and the state of swallowing water,and the SWAL-QOL score in the observation group were higher than those in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Compared to CTAR treatment alone,coiling dragon needling plus CTAR treatment can enhance the clinical efficacy in treating patients with post-stroke deglutition disorders,enhancing the contraction ability of swallowing muscles and improving their swallowing function and quality of life.

Hyperemesis gravidarum(HG)refers to persistent and severe nausea and vomiting during early pregnancy.Severe HG may lead to maternal dehydration,electrolyte imbalances,malnutrition,and even hypotension and arrhythmias,potentially affecting fetal growth and development.Due to the unique physiological state of pregnancy,treatment options for HG are limited.Metoclopramide,has become a commonly used drug in treating HG due to its prove efficacy and safety.Previous studies have primarily focused on the extrapyramidal side effects of metoclopramide,but research on its psychiatric adverse effects,such as mania and somnolence,remains limited,particularly in pregnant patients.This paper reports a case of psychiatric abnormalities in an HG patient following metoclopramide administration.By analyzing the patient's condition,medication use,and adverse reactions,this study explores the potential mechanisms underlying metoclopramide-induced psychiatric abnormalities and provides clinical recommendations for preventing and managing such psychiatric adverse effects during pregnancy.These findings offer valuable guidance for healthcare professionals regarding the appropriate use of this medication.

Objective:To develop a self-efficacy scale of milk donation and test its reliability and validity, in order to provide a scientific evaluation tool for the corresponding study.Methods:According to Bandura′s self-efficacy theory and consensus-based standards for the selection of health measurement instruments, the scale was developed by means of literature search, article pool establishment and expert letter consultation. A pre-survey was conducted on 30 newborn bereaved women, a formal investigation was conducted on 231 newborn bereaved women, and 115 newborn bereaved women were selected for exploratory factor analysis. Confirmatory factor analysis was performed on 116 parturients with neonatal loss to determine the reliability and validity of the scale.Results:The final scale includes 3 dimensions and 13 items. Three common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 77.962%. A scale with three dimensions, included breast milk donation resilience, breast milk donation cognition and breast milk donation motivation, and 13 items was determined. Confirmatory factor analysis showed that the model fit of the scale was good ( χ2/ df = 1.390, RMSEA = 0.063, RMR = 0.046, NFI = 0.924, NNFI = 0.971, GFI = 0.924, CFI = 0.977). The content validity index was 0.835. Cronbach′s α coefficient of the total volume table was 0.919, and the coefficients of each dimension were 0.892, 0.905 and 0.844, respectively. The broken half reliability of the scale was 0.893, and the broken half reliability of each dimension was 0.857, 0.881 and 0.711, respectively. The retest reliability of the scale was 0.814, and the retest reliability of each dimension was 0.803, 0.825 and 0.767, respectively. Conclusions:The scale has good reliability and validity, and can be used to evaluate the self-efficacy of milk donation in lost newborns.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. METHODS: Four patients diagnosed with PMS at Guangzhou Women and Children's Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Hospital (Ethics No. 2025-007). RESULTS: All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 Kb to 112.64 Kb, primarily involving the SHANK3 gene. CONCLUSION PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.
Child ; Humans ; Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 22/genetics* ; Exome Sequencing ; Nerve Tissue Proteins/genetics* ; Phenotype