Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

OBJECTIVES: To investigate the inhibitory effect of Zheng GanDecoction (ZGF) on tumor progression in a rat model of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and explore the possible mechanism. METHODS: Seventy SD rats were subjected to regular intraperitoneal injections of DEN (50 mg/kg) for 12 weeks to induce HCC tumorigenesis, with another 10 rats receiving saline injections as the normal control. After successful modeling, the rats were randomized into 5 groups (n=10) for daily treatment with distilled water ( model group), Huaier Granules (4 g/kg; positive control group), or ZGF at low, medium, and high doses (2, 4, and 8 g/kg, respectively) via gavage for 17 weeks. Body weight changes of the rats were monitored, and after completion of the treatments, the rats were euthanized for measurement of liver, spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining. The expressions of YAP, p-YAP, MST1, LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting. RESULTS: Compared with the normal control rats, the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate, increased body weight and liver and spleen indices, and a lowered thymus index. ZGF treatment obviously reduced liver and spleen indices, increased the thymus index, and improved pathologies of the liver tissues of the rat models. Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats, which also exhibited significantly upregulated hepatic expressions of MST1, LATS1 and p-LATS1. CONCLUSIONS ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression, which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Diethylnitrosamine ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Protein Serine-Threonine Kinases/metabolism* ; Carcinoma, Hepatocellular/drug therapy* ; YAP-Signaling Proteins ; Liver Neoplasms/drug therapy* ; Hippo Signaling Pathway ; Male ; Liver Neoplasms, Experimental/metabolism* ; Transcription Factors/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

Objectives:To assess the situation of retained cardiac implantable electronic device(CIED)leads after cardiac transplantation,the associated factors,and their impact on long-term prognosis.Methods:A retrospective analysis was conducted on 1 096 patients who underwent cardiac transplantation at Fuwai Hospital of the Chinese Academy of Medical Sciences from January 1,2005 to January 1,2022.Among them,204 patients(18.6%)received CIED therapy before cardiac transplantation.Two physicians independently reviewed the pre-and post-transplant chest X-rays to determine the presence of retained CIED leads.Logistic multivariate regression analysis was used to assess factors associated with retained CIED leads,and Kaplan-Meier survival curves were plotted to analyze the impact of retained CIED leads on long-term prognosis.Results:Among the 204 patients who received CIED therapy before cardiac transplantation,the highest proportion were those treated with implantable cardioverter defibrillator(ICD)and cardiac resynchronization therapy-defibrillator(CRT-D),accounting for 47.5%(97/204)and 40.7%(83/204),respectively.The mean duration from CIED implantation to cardiac transplantation was(45.1±40.0)months,and 38 patients(18.6%)had retained CIED leads after cardiac transplantation.The results of the logistic multivariate regression analysis showed that the duration from CIED implantation to cardiac transplantation was the only factor associated with retained CIED leads after cardiac transplantation(OR=1.020,95%CI:1.011-1.030,P=0.000).Cumulative all-cause survival rates among patients without CIED implantation(n=892),those without retained CIED leads(n=166),and those with retained CIED leads(n=38)were 88.5%,93.3%and 84.2%,respectively.Kaplan-Meier survival curve analysis showed no significant difference in cumulative all-cause survival among the three groups(log-rank P=0.643).Conclusions:In patients who received CIED implantation before cardiac transplantation,18.6%had retained leads after surgery.The duration from CIED implantation to cardiac transplantation is the only factor associated with lead retained after cardiac transplantation,but retained leads does not affect the outcome post heart transplantation.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective:This study aims to initially establish a scoring system for comprehensively reflecting the severity of intracranial atherosclerotic lesions and to explore the correlation between this score and atherosclerotic risk factors as well as stroke events.Methods:This study retrospectively analyzed patients who underwent head and neck computer tomography angiography(CTA)examinations and had head MRI examinations within one month before or after the CTA examination from January 2021 to August 2024 in Beijing Hospital.An intracranial atherosclerosis disease score(ICADS)system was constructed based on the degree and number of vascular stenosis.The relationship between ICADS and atherosclerotic risk factors was explored by grouping patients according to the quartile of ICADS.Patients were divided into acute stroke group and non-acute stroke group to compare differences in ICADS and cerebrovascular disease risk factors between the two groups, and to investigate the correlation between stroke events and ICADS.Results:There were statistically significant differences in the proportions of patients with hypertension and diabetes among different ICADS groups.Multiple linear regression analysis showed that hypertension( B=1.17, 95% CI: 0.20-2.14, P<0.05)and diabetes( B=2.75, 95% CI: 1.85-3.64, P<0.001)were risk factors for higher ICADS.The ICADS was higher in the acute stroke group than in the non-acute stroke group(9 vs.6, P<0.001), and a higher ICADS was identified as a risk factor for stroke( OR=1.10, 95% CI: 1.07-1.14, P<0.001). Conclusions:ICADS can comprehensively reflect the severity of intracranial atherosclerotic lesions and is correlated with stroke events, making it useful for clinical screening of high-risk patients for stroke.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective To investigate the inhibitory effect of Zheng Gan Decoction(ZGF)on tumor progression in a rat model of diethylnitrosamine(DEN)-induced hepatocellular carcinoma(HCC)and explore the possible mechanism.Methods Seventy SD rats were subjected to regular intraperitoneal injections of DEN(50 mg/kg)for 12 weeks to induce HCC tumorigenesis,with another 10 rats receiving saline injections as the normal control.After successful modeling,the rats were randomized into 5 groups(n=10)for daily treatment with distilled water(model group),Huaier Granules(4 g/kg;positive control group),or ZGF at low,medium,and high doses(2,4,and 8 g/kg,respectively)via gavage for 17 weeks.Body weight changes of the rats were monitored,and after completion of the treatments,the rats were euthanized for measurement of liver,spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining.The expressions of YAP,p-YAP,MST1,LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting.Results Compared with the normal control rats,the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate,increased body weight and liver and spleen indices,and a lowered thymus index.ZGF treatment obviously reduced liver and spleen indices,increased the thymus index,and improved pathologies of the liver tissues of the rat models.Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats,which also exhibited significantly upregulated hepatic expressions of MST1,LATS1 and p-LATS1.Conclusion ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression,which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.

AIM To study the chemical constituents from the stems and leaves of Dendrobium formosum Roxb.ex Lindl.and their biological activities.METHODS The 95％ethanol extract from the stems and leaves of D.formosum was isolated and purified by silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their inhibitory activities onα-glucosidase were determined by PNPG method,and their in vitro anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Fifteen compounds were isolated and identified as coniferyl p-coumarate(1),(-)-pinoresinol(2),2,5,7-trihydroxy-4-methoxy-9,10-dihydrophenanthrene(3),naringenin(4),spiropreussomerin A(5),7-hydroxy-14-de-O-methyl-lasiodiplodin(6),(4S,5S,6Z,8E)-5-hydroxydeca-6,8-dien-4-olide(7),(6S,9R)-blumenol C(8),p-hydroxybenzoic acid(9),m-hydroxybenzoic acid(10),p-hydroxy benzenepropanoic acid(11),5,7-dihydroxy-isobenzofuran(12),2-(4-hydroxyphenyl)-ethanol(13),β-sitostenone(14),β-sitosterol(15).The IC50 values of compounds 1 and 4 on α-glucosidase inhibition were(65.60±3.31)and(98.95±2.53)μmol/L,respectively.Compound 3 presented inhibitory activity on NO production in RAW 264.7 cells,with IC50 value of(3.97±0.12)μmol/L.CONCLUSION Compounds 5-6,8 and 12 are isolated from Orchidacae family for the first time,and 2-15 are first isolated from this plant.Compounds 1 and 4 have α-glucosidase inhibitory activities,and 3 has anti-inflammatory activity.