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.

Objective To analyze the clinical characteristics,laboratory test,imaging examination,and treatment outcome of invasive Klebsiella pneumoniae liver abscess syndrome(IKPLAS)in the elderly,and improve clinicians' understanding on this disease.Methods Clinical data of 7 elderly patients who were diagnosed with IKPLAS in a hospital from January 2020 to February 2024 were analyzed retrospectively.Results Among the 7 elderly patients with IKPLAS,there were 3 males and 4 females,ranging in age from 60 to 78 years old.All 7 patients were with community-acquired infection.The main clinical symptoms were fever(n=7),chills(n=6),upper abdominal pain(n=4),fatigue and poor appetite(n=3),cough and expectoration(n=5),vomiting(n=3),vision decrease(n=2),and disturbance of consciousness(n=1).All 7 patients had pathogenic evidence of Klebsiella pneumoniae(KP),including 4 cases with KP isolated from liver puncture pus,3 from blood culture,and 1 from both liver puncture pus and intraocular pus.Among the 7 patients,there were 5,2,1,3,1,1 cases combined with pulmonary abscess,endophthalmitis,brain abscess,bloodstream infection,urinary system infection,and pelvic infection,re-spectively.Conclusion Elderly patients with IKPLAS have a variety of underlying diseases and diverse clinical symptoms,showing no specificity.Once IKPLAS was suspected,timely testing for pathogen and screening for other metastatic infection sites outside the liver should be performed.Timely drainage of liver abscess and selection of ap-propriate antimicrobial agents for treatment based on antimicrobial susceptibility testing result can improve patients' survival rate.

Objective To analyze the clinical characteristics,laboratory test,imaging examination,and treatment outcome of invasive Klebsiella pneumoniae liver abscess syndrome(IKPLAS)in the elderly,and improve clinicians' understanding on this disease.Methods Clinical data of 7 elderly patients who were diagnosed with IKPLAS in a hospital from January 2020 to February 2024 were analyzed retrospectively.Results Among the 7 elderly patients with IKPLAS,there were 3 males and 4 females,ranging in age from 60 to 78 years old.All 7 patients were with community-acquired infection.The main clinical symptoms were fever(n=7),chills(n=6),upper abdominal pain(n=4),fatigue and poor appetite(n=3),cough and expectoration(n=5),vomiting(n=3),vision decrease(n=2),and disturbance of consciousness(n=1).All 7 patients had pathogenic evidence of Klebsiella pneumoniae(KP),including 4 cases with KP isolated from liver puncture pus,3 from blood culture,and 1 from both liver puncture pus and intraocular pus.Among the 7 patients,there were 5,2,1,3,1,1 cases combined with pulmonary abscess,endophthalmitis,brain abscess,bloodstream infection,urinary system infection,and pelvic infection,re-spectively.Conclusion Elderly patients with IKPLAS have a variety of underlying diseases and diverse clinical symptoms,showing no specificity.Once IKPLAS was suspected,timely testing for pathogen and screening for other metastatic infection sites outside the liver should be performed.Timely drainage of liver abscess and selection of ap-propriate antimicrobial agents for treatment based on antimicrobial susceptibility testing result can improve patients' survival rate.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To compare the feasibility and efficacy of translocator protein (TSPO) molecular probes N, N-diethyl-2-(2-(4- 18F-fluorophenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-FDPA) and 18F-(R)-( N-sec-butyl)-3-fluoromethyl- N-methyl-4-phenylquinoline-2-carboxamide (LW223) for the detection of abdominal vulnerable atherosclerotic plaques (VAP) in rabbit models. Methods:Nine healthy New Zealand white rabbits were divided into group A (control group, n=3), group B (VAP group, n=3) and group C (VAP treatment group, n=3) using completely randomized design. Animals were injected with 18F-FDPA and 18F-LW223 at the end of 12, 16 and 24 weeks. PET/CT and CT angiography (CTA) was performed 40-50 min post injection. All rabbits were sacrificed at the end of 24 weeks after imaging studies. All abdominal aortas were collected for pathological and immunofluorescence examination. Repeated measures analysis of variance (Bonferroni test) and paired t-test were used to analyze the data. Results:Target-to-background ratio (TBR; abdominal aortic lesion/left ventricular blood pool) values of 18F-FDPA in 3 groups at the end of 12, 16 and 24 weeks were significantly different ( F values: 68.09-144.88, all P<0.001). At the end of 12 weeks, there was no increased uptake of 18F-FDPA in the abdominal aorta region in 3 groups. The local 18F-FDPA uptake of the abdominal aorta in group B was significantly higher than the uptake in group C and that in group A at the end of 16 and 24 weeks( P<0.05 or P<0.001), and there were significant differences between group C and group A, with higher uptake in group C (both P<0.01). In 3 groups, there was no significant 18F-LW223 uptake in the abdominal aorta region at 3 time points of PET/CTA imaging. At the end of 12, 16 and 24 weeks, TBR values of 18F-FDPA and 18F-LW223 in 3 groups exhibited statistical differences ( t values: 2.88-36.79, all P<0.05). HE, immunofluorescent CD68 and TSPO staining showed more macrophage infiltration in group B than group C. Conclusion:18F-FDPA can be used to detect VAP in rabbits′ abdominal arteries at early time compared to 18F-LW223, and to evaluate the changes in the stability of vulnerable plaque after lipid-lowering drug intervention.

AIM: To explore the key genes and molecular markers involved in the retinoblastoma development through bioinformatics.METHODS: The mRNA microarray datasets from the Gene Expression Omnibus(GEO)database were obtained, and the differentially expressed gene(DEG)between retinoblastoma cell lines and normal retinal pigment epithelial(RPE)cell lines were analyzed through gene ontology(GO)and KEGG enrichment analysis. To screen key genes, establish protein-protein interaction(PPI)network, and use receiver operating characteristic(ROC)curve to assess clinical diagnostic efficacy. The RNA expressions of key genes in retinoblastoma cell lines and normal RPE cell lines were compared by qRT-PCR.RESULTS: A total of 121 DEGs were obtained from the retinoblastoma dataset of GSE97508 and GSE110811. KEGG pathway analysis showed that DEG were enriched in phototransduction, cell cycle, and p53 signaling pathways. A total of 9 key genes, including MCM6, DTL, UBE2T, TOP2A, NUSAP1, CENPK, RRM2, RLBP1, and RHO, were obtained from the intersection of PPI network analysis and the top 30 DEG from each dataset. The differentially expressed 9 key genes were verified in GSE24673. ROC analysis showed that the area under the curve(AUC)for UBE2T, RRM2, and RHO was ≥80%, and there was a statistical significance(P>0.05). The mRNA level of UBE2T and RRM2 in retinoblastoma was significantly higher than APRE-19 cell line, while the mRNA level of RHO was significantly lower than that of ARPE-19 cell line.CONCLUSION: UBE2T, RRM2, and RHO may be served as potential molecular markers and potential therapeutic targets for retinoblastoma.

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by ^99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with ¹⁸F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with ¹⁸F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and ¹⁸F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and ¹⁸F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.
Male ; Humans ; Middle Aged ; Aged ; Stroke Volume ; Heart Failure ; Fluorodeoxyglucose F18 ; Retrospective Studies ; Reproducibility of Results ; Prospective Studies ; Coronary Artery Bypass ; Ventricular Dysfunction, Left ; Tomography, Emission-Computed, Single-Photon ; Perfusion ; Myocardium

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

Objective: To construct chimeric antigen receptor (CAR) T cells targeting CD52 (CD52 CAR-T) and validate the effect of CD52 CAR-T cells on CD52-positive leukemia. Methods: A second-generation CD52-targeting CAR bearing 4-1BB costimulatory domain was ligated into a lentiviral vector through molecular cloning. Lentivirus was prepared and packaged by 293 T cells with a four-plasmid system. Fluorescein was used to label cell surface antigens to evaluate the phenotype of CD52 CAR-T cells after infection. Flow cytometry and ELISA were used to evaluate the specific cytotoxicity of CD52 CAR-T cells to CD52-positive cell lines in vitro. Results: ①A pCDH-CD52scFv-CD8α-4-1BB-CD3ζ-GFP expressing plasmid was successfully constructed and used to transduce T cells expressing a novel CD52-targeting CAR. ②On day 6, CD52-positive T cells were almost killed by CD52-targeted CAR-T post lentivirus transduction [CD52 CAR-T (4.48 ± 4.99) %, vs Vector-T (56.58±19.8) %, P=0.011]. ③T cells transduced with the CAR targeting CD52 showed low levels of apoptosis and could be expanded long-term ex vivo. ④The CD52 CAR could promote T cell differentiation into central and effector memory T cells, whereas the proportion of T cells with a CD45RA(+) effector memory phenotype were reduced. ⑤CD52 CAR-T cells could specifically kill CD52-positive HuT78-19t cells but had no killing effect on CD52-negative MOLT4-19t cells. For CD52 CAR-T cells, the percentage of residual of HuT78-19t cells was (2.66±1.60) % at an the E:T ratio of 1∶1 for 24 h, while (56.66±5.74) % of MOLT4-19t cells survived (P<0.001) . ⑥The results of a degranulation experiment confirmed that HuT78-19t cells significantly activated CD52 CAR-T cells but not MOLT4-19t cells[ (57.34±11.25) % vs (13.06± 4.23) %, P<0.001]. ⑦CD52 CAR-T cells released more cytokines when co-cultured with HuT78-19t cells than that of vector-T cells [IFN-γ: (3706±226) pg/ml, P<0.001; TNF-α: (1732±560) pg/ml, P<0.01]. Conclusions: We successfully prepared CD52 CAR-T cells with anti-leukemia effects, which might provide the foundation for further immunotherapy.
CD52 Antigen ; Cell Line, Tumor ; Humans ; Immunotherapy, Adoptive/methods* ; Lentivirus/genetics* ; Leukemia ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen/genetics*