Plant-derived extracellular vesicles (PDEVs) are nanoscale extracellular vesicles secreted by plant cells, characterized by a lipid bilayer structure. These vesicles carry a variety of bioactive molecules, including proteins, nucleic acids, and lipids, and play essential roles in intercellular communication and physiological regulation in plants. Compared to animal-derived extracellular vesicles, PDEVs offer several advantages, such as a broad range of sources, high biocompatibility, low immunogenicity, and low production costs. Furthermore, PDEVs have demonstrated remarkable potential as natural nanocarriers for drug delivery, due to their ability to efficiently traverse biological barriers, such as the blood-brain barrier, making them promising candidates for drug delivery systems. This review systematically elaborates on the complex composition of PDEVs, which consists of lipids, proteins, and nucleic acids, the typical structural characteristics of their lipid bilayers ranging from 30 to 150 nm, and their versatile loading capabilities as drug carriers, efficiently encapsulating various types of therapeutic agents such as hydrophilic small molecules, hydrophobic drugs, nucleic acids, and proteins. We systematically summarize the recent advancements in strategies for enhancing the loading efficiency of PDEVs, which include methods such as co-incubation, ultrasound-assisted loading, electroporation, freeze-thaw cycles, and microfluidic technology. These techniques are evaluated based on their underlying principles, suitable drug types, and their respective advantages. In addition to loading strategies, we focus on the engineered approaches to achieve targeted delivery using PDEVs, such as genetic engineering modifications, chemical ligand conjugation, membrane fusion technology, and polyethylene glycol (PEG) modification. We discuss the mechanisms of these strategies in enhancing targeting efficiency, prolonging in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.

Objective To construct and evaluate a prognostic model for clear cell renal cell carcinoma(ccRCC)based on preoperative lipid ratios, cM0(i+)staging, and other clinical characteristics, so as to provide a precise tool for clinical prognosis assessment. Methods A retrospective analysis was conducted on the clinical data of 215 ccRCC patients treated in our hospital during May 2014 and May 2023. Lipid ratios were calculated using preoperative lipid data, and patients were divided into cM0(i+)stage or cM0 stage according to postoperative circulating tumor cells(CTCs)test results. The optimal lipid ratio and cutoff value were selected using receiver operating characteristic(ROC)curves and the X-tile method. Patients were subdivided into three groups based on the level of the low-density lipoprotein cholesterol to non-low-density lipoprotein cholesterol ratio(LNLR)and cM0(i+)staging:Group A [LNLR＞1.68 and diagnosed with cM0(i+)], Group B [LNLR＞1.68 or diagnosed with cM0(i+)], and Group C(LNLR ≤1.68 and diagnosed with cM0). Kaplan-Meier survival analysis was used to plot survival curves for patients in different groups. The log-rank test was employed to compare differences in recurrence-free survival(RFS)among the subgroups. Multivariate Cox regression analysis was conducted to identify the independent risk factors influencing RFS, and a nomogram prediction model was constructed based on these results. The predictive performance of the model was validated using ROC curves, calibration curves, and decision curves. Results ROC curves were plotted for lipid markers, and LNLR was identified as the most predictive for RFS. Its optimal cutoff point was 1. 68. Patients in Group A experienced a significantly shorter postoperative RFS. Multivariate Cox regression analysis identified preoperative LNLR, cM0(i+)staging, pathological grade, and stage as independent risk factors for RFS. A nomogram model was constructed based on these risk factors. The area under the ROC curve(AUC)for 1-, 3-, and 5-year RFS was 0.896(95% CI:0.8121-0.9627), 0.890(95%CI:0.7879-0.9641), and 0.870(95%CI:0.7697-0.9526), indicating good discriminatory ability and predictive performance. Calibration plots demonstrated good agreement between predicted and actual outcomes. Clinical decision curve analysis showed high clinical net benefit. Conclusion Preoperative LNLR level is an independent risk factor for RFS in ccRCC patients. The prognostic prediction model based on LNLR, cM0(i+)staging, patient pathological grade, and staging demonstrates good predictive performance for RFS and holds potential clinical application value.

Objective To observe the clinical efficacy of mind-regulating and meridians-dredging acupuncture combined with rehabilitation training in treating limb dysfunction in recovery period of cerebral infarction(CI).Methods A total of 110 cases of patients with limb dysfunction in recovery period of CI were randomly divided into observation group and control group,55 cases in each group,the control group was given routine rehabilitation training,and the observation group was treated with mind-regulating and meridians-dredging acupuncture on the basis of intervention of the control group,the course of treatment covered two consecutive weeks.After two weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of scores of traditional Chinese medicine(TCM)syndrome,Fugl-Meyer Assessment(FMA),Berg Balance Scale(BBS)and Modified Barthel Index(MBI)before and after treatment of patients in the two groups were observed.The changes of electromyographic signal before and after treatment were compared between the two groups.And the safety and the occurrence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate was 98.18%(54/55)in the observation group and 87.27%(48/55)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(3)After treatment,the FMA scores of patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the BBS scores and MBI scores of the patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the root mean square value(RMS)of biceps brachii muscle elbow flexion and triceps brachii muscle elbow extention of the two groups of patients improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(6)During the treatment,there were no obvious adverse reactions occurred in both groups.Conclusion Mind-regulating and meridians-dredging acupuncture combined with rehabilitation training in treating limb dysfunction in recovery period of CI can significantly improve the motor ability of patients,and adjust the electromyographic signals of the affected limbs,with high safety.

During long-duration space missions,astronauts face health challenges such as bone density loss,muscle atrophy,cardiovascular dysfunction,immune function suppression caused by microgravity,as well as mental health issues in a confined environment.There is an urgent need for real-time,continuous,and multi-dimensional health monitoring technologies to safeguard the health and safety of astronauts.This paper systematically reviews the technical requirements and current development status of astronaut on-orbit health monitoring,with a focus on analyzing breakthroughs in technologies such as dynamic electrocardiography,non-invasive blood pressure assessment,flexible electronic skin,and molecular probe spectroscopy.It also elaborates on how the integration of artificial intelligence and bionics technologies is propelling the monitoring system towards intelligence and autonomy,providing a reference for the medical support of astronauts during long-duration spaceflight missions.

Objective:To investigate the effects of cerebellar intermittent theta burst stimulation(iTBS)combined with ex-ercise therapy on balance and walking function in stroke patients.Method:Sixty stroke patients with balance and gait disturbances were randomly assigned to an experimental group(n=30)and a control group(n=30).Both groups received exercise therapy.Before exercise therapy,the experimental group received iTBS treatment on the cerebellar hemisphere contralateral to the lesion,while the control group received sham stimulation at the same site.iTBS treatment was administered once daily,6 times a week,for 2 consecutive weeks.The balance and gait functions were evaluated before and after treatment us-ing the Berg balance scale(BBS),Pro-kin balance master static balance test,Timed Up and Go Test(TUGT),10-meter walking test(10MWT),and Tinetti performance oriented mobility assessment-gait(Tinetti POMA-G).Result:After treatment,both groups of patients showed improvements in BBS scores,Pro-kin balance master static balance test parameters,TUGT time,10MWT walking speed,and POMA-G scores compared to before treatment(P＜0.001).The experimental group showed better BBS scores,Pro-kin balance master static balance test parameters in eyes closed condition,TUGT time,10MWT walking speed,and Tinetti POMA-G scores compared to the control group after treatment(P＜0.05).Conclusion:The combination of cerebellar iTBS and exercise therapy effectively improve balance and walking function in stroke patients.

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

OBJECTIVE: To investigate hypertension (HTN) trends, key risk factors, and gender disparities in rural China, and to propose targeted strategies for improving HTN control in resource-limited settings. METHODS: This longitudinal study used data from the Henan Rural Cohort Study, including baseline (2015-2017; n = 39,224) and follow-up (2018-2022; n = 28,621) participants. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg, self-reported diagnosis, or use of antihypertensive medication. Severity was classified using a 7-tier blood pressure (BP) staging system (optimal, normal, high normal, and HTN stages 1-4). A generalized linear mixed-effects model (GLMM) identified associated risk factors. RESULTS: HTN prevalence increased modestly from 32.7% (95% CI: 32.2-33.2) to 33.9% (95% CI: 33.3%-34.4%). Awareness and treatment improved from 20.1% to 25.3%, and from 18.8% to 24.4%, respectively, but control rates remained low (6.2% to 12.3%). After adjustment, women had a 1.53-fold higher HTN risk than men ( OR = 1.53, 95% CI: 1.43-1.63), revealing gender-specific trends. Key risk factors included alcohol use ( OR = 1.37, 95% CI: 1.27-1.47) and overweight status ( OR = 1.76, 95% CI: 1.66-1.86). BP staging showed an increase in optimal BP (42.3% to 45.8%), but stagnant management of advanced HTN stages. CONCLUSION Hypertension in rural China is shaped by behavioral risk factors and healthcare access gaps. Gender-sensitive, community-based interventions, including task-shifting models, are necessary to mitigate the growing burden of hypertension.
Humans ; Hypertension/etiology* ; China/epidemiology* ; Female ; Male ; Rural Population/statistics & numerical data* ; Prevalence ; Risk Factors ; Middle Aged ; Adult ; Aged ; Longitudinal Studies ; Sex Factors ; Cohort Studies ; East Asian People

Objective To explore the clinical and pathological characteristics of middle-aged and elderly patients with pulmonary ciliated muconodular papillary adenoma(CMPA).Methods Clinical and pathological data as well as follow-up information of 6 middle-aged and elderly patients with CMPA were collected and or-ganized.Tumor tissue samples were observed,and HE staining and immunohistochemical analysis were per-formed on the slices.Results The age range of onset for 6 patients was 55-74 years old,with a median age of 65 years old,and a male to female ratio of 1∶5.In terms of lesion location,there were 2 cases in the left lung and 4 cases in the right lung.CT scan showed that the tumor presents as ground glass nodules or single round solid nodules,with short spikes visible at the edges of some nodules.All patients underwent wedge resection of lung tissue for treatment.Histologically,tumors consist of a bilayer cell structure consisting of luminal epi-thelial cells(including ciliated cells and mucinous cells)and basal cells,forming an glandular or papillary mor-phology.Mucus deposition could be observed within and around the cavity.Immunohistochemical results showed that all cells expressed thyroid transcription factor-1(TTF-1)positively,focal positive expression of aspartic protease A(Napsin A),and no expression of cytokeratin 20(CK20);Basal cells expressed p63 and CK5/6,with lower expression of Ki-67.Molecular testing did not detect any clear gene mutations.Conclusion CMPA has a biological behavior that is either benign or low-grade malignant,and has a good prognosis.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men, the incidence of which gradually increases with age and leads to lower urinary tract symptoms (LUTS), which seriously affects the quality of life of patients. Chinese herbal medicines (CHMs) are widely used for the treatment of BPH in China and some other countries. To explore the molecular mechanisms of CHMs for BPH, we conducted a review based on peer-reviewed English-language publications in PubMed and Web of Science databases from inception to December 31, 2023. This article primarily reviewed 32 papers on the use of CHMs and its active compounds in the treatment of BPH, covering animal and cell experiments, and identified relevant mechanisms of action. The results suggest that the mechanisms of action of CHMs in treating BPH may involve the regulation of sex hormones, downregulation of cell growth factors, anti-inflammatory and antioxidative effects, inhibition of cell proliferation, and promotion of apoptosis. CHMs also exhibit α-blocker-like effects, with the potential to relax urethral smooth muscle and alleviate LUTS. Additionally, we also reviewed 4 clinical trials and meta-analyses of CHMs for the treatment of BPH patients, which provided initial evidence of the safety and effectiveness of CHMs treatment. CHMs treatment for BPH shows advantages as a multi-component, multi-target, and multi-pathway therapy, which can mitigate the severity of the disease, improve LUTS, and may become a reliable treatment option in the future.
Prostatic Hyperplasia/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Male ; Animals