BACKGROUND:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

BACKGROUND:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

The " liver disease affecting to the spleen" theory first appeared in Nanjing and was further elaborated in Jingui Yaolue. This theory encapsulates the traditional Chinese medicine principles of the " unity of the five viscera" and the " preventive treatment of disease" . The theory emphasizes that the spleen is the pivotal point where depression may progress from a functional disorder to an organic disease. The liver governs the emotions and qi flow, whereas the spleen is responsible for qi, blood, and body. In the early stages of the disease, emotional disorders and qi flow disorders primarily affect the liver, manifesting as depression or low mood. As the condition progresses, the liver (Wood) overacts on the spleen (Earth), disrupting liver and spleen functions and causing qi and blood disharmony. This stage is marked by fatigue and psychomotor retardation. Prolonged illness depletes qi and blood, eventually involving all five viscera, disrupting the harmony of the five spirits, and affecting both body and spirit. At this advanced phase, intense emotional distress or agitation often arises, accompanied by a heightened risk of suicide. The disease progression follows a dynamic " qi-blood-spirit" pattern, in which depression begins in the liver, characterized by qi stagnation, then affects the spleen, involving blood disharmony. In later stages, the disease eventually affects all viscera, with profound effects on both physical and mental health. Treatment strategies should align with the disease stage. Early intervention should focus on regulating the flow of qi, treating the liver, and strengthening the spleen. In the middle stages, qi and blood should be harmonized while promoting the harmonized functions of the liver and spleen. In the later stages, treatment should harmonize the five viscera to restore balance between body and spirit. Guided by this theory, integrating modern medical understanding of the progression of depression from emotional to somatic symptoms and adopting a stage-based approach to treatment in clinical practice can yield effective therapeutic outcomes for managing depression and related disorders.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO₂) (200 mg·mL^-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO₂ group, (2) SiO₂+negative control siRNA (siRNA-NC) group and SiO₂+Smurf2 gene silencing (si-Smurf2) group, (3) SiO₂+solvent (DMSO) group and SiO₂+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO₂+miR-NC group and SiO₂+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO₂-induced MLE-12 cells, compared to the control group, the SiO₂-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO₂, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO₂ group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in its early stages. Most patients are diagnosed at a locally advanced or metastatic stage. Systemic therapy has become the key to improve survival. To bridge the differences in guidelines across Asian countries and address regional clinical practice needs, 14 leading experts in the Asia-Pacific region developed the “Asian Consensus on systemic therapy for pancreatic ductal adenocarcinoma” on the Delphi method. The consensus centers on 14 core recommendations (R1-R14) and proposes stratified management strategies based on disease stage. For resectable PDAC, adjuvant modified FOLFIRINOX (mFOLFIRINOX) is the preferred option, while for the patients with poor performance status gemcitabine plus capecitabine, S-1 monotherapy, and other regimens can be selected. For borderline resectable PDAC, neoadjuvant therapy is recommended, with GnP or FOLFIRINOX as the preferred regimens. For locally advanced PDAC, combination or monochemotherapy is selected based on their performance status. For metastatic PDAC, first-line options include GnP, NALIRIFOX, or mFOLFIRINOX, with second-line therapy the cross-use of gemcitabine-based and 5-FU-based regimens are emphasized. This consensus provides for the first time a comprehensive and standardized management framework for systemic therapy of PDAC in Asia, aiming to enhance regional homogeneity in clinical practice and improve patient outcomes. This article interpreted the consensus content with the goal of guiding clinical practice.

Objective:To investigate the role of heat shock transcription factor 1(HSF1)in hepatitis B virus X protein(HBx)-driven migration and invasion of hepatocellular carcinoma(HCC)cells,and to preliminarily explore the mechanism of HSF1 mediating HBx-driven HCC progression.Methods:4D label-free quantitative proteomics and Western blot were used to analyze the effect of HBx on HSF1 expression.HBx was overexpressed in the HCC cell lines Huh7 and MHCC97H,and its impact on the mRNA and protein levels and stability of HSF1 was assessed by RT-PCR and Western blot.The Cancer Genome Atlas database was used to analyze the expres-sion of HSF1 in hepatitis B virus(HBV)-associated HCC tissues and its relationship with tumor stage/grade and patient prognosis,and Western blot was used to measure the expression of HSF1 in HBV-associated HCC tissues.HBx was overexpressed in HCC cells,fol-lowed by HSF1 knockdown or cell treatment with the HSF1 inhibitor KRIBB11,and Transwell migration and invasion assay,scratch as-say,and F-actin staining experiment were performed to analyze the role of HSF1 in HBx-driven HCC cell migration and invasion.GEO and HCMDB datasets were used to identify the downstream target of HSF1,and the role of downstream target c-Myb in HSF1-me-diated HBx-driven HCC progression.Results:HBx upregulated HSF1 protein levels without significantly affecting its mRNA expres-sion,through enhancing HSF1 protein stability.HSF1 was highly ex-pressed in HBV-associated HCC tissues,and its elevated expres-sion correlated with tumor stage/grade and poor prognosis.HBx overexpression significantly promoted the migration,invasion,wound-healing capacity,and pseudopodia formation capacity of Huh7 and MHCC97H cells,while HSF1 knockdown or KRIBB11 treatment significantly attenuated the HBx-driven migration and in-vasion of HCC.HSF1 promoted the expression of the metastasis-associated protein c-Myb,and c-Myb overexpression in HSF1-knock-down HCC cells restored the promotive effect of HBx on HCC cell migration and invasion.Conclusion:HBx enhances HSF1 protein stability to promote its expression.Upregulation of c-Myb by HSF1 plays a pivotal role in HBx-driven HCC cell migration and inva-sion.Targeting HSF1 may help to delay the progression of HBV-associated HCC.

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

Objective To explore the mechanism of the intervention effect of Qizhu Xiaozheng Fang(QZXZF),a representative prescription of Yiqi Jianpi Jiedu(replenishing qi,strengthening spleen,and removing toxicity),in treating HBx-mediated liver cancer stem cells(LCSCs).Methods The Kaplan-Meier survival analysis was used to investigate the effects of Yiqi Jianpi Jiedu on the prognosis of patients with HBV-HCC.The network pharmacology method was utilized to predict the targets and pathways of QZXZF in treating HBx-related LCSCs(HBx-LCSCs).HBx-LCSCs cells were screened by stably transfecting HBx and serum-free culture.The therapeutic effect of QZXZF on HBx-LCSCs was tested in vitro,and its effect on stemness markers and PI3K/Akt pathway was verified by qRT-PCR and Western blot.Results Yiqi Jianpi Jiedu could improve the overall survival time of HBV-HCC patients.Combined with the results of network pharmacology,the mechanism of action of QZXZF against HBx-LCSCs was explored from the PI3K/Akt pathway.Compared with the blank vector group,HBx can promote the expression of stemness markers in HBx-LCSCs cells;compared with the HBx-LCSCs control group,QZXZF could significantly inhibit the proliferation and colony formation of HBx-LCSCs cells(in a concentration-dependent manner),and could reduce the expression of stemness markers(EpCAM,NANOG,SOX2,and OCT4),phosphorylated PI3K(p-PI3K)and phosphorylated AKT(p-AKT)proteins.Conclusion QZXZF may regulate HBx-mediated LCSCs through PI3K/AKT pathways,providing a reference for the mechanism of TCM intervention in LCSCs.

Objectives:This study aims to explore the relationship between the pericoronary fat attenuation index(FAI)and triglyceride-glucose(TyG)index and atrial fibrillation recurrence after radiofrequency catheter ablation(RFCA)in patients with atrial fibrillation(AF).Methods:This retrospective study enrolled consecutive AF patients who underwent their first successful RFCA at the Affiliated Hospital of Xuzhou Medical University from 2019 to 2023.Pericoronary FAI was quantitatively measured,and the TyG index was calculated.Patients were divided into three groups according to the TyG index quartile:T1 group(TyG index<8.45,n=114);T2 group(8.45≤TyG index≤8.93,n=114);T3 group(TyG index>8.93,n=120).Linear regression was used to analyze the correlation between the TyG index and proximal FAI of three coronary arteries.Logistic regression was employed to explore the correlation between pericoronary FAI,TyG index,and AF recurrence post-RFCA,restrictive cubic splines(RCS)were plotted.Additive interaction and mediation analyses were used to explore the role of pericoronary FAI in the relationship between the TyG index and post-RFCA AF recurrence.Subgroup analysis was performed to explore the predictive value of the TyG index for postoperative recurrence in different patient subgroups.Results:A total of 348 patients were included.After adjusting for confounding factors using linear regression analysis,each unit increase in the TyG index was associated with a 5.389 HU increase in left circumfleex artery(LCX-FAI)(95%CI:3.874-6.904,P<0.001).During one-year follow-up,90 cases(25.86%)experienced AF recurrence.RCS analysis indicated that there was no significant nonlinear relationship between LCX-FAI,TyG index,and AF recurrence after RFCA(Pnon-linear=0.378,Pnon-linear=0.469).The recurrence rate of AF in patients with TyG index>9.08 and LCX-FAI>-83.65 HU was about 57.737 times higher than those with TyG index≤9.08 and LCX-FAI≤-83.65 HU(OR=57.737,95%CI:23.755-155.656,P<0.001).There was an additive interaction between the TyG index and LCX-FAI:relative excess risk due to interaction(RERI)was 50.901(95%CI:0.215-101.587),attributable proportion due to interaction(AP)was 0.882(95%CI:0.769-0.994),and the synergy index(S)was 9.713(95%CI:3.380-27.910).Mediation analysis indicated that LCX-FAI mediated 22%of the relationship between the TyG index and AF recurrence.Subgroup analysis revealed no multiplicative interaction between the type of atrial fibrillation and the TyG index in terms of AF recurrence risk(Pinteraction=0.562).Conclusions:In patients with atrial fibrillation,the TyG index is positively correlated with LCX-FAI,patients with TyG index>9.08 and LCX-FAI>-83.65 HU have significantly increased risk of AF recurrence after RFCA.LCX-FAI partially mediates the relationship between the TyG index and post-RFCA recurrence.Furthermore,the TyG index can effectively predict AF recurrence in both persistent and paroxysmal atrial fibrillation patients.