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.

Objective: To investigate the protective effects of Gouqizi (Lycii Fructus, GQZ)-Danshen (Salviae Miltiorrhizae Radix et Rhizoma, DS) against hydrogen peroxide (H2O2)-induced oxidative injury in 661W retinal photoreceptor cells and to explore whether these effects involve angiopoietin-like 4 (ANGPTL4). Methods: Liquid chromatography-mass spectrometry (LC-MS) was used to identify the major components of GQZ-DS aqueous extract. An H2O2-induced oxidative injury model was established in 661W cells. Working concentrations of H2O2 and GQZ-DS were determined using the cell counting kit-8 (CCK-8) assay. Cells were subjected to GQZ-DS, ANGPTL4 knockdown, or ANGPTL4 overexpression as indicated. Flow cytometry was used to analyze cell cycle distribution, apoptotic rate, and intracellular reactive oxygen species (ROS). Colorimetric determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity using the thiobarbituric acid (TBA) method was performed. The protein expression level of ANGPTL4 was assessed by immunofluorescence. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify the mRNA level of ANGPTL4. Western blot was used to detect the protein levels of ANGPTL4 and cleaved caspase-3. Results: LC-MS identified five major constituents in the GQZ-DS aqueous extract: 2-O-β-D-glucopyranosyl-L-ascorbic acid, rutin, D-galactose, salvianolic acid A, and tanshinone IIA. The CCK-8 method selected 300 μmol/L H2O2 as the oxidative stress condition for experiments, and 0.05 and 0.1 g/mL were selected as the low and high doses of GQZ-DS, respectively, for subsequent experiments. The intervention with H2O2 resulted in reduced cell viability, elevated ROS and MDA levels, decreased SOD activity, increased apoptotic rate, upregulated cleaved caspase-3 expression, and G0/G1 phase cell cycle arrest of 661W cells. Both low and high doses of GQZ-DS alleviated these alterations, with high dose exhibiting stronger protective effects (P < 0.05 or P < 0.01). GQZ-DS also downregulated ANGPTL4 expression at both the mRNA and protein levels. Following plasmid transfection of cells, the study further revealed that ANGPTL4 knockdown mitigated oxidative stress and apoptosis-related injury, whereas ANGPTL4 overexpression exacerbated these pathological changes. Moreover, GQZ-DS partially reversed the degree of cellular oxidative damage induced by ANGPTL4 overexpression. Conclusion GQZ-DS can alleviate the H2O2-induced oxidative injury of 661W retinal photoreceptor cells, and the effects are related to the down-regulation of ANGPTL4 expression.

Objective:To investigate the efficacy of venetoclax combined with hypomethylating agents (Ven-HMA), in patients with core binding factor acute myeloid leukemia (CBF-AML) intolerant to intensive induction therapy.Methods:This study retrospectively analyzed patients newly diagnosed with CBF-AML who were aged <60 years and who received Ven-HMA as induction therapy at the Department of Hematology, the First Affiliated Hospital of Soochow University, between January 2020 and June 2023. Baseline characteristics and treatment responses of the patients were collected.Results:A total of 70 treatment-na?ve patients receiving Ven-HMA induction therapy were enrolled, of which 38 were men and 32 women [median age: 43 (34 - 55) years]. Of the 70 patients, 44 (62.9%) achieved complete remission (CR) /CR with incomplete hematologic recovery (CRi), 16 (22.9%) achieved partial remission, and 10 (14.2%) exhibited no response after one induction cycle. Among the 32 t (8;21) -positive patients with AML, only 8 (25.0%) achieved CR/CRi, of whom 3 (37.5%) remained measurable residual disease (MRD) -positive; among the 38 inv (16) -positive patients, 36 (94.7%) achieved CR/Cri, of whom 12 (33.3%) remained MRD-positive. Patients harboring the CBFβ::MYH11 fusion gene showed significantly higher response rates to Ven-HMA induction than those with the RUNX1:: RUNX1T1 fusion gene ( P<0.01) . Conclusion:Ven-HMA represents a novel therapeutic strategy that exhibits significant efficacy in inv (16) -positive patients; however, it demonstrates relatively lower remission rates in t (8; 21) -positive patients.

ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

Generative artificial intelligence (GAI) represents a prominent research focus in medicine, with medical education being a key application area. GAI demonstrates potential to enhance residency training efficacy through personalized instruction, automated assessment item generation, question bank updating, and intelligent scoring systems. However, current limitations exist regarding output accuracy and content consistency. To address these constraints, strategic measures are required: continuous GAI model refinement, development of standardized usage guidelines, enhanced data quality control, and implementation of human verification protocols for generated content. Concurrently, residents should proactively acquire GAI utilization skills to strengthen the practical application of theoretical knowledge. With these advancements, GAI is anticipated to evolve into a valuable asset for improving the efficiency and quality of residency training programs.

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

To explore the application effectiveness of generative artificial intelligence(GAI) in the standardized training assessment of critical care medicine residents.

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.