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 explore the relationship between depressive symptoms and childhood abuse and neg-lect in college students,and the roles of attentional control and attentional bias in their relationship.Methods:Total-ly 871 students from a medical university in Guangzhou were recruited to complete the Patient Health Question-naire-9(PHQ-9),Childhood Trauma Questionnaire(CTQ),Attention Control Scale(ACS),and Attention to Posi-tive and Negative Information Scale(APNI).The summed scores of emotional abuse,physical abuse and sex abuse subscale of CTQ were computed to measure childhood abuse,while the summed scores of emotional neglect and physical neglect subscale of CTQ were computed to measure childhood neglect.Results:Childhood abuse and child-hood neglect scores were both positively associated with PHQ-9 scores(β=0.01,0.01),and negatively associated with ACS scores(β=-0.30,-0.14).Childhood abuse scores were positively associated with negative attentional bias scores(β=0.24),and negatively associated with positive attentional bias scores(β=-0.14).Childhood neg-lect scores were negatively associated with positive attentional bias scores(β=-0.22).Attentional control and at-tentional bias played mediating roles between childhood abuse,childhood neglect and depressive symptoms,and the mediating effects accounted for 53.99％and 40.28％of the total effects,respectively.Conclusion:Depressive symptoms in college students are related to both childhood abuse and neglect,and attentional control and positive,negative attentional bias mediate such associations.

Objective To study the effect and possible mechanism of Siraitiae fructus Qingyan Formula(SQF)on acute pharyngitis(AP)rats induced by ammonia water.Methods The active ingredients and targets of SQF were obtained from TCMSP database,pharyngitis targets were acquired from disease databases such as DrugBank,and the common targets were identified through intersections.Constructing protein-protein interaction(PPI)networks to obtain key targets.GO and KEGG enrichment analysis were carried out,and the"active ingredients-targets-pathways"network was constructed.Discovery Studio 2019 was used for molecular docking of active ingredients.The acute pharyngitis model was induced by fixed point quantitative application of ammonia water.After Siraitiae fructus Qingyan oral thick paste(SQP)low-,medium-and high-dose(4,8,16 g/kg)administration,The body mass,general behavior and symptoms of the rats were monitored continuously,and the score of pharyngeal swelling was recorded;the pathological changes of pharyngeal were observed by HE staining.The classification and the count of inflammatory cells were determined.The expression of inflammatory factors(IL-6,IL-1β,PGE2)and PI3K-AKT signaling pathways in pharyngeal tissues were assessed by quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 35 active ingredients,223 action targets and 2549 pharyngitis related targets were obtained through network pharmacology,with 153 common targets in total.The key targets were protein kinase B(PKB or AKT).Pathways involved PI3K-AKT signaling pathway.Combined with key targets,it was speculated that PI3K-AKT is an important signaling pathway for the treatment of acute pharyngitis with SQF.Compared with the model group,the related symptoms of AP rats were alleviated after the treatment of SQP.The redness and swelling of pharynx were significantly improved(P<0.001).The hyperplasia of the upper mucosa of pharyngeal was alleviated or disappeared,infiltration of a small amount of inflammatory cells,and hypertrophy and hyperplasia of submucosa glandular cells were alleviated.The numbers of inflammatory cells in blood of rats significantly decreased(P<0.05).And the mRNA expression levels of IL-6,IL-1β and PGE2 in pharyngeal tissues were significantly decreased(P<0.05,P<0.01,P<0.001),while the mRNA expression levels of PI3K,AKT and mTOR mRNA were remarkably raised(P<0.05,P<0.01).Conclusion SQF has obvious improvement effect on AP rats,and its mechanism may be related to reducing inflammation level,improving pharyngeal mucosa hyperplasia,inflammatory cells infiltration,hypertrophy and hyperplasia of submucosal glandular cells,and regulating PI3K-AKT signaling pathway.

Objective To study the effect and possible mechanism of Siraitiae fructus Qingyan Formula(SQF)on acute pharyngitis(AP)rats induced by ammonia water.Methods The active ingredients and targets of SQF were obtained from TCMSP database,pharyngitis targets were acquired from disease databases such as DrugBank,and the common targets were identified through intersections.Constructing protein-protein interaction(PPI)networks to obtain key targets.GO and KEGG enrichment analysis were carried out,and the"active ingredients-targets-pathways"network was constructed.Discovery Studio 2019 was used for molecular docking of active ingredients.The acute pharyngitis model was induced by fixed point quantitative application of ammonia water.After Siraitiae fructus Qingyan oral thick paste(SQP)low-,medium-and high-dose(4,8,16 g/kg)administration,The body mass,general behavior and symptoms of the rats were monitored continuously,and the score of pharyngeal swelling was recorded;the pathological changes of pharyngeal were observed by HE staining.The classification and the count of inflammatory cells were determined.The expression of inflammatory factors(IL-6,IL-1β,PGE2)and PI3K-AKT signaling pathways in pharyngeal tissues were assessed by quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 35 active ingredients,223 action targets and 2549 pharyngitis related targets were obtained through network pharmacology,with 153 common targets in total.The key targets were protein kinase B(PKB or AKT).Pathways involved PI3K-AKT signaling pathway.Combined with key targets,it was speculated that PI3K-AKT is an important signaling pathway for the treatment of acute pharyngitis with SQF.Compared with the model group,the related symptoms of AP rats were alleviated after the treatment of SQP.The redness and swelling of pharynx were significantly improved(P<0.001).The hyperplasia of the upper mucosa of pharyngeal was alleviated or disappeared,infiltration of a small amount of inflammatory cells,and hypertrophy and hyperplasia of submucosa glandular cells were alleviated.The numbers of inflammatory cells in blood of rats significantly decreased(P<0.05).And the mRNA expression levels of IL-6,IL-1β and PGE2 in pharyngeal tissues were significantly decreased(P<0.05,P<0.01,P<0.001),while the mRNA expression levels of PI3K,AKT and mTOR mRNA were remarkably raised(P<0.05,P<0.01).Conclusion SQF has obvious improvement effect on AP rats,and its mechanism may be related to reducing inflammation level,improving pharyngeal mucosa hyperplasia,inflammatory cells infiltration,hypertrophy and hyperplasia of submucosal glandular cells,and regulating PI3K-AKT signaling pathway.

Objective:To explore the relationship between depressive symptoms and childhood abuse and neg-lect in college students,and the roles of attentional control and attentional bias in their relationship.Methods:Total-ly 871 students from a medical university in Guangzhou were recruited to complete the Patient Health Question-naire-9(PHQ-9),Childhood Trauma Questionnaire(CTQ),Attention Control Scale(ACS),and Attention to Posi-tive and Negative Information Scale(APNI).The summed scores of emotional abuse,physical abuse and sex abuse subscale of CTQ were computed to measure childhood abuse,while the summed scores of emotional neglect and physical neglect subscale of CTQ were computed to measure childhood neglect.Results:Childhood abuse and child-hood neglect scores were both positively associated with PHQ-9 scores(β=0.01,0.01),and negatively associated with ACS scores(β=-0.30,-0.14).Childhood abuse scores were positively associated with negative attentional bias scores(β=0.24),and negatively associated with positive attentional bias scores(β=-0.14).Childhood neg-lect scores were negatively associated with positive attentional bias scores(β=-0.22).Attentional control and at-tentional bias played mediating roles between childhood abuse,childhood neglect and depressive symptoms,and the mediating effects accounted for 53.99％and 40.28％of the total effects,respectively.Conclusion:Depressive symptoms in college students are related to both childhood abuse and neglect,and attentional control and positive,negative attentional bias mediate such associations.

Objective:For small molecule drug 630120 based on proteolysis-targeting chimeras(PROTAC)that targets nicotinamide phosphoribosyltransferase(NAMPT),to explore its effect on the proliferation ability of colorectal cancer cells with low expression of nicotinate phosphoribosyltransferase(NAPRT).Methods:This study detected the protein expression levels of NAMPT and Tubby in tumor tissues and adjacent normal tissues from 5 colorectal cancer patients by immunohistochemical staining.Additionally,the Gene Expression Profiling Interactive Analysis(GEPIA)platform was used to analyze the expression level of NAMPT mRNA in colorectal cancer tissues and corresponding adjacent normal tissues from The Cancer Genome Atlas(TCGA)database.Based on previous studies in hematologic malignancies,to detect the degradation of NAMPT protein in colorectal cancer(CRC)cell lines(SW480,HT29,RKO,SW620 and HCT116)treated with the drug PROTAC-630120.Furthermore,to create NAPRT knockdown and knockout colorectal cancer cell lines by using shNAPRT plasmids and CRISPR-Cas9 technology.The impact of different concentrations of PROTAC-630120 on the proliferation of NAPRT knockdown and knockout colorectal cancer cells was validated by Cell Titer-Glo(CTG)luminescence assay and colony formation assay.Finally,Western blotting was also used to detect the effect of PROTAC-630120 on the expression of downstream proteins in the MAPK signaling pathway in colorectal cancer cells.Results:In colorectal cancer tissues,the expression levels of NAMPT protein and mRNA were significantly upregulated.The drug PROTAC-630120 can effectively degrade NAMPT protein in different colorectal cancer cells.Moreover,it can significantly inhibit the proliferation of NAPRT knockdown and knockout colorectal cancer cells.The IC50 values(half-maximal inhibitory concentration)for different colorectal cancer cell lines treated with PROTAC-630120 were as follows:RKOshNAPRT～49.03 nmol/L,HCT116shNAPRT～42.28 nmol/L,SW620shNAPRT～55.59 nmol/L,HT29shNAPRT～29.66 nmol/L,SW480shNAPRT～76.17 nmol/L,and SW480sgNAPRT～27.01/34.23 nmol/L.Finally,the drug PROTAC-630120 can inhibit the MAPK-ERK signaling pathway in colorectal cancer cells.Conclusion:The small molecule drug 630120 based on PROTAC that targets NAMPT protein,can inhibit the proliferation of NAPRT knockdown and knockout colorectal cancer cells,so it is expected to become a drug option for adjuvant therapy of cancer patients.

Objective:To analyze the clinical situation of critically ill children with Montgomery T-tube，aiming to summarize the characteristics of T-tube application in pediatric and the experience of postoperative airway management in PICU.Methods:The etiology，clinical characteristics，complications and ICU admissions of patients with Montgomery T-tube admitted to the Pediatric Hospital of Fudan University from April 2019 to December 2021 were analyzed，and the application of T-tube in patients with critical conditions requiring long-term mechanical ventilation was described in the light of clinical experience.Results:During the study period,seven children were admitted to the PICU after T-tube insertion,including three males and four females,aged 9~75 months.Five children received mechanical ventilation.Among them,there were five cases with congenital laryngeal malformations,one case with tracheoesophageal fistula,and one case with laryngeal papilloma.The main complications were sputum blockage,infection,and granulation proliferation.One child died of secretion blockage,while the other children were successfully evacuated from the T-tube.The longest retention time of the T-tube was 367 days.Five patients experienced hoarseness after removing the T-tube,and upon re-examination with fiberoptic bronchoscopy,no recurrence of subglottic stenosis was observed.There was no respiratory distress or wheezing,and there were no abnormalities observed during regular outpatient follow-up after discharge.After discharge,the quality of life of the six surviving children improved compared to preoperative,and they all resumed oral feeding.There were no complaints of swallowing difficulties or aspiration during outpatient follow-up.But they were all combined with malnutrition.Conclusion:The Montgomery T-tube is a secure and dependable airway stent utilized for airway remodeling and the maintenance of airway patency following interventional surgery.For critically ill children,early management of airway clearance and infection prevention are imperative.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.

Objective To cultivate competent rehabilitation assistive technology workers and systematically develop the undergradu-ate curriculum courses of assistive technology using World Health Organization Rehabilitation Competency Framework(RCF)and International Classification of Functioning,Disability and Health(ICF). Methods The competence of assistive technology workers was discussed based on the ICF,RCF and the service needs of modern assistive devices and technology,and the undergraduate curriculum courses of rehabilitation assistive technology were developed referring to the national vocational competence standards. Results Referring to the national vocational competence standards,the entry-level competence of assistive technology workers was developed based on ICF and RCF.The objectives of undergraduate education were set.Moreover,the undergraduate curriculum courses and core course of assistive technology were developed. Conclusion The undergraduate curriculum courses of assistive technology are developed using ICF and RCF.This will help improve the quantity and competency of rehabilitation assistive technology workers and increase the access for people with disabilities to obtain assistive technology.