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.

AIM:This study aims to investigate the therapeutic impact of bone marrow mesenchymal stem cell(MSC)-derived exosomes(MSC-Exos)on septic lung injury by targeting Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:MSC-Exos were isolated from bone marrow MSCs using ultracentrifugation.The exosomes were characterized by transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blot.A septic lung injury model was established via cecal ligation and puncture(CLP).MSC-Exos were adminis-tered intraperitoneally 3 h after CLP.Blood and lung tissue samples were collected at 6,12,24,and 72 h after CLP.Con-centrations of interleukin-10(IL-10),IL-6,IL-1β,and tumor necrosis factor-α(TNF-α)were measured by ELISA.The lung tissue damage in mice was assessed by HE staining.Expression levels of TLR4 and NF-κB were detected by RT-qP-CR and Western blot.RESULTS:The results of TEM revealed typical round and oval exosome-like structures of MSC-Exos.Western blot showed positive expression of CD63,TSG101 and HSP-70.The results of NTA indicated that the parti-cle size of MSC-Exos was(107.5±16.6)nm.Septic lung injury began to manifest 12 h after CLP and progressively worsened,peaking at 72 h after CLP.At 6 h after CLP,the level of TNF-α was markedly elevated compared to the control group,reaching its peak at 72 h after CLP.At 12 h after CLP,the levels of IL-1β,IL-10,and IL-6 were elevated com-pared to the control group,and they reached their maximum point 72 h post-CLP.The MSC-Exos intervention group ex-hibited significantly reduced lung injury compared to the CLP group,as indicated by the lung pathology scoring.In the MSC-Exos intervention group,concentrations of IL-10,IL-1β,IL-6,and TNF-α peaked at 12 h after CLP,gradually de-clined,and returned to baseline levels by 72 h.TLR4 and NF-κB expression levels were significantly increased at 6 h af-ter CLP in the CLP group,peaking at 72 h.In contrast,MSC-Exos treatment normalized TLR4 and NF-κB expression levels at 72 h after CLP.CONCLUSION:Early intervention with bone marrow MSC-Exos significantly alleviated septic lung injury by reducing the inflammatory cytokine storm,likely through downregulation of the TLR4/NF-κB signaling path-way.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective To analyze the correlations between the thoracic electrical impedance tomography(EIT)-derived parameters global inhomogeneity(GI),center of ventilation(COV),regional ventilation delay(RVD),and atelectasis in hospitalized patients,and to explore their effectiveness in evaluating atelectasis.Methods The clinical data of 140 hospitalized patients monitored by thoracic EIT between Sep.2024 and Jan.2025 were retrospectively analyzed.Patients were assigned to 2 groups based on chest computed tomography confirmation of atelectasis within the preceding short-term period during EIT monitoring:non-atelectasis group or atelectasis group.The algorithm software designed with MATLAB was used to acquire GI and COV.RVD was obtained through analysis with the Dr?ger EIT Data Analysis Tool 6.3 software,and patients'general data were concurrently documented.Comparative analysis of EIT-derived parameters between groups was conducted.Multivariate logistic regression analysis was employed to investigate the correlations of GI,COV,and RVD with atelectasis,while receiver operating characteristic curve analysis was performed to assess the efficacy of EIT-derived parameters in evaluating atelectasis.Results A total of 140 patients were enrolled,with 19(13.6%)cases presenting atelectasis.Compared to the non-atelectasis group,the atelectasis group demonstrated significantly higher proportions of male patients and cardiovascular disease and thoracic surgery(non-pulmonary)histories,lower body mass index(BMI),and alongside elevated GI and RVD values with reduced COV(all P＜0.05).Multivariate logistic regression analysis revealed that GI,COV,and RVD maintained independent associations with atelectasis after adjusting for age,gender,BMI,pleural effusion,and emphysema(odds ratio[OR]=1.39,95%confidence interval[CI]1.20-1.67;OR=0.85,95%CI 0.75-0.96;OR=1.22,95%CI 1.09-1.39;all P＜0.05).The area under curve(AUC)values of GI,COV,and RVD for evaluating atelectasis in hospitalized patients were 0.82,0.80,and 0.82,respectively(while RVD demonstrated a higher AUC,its clinical applicability was influenced by respiratory patterns).Conclusion Thoracic EIT-derived parameters GI and COV demonstrate significant correlations with atelectasis and may serve as valuable indicators for evaluating atelectasis in hospitalized patients.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To evaluate the clinical efficacy and the mid- and long-term follow-up outcomes of transanal anaplasty for treating rectovestibular fistula.Methods:The clinical data of 68 female infants diagnosed with rectovestibular fistula undergoing transanal anoplasty at the Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from Oct 2014 to Dec 2023 was collected. Postoperative complications, perineal and anal appearances, and defecation function of postoperative children aged 3 years or older were recorded.Results:After surgery 68 children followed-up for 6 months of recent with short-term complications in 6 cases, including 3 cases of incision infection, 2 cases of rectal mucosal prolapse, and 1 case of anal stenosis. Rintala score was (18.65±1.99). Twenty-five children underwent anorectal manometry, no significant differences were observed in the maximal systolic pressure of the anal canal( t=-0.596, P=0.563) and the maximum systolic time( t=-0.183, P=0.854). The resting pressure( t=-3.050, P=0.005), functional length( t=2.696, P=0.012), and positive rate of rectal anal inhibitory reflex( χ2=6.382, P=0.012) of the anal canal were significantly lower than those of the normal group( P<0.05). Conclusions:Transanal anaplasty for the treatment of rectovestibular fistula in girls has a low incidence of complications. It results in a normal perineal body appearance, good anal bowel control, and high quality of life.

AIM:This study aims to investigate the therapeutic impact of bone marrow mesenchymal stem cell(MSC)-derived exosomes(MSC-Exos)on septic lung injury by targeting Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:MSC-Exos were isolated from bone marrow MSCs using ultracentrifugation.The exosomes were characterized by transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blot.A septic lung injury model was established via cecal ligation and puncture(CLP).MSC-Exos were adminis-tered intraperitoneally 3 h after CLP.Blood and lung tissue samples were collected at 6,12,24,and 72 h after CLP.Con-centrations of interleukin-10(IL-10),IL-6,IL-1β,and tumor necrosis factor-α(TNF-α)were measured by ELISA.The lung tissue damage in mice was assessed by HE staining.Expression levels of TLR4 and NF-κB were detected by RT-qP-CR and Western blot.RESULTS:The results of TEM revealed typical round and oval exosome-like structures of MSC-Exos.Western blot showed positive expression of CD63,TSG101 and HSP-70.The results of NTA indicated that the parti-cle size of MSC-Exos was(107.5±16.6)nm.Septic lung injury began to manifest 12 h after CLP and progressively worsened,peaking at 72 h after CLP.At 6 h after CLP,the level of TNF-α was markedly elevated compared to the control group,reaching its peak at 72 h after CLP.At 12 h after CLP,the levels of IL-1β,IL-10,and IL-6 were elevated com-pared to the control group,and they reached their maximum point 72 h post-CLP.The MSC-Exos intervention group ex-hibited significantly reduced lung injury compared to the CLP group,as indicated by the lung pathology scoring.In the MSC-Exos intervention group,concentrations of IL-10,IL-1β,IL-6,and TNF-α peaked at 12 h after CLP,gradually de-clined,and returned to baseline levels by 72 h.TLR4 and NF-κB expression levels were significantly increased at 6 h af-ter CLP in the CLP group,peaking at 72 h.In contrast,MSC-Exos treatment normalized TLR4 and NF-κB expression levels at 72 h after CLP.CONCLUSION:Early intervention with bone marrow MSC-Exos significantly alleviated septic lung injury by reducing the inflammatory cytokine storm,likely through downregulation of the TLR4/NF-κB signaling path-way.

Objective:To evaluate the clinical efficacy and the mid- and long-term follow-up outcomes of transanal anaplasty for treating rectovestibular fistula.Methods:The clinical data of 68 female infants diagnosed with rectovestibular fistula undergoing transanal anoplasty at the Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from Oct 2014 to Dec 2023 was collected. Postoperative complications, perineal and anal appearances, and defecation function of postoperative children aged 3 years or older were recorded.Results:After surgery 68 children followed-up for 6 months of recent with short-term complications in 6 cases, including 3 cases of incision infection, 2 cases of rectal mucosal prolapse, and 1 case of anal stenosis. Rintala score was (18.65±1.99). Twenty-five children underwent anorectal manometry, no significant differences were observed in the maximal systolic pressure of the anal canal( t=-0.596, P=0.563) and the maximum systolic time( t=-0.183, P=0.854). The resting pressure( t=-3.050, P=0.005), functional length( t=2.696, P=0.012), and positive rate of rectal anal inhibitory reflex( χ2=6.382, P=0.012) of the anal canal were significantly lower than those of the normal group( P<0.05). Conclusions:Transanal anaplasty for the treatment of rectovestibular fistula in girls has a low incidence of complications. It results in a normal perineal body appearance, good anal bowel control, and high quality of life.