OBJECTIVE To investigate the impact of lysosomal associated membrane protein 2b(Lamp2b)modification on the mucosal immune efficacy of engineered exosome-based vaccines.METHODS In vitro experiments:The murine dendritic cell line DC2.4 was transfected with a plasmid encoding the Lamp2b-RBD fusion protein.Real-time quantitative PCR and Western blotting were employed to assess Lamp2b-RBD expressions,flow cytometry was used to evaluate the proportion of Lamp2b-RBD-positive cells,and immunofluorescence staining was performed to determine their membrane localization.Exosomes were isolated via ultracentrifugation,and their morphology and particle size distribution were examined using transmission electron microscopy and nanoparticle tracking analysis.Western blotting was applied to confirm exosomal marker proteins[cluster of differentiation 9(CD9),CD63,ALG-2-interacting protein X(Alix),and Golgi marker GM130]and Lamp2b-RBD expression.In vivo experiments:① Female BALB/c mice were divided into the Lamp2b-RBD-Exo group and the lipid nanoparticle(LNP)group,and administered intratracheally for mucosal immunization.Pulmonary reten-tion was assessed by immunofluorescence staining.② Female BALB/c mice were divided into three groups:placebo group(PBS group),Lamp2b-RBD-Exo intratracheal administration group,and Lamp2b-RBD-Exo intramuscular injection group(im).Immunizations were performed on days 0 and 14,and on days 7 and 21.The titers of RBD-specific immunoglobulin G(IgG)in serum and RBD-specific IgA and IgG antibodies in bronchoalveolar lavage fluid were determined by enzyme-linked immunosor-bent assay(ELISA).RESULTS In vitro experiments:Lamp2b-RBD-positive cells accounted for 71.16％.Lamp2b-RBD mRNA levels were upregulated 1 979-fold compared with controls,with Lamp2b-RBD proteins localized on the cell membrane.Purified engineered exosomes displayed regular morphology,expressed CD9,CD63,and Alix but not GM130,had an average diameter of approximately 124 nm,and carried 3 009 pg of RBD protein per 1×109 exosomes.In vivo experiments:At 4 h after administra-tion,fluorescence signals were observed in the lung tissues of both the Lamp2b-RBD-Exo and LNPs groups.At 24 h,the fluorescence signal in the LNPs group shifted to the liver,while in the Lamp2b-RBD-Exo group,the fluorescence expanded from the trachea to the bronchioles and lung tissue,showing significantly better distribution and retention capacity than the LNPs group.Seven days after immuniza-tion,both the Lamp2b-RBD-Exo and Lamp2b-RBD-Exo(im)groups induced RBD-specific IgG antibody titers.At 21 days after immunization,Lamp2b-RBD-Exo elicited a higher level of RBD-specific immune response,with serum IgG titers reaching 1∶8 100 and bronchoalveolar lavage fluid(BALF)IgA titers reaching 1∶300.No RBD-specific IgA antibody titers were detected in the BALF of the Lamp2b-RBD-Exo(im)group.CONCLUSION Lamp2b-RBD modification enables efficient RBD protein loading and enhances pulmonary retention of engineered exosomes,thereby inducing potent antigen-specific mucosal immune responses.

Objective:Using bacterial culture as the gold standard, to evaluate the agreement of rapid antigen detection test (RADT) and rapid nucleic acid test (RNAT) in diagnosing group A Streptococcus (GAS) pharyngitis in pediatric outpatients, and assess their potential clinical utility. Methods:This cross-sectional study prospectively collected throat swab specimens and clinical data of 338 children diagnosed with acute pharyngitis at the Department of Outpatient Beijing Children′s Hospital, Capital Medical University, between July 2023 and February 2024. The specimens were tested for GAS bacterial culture, RADT and RNAT. Using bacterial culture results as the reference standard, Kappa consistency analysis was performed to assess the diagnostic concordance between RADT and RNAT. Chi-square test was used to compare clinical characteristics between cases diagnosed by different methods.Results:In the 338 children diagnosed with pharyngitis, 195 were male and 143 were female, with an age at the visit of 7.4 (5.9, 7.4) years. The positivive rates for GAS detection were 25.7% (87/338) by bacterial culture, 20.7% (70/338) by RADT, and 41.7% (141/338) by RNAT. In terms of diagnostic performance, RADT exhibited a higher specificity (96.8% (243/251)) and better agreement with bacterial culture results ( κ=0.73), whereas RNAT showed greater sensitivity (95.4% (83/87)) but lower specificity (76.9% (193/251)) and moderate agreement ( κ=0.61). Among the 87 children with positive bacterial culture for GAS, 56 were male and 31 were female, with an age at visit of 7.3 (6.2, 8.8) years. Clinically, body temperature predominantly ranged from 38.1 to 39.0 ℃ in 48 cases (55.2%), and common accompanying symptoms included sore throat 62 cases (71.3%), cough 33 cases (37.9%), and cervical lymphadenopathy or tenderness 16 cases (18.4%). On physical examination, tonsillar enlargement was present in 73 cases (83.9%) and exudate in 37 cases (42.5%). The McIsaac score was most frequently 4 points, observed in 37 cases (42.5%). Laboratory tests showed a peripheral white blood cell (WBC) count of 14.5 (12.3, 18.7)×10?/L and C-reactive protein (CRP) concentration of 22.0 (10.1, 41.4) mg/L. There were no statistically significant differences in the proportion of fever, sore throat, cough, tender cervical lymphadenopathy, tonsillar exudates, or tonsillar enlargement, nor in WBC count or CRP, among children who tested positive by RADT, RNAT, or bacterial culture (all P>0.05). Conclusions:Compared with bacterial culture,the RADT demonstrates higher specificity, while the RNAT exhibits greater sensitivity. Both methods show good concordance with culture results and may serve as effective adjunctive tools for the early screening of GAS pharyngitis.

Objective With the increasing demand from the country for optimizing the allocation of medical resources and improving service balance,this study aims to promote the improvement of regional medical service levels through the explora-tion and practice of the management model of provincial medical quality control centers.Methods The First Affiliated Hospital of Sun Yat-sen University,as the affiliated unit of one of the 14 provincial quality control centers,organizes the quality control center to play a professional role and improve its management efficiency through stable construction,solid framework,reorgani-zation,and multiple support.Results With the leadership and support of the health administrative department in Guangdong Province,the hospital has organized the provincial quality control center to carry out its work in an orderly manner,promoting the continuous improvement of the comprehensive strength of regional medical services and key indicators of various professional qual-ity control centers.Conclusion The management model of the quality control center in this study has shown initial effectiveness.

OBJECTIVE To investigate the impact of lysosomal associated membrane protein 2b(Lamp2b)modification on the mucosal immune efficacy of engineered exosome-based vaccines.METHODS In vitro experiments:The murine dendritic cell line DC2.4 was transfected with a plasmid encoding the Lamp2b-RBD fusion protein.Real-time quantitative PCR and Western blotting were employed to assess Lamp2b-RBD expressions,flow cytometry was used to evaluate the proportion of Lamp2b-RBD-positive cells,and immunofluorescence staining was performed to determine their membrane localization.Exosomes were isolated via ultracentrifugation,and their morphology and particle size distribution were examined using transmission electron microscopy and nanoparticle tracking analysis.Western blotting was applied to confirm exosomal marker proteins[cluster of differentiation 9(CD9),CD63,ALG-2-interacting protein X(Alix),and Golgi marker GM130]and Lamp2b-RBD expression.In vivo experiments:① Female BALB/c mice were divided into the Lamp2b-RBD-Exo group and the lipid nanoparticle(LNP)group,and administered intratracheally for mucosal immunization.Pulmonary reten-tion was assessed by immunofluorescence staining.② Female BALB/c mice were divided into three groups:placebo group(PBS group),Lamp2b-RBD-Exo intratracheal administration group,and Lamp2b-RBD-Exo intramuscular injection group(im).Immunizations were performed on days 0 and 14,and on days 7 and 21.The titers of RBD-specific immunoglobulin G(IgG)in serum and RBD-specific IgA and IgG antibodies in bronchoalveolar lavage fluid were determined by enzyme-linked immunosor-bent assay(ELISA).RESULTS In vitro experiments:Lamp2b-RBD-positive cells accounted for 71.16％.Lamp2b-RBD mRNA levels were upregulated 1 979-fold compared with controls,with Lamp2b-RBD proteins localized on the cell membrane.Purified engineered exosomes displayed regular morphology,expressed CD9,CD63,and Alix but not GM130,had an average diameter of approximately 124 nm,and carried 3 009 pg of RBD protein per 1×109 exosomes.In vivo experiments:At 4 h after administra-tion,fluorescence signals were observed in the lung tissues of both the Lamp2b-RBD-Exo and LNPs groups.At 24 h,the fluorescence signal in the LNPs group shifted to the liver,while in the Lamp2b-RBD-Exo group,the fluorescence expanded from the trachea to the bronchioles and lung tissue,showing significantly better distribution and retention capacity than the LNPs group.Seven days after immuniza-tion,both the Lamp2b-RBD-Exo and Lamp2b-RBD-Exo(im)groups induced RBD-specific IgG antibody titers.At 21 days after immunization,Lamp2b-RBD-Exo elicited a higher level of RBD-specific immune response,with serum IgG titers reaching 1∶8 100 and bronchoalveolar lavage fluid(BALF)IgA titers reaching 1∶300.No RBD-specific IgA antibody titers were detected in the BALF of the Lamp2b-RBD-Exo(im)group.CONCLUSION Lamp2b-RBD modification enables efficient RBD protein loading and enhances pulmonary retention of engineered exosomes,thereby inducing potent antigen-specific mucosal immune responses.

Objective With the increasing demand from the country for optimizing the allocation of medical resources and improving service balance,this study aims to promote the improvement of regional medical service levels through the explora-tion and practice of the management model of provincial medical quality control centers.Methods The First Affiliated Hospital of Sun Yat-sen University,as the affiliated unit of one of the 14 provincial quality control centers,organizes the quality control center to play a professional role and improve its management efficiency through stable construction,solid framework,reorgani-zation,and multiple support.Results With the leadership and support of the health administrative department in Guangdong Province,the hospital has organized the provincial quality control center to carry out its work in an orderly manner,promoting the continuous improvement of the comprehensive strength of regional medical services and key indicators of various professional qual-ity control centers.Conclusion The management model of the quality control center in this study has shown initial effectiveness.

Objective:Using bacterial culture as the gold standard, to evaluate the agreement of rapid antigen detection test (RADT) and rapid nucleic acid test (RNAT) in diagnosing group A Streptococcus (GAS) pharyngitis in pediatric outpatients, and assess their potential clinical utility. Methods:This cross-sectional study prospectively collected throat swab specimens and clinical data of 338 children diagnosed with acute pharyngitis at the Department of Outpatient Beijing Children′s Hospital, Capital Medical University, between July 2023 and February 2024. The specimens were tested for GAS bacterial culture, RADT and RNAT. Using bacterial culture results as the reference standard, Kappa consistency analysis was performed to assess the diagnostic concordance between RADT and RNAT. Chi-square test was used to compare clinical characteristics between cases diagnosed by different methods.Results:In the 338 children diagnosed with pharyngitis, 195 were male and 143 were female, with an age at the visit of 7.4 (5.9, 7.4) years. The positivive rates for GAS detection were 25.7% (87/338) by bacterial culture, 20.7% (70/338) by RADT, and 41.7% (141/338) by RNAT. In terms of diagnostic performance, RADT exhibited a higher specificity (96.8% (243/251)) and better agreement with bacterial culture results ( κ=0.73), whereas RNAT showed greater sensitivity (95.4% (83/87)) but lower specificity (76.9% (193/251)) and moderate agreement ( κ=0.61). Among the 87 children with positive bacterial culture for GAS, 56 were male and 31 were female, with an age at visit of 7.3 (6.2, 8.8) years. Clinically, body temperature predominantly ranged from 38.1 to 39.0 ℃ in 48 cases (55.2%), and common accompanying symptoms included sore throat 62 cases (71.3%), cough 33 cases (37.9%), and cervical lymphadenopathy or tenderness 16 cases (18.4%). On physical examination, tonsillar enlargement was present in 73 cases (83.9%) and exudate in 37 cases (42.5%). The McIsaac score was most frequently 4 points, observed in 37 cases (42.5%). Laboratory tests showed a peripheral white blood cell (WBC) count of 14.5 (12.3, 18.7)×10?/L and C-reactive protein (CRP) concentration of 22.0 (10.1, 41.4) mg/L. There were no statistically significant differences in the proportion of fever, sore throat, cough, tender cervical lymphadenopathy, tonsillar exudates, or tonsillar enlargement, nor in WBC count or CRP, among children who tested positive by RADT, RNAT, or bacterial culture (all P>0.05). Conclusions:Compared with bacterial culture,the RADT demonstrates higher specificity, while the RNAT exhibits greater sensitivity. Both methods show good concordance with culture results and may serve as effective adjunctive tools for the early screening of GAS pharyngitis.

Group A Streptococci(GAS)can cause multiple diseases such as pharyngotonsillitis, scarlet fever, streptococcal toxic shock syndrome(STSS), necrotizing fasciitis, and so on, making it extremely difficult to monitor all GAS infections.Developed countries such as the United States and the United Kingdom have classified invasive GAS diseases/infections(iGAS) or certain specific types, such as STSS, as notifiable diseases.China only includes scarlet fever caused by GAS infections in the legal infectious diseases.Although case reports or clinical studies of STSS and necrotizing fasciitis in China can be found, there is a lack of investigation and summary on iGAS, and there are few materials to introduce its definition and diagnostic criteria.Based on a recently diagnosed typical case, this paper intends to introduce the definition and diagnostic criteria of iGAS adopted in the United States, the United Kingdom and other developed countries, as well as the valuable early manifestations and risk factors, and the incidence of iGAS.Given the epidemiological changes in GAS infections in recent years, this paper also emphasizes the importance of paying attention to GAS infections, especially iGAS, aiming to arouse the attention of China′s clinical doctors and urge them to carry out research on this group of diseases.

Objective: To establish a nomograph model for prediction of cervical central lymph node metastasis (CLNM) among patients with thyroid papillary carcinoma (PTC), so as to provide the evidence for designing personalized treatment plans for PTC. Methods : The data of patients that underwent thyroidectomy and were pathologically diagnosed with PTC post-surgery in the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from 2018 to 2021 were collected. Patients' data captured from 2018 to 2020 and from 2021 were used as the training set and the validation set, respectively. Predictive factors were screened using a multivariable logistic regression model, and the nomograph model for prediction of CLNM risk was established. The predictive value of the model was evaluated using the receiver operating characteristic (ROC) curve and the adjusted curve. Results: Totally 1 820 PTC cases were included in the training set, including 458 cases with CLNM (25.16%), and 797 cases in the validation set, including 207 cases with CLNM (25.98%). The prediction model is p=ey/(1+ey), y=0.761 + 0.525 × sex + (-0.039) ×age + 0.351 × extrathyroid invasion + 0.368 × neck lymph node enlargement + 1.021×maximum tumor diameter + (-0.009) × TT4 + (-0.001) × anti-TPOAb. The area under the ROC curve was 0.732 for the training set and 0.731 for the validation set, and Hosmer-Lemeshow test showed a good fitting effect (P=0.936, 0.722). Conclusion The nomograph model constructed in this study has a high predictive value for CLNM among patients with PTC.

The current targeting drug delivery mainly relies on cancer cell surface receptors. However, in many cases, binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant. Distinct from conventional targeting strategies, we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as "overexpressed" biomarker through a metabolic glycan engineering. Different from the reported bioconjugation for drug targeting, the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction. The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug, which ultimately leads to effective and safe cancer therapy.

Background and Objectives: This study investigated the relative incidence of contrast induced nephropathy (CIN) and long-term outcomes between iso-osmolar contrast media (IOCM) and low-osmolar contrast media (LOCM) undergoing elective percutaneous coronary intervention (PCI). Methods: A total of 9,431 patients receiving elective PCI were enrolled in the cohort. The patients were divided into IOCM group and LOCM group. Propensity score matching (PSM) was applied to minimize the selection bias between groups. Results: The multivariate analysis showed that the use of IOCM compared with LOCM did not affect the CIN incidence (odds ratio [OR], 0.912; 95% confidence interval [CI], 0.576–1.446; p=0.696). After PSM, the incidence of CIN was 1.5% and 4.0% in IOCM group (n=979) and LOCM group (n=979), respectively, p=0.001. IOCM significantly reduced the incidence of CIN compared with LOCM (OR, 0.393; 95% CI, 0.214–0.722; p=0.003). After 2 years of follow-up, the all-cause mortality was higher in IOCM group than LOCM group (2.1% vs. 0.9%, p<0.001). Cox regression analysis showed IOCM was not independent risk factor of 2-years all-cause mortality (OR, 0.849; 95% CI, 0.510–1.412; p=0.528). After PSM, the difference of all-cause death between groups disappeared (1.7% vs. 1.9%, p=0.739). Cox regression analysis showed that the use of IOCM compared with LOCM did not affect the incidence of 2-year all-cause mortality (OR, 1.037; 95% CI, 0.534–2.014; p=0.915). Conclusions Compared with LOCM, IOCM significantly reduced the incidence of CIN after elective PCI, but had no significant effect on 2-year all-cause mortality.