BACKGROUND:The use of exosomes as drug carriers can not only precisely target the therapeutic site,but also increase the local concentration,opening up a new way for drugs to enter the central nervous system.OBJECTIVE:To explore the biogenesis and biological functions of exosomes and summarize the current state-of-the-art regarding extracellular vesicles as drug carriers in the treatment of central nervous system diseases.METHODS:The first author searched Web of Science,PubMed,and CNKI for relevant literature from January 1976 to January 2024.The English search terms were"exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."The Chinese search terms were"exosomes,extracellular vesicles,central nervous system diseases,drug delivery,stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."Finally,94 articles were included for analysis.RESULTS AND CONCLUSION:(1)Exosomes can easily cross the blood-brain barrier and deliver proteins,metabolites,and nucleic acids to recipient cells to regulate cellular metabolism.Since exosomes are small vesicles secreted by cells,they have a much lower circulating immunogenicity and can be less likely to be recognized and cleared by macrophages in the internal circulation.(2)Exosomes can be engineered to deliver different therapeutically ingredients,including RNA,proteins,chemotherapeutic drugs,and immunomodulators,and are capable of delivering them to the desired target areas.Engineered modified exosomes have better targeting properties.Furthermore,this exosome-mediated delivery is extremely low in immunogenicity and is expected to provide a safer and more effective method for precision therapy of central nervous system diseases in the future.

Objective:To explore the correlation between the elevation of glycated hemoglobin A1c (HbA1c) in the first trimester and its change from the first to the second trimester and adverse pregnancy outcomes.Methods:This was a bidirectional cohort study. Singleton pregnant women who delivered in the First Affiliated Hospital, Sun Yat-sen University from March 1, 2021, to July 31, 2024, and had HbA1c results in the first and second trimesters were included. Those with HbA1c<5.7% in the first trimester were described as group E1, and those with HbA1c between 5.7% and 6.4% were described as group E2. Those with HbA1c<5.2% in the second trimester were described as group S1, and those with HbA1c between 5.2% and 6.4% were described as group S2. Accordingly, the changing trend of HbA1c from the first to the second trimester was divided into group E1-S1, group E1-S2, group E2-S1, and group E2-S2. Clinical indicators such as gestational diabetes mellitus (GDM), preeclampsia, preterm birth, preterm premature rupture of membranes (PPROM), polyhydramnios, large for gestational age infants, small for gestational age infants, neonatal hypoglycemia, and neonatal transfer were collected. Comparisons between groups were performed using t-tests, analysis of variance, Mann-Whitney U tests, Kruskal-Wallis tests, Chi square tests, and Fisher's exact test. Multivariate logistic regression analysis was used to analyze the impact of HbA1c in the first trimester and the changing trend of HbA1c from the first to the second trimester on pregnancy outcomes. Results:During the study period, a total of 6 500 pregnant women were included for analysis, among which 209 (3.2%) had HbA1c between 5.7% and 6.4% in the first trimester. Taking those with HbA1c<5.7% as a reference, HbA1c between 5.7% and 6.4% in the first trimester was an independent risk factor for GDM, preterm birth, and PPROM [ OR (95% CI) were 3.304 (2.465-4.427), 1.545 (1.008-2.368), and 1.872 (1.042-3.361), respectively]. Taking group E1-S1 as a reference, HbA1c<5.7% in the first trimester and 5.2%-6.4% in the second trimester (group E1-S2) was an independent risk factor for GDM, preterm birth, PPROM, and neonatal hypoglycemia [ OR (95% CI) were 2.770 (2.370-3.237), 1.424 (1.132-1.791), 1.614 (1.179-2.211), and 2.047 (1.024-4.092), respectively]; HbA1c between 5.7% and 6.4% in the first trimester and<5.2% in the second trimester (group E2-S1) was an independent risk factor for PPROM [ OR (95% CI) was 3.408 (1.187-9.784)]; HbA1c between 5.7% and 6.4% in the first trimester and 5.2%-6.4% in the second trimester (group E2-S2) was an independent risk factor for GDM and preterm birth [ OR (95% CI) were 4.651 (3.282-6.592) and 1.724 (1.066-2.786), respectively]. Conclusions:HbA1c between 5.7% and 6.4% in the first trimester was significantly associated with an increased risk of GDM, preterm birth, and PPROM. For those with HbA1c between 5.7% and 6.4% in the first trimester, if the HbA1c level decreased in the second trimester, only the risk of PPROM increased significantly; conversely, if the HbA1c level continued to increase in the second trimester, the risks of GDM and preterm birth both increased significantly.

Objective:To describe the prevalence of anxiety disorders and its distribution in Inner Mongolia Autonomous Region,and to explore the relevant factors of anxiety disorders.Methods:From June 2019 to Decem-ber 2019,representative multi-stage disproportionate stratified sampling procedure was used to sample in residents aged 18 and over in the Inner Mongolia Autonomous Region.All respondents were face-to-face interviewed by trained interviewers.Composite International Diagnostic Interview-3.0(CIDI-3.0)was used to diagnose anxiety disorders according to the criteria and definition of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ).Chi-square test and multivariate logistic regression analysis were used for statistical anal-ysis.Results:Totally 12 315 people were interviewed in the survey.The weighted 12-mouth prevalence rate of any anxiety disorder was 4.64％,and the lifetime prevalence rate was 6.25％.The weighted 12-month prevalence rate of anxiety disorders was higher in female than that in male(5.38％vs.3.92％).The rate was higher in rural resi-dents than that in urban residents(5.67％vs.3.95％).The rate was higher in people with chronic diseases than that in people without chronic diseases(6.81％vs.2.29％).Logistic regression analysis showed that unmarried(OR=2.32,95％CI:1.31-4.10),separated/divorced(OR=2.49,95％CI:1.33-4.67),in debt(OR=1.55,95％CI:1.04-2.32),chronic disease(OR=2.22,95％CI:1.39-3.53),family history of anxiety disorders(OR=12.05,95％CI:8.78-16.53),poor sleep(OR=2.64,95％CI:1.97-3.54)were risk factors of occurrence of anxiety disorders,while junior high school(OR=0.65,95％CI:0.44-0.96)was protective factor of anxiety disor-ders.Conclusion:Adults with chronic diseases,poor sleep,unmarried or separated/divorced,family history of anxi-ety disorders,and financial debt are at higher risk groups of anxiety disorder in Inner Mongolia Autonomous Re-gion.

Objective:To describe the prevalence and distributions of mood disorder in Inner Mongolia Au-tonomous Region,and analyze the related risk factors.Methods:The multistage stratified sampling method with un-equal probability was used to select permanent residents aged 18 years and over in Inner Mongolia Autonomous Re-gion.The Composite International Diagnostic Interview 3.0 was used as a diagnostic tool.Mood disorders were di-agnosed according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition(DSM-Ⅳ).Single and multivariate analyses were used to investigate the related factors of mood disorders.Results:Totally,12 315 community residents were interviewed in the survey.The weighted 12-month prevalence and lifetime prevalence of mood disorder were 5.4％and 8.7％,respectively.Weighted 12-month prevalence of depressive disorder was 4.9％,and that of bipolar disorder was 0.3％.Among all subtypes of mood disorder,the 12-month prevalence rate of major depressive disorder(3.1％)was the highest.Multivariate logistic regression analysis showed that female,unmarried,separated or divorced,unemployment,family history,other mental disorders,sleep disorders and chronic diseases(OR=1.56,2.80,2.07,1.42,13.46,7.97,3.23,2.13)were risk factors of mood disorder,while aged 65 years and over(OR=0.44)was protective factor of mood disorders.The lifetime consultation rate in patients with mood disorders was 15.5％,the rate of psychiatric consultation was 3.7％,the rate of medication was 1.8％.Con-clusion:It indicates that female residents and people who are unmarried,separated and divorced,unemployed,with family history,suffering from other mental disorders,suffering from sleep disorders,and suffering from chronic dis-eases may be high risk groups of mood disorders,and the utilization rate of health services is rather low in Inner Mongolia Autonomous Region.

Objective This study aims to investigate controversial cases of forensic clinical re-identification of fractures,exploring the characteristics,causes,and countermeasures related to identification errors in primary bone injuries,complications,and subsequent changes.The goal is to provide identification strategies for similar cases regarding the collection of identification materials,timing,and examination method selection,ultimately establishing a paradigm for such identifications.Methods A total of 103 cases of clinical re-identification of fractures accepted by the West China Forensic Identification Center from 2020 to 2024 were collected,and the data from initial identifications and re-identifications were retrospectively analyzed.Results Male cases accounted for 69.90%of the re-identifications,with disability grade(67.96%)and injury degree(30.10%)being the primary concerns.Individual requests represented a high proportion(92.86%)in the initial assessment of disability levels,while unit or joint requests dominated the re-assessment(92.86%).The agreement rates for disability grade and injury degree were 55.26%and 59.38%,respectively.The reassessment of disability grades primarily involved fractures of limb long bones,spine,and ribs,with 75.53%of opinions resulting in downgraded disability levels.Rib,orbital,and nasal bone fractures were the main focus in injury degree reassessments,with 84.62%of opinions indicating aggravated injuries.The consistency rates for fracture identification in disability grade assessments was 92.21%,while rates for injury degree and sequelae were 65.63%and 48.94%,respectively.Inconsistencies in identifying damage facts—including the presence of fractures,distinguishing between fresh and old fractures,and determining the nature of fractures and sequelae—were primarily noted in rib,orbital,and nasal bone fractures.The utilization rate of CT metadata in initial evaluations(25.00%)was significantly lower than in re-evaluations(95.00%).The identification time for joint mobility dysfunction after fracture in re-identifications was significantly longer than in initial identifications(P=0.0002),and the identification time for cases with agreement was significantly shorter than for cases with disagreement(P=0.036).Conclusion Image data type and identification timing are critical factors that may influence the accuracy and consistency of forensic clinical identification of bone injuries.When necessary,dynamic CT metadata in conjunction with image post-processing technology can be routinely employed to identify fractures of the ribs,orbital bones,or nasal bones,thereby reducing the risk of misidentification.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

BACKGROUND:The use of exosomes as drug carriers can not only precisely target the therapeutic site,but also increase the local concentration,opening up a new way for drugs to enter the central nervous system.OBJECTIVE:To explore the biogenesis and biological functions of exosomes and summarize the current state-of-the-art regarding extracellular vesicles as drug carriers in the treatment of central nervous system diseases.METHODS:The first author searched Web of Science,PubMed,and CNKI for relevant literature from January 1976 to January 2024.The English search terms were"exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."The Chinese search terms were"exosomes,extracellular vesicles,central nervous system diseases,drug delivery,stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."Finally,94 articles were included for analysis.RESULTS AND CONCLUSION:(1)Exosomes can easily cross the blood-brain barrier and deliver proteins,metabolites,and nucleic acids to recipient cells to regulate cellular metabolism.Since exosomes are small vesicles secreted by cells,they have a much lower circulating immunogenicity and can be less likely to be recognized and cleared by macrophages in the internal circulation.(2)Exosomes can be engineered to deliver different therapeutically ingredients,including RNA,proteins,chemotherapeutic drugs,and immunomodulators,and are capable of delivering them to the desired target areas.Engineered modified exosomes have better targeting properties.Furthermore,this exosome-mediated delivery is extremely low in immunogenicity and is expected to provide a safer and more effective method for precision therapy of central nervous system diseases in the future.