OBJECTIVE To explore the epidemiological characteristics of the children with acute respiratory tract in-fection and analyze the changes of peripheral blood prealbumin(PA),serum amyloid protein A(SAA)and pro-calcitonin(PCT)so as to provide bases for the clinical diagnosis.METHODS A total of 177 children with acute re-spiratory tract infection who were treated in Qingdao Haici Hospital Affiliated to Qingdao University from Nov.2021 to Nov.2023 were assigned as the infection group,meanwhile,195 healthy children who received physical examination were chosen as the healthy group.The distribution of pathogens isolated from the patients of the in-fection group was statistically analyzed.The levels of PA,SAA,CRP and PCT were compared between the two groups.The values of the indexes in diagnosis of the acute respiratory tract infection were analyzed.RESULTS The total positive rate of isolation of pathogens was 31.07％(55/177)among the children with acute respiratory tract infection,and Mycoplasma pneumoniae was the predominant species of pathogen.There was significant difference in the isolation rate of pathogens among the different age groups of children with acute respiratory tract infection(x2=8.270,P=0.041);the children of the preschool age group were dominant.There was significant difference in the isolation rate of pathogens from the children with acute respiratory tract infection among the different sea-sons(x2=9.557,P=0.023);the isolation rates were relatively high in spring and winter.There were significant differences in the levels of serum PA,SAA,CRP and PCT between the infection group and the healthy group(P＜0.05);the CRP level was(13.48±4.25)mg/L in the infection group,(7.85±2.51)mg/L in the healthy group,with the difference value maximum(t=15.724,P＜0.001).The area under the curve(AUC)value of the joint detection of the four indexes was higher than that of the single detection in diagnosis of the acute respiratory tract infection in the children(P＜0.05).CONCLUSIONS M.pneumoniae is dominant among the pathogens isolated from the children with acute respiratory tract infection,the preschool age children are in the majority.The infec-tion is prevalent in spring and winter.The children with the infection show the abnormal expressions of PA,SAA,CRP and PCT,and the joint detection of the four indexes has high value in diagnosis of the infection.

Bone tissue engineering(BTE)is expected to be used as an autologous bone graft substitute for bone defects,and in the se-lection of BTE scaffold materials,collagen(Col)and hydroxyapatite(HA)have attracted attention due to their unique biomimetic ad-vantages.Collagen/hydroxyapatite(CHA)composite scaffolds made by combining the two have been shown to have excellent biocompat-ibility and bone-enhancing potential in various in vitro,in vivo,and clinical studies.With the development of three-dimensional(3D)printing technology in the field of tissue engineering,bone scaffolds constructed using 3D printing methods have been shown to possess superior clinical potential.This review describes new advances in 3D printed CHA composite scaffolds and introduces the application of 3D printed CHA scaffolds in oral and maxillofacial bone regenerative repair.

OBJECTIVE To explore the epidemiological characteristics of the children with acute respiratory tract in-fection and analyze the changes of peripheral blood prealbumin(PA),serum amyloid protein A(SAA)and pro-calcitonin(PCT)so as to provide bases for the clinical diagnosis.METHODS A total of 177 children with acute re-spiratory tract infection who were treated in Qingdao Haici Hospital Affiliated to Qingdao University from Nov.2021 to Nov.2023 were assigned as the infection group,meanwhile,195 healthy children who received physical examination were chosen as the healthy group.The distribution of pathogens isolated from the patients of the in-fection group was statistically analyzed.The levels of PA,SAA,CRP and PCT were compared between the two groups.The values of the indexes in diagnosis of the acute respiratory tract infection were analyzed.RESULTS The total positive rate of isolation of pathogens was 31.07％(55/177)among the children with acute respiratory tract infection,and Mycoplasma pneumoniae was the predominant species of pathogen.There was significant difference in the isolation rate of pathogens among the different age groups of children with acute respiratory tract infection(x2=8.270,P=0.041);the children of the preschool age group were dominant.There was significant difference in the isolation rate of pathogens from the children with acute respiratory tract infection among the different sea-sons(x2=9.557,P=0.023);the isolation rates were relatively high in spring and winter.There were significant differences in the levels of serum PA,SAA,CRP and PCT between the infection group and the healthy group(P＜0.05);the CRP level was(13.48±4.25)mg/L in the infection group,(7.85±2.51)mg/L in the healthy group,with the difference value maximum(t=15.724,P＜0.001).The area under the curve(AUC)value of the joint detection of the four indexes was higher than that of the single detection in diagnosis of the acute respiratory tract infection in the children(P＜0.05).CONCLUSIONS M.pneumoniae is dominant among the pathogens isolated from the children with acute respiratory tract infection,the preschool age children are in the majority.The infec-tion is prevalent in spring and winter.The children with the infection show the abnormal expressions of PA,SAA,CRP and PCT,and the joint detection of the four indexes has high value in diagnosis of the infection.

Objective To analyze the diagnostic value of serum biomarkers in patients with pulmonary tuberculosis complicated by invasive pulmonary aspergillosis.Methods A retrospective collection of laboratory test results,including blood analysis,liver function,lymphocyte counts,and cytokine levels,from 54 patients diagnosed with pulmonary tuberculosis and invasive pulmonary aspergillosis admitted to the Third People's Hospital of Kunming between January 2021 and May 2024.Additionally,70 patients with simple pulmonary tuberculosis and 50 healthy individuals were collected as control groups to compare serum biomarker levels across the three groups and analyze relevant factors and diagnostic value for pulmonary tuberculosis patients with invasive pulmonary aspergillosis.Results Among different age groups,the incidence of pulmonary tuberculosis with invasive pulmonary aspergillosis was 29 cases(53.7％)in youth,15 cases(27.8％)in middle age,and 10 cases(18.5％)in the elderly.In terms of gender distribution,there were 41 males(75.9％)and 13 females(24.1％).The serum levels of CRP(6.85[2.10,27.0])ng/L,PCT(0.05[0.05,0.15])ng/mL,RBC(4.55±0.65)× 1012/L,Hb(129.13±19.10)g/L,TP(66.23±6.82)g/L,ALB(37.03±4.77)g/L,and CHOL(4.30[3.71,4.91])mmol/L in the invasive pulmonary aspergillosis group showed no significant difference compared to the simple tuberculosis group and healthy control group(P＞0.05).The levels of CD3+T,CD4+T,and CD8+T in the invasive pulmonary aspergillosis group were significantly lower than those in the simple tuberculosis group and healthy control group(P＜0.05).The levels of IL-2,IL-4,IL-5,IL-8,IL-10,IL-12p70,IFN-α,and TNF-α in the invasive pulmonary aspergillosis group were significantly higher than those in the healthy control group(P＜0.05);IL-8,IL-12p70,and IFN-α were also higher compared to the simple tuberculosis group,with statistical significance(P＜0.05).Conclusion The population with pulmonary tuberculosis complicated by invasive pulmonary aspergillosis is predominantly male and younger.The serum indicators of infection severity and nutritional status in these patients are similar to those with simple tuberculosis and lack specificity;however,their immune function is significantly lower than that of simple tuberculosis patients.Multiple cytokines are elevated,particularly IL-8,IL-12p70,and IFN-α,which can aid in the differential diagnosis of pulmonary tuberculosis infection.

Objective:To study the changes of the perception of drug welfare of chronic disease patients and their impact on health level under the centralized drug procurement policy.Methods:It conducted a questionnaire survey and empirical analysis on the perception of drug welfare and health status of chronic disease patients after the implementation of the centralized drug procurement policy;set up an ordered logit regression model to investigate the impact of the perception of drug welfare on the health level of chronic disease patients and influencing factors,and analyzed the heterogeneity for geographic areas,populations and chronic disease types.Results:After the implementation of the centralized drug procurement policy,the perception of drug welfare of chronic disease patients was significantly improved,including the reduction of drug burden,the decrease of drug price and the increase of drug accessibility.Moreover,the health status of chronic disease patients is significantly affected by the perceived drug affordability,and the policy has greatly improved the health of this group,but there is still inequality.Conclusion:The implementation of the centralized drug procurement policy has been effective,the state should strengthen the policy propaganda,optimize the procurement strategy,so as to further enhance the drug welfare of chronic disease patients and improve their health.

BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.