ObjectiveTo investigate the epidemiological and clinical characteristics of human bocavirus (HBoV) in hospitalized children with acute lower respiratory tract infection (ALRTI) at a single-center children’s hospital in Shanghai, thereby providing evidence for the diagnosis, treatment, and prevention of HBoV infection. MethodsA retrospective study was conducted on 19 537 hospitalized children with ALRTI at Shanghai Children’s Hospital from January 2021 to December 2023. Multiplex polymerase chain reaction (PCR) combined with capillary electrophoresis was used to detect HBoV and 12 other common respiratory viruses /atypical pathogens. The positive detection rate, demographic characteristics (sex, age), temporal distribution (year, season) of HBoV, as well as the clinical characteristics of severe and non-severe pneumonia were analyzed. ResultsThe overall HBoV-positive rate was 2.57% (503/19 537), with 59.44% (299/503) being single infections and 40.56% (204/503) being co-infections. The positive detection rate was significantly higher in boys than that in girls (2.78% vs 2.33%, χ²=3.88, P=0.049). The highest infection rate was observed in toddlers, followed by infants (χ²=379.57, P<0.001). The positive rate peaked in 2021 and reached its lowest point in 2023 (χ²=45.49, P<0.001), with epidemics mainly prevalent in summer and autumn. The main clinical symptoms were cough (90.06%, 453/503), fever (75.94%, 382/503), and wheezing (39.96%, 201/503). Children with severe pneumonia showed a higher incidence of wheezing compared with the non-severe group (P<0.001), while underlying diseases and co-infections had no significant association with disease severity (P>0.05). ConclusionHBoV was an important pathogen of ALRTI in children, predominantly affecting infants and toddlers, with higher susceptibility in boys and seasonal peaks in autumn and summer. The main clinical manifestations included cough, fever, and wheezing, with wheezing being more prevalent in children with severe pneumonia.

To compare the performance differences between the multidisciplinary team (MDT) model and the conventional diagnostic and treatment model for lung cancer, and to explore a high-quality development pathway for optimizing lung cancer diagnostic and treatment resources.

ObjectiveTo investigate the effects of Hei Xiaoyaosan on neuroinflammation in APP/PS1 mice and decipher the mechanism based on the C-X3-C chemokine ligand 1 （CX3CL1）-CX3CL1 receptor 1 （CX3CR1） signaling axis. MethodsSixty 16-week-old male APP/PS1 mice were selected and acclimatized for one week， and they were then randomly allocated into a model group， a CX3CL1 group （bilateral hippocampal injection of CX3CL1 at 0.5 g·L^-1）， and high-， medium-， and low-dose （22.10， 11.05， and 5.53 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 12 mice in each group. Twelve age-matched male C57BL/6J mice served as the blank group （bilateral hippocampal injection of an equal volume of PBS）. The high-， medium-， and low-dose Hei Xiaoyaosan groups received corresponding drugs via gavage， while the blank group received an equal volume of normal saline， with an intervention period of 90 days. Morris water maze was used to assess learning and memory abilities. Nissl staining was performed to observe the pathological changes in neurons of the hippocampal CA1 region. Immunohistochemistry was adopted to detect amyloid-β_1-42 （Aβ_1-42） deposition in the hippocampal CA1 region. The immunofluorescence assay was employed to detect the expression of M1 and M2 microglial markers， including cluster of differentiation 86 （CD86）/ionized calcium-binding adapter molecule 1 （Iba-1） and arginase-1 （Arg1）/Iba1. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-8 （IL-8） and interleukin-13 （IL-13） in the hippocampal tissue. Western blot was employed to determine the protein levels of CX3CL1， CX3CR1， CREB-binding protein （CBP）， cyclic AMP response element-binding protein （CREB）， phosphorylated （p）-CREB， and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group exhibited prolonged escape latency on day 5 and a reduced swimming distance in the target quadrant （P<0.01）， disarrangement of hippocampal neurons， with a reduced number of cells and uneven Nissl body staining， increased CD86/Iba1 expression， decreased Arg1/Iba1 expression （P<0.01）， enhanced Aβ expression （P<0.01）， an elevated IL-8 level and a declined IL-13 level （P<0.01）， and downregulated protein levels of CX3CL1， CX3CR1， CBP， p-CREB， and BDNF （P<0.01）. Compared with the model group， all treatment groups showed shortened escape latency on day 5 and an increased swimming distance in the target quadrant （P<0.05， P<0.01）， regular arrangement of neurons with an increased number and increased Nissl bodies， reduced CD86/Iba1 expression， increased Arg1/Iba1 and decreased Aβ expression （P<0.01）， and a declined IL-8 level and an elevated IL-13 level （P<0.05， P<0.01）. In the CX3CL1 group and the high- and medium-dose Hei Xiaoyaosan groups， the relative expression levels of CX3CL1， CX3CR1， CBP， and p-CREB were upregulated （P<0.01）. In the low-dose Hei Xiaoyaosan group， the relative expression levels of CX3CL1， CX3CR1， CBP， p-CREB/CREB， and BDNF were upregulated （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can improve learning and cognitive abilities in APP/PS1 mice. Specifically， it may regulate the CX3CL1/CX3CR1 signaling axis to activate the CREB/BDNF signaling pathway for the subsequent release of BDNF， modulation of microglial polarization， reduction of inflammatory cytokine levels， and attenuation of Aβ deposition.

Objective To construct a competency evaluation model for forensic practitioners,providing a reference for their training and assessment.Methods Based on the iceberg and onion models of com-petency,and with reference to Spencer's Competency Dictionary,literature research was conducted and focus group interviews were employed to preliminarily construct core indices and measurement items for evaluating the competency of forensic practitioners.The Delphi method was applied for two rounds of expert consultation to further refine the competency evaluation index system.The analytic hierarchy process(AHP)was used to calculate the weights of the indices.Results A competency evaluation model for forensic practitioners was constructed,consisting of 7 core indices,encompassing forensic skills,identification service capabilities,and the ability to apply relevant legal knowledge and 49 mea-surement items.The weights of the core indices and measurement items were determined.Conclusion The constructed competency evaluation model for forensic practitioners is scientifically sound and inno-vative,and has unique characteristics of forensic medicine compared with other medical models.

Cyclic GMP-AMP synthase(cGAS)is a congenital immune sensor that can recognize cytoplasm abnormal dsDNA.By catalyzing the second messenger cyclic GMP-AMP(cGAMP)formation,it activates stimulator of interferon genes(STING),releases type Ⅰ interferon and inflammatory cytokines,activates the host immune response,and participates in cerebral ischemia reperfusion injury(CIRI)cascade reaction.This article reviews the research progress of the mechanism of cGAS-STING signaling pathway participation in CIRI,hoping to provide ideas for its treatment.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.