Objective This study aims to investigate the association between remnant cholesterol(RC)and the risk of metabolic-associated fatty liver disease(MAFLD)under the optimal triglyceride(TG)levels recom-mended by different guidelines.Methods The data were derived from the annual physical examinations of elderly people aged 65 and above in a community in 2023.Regression analysis was used to evaluate the association between RC and MAFLD risk.According to the TG normal level(<1.7 mmol/L)recommended by the Chinese Lipid Management Consensus and the TG ideal target(<1.2 mmol/L)proposed by the European Atherosclerosis Society,the individuals were divided into subgroups with different TG levels to explore the association between RC and MAFLD risk in each subgroup.Results A total of 2,800 elderly individuals aged 65 and above were included in this study.The proportion of the individuals meeting the diagnostic criteria for MAFLD was 20.85%,and RC was identified as an independent risk factor for MAFLD(P<0.001).In the elderly individuals with TG<1.7 mmol/L,RC level was not significantly associated with MAFLD risk(P=0.888).In contrast,in the elderly individuals with TG≥1.7 mmol/L,RC level was significantly and positively correlated with MAFLD risk(P<0.001).Interaction tests revealed no significant interaction between the stratification factor and the effect size of RC(P=0.115).In the elderly individuals with TG<1.2 mmol/L,RC level was not associated with MAFLD risk(P=0.505),while in the elderly individuals with TG≥1.2 mmol/L,RC level was significantly associated with MAFLD risk(P<0.001).Interaction tests showed a significant interaction between the stratification factor and the effect size of RC(P=0.011).Conclusion RC is an independent risk factor for MAFLD in older individuals.To reduce the risk of MAFLD related to RC in the elderly,a triglyceride level of<1.2 mmol/L can serve as a reference for identifying early-stage risk.

Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

Objective : To identify autophagy-related genes involved in pulmonary infection caused by the highly drug-resistant and virulent methicillin-resistant Staphylococcus aureus strain USA300 ( USA300) ，and to explore the underlying molecular mechanisms ， thereby providing potential targets for immunotherapy． Methods: The GSE220943 dataset of a USA300-induced pulmonary infection mouse model was obtained from the GEO database． Differentially expressed genes ( DEGs ) were identified using the DESeq2 package． Autophagy-related genes ( ARGs) were retrieved from the MSigDB and Autophagy databases．Weighted gene co-expression network analysis ( WGCNA) was performed to construct gene co-expression modules．Genes overlapping among DEGs，ARGs，and WGCNA modules were identified as autophagy-related DEGs．Gene Ontology ( GO) enrichment analysis was con- ducted using the clusterProfiler R package，while Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway en- richment analysis was performed via the Metascape platform．Immune cell infiltration was analyzed using the Immu- CellAI-mouse website．A protein - protein interaction ( PPI) network was constructed using the STRING database， and hub genes were identified through topological analysis in Cytoscape． Receiver operating characteristic curve ( ROC) curves were plotted via the website https: / /www．bioinformatics．com．cn． Finally，key gene expression was validated in mouse lung tissues by real-time quantitative reverse transcription PCR ( RT-qPCR) ． Results: A total of 6 135，4 075，3 680，and 2 342 differentially expressed genes ( DEGs) were identified at 12，24，48，and 96 hours post-infection，respectively．By integrating DEGs，autophagy-related genes ( ARGs) ，and WGCNA mod- ules，19 autophagy-related DEGs were identified． GO and KEGG enrichment analyses indicated that these genes were mainly involved in CD4 + T cell activation and regulation，innate immune responses，and autophagosome mem- brane formation．Immune infiltration analysis revealed that innate immune cells such as neutrophils and dendritic cells predominated during the early phase of infection，while γδ T cells and M2 macrophages became more promi- nent in the later stages．PPI network analysis identified 12 hub autophagy-related genes，among which three upreg- ulated key genes ( Eif2ak2，Ikbke，and Nfkbiz) were further confirmed．The area under the ROC curve for all three genes was 1. 000．RT-qPCR validation demonstrated significantly elevated expression of these three genes in lung tissues at 24 hours post-infection ( all P＜0. 05) ． Conclusion Eif2ak2，Ikbke，and Nfkbiz may be involved in the pulmonary infection caused by USA300 by promoting autophagy and hold promise as potential targets for immuno- therapy．

Due to the wide application of silver-containing dressings and silver-coated medical devices in clinical treatment; the extensive use of antibacterial agents and heavy metal agents in feed factories, Escherichia coli has formed the tolerance to silver ions. To systematically understand the known silver ion resistance mechanisms of E. coli, this article reviews the complex regulatory network and various physiological mechanisms of silver ion tolerance in E. coli, including the regulation of outer membrane porins, energy metabolism modulation, the role of efflux systems, motility regulation, and silver ion reduction. E. coli reduces the influx of silver ions by missing or mutating outer membrane porins such as OmpR, OmpC, and OmpF. It adapts to high concentrations of silver ions by altering the expression of ArcA/B and enhances the efflux capacity of silver ions under high-concentration silver stress via the endogenous Cus system and exogenous Sil system. Furthermore, the motility of bacteria is related to silver tolerance. E. coli has the ability to reduce silver ions, thereby alleviating the oxidative stress induced by silver ions. These findings provide a new perspective for understanding the formation and spread of bacterial tolerance and provide directions for the development of next-generation silver-based antimicrobials and therapies.
Escherichia coli/genetics* ; Silver/pharmacology* ; Drug Resistance, Bacterial ; Anti-Bacterial Agents/pharmacology* ; Porins/metabolism*

Objective : To investigate the effect and mechanism of sex-determining region Y-box transcription factor 4(SOX4) on autophagy in small cell lung cancer(SCLC) cells. Methods : Human SCLC cell line NCI-H446 was transfected with small interfering RNA(siRNA) to knockdown SOX4. RT-qPCR and Western blot were used to verify the transfection efficiency. NCI-H446 cells were divided into control group, si-SOX4 group, si-SOX4+oe-Beclin1 group and oe-Beclin1 group. Western blot analysis was performed to detect the ratio of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ expression and the expression of Beclin1 and p62 in different groups of cells. The transcriptional regulation of Beclin1 by SOX4 was detected by dual luciferase reporter assay and chromatin immunoprecipitation PCR(ChIP-PCR) assay. CCK-8 assay was used to detect the proliferation ability of NCI-H446 cells in different groups. Flow cytometry was used to detect the apoptosis rate of NCI-H446 cells in different groups. Transwell assay was performed to determine the cell migration and invasion ability in different groups. Results: Compared with the control group or the si-NC group, the relative mRNA and protein expression level of SOX4 in si-SOX4 group were down-regulated(P<0.05), and the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression level of Beclin1 in si-SOX4 group decreased(P<0.05), the relative protein expression of p62 increased(P<0.05). The relative luciferase activity of Beclin1 WT in the si-SOX4 group was lower than that in the si-NC group(P<0.05); the relative enrichment of Beclin1 promoter in the Anti-SOX4 group was higher than that in the Anti-Ig G group( P<0. 05). Compared with control group,cell proliferation activity decreased,cell apoptosis rate increased,migration number and invasion number decreased in si-SOX4 group( P<0. 05). Compared with the si-SOX4 group,the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression of Beclin1 increased in si-SOX4 + oe-Beclin1 group,while the relative protein expression of p62 decreased,cell proliferation activity increased,apoptosis rate decreased,migration number and invasion number increased( P<0. 05). Conclusion Down-regulation of SOX4 can inhibit autophagy,decrease proliferation activity of NCI-H446 cells,and inhibit cell migration and invasion by inhibiting Beclin1 expression.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

We report the clinical course from birth to adolescence of a patient carrying a compound heterozygous variation in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1(ENPP1) gene. The patient was diagnosed with generalized arterial calcification of infancy shortly after birth, and subsequently with autosomal recessive hypophosphatemic rickets type 2 at the age of 11 years. Following effective blood pressure control, treatment with neutral phosphate, calcitriol, and vitamin D was initiated. During follow-up, no progression of vascular calcification was observed. Through this case report and a review of relevant literature, we aim to enhance clinicians′ understanding of this rare condition.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective:To analyze the clinical features of children with infection-related eosinophilic lung diseases (ELD) caused by common respiratory pathogens.Methods:A retrospective cohort study was conducted. The clinical features, auxiliary examinations, treatments, and prognoses of 134 children with infection-related ELD caused by common respiratory pathogens at Yuying Children′s Hospital from January 2014 to June 2024 were collected. Participants were divided into the mild and severe groups based on whether the proportion of eosinophils in bronchoalveolar lavage fluid (BALF) exceeded 0.25. Chi-square test or Fisher exact test was used to analyze the differences between the two groups, and Logistic regression was performed to examine the correlation between BALF eosinophilia and the clinical outcomes.Results:Among the 134 children, 73 were males and 61 were females, with an age of 6.9 (4.6, 8.8) years on admission. A total of 154 pathogen detections were recorded, including 116 cases (75.3%) of Mycoplasma pneumoniae, 8 cases (5.2%) of influenza A virus, 6 cases (3.9%) of Streptococcus pneumoniae, and 6 cases (3.9%) of Chlamydia pneumoniae, among others. The percentage of eosinophils in the BALF of all children was 0.10 (0.07, 0.15). There were 117 cases in the mild group and 17 cases in the severe group. Compared with the mild group, significantly greater proportion of children in the severe group presented dyspnea (10/17 vs. 17.1% (20/117)), wheezing (7/17 vs. 8.5% (10/117)), respiratory failure (8/17 vs. 7.7% (9/117)), single lobe ≥2/3 consolidation (7/17 vs. 12.8% (15/117)), atelectasis (7/17 vs. 12.0% (14/117)), pleural effusion (7/17 vs. 16.2% (19/117)), plastic bronchiolitis (4/17 vs. 4.3% (5/117)), and systemic corticosteroid prescription (14/17 vs. 51.3% (60/117)) (all P<0.05). Univariate Logistic regression analysis revealed that severe eosinophilia in BALF was significantly associated with an elevated risk of respiratory failure ( OR=10.67, 95% CI 3.31-34.38, P<0.001), single lobe ≥2/3 consolidation ( OR=4.76, 95% CI 1.57-14.41, P=0.006), atelectasis ( OR=5.15, 95% CI 1.69-15.72, P=0.004), pleural effusion ( OR=3.61, 95% CI 1.22-10.67, P=0.020), and plastic bronchitis ( OR=6.89, 95% CI 1.64-28.94, P=0.008). Among the 126 children who were followed up, 106 cases (84.1%) were cured, 20 cases (15.9%) improved, and no relapses or deaths occurred. Conclusions:Mycoplasma pneumoniae and influenza A virus are common pathogens in children with infection-related ELD and the percentage of eosinophils in BALF is mildly increased, and the severe cases exhibit more severe clinical features and more significant pulmonary abnormalities, such as lobar consolidation and lung atelectasis. The prognosis is generally favorable.