ObjectiveTo investigate the regulatory effects of Huanglian Jiedutang （HLJDT） on immune cell migration， blood-brain barrier protection， and cellular functional recovery in a model of ischemic stroke. MethodsA transient middle cerebral artery occlusion （tMCAO） model was established in mice to induce ischemic stroke. Cerebral blood flow and neurological function were evaluated using laser speckle imaging and neurological deficit scoring. Histopathological damage in brain tissues was assessed by hematoxylin-eosin （HE） and Nissl staining. Mice were divided into a sham group， a model group， an HLJDT group， and a Ginkgo biloba extract （GBE） group. After one week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the HLJDT group received HLJDT at 1.82 g·kg^-¹， and the GBE group received GBE at 0.432 g·kg^-¹. Administration was continued for 5 consecutive days， and the tMCAO model was established after the final dose on day 6. Single-cell RNA sequencing was performed on brain tissues and peripheral immune cells. UMAP and odds ratio （OR） indices were used to analyze cell distribution. Differential expression analysis was conducted to evaluate the effects of HLJDT on endothelial cells， pericytes， and macrophages， combined with CellChat and decoupler to analyze cell-cell communication and transcription factor regulation. Finally， PCR and ELISA were used to validate the mRNA and protein expression of relevant genes. ResultsCompared with the sham group， the model group showed significantly increased neurological deficit scores （P<0.01） and significantly decreased cerebral blood flow （P<0.01）， accompanied by cortical structural disorder， aggravated cytoplasmic vacuolization， and increased numbers of Nissl bodies. Compared with the model group， both the HLJDT and GBE groups exhibited significantly reduced neurological deficit scores （P<0.01） and markedly improved cerebral blood flow （P<0.01）， along with amelioration of cortical structural disorder， alleviated cytoplasmic vacuolization， and reduced numbers of Nissl bodies. Single-cell analysis showed that HLJDT protected endothelial cells and pericytes by preventing their reduction， restored the expression of functional genes in these cells （e.g.， PECAM1 and NOS3）， and downregulated the expression of chemokines and adhesion-related factors （e.g.， CCL2 and CXCL2）. In macrophages， HLJDT reduced their recruitment to the central nervous system and downregulated the expression of chemokine receptors and inflammatory factors （e.g.， IL-6， CCR2， and CXCR2）. Cell-cell communication analysis further indicated that HLJDT， through the above mechanisms， alleviated damage to pericytes and endothelial cells， reduced their recruitment of macrophages， and decreased ligand-receptor interactions in chemokine signaling pathways （including CCL， CXCL， and CSF3） between pericytes/endothelial cells and macrophages， thereby preventing secondary injury. Compared with the sham group， the model group showed significantly upregulated mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， while mRNA expression levels of endothelial- and pericyte function-related genes （RGS5， PECAM1， VEGFB， and NOS3） were significantly downregulated （P<0.01）. In contrast， compared with the model group， the HLJDT and GBE groups exhibited significantly decreased mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， and significantly increased expression of RGS5， PECAM1， VEGFB， and NOS3 （P<0.01）. At the protein level， compared with the sham group， the model group showed significantly increased expression of IL-1β， IL-6， and TNF-α （P<0.01）， whereas these protein levels were significantly reduced in the HLJDT and GBE groups compared with the model group （P<0.01）. ConclusionHLJDT reduces neuronal damage in ischemic stroke by protecting endothelial cells and pericytes， while inhibiting their interaction with macrophages， thereby mitigating secondary injury in the central nervous system.

Objective To explore the characteristics of TCM syndromes in patients with obesity with metabolic associated fatty liver disease(MAFLD).Methods TCM Symptom Collection Form was developed to collect the clinical symptoms of obesity patients who attended the Department of Acupuncture and Moxibustion of Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,from July to December of 2024.Factor analysis and clustering analysis were used to explore the distribution law of different syndrome elements and TCM syndromes.Results A total of 309 obese patients(221 with MAFLD)were included,with 20 symptoms with a frequency of≥5%.Factor analysis suggested that there was a significant difference between the two groups in the pathogenic syndrome elements of qi stagnation,yin deficiency,qi deficiency,hyperactivity of yang,yang deficiency,dampness,dynamic wind,and the locus of disease syndrome elements of the spleen and the heart spirit(P<0.05).Clustering analysis showed that the syndrome types of patients with MAFLD were mainly the syndrome of liver and stomach stagnation and heat,the syndrome of spleen deficiency and stomach heat,and the syndrome of spleen and kidney deficiency;the syndrome types of patients without MAFLD were mainly spleen-stomach qi stagnation,gastrointestinal excess-heat,spleen-deficiency-dampness obstruction,and spleen-kidney deficiency.Conclusion Patients of obesity with MAFLD are more likely to have the co-existence of the pathogenesis of damp-heat obstruction and spleen-kidney deficiency.

Background and Aims:Papillary thyroid carcinoma(PTC),the most common type of thyroid cancer,has been rapidly increasing in incidence worldwide,posing a serious threat to individual health and public healthcare systems.Exposure to low-to-moderate doses of ionizing radiation is more relevant to the daily lives of the general population and,therefore,raises greater public health concerns.It has also been widely recognized as a potential factor in immune system remodeling.This study was conducted to investigate the impact of low-to-moderate dose ionizing radiation on the tumor immune microenvironment of PTC,aiming to reveal the potential hazards of such radiation exposure in PTC patients.Methods:Two datasets(GSE29265 and GSE35570)containing RNA-seq data and corresponding clinical information were retrieved and downloaded from the GEO database.These datasets included thyroid cancer samples from patients exposed to ionizing radiation due to the Chernobyl disaster,as well as sporadic thyroid cancer cases.After data cleaning,merging,batch effect correction,differential gene expression analysis,functional enrichment analysis,immune cell infiltration analysis,and tumor microenvironment analysis were performed using R language.Results:In tumor samples,the radiation-exposed group exhibited significant differential gene expression compared to the sporadic group,with three genes upregulated and 27 genes downregulated.These differentially expressed genes were primarily enriched in biological functions closely related to immune responses,including chemokine activity,immune cell chemotaxis,and tumor immunity.Immune cell infiltration analysis indicated that radiation exposure had a limited impact on immune cell infiltration in normal samples.However,in tumor samples,the immune and ESTIMATE scores were significantly lower in the radiation-exposed group than in the sporadic group.Further analysis revealed that total T cells,CD4+T cells,CD8+T cells,B cells,and cytotoxic lymphocytes exhibited significantly lower infiltration levels in the tumor microenvironment of the radiation-exposed group than the sporadic group.Conclusion:Although low-to-moderate dose ionizing radiation has a relatively minor impact on normal thyroid tissue,it significantly reduces the infiltration of various immune cell subtypes in the PTC tumor microenvironment.This reduction in immune infiltration may have important implications for disease progression.

Background and Aims:Papillary thyroid carcinoma(PTC),the most common type of thyroid cancer,has been rapidly increasing in incidence worldwide,posing a serious threat to individual health and public healthcare systems.Exposure to low-to-moderate doses of ionizing radiation is more relevant to the daily lives of the general population and,therefore,raises greater public health concerns.It has also been widely recognized as a potential factor in immune system remodeling.This study was conducted to investigate the impact of low-to-moderate dose ionizing radiation on the tumor immune microenvironment of PTC,aiming to reveal the potential hazards of such radiation exposure in PTC patients.Methods:Two datasets(GSE29265 and GSE35570)containing RNA-seq data and corresponding clinical information were retrieved and downloaded from the GEO database.These datasets included thyroid cancer samples from patients exposed to ionizing radiation due to the Chernobyl disaster,as well as sporadic thyroid cancer cases.After data cleaning,merging,batch effect correction,differential gene expression analysis,functional enrichment analysis,immune cell infiltration analysis,and tumor microenvironment analysis were performed using R language.Results:In tumor samples,the radiation-exposed group exhibited significant differential gene expression compared to the sporadic group,with three genes upregulated and 27 genes downregulated.These differentially expressed genes were primarily enriched in biological functions closely related to immune responses,including chemokine activity,immune cell chemotaxis,and tumor immunity.Immune cell infiltration analysis indicated that radiation exposure had a limited impact on immune cell infiltration in normal samples.However,in tumor samples,the immune and ESTIMATE scores were significantly lower in the radiation-exposed group than in the sporadic group.Further analysis revealed that total T cells,CD4+T cells,CD8+T cells,B cells,and cytotoxic lymphocytes exhibited significantly lower infiltration levels in the tumor microenvironment of the radiation-exposed group than the sporadic group.Conclusion:Although low-to-moderate dose ionizing radiation has a relatively minor impact on normal thyroid tissue,it significantly reduces the infiltration of various immune cell subtypes in the PTC tumor microenvironment.This reduction in immune infiltration may have important implications for disease progression.

Objective To explore the characteristics of TCM syndromes in patients with obesity with metabolic associated fatty liver disease(MAFLD).Methods TCM Symptom Collection Form was developed to collect the clinical symptoms of obesity patients who attended the Department of Acupuncture and Moxibustion of Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,from July to December of 2024.Factor analysis and clustering analysis were used to explore the distribution law of different syndrome elements and TCM syndromes.Results A total of 309 obese patients(221 with MAFLD)were included,with 20 symptoms with a frequency of≥5%.Factor analysis suggested that there was a significant difference between the two groups in the pathogenic syndrome elements of qi stagnation,yin deficiency,qi deficiency,hyperactivity of yang,yang deficiency,dampness,dynamic wind,and the locus of disease syndrome elements of the spleen and the heart spirit(P<0.05).Clustering analysis showed that the syndrome types of patients with MAFLD were mainly the syndrome of liver and stomach stagnation and heat,the syndrome of spleen deficiency and stomach heat,and the syndrome of spleen and kidney deficiency;the syndrome types of patients without MAFLD were mainly spleen-stomach qi stagnation,gastrointestinal excess-heat,spleen-deficiency-dampness obstruction,and spleen-kidney deficiency.Conclusion Patients of obesity with MAFLD are more likely to have the co-existence of the pathogenesis of damp-heat obstruction and spleen-kidney deficiency.

Objective:To analyze the spatial-temporal epidemiological characteristics of pertussis from 2013 to 2022 in Hebei Province and to provide a reference for improving prevention and control measures.Methods:Based on the data of pertussis reported in Hebei Province during 2013-2022 to analyze the popular characteristic, the ArcGIS 10.8 software was used to construct a ring map and to perform spatial autocorrelation analysis; the SaTScan 10.1 software was used for spatial-temporal scan statistics.Results:There were 6 715 cases of the cumulative report in Hebei Province from 2013 to 2022 without death. The annual report incidence was 0.90/100 000. The overall incidence rate showed an upward trend from 2013 to 2019, and during 2020-2021, it showed a sharp decline, but in 2022, it showed a sharp increase. Summer and autumn are the peak seasons of the epidemic. The incidence was highest in age group <1 year (48.67%), and the lowest age group in age group ≥15 years (0.45%) and mainly scattered children (78.03%); the incidence about men is higher than women. Spatial autocorrelation analysis showed that the onset of pertussis has spatial clustering, and high-high clusters were found in Langfang, Baoding, and Cangzhou, the top three countries with reported incidence. The area covered by a low-low cluster was consistent with the distribution of the corresponding low-incidence areas in this study. Space-time scan detects five statistically significant areas, and three zones were concentrated in 2022.Conclusions:The incidence of pertussis in Hebei had obvious season, population, and area-specific differences. There was obvious spatiotemporal and clustering, so the control of key areas should target the characteristics of time and space.

BACKGROUND:At present,the treatment of infected bone defects has the problems of long course of disease,poor treatment effect and high cost.The osteogenic effect of personalized bone replacement materials in clinical treatment is limited.Therefore,a 3D-printed bone graft material with both good osteogenic effect and antibacterial effect is urgently needed for clinical treatment. OBJECTIVE:To summarize the research status of 3D-printed scaffolds loaded with antimicrobial agents for the treatment of infected bone defects. METHODS:PubMed,Web of Science,Elsevier,and CNKI databases from January 2010 to June 2022 were searched for related articles.The Chinese search terms were"bone defect,3D printing,scaffold material,antibacterial,animal experiments,in vitro experiments".English search terms were"bone defect,3D printing,scaffold,antibiosis,animal experiment,in vitro".Finally,60 articles were included for review and analysis. RESULTS AND CONCLUSION:The 3D scaffolds made of titanium,magnesium,tantalum and other metals and their alloys have certain osteogenic properties,but do not have antibacterial function.Hydroxyapatite and other bioceramic materials have good biocompatibility and are prone to be degraded,whereas due to the lack of strength,they are usually combined with artificial polymer materials to form composite materials,which respectively mimic the inorganic and organic components in natural bone,and play their respective excellent functions.Antibiotics,silver/copper nanoparticles,antimicrobial peptides,gallium and other antibacterial agents play an antibacterial role by destroying bacterial cell membrane,producing reactive oxygen species to interfere with bacterial DNA replication,inhibiting iron absorption and other mechanisms.As a result,the 3D-printed scaffold has both antibacterial and osteogenic effects.However,there are still some problems such as drug resistance and difficult to control effective concentrations.3D-printed scaffolds are often loaded with antibacterial agents by loading drug-loaded microspheres on scaffolds,preparing antibacterial coating on the scaffold surface,and participating in joint 3D printing with drugs.The loading mode of antibacterial coating prepared on the scaffold surface is the most widely used,and its antibacterial effect is more stable.Nonetheless,the selection of the most suitable loading mode for antibacterial agents needs to be further discussed and summarized.It is a future research prospect to optimize the mechanical properties of composite scaffolds and prepare biomimetic bone scaffolds so that the degradation rate is consistent with the bone reconstruction rate in infected bone defects.The ideal antibacterial agents may play a role through a variety of antibacterial mechanisms,thus being expected to play a good antibacterial effect through low antibacterial concentration,which should be a hot spot of anti-bone infection research.After loading antibacterial agents on the surface of the scaffold,antibacterial agents can"intelligently"react to the local microenvironment,achieving controlled release,and regulating the osteogenesis,vascularization and immune response of the microenvironment,which is the focus of current research.

Objective To investigate the distribution and antimicrobial resistance profiles of pathogenic bacteria in Children's Hospital of Hebei Province to inform reasonable use of antibiotics.Methods Antimicrobial susceptibility of the bacterial isolates was tested using Kirby-Bauer method,VITEK-2 Compact,BD Phoenix 100 automated systems,and E-test method.The results were interpreted according to the breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2022.Results were analyzed by WHONET 5.6 software.Results A total of 11909 isolates were collected from 2020 to 2022,of which 45.1％ were Gram positive organisms and 54.9％ were Gram negative organisms.The prevalence of MRSA and in S.aureus and MRCNS in coagulase-negative Staphylococcus was 36.8％ and 73.8％,respectively.The resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin was 2.6％ and 93.5％,respectively,while the resistance rates of E.faecalis and E.faecium to high concentration gentamicin was 42.2％ and 66.2％,respectively.E.faecium showed significantly higher resistance rates to the antibiotics tested than E.faecalis.The prevalence of PRSP and PSSP was 1.7％ and 95.7％ respectively in the non-meningitis S.pneumoniae isolates.No vancomycin-or linezolid-resistant strains were found in Staphylococcus,Enterococcus,or Streptococcus.The prevalence of ESBLs-producing E.coli and K.pneumoniae was 47.4％ and 32.3％,respectively.The prevalence of carbapenem-resistant E.coli and K.pneumoniae was 2.0％ and 22.4％,respectively.The prevalence of carbapenem-resistant P.aeruginosa (CRPA) and carbapenem-resistant A.baumannii (CRAB) was 9.5％ and 22.1％,respectively.The resistance rate of Haemophilus influenzae to ampicillin was 83.8％.The prevalence of β-lactamase-producing H.influenzae and β-lactamase-non-producing ampicillin-resistant (BLNAR) H.influenzae was 76.1％ and 7.7％,respectively.No meropenem-resistant strains were found in H.influenzae.Majority (98.0％) of Moraxella catarrhalis strains produced β-lactamase.Conclusions Multi-drug resistant bacterial pathogens are still serious in pediatric inpatients.The common clinical isolates showed various levels of resistance to different antimicrobial agents.It is important to continue the surveillance of bacterial resistance in children,take proactive measures to curb the spread of drug-resistant bacteria,and use antibiotics rationally.

Objective:To analyze 80 strains of Streptococcus pneumoniae by using whole-genome sequencing technology, including serotype characteristics, drug resistance genes, carriage of virulence genes, multilocus sequence typing (MLST), and relatedness between strains. Methods:Whole-genome sequencing was performed on Streptococcus pneumoniae. Serotypes, resistance genes, virulence genes, and sequence typing (ST) were analyzed in conjunction with the CARD database, the NCBI database, the VFDB database, and the PubMLST website. The strains were compared by using KSNP4 based on the analysis of single-nucleotide polymorphisms (SNPs). An evolutionary tree was constructed with the IQ-TREE software and beautified by using EvolView software. Results:Of all 80 Streptococcus pneumoniae strains, serotypes 19F, 19A, 14 and 23F were predominant, 30 strains were from cases of invasive pneumococcal disease (IPD) and 50 strains were from cases of non-invasive pneumococcal disease (NIPD). The virulence genes psaA, nanB, lytA, lytC, and ply were detected in all cases, while cps4 A, cps4 B, and hysA were detected in 98.75% of cases, and nanA was detected in 90.00%, rrgA and rrgB showed statistical differences between IPD and NIPD( P<0.05). The resistance genes patA, patB, tetM, pmrA, PBP1 b, RlmA( II), and ermB were detected in all cases, while PBP1 a was detected in 98.75% of cases. There was a statistically significant difference between IPD and NIPD for mefA and msrD( P<0.05). MLST analysis of 80 strains of bacteria showed that the ST types were mainly ST271, ST320, ST876, ST81, in which seven new ST types were emerged; the phylogenetic tree could be divided into three branches, The dominant ST types of the strains with serotypes 14, 23F, 19F, and 19A were ST876, ST81, ST271, and ST320, respectively. Conclusions:The study finds that the main serotypes of the 80 strains are 19F, 19A, 14 and 23F. The strains have more varieties of virulence genes, resistance genes and high carriage of some genes; rrgA, rrgB and mefA, msrD differ between IPD and NIPD. ST-types are characterised by diversity and new ST-types are constantly emerged. A correlation exists between serotypes and systemic evolution in the phylogenetic analyses, with each serotype contains its own dominant ST-types.