Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

OBJECTIVE: To analyze the clinical effectiveness of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in rescuing children with severe pulmonary contusion. METHODS: A retrospective analysis was conducted on the clinical data of four children with severe pulmonary contusion who were treated with VV-ECMO in the pediatric intensive care unit of Xi'an Children's Hospital from April 2021 to December 2024. The general data, laboratory indicators within 24 hours after admission, imaging features, bronchoscopic findings, diagnostic and treatment processes, as well as therapeutic outcomes of the children were analyzed. RESULTS: All four pediatric cases were male, aged 4 years and 9 months, 6 years and 5 months, 8 years and 10 months, and 9 years and 7 months, respectively. One case resulted from a high-altitude fall and three from traffic accidents, all presenting with multiple fractures. All four cases progressed to dyspnea within 1-4 hours post-injury and received endotracheal intubation with invasive ventilator support within 2-5 hours. Three cases exhibited tachycardia upon admission and were treated with norepinephrine, all four cases presented with fine moist rales in the lungs. Imaging studies revealed diffuse exudative changes in all four cases. Bronchoscopy identified diffuse pulmonary hemorrhage, with one case additionally showing rupture of the right intermediate bronchus. Conventional mechanical ventilation failed to correct oxygenation in all cases, prompting initiation of VV-ECMO therapy within 8-22 hours post-injury. One case underwent right thoracic exploration under ECMO support. Following treatment, all four cases demonstrated gradual reduction in bloody airway secretions, resolution of pulmonary exudative changes on imaging, and absence of hemorrhage on bronchoscopy. They were successfully weaned off ECMO and ultimately discharged as cured. CONCLUSIONS Severe pulmonary contusion rapidly leads to respiratory distress, requiring ventilator-assisted ventilation within hours of injury. When conventional ventilator support is ineffective, ECMO can be life-saving, with timely intervention yielding favorable prognosis.
Humans ; Extracorporeal Membrane Oxygenation/methods* ; Male ; Retrospective Studies ; Child, Preschool ; Child ; Contusions/therapy* ; Lung Injury/therapy* ; Treatment Outcome

Objective:To investigate the efficacy of neutrophil elastase inhibitor in children with acute respiratory distress syndrome（ARDS）.Methods:A total of 168 children with moderate to severe ARDS who were hospitalized in the Department of Pediatric Intensive Care Unit，the Affiliated Children′s Hospital of Xi′an Jiaotong University and Children's Emergency Center of Gansu Provincial Central Hospital from January 2022 to December 2023 were selected. Eighty-seven children receiving neutrophil elastase inhibitors were treated as the treatment group and 81 children receiving conventional treatment as the control group. The dynamic changes of general data，clinical indicators and ventilator parameters at 24 h，48 h and 72 h were compared between the two groups. Mortality at 28 days was the primary endpoint. Kaplan-Meier curve and Log-Rank test were used to evaluate cumulative survival.Results:There was no significant difference in general information and clinical characteristics between the two groups.Compared with the control group，arterial partial pressure of oxygen（PaO 2）/fraction of inspired oxygen（FiO 2）in the treatment group increased significantly at 48 h［（160.28±5.90）mmHg（1 mmHg=0.133 kPa）vs（141.04±4.01）mmHg， P<0.05］and 72 h［（227.58±6.85）mmHg vs（180.86±4.08）mmHg， P<0.05］，and the differences were statistically significant.The platform pressure in the treatment group were lower than that of the control group at 24 h［（28.18±3.95）cmH 2O（1cmH 2O=0.098 kPa）vs（30.15±7.75）cmH 2O， P<0.05］，48 h［（25.56±4.06）cmH 2O vs（29.07±5.01）cmH 2O， P<0.05］，72 h［（24.95±2.82）cmH 2O vs（27.12±6.51）cmH 2O， P<0.05］，and the differences were statistically significant. IL-8 in the treatment group were lower than that of the control group at 48 h［（78.26±14.05）ng/L vs（86.02±15.01）ng/L， P<0.05］and 72 h［（58.38±15.56）ng/L vs（68.68±18.05）ng/L， P<0.05］，and the differences were statistically significant.The survival curve showed that the cumulative survival rate of the treatment group was higher than that of the control group，the difference between the two groups was statistically significant（ χ2=4.549， P=0.033）. Conclusion:Neutrophil elastase inhibitors can reduce the lung injury of ARDS patients by inhibiting the inflammatory response induced by neutrophils，and ultimately improve the prognosis of the disease.

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Mitochondrial autophagy is a unique mechanism that selectively clears dysfunctional or excess mitochondria,closely related to Alzheimer's disease(AD),which is characterized by aggregated neurotoxic proteins and dysfunctional mitochondria.Numerous recent studies have confirmed that traditional Chinese medicine can have significant therapeutic effects against AD,and its advantages including multi-target,multi-pathway,and multi-action mechanisms have become an important component of AD research.Chinese medicine formulas and monomeric active ingredients,such as Jiannaoyizhi Fang,Danggui Shaoyao Tang,alkaloids,and flavonoids,can regulate mitochondrial autophagy-related signaling pathways and targets,inhibit neuronal mitochondrial autophagy defects,and play a neuroprotective role.This review elaborates on the basic process of mitochondrial autophagy and its related signaling pathways and molecular mechanisms in the pathogenesis of AD,and considers the latest research progress on the use of traditional Chinese medicine to improve AD by regulating mitochondrial autophagy,to provide ideas and references for future basic research and clinical treatment.

Objective:To evaluate the safety and efficacy of immunoadsorption with protein A column(PA-IA) in refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children.Methods:The clinical data of 8 children with anti-NMDAR encephalitis who failed to receive first-line treatment from January 2022 to June 2023 in PICU of Xi'an Children's Hospital were retrospectively collected.Clinical features,modified Rankin score (mRS),anti-NMDAR antibody titers in serum and cerebrospinal fluid(CSF),cells count in CSF,protein level in CSF,serum IgG,complement C3,C4 level were analyzed before and after immunoadsorption therapy. All adverse events that occurred during treatment were recorded in detail.Result:Among the 8 children,there were 5 males and 3 females,aged 5 to 12 years old,and each patient was immunized 6 to 10 times,and 75 times of PA-IA treatment were performed. The mRS score decreased in 8 children after PA-IA treatment. Blood IgG level,CSF cell number,protein level in CSF,blood complement C3 and C4 levels,and antibody titers related in blood and CSF were all lower than those before PA-IA treatment. The differences were all statistically significant ( P<0.001).During 75 times of treatment,only 1 case of membrane rupture occurred during treatment,the treatment was stopped and continued after the plasma separator was replaced,with no other adverse reactions. Conclusion:PA-IA could effectively improve the clinical symptoms and neurological function of children with refractory anti-NMDAR encephalitis with good safety,but its exact efficacy in children with anti-NMDAR encephalitis needs to be verified by prospective studies with larger samples.

Mitochondrial autophagy is a unique mechanism that selectively clears dysfunctional or excess mitochondria,closely related to Alzheimer's disease(AD),which is characterized by aggregated neurotoxic proteins and dysfunctional mitochondria.Numerous recent studies have confirmed that traditional Chinese medicine can have significant therapeutic effects against AD,and its advantages including multi-target,multi-pathway,and multi-action mechanisms have become an important component of AD research.Chinese medicine formulas and monomeric active ingredients,such as Jiannaoyizhi Fang,Danggui Shaoyao Tang,alkaloids,and flavonoids,can regulate mitochondrial autophagy-related signaling pathways and targets,inhibit neuronal mitochondrial autophagy defects,and play a neuroprotective role.This review elaborates on the basic process of mitochondrial autophagy and its related signaling pathways and molecular mechanisms in the pathogenesis of AD,and considers the latest research progress on the use of traditional Chinese medicine to improve AD by regulating mitochondrial autophagy,to provide ideas and references for future basic research and clinical treatment.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To evaluate the safety and efficacy of immunoadsorption with protein A column(PA-IA) in refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children.Methods:The clinical data of 8 children with anti-NMDAR encephalitis who failed to receive first-line treatment from January 2022 to June 2023 in PICU of Xi'an Children's Hospital were retrospectively collected.Clinical features,modified Rankin score (mRS),anti-NMDAR antibody titers in serum and cerebrospinal fluid(CSF),cells count in CSF,protein level in CSF,serum IgG,complement C3,C4 level were analyzed before and after immunoadsorption therapy. All adverse events that occurred during treatment were recorded in detail.Result:Among the 8 children,there were 5 males and 3 females,aged 5 to 12 years old,and each patient was immunized 6 to 10 times,and 75 times of PA-IA treatment were performed. The mRS score decreased in 8 children after PA-IA treatment. Blood IgG level,CSF cell number,protein level in CSF,blood complement C3 and C4 levels,and antibody titers related in blood and CSF were all lower than those before PA-IA treatment. The differences were all statistically significant ( P<0.001).During 75 times of treatment,only 1 case of membrane rupture occurred during treatment,the treatment was stopped and continued after the plasma separator was replaced,with no other adverse reactions. Conclusion:PA-IA could effectively improve the clinical symptoms and neurological function of children with refractory anti-NMDAR encephalitis with good safety,but its exact efficacy in children with anti-NMDAR encephalitis needs to be verified by prospective studies with larger samples.