Objective: To analyze the drug resistance of multidrug-resistant organism (MDRO) among hospitalized children in a children's hospital in Hebei Province from 2019 to 2023, so as to provide the basis for the rational clinical application of antibacterial drugs. Methods: Specimens including sputum, blood, urine, pus, bronchoalveolar lavage fluid, secretions, pleural fluid, and peritoneal fluid of hospitalized children from January 2019 to December 2023 were collected. Pathogen identification and drug susceptibility tests were performed on methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing Escherichia coli (ESBLs-EC), extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBLs-KP), carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Escherichia coli (CREC). The department distribution, specimen distribution, and drug resistance of MDROs were analyzed. Results: A total of 279 086 samples were submitted for testing, with 3 512 MDROs detected. Among these, MRSA and ESBLs-EC had relatively high detection rates of 35.76% and 41.50%, respectively. In the internal medicine pediatric patients, 1 869 MDROs were detected, accounting for 53.22%. The main departments were respiratory medicine, neonatology, and intensive care. In the surgical department, 1 643 MDROs were detected, accounting for 46.78%, with the main sources being general surgery and cardiac surgery. The highest numbers of MDROs were detected in sputum, pus, and urine samples, with 1 372, 527, and 494 isolates, representing 39.07%, 15.01%, and 14.07%, respectively. The resistance rates of MRSA to penicillin, oxacillin, and erythromycin were between 81.76% and 100.00%. ESBLs-EC and ESBLs-KP had a resistance rate of 100.00% to ceftriaxone. CRKP had a resistance rate of 100.00% to ampicillin/sulbactam and imipenem. CRAB had a resistance rate of 100.00% to cefoxitin, imipenem, and meropenem. CRPA had a resistance rate of 100.00% to ampicillin/sulbactam, ceftriaxone, cefoxitin, and imipenem. CREC had a resistance rate of 100.00% to imipenem. Conclusions In a children's hospital in Hebei Province, infections with MDROs among hospitalized pediatric patients are primarily caused by MRSA and ESBLs-EC. These infections are mainly distributed in the departments of respiratory medicine, neonatology, intensive care, general surgery, and cardiac surgery, with the highest detection rates in sputum, pus, and urine samples. Additionally, MRSA, ESBLs-EC, ESBLs-KP, CRKP, CRAB, CRPA, and CREC show high resistance rate to most antimicrobial agents.

Objective:To explore the epidemiological characteristics of human metapneumovirus (hMPV) in children hospitalized for acute respiratory tract infections in Hebei, and provide a theoretical basis for the clinical diagnosis and treatment of acute respiratory tract infections in children in Hebei.Methods:Retrospectively, 41 499 children hospitalized in Hebei Children′s Hospital for acute respiratory tract infections from January 2017 to December 2021 were included to analyze the morbidity of children of different genders and ages, and in different seasons, and to statistically analyze the epidemiological data such as the positive detection rate of hMPV, the detection rates of mixed infections with other pathogens, and the clinical diagnosis.Results:The overall positive detection rate of hMPV in hospitalized children with acute respiratory infections from 2017 to 2021 was 5.94%(2 464/41 499), with the highest positive detection rate of hMPV in the age group of 3 to 4 years (7.66%, 520/6 789) and the lowest in the age group of ≥5 years (2.89%, 180/6 225), with a statistically significant difference ( P<0.001); the positive detection rates in male and female children were respectively 5.97%(1 496/25 056) and 5.94%(968/16 443), and the difference was not statistically significant ( P>0.05). The positive detection rates of hMPV from 2017 to 2021 were 5.10%(408/7 998), 9.64%(915/9 491), 4.27%(426/9 969), 5.91%(368/6 226), and 4.44%(347/7 815), respectively, and the positive detection rate of hMPV in 2018 was significantly higher than that in the other years ( P<0.001). hMPV circulated throughout the year, with obvious seasonality, with the highest positive detection rate in spring and winter.The mixed detection rate of hMPV with other respiratory pathogens was 42.74% (1 053/2 464), of which mixed detection with rhinovirus was the most common, with a mixed detection rate of 48.24%(508/1 053).Clinical diagnosis of hPMV-positive children was mostly bronchopneumonia. Conclusions:hMPV is one of the important pathogens in hospitalized children with acute respiratory infections in Hebei, which is common in children under 5 years of age and can occur throughout the year, with peak epidemics in winter and spring. Mixed infections of hMPV with other respiratory pathogens are common and can increase the risk of worsening clinical symptoms in children.

OBJECTIVES: To investigate pharmacologically active components of Yiqi Zishen Formula (YZF) and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease (COPD). METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum. A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis. A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways. Fifty male C57BL/6J mice were randomized equally into control group, COPD model group, high- and low-dose YZF treatment groups, and N-acetylcysteine treatment group. Pulmonary function of the mice was assessed using whole-body plethysmography, and lung histopathology, alveolar structure, and airway remodeling were analyzed using HE staining. The levels of IL-1β, IL-6, and TNF‑α in bronchoalveolar lavage fluid (BALF) were determined with ELISA, and pulmonary expressions of PI3K, Akt, phosphorylated Akt (p-Akt), p65, and phosphorylated p65 (p-p65) were detected using immunohistochemistry. RESULTS: We identified a total of 156 chemical components (including 26 flavonoids or flavonoid glycosides, 27 alkaloids, and 11 saponins) in YZF and 43 prototype components in medicated rat serum. Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets. Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway. In mouse models of COPD, YZF treatment significantly increased mean alveolar number and peak expiratory flow (P<0.05), reduced mean linear intercept, bronchial wall thickness, lung coefficient, and BALF cytokine levels, and suppressed the expressions of PI3K, Akt, p-Akt, p65, and p-p65 in the lung tissues. CONCLUSIONS YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF‑κB pathway through its multiple components that interact with multiple targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Male ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; NF-kappa B/metabolism* ; Inflammation/drug therapy* ; Rats

Objective To investigate pharmacologically active components of Yiqi Zishen Formula(YZF)and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease(COPD).Methods Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum.A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis.A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways.Fifty male C57BL/6J mice were randomized equally into control group,COPD model group,high-and low-dose YZF treatment groups,and N-acetylcysteine treatment group.Pulmonary function of the mice was assessed using whole-body plethysmography,and lung histopathology,alveolar structure,and airway remodeling were analyzed using HE staining.The levels of IL-1β,IL-6,and TNF-α in bronchoalveolar lavage fluid(BALF)were determined with ELISA,and pulmonary expressions of PI3K,Akt,phosphorylated Akt(p-Akt),p65,and phosphorylated p65(p-p65)were detected using immunohistochemistry.Results We identified a total of 156 chemical components(including 26 flavonoids or flavonoid glycosides,27 alkaloids,and 11 saponins)in YZF and 43 prototype components in medicated rat serum.Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets.Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway.In mouse models of COPD,YZF treatment significantly increased mean alveolar number and peak expiratory flow(P<0.05),reduced mean linear intercept,bronchial wall thickness,lung coefficient,and BALF cytokine levels,and suppressed the expressions of PI3K,Akt,p-Akt,p65,and p-p65 in the lung tissues.Conclusion YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF-κB pathway through its multiple components that interact with multiple targets.

Objective:To explore the epidemiological characteristics of human metapneumovirus (hMPV) in children hospitalized for acute respiratory tract infections in Hebei, and provide a theoretical basis for the clinical diagnosis and treatment of acute respiratory tract infections in children in Hebei.Methods:Retrospectively, 41 499 children hospitalized in Hebei Children′s Hospital for acute respiratory tract infections from January 2017 to December 2021 were included to analyze the morbidity of children of different genders and ages, and in different seasons, and to statistically analyze the epidemiological data such as the positive detection rate of hMPV, the detection rates of mixed infections with other pathogens, and the clinical diagnosis.Results:The overall positive detection rate of hMPV in hospitalized children with acute respiratory infections from 2017 to 2021 was 5.94%(2 464/41 499), with the highest positive detection rate of hMPV in the age group of 3 to 4 years (7.66%, 520/6 789) and the lowest in the age group of ≥5 years (2.89%, 180/6 225), with a statistically significant difference ( P<0.001); the positive detection rates in male and female children were respectively 5.97%(1 496/25 056) and 5.94%(968/16 443), and the difference was not statistically significant ( P>0.05). The positive detection rates of hMPV from 2017 to 2021 were 5.10%(408/7 998), 9.64%(915/9 491), 4.27%(426/9 969), 5.91%(368/6 226), and 4.44%(347/7 815), respectively, and the positive detection rate of hMPV in 2018 was significantly higher than that in the other years ( P<0.001). hMPV circulated throughout the year, with obvious seasonality, with the highest positive detection rate in spring and winter.The mixed detection rate of hMPV with other respiratory pathogens was 42.74% (1 053/2 464), of which mixed detection with rhinovirus was the most common, with a mixed detection rate of 48.24%(508/1 053).Clinical diagnosis of hPMV-positive children was mostly bronchopneumonia. Conclusions:hMPV is one of the important pathogens in hospitalized children with acute respiratory infections in Hebei, which is common in children under 5 years of age and can occur throughout the year, with peak epidemics in winter and spring. Mixed infections of hMPV with other respiratory pathogens are common and can increase the risk of worsening clinical symptoms in children.

Objective:To preliminarily explore the long-term improvement of low-frequency deep brain stimulation (DBS) on the nucleus basalis of Meynert (NBM) in cognitive disorders, neuropsychiatric symptoms and sleep disorders of patients with early-onset severe Alzheimer's disease (AD).Methods:A retrospective study was performed; 18 patients with early-onset severe AD admitted to Department of Neurosurgery, First Medical Center of PLA General Hospital from January 2016 to December 2022 were included. These patients were divided into NBM-DBS group and control group according to different treatments; 6 patients received low-frequency NBM-DBS on basis of conservative treatments; 12 patients accepted conservative treatments. Changes in Brief Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Hamilton Depression Rating Scale (HAMD), Becker-Lavanson Mania Scale (BRMS), Pittsburgh Sleep Quality Index (PSQI), and Zarit Caregiver Burden Interview (ZBI) were observed before treatment and 1 year after follow up.Results:MMSE and MoCA scores 1 year after follow up obviously reduced compared with those before treatment in both NBM-DBS and control patients; MMSE and MoCA scores in NBM-DBS patients showed no significant differences between 1 year after follow up and before treatment ( P>0.05), while significant differences were noted in the control group between 1 year after follow-up and before treatment ( P<0.05); and no significant differences in MMSE and MoCA scores were noted between the 2 groups 1 year after follow up ( P>0.05). NPI, HAMD, BRMS and ZBI scores in the NBM-DBS group 1 year after follow up were significantly different compared with those before treatment ( P<0.05); no significant differences were noted in NPI, HAMD and ZBI scores in the control group between 1 year after follow up and before treatment ( P>0.05), while significant difference was noted in BRMS scores ( P<0.05); significant differences in NPI, HAMD, BRMS and ZBI scores were noted between the 2 groups 1 year after follow up ( P<0.05). Conclusion:Low-frequency NBM-DBS is not only effective in improving cognitive disorders, but also effective in improving neuropsychiatric symptoms and sleep disorders, as well as reducing caregiver burden in patients with early-onset severe AD.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

Chronic lung diseases(CLD)include chronic obstructive pulmonary disease,asthma,and idiopathic pulmonary fibrosis.Studies have shown that CLD are closely related to disorders in lipid metabolism.Therefore,lipids,as biomarkers of CLD,may be of great value in the diagnosis,prevention,and monitoring of disease treatment.This review discusses lipidomics from four major aspects:the technical methods of lipidomics,the selection of clinical samples for lipidomics,the discovery of biomarkers for CLD,and the differentiation of traditional Chinese medicine syndromes from CLD.

AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P＜0.05 or P＜0.01),significantly increased mean alveolar number and PEF(P＜0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P＜0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P＜0.05 or P＜0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P＜0.05 or P＜0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.