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.

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 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.

Objective:To investigate the significance and importance of the interaction between surgeons and engineers during the preoperative planning phase of total knee arthroplasty (TKA) when utilizing patient-specific instrumentation (PSI).Methods:A retrospective review was conducted on 202 knees of PSI-assisted TKA performed on 178 patients between June 2018 and August 2022. The patients' mean age was 68.4±6.2 years, ranging from 53 to 86 years. Among the participants, there were 149 females and 29 males, 93 left knees and 109 right knees. The study involved 171 patients of osteoarthritis (193 knees) and 7 patients of rheumatoid arthritis (9 knees), with 194 knees presenting varus knees and 8 knees with valgus knees. The preoperative plan documents, from the initial engineer-designed plan to the final plan approved by the surgeon, were analyzed to assess the frequency, parameters, and reasons for adjustments made during the planning process.Results:The planning of the 202 PSI-assisted TKA was subjected to at least one round of surgeon-engineer interaction. Among the 202 TKA planning, 117 knees (57.9%) underwent modifications after discussion, with most plans (100 knees, 49.5%) being confirmed after one round of modification. Two rounds of modifications were performed on 10 knees (5.0%), and three rounds on 5 knees (2.5%). A maximum of four rounds of modifications were made on two knees (0.9%). Furthermore, in the case of the remaining 85 knees (42.1%), the surgeons promptly consented to the engineers' initial planning following the discussions. Specific adjustments were made in 106 knees (52.5%) regarding femoral parameters, 57 knees (28.2%) concerning tibial parameters, and 46 knees (22.8%) requiring adjustments to both femoral and tibial parameters. Notably, the most frequently adjusted parameter was the osteotomy thickness of the posterior femoral condyles, which was modified in 94 knees (80.3%). The reasons for adjusting femoral or tibial parameters were summarized, revealing the main factors as follows: 1) Discrepancy between the mediolateral and anteroposterior diameters of the femoral condyle; 2) Twisted deformity of the proximal tibia; 3) Severe flexion contracture deformity of the knee; 4) Collapse of the medial or lateral tibial plateau; 5) Evident anterior arch deformity of the femur.Conclusion:The interaction between surgeons and engineers plays a pivotal role in the preoperative phase of PSI-assisted TKA. Effective collaboration allows surgeons to accurately analyze the unique anatomical characteristics and pathological changes of each patient in a three-dimensional perspective, facilitating the formulation of individualized surgical plans.

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.

Objectives To explore the dose-response relationship between low-dose ionizing radiation and thyroid hormone levels of radiation medical workers and provide theoretical basis for occupational health protection to this population. Methods Using a prospective cohort study design, we collected health examination reports on employees that worked on jobs with occupational exposure to radiation at hospital with individually dose monitoring data for 1 237 workers. The effective cumulative radiation dose was divided into three groups: 0～2.586 mSv, 2.586～3.757 mSv, 3.758～31.272 mSv by the interquartile range. The low-dose group was used as a reference to compare the changes in thyroid hormones of medical workers in different cumulative radiation dose groups. The generalized linear models and restricted cubic spline model were used to examine the association and dose-response relationship between the cumulative effective dose and changing thyroid hormones. Results There were statistically significant differences in changing thyroxine (T4) and Free triiodothyronine (FT3) levels among three different dose groups of 1237 subjects (P < 0.05). The results of generalized linear models analysis revealed that 2.586～3.757 mSv was a significant risk factors of changing T4, with β of 3.514 (95% confidence interval [95% CI]: 0.900～6.128) after adjusting for gender, age, working duration, occupation, medical level and smoking, while the association with changing FT3 was not observed (P > 0.05). The restrictive cubic spline (RCS) model analysis indicated a non-linear dose-response correlation between cumulative radiation dose with changing T4 (P = 0.023). Conclusion Long-term exposure to low-dose ionizing radiation could induce the thyroid damage among medical occupational population. And there is a dose-response relationship between cumulative radiation dose and changing thyroxine.

Objective To measure the peripheral dose distributions of the mobile head cone beam computed tomography (CBCT) and evaluate the impact of CBCT on the surrounding personnel and environment, and provide data support for clinical radiation protection management. Methods Combined with the structural characteristics of CBCT, AT1123 was used in the direction of 0° (counterclockwise), 45°, 90°, 135°, 180°, 225°, 270° and 315° in front of CBCT to measure the ambient dose equivalent rate of 30 cm, 80 cm and 130 cm away from the ground when the equipment was normally out of the beam, and the boundary of the temporary control area was drawn. At the same time, the dose level behind the lead screen 1 m away from the external surface of the equipment was measured and analyzed. Results The dose field around CBCT was symmetrically distributed with the dividing line of 0° and 180°, and the radiation dose level of 5.5 m in the direction of 0°, 3.5 m in the direction of 45°, 0.5 m in the direction of 90° and within 1.0 m in the direction of 180° (inside the "spoon" type) was higher than 2.5 μSv/h. The radiation dose levels of CT aperture 0° (straight forward), 45° and 315° behind the lead screen 1 m away from the equipment surface were 0.37 μSv/h, 0.22 μSv/h and 0.54 μSv/h, respectively. Conclusion The results show that the radiation dose around the mobile head cone beam CT is in a low dose level, the distribution of the dose field can provide necessary reference for the administrative and medical personnel to strengthen the radiation safety management. At the same time, it is suggested that lead screens should be set up in the clinical use of mobile CT to ensure the health and safety of the surrounding people and the environment.