PD-1/PD-L1 Provides Protective Role in Hypoxia-Induced Pulmonary Vascular Remodeling.

BACKGROUND: Hypoxia-induced pulmonary hypertension (HPH) is a T helper 17 cell response-driven disease, and PD-1 (programmed cell death 1)/PD-L1 (programmed cell death-ligand 1) inhibitor-associated pulmonary hypertension has been reported recently. This study is designed to explore whether the PD-1/PD-L1 pathway participates in HPH via regulating endothelial dysfunction and T helper 17 cell response. METHODS: Lung tissue samples were obtained from eligible patients. Western blotting, immunohistochemistry, and immunofluorescence techniques were used to assess protein expression, while immunoprecipitation was utilized to detect ubiquitination. HPH models were established in C57BL/6 WT (wild-type) and PD-1-/- mice, followed by treatment with PD-L1 recombinant protein. Adeno-associated virus vector delivery was used to upregulate PD-L1 in the endothelial cells. Endothelial cell function was assessed through assays for cell angiogenesis and adhesion. RESULTS: Expression of the PD-1/PD-L1 pathway was downregulated in patients with HPH and mouse models, with a notable decrease in PD-L1 expression in endothelial cells compared with the normoxia group. In comparison to WT mice, PD-1-/- mice exhibited a more severe HPH phenotype following exposure to hypoxia, However, administration of PD-L1 recombinant protein and overexpression of PD-L1 in lung endothelial cells mitigated HPH. In vitro, blockade of PD-L1 with a neutralizing antibody promoted endothelial cell angiogenesis, adhesion, and pyroptosis. Mechanistically, hypoxia downregulated PD-L1 protein expression through ubiquitination. Additionally, both in vivo and in vitro, PD-L1 inhibited T helper 17 cell response through the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) pathway in HPH. CONCLUSIONS: PD-1/PD-L1 plays a role in ameliorating HPH development by inhibiting T helper 17 cell response through the PI3K/AKT/mTOR pathway and improving endothelial dysfunction, suggesting a novel therapeutic indication for PD-1/PD-L1-based immunomodulatory therapies in the treatment of HPH.

Airways epithelial exposure to Streptococcus pneumoniae in the presence of the alarmin IL-33 induces a novel subset of pro-inflammatory ILC2s promoting a mixed inflammatory response.

BACKGROUND: We have previously shown that asthma-like airways inflammation may be induced by topical exposure to respiratory tract pathogens such as S. pneumoniae (SP) in concert with epithelial alarmins such as IL-33. Details of the pathogenesis of this murine surrogate remain however unexplored. METHODS: Airways inflammation was induced by repeated, intranasal exposure of Il-4-/-, Rag1-/- and Rag2-/-Il2rg-/- mice (in which B lymphocyte IgE switching, adaptive and innate immunity are respectively ablated) as well as wild type mice to inactivated SP, IL-33 or both. Airways pathological changes were analysed, and the subsets and functions of locally accumulated ILC2s investigated by single cell RNA sequencing and flow cytometry. RESULTS: In the presence of IL-33, repeated exposure of the airways to inactivated SP caused marked eosinophil- and neutrophil-rich inflammation and local accumulation of ILC2s, which was retained in the Il-4-/- and Rag1-/- deficient mice but abolished in the Rag2-/-Il2rg-/- mice, an effect partly reversed by adoptive transfer of ILC2s. Single cell sequencing analysis of ILC2s recruited following SP and IL-33 exposure revealed a Klrg1+Ly6a+subset, expressing particularly elevated quantities of the pro-inflammatory cytokine IL-6, type 2 cytokines (IL-5 and IL-13) and MHC class II molecules, promoting type 2 inflammation as well as involved in neutrophil-mediated inflammatory responses. CONCLUSION: Local accumulation of KLRG1+Ly6a+ ILC2s in the lung tissue is a critical aspect of the pathogenesis of airways eosinophilic and neutrophil-rich inflammation induced by repeated exposure to SP in the presence of the epithelial alarmin IL-33.

Bacterial antigens and asthma: a comparative study of common respiratory pathogenic bacteria.

Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae (S. pneumoniae) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens.Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae, Moraxella catarrhalis (M.catarrhalis) and Haemophilus influenzae (H.influenzae) lysates-specific IgE were measured in patients with asthma and control subjects.Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable.Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive (S. pneumoniae) and Gram-negative (M. catarrhalis and H. influenzae) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae-specific IgE.

Staphylococcus aureus lysate induces an IgE response via memory B cells in nasal polyps.

BACKGROUND: Locally increased IgE levels plays a pathologic role in chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: This study aimed to investigate whether Staphylococcus aureus could induce aberrant IgE synthesis in CRSwNP and the potential mechanisms involved. METHODS: Total IgE, IL-4, IL-5, and IL-13 concentrations in the supernatants of the cultures stimulated with S aureus lysate were assessed by ELISA. S aureus-induced cellular responses were investigated by single-cell RNA sequencing. Flow cytometry and quantitative reverse transcription PCR were used to analyze B-cell subsets and stimulated cell ε-germline transcript expression, respectively. IgE-positive B-cell and germinal center localization were assessed by immunohistochemistry and immunofluorescence. RESULTS: S aureus lysate induced IgE production in the supernatants of nasal polyp (NP) tissues but not in those of healthy nasal mucosa. Moreover, IgE levels increased from days 2 to 4 after stimulation, paralleling the enhanced ε-germline transcript, IL-5, and IL-13 expression. Single-cell RNA sequencing revealed that there were increased IL-5 and IL-13 in group 2 innate lymphoid cells and identified a clonal overlap between unstimulated memory B cells and S aureus-stimulated plasma cells. The enriched IgE within NPs was mainly produced by IgE-negative memory B cells. Cellular evidence indicated that the IgE memory response to S aureus might also exist in the peripheral blood of CRSwNP patients. The S aureus-induced IgE memory response was associated with elevated IgE levels in NPs, asthma, and postoperative CRSwNP recurrence. CONCLUSIONS: S aureus induced an IgE response via IgE-negative memory B cells in CRSwNP patients, possibly contributing to CRSwNP development.

Psychological resilience characteristics of visually impaired adolescents: a qualitative study / 中国康复理论与实践

ObjectiveTo analyze the psychological resilience characteristics of visually impaired adolescents. MethodsFrom February to May, 2023, 13 visually impaired adolescents (average age of 16.5 years) from Nanjing Normal University of Special Education, Yangzhou Special Education School and Nanjing School for the Blind in Jiangsu, China were selected for semi-structured interviews with phenomenological method, and the interview data were sorted by theme analysis method. ResultsFour themes and twelve sub-themes were obtained; namely multiple sources of difficulties, including travel difficulties, learning difficulties, social difficulties and difficulties in daily life; need for external support, including insufficient family support, school support needs to be improved, need for peer support and insufficient social support; negative and positive adaptation coexist, including negative adaptation and positive adaptation; and negative coping and positive coping coexist, including positive coping and negative coping. ConclusionThe psychological resilience of visually impaired adolescents is characterized by multiple sources of difficulties, insufficient external support, coexistence of positive and negative adaptation, and coexistence of positive and negative coping. A joint family-school-society support system should be formed to reduce the source of their difficulties, and help them establish positive adaptation and positive coping methods, to enhance their psychological resilience.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes / 中国结合医学杂志

OBJECTIVE@#To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.@*METHODS@#Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.@*RESULTS@#TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).@*CONCLUSIONS@#TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

Correlation between Helicobacter pylori infection and gastrointestinal tumor in the physical examination population in Xi'an City / 公共卫生与预防医学

Objective To analyze the spatial distribution of Helicobacter Pylori (Hp) infection and its correlation with gastrointestinal tumors in the physical examination population of Xi'an city, and to provide reference for the prevention of gastrointestinal tumors in this area. Methods A total of 23 200 subjects who underwent physical examination in 25 public hospitals in Xi'an from January 2019 to January 2023 were selected as the research objects. The basic Information of the patients was derived through the Hospital Information System (HIS), and all subjects underwent 13C-breath test and gastroenterological endoscope. ArcGIS 10.6 software was used to draw a statistical map of Hp infection in Xi 'an for spatial autocorrelation analysis. Hp infection in patients with different gastrointestinal tumors was analyzed. Results In this study population, there were 10 858 cases of Hp infection , with an infection rate of 46.80% ; among them , 5 491 cases were male, with an infection rate of 46.60% , and 5,367 cases were female, with an infection rate of 47.01% , and there was no significant difference in the infection rate between genders (P>0.05). The prevalence of HP infection was higher in the 30-year-old and 20-year-old groups, 55.62% and 42.71%, respectively, and the infection rate showed a first increase and then a decreasing trend with age (χ2trend = 6201.21, 6945.22 , P2=13.49, 16.16, 17.27, 24.66, P<0.05 for all). Conclusion The distribution of Hp infection in the physical examination population of Xi'an city has the characteristics of spatial aggregation and is related to gastrointestinal tumor diseases. It is suggested to carry out Hp infection education for the population in key areas to prevent the occurrence of gastrointestinal tumor diseases.

Culin5 aggravates hypoxic pulmonary hypertension by activating TRAF6/NF-κB/HIF-1α/VEGF.

Hypoxic pulmonary hypertension (HPH) lacks effective pharmacologic treatments. Microarray-based gene expression indicates the crucial role of Cullin 5 (Cul 5) in HPH. This study showed that Cul 5 was upregulated in HPH patients and a murine model of HPH. In vitro, Cul 5 promoted the angiogenesis and adhesion capacity of human pulmonary artery endothelial cells (PAECs), which could be mitigated by Cul 5 inactivation mediated by pevonedistat or NEDD8 silence. In vivo, silencing of Cul 5 in the endothelium and Cul 5 inactivation by pevonedistat could also alleviate hypoxic vascular remodeling. Mechanistic research showed that Cul 5 participated in HPH pathogenesis via the TRAF6/NF-κB/HIF-1α/VEGF pathway. Inhibition of the TRAF6/NF-κB/HIF-1α/VEGF pathway could reverse Cul 5-induced human PAEC dysfunction. These findings demonstrate that Cul 5 is an important mediator of HPH via the TRAF6/NF-κB/HIF-1α/VEGF pathway firstly, and could be considered as a potential therapeutic target in the clinical treatment of HPH.

Cigarette smoke aggravates asthma via altering airways inflammation phenotypes and remodelling.

INTRODUCTION: Many asthmatic patients are exposed to cigarette smoke actively or passively, which contributes to asthma exacerbation and poor control. This study is to explore the effects of cigarette smoke on pathological changes in murine surrogate of asthma. METHODS: C57BL/6 mice were sensitised and challenged with ovalbumin (OVA) to establish a surrogate of asthma and then administered with cigarette smoke extract (CSE). Airways hyperresponsiveness (AHR) was measured using the Flexivent system. Histological staining (haematoxylin-eosin [HE], periodic acid Schiff [PAS], Congo red and Masson's trichrome) was employed to measure pathological changes in sections of lung tissue of experimental mice. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of total and OVA-specific IgE, cytokines and chemokines (eotaxin-1, IL-13, IL-1ß, TNF-α, IL-17A, IL-33) in the lung tissue homogenates. Immunoreactivity for vWF and α-SMA in lung tissue sections was detected by immunohistochemistry. RESULTS: Exposure of the animals to CSE significantly reduced OVA-induced AHR, the number of eosinophils in bronchoalveolar lavage fluid (BALF) and eosinophils infiltrating into the lung tissue, as well as concentrations of some cytokines in lung homogenate. In contrast, it significantly enhanced the number of macrophages and M2 in BALF, as well as collagen deposition, smooth muscle thickness and alveolar destruction in lung tissue. CONCLUSION: CSE inhibits OVA-induced AHR, changes inflammation 'phenotypes', while accelerates some aspects of airways remodelling, which might contribute to worse symptoms and be refractory to anti-inflammation therapies for asthmatics.

Attenuated airways inflammation and remodeling in IL-37a and IL-37b transgenic mice with an ovalbumin-induced chronic asthma.

BACKGROUND: Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown. METHODS: Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis. RESULTS: Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice. CONCLUSION: Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.

High level of serum complement 3 is a risk factor for vascular stenosis progression in TA patients receiving tocilizumab: a prospective observational study.

BACKGROUND: The IL-6R antibody tocilizumab has been proven effective in treating Takayasu arteritis (TA). However, some patients show silent vascular stenosis progression (VSP) despite treatment with tocilizumab. The aim of the study was to explore the related risk factors of VSP in patients treated with tocilizumab. METHODS: Patients receiving tocilizumab were enrolled from the prospective living ongoing East China Takayasu Arteritis cohort. Their medical information was uniformly recorded with a homogenized evaluation method. Magnetic resonant angiography or computed tomographic angiography was employed to monitor VSP during the follow-up period, and Cox regression analysis was performed to explore the related risk factors. RESULTS: Thirty-eight patients were enrolled, among whom 18 (47.4%) experienced VSP, and seven and three patients experienced new and worsened vascular ischemic symptoms and events (VISE) during follow-up, respectively. The median period for VSP occurrence was 6.9 months during follow-up. Patients with VSP showed higher levels of baseline complement 3 (C3) than those in the patients without VSP. Multivariate Cox regression analysis revealed baseline C3 level (hazard ratio [HR] = 7.05, 95% confidence interval: 1.50-33.07, p = 0.013) was independently associated with VSP, with a cut-off value of 1.22 g/L. CONCLUSIONS: 47.4% of TA patients treated with tocilizumab would suffer VSP. A high C3 level is a risk factor for VSP in TA patients receiving tocilizumab, which may facilitate the option of tocilizumab in the future.

Similarities and differences in kinetic characteristics of airways inflammation, formation of inducible bronchial-associated lymphoid tissue and remodeling between young and old murine asthma surrogates induced with house dust mite.

Elderly asthmatics have higher morbidity and mortality compared with those of youngers. It has been shown that there are also some differences in clinic phenomena between young and elderly asthmatics, however, there is lack of the kinetic comparisons of the changes in the development of asthma between two populations. To better understand the specific pathophysiological manifestations in older patients with asthma, we dynamically and parallelly compared pathophysiological changes in the airways and lung tissues between young and old murine asthma surrogates based on sensitization and challenge with house dust mite (HDM). Murine models were established in young (6-8-week-old) and old (16-17-month-old) female wild-type C57BL/6 mice. Our data showed that repetitive HDM exposure induced relatively low type 2 immune responses (airway hyperresponsiveness, eosinophils recruitment, expression of type 2 cytokines, mucus secretion, serum HDM specific immunoglobulin E (IgE) and IgG) in old mice. However, the type 3 immune responses (neutrophils infiltration and IL-17A expression) were enhanced in old HDM exposed mice, which sustained longer and higher than that of young mice. Notably, the relatively weakened allergic inflammation characteristics might be associated with lower numbers of CD20+ B cells and IgE+ cells in the iBALTs in old mice compared with those in young mice. Our data suggest that aging might compromise the ability to induce type 2 immune responses, but enhance type 3 immune responses upon repetitive HDM challenge, which might cause relevant phenomena in old experimental mice and might even be applicable to elderly patients with asthma in the clinic.

IRAK-M Regulates Proliferative and Invasive Phenotypes of Lung Fibroblasts.

Lung fibroblasts play an important role in subepithelial fibrosis, one feature for airway remodeling. IL-1 receptor-associated kinase (IRAK)-M was shown to involve fibrosis formation in airways and lung through regulation of inflammatory responses. IRAK-M is expressed by lung fibroblasts, whether IRAK-M has direct impact on lung fibroblasts remains unclear. In this investigation, we evaluated in vitro effect of IRAK-M on phenotypes of lung fibroblasts by silencing or overexpressing IRAK-M. Murine lung fibroblasts (MLg) were stimulated with house dust mite (HDM), IL-33, and transforming growth factor (TGF) ß1. Techniques of small interfering RNA or expression plasmid were employed to silence or overexpress IRAK-M in MLg fibroblast cells. Proliferation, migration, invasiveness, and fibrosis-related events were evaluated. Significant upregulation of IRAK-M expression in MLg cells was caused by these stimuli. Silencing IRAK-M significantly increased proliferation, migration, and invasiveness of lung fibroblasts regardless of stimulating conditions. By contrast, IRAK-M overexpression significantly inhibited proliferation and motility of MLg lung fibroblasts. IRAK-M overexpression also significantly decreased the expression of fibronectin, collagen I, and α-SMA in MLg cells. Under stimulation with TGFß1 or IL-33, IRAK-M silencing reduced MMP9 production, while IRAK-M overexpression increased MMP9 production. Modulation of IRAK-M expression affected cytokines production, either decreased or increased expression of TNFα and CXCL10 by the cells regardless of stimulation. Our in vitro data reveal that IRAK-M directly impacts on lung fibroblasts through modulation of cellular motility, release of inflammatory, and fibrotic cytokines of lung fibroblasts. These might suggest a new target by regulation of IRAK-M in slowing airway remodeling.

A single center survey and analysis on the psychological stress status and influencing factors of medical staff / 中华健康管理学杂志

Objective:To investigate and analyze the psychological stress status and influencing factors of medical staff in comprehensive grade A hospitals.Methods:This was a cross-sectional survey using a convenient sampling method. A questionnaire survey was conducted among 2 048 staff members of the Affiliated Hospital of Qingdao University from February 25 to June 16, 2022. The questionnaires included the Self-rating Stress Questionnaire (SSQ-53), the Self-rating Anxiety Scale, and the Self-rating Depression Scale. A total of 2 048 questionnaires were distributed and 2 048 were collected. Among them, 2 006 (97.95%) were valid questionnaires, and 2 006 medical staff were ultimately included in the analysis. According to the results of the scale, they were divided into the increased psychological stress group and the non increased psychological stress group. Descriptive analysis, independent sample t-test/chi-square test, correlation analysis, and other methods were used to analyze the psychological stress status of medical staff and the distribution of related factors, and multivariate logistic regression was used to analyze their influencing factors. Results:A total of 310 (15.5%) out of 2 006 study subjects showed increased psychological stress. Women had a statistically significant increase in physical (14.7% vs 8.0%, χ2=12.40, P<0.001) and emotional dimensions (18.2% vs 13.5%, χ2=5.04, P=0.025) of stress compared to men. The level of psychological stress was positively correlated with anxiety and depression ( r=0.810, 0.749, respectively, P<0.001). Univariate analysis showed that those who were women ( χ2=6.76, P=0.009), with low education backgrounds ( Z=-2.50, P=0.012), nurses ( χ2=15.72, P<0.001), or working in emergency departments ( χ2=13.64, P=0.009) had a higher rate of increased psychological stress, while the serum calcium level in the increased psychological stress group was lower than that in the non increased psychological stress group ( t=2.82, P=0.005). Multivariate analysis showed that low educational backgrounds ( OR=2.238, 95% CI: 1.090-4.597, P=0.028) and working in emergency department ( OR=1.589, 95% CI: 1.012-2.493, P=0.044) were independent risk factors for increased psychological stress of medical staff. Working in administrative and logistics departments ( OR=0.466, 95% CI: 0.229-0.950, P=0.036) and serum calcium level ( OR=0.213, 95% CI: 0.059-0.760, P=0.017) were negatively correlated with increased psychological stress. Conclusions:In comprehensive grade A hospitals, medical staff working in the emergency department or with lower educational backgrounds face greater psychological stress. Serum calcium level is negatively correlated with increased psychological stress, but the causal relationship needs further study.

Analysis of influencing factors of tuberculosis related health behaviors among college freshmen with health belief model / 中华行为医学与脑科学杂志

Objective:To explore the influencing factors of tuberculosis related health behaviors among college freshmen with health belief model, so as to provide a scientific basis for the intervention of health behaviors among students.Methods:From January to February 2021, the questionnaire survey was conducted among 5 254 college freshmen from 11 universities.The survey included general demographic data, tuberculosis related health behaviors, and tuberculosis related knowledge, disease threat perception and disease policy cognition.The SPSS 23.0 software was used for data analysis, independent sample t-test and one-way ANOVA were used for inter group comparison, and Logistic regression analysis was used to explore the influencing factors of health behavior holding. Results:The total score of tuberculosis related health behaviors among freshmen was 3~12 (11.01±1.10), and the overall holding rate of tuberculosis related health behaviors was higher.Male( B=-0.753, OR(95% CI)=0.471(0.417-0.531)), and tuberculosis history ( B=-1.088, OR(95% CI)=0.337(0.157-0.722)) were risk factors for tuberculosis related health behaviors among freshmen.Birth in city( B=0.117, OR(95% CI)=1.124(0.944-1.338)), father's education level college /undergraduate and above ( B=0.177, OR(95% CI)=1.194(1.024-1.392)), mother's education level high school/secondary school( B=0.356, OR(95% CI)=1.428(1.126-1.810)), college/undergraduate and above( B=0.194, OR(95% CI)=1.214(1.029-1.433)), take the initiative to understand tuberculosis knowledge ( B=0.208, OR(95% CI)=1.231(1.095-1.385)), higher tuberculosis knowledge score ( B=0.088, OR(95% CI)=1.092(1.041-1.145)), higher disease threat perception score ( B=0.082, OR(95% CI)=1.086(1.031-1.144)) and higher disease policy cognition score( B=0.320, OR(95% CI)=1.378(1.265-1.500)) were protective factors for tuberculosis related health behaviors among first-year undergraduates(all P<0.05). Conclusion:The application of health belief model can analyze and explain the influencing factors of tuberculosis-related health behaviors of freshmen, which is helpful to strengthen health education and advocate tuberculosis-related health behaviors.

The application of scenario simulation teaching in acute ST-segment elevation myocardial infarction course for the training of "5+3" professional master / 中华医学教育探索杂志

Objective:To explore the application and effect of scenario simulation teaching in ST-segment elevation myocardial infarction (STEMI) course for emergency training of "5+3" professional master.Methods:A randomized controlled trial was conducted among 48 "5+3" professional masters who would rotate in the emergency department, to compare the test results of the total and three scenes between scenario simulation teaching group ( n=24) and traditional teaching group ( n=24). The STEMI teaching was carried out through simulating the emergency room, standardized patients and first-aid simulators in the simulation teaching group, and the traditional teaching group was taught by conventional classroom teaching. After the class, "Theoretical Examination" and "Questionnaire Survey" were used to evaluate the teaching effect. The former was further divided into "first diagnosis and differential diagnosis of chest pain", "fast identification and processing of STEMI" and "rescue of cardiac arrest" for inter-group and intra-group evaluation. SPSS 20.0 was used to conduct t-test. Results:In the theoretical examination, the scenario simulation teaching group was superior to the traditional teaching group in the test of emergency processing for STEMI course [(82.38±2.41) vs . (68.00±1.95), t=4.64, P<0.001]. In the sub-analysis of scenario simulation teaching group, students in the role-play group had significantly higher scores than others in the non-role-play group [(90.50±3.04) vs . (79.67±2.79), t=2.09, P=0.049]. Scenario simulation teaching group was also superior to traditional teaching group in the "Questionnaire Survey". Conclusion:In the training and teaching of STEMI emergency processing, scenario simulation teaching group proves to be superior to traditional teaching, which deserves further promotion.

Effects of Qingfei Shenshi Decoction on the expressions of MMP-2, MMP-9 and TIMP-1 in lung tissue of bronchial asthma mice / 国际中医中药杂志

Objective:To investigate the effects of Qingfei Shenshi Decoction on the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 and tissue inhibitor of metalloproteinase timps-1 (TIMP-1) in lung tissue of asthma mice.Methods:Totally 50 male BALB/C mice were divided into 5 groups: normal group, model group, dexamethasone group, Qingfei Shenshi Decoction low- and high-dosage groups (10 mice /group) according to random number table method. Asthma model mice were prepared by ovalbumin (OVA) challenge method. After successful modeling, the dexamethasone group was given dexamethasone for gavage at the rate of 1.56 mg/kg, while Qingfei Shenshi Decoction groups were given high and low doses of Qingfei Shenshi Decoction for gavage at the rate of 14.235 g/kg and 28.470 g/kg, respectively. Normal group and model group were given 0.9% sodium chloride solution by gavage. At the end of gavage administration for 4 weeks, the airway reactivity (Penh value) in each group was detected; HE staining was used to observe the pathological changes of lung tissue; the contents of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor -α (TNF-α) in alveolar lavage fluid were determined by enzyme Linked immunosorbent assay (ELISA); the expressions of MMP-2, MMP-9 and TIMP-1 in lung tissue were detected by Western-blot.Results:Compared with model group, the damage of airway wall and alveolar wall of lung tissue in Qingfei Shenshi Decoction groups was significantly reduced. Compared with model group, the Penh value, IL-6, IL-1β and TNF-α levels in Qingfei Shenshi Decoction low- and high-dosage groups decreased ( P<0.05), and the expressions of MMP-9, MMP-2 and TIMP-1 in lung tissue decreased ( P<0.05), with a certain dose dependence. Conclusion:Qingfei Shenshi Decoction can effectively alleviate airway inflammation, reduce airway hyperresponsiveness, improve lung function and inhibit airway remodeling in asthmatic mice. Its mechanism may be related to down-regulating the expressions of MMP-2, MMP-9 and TIMP-1.

Analysis on infection sources and transmission chains of three outbreaks caused by 2019-nCoV Omicron variant in Beijing, China / 中华流行病学杂志

Objective: To investigate the infection sources and the transmission chains of three outbreaks caused by 2019-nCoV Omicron variant possibly spread through cross-border logistics in Beijing. Methods: Epidemiological investigation and big data were used to identify the exposure points of the cases. Close contacts were traced from the exposure points, and the cases' and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: The Omicron variant causing 3 outbreaks in Beijing from January to April, 2022 belonged to BA.1, BA.1.1 and BA.2. The outbreaks lasted for 8, 12 and 8 days respectively, and 6, 42 and 32 cases infected with 2019-nCoV were reported respectively. International mail might be the infection source for 1 outbreak, and imported clothes might be the infection sources for another 2 outbreaks. The interval between the shipment start time of the imported goods and the infection time of the index case was 3-4 days. The mean incubation period (Q1, Q3) was 3 (2,4) days and the mean serial interval (Q1, Q3) was 3 (2,4)days. Conclusions: The 3 outbreaks highlighted the risk of infection by Omicron variant from international logistics-related imported goods at normal temperature. Omicron variant has stronger transmissibility, indicating that rapid epidemiological investigation and strict management are needed.

Clinical and etiological characteristics of infectious vulvovaginitis in children in Zhejiang province from 2009 to 2019 / 中华儿科杂志

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.