Non-allergic eosinophilic inflammation and airway hyperresponsiveness induced by diesel engine exhaust through activating ILCs.

RATIONALE: Diesel engine exhaust (DEE) is associated with the development and exacerbation of asthma. Studies have shown that DEE can aggravate allergen-induced eosinophilic inflammation in lung. However, it remains not clear that whether DEE alone could initiate non-allergic eosinophilic inflammation and airway hyperresponsiveness (AHR) through innate lymphoid cells (ILCs) pathway. OBJECTIVE: This study aims to investigate the airway inflammation and hyperresponsiveness and its relationship with ILC after DEE exposure. METHOD: Non-sensitized BALB/c mice were exposed in the chamber of diesel exhaust or filtered air for 2, 4, and 6 weeks (4 h/day, 6 days/week). Anti-CD4 mAb or anti-Thy1.2 mAb was administered by intraperitoneal injection to inhibit CD4+T or ILCs respectively. AHR、airway inflammation and ILCs were assessed. RESULT: DEE exposure induced significantly elevated level of neutrophils, eosinophils, collagen content at 4, 6 weeks. Importantly, the airway AHR was only significant in the 4weeks-DEE exposure group. No difference of the functional proportions of Th2 cells was found between exposure group and control group. The proportions of IL-5+ILC2, IL-17+ILC significantly increased in 2, 4weeks-DEE exposure group. After depletion of CD4+T cells, both the proportion of IL-5+ILC2 and IL-17A ILCs was higher in the 4weeks-DEE exposure group which induced AHR, neutrophilic and eosinophilic inflammation accompanied by the IL-5, IL-17A levels. CONCLUSION: Diesel engine exhaust alone can imitate asthmatic characteristics in mice model. Lung-resident ILCs are one of the major effectors cells responsible for a mixed Th2/Th17 response and AHR.

Evaluation and clinical practice of pathogens and antimicrobial resistance genes of BioFire FilmArray Pneumonia panel in lower respiratory tract infections.

BACKGROUND: Existing panels for lower respiratory tract infections (LRTIs) are slow and lack quantification of important pathogens and antimicrobial resistance, which are not solely responsible for their complex etiology and antibiotic resistance. BioFire FilmArray Pneumonia (PN) panels may provide rapid information on their etiology. METHODS: The bronchoalveolar lavage fluid of 187 patients with LRTIs was simultaneously analyzed using a PN panel and cultivation, and the impact of the PN panel on clinical practice was assessed. The primary endpoint was to compare the consistency between the PN panel and conventional microbiology in terms of etiology and drug resistance, as well as to explore the clinical significance of the PN panel. The secondary endpoint was pathogen detection using the PN panel in patients with community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). RESULTS: Fifty-seven patients with HAP and 130 with CAP were included. The most common pathogens of HAP were Acinetobacter baumannii and Klebsiella pneumoniae, with the most prevalent antimicrobial resistance (AMR) genes being CTX-M and KPC. For CAP, the most common pathogens were Haemophilus influenzae and Staphylococcus aureus, with the most frequent AMR genes being CTX-M and VIM. Compared with routine bacterial culture, the PN panel demonstrated an 85% combined positive percent agreement (PPA) and 92% negative percent agreement (NPA) for the qualitative identification of 13 bacterial targets. PN detection of bacteria with higher levels of semi-quantitative bacteria was associated with more positive bacterial cultures. Positive concordance between phenotypic resistance and the presence of corresponding AMR determinants was 85%, with 90% positive agreement between CTX-M-type extended-spectrum beta-lactamase gene type and phenotype and 100% agreement for mecA/C and MREJ. The clinical benefit of the PN panel increased by 25.97% compared with traditional cultural tests. CONCLUSION: The bacterial pathogens and AMR identified by the PN panel were in good agreement with conventional cultivation, and the clinical benefit of the PN panel increased by 25.97% compared with traditional detection. Therefore, the PN panel is recommended for patients with CAP or HAP who require prompt pathogen diagnosis and resistance identification.

The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model.

Objective: Semaphorin3E (Sema3E) mediates reorganization of the actin cytoskeleton, and plays an important role in ensuring the specificity of synapse formation and angiogenesis. However, the role of Sema3E in allergic asthma (AS) and eosinophilic bronchitis (EB) is still elusive. This study aimed to investigate the relationship between Sema3E in vagal ganglion and lung tissue, airway reactivity, and eosinophilic inflammation. Methods: The frequency of coughs and airway reactivity as well as the airway inflammation were observed in ovalbumin- (OVA-) induced AS and EB mouse models. The expression of Sema3E was examined in the vagal ganglion and lung tissues by immunofluorescence staining and western blotting analyses. In the Sema3E treatment protocol, exogenous Sema3E was administrated intranasally before challenge in AS model to study the effect of Sema3E on airway hyperresponsiveness, airway inflammation, mucus production, and collagen deposition. Results: The similar higher frequency of coughs and airway eosinophilic inflammation could be seen in AS and EB groups compared with nasal saline (NS) and dexamethasone (DXM) groups. The absence of the airway hyperresponsiveness was observed in EB and DXM group, while AS group showed increase in airway reactivity to methacholine. The expression of Sema3E in vagal ganglion and lung tissue was remarkably decreased in AS and DXM group compared with EB group. Sema3E-treated asthma mice displayed ameliorated airway hyperresponsiveness, mucus production, and collagen deposition. Conclusion: Sema3E in lungs and vagal ganglia is related to eosinophilic inflammation and has a protective effect on OVA-induced AHR in asthma.

Heavy metals in paired samples of hair and nails in China: occurrence, sources and health risk assessment.

The occurrence of heavy metals including chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd) and lead (Pb) was investigated in paired samples of hair and nails collected from 121 volunteers in 16 cities, China. Results showed that the mean concentrations of Zn, Cu, As, Pb, Cr, Ni and Cd were 205, 18.0, 7.79, 6.18, 3.54, 2.02, 0.533 µg g-1 in hair and 103, 8.09, 0.760, 7.27, 6.07, 8.81, 0.485 µg g-1 in nails, respectively. The concentrations of Zn, Ni, Cr, Cd and Pb were positively correlated in paired samples of hair and nails, whereas a negative correlation was found for Cu and As between hair and nails. Higher concentrations of heavy metals were found in northern China than southern China. The multivariate analysis of variance revealed that dwelling environment was the dominant factor influencing the levels of Cd in hair (p < 0.05), while age was the dominant factor influencing the levels of Cr in nails (p < 0.05). Moreover, industrial pollution and smoking were also the important factors leading to the accumulation of heavy metals in human body. Principal component analysis (PCA) showed that industrial pollution and decoration material immersion were the main factors for the high concentrations of Cr and Ni in hair, accounting for 62.9% of the total variation; As in hair was dominantly related to groundwater pollution. The concentrations of heavy metals were within the recommended ranges in nails from this study. However, the mean levels of Cr, Ni and As in hair exceeded their recommended reference values, indicating potential health risks from heavy metals for residents in China.

Construction of m7G subtype classification on heterogeneity of sepsis.

Sepsis is a highly heterogeneous disease and a major factor in increasing mortality from infection. N7-Methylguanosine (m7G) is a widely RNA modification in eukaryotes, which involved in regulation of different biological processes. Researchers have found that m7G methylation contributes to a variety of human diseases, but its research in sepsis is still limited. Here, we aim to establish the molecular classification of m7G gene-related sepsis, reveal its heterogeneity and explore the underlying mechanism. We first identified eight m7G related prognostic genes, and identified two different molecular subtypes of sepsis through Consensus Clustering. Among them, the prognosis of C2 subtype is worse than that of C1 subtype. The signal pathways enriched by the two subtypes were analyzed by ssGSEA, and the results showed that the amino acid metabolism activity of C2 subtype was more active than that of C1 subtype. In addition, the difference of immune microenvironment among different subtypes was explored through CIBERSORT algorithm, and the results showed that the contents of macrophages M0 and NK cells activated were significantly increased in C2 subtype, while the content of NK cells resting decreased significantly in C2 subtype. We further explored the relationship between immune regulatory genes and inflammation related genes between C2 subtype and C1 subtype, and found that C2 subtype showed higher expression of immune regulatory genes and inflammation related genes. Finally, we screened the key genes in sepsis by WGCNA analysis, namely NUDT4 and PARN, and verified their expression patterns in sepsis in the datasets GSE131761 and GSE65682. The RT-PCR test further confirmed the increased expression of NUDTA4 in sepsis patients. In conclusion, sepsis clustering based on eight m7G-related genes can well distinguish the heterogeneity of sepsis patients and help guide the personalized treatment of sepsis patients.

Heavy Metals in Indoor Dust Across China: Occurrence, Sources and Health Risk Assessment.

In this study, the occurrence of heavy metals including cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), and zinc (Zn) was investigated in indoor dust samples collected from 33 urban and rural areas in 11 provinces, China. The concentrations of the selected heavy metals were determined by an inductively coupled plasma mass spectrometry. The mean concentrations of Zn (166 mg kg-1), Pb (40.7 mg kg-1), Cr (19.8 mg kg-1), Cu (16.9 mg kg-1), and Cd (2.29 mg kg-1) in indoor dust are in low or moderate levels compared with other countries or regions. Cd was significantly enriched with the highest enrichment factor of 23.7, followed by Zn, Pb, Cu, and Cr, which were all lower than 3. The concentrations of Pb from Northern China (61.4 mg kg-1) were significantly higher than those from Southern China (8.88 mg kg-1). The concentrations of heavy metals in indoor dusts from rural areas were higher than those from urban areas except for Cu. The multivariate analysis of variance revealed that wall cover, fuel types, and air conditioning were dominant factors influencing the levels of heavy metals in indoor dust. Principal component analysis showed that outdoor dust and wall paint were main factors for the high concentrations of Cd, Pb, and Cr, accounting for 40.6% of the total contribution; traffic sources contributed to the high levels of Cu and Zn explained 20.6% of the total variance. The hazard indexes of selected heavy metals were less than 1 and carcinogenic risk value of Cr were between 1.01 × 10-6 and 1 × 10-4, indicating minor noncarcinogenic and carcinogenic risks from heavy metals in indoor dust for residents in China. Pb contributed 72.0% and 86.9% to the sum of noncarcinogenic risk values of selected heavy metals for adults and children, respectively. The carcinogenic risk value of Cr was approximately 13-fold higher than that of Cd for both adults and children. Children endured higher risks from heavy metals in indoor dust compared with adults.

Inhibition of TRPA1 reduces airway inflammation and hyperresponsiveness in mice with allergic rhinitis.

This study was conducted to investigate whether a transient receptor potential ankyrin 1 (TRPA1) antagonist (HC-030031) can reduce airway inflammation and hyperresponsiveness in a murine allergic rhinitis (AR) model. BALB/c mice were sensitized and challenged by ovalbumin (OVA) to induce AR. HC-030031 or vehicle was administrated to mice via intraperitoneal injection prior to OVA challenges. Nose-scratching events, histopathologic alterations of the airways, and bronchial hyperresponsiveness (BHR) were assessed. Differential cells and proinflammatory cytokines in the nasal lavage (NAL) and bronchoalveolar lavage (BAL) fluid were measured. Expressions of TRPA1 in nasal mucosa were examined by immunohistochemistry. TRPA1-expressing vagal neurons were labeled by immunofluorescent staining. HC-030031-treated AR mice had markedly reduced type-2 inflammation in nasal mucosa and ameliorated-nose-scratching events than AR mice received vehicle. HC-030031 treatment also dramatically reduced leucocyte numbers and IL-8 level in the BAL fluid, inhibited lower airway remodeling and fibrosis, and nearly abolished BHR. HC-0300031 treatment significantly inhibited the upregulated number of TRPA1 expressing nasal epithelial cells and TRPA1 expressing sensory neurons, leading to downregulation of SP in both upper and lower airways. Targeting TRPA1 may represent a promising strategy for treating AR and AR-related asthma.

Glial activation and inflammation in the NTS in a rat model after exposure to diesel exhaust particles.

Airway pollution can affect the central nervous system, but whether this causes glial activation and inflammation in the nucleus of solitary tract (NTS) remains unclear. We used a rat model with exposure to diesel exhaust particulate matter (DEP) at 200 µg/m3 (low exposure) and 1000 µg/m3 (high exposure) for 14 days. Activation of microglia and astrocytes in the NTS was assessed using Iba-1 and glial fibrillary acidic protein (GFAP) staining. The expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) in the NTS were evaluated by immunofluorescence. Changes in the intracellular structure of NTS neurons were observed via electron microscopy. Inflammatory cytokines and oxidant stress levels in the medulla were also measured. Exposure to DEP can cause NTS inflammation as well as airway inflammation, especially in the H-exposure group. We showed that the numbers of microglia and astrocytes in the NTS, as well as NGF expression in the NTS, were significantly higher in both exposure groups than in controls, but BDNF or GDNF expression was not detected. Exposure to DEP induced ultrastructural changes in NTS neurons as reflected by endoplasmic reticulum dilation, ribosomal loss, mitochondrial vacuolization, and a sparse myelin sheath. Medulla inflammation and an imbalance of oxidants and antioxidants also resulted from exposure to DEP. The H-exposure group showed an imbalance of oxidants and antioxidants with decreased levels of SOD and GSH and increased levels of MDA and ROS compared to the control group (both p < 0.01) in the medulla. Inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were also significantly increased in the H-exposure group. Fourteen days of exposure to DEP can affect the NTS neurons in rat. Glial activation and inflammation may play important roles in the response of the NTS to DEP.

Suspected SARS-CoV-2 infection with fever and coronary heart disease: A case report.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Suspected cases accounted for a large proportion in the early stage of the COVID-19 outbreak. The deviation of the nucleic acid test by throat swab (the current gold standard of COVID-19) caused by variation in sampling techniques and reagent kits and coupled with nonspecific clinical manifestations make confirmation of the suspected cases difficult. Proper management of the suspected cases of COVID-19 is crucial for disease control. CASE SUMMARY: A 65-year-old male presented with fever, lymphopenia, and chest computed tomography (CT) images similar to COVID-19 after percutaneous coronary intervention. The patient was diagnosed as having bacterial pneumonia with cardiogenic pulmonary edema instead of COVID-19. This was based on four negative results for throat swab detection of SARS-CoV-2 nucleic acid using reverse transcriptase-polymerase chain reaction assay and one negative result for serological antibody of SARS-CoV-2 with the serological assay. Additionally, the distribution of ground-glass opacities and thickened blood vessels from the CT images differed from COVID-19 features, which further supported the exclusion of COVID-19. CONCLUSION: Distinguishing COVID-19 patients from those with bacterial pneumonia with cardiogenic pulmonary edema can be difficult. Therefore, it requires serious identification.