BackgroundIncreasing numbers of refractory or severe, even fatal, cases of Mycoplasma pneumoniae infections have been reported in recent years. Excessive inflammatory responses play a vital role in the pathogenesis of refractory M. pneumoniae pneumonia (RMPP). HMGB1 is an actively secreted cytokine produced by macrophages and other inflammatory cells that participates in various infectious diseases. The present study aimed to explore the role and clinical significance of HMGB1 in children with RMPP and the potential mechanism of HMGB1 expression.MethodsFour hundred and fifty-two children diagnosed with M. pneumoniae pneumonia, including 108 children with RMPP, were enrolled from January 2013 to December 2015 at the Children’s Hospital of Soochow University. HMGB1, TNF-α, and IL-6 in peripheral blood from RMPP and non-RMPP (NRMPP) cases were detected by real-time PCR and ELISA. Lipid-associated membrane proteins (LAMPs) were extracted from live M. pneumoniae and prepared at different concentrations for stimulation of THP-1 cells. After coculture with LAMPs, HMGB1, TNF-α, IL-6, RAGE, TLR2, and TLR4 in THP-1 cells were detected by real-time PCR.ResultsOccurrences of cough, fever, and abnormal lung signs were more frequent in RMPP cases compared with NRMPP cases (all p < 0.05). Children with RMPP had longer hospital stays than children with NRMPP (p < 0.05). Different distributions of lymphocytes were noted between RMPP and NRMPP cases. HMGB1, TNF-α, and IL-6 levels were significantly higher in RMPP cases compared with NRMPP cases (all p < 0.05). HMGB1 had good diagnostic ability to differentiate RMPP with AUC of 0.876, sensitivity of 0.833, and specificity of 0.824 compared with TNF-α and IL-6. HMGB1 expression in THP-1 cells was increased by stimulation with 10 μg/ml LAMPs. TLR2 expression was increased after stimulation with 6 μg/ml LAMPs. HMGB1 level was positively associated with TNF-α, IL-6, and TLR2 levels.ConclusionsHMGB1 is a good diagnostic biomarker for differentiating RMPP and NRMPP. LAMPs from M. pneumoniae may induce HMGB1 expression in immune cells through the TLR2 pathway. Further in vitro and in vivo studies are needed for the development of a new treatment strategy to inhibit the HMGB1 pathway, thereby preventing the inflammation in RMPP.

To assess the impact of human bocavirus (HBoV) virus load on epidemiologic and clinical characteristics in children with lower respiratory tract infection (LRTI). Clinical records of a total of 654 patients with HBoV infection during January 2013 and December 2014 were retrospectively reviewed. Patients with high HBoV virus load infection had a similar age distribution with the total HBoV infection, which had a peak age group of 6–24 months. Patients with high virus load are significantly younger (P < 0.01) than those with low load. The patients who had wheeze and tachypnea/dyspnea at presentation were more strongly affiliated with the patients with high virus load (both P < 0.01). Co-infection was found significantly more frequently among patients with low virus load than those with high virus load (57.0% vs 38.9%; P < 0.01). High virus load was a significant predictor of severe LRTI (P < 0.05). HBoV infections are found in an important proportion of the hospitalized children with respiratory illnesses (8.85% in our series). A high HBoV virus load could be an etiologic agent for LRTI, which may lead to more severe lower respiratory tract symptom and severe disease.

The objective of this study was to obtain a better understanding of the effects of meteorological factors on the prevalence and seasonality of common respiratory viruses in China, which has a subtropical climate. A retrospective study was conducted by identifying children admitted to a hospital with acute respiratory infections due to seven common viruses between January 2001 and December 2011. A total of 42,104 nasopharyngeal samples were tested for respiratory syncytial virus (RSV), influenza A and B viruses (IV-A and IV-B), parainfluenza viruses 1-3 (PIV-1, PIV-2, PIV-3), and adenovirus (ADV) by direct immunofluorescence assay. Meteorological data were obtained from Suzhou Weather Bureau. Correlations of viral prevalence with meteorological factors were evaluated using Spearman rank correlation and partial correlation. Multivariate time-series analysis including an autoregressive integrated moving average (ARIMA) model and generalized linear Poisson models was conducted to study the effect of meteorological factors on the prevalence of respiratory virus infection. RSV and IV-A activity showed distinctive winter peak, whereas PIV-3 and ADV peaked in the summer. Incidence of RSV was correlated with low environmental temperature, and PIV-3 only with high temperature. IV-A activity was correlated with both low temperature and high relative humidity. ADV activity was correlated with high total rainfall. In the ARIMA model, RSV-associated hospitalizations were predictable, and the monthly number of RSV cases decreased by 11.25 % (95 % CI: 5.34 % to 16.79 %) for every 1 °C increase in the average temperature. Seasonality of certain respiratory virus may be explained by meteorological influences. The impact of meteorological factors on the prevalence of RSV may be useful for predicting the activity of this virus.

The role of Toll-like receptor (TLR) 2 in modulating allergy-induced asthma is contradictory. We investigated the effect of TLR2 gene deletion in a murine model of ovalbumin (OVA)-challenged asthma. TLR2 wild-type (TLR2(+/+)) and TLR2-deficient (TLR2(-/-)) mice were sensitized to soluble OVA antigens and challenged with OVA, and the extent of allergic airways disease was analyzed in both groups of mice at day 8 after being challenged with OVA aerosol. At day 8 post-OVA, TLR2(-/-) mice exhibited significantly lower airway hyperresponsiveness, airway inflammation, and whole lung T-helper type 2 (Th2) cytokine levels compared with the TLR2(+/+) group. TLR2 deletion also significantly reduced mucus cell metaplasia and peribronchial fibrosis in mice at day 8 after challenged by OVA. The p38/AKT/nuclear factor kappaB (NF-kappaB) p65 and phosphate extracellular signal-regulated kinase (ERK)/p38/AKT was decreased in TLR2(-/-) mouse lungs. Thus, during OVA asthma in mice, TLR2 is a major contributor to the maintenance of the adaptive Th2-cytokine-driven inflammatory disorder and ERK/p38 as well as AKT/NF-κB playing a role in it.

ObjectiveChanges in microRNAs (miRNAs) in the cerebrospinal fluid (CSF) are associated with different neurological diseases. Since alternations of miRNAs in neurosyphilis are insufficiently investigated, we analysed miRNAs in the CSF of patients suffering from neurosyphilis.MethodsExosomes were isolated from serum and CSF. Levels of 44 miRNAs were determined using quantitative real-time PCR-based miRNA array.ResultsIn patients with neurosyphilis (NSP), miR-590-5p, miR-570-3p and miR-570-5p were upregulated in the CSF and serum, when compared with patients with syphilis without neurosyphilis (SP). miR-590-5p and miR-570-3p were significantly upregulated (p<0.001). The expression of miR-21-5p was upregulated only in the CSF of NSP. Significant downregulation was observed for miR-93-3p in the CSF and serum of NSP. No statistical difference was found in the expression of miR-7-5p, miR-1307-5p, miR-203a-3p, miR-16, miR-23b-3p and miR-27b-5p in the CSF and serum of NSP and SP.ConclusionFor the first time, regulation profiles in miRNA in the CSF and serum were analysed in NSP. We found significant differences in upregulation and downregulation. Therefore, miRNAs may be potential biomarkers for the presence of neurosyphilis.