This study indicates that a direct microbe effect and the subsequent induced excessive host immune response contribute in part to the progression of RMPP.
Background Early distinction between refractory M. pneumoniae pneumonia (RMPP) and non-RMPP (NRMPP) is still difficult. The community-acquired respiratory distress syndrome (CARDS) toxin can induce inflammatory and histopathological phenotypes associated with M. pneumoniae infection. This study aimed to investigate the clinical significance of CARDS toxin and pro-inflammatory cytokines in children with RMPP and to explore whether CARDS toxin can induce TNF-α expression. Methods Levels of CARDS toxin and cytokines in BALF from control and children with MPP were determined by real-time PCR and ELISA, respectively. A receiver-operating characteristic (ROC) analysis was performed to assess the diagnostic values of CARDS toxin, TNF-α, and IL-6 in RMPP. The recombinant CARDS toxin was constructed and prepared at different concentrations for stimulation of RAW264.7 cells. After co-culture with CARDS toxin, cytokines were detected by ELISA and the mRNA levels were measured by real-time PCR. Effects of CARDS toxin and TNF-α on inflammatory cell infiltration and mucus secretion in mouse lungs were also evaluated. Results Levels of CARDS toxin, TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were significantly higher in RMPP cases compared with NRMPP cases. Furthermore, TNF-α had better diagnostic ability for differentiation of RMPP with AUC of 0.824 and Youden index of 0.692 compared with CARDS toxin and IL-6. Moreover, CARDS toxin was positively correlated with TNF-α level in MPP cases. In vitro assay revealed that CARDS toxin induced RAW264.7 macrophages to secrete TNF-α. Further in vivo assay showed that TNF-α deletion partially abrogated the CARDS toxin-mediated induction of inflammatory cell infiltration and mucus secretion in mouse lungs. Conclusions The high co-expression of TNF-α and CARDS toxin in BALF is a good diagnostic biomarker for differentiating children with RMPP and NRMPP.
Neutrophil infiltration is the characteristic pathological feature of M. pneumoniae pneumonia (MPP). This study aimed to explore the associations among neutrophil activity, clinical presentation, and role of the M. pneumoniae/interleukin-8 (IL-8)/neutrophil axis in the pathogenesis of MPP. A total of 42 patients with MPP were prospectively enrolled in the study. Neutrophil activity, including matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), and neutrophil elastase (NE), were measured. Clinical information was collected for all patients and control group. In vitro, IL-8 production was measured at different time points after M. pneumoniae infection of bronchial epithelial cells, and neutrophil activity was analyzed after IL-8 stimulation. The percentage of neutrophil in the bronchoalveolar lavage fluid was higher in the group of patients with high levels of M. pneumoniae DNA than in those with low levels of M. pneumoniae DNA (P < 0.05). IL-8, MMP-9, and NE in patients with MPP significantly increased compared with controls and decreased after treatment (P < 0.05). MPO and MMP-9 were associated with duration of fever (r = 0.332, P < 0.05) and length of stay (r = 0.342, P < 0.05), respectively. In vitro, M. pneumoniae induced IL-8 production by bronchial epithelial cells in a time dependent manner. MPO, MMP-9 and NE production by neutrophils significantly increased compared with medium controls after IL-8 stimulation. In summary, the M. pneumoniae/IL-8/neutrophil axis likely plays a vital role in the pathogenesis of MPP.
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.
BackgroundProstate cancer (PCa) is a common malignant human tumor and one of the main causes of cancer-related deaths in men. At present, prostate-specific antigen levels are widely used to diagnose PCa in the clinic, but they are not sufficient for an accurate early diagnosis or prognosis.MethodsTo identify potential molecular markers for PCa, we used real-time PCR to measure the expression levels of various microRNAs, including miR-1825, miR-484, miR-205, miR-141, and let-7b, in the serum of 72 PCa patients and 34 healthy controls.ResultsmiR-1825, miR-484, miR-205, miR-141, and let-7b were shown to be highly specific for PCa, suggesting that they could be used as PCa tumor screening biomarkers. miR-205 may also be used as a biomarker for indicating bone metastasis in PCa patients, miR-1825 levels may help indicate tumor–node–metastasis classification, the evaluation of treatment effects, and determining prognosis, while let-7b levels may indicate potential tumor malignancy and the hormone resistance status and could be used as a basis to adjust individual treatments for the high-risk, early diagnosis of refractory PCa.ConclusionThis study identified possible PCa tumor markers to more accurately predict the occurrence, progression, and prognosis of PCa, and which could be used in the development of tumor drug therapy.Electronic supplementary materialThe online version of this article (10.1007/s11255-018-2009-4) contains supplementary material, which is available to authorized users.
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