Increasing 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. Four 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. Occurrences 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. HMGB1 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 develop an interpretable machine learning (ML) model for predicting severe Mycoplasma pneumoniae pneumonia (SMPP) in order to provide reliable factors for predicting the clinical type of the disease. We collected clinical data from 483 school-aged children with M. pneumoniae pneumonia (MPP) who were hospitalized at the Children's Hospital of Soochow University between September 2021 and June 2024. Difference analysis and univariate logistic regression were employed to identify predictors for training features in ML. Eight ML algorithms were used to build models based on the selected features, and their effectiveness was validated. The area under the curve (AUC), accuracy, five-fold cross-validation, and decision curve analysis (DCA) were utilized to evaluate model performance. Finally, the best-performing ML model was selected, and the Shapley Additive Explanations (SHAP) method was applied to rank the importance of clinical features and interpret the final model. After feature selection, 30 variables remained. We constructed eight ML models and assessed their effectiveness, finding that the CatBoost model exhibited the best predictive performance, with an AUC of 0.934 and an accuracy of 0.9175. DCA was used to compare the clinical benefits of the models, revealing that the CatBoost model provided greater net benefits than the other ML models within the threshold probability range of 34% to 75%. Additionally, we applied the SHAP method to interpret the CatBoost model, and the SHAP diagram was used to visually show the influence of predictor variables on the outcome. The results identified the top six risk factors as the number of days with fever, D-dimer, platelet count (PLT), C-reactive protein (CRP), lactate dehydrogenase (LDH), and the neutrophil-to-lymphocyte ratio (NLR). The interpretable CatBoost model can help physicians accurately identify school-aged children with SMPP. This early identification facilitates better treatment options and timely prevention of complications. Furthermore, the SHAP algorithm enhances the model's transparency and increases its trustworthiness in practical applications.

Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1–3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3⁺, CD4⁺, CD8⁺, NK, and CD3-CD19⁺ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 μg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively. Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

Objective: We studied the short-term effects of air pollutant concentrations in Suzhou City on respiratory infections in children of different age groups. Methods: We employed clinical data from children hospitalized with respiratory infections at the Children’s Hospital of Soochow University during 2014–2016, and air quality for Suzhou City covering the same period.We investigated the relationships between the air pollutant concentrations and respiratory tract infections in children by causative pathogen using time series models with lagged effects. Results: The results of single-pollutant models showed that PM2.5, PM10, NO₂, SO₂ and CO had statistically significant associations with respiratory tract infections in children under 3 years, with the largest effect sizes at a lag of 3 weeks. Notably, the multi-pollutant model found PM2.5 was significantly associated with viral respiratory in children under 7 months, and bacterial respiratory infections in other age groups, while PM10 concentrations were associated with viral infections in preschool children. Conclusion: PM2.5, PM10 and NO₂ are the main atmospheric pollutants in Suzhou. The associations between pollutant concentrations and viral and bacterial respiratory infections were stronger among children under 3 years than for older age group.s PM2.5 had the strongest influence on viral and Mycoplasma pneumoniae respiratory infections when multiple pollutants were tested together.

Background: To explore the roles of Toll-like receptor (TLR)2 in Th2 cytokine production and immunoglobulin (Ig) class switching following ovalbumin (OVA) sensitization.Methods: TLR2^−/−and wild-type C57BL/6 mice were sensitized by intraperitoneal injection with OVA. Lung pathology was assessed by hematoxylin and eosin staining. Abundance of interleukin (IL)4, IL5, IL13, and IL21 transcripts in the lungs was quantified by RT-PCR. OVA-specific IgG1, IgG2a, IgG2b, IgE and IgM were quantified by enzyme-linked immunosorbent assay. Phosphorylated signal transducer and activator of transcription (STAT)3 in lung tissue was detected by immunohistochemistry staining and nuclear factor (NF) κB activation was measured by immunofluorescence staining. STAT3 activation was inhibited using cryptotanshinone (CPT) treatment. Germline transcripts (Iμ-Cμ, Iγ-Cγ, Iα-Cα or Iε-Cε), post-recombination transcripts (Iμ-Cγ, Iμ-Cα or Iμ- Cε) and mature transcripts (V_HDJ_H-Cγ, V_HDJ_H-Cα or V_HDJ_H-Cε) were analyzed from splenic B cells of OVA-sensitized wild-type mice (with or without CPT treatment) and TLR2^−/−mice (with or without IL21 treatment).Results: The lungs of TLR2^−/−mice showed a lesser degree of inflammation than wild-type mice after OVA sensitization. Following OVA sensitization, levels of IL4, IL13, and IL21, but not IL5, were significantly lower in TLR2^−/−compared with wild-type mice. Moreover, OVA-specific IgG1 and IgE titers were markedly lower and higher, respectively, in TLR2^−/−mice. TLR2 deficiency inhibited STAT3 activation but not NF-κB p65 activation. CPT treatment reduced IgG1 titers via inhibition of Stat3 phosphorylation. Both TLR2 knockout and CPT treatment reduced the frequencies of Iγ1-Cγ1, Iγ3-Cγ3 and Iα-Cα transcripts, but IL21 treatment compensated for the effects of TLR2 deficiency.Conclusion: These results suggest a role of TLR2 in restricting OVA-sensitized lung inflammation via promotion of IgG1 and inhibition of IgE class switching regulated by IL21 and STAT3.

Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3 + , CD4 + , CD8 + , NK, and CD3-CD19 + cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively. Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.