Clinical profiles of Mycoplasma pneumoniae pneumonia in children with different pleural effusion patterns: a retrospective study.

BACKGROUND: The clinical significance of the presence or absence of Mycoplasma pneumoniae (MP) in pleural effusion in Mycoplasma pneumoniae pneumonia (MPP) children has not yet been elucidated. Herein, we investigated the clinical implication of pleural fluid MP positive in children with MPP. METHODS: A total of 165 MPP children with pleural effusion requiring thoracocentesis were enrolled in this study. They were subsequently divided into two groups according to the presence or absence of MP in pleural effusion, namely positive group (n = 38) and negative group (n = 127). Information on their clinical manifestations, laboratory findings, radiological characteristics and treatment modalities was retrospectively collected from medical chart reviews. RESULTS: The length of hospitalization (15.00 (10.75-19.25) vs. 11.00 (9.00-14.00) days, p=0.001) and total course of illness (23.00 (18.00-28.00) vs. 20.00 (17.00-24.00) days, p=0.010) were significantly longer in the positive group than in the negative group. The occurrence of pericardial effusion (23.7% vs. 7.9%, p=0.017), atelectasis (73.7% vs. 53.5%, p=0.027) and necrotizing pneumonia (23.7% vs. 7.9%, p=0.017) were more frequent in the positive group compared to the negative group. The levels of neutrophil percentages (82.35% (75.40%-85.78%) vs. 72.70% (64.30%-79.90%), p<0.001), C-reactive protein (CRP) (71.12 (37.75-139.41) vs. 31.15 (13.54-65.00) mg/L, p<0.001), procalcitonin (PCT) (0.65 (0.30-3.05) vs. 0.33 (0.17-1.13) ng/ml, p=0.005), serum lactate dehydrogenase (LDH) (799.00 (589.00-1081.50) vs. 673.00 (503.00-869.00) U/L, p=0.009), D-dimer (6.21 (3.37-16.11) vs. 3.32 (2.12-6.62) mg/L, p=0.001) on admission were significantly higher in the positive group than in the negative group. These pronounced differences significantly contributed to the identification of MPP with MP positive pleural effusion, as evidenced by the ROC curve analysis. Marked elevations in adenosine deaminase (49.25 (36.20-60.18) vs. 36.20 (28.10-46.50) U/L, p<0.001) and LDH levels (2298.50 (1259.75-3287.00) vs. 1199.00 (707.00-1761.00) U/L, p<0.001) were observed in pleural fluid of the positive group when compared to the negative group. Meanwhile, the number of patients on low molecular weight heparin (LMWH) therapy (9 (23.7%) vs. 12 (9.4%), p=0.028) was higher in the positive group. Multivariate logistic regression analysis revealed that D-dimer > 7.33 mg/L was significantly associated with the incidence of MP positive pleural effusion in MPP (OR=3.517). CONCLUSIONS: The presence of MP in pleural fluid in MPP children with pleural effusion indicated a more serious clinical course. D-dimer > 7.33 mg/L was a related factor for MP positive pleural effusion in MPP. The results of the present study would help in the creation of a therapeutic plan and prediction of the clinical course of MPP in children.

Patterns of antibiotic administration in Chinese neonates: results from a multi-center, point prevalence survey.

OBJECTIVES: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. METHODS: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. RESULTS: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. CONCLUSION: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.

Effects of subcutaneous immunotherapy in allergic rhinitis children sensitive to dust mites.

BACKGROUND: Subcutaneous immunotherapy (SCIT) is now the only treatment that can modify the natural course of allergic rhinitis (AR). However, not all children with AR benefit from SCIT. OBJECTIVE: To evaluate the efficacy of SCIT in dust-mites-induced AR children and explore correlative factors predicting treatment response to SCIT. METHODS: 225 children aged 4-17 years old with AR were recruited from January 2016 to September 2019, and monitored at baseline, 4, 12, and 24 months after the start of SCIT treatment. The visual-analogue-score (VAS) was used to assess the clinical symptoms. Multivariate binary logistic regression analyses and receiver operating characteristic curves were used to explore correlative factors in predicting the efficacy of SCIT. RESULTS: The significant declines in VAS started after 4 months of SCIT and continued to improve throughout the study compared with baseline. An increase in children's age (OR=0.688, 95%CI: 0.479-0.988) and those with allergic history (OR=0.097, 95%CI: 0.009-1.095) were negatively associated with the risk of poor efficacy. Polysensitized children were more likely to suffer poor efficacy (OR=15.511 95%CI: 1.319-182.355). The clinical response at month 4 (r=0.707) and month 12 (r=0.925) was related to that at month 24. The area under the curve (AUC) for improvement at month 4 and month 12 was 0.746 and 0.860, respectively. CONCLUSION: Our study confirmed the clinical efficacy of SCIT in AR children. Children with younger age, negative allergic history, and multiple allergens may predict a worse efficacy. The onset of action and the clinical response to SCIT in the second year can be predicted as early as by month 4.

CircZNF652 promotes the goblet cell metaplasia by targeting the miR-452-5p/JAK2 signaling pathway in allergic airway epithelia.

BACKGROUND: Circular RNAs (circRNAs) play potentially important roles in various human diseases; however, their roles in the goblet cell metaplasia of asthma remain unknown. OBJECTIVE: We sought to investigate the potential role and underlying mechanism of circZNF652 in the regulation of allergic airway epithelial remodeling. METHODS: The differential expression profiles of circRNAs were analyzed by transcriptome microarray, and the effects and mechanisms underlying circZNF652-mediated goblet cell metaplasia were investigated by quantitative real-time PCR, RNA fluorescence in situ hybridization, Western blot, RNA pull-down, and RNA immunoprecipitation analyses. The roles of circZNF652 and miR-452-5p in allergic airway epithelial remodeling were explored in both the mouse model with allergic airway inflammation and children with asthma. RESULTS: One hundred sixty circRNAs were differentially expressed in bronchoalveolar lavage fluid of children with asthma versus children with foreign body aspiration, and 52 and 108 of them were significantly upregulated and downregulated, respectively. Among them, circZNF652 was predominantly expressed and robustly upregulated in airway epithelia of both the children with asthma and the mouse model with allergic airway inflammation. circZNF652 promoted the goblet cell metaplasia by functioning as a sponge of miR-452-5p, which released the Janus kinase 2 (JAK2) expression and subsequently activated JAK2/signal transducer and activator of transcription 6 (STAT6) signaling in the allergic airway epithelia. In addition, epithelial splicing regulatory protein 1, a splicing factor, accelerated the biogenesis of circZNF652 by binding to its flanking intron to promote the goblet cell metaplasia in allergic airway epithelial remodeling. CONCLUSIONS: Upregulation of circZNF652 expression in allergic bronchial epithelia contributed to the goblet cell metaplasia by activating the miR-452-5p/JAK2/STAT6 signaling pathway; thus, blockage of circZNF652 or agonism of miR-452-5p provided an alternative approach for the therapeutic intervention of epithelial remodeling in allergic airway inflammation.

Research on the Impact of Deep Eutectic Solvent and Hot-Water Extraction Methods on the Structure of Polygonatum sibiricum Polysaccharides.

Deep eutectic solvent (DES) and hot-water extraction (HWE) methods were utilized to extract polysaccharides from Polygonatum sibiricum, referred to as DPsP and WPsP, respectively. The extracted polysaccharides were purified using the Superdex-200 dextran gel purification system, resulting in three components for each type of polysaccharide. The structures of these components were characterized. The molecular weight analysis revealed that DPsP components had slightly larger molecular weights compared with WPsP, with DPsP-A showing a slightly higher dispersity index and broader molecular weight distribution. The main monosaccharide components of both DPsP and WPsP were mannose and glucose, while DPsP exhibited a slightly greater variety of sugar components compared with WPsP. FTIR analysis demonstrated characteristic polysaccharide absorption peaks in all six PSP components, with a predominance of acidic pyranose sugars. NMR analysis revealed the presence of pyranose sugars, including rhamnose and sugar aldehyde acids, in both DPsP-B and WPsP-A. DPsP-B primarily exhibited ß-type glycosidic linkages, while WPsP-A predominantly displayed α-type glycosidic linkages, with a smaller fraction being ß-type. These findings indicated differences in monosaccharide composition and structure between PSPs extracted using different methods. Overall, this study provided experimental evidence for future research on the structure-function relationship of PSPs.

Pulmonary Nocardia infection in a child with idiopathic pulmonary hemosiderosis.

BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) encompasses a rare and agnogenic group of diffuse alveolar capillary hemorrhagic diseases. Corticosteroid treatment is the globally preferred therapeutic strategy for IPH; however, it can cause immunodeficiency. Nocardia infection often occurs in immunocompromised patients and primarily involves the pleura and lungs. Herein, we describe a case of pediatric pulmonary Nocardia infection after the corticosteroid treatment of IPH. CASE PRESENTATION: A 7-year-old girl presented with chief complaints of pale complexion persisting for 1 year and a cough for 20 days. Abundant hemosiderin-laden macrophages were detected in the gastric juice, which supported the diagnosis of IPH. Uninterrupted doses of corticosteroids were administered during the last hospitalization. After nearly 2 months of corticosteroids therapy, the patient began to cough and produce a purulent sputum. Next-generation sequencing of the bronchoalveolar lavage fluid revealed Nocardia abscessus (N. abscessus) DNA. Linezolid was administered with good response, and the patient was discharged after 18 days of hospitalization. Her symptoms and pulmonary lesions had recovered, and the IPH appeared to be well-controlled with low dose of corticosteroids in follow-up. CONCLUSIONS: Nocardia infection should be considered in the differential diagnoses for IPH patients receiving corticosteroid therapy, especially in patients with poor response to conventional empirical antibiotic therapy. Next-generation sequencing of bronchoalveolar lavage fluid may be used to quickly identify the Nocardia. Sulfonamides or linezolid are effective for pediatric pulmonary Nocardia infection.

IL-4/IL-13 upregulates Sonic hedgehog expression to induce allergic airway epithelial remodeling.

We have previously demonstrated that upregulation of Sonic hedgehog (SHH) expression in allergic airway epithelia essentially contributes to the goblet cell metaplasia and mucous hypersecretion. However, the mechanism underlying the upregulation of SHH expression remains completely unknown. In cultured human airway epithelial cells, IL-4/IL-13 but not IL-5 robustly induces the mRNA and protein expression of SHH and in turn activates SHH signaling by promoting the JAK/STAT6-controlling transcription of SHH gene. Moreover, intratracheal instillation of IL-4 and/or IL-13 robustly activates STAT6 and concomitantly upregulates SHH expression in mouse airway epithelia, whereas, in Club cell 10-kDa protein (CC10)-positive airway epithelial cells of children with asthma, activated STAT6 closely correlates with the increased expression of SHH and high activity of SHH signaling. Finally, intratracheal inhibition of STAT6 by AS-1517499 significantly diminished the allergen-induced upregulation of SHH expression, goblet cell phenotypes, and airway hyperresponsiveness, in an ovalbumin- or house dust mite-induced mouse model with allergic airway inflammation,. Together, upregulation of SHH expression by IL-4/IL-13-induced JAK/STAT6 signaling contributes to allergic airway epithelial remodeling, and this study thus provides insight into how morphogen signaling is coordinated with Th2 cytokine pathways to regulate tissue remodeling in chronic airway diseases.

Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.

Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP2) participates in multiple cell functions including cell shape, movement, and differentiation. Therefore, we investigated the potential role of SHP2 in eosinophil recruitment into lungs in allergic airway inflammation and explored the underlying mechanism. Both SHP2 and Ras homolog family member A (RhoA) kinase were robustly activated in the airway eosinophils of children with allergic asthma and of a mouse model with allergic airway inflammation. Moreover, inhibition of SHP2 activity by its specific inhibitors reverses the dephosphorylation of p190-A Rho GTPase-activating protein and in turn attenuates RhoA/Rho-associated protein kinase (ROCK) signaling, resulting in the attenuation of eosinophil migration in response to platelet-activating factor stimulation. Specifically, SHP2 deletion in myeloid cells did not affect the number and classification of circulating leukocytes but significantly attenuated the allergen-induced inflammatory cell, especially eosinophil, infiltration into lungs, and airway hyperreactivity. Notably, genetic interaction between RhoA and SHP2 indicated that RhoA inactivation and SHP2 deletion synergistically attenuated the allergen-induced eosinophil infiltration into lungs and airway hyperreactivity, whereas overexpression of active RhoA robustly restored the SHP2 deletion-resultant attenuation of allergen-induced eosinophil recruitment into lungs and airway hyperreactivity as well. Thus, this study demonstrates that SHP2 via RhoA/ROCK signaling regulates eosinophil recruitment in allergic airway inflammation and possibly in allergic asthma.-Xu, C., Wu, X., Lu, M., Tang, L., Yao, H., Wang, J., Ji, X., Hussain, M., Wu, J., Wu, X. Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.

[Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)].

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

Notch Signaling: Linking Embryonic Lung Development and Asthmatic Airway Remodeling.

Lung development is mediated by assorted signaling proteins and orchestrated by complex mesenchymal-epithelial interactions. Notch signaling is an evolutionarily conserved cell-cell communication mechanism that exhibits a pivotal role in lung development. Notably, both aberrant expression and loss of regulation of Notch signaling are critically linked to the pathogenesis of various lung diseases, in particular, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and asthmatic airway remodeling; implying that precise regulation of intensity and duration of Notch signaling is imperative for appropriate lung development. Moreover, evidence suggests that Notch signaling links embryonic lung development and asthmatic airway remodeling. Herein, we summarized all-recent advances associated with the mechanistic role of Notch signaling in lung development, consequences of aberrant expression or deletion of Notch signaling in linking early-impaired lung development and asthmatic airway remodeling, and all recently investigated potential therapeutic strategies to treat asthmatic airway remodeling.