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.

Panax notoginseng saponin R1 improves glucocorticoid-inhibited airway epithelium repair via glucocorticoid receptor ß.

BACKGROUND: Panax notoginseng saponin R1(PNS-R1), derived from Panax notoginseng roots, promotes wound repair, whereas glucocorticoids can inhibit the repair of airway epithelial damage in asthma. OBJECTIVE: This study investigated whether PNS-R1 counteracts the inhibitory effects of glucocorticoids on the repair of airway epithelial damage in asthma. METHODS: In vivo, female C57BL/6 mice were sensitized, challenged with house dust mites (HDM), and treated with dexamethasone, PNS-R1, and/or adenovirus GRß-shRNA. Airway epithelium damage was examined using pathological sections of the trachea and bronchi, markers of airway inflammation, epithelial cells in bronchoalveolar lavage fluid, and expression of the E-cadherin protein. In vitro, we treated 16HBE cells with dexamethasone, PNS-R1, and/or GRß-siRNA and detected cell proliferation and migration. The expression of GRß and key components of MKP-1 and Erk1/2 were detected by western blotting. RESULTS: In vivo, PNS-R1 reduced airway inflammation, hyperresponsiveness, and mucus hypersecretion; the combination of PNS-R1 and dexamethasone promoted airway epithelial integrity and reduced cell detachment. In vitro, PNS-R1 alleviated the inhibition of bronchial epithelial cell growth, migration, and proliferation by dexamethasone; PNS-R1 promoted GRß expression, inhibited MKP-1 protein expression, and activated MAPK signaling, thereby promoting airway epithelial cell proliferation and repair. CONCLUSIONS: Panax notoginseng saponin R1 alleviated the inhibitory effect of dexamethasone on the repair of airway epithelial damage in asthmatic mice, likely by promoting the proliferation of airway epithelial cells by stimulating GRß expression and activating the MAPK pathway.

Epidemiological characteristics of respiratory viruses in hospitalized children during the COVID-19 pandemic in southwestern China.

Background: Multinational studies have reported that the implementation of nonpharmaceutical interventions (NPIs) to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission coincided with the decline of other respiratory viruses, such as influenza viruses and respiratory syncytial virus. Objective: To investigate the prevalence of common respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Respiratory specimens of children with lower respiratory tract infections (LRTIs) hospitalized at the Children's Hospital of Chongqing Medical University from January 1, 2018 to December 31, 2021 were collected. Seven common pathogens, including respiratory syncytial virus (RSV), adenovirus (ADV), influenza virus A and B (Flu A, Flu B), and parainfluenza virus types 1-3 (PIV1-3), were detected by a multiplex direct immunofluorescence assay (DFA). Demographic data and laboratory test results were analyzed. Results: 1) A total of 31,113 children with LRTIs were enrolled, including 8141 in 2018, 8681 in 2019, 6252 in 2020, and 8059 in 2021.The overall detection rates decreased in 2020 and 2021 (P < 0.001). The detection rates of RSV, ADV, Flu A, PIV-1, and PIV-3 decreased when NPIs were active from February to August 2020, with Flu A decreasing most predominantly, from 2.7% to 0.3% (P < 0.05). The detection rates of RSV and PIV-1 resurged and even surpassed the historical level of 2018-2019, while Flu A continued decreasing when NPIs were lifted (P < 0.05). 2) Seasonal patterns of Flu A completely disappeared in 2020 and 2021. The Flu B epidemic was observed until October 2021 after a long period of low detection in 2020. RSV decreased sharply after January 2020 and stayed in a nearly dormant state during the next seven months. Nevertheless, the detection rates of RSV were abnormally higher than 10% in the summer of 2021. PIV-3 decreased significantly after the COVID-19 pandemic; however, it atypically surged from August to November 2020. Conclusion: The NPIs implemented during the COVID-19 pandemic affected the prevalence and seasonal patterns of certain viruses such as RSV, PIV-3, and influenza viruses. We recommend continuous surveillance of the epidemiological and evolutionary dynamics of multiple respiratory pathogens, especially when NPIs are no longer necessary.

Global research status and trends of bronchiectasis in children from 2003 to 2022: A 20-year bibliometric analysis.

Background: This study aims to analyze the research hotspots, evolution, and developing trends in pediatric bronchiectasis over the past 20 years using bibliometric analysis and visualization tools to identify potential new research directions. Methods: Publications related to bronchiectasis in children were retrieved from the Web of Science Core Collection (WoSCC) database from 2003 to 2022. Knowledge maps were performed through VOSviewer1.6.18 and CiteSpace6.1 R2. Results: A total of 2,133 publications were searched, while only 1,351 original articles written in English between 2003 and 2022 were incorporated. After removing duplicates, we finally included 1,350 articles published by 6,593 authors from 1,865 institutions in 80 countries/regions in 384 different academic journals with an average citation frequency of 24.91 times. The number of publications shows an extremely obvious binomial growth trend. The majority of publications originated from the United States, Australia, and England. The institutes in Australia, especially Charles Darwin University, published the most articles associated with pediatric bronchiectasis. In addition, Pediatric Pulmonology was the most published journal. In terms of authors, Chang AB was the most productive author, while Gangell CL had the highest average citation frequency. The five keywords that have appeared most frequently during the last two decades were "children," "cystic fibrosis," "bronchiectasis," "ct," and "pulmonary-function." According to keyword analysis, early diagnosis and intervention and optimal long-term pediatric-specific management were the most concerned topics for researchers. Conclusion: This bibliometric analysis indicates that bronchiectasis in children has drawn increasing attention in the last two decades as its recognition continues to rise, providing scholars in the field with significant information on current topical issues and research frontiers.

Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Type II Cell Proliferation and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia.

Although it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide- (LPS-) induced BPD rat model and to clarify the underlying mechanism. We demonstrate that antenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature, which restored by hUCMSCs and MVs treatment. Furthermore, MVs were large vesicles with a diameter of 100-900 nanometers and mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, PTEN/AKT and MAPK pathways were associated with the protection of MVs. Taken together, this study suggests MVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuating lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.

Clinical and genetic features of primary ciliary dyskinesia in a cohort of consecutive clinically suspect children in western China.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare, inherited disorder of the motile cilia that exhibits genetic and clinical heterogeneity among different populations. PCD diagnosis remains challenging owing to the heterogeneity of associated clinical features and lack of a gold standard diagnostic test. OBJECTIVE: The aim of this study was to analyze the clinical and genetic characteristics of a group of children with clinically suspected PCD in one region of China, with the goal of providing a more robust knowledge base regarding the genetic stratification underlying this disease in Chinese populations. METHODS: We retrospectively analyzed the data from 38 patients with clinically suspected PCD who had undergone next-generation sequencing (NGS) between November 2016 and March 2021 in the respiratory department of a tertiary Children's hospital in Western China. The genetic features of the confirmed cases were summarized by reviewing data associated with other cohorts of Chinese children. RESULTS: Overall, 16 patients were ultimately diagnosed with PCD with a median age of 8.5 years. All patients presented with a chronic wet cough, 93.75% exhibited chronic or recurrent sinusitis/rhinitis, 43.75% experienced recurrent wheezing, 56.25% reported respiratory symptoms present since infancy, 31.25% had a history of neonatal respiratory distress (NRD), and 25% exhibited otitis media. Only 18.75% of these patients exhibited laterality defects. High frequencies of DNAH11 mutations were detected by integrating data from PCD patient cohorts in China. CONCLUSION: The high frequency of DNAH11 mutations may limit the utility of transmission electron microscopy (TEM) as a first-line approach to diagnosing PCD in China in the absence of other indicators.

Clinical Analysis of Primary Tracheobronchial Tumors in Children and Evaluation of the Predicting Models for Mucoepidermoid Carcinoma.

OBJECTIVE: To determine the clinical characteristics and prognosis of primary tracheobronchial tumors (PTTs) in children, and to explore the most common tumor identification methods. METHODS: The medical records of children with PTTs who were hospitalized at the Children's Hospital of Chongqing Medical University from January 1995 to January 2020 were reviewed retrospectively. The clinical features, imaging, treatments, and outcomes of these patients were statistically analyzed. Machine learning techniques such as Gaussian naïve Bayes, support vector machine (SVM) and decision tree models were used to identify mucoepidermoid carcinoma (ME). RESULTS: A total of 16 children were hospitalized with PTTs during the study period. This included 5 (31.3%) children with ME, 3 (18.8%) children with inflammatory myofibroblastic tumors (IMT), 2 children (12.5%) with sarcomas, 2 (12.5%) children with papillomatosis and 1 child (6.3%) each with carcinoid carcinoma, adenoid cystic carcinoma (ACC), hemangioma, and schwannoma, respectively. ME was the most common tumor type and amongst the 3 ME recognition methods, the SVM model showed the best performance. The main clinical symptoms of PPTs were cough (81.3%), breathlessness (50%), wheezing (43.8%), progressive dyspnea (37.5%), hemoptysis (37.5%), and fever (25%). Of the 16 patients, 7 were treated with surgery, 8 underwent bronchoscopic tumor resection, and 1 child died. Of the 11 other children, 3 experienced recurrence, and the last 8 remained disease-free. No deaths were observed during the follow-up period. CONCLUSION: PTT are very rare in children and the highest percentage of cases is due to ME. The SVM model was highly accurate in identifying ME. Chest CT and bronchoscopy can effectively diagnose PTTs. Surgery and bronchoscopic intervention can both achieve good clinical results and the prognosis of the 11 children that were followed up was good.

ZEB1 recruits BRG1 to regulate airway remodelling epithelial-to-mesenchymal transition in asthma.

NEW FINDINGS: What is the central question of this study? The aim was to investigate the function of brahma-related gene-1 (BRG1) in airway remodelling epithelial-to-mesenchymal transition (EMT) of asthma and identify the transcription factor of BRG1 that binds to the protomer of E-cadherin. What is the main finding and its importance? This study highlighted an important molecular mechanism involving chromatin remodelling factor BRG1 that played a crucial role in airway remodelling EMT of asthma and demonstrated that ZEB1 was the key transcription factor recruiting BRG1. This finding might offer new insights into gene-based therapy for asthma. ABSTRACT: Epithelial-to-mesenchymal transition (EMT) of airway remodelling happens in children with asthma. A reduction in the epithelial marker E-cadherin is reported to be one of the initiating factors of EMT. Our previous study showed that chromatin remodelling factor brahma-related gene-1 (BRG1) could regulate the expression of E-cadherin indirectly. However, the transcription factor involved in the recruitment of BRG1 in asthma is unknown. Here, we studied the function of Brg1 in an ovalbumin-induced asthma model [lung-specific conditional Brg1 knockdown (Brg1-/- ) mice] and human bronchial epithelial 16HBE cells stably expressing BRG1 short hairpin RNA. Our results showed that Brg1 was involved in EMT in asthmatic mice by detecting the expression of EMT markers. We also identified that BRG1 participated in the transforming growth factor-ß-induced EMT of 16HBE cells. We observed that zinc finger E-box binding homeobox 1 (ZEB1) and BRG1 co-localized in the EMT of TGF-ß-induced 16HBE cells. Further results revealed that ZEB1 recruited BRG1 and bound to the promoter region (+3563/3715) to regulate E-cadherin expression. Thus, ZEB1 might be the key transcription factor to recruit BRG1 in airway remodelling EMT of asthma and might be a new therapeutic target.

Reassessing the role of tracheobronchomalacia in persistent wheezing.

BACKGROUND: Tracheobronchomalacia (TBM) is often manifested as wheezing. Reassessing the role of TBM in persistent wheezing in children is essential. METHODS: We selected children who were diagnosed with TBM by bronchoscopy and who underwent bronchoscopic reexamination for persistent wheezing or chronic cough between January 2009 and July 2019. The clinical and bronchoscopy data were collected and retrospectively reviewed. For statistical analysis, we used the Kaplan-Meier method, Kruskal-Wallis test, and Fisher exact test. RESULTS: A total of 79 patients (57 males and 22 females) were included. The median age of the first TBM diagnosis was 7 (interquartile [IQR] 4-11) months. The median age of the first wheezing episode was 4 (IQR 3-7) months. During the time interval between the two bronchoscopies, malacia lesions resolved in 50 patients (63.3%), improvement was seen in 14 patients (17.7%), no change was observed in 11 patients (13.9%), and the condition was aggravated in 4 patients (5.1%). The malacia lesions in 37 patients resolved before 2 years of age. Among the 50 resolved patients, 22 patients (44.0%) reported wheezing three times or more between bronchoscopy evaluations, and 13 of these 22 patients (59.1%) with atopy or family history of allergic diseases were ultimately diagnosed with bronchial asthma. CONCLUSIONS: In children with persistent wheezing, the role of TBM should be reassessed, especially in those with atopy or family history of allergic diseases, and bronchial asthma should be considered early.

Pattern of Antibiotic Prescriptions in Chinese Children, A Cross-Sectional Survey From 17 Hospitals Located Across 10 Provinces of China.

Objectives: Use of Broad-spectrum antibiotics is related closely to increasing antimicrobial resistance. Reports on antibiotic prescriptions for Chinese children were rare. We described the prescribing patterns of antibiotic prescriptions for Chinese children from 2017 to 2019 based on the Anatomical Therapeutic Chemical Classification (ATC classification); the Access, Watch, and Reserve (AWaRe) classification from the World Health Organization (WHO), and the Management of Antibiotic Classification in China. Methods: A 1-day point-prevalence survey (PPSs) on antibiotics prescribing for Chinese children was conducted in hospitalized children from 17 centers in 10 Chinese provinces from 1 September 2017 to 30 November 2019. Results: A total of 4,982 antibiotic prescriptions for Chinese children were included in the analysis. There were 76 types of antibiotic agents in total, 22 (28.9%) of which accounted for 90% of all antibiotic prescriptions. The top-three antibiotics prescribed for children were azithromycin (684, 13.7%), ceftriaxone (508, 10.2%) and latamoxef (403, 8.1%). Third-generation cephalosporins (1,913, 38.4%) were the most commonly prescribed antibiotic classes. On the basis of the AWaRe classification, the Watch group antibiotics accounted for 76.3% and Access group antibiotics accounted for 12.1% of all antibiotic prescriptions. On the basis of the China classification, we showed that 26.5% of antibiotic prescriptions were in the Unrestricted group, 53.6% in the Restricted group, and 14.5% in the Special group. Conclusion: The proportion of antibiotics included in the Watch group and the Special group was high in children in China. The AWaRe classification and China classification for antibiotic prescriptions could be used to supply detailed data for antibiotic stewardship as a simple metric.

Antimicrobial prescribing for children in China: data from point prevalence surveys in 18 tertiary centres in China in 2016-2017.

OBJECTIVES: The reports on evaluating the classification of antibiotic agents prescribed for Chinese children by combining WHO's and China's administrative categories were rare. This study aimed to investigate the pattern of antimicrobial agents prescribing for Chinese children in 2016. SETTINGS: 18 tertiary centres from nine provinces located in northern, southern, eastern and western China. PARTICIPANTS: The antimicrobial prescribing data from the children admitted in medical wards, surgical wards and intensive care units were collected and analysed. A total of 3680 antibiotic prescriptions for Chinese children were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: One-day point-prevalence surveys (PPSs) on antimicrobial prescribing were conducted among hospitalised children in China between 1 February 2016 and 28 February 2017. Five hospitals participated in the first PPS, 13 hospitals in the second PPS, 17 hospitals in the third PPS and 18 hospitals in the fourth PPS. Patterns of antibiotic use with a drug utilisation of 90%, Anatomical Therapeutical Chemical Classification, WHO Access, Watch and Reserve (AWaRe) (version 2019) and antibiotic classification in China were described retrospectively. RESULTS: A total of 4442 children and 3680 antibiotic prescriptions for Chinese children were included in the analysis. 2900 (65.3%) children received at least one ongoing antibiotic during the survey days. On the basis of WHO AWaRe classification, the proportion of antibiotics in the Watch group was 76.5% (2814/3680). According to the Management of Antibiotic Classification in China, 56.8% (2089/3680) and 16.1% (594/3680) of antibiotic prescriptions in the Restricted group and the Special group, respectively, were included into broad-spectrum antibiotics. The most common indication for antibiotics was bacterial lower respiratory tract infection (2044/3680, 55.5%). CONCLUSIONS: The use of broad-spectrum antibiotics was frequent and excessive in hospitalised children in China in 2016.

Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling.

GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.

GITRL on dendritic cells aggravates house dust mite-induced airway inflammation and airway hyperresponsiveness by modulating CD4+ T cell differentiation.

BACKGROUND: Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action. METHODS: In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested. RESULTS: GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children. CONCLUSIONS: This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

Low-Dose LPS Induces Tolerogenic Treg Skewing in Asthma.

The mechanism(s) underlying endotoxin tolerance in asthma remain elusive. As the endotoxin lipopolysaccharide (LPS) affects the expression of the regulatory T-cell (Treg)-suppressive glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) on antigen-presenting dendritic cells (DCs), we hypothesized that LPS-induced changes in DC GITRL expression may impact Treg-mediated T-helper (Th) cell suppression and the induction of endotoxin tolerance. Here, we propose a novel mechanism by which low-dose LPS inhalation in neonatal mice induces endotoxin tolerance, thereby offering protection from later asthma development. Three-day old wild-type and Toll-like receptor 4 (TLR4)-deficient neonatal mice were exposed to low-dose LPS (1 µg) intranasally for 10 consecutive days prior to ovalbumin (OVA)-induced asthma to better understand the tolerogenic mechanism(s) of low-dose LPS pre-exposure. In vivo findings were validated using in vitro co-culturing studies of primary CD11c+ DCs and CD4+ T-cells with or without low-dose LPS pre-exposure before OVA stimulation. Low-dose LPS pre-exposure upregulated the Treg response and downregulated pathogenic Th2 and Th17 responses through promoting apoptosis of Th2 and Th17 cells. Low-dose LPS pre-exposure downregulated DC GITRL expression and T-cell GITR expression. Artificial DC GITRL expression abrogated the tolerogenic Treg-skewing effect of low-dose LPS pre-exposure. Low-dose LPS pre-exposure inhibited TRIF/IRF3/IFNß signaling and upregulated expression of tolerogenic TRIF/IRF3/IFNß negative regulators in a TLR4-dependent manner. This tolerogenic DC GITRL downregulation was attributable to TRIF/IRF3/IFNß signaling inhibition. Low-dose LPS pre-exposure produces tolerogenic Treg skewing in neonatal asthmatic mice, a phenomenon attributable to TLR4-dependent TRIF/IRF3/IFNß-mediated DC GITRL downregulation.

Correlation Between the Clinical Severity, Bacterial Load, and Inflammatory Reaction in Children with Mycoplasma Pneumoniae Pneumonia.

Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia (MPP), quantitative polymerase chain reaction (qPCR) has become a useful diagnostic method. This study was performed to explore the relationship between the qPCR findings, clinical symptoms, and inflammatory markers in children with MPP. Four hundred children with MPP have been enrolled in this retrospective analysis. All clinical and analytical information, including mycoplasma pneumoniae (MP) PCR results, has been collected. Based on the PCR results, the patients were divided into groups with load values (copy number) < 105 (54 cases), ≥105 and <106 (71 cases), ≥106 and <107 (112 cases), ≥107 and ≤108 (114 cases), and >108 (49 cases). The clinical features (including symptoms and signs) and inflammatory indicators were compared among the groups. The incidence of high fever (above 39°C), thermal peak during the entire hospitalization period, fever duration, days of hospitalization, and plasma lactate dehydrogenase (LDH) levels were statistically correlated with the MP PCR load value in children with MPP. The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization > duration of fever > period of hospitalization > LDH value > C-reactive protein value. The host immune response was significantly greater in the complication group than in the non-complication group.

Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Lung Injury in Rat Model of Bronchopulmonary Dysplasia by Affecting Cell Survival and Angiogenesis.

Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease in premature newborns, with high morbidity and mortality rates. Mesenchymal stem cell (MSC) transplantation has developed into a promising approach to alleviate BPD. Small extracellular vesicles, which are an important therapeutic component of MSCs, have been reported to be effective in a mouse model of BPD. However, the affected cell types and detailed underlying mechanisms are unclear. In this study, we found that human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hucMSC-sEVs) were successfully absorbed by lung tissue after intratracheal administration, and remained in the lungs for at least 72 h. The results showed that hucMSC-sEVs restored alveolar structure and lung function, and ameliorated pulmonary hypertension in a rat model of BPD. The number of Ki-67-positive lung cells were improved, while the number of TUNEL-positive lung cells were reduced in our hucMSC-sEV-treated BPD model. Additionally, SP-C staining (a marker of type II alveolar epithelial cells, TIIAECs) and CD31 staining (a marker of pulmonary vascular endothelial cells, PVECs) were both increased in a hyperoxia-induced BPD model treated with hucMSC-sEVs. In vitro, under hyperoxic conditions, the tube-like structure formation was improved in human umbilical vein endothelial cells, and the proliferation was increased and the apoptosis was attenuated in MLE-12 cells treated with hucMSC-sEVs. Furthermore, we observed downregulated expression of PTEN and cleaved-caspase3, and upregulated expression of p-Akt and vascular endothelial growth factor-A in our hucMSC-sEV-treated BPD model. In conclusion, hucMSC-sEVs improved alveolarization and angiogenesis in a rat BPD model by protecting TIIAECs and PVECs, which were associated with the PTEN/Akt signaling pathway.

Panax notoginseng saponin R1 modulates TNF-α/NF-κB signaling and attenuates allergic airway inflammation in asthma.

BACKGROUD: Panax notoginseng saponin R1 (PNS-R1) is one of the most important chemical monomers derived from the panax notoginseng, and our previous study found that PNS-R1 reduced glucocorticoid-induced apoptosis in asthmatic airway epithelial cells. Thus, in this study, we explored the effects of the PNS-R1 on inflammation of allergic asthma. METHODS: The asthmatic mice were administered 15 mg/kg PNS-R1 by intraperitoneal injection three days before sensitized to OVA. The effects of PNS-R1 on asthmatic mice were detected by airway hyperresponsiveness, inflammation, mucus hypersecretion and inflammatory cytokines such as interleukin (IL)-13, IL-4, IL-5, IL-8 and tumor necrosis factor (TNF)-α were studied. We also treated human bronchial epithelial cells (16HBE) with house dust mites (HDM) and then detected the secretion of cellular inflammatory factors (IL-13 and TNF-α). Western blot and immunofluorescence were used to examine the effect of PNS-R1 on TNF-α/NF-κB pathway. TNF-α/NF-κB/IKK signal pathway activator was used in PNS-R1-treated asthmatic mice. RESULTS: PNS-R1 significantly reduced the airway inflammatory, mucus secretion and hyperresponsiveness in asthma model. It also reduced the levels of IL-13, IL-4, IL-5 and IL-8 in bronchoalveolar lavage fluid (BALF) and IgE and OVA-specific IgE in serum for asthma mice. PNS-R1 reduced IL-13 and TNF-α secretion in HDM-treated 16HBE cells. In addition, PNS-R1 suppressed TNF-α/NF-κB pathway in both asthmatic mice and 16HBE. Activation of NF-kB pathway reversed the therapeutic effect of PNS-R1 on asthmatic mice. CONCLUSION: The results indicated that PNS-R1 effectively suppresses allergic airway inflammation of asthma partly through TNF-α/NF-κB pathway. PNS-R1 may play a potential role in allergic asthma treatment in the future.

Application of telemedicine during the coronavirus disease epidemics: a rapid review and meta-analysis.

BACKGROUND: As COVID-19 has become a global pandemic, early prevention and control of the epidemic is extremely important. Telemedicine, which includes medical advice given over telephone, Internet, mobile phone applications or other similar ways, may be an efficient way to reduce transmission and pressure on medical institutions. METHODS: We searched MEDLINE, Web of Science, Embase, Cochrane, CBM, CNKI and Wanfang databases for literature on the use of telemedicine for COVID-19, SARS and MERS from their inception to March 31st, 2020. We included studies about the content of the consultation (such as symptoms, therapy and prevention, policy, public service), screening of suspected cases, the provision of advice given to those people who may have symptoms or contact history. We conducted meta-analyses on the main outcomes of the studies. RESULTS: A total of 2,041 articles were identified after removing duplicates. After reading the full texts, we finally included nine studies. People were most concerned about symptoms (64.2%), epidemic situation and public problems (14.5%), and psychological problems (10.3%) during COVID-19 epidemic. During the SARS epidemic, the proportions of people asking for consultation for symptoms, prevention and therapy, and psychological problems were 35.0%, 22.0%, and 23.0%, respectively. Two studies demonstrated that telemedicine can be used to screen the suspected patients and give advice. One study emphasized the limited possibilities to follow up people calling hotlines and difficulties in identifying all suspect cases. CONCLUSIONS: Telemedicine services should focus on the issues that the public is most concerned about, such as the symptoms, prevention and treatment of the disease, and provide reasonable advice to patients with symptoms or people with epidemic history.

Correction: Pseudomonas aeruginosa-derived exosomes ameliorates allergic reactions via inducing the Treg response in asthma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.