Childhood Mycoplasma pneumoniae: epidemiology and manifestation in Northeast and Inner Mongolia, China.

Mycoplasma pneumoniae (MP) is commonly detected in children. However, the epidemiological trends of MP in Northeast (NE) China are unclear. This retrospective study aimed to investigate the prevalence of MP infections in this understudied region. The clinical manifestations and bronchoscopic findings observed in hospitalized patients with severe Mycoplasma pneumoniae pneumonia (SMPP) were collected from comprehensive data obtained from six tertiary hospitals in NE and Inner Mongolian (IM) China, from 1 January 2017 to 31 December 2023. A total of 5,593,530 children who visited the outpatient and emergency departments, and 412,480 inpatient hospitalized children were included in the study. The positivity rate of MP immunoglobulin M (IgM) in the children who visited the outpatient and emergency departments varied from 7.80% to 10.12%, whereas that of MP infection in hospitalized children ranged from 27.18% to 30.10%. Children hospitalized for MP infection were mainly concentrated in the 1- to 4-year (41.39%) and 4- to 7-year (24.25%) age groups. Before 2020, the season with the highest incidence of MP was winter. After the implementation of non-pharmaceutical interventions (NPIs), the MP epidemic season changed, and the number of children with MP infections decreased; however, the proportion of MP infections in hospitalized children did not change significantly. Starting from August 2023, the MP infection rate in outpatient, emergency, and hospitalized children increased sharply, with SMPP and its complications (e.g., plastic bronchitis and pleural effusion) increasing significantly. MP is prevalent in NE and IM, China. When the NPIs ended, MP infection showed a delayed outbreak trend, and the number of children with severe infection increased significantly. IMPORTANCE: In Northeastern (NE) and Inner Mongolia (IM), the incidence of Mycoplasma pneumoniae (MP) infections, including severe Mycoplasma pneumoniae pneumonia (SMPP), is high, posing health risks and imposing substantial economic burdens on the local population. Therefore, it is imperative to prioritize the study of MP prevalence and address the research gaps in MP epidemiology in these areas of China. We obtained a comprehensive collection of pediatric outpatient, emergency, and inpatient data from six public Grade III hospitals. We believe that our study makes a significant contribution to the literature because understanding regional variations in MP infections can help healthcare professionals tailor prevention and treatment strategies, and studying bronchoscopic manifestations can provide insights into the impact of the disease on the respiratory system, potentially leading to a more effective clinical management.

Radical S-adenosyl methionine domain-containing 2, a potential target of D-tryptophan in asthma treatment, regulates T helper cell type 1/2 balance.

Asthma is a common chronic respiratory disease. D-tryptophan (D-TRP) can inhibit allergic airway inflammation and T helper cell type 2 (Th2) immune response. RNA-sequencing results have indicated that radical S-adenosyl methionine domain-containing 2 (RSAD2) might be a potential molecular target of D-TRP in asthma treatment. Herein, we established a mouse model of asthma using ovalbumin (OVA) via intraperitoneal injection and inhalational challenge. Gain- and loss-of-function studies of RSAD2 were performed in mice following the intratracheal delivery of lentiviral vectors (3 × 106 TU/mL). Naïve CD-4+ T cells were isolated from the spleen and used to explore the effects of RSAD2 on Th2 cell differentiation. RSAD2 expression was higher in the asthma group than in the control group. RSAD2 knockdown alleviated inflammatory cell infiltration and reduced the number of goblet cells. Low RSAD2 expression decreased the levels of IgE, IL-25, IL-33, and TSLP, and it reduced the number of inflammatory cells in the bronchoalveolar lavage fluid. RSAD2 silencing suppressed Th2-related cytokine levels (such as IL-4, IL-5, and IL-13) and increased Th1-related cytokine levels (such as IFN-γ). Additionally, RSAD2 knockdown inhibited the phosphorylation of JAK1, JAK3, and STAT6, and downregulated GATA-3 expression. RSAD2 overexpression increased inflammatory cell infiltration and mucus secretion in the lung tissues of mice pretreated with D-TRP. D-TRP pretreatment reduced OVA-specific IgE content and IL-4 and IL-5 levels, and it increased the IFN-γ levels; however, RSAD2 overexpression reversed these effects. In conclusion, RSAD2 knockdown can mitigate OVA-induced asthma by regulating the Th2 immune response via JAK/STAT6 pathway inhibition.

Case Report: In situ pulmonary artery thrombosis in a 12-year-old girl classified as systemic lupus erythematosus.

In situ pulmonary artery thrombosis (ISPAT) is a relatively rare but potentially life-threatening complication of systemic lupus erythematosus (SLE) in children. We report the case of a 12-year-old girl who presented with fever, chest pain, and dyspnea. Immune thrombocytopenia was identified due to purpura and menorrhagia 3 months before presentation with a lowest platelet count of 12 × 109/L. The sudden onset of fever, chest pain, and dyspnea were misdiagnosed as hyperinflammatory responses caused by pneumonia; these symptoms ameliorated with glucocorticoid and antibiotic treatment. The reappearance of symptoms after dose reduction of glucocorticoids and the observation of bloody bronchoalveolar lavage fluid necessitated further evaluation. Pulmonary artery thrombosis/embolism was identified using computed tomography pulmonary angiography and high D-dimer quantitative level of 4,118 µg/L (normal <252 µg/L). Ultrasonography of the deep and superficial veins of both lower limbs and renal veins revealed no thrombosis, suggesting the diagnosis of ISPAT. Further etiological evaluation revealed positive antinuclear antibodies, lupus anticoagulant, and anti-SSA antibodies, confirming SLE. Repeated normal urine analysis indicated that lupus nephritis was unlikely. Further, the negative anticardiolipin and anti-ß2 glycoprotein antibodies and temporary positive lupus anticoagulant suggested that antiphospholipid syndrome was unlikely. The patient received anticoagulants, glucocorticoids, hydroxychloroquine, and mycophenolate therapy. Her symptoms gradually improved, and she was discharged. At the 1-month follow-up, the thrombosis had resolved. During the 1-year follow-up, her condition remained well without SLE relapse. Our experience with this case emphasizes searching for SLE in the case of ISPAT and pulmonary hemorrhages. ISPAT can occur in children with SLE and may be caused by hyperinflammatory response during SLE flare.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

The initial angle of the maximum expiratory flow-volume curve: a novel start-of-test criteria of spirometry in children.

The aim of the present study was to define an initial angle called ß and to assess its diagnostic value for identifying poor-quality maneuvers in spirometry testing in children. Furthermore, its predictive equation or normal value was explored. Children aged 4-14 years with respiratory symptoms who underwent spirometry were enrolled. Based on the efforts labeled during maneuvering and the quality control criteria of the guidelines, children were categorized into good-quality and poor-quality groups. According to ventilatory impairment, children in the good-quality group were divided into three subgroups: normal, restricted, and obstructed. Angle ß was the angle between the line from the expiratory apex to the origin of coordinates and the x-axis of the maximal expiratory flow-volume (MEFV) curve. Demographic characteristics, angle ß, and other spirometric parameters were compared among groups. The diagnostic values of angle ß, forced expiratory time (FET), and their combination were assessed using receiver operating characteristic curves. Data from 258 children in the good-quality group and 702 healthy children in our previous study were used to further explore the predictive equation or normal value of angle ß. The poor-quality group exhibited a significantly smaller angle ß (76.44° vs. 79.36°; P < 0.001), significantly lower peak expiratory flow (PEF), FET, and effective FET (ETe), and significantly higher expiratory volume at peak flow rate (FEV-PEF) and ratio of extrapolated volume and forced vital capacity (EV/FVC) than the good-quality group. There was no significant difference in angle ß among the normal, restricted, and obstructed groups. Logistic regression analysis revealed that smaller angle ß and FET values indicated poor-quality MEFV curves. The combination of angle ß < 74.58° and FET < 4.91 s had a significantly larger area under the curve than either one alone. The normal value of angle ß of children aged 4-14 years was 78.40 ± 0.12°.   Conclusions: Angle ß contributes to the quality control evaluation of spirometry in children. Both angle ß < 74.58° and FET < 4.91 s are predictors of poor-quality MEFV curves, while their combination offers the highest diagnostic value. What is Known: • A slow start is one of the leading causes of poor-quality maximal expiratory flow-volume (MEFV) curves, which is a particularly prominent issue among children due to limited cooperation, especially those younger than 6 years old. • It is relatively difficult to differentiate between ventilatory dysfunction and poor cooperation when a slow start occurs in children; therefore, there is an urgent need for an objective indicator that is unaffected by ventilatory impairment to evaluate quality control of spirometry. What is New: • The initial angle ß, which was introduced at the ascending limb of the MEFV curve in the present study, has a certain diagnostic value for poor-quality MEFV curves in children. • Angle ß < 74.58° is a predictor of poor-quality MEFV curves, and its combination with FET < 4.91 s offers a higher diagnostic value.

Histone acetylation regulates ORMDL3 expression-mediated NLRP3 inflammasome overexpression during RSV-allergic exacerbation mice.

Whether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1-like protein 3 (ORMDL3) and lead to NOD-like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV-induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV-bronchiolitis follow-up. In BEAS-2B, ORMDL3-induced NLRP3 inflammasome expression. BEAS-2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3-small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression.

Multicenter analysis of epidemiological and clinical features of pediatric acute lower respiratory tract infections associated with common human coronaviruses in China, 2014-2019.

The common human coronaviruses (HCoVs) HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 which are members of the coronavirus family are long co-existed with humans and widely distributed globally. Common HCoVs usually cause mild, self-limited upper respiratory tract infections (URTI), and also associated with lower respiratory tract infections (LRTI), especially in children. However, there are little multicentre studies have been conducted in children of several different areas in China, and the epidemic potential of common HCoVs remains unclear. Understanding of the common HCoVs is valuable for clinical and public health. Herein, we retrospectively analysed the medical records of children with acute lower respiratory tract infection admitted to 9 hospitals from different regions in China from 2014 to 2019. Of the 124 patients who tested positive for coronaviruses, OC43 was the predominant type, accounting for 36.3% (45/124) of the detections. Children aged ≤ 6 months and 12-23 months had the highest detection rate of common HCoVs, and the detection rate gradually declined after 2 years old. These four HCoVs could be detected all year round. Among the areas of our study, the overall positive rate was higher in southern China, especially in Guangzhou (29/124, 23.4%). Moreover, common HCoV-positive patients were codetected with 9 other common respiratory pathogens. 229E (11/13, 84.6%) was the most frequently associated with codetection, with EV/RhV was the most frequently codetected virus. Cough (113/124, 91.1%) and fever (73/124, 58.9%) were the most common symptoms of common HCoVs infection.

Case report: Miliary tuberculosis complicated by pediatric acute respiratory distress syndrome in a 12-year-old girl.

Acute respiratory distress syndrome (ARDS) is a rare complication of miliary tuberculosis, particularly in pediatric patients. Comorbidities and delayed diagnosis can worsen the prognosis of patients with miliary tuberculosis. A 12-year-old girl presented with fever for 20 days, and cough and tachypnea for 4 days. She was diagnosed with miliary tuberculosis complicated by pediatric ARDS. She had atypical clinical manifestations and imaging findings, a negative contact history, and negative results of a tuberculin skin test (TST) and T-SPOT.TB. Diagnostic bronchoscopy and bronchoalveolar lavage helped make the diagnosis of tuberculosis. Effective treatment was promptly initiated after confirmation of the diagnosis, and the patient's condition improved. This case illustrates that a negative contact history and laboratory results cannot rule out tuberculosis. False-negative TST and T-SPOT.TB results should be evaluated carefully. Bronchoscopy may be useful for identifying pathogens in patients with pneumonia of unknown etiology, and corticosteroids should be administered with caution.

Hypermethylation of RNF125 promotes autophagy-induced oxidative stress in asthma by increasing HMGB1 stability.

Asthma is a global chronic airway disease. The expression and role of RNF125, an E3 ubiquitin ligase, in asthma remain uncertain. In this study, we revealed that RNF125 was downregulated in the bronchial epithelium of mice and patients with asthma. Rnf125 hypermethylation was responsible for the low expression of RNF125 in primary airway epithelial cells of mice treated with OVA. Moreover, we demonstrated that RNF125 could attenuate autophagy, oxidative stress, and protect epithelial barrier in vivo and in vitro. Additionally, we identified HMGB1 as a substrate of RNF125, which interacted with the HMG B-box domain of HMGB1 and induced degradation via the ubiquitin proteasome system, reducing autophagy and oxidative stress. Overall, our findings elucidated that hypermethylation of Rnf125 reduced its expression, which promoted autophagy-induced oxidative stress in asthma by increasing HMGB1 stability. These findings offer a theoretical and experimental basis for the pathogenesis of asthma.

Growth differentiation factor 15 protects the airway by inhibiting cell pyroptosis in obese asthmatic mice through the phosphoinositide 3-kinase/AKT pathway.

Obese asthma is a form of refractory asthma with inflammation as the underlying mechanism. The specific mechanism of action of anti-inflammatory growth differentiation factor 15 (GDF15) in obese asthma is unclear. The purpose of this study was to explore the effect of GDF15 on cell pyroptosis in obese asthma and to determine its mechanism of airway protection. Male C57BL6/J mice were fed with a high-fat diet, sensitized, and challenged with ovalbumin. Recombinant human (rh)GDF15 was administered 1 h before the challenge. GDF15 treatment significantly reduced airway inflammatory cell infiltration, mucus hypersecretion and airway resistant, and decreased cell counts and inflammatory factors in bronchoalveolar lavage fluid. Serum inflammatory factors decreased, and the increased levels of NLR family pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and gasdermin-D (GSDMD-N) in obese asthmatic mice were inhibited. Furthermore, the suppressed phosphoinositide 3-kinase (PI3K)/AKT signal pathway was activated after rhGDF15 treatment. The same result was obtained by overexpression of GDF15 in human bronchial epithelial cells induced by lipopolysaccharide (LPS) in vitro, and the effect of GDF15 was reversed after the application of a PI3K pathway inhibitor. Thus, GDF15 could protect the airway by inhibiting cell pyroptosis in obese asthmatic mice through the PI3K/AKT signaling pathway.

Asthma with recurrent middle lobe syndrome in children: Clinical features and lung function patterns.

Background: Middle lobe syndrome (MLS) is a complication of childhood asthma. This study aimed to compare the clinical features and lung function between asthmatic children with recurrent MLS and transient right middle lobe (RML) and/or lingula atelectasis. Methods: This study retrospectively analyzed asthmatic children with RML and/or lingula atelectasis between 2010 and 2020 using data from the pediatric pulmonary department. According to the episodes of atelectasis, children were divided into recurrent (≥2 episodes) and non-recurrent (only 1 episode) MLS groups, to compare clinical features and lung function. Spirometry during acute asthma exacerbation and stable stages were recorded, and variations were calculated. Results: A total of 35 children with asthma and RML and/or lingula atelectasis were included, 15 of whom had recurrent MLS. The recurrent MLS group had a higher proportion of girls, infections, family allergy history, severe asthma, severe exacerbation, and higher levels of total IgE than the non-recurrent MLS group (P < 0.05). The recurrent MLS group had a significantly higher % predicted and z-scores for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), a greater proportion of high FEV1 and higher variations in FEV1 and FVC than that in the non-recurrent group (P < 0.05). After excluding children with mild to moderate asthma in the recurrent MLS group, the differences in clinical features disappeared, but the results regarding lung function remained similar, when compared to severe asthma patients without RML and/or lingula atelectasis. Conclusions: Childhood asthma with recurrent MLS has more frequent severe asthma and exacerbation but high lung function and variations.

Clinical features and risk factors of plastic bronchitis caused by refractory Mycoplasma pneumoniae pneumonia in children: a practical nomogram prediction model.

Early assessment of refractory Mycoplasma pneumoniae pneumonia (RMPP) with plastic bronchitis (PB) allows timely removal of casts using fiberoptic bronchoscopic manipulation, which relieves airway obstruction and limit sequelae development. This study aimed to analyze clinical data for risk factors and develop a nomogram for early predictive evaluation of RMPP with PB. The clinical data of 1-14 year-old patients with RMPP were retrospectively analyzed. Patients were classified into a PB or non-PB group. The general characteristics, clinical symptoms, laboratory test results, imaging findings, and microscopic changes of the two groups were compared. A statistical analysis of the risk factors for developing PB was performed, and a nomogram model of risk factors was constructed. Of 120 patients with RMPP included, 68 and 52 were in the non-PB and PB groups, respectively. Using multivariate logistic regression analysis, fever before bronchoscopy, extrapulmonary complications, pleural effusion, cough duration, and lactate dehydrogenase (LDH) levels were identified as risk factors. A nomogram was constructed based on the results of the multivariate analysis. The area under the receiver operating characteristic curve value of the nomogram was 0.944 (95% confidence interval: 0.779-0.962). The Hosmer-Lemeshow test displayed good calibration of the nomogram (p = 0.376, R2 = 0.723). CONCLUSION: The nomogram model constructed in this study based on five risk factors (persistent fever before bronchoscopy, extrapulmonary complications, pleural effusion, cough duration, and LDH levels) prior to bronchoscopy can be used for the early identification of RMPP-induced PB. WHAT IS KNOWN: • Refractory Mycoplasma pneumoniae pneumonia (RMPP) in children has been increasingly reported and recognized, which often leads to serious complications. • Plastic bronchitis (PB) is considered to be one of the causes of RMPP, and bronchoscopic treatment should be improved as soon as possible to remove plastic sputum thrombus in bronchus. WHAT IS NEW: • This study determined the risk factors for RMPP-induced PB. • The nomogram model constructed in this study prior to bronchoscopy can be used for the early identification of RMPP-induced PB, which facilitate the early bronchoscopic removal of casts, thereby promoting recovery and reducing cases with poor RMPP prognosis.

A multicentre study on the incidence of respiratory viruses in children with community-acquired pneumonia requiring hospitalization in the setting of the zero-COVID policy in China.

BACKGROUND: Stringent nonpharmaceutical interventions (NPIs) have been implemented worldwide to combat the COVID-19 pandemic, and the circulation and seasonality of common respiratory viruses have subsequently changed. There have been few multicentre studies or comparisons of the prevalence of respiratory viruses accounting for community-acquired pneumonia (CAP) in hospitalized children between the pre-COVID period and the period after community and school reopening in the setting of the zero-COVID policy. METHODS: We included 1543 children with CAP who required hospitalization from November 1, 2020 to April 30, 2021 (period 1), and 629 children with the same conditions from November 1, 2018, to April 30, 2019 (period 2), in our study. All respiratory samples from these patients were screened for six respiratory viruses (respiratory syncytial virus [RSV], adenovirus [ADV], influenza A virus [Flu A], influenza B virus [Flu B], parainfluenza virus type 1 [PIV1], and parainfluenza virus type 3 [PIV3]) using a multiplex real-time PCR assay. RESULTS AND CONCLUSIONS: The median ages of the enrolled patients at the time of diagnosis were 1.5 years and 1.0 years for period 1 and period 2, respectively. In period 1, viral pathogens were detected in 50.3% (776/1543) of the enrolled patients. The most frequently identified viral pathogen was RSV (35.9%, 554/1543), followed by PIV3 (9.6%, 148/1543), PIV1 (3.6%, 56/1543), ADV (3.4%, 52/1543), Flu A (1.0%, 16/1543), and Flu B (0.8%, 13/1543). The total detection rates of these six viruses in the peak season of CAP were at the pre-COVID level. The prevalence of Flu A decreased dramatically, and circulation activity was low compared to pre-COVID levels, while the incidence of PIV3 increased significantly. There were no significant differences in the detection rates of RSV, ADV, Flu B, and PIV1 between the two periods. Our results showed that respiratory viruses accounted for CAP in hospitalized children at pre-COVID levels as communities and schools reopened within the zero-COVID policy, although the prevalence aetiology spectrum varied.

Collagen Triple Helix Repeat Containing 1 Deficiency Protects Against Airway Remodeling and Inflammation in Asthma Models In Vivo and In Vitro.

Asthma is a chronic inflammatory disease characterized by airway remodeling and lung inflammation. Collagen triple helix repeat containing 1 (CTHRC1), a glycoprotein, is involved in multiple pathological processes, including inflammation and fibrosis. However, the function of CTHRC1 in asthma remains unclear. In the present study, the mouse asthma model was successfully generated by sensitizing and challenging mice with ovalbumin (OVA). CTHRC1 expression at both RNA and protein levels was significantly upregulated in lung tissues of asthmatic mice. Asthmatic mice exhibited significant airway remodeling as evidenced by increased bronchial wall and smooth muscle cell layer thickness, goblet cell hyperplasia and collagen deposition, and epithelial-mesenchymal transition (EMT), but those characteristics were reversed by CTHRC1 silencing. The cell model with transforming growth factor-ß1 (TGF-ß1) induction in bronchial epithelial cells (BEAS-2B) was conducted to verify the effects of CTHRC1 on EMT, a classic mechanism that mediates airway remodeling. The results showed that TGF-ß1 stimulation increased CTHRC1 expression, and CTHRC1 knockdown inhibited TGF-ß1-induced EMT. OVA-treated mice also showed increased inflammatory cell infiltration and the production of OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-5, and IL-13, which were decreased by CTHRC1 downregulation. The effects of CTHRC1 on OVA-induced airway inflammation were further determined by treating BEAS-2B cells with IL-13, in which CTHRC1 knockdown reduced the IL-13-induced secretion of pro-inflammatory factors, including IL-4 and IL-5. In conclusion, these results indicate that CTHRC1 silencing attenuates asthmatic airway remodeling and inflammation in vivo and in vitro, suggesting that CTHRC1 may be a potential target for asthma treatment.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

A multicenter study on molecular epidemiology of rhinovirus isolated from children with community acquired pneumonia in China during 2017-2019.

Rhinoviruses (RVs) are a major pathogen of community acquired pneumonia in children. To investigate the prevalence and genetic characteristics of RVs in China, we performed a molecular epidemiological study during 2017-2019 in community acquired pneumonia (CAP) in pediatric patients. In this multicenter study, 109 RV-A, 20 RV-B and 80 RV-C were identified. Among them, RV-A12, RV-A101, RV-A78, RV-A49, RV-A22, RV-B52, RV-C2, RV-C53 and RV-C5 were the common genotypes in the study. A total of 23 complete genome of RVs including 4 RV-A, 1 RV-B and 18 RV-C were obtained. Furthermore, in the RV-C isolates, one RV-C5 and five RV-C53 genotypes were found, which have a limited number in the GenBank. Phylogenetic analysis of the complete genome showed that most of the RVs isolated in the study have high nucleotide sequence identities (>95%) compared with the corresponding reference sequence in the GenBank. In RV-A9, RV-A28, RV-A61 and RV-B52, amino acid mutations were found in the potential neutralizing immunogenic (Nim) sites (Nim-1a and Nim-1b) of the VP1. In RV-B52, one of RV-C2 and RV-C5 isolates, amino acid mutations were found in the P1a peptide of the VP1. However, no recombination events were found in the study. In conclusion, RV-A was the predominant specie of RVs followed by RV-C in the study. The complete genomes of one RV-C5 and five RV-C53 genotypes were obtained which have a limited number sequence in the GenBank. High nucleotide sequence identities (>95%) were found among the complete genome obtained in the study and the corresponding reference sequence in the GenBank. Amino acid mutations were found in the potential Nim-1a, Nim-1b sites and P1a peptide region of the VP1 in parts of RVs.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study.

Human metapneumovirus (HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples (5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two (67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus (EV) or rhinovirus (RhV) (38.0%, followed by respiratory syncytial virus (RSV) (32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36 strains were subgrouped into subtypes A2c (75%), eight strains were included in subtype B1 (16.7%), and four strains were included in subtype B2 (8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25 (92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

Carbenoxolone Ameliorates Allergic Airway Inflammation through NF-κB/NLRP3 Pathway in Mice.

Asthma is a respiratory disease characterized by heterogeneous chronic airway inflammation. Activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome is involved in the development of many pulmonary inflammatory diseases. The role and regulatory mechanism of carbenoxolone (CBX) in ovalbumin (OVA)-induced asthma models are not fully clear. Therefore, the study investigated whether CBX ameliorates airway inflammation and remodeling, as well as its mechanism in OVA induced-inflammation in mice. Wright-Giemsa staining was used to count inflammatory cells in bronchoalveolar lavage fluid (BALF). The level of inflammatory cells infiltration, mucus cell proliferation, and collagen deposition in lung tissue were separately assessed by hematoxylin and eosin, periodic acid-Schiff, and Masson trichrome staining, respectively. Airway resistance (AR) was measured by non-invasive airway system. Immunohistochemical assay was used to observe NLRP3 expression area. The expression of nuclear factor-kappaB (NF-κB), p-NF-κB, inhibitor of kappaB (IκB)-α, p-IκB-α, NLRP3, pro-caspase-1, caspase-1, and interleukin (IL)-1ß in lung tissue were measured using quantitative real-time PCR or Western blotting. Our results showed that CBX can significantly attenuate the leukocyte count and the percentage of eosinophils and neutrophils in the BALF, peribronchial inflammation, airway mucus secretion, collagen deposition area, and AR in OVA-induced airway inflammation. In addition, the expression of p-NF-κB, p-IκB-α, NLRP3 and related factors were dramatically alleviated after CBX treatment. These data suggest that CBX has a significant protective effect on allergic airway inflammation by suppressing the activation of NLRP3 inflammasome through NF-κB pathway in asthmatic mice.