Case Report: Mycoplasma pneumoniae-associated acute pancreatitis.

Mycoplasma pneumoniae is the primary pathogen causing community-acquired pneumonia in children, accounting for approximately 10%-40% of cases. It can lead to various extrapulmonary complications, including acute pancreatitis, which has been reported in approximately 30 cases to date. Here, we report a 4-year-old girl who presented with fever, cough, and elevated levels of M. pneumoniae IgM antibodies, followed by the onset of abdominal pain, elevated lipase, and elevated blood and urine amylase. Abdominal CT implied diffuse inflammation of the pancreas. Serum inflammatory cytokines, such as interleukin (IL)-2, IL-6, IL-17A, tumor necrosis factor, and interferon-gamma, were elevated. After excluding other causes, it was determined that M. pneumoniae infection was the cause of her acute pancreatitis. She was treated with macrolides and glucocorticoids and ultimately made a full recovery. Therefore, acute pancreatitis should be included in the differential diagnosis for patients with M. pneumoniae infection who present with abdominal pain. Inflammatory cytokines may play a role in mediating pancreatic damage.

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.

Cotton Ball Aspiration Leading to Pulmonary Complications in a Child.

BACKGROUND Foreign body aspiration (FBA) is a common and serious problem in childhood that requires early recognition and treatment. Common complications include asphyxia, hemorrhage, infection, and pneumothorax. In severe cases of foreign body obstruction, death can result from asphyxia. We report an interesting case in which a forgotten cotton ball was inhaled into the lungs. CASE REPORT A 5-year-old boy presented to the local hospital with coughing for 6 days and fever for 4 days, without any information of foreign body aspiration upon admission. Laboratory findings indicated an elevated white blood cell; therefore, cefprozil was given as anti-infective treatment. However, the child's condition did not improve. A computed tomography scan showed left pulmonary atelectasis. Considering that the child's condition was serious, he was referred to our hospital for diagnosis and treatment. After referral, auscultation revealed decreased breath sounds over the left lung. After multidisciplinary discussion, combined with the results of auxiliary examination, the possibility of a foreign body was considered. He underwent rigid bronchoscopy, which confirmed a yellow-white foreign body in the left main bronchus that was later verified as a cotton ball. The operation was very successful. Eventually, his condition improved and he was discharged, without additional complications. CONCLUSIONS For children with unclear history of foreign body aspiration, bronchoscopy is recommended if there is recurrent pulmonary infection, low auscultation breath sounds, or abnormal imaging. The choice of surgical method depends on the location and type of foreign body and the experience of the surgeon, which is also very important.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Angiotensin II Type 2 Receptor Inhibits M1 Polarization and Apoptosis of Alveolar Macrophage and Protects Against Mechanical Ventilation-Induced Lung Injury.

Angiotensin II (Ang II) is associated with macrophage polarization and apoptosis, but the role of the angiotensin type 2 receptor (AT2R) in these processes remains controversial. However, the effect of AT2Rs on alveolar macrophages and mechanical ventilation-induced lung injury has not been determined. Mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats and LPS-stimulated rat alveolar macrophages (NR8383) were used to determine the effects of AT2Rs, selective AT2R agonists and selective AT1Rs or AT2R antagonists. Macrophage polarization, apoptosis, and related signaling pathways were assessed via western blotting, QPCR and flow cytometry. AT2R expression was decreased in LPS-stimulated rat alveolar macrophages (NR8383). Administration of the AT2R agonist CGP-42112 was associated with an increase in AT2R expression and M2 polarization, but no effect was observed upon administration of the AT2R antagonist PD123319 or the AT1R antagonist valsartan. In mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats, the administration of the AT2R agonist C21 was associated with attenuation of the pathological damage score, lung wet/dry weight, cell count and protein content in BALF. C21 can significantly reduce proinflammatory factor TNF-α, IL-1ß levels, increase anti-inflammatory factor IL-4, IL-10 levels in BALF, compared with the model group (p < 0.01). Similarly, compared with those at the same time points, the M1/M2 ratios in alveolar macrophages and apoptosis in peritoneal macrophages at 4 h, 6 h and 8 h in the mechanical ventilation models were lower after C21 administration. These findings indicated that the expression of AT2Rs in alveolar macrophages mediates M1 macrophage polarization and apoptosis and that AT2Rs play a protective role in mediating mechanical ventilation-induced lung injury.

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.

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 mucoepidermoid carcinoma in children: two case reports and a review of the literature.

Pulmonary mucoepidermoid carcinoma (PMEC) is a rare tumor, particularly in children, and its clinical manifestations vary. When the tumor is small, it may be asymptomatic; however, with larger tumors, patients may present with symptoms such as recurring pneumonia, atelectasis, persistent cough, chest pain, and even hemoptysis. PMEC appears as an exophytic intrabronchial mass. This study aims to report on the clinical manifestations, imaging findings, treatment approaches, and prognosis of two children diagnosed with PMEC at our hospital between January 2018 and December 2022. The age of onset for both children was 9 years, and the masses were located in the right upper lobe bronchi. Following surgical treatment, both patients showed a good prognosis. In addition, we conducted a comprehensive review of the relevant literature to enhance the overall understanding of PMEC.

SUMOylation of Rho-associated protein kinase 2 induces goblet cell metaplasia in allergic airways.

Allergic asthma is characterized by goblet cell metaplasia and subsequent mucus hypersecretion that contribute to the morbidity and mortality of this disease. Here, we explore the potential role and underlying mechanism of protein SUMOylation-mediated goblet cell metaplasia. The components of SUMOylaion machinery are specifically expressed in healthy human bronchial epithelia and robustly upregulated in bronchial epithelia of patients or mouse models with allergic asthma. Intratracheal suppression of SUMOylation by 2-D08 robustly attenuates not only allergen-induced airway inflammation, goblet cell metaplasia, and hyperreactivity, but IL-13-induced goblet cell metaplasia. Phosphoproteomics and biochemical analyses reveal SUMOylation on K1007 activates ROCK2, a master regulator of goblet cell metaplasia, by facilitating its binding to and activation by RhoA, and an E3 ligase PIAS1 is responsible for SUMOylation on K1007. As a result, knockdown of PIAS1 in bronchial epithelia inactivates ROCK2 to attenuate IL-13-induced goblet cell metaplasia, and bronchial epithelial knock-in of ROCK2(K1007R) consistently inactivates ROCK2 to alleviate not only allergen-induced airway inflammation, goblet cell metaplasia, and hyperreactivity, but IL-13-induced goblet cell metaplasia. Together, SUMOylation-mediated ROCK2 activation is an integral component of Rho/ROCK signaling in regulating the pathological conditions of asthma and thus SUMOylation is an additional target for the therapeutic intervention of this disease.

Salivary IgG4 Levels Contribute to Assessing the Efficacy of Dermatophagoides pteronyssinus Subcutaneous Immunotherapy in Children with Asthma or Allergic Rhinitis.

At present, there are no effective, non-invasive, and objective indicators to evaluate the efficacy of pediatric house dust mite (HDM)-specific allergen immunotherapy (AIT). A prospective, observational study was performed in children with Dermatophagoides pteronyssinus (Der p) asthma and/or allergic rhinitis (AR). Forty-four patients received subcutaneous Der p-AIT for 2 years, and eleven patients received only symptomatic treatment. The patients needed to finish their questionnaires at each visit. Serum and salivary Der p-specific IgE, IgG4, and IgE-blocking factors (IgE-BFs) were measured at 0, 4, 12, and 24 months during AIT. A correlation between them was also evaluated. Subcutaneous Der p-specific AIT improved the clinical symptoms of children with asthma and/or AR. The Der p-specific IgE-BF significantly increased at 4, 12, and 24 months after AIT treatment. Serum and salivary Der p-specific IgG4 significantly increased with the time of the AIT treatment, and significant correlations between them at different time points were observed (p < 0.05). Furthermore, there were significant correlations (R = 0.31-0.62) between the serum Der p-specific IgE-BF and Der p-specific IgG4 at the baseline, 4, 12, and 24 months after the AIT (p < 0.01). The salivary Der p-specific IgG4 levels also demonstrated a certain correlation with the Der p-specific IgE-BF. Der p-specific AIT is an effective treatment for children with asthma and/or AR. Its effect was associated with increased serum and salivary-specific IgG4 levels, as well as an increased IgE-BF. Non-invasive salivary-specific IgG4 may be useful for monitoring the efficacy of AIT in children.

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 (AU)

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.

The clinical significance of allergen-specific IgG4 in allergic diseases.

IgG4 is a subclass of IgG antibody with a unique molecular feature of (Fragment antigen- binding) Fab-arm exchange, allowing bispecific antigen binding in a mono-valent manner. With low binding affinity to C1q and Fcγreceptors, IgG4 is incapable of forming immune complexes and activating the complement pathway, exhibiting a non-inflammatory feature. IgG4 is produced similarly to IgE and is considered a modified reaction to IgE class-switching response under certain conditions. It could also counteract IgE-activated inflammation. However, the clinical significance of IgG4 in allergic diseases is complex and controversial. Three viewpoints have been suggested to describe the role of IgG4. IgG4 can act as a tolerance-inducer to play a protective role under repeated and rapid incremental dosing of allergen exposure in allergen immunotherapy (AIT), supported by allergies in cat raisers and venom desensitization in beekeepers. Another viewpoint accepted by mainstream specialists and guidelines of Food Allergy and Management in different countries points out that food-specific IgG4 is a bystander in food allergy and should not be used as a diagnostic tool in clinical work. However, eosinophilic esophagitis (EoE) investigation revealed a direct clinical relevance between physiopathology and serum IgG4 in cow milk and wheat. These factors indicate that allergen-specific IgG4 plays a multifaceted role in allergic diseases that is protective or pathogenic depending on different allergens or exposure conditions.

The clinical application of flexible bronchoscopy in a neonatal intensive care unit.

Objective: Flexible bronchoscopy is widely used in infants and it plays a crucial role. The aim of this study was to investigate the value and clinical safety of flexible bronchoscopy in a neonatal intensive care unit. Methods: A retrospective analysis was performed on the clinical data of 116 neonates who underwent flexible bronchoscopy and the outcomes of 147 procedures. A correlation analysis was performed on the relationship between flexible bronchoscopy findings, microscopic indications, and clinical disease. Results: The 147 procedures performed were due to the following reasons: problems related to artificial airways, 58 cases (39.45%); upper respiratory problems, 60 cases (40.81%) (recurrent dyspnea, 23 cases; upper airway obstruction, 17 cases; recurrent stridor, 14 cases; and hoarseness, six cases), lower respiratory problems, 51 cases (34.69%) (persistent pneumonia, 21 cases; suspicious airway anatomical disease, 21 cases; recurrent atelectasis, eight cases; and pneumorrhagia, one case), feeding difficulty three cases (2.04%). The 147 endoscopic examinations were performed for the following reasons: pathological changes, 141 cases (95.92%); laryngomalacia, 78 cases (53.06%); mucosal inflammation/secretions, 64 cases (43.54%); vocal cord paralysis, 29 cases (19.72%); trachea/bronchus stenosis, 17 cases (11.56%) [five cases of congenital annular constriction of the trachea, seven cases of left main tracheal stenosis, one case of the right middle bronchial stenosis, two cases of tracheal compression, and two cases of congenital tracheal stenosis]; subglottic lesions, 15 cases (10.20%) [eight cases of subglottic granulation tissue, six cases of subglottic stenosis, one cases of subglottic hemangioma]; tracheomalacia, 14 cases (9.52%); laryngeal edema, five cases (3.40%); tracheoesophageal fistula, four cases (2.72%); rhinostenosis, three cases (2.04%); tracheal bronchus, three cases (2.04%); glossoptosis, two cases (1.36%); laryngeal cyst, two cases (1.36%); laryngeal cleft, two cases (1.36%); tongue base cysts, one case (0.68%); and pneumorrhagia, one case (0.68%). Complications were rare and mild. Conclusion: Flexible bronchoscopy is safe and effective for diagnosing and differentiating neonatal respiratory disorders in neonatal intensive care units.

An isolated pulmonary nodule secondary to Streptococcus intermedius infection in an otherwise healthy 10-year-old boy: A case report and literature review.

Streptococcus intermedius, as a Gram-positive commensal bacterium, tends to cause various infections, such as brain and liver abscesses, endocarditis, and empyema, especially in immunocompromised patients. However, an isolated pulmonary nodule caused by S. intermedius in previously healthy individuals without traditional risk factors is rarely reported. Herein, we present a case of a 10-year-old immunocompetent boy referred to our department with a 5-day history of intermittent, left-sided chest pain. Chest X-ray and computed tomography revealed a left lung nodule. Although his blood, sputum, and bronchoalveolar lavage fluid cultures were negative, metagenomic next-generation sequencing (mNGS) showed only the presence of S. intermedius in ultrasonography-guided lung biopsy tissue and pleural fluid (416 and 110 reads, respectively). He was then successfully treated with appropriate intravenous antibiotics and avoided surgical intervention. To the best of our knowledge, this is the first report of S. intermedius-related pulmonary nodule confirmed by mNGS analysis in healthy children. For achieving proper diagnosis and treatment, infection with S. intermedius should be included in the differential diagnosis when coming across such a similar pulmonary nodule. mNGS, as a valuable supplement to conventional culture methods, is an essential diagnostic tool for identifying pathogens without typical characteristics.

Case Report: Intermittent Chest Pain With Cough, Fever, and Pericardial Effusion Over the Course of 1 Year in an 11-Year-Old Girl.

An 11-year-old girl presented with frequent chest pain, fever, and a cough that she had had for more than 13 months, as well as pleural effusion and large pericardial effusion. She was misdiagnosed with tuberculosis and received anti-tuberculosis drugs for 6 months. Within the past year, she also underwent two more thoracotomies and a thoracoscopic partial pericardiectomy. The final diagnosis of pulmonary paragonimiasis was established once it was known that she had eosinophilia, always drank stream water, and tested positive for antibodies against Paragonimus. Since antiparasitic praziquantel therapy was effective, paragonimiasis should be considered as a possibility in the differential diagnosis of tuberculosis in children.

Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3ß.

Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the last step of VC synthesis, VC deprivation resulted in persistent hypoglycemia and subsequent impairment of cognitive functions in female but not male mouse pups. The cognitive disorders caused by VC deprivation were largely reversed when these female pups were given glucose. VC deprivation-induced S-nitrosylation of glycogen synthase kinase 3ß (GSK3ß) at Cys14, which activated GSK3ß and inactivated glycogen synthase to decrease glycogen synthesis and storage under the feeding condition, while VC deprivation inactivated glycogen phosphorylase to decrease glycogenolysis under the fasting condition, ultimately leading to hypoglycemia and cognitive disorders. Treatment with Nω-Nitro-l-arginine methyl ester (l-NAME), a specific inhibitor of nitric oxide synthase, on the other hand, effectively prevented S-nitrosylation and activation of GSK3ß in female pups in response to the VC deprivation and reversed hypoglycemia and cognitive disorders. Overall, this research identifies S-nitrosylation of GSK3ß and subsequent GSK3ß activation as a previously unknown mechanism controlling glucose homeostasis in female pups in response to VC deprivation, implying that VC supplementation in the prevention of hypoglycemia and cognitive disorders should be considered in the certain groups of people, particularly young females.

Evaluation of a Novel Simulation Curriculum With the Segmented Model in Pediatric Cardiovascular Education.

Objective: The need to develop the full range of knowledge, skills, and professionalism poses new challenges for pediatric cardiovascular education. This study aimed to investigate the effectiveness of a novel simulation curriculum with the segmented model for pediatric cardiovascular residents. Materials and Methods: First, the simulation course was designed according to a prior survey and based on a human patient simulator setting. Then, another 55 residents were randomly selected and assigned to participate in a simulation course (about acute fulminant myocarditis in children), either in the experimental group or the control group. Taking full advantage of the simulation education, the simulation case in the experimental group was divided into three segments and included a micro-debriefing at the end of each segment. The three segments were independent but together formed the whole case. It was designed through three cycles of running and debriefing, and more challenging tasks were gradually proposed to residents. The case in the control group was not split and included only one case running and debriefing. The assessments of the residents' knowledge, skills, professionalism performance, and satisfaction feedback from residents were analyzed to evaluate the effectiveness of the course. Results: In total, 44 residents completed the whole experimental period, including 23 participants in the experimental group and 21 participants in the control group. The pre-course knowledge assessment scores of the two groups were comparable, while the mean post-course score in the experimental group was 82.61 ± 17.38, which was significantly higher than that in the control group (50.48 ± 18.57, p < 0.01). The mean skills assessment score of residents in the experimental group was 84.17 ± 6.01, which was significantly higher than the control group (54.50 ± 5.72, p < 0.01). In terms of the professionalism assessment, the residents in the experimental group achieved better performance than those in the control group in all aspects (respect, privacy, communication, responsibility, and cooperation) (p < 0.05). Satisfaction feedback from residents showed that self-confidence regarding knowledge mastery in the experimental group was significantly higher than that in the control group (p < 0.05), while there were no significant differences in the evaluations of the teacher's performance (p > 0.05). Conclusions: The novel simulation curriculum with the segmented model helps residents achieve better performance in terms of knowledge, skills, and professionalism while improving self-confidence. It has some value in pediatric cardiovascular education and is worthy of further promotion.

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.