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OBJECTIVE: To summarize the clinical features of primary nephrotic syndrome (PNS) complicated by plastic bronchitis (PB) in children to provide guidance for treatment. METHODS: We conducted a retrospective review of the clinical data of 25 children hospitalized with NS complicated by PB in our Hospital between 10/2016 and 03/2019, and summarized the clinical manifestations, imaging and fiberoptic bronchoscopy (FOB) examinations, treatment course and outcome of them. RESULTS: 1). The 25 children, with a nephrotic syndrome (NS) course of one to 36 months, were all diagnosed with PB after FOB, among which 8 cases (32%) had respiratory failure and required ventilatory support. All of them started with respiratory symptoms such as fever and cough, and then suffered from dyspnea and progressive aggravation after 1-3 day(s) of onset, with rapid occurrence of bidirectional dyspnea and even respiratory failure in severe cases. 2). Laboratory test for pathogens: influenza A virus H1N1 (11 cases), influenza B virus (9 cases), adenovirus (3 cases) and mycoplasma pneumoniae (2 cases). There was no statistically significant difference (P>0.05) between children with common NS complicated by influenza virus (IV) infection (not accompanied by dyspnea) and those with kidney disease who developed PB in the white blood cell count, lymphocyte count, the inflammatory biomarkers C-reactive protein (CRP), procalcitonin (PCT) and humoral immunity (IgG level), yet the total IgG level was found significantly higher and the blood albumin level lower in the latter (P<0.05). 3). The 25 children were all examined with the FOB and treated with lavage, 15 of which had typical bronchial tree-like casts and 10 broken and stringy casts. Based on histopathological classification, all children were of Type I. 4). Twenty children (80%) with influenza were administered the antiviral drug Oseltamivir, 20 (80%) were treated with antibiotics, oral hormones were replaced with the same dosage of intravenous Methylprednisolone for 5 cases (20%), and 20 (80%) were intravenously administered gamma globulins (400-500 mg/kg x 3 days). These children showed a remarkable improvement after treatment and there were no deaths. CONCLUSION: NS children are at high risk of influenza virus infection. Children with a severe case of NS are more susceptible to PB. If symptoms like shortness of breath, wheezing and progressive bidirectional dyspnea occur, FOB examination and lavage treatment should be performed as early as possible. Hyper-IgE-emia and hypoproteinemia may be the high risk factors for PNS complicated by PB in children. ZIEL: Ziel der Studie war es, durch Zusammenfassung der klinischen Merkmale des primären nephrotischen Syndroms (PNS) mit komplizierender plastischer Bronchitis (PB) im Kindesalter eine Orientierungshilfe für die Therapie der Erkrankung zu geben. METHODIK: Wir führten eine retrospektive Prüfung der klinischen Daten von 25 Kindern durch, die zwischen Oktober 2016 und März 2019 in unser Krankhaus aufgenommen wurden, und erstellten eine Zusammenfassung der klinischen Symptome, Untersuchungen mit bildgebenden Verfahren und fiberoptischer Bronchoskopie (FOB), des Therapieverlaufs und des Outcomes der Patienten. ERGEBNISSE: 1). Bei den 25 Kindern bestand ein nephrotisches Syndrom (NS) über einen Zeitraum von einem bis 36 Monaten. Bei allen Patienten wurde die Diagnose PB nach FOB gestellt, wobei in 8 Fällen (32%) eine beatmungspflichtige respiratorische Insuffizienz vorlag. Alle Patienten zeigten anfänglich Symptome einer Atemwegserkrankung wie Fieber und Husten, gefolgt von Atemnot und progredienter Verschlechterung 1 bis 3 Tage nach Erkrankungsbeginn. Dabei kam es rasch zum Auftreten bidirektionaler Atemnot, in schweren Fällen bis hin zur respiratorischen Insuffizienz. 2). Laboruntersuchung auf Erreger: Influenza-A-Virus H1N1 (11 Fälle), Influenza-B-Virus (9 Fälle), Adenovirus (3 Fälle) und Mycoplasma pneumoniae (2 Fälle). Es fand sich kein statistisch signifikanter Unterschied (P>0,05) zwischen Kindern, die ein "gewöhnliches" NS mit komplizierender Influenza-Virus (IV)-Infektion (ohne begleitende Atemnot) aufwiesen, und Kindern mit Nierenerkrankung, die eine PB entwickelten, hinsichtlich der Leukozyten- und Lymphozytenwerte sowie der Entzündungsmarker C-reaktives Protein (CRP), Procalcitonin (PCT) und humorale Immunität (IgG-Wert). Allerdings wurde bei der letzteren Patientengruppe ein signifikant höherer Gesamt-IgG-Wert und ein signifikant niedriger Albumin-Spiegel im Blut nachgewiesen (P<0.05). 3). Bei allen 25 Kindern erfolgte eine FOB und Therapie mit Lavage, bei 15 Kinder fanden sich typische verzweigte Ausgüsse der Bronchialäste und bei 10 Patienten desintegrierte und zähe Ausgüsse. Gemäß der histopathologischen Klassifikation waren alle Kinder vom Typ I. 4). Zwanzig Kinder (80%) mit Influenza erhielten das Virostatikum Oseltamivir, 20 Kinder (80%) eine Antibiotikatherapie, in 5 Fällen (20%) wurden oral gegebene Hormone durch intravenös in derselben Dosis verabreichtes Methylprednisolon ersetzt und 20 Kinder (80%) erhielten intravenös verabreichte Gammaglobuline (400-500 mg/kg Körpergewicht x 3 Tage). Diese Kinder zeigten eine bemerkenswerte Verbesserung nach der Therapie und es traten keine Todesfälle auf. SCHLUSSFOLGERUNG: Bei Kindern mit NS besteht ein hohes Risiko für eine Influenza-Virus-Infektion. Kinder mit schwerem NS sind anfälliger für PB. Bei Auftreten von Symptomen wie Atemnot, Giemen und Brummern sowie progredienter bidirektionaler Dyspnoe sollte baldmöglichst eine FOB-Untersuchung und eine therapeutische Lavage durchgeführt werden. Erhöhte IgE-Werte im Blut und Hypoproteinämie stellen möglicherweise Risikofaktoren für PNS mit komplizierender PB im Kindesalter dar.
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Bronquite , Vírus da Influenza A Subtipo H1N1 , Síndrome Nefrótica , Bronquite/diagnóstico , Bronquite/tratamento farmacológico , Criança , Humanos , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Plásticos , Estudos RetrospectivosRESUMO
Introduction: Immune dysfunction contributes to the progression of idiopathic nephrotic syndrome (INS), but the details of the pathogenesis of progression remain unknown. This study of children with INS investigated the relationship of activation of the mechanistic target of rapamycin (mTOR) pathway (PI3K/AKT/mTOR/p70S6K) with the levels of T helper 2/regulatory T (Th2/Treg) cells. Materials and Methods: Twenty children with active INS (before steroid treatment), 20 children with remitting INS (INS-R, after steroid treatment), and 20 healthy control children (Ctrl) were enrolled. The levels of Th2/Treg cells in their peripheral circulatory systems were measured using flow cytometry, and the concentration of interleukin (IL)-4 was determined using a cytometric bead array (CBA). The levels of PI3K, AKT, mTOR, p70S6K, and transcription factors associated with Th2/Treg cells were measured using real-time polymerase chain reaction. Results: The INS group had a greater proportion of circulating Th2 cells; level of IL-4 protein; and levels of GATA, PI3K, AKT, mTOR, and p70S6K mRNAs than the Ctrl group (all P < 0.05), but a lower proportion of circulating Tregs and expression of Foxp3 (both P < 0.05). Patients in the INS-R group had normalization of these markers (all P < 0.05). Patients in the INS group had negative correlation in the percentage of Treg cells with Th2 cells and with IL-4 level and a negative correlation in the levels of GATA3 and Foxp3 mRNAs. Conclusions: Patients with active INS had an imbalance of Th2/Treg cells, which might result from the aberrant signaling of the mTOR pathway (PI3K/AKT/mTOR/p70S6K).
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OBJECTIVE: Significant cardiac dysfunction has been found in children with severe hand-foot-mouth disease and heart failure is the major cause of death in these patients. Evaluation of cardiac function is essential for the treatment of severe cases. This study evaluated the clinical value of cardiac output monitoring in children with severe hand-foot-mouth disease. METHODS: A total of 107 children with severe hand-foot-mouth disease admitted to the pediatric intensive care unit from April 2011 to September 2011 were enrolled and divided into three groups by clinical stage: 73 cases in stage 2, 23 cases in stage 3 and 11 cases in stage 4. Cardiac output and stroke volume were measured by ultrasonic cardiac output monitors (USCOM). Ninety-five children received MRI scanning and were grouped according to the results of MRI: 41 cases (medulla oblongata involvements in 9 cases) in abnormal MRI group and 54 cases in normal MRI group. Cardiac output was compared between the children in different clinical stages and between different MRI results. RESULTS: Compared with children in clinical stages 2 and 3, cardiac output in children in clinical stage 4 decreased significantly (P<0.05). There was no differences in cardiac output between the normal and abnormal MRI groups, however cardiac output was significantly lower in children with medulla oblongata involvement than in those with other involvements and normal MRI. CONCLUSIONS: Significant decrease in cardiac output suggests critical conditions and medulla oblongata cardiovascular center involvement in children with severe hand-foot-mouth disease. Dynamic measurement of cardiac output is valuable for treatment of the disease.
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Débito Cardíaco/fisiologia , Doença de Mão, Pé e Boca/fisiopatologia , Monitorização Fisiológica , Criança , Pré-Escolar , Feminino , Doença de Mão, Pé e Boca/terapia , Humanos , Lactente , Imageamento por Ressonância Magnética , MasculinoRESUMO
Purpose: We investigated the pathogenesis of idiopathic nephrotic syndrome (INS) by measuring the effects two specific miRNAs on Th2 cells in children with this disease. Methods: After informed consent, we enrolled 20 children with active INS before steroid initiation, 20 children with INS in remission after steroid therapy, and 20 age-matched healthy controls. Flow cytometry was used to measure the levels of Th2 cells and a cytometric bead array was used to measure the levels of IgE, interleukin (IL)-4, and IL-13. RT-PCR was used to measure the levels of miR-24 and miR-27 in CD4+TCD25- cells. PBMCs were isolated using Ficoll density gradient centrifugation, and transfected with different mimic or inhibitor miRNAs. RT-PCR was used to measure the expression of different RNAs, and flow cytometry was used to determine the percentage of Th2 cells. Results: Relative to healthy controls, children with active INS had higher percentages of Th2 cells (P < 0.05), but there was no significant difference in controls and children in remission. The plasma levels of IgE, IL-4, and IL-13 were significantly increased in children with active INS (P < 0.05). There were lower levels of miR-24 and miR-27 in children with active non-atopic INS (P < 0.05). Transfection experiments indicated that upregulation of each miRNA decreased the percentage of Th2 cells and the level of IL-4 (P < 0.05), and down-regulation of each miRNA had the opposite effects (P < 0.05). Conclusion: Children with active INS, with or without atopy, had higher levels of IgE, possibly related to their higher levels of IL-13 and IL-4 due to a drift toward Th2 cells. miR-24 and miR-27 suppressed the expression of Th2 cells and have a critical function regulating Th2 cell expression in INS.
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Tumor necrosis factor (TNF) and the TNF receptor superfamily (TNF-TNFR) plays very important roles in the pathogenesis of Kawasaki disease (KD) by leukocyte recruitment, upregulation of matrix-degrading enzymes and proinflammatory cytokines. This study aims to investigate whether potential polymorphisms in TNF receptor superfamily member 1A gene (TNFR1) are associated with KD and its effects on transcriptions activity of TNFR1. Genetic variations of TNFR1 promoter and coding regions in 132 unrelated patients with KD and 212 age-matched healthy controls recruited from a population of Chinese individuals were screened by direct sequencing. Bioinformatics analysis and function assays were performed to investigate the association between genetic variations and KD, and its effects on transcription activity of TNFR1. Five polymorphisms, termed -609T/G, -581A/G, -421G/A, -383A/C, and +36A/G, were identified in the subjects, of which -421A/G was reported for the first time. In particular, bioinformatics analysis and function assay confirmed that -609T allele resulted in allele-specific strengthening of TNFR1 transcription and was significantly associated with KD (p = 2.951E-08, odds ratio = 2.42, 95% confidence interval = 1.76-3.13). Furthermore, the haplotype TAGAA showed a relatively higher frequency in patients with KD compared with healthy controls (p = 3.446E-07, odds ratio = 2.26, 95% confidence interval = 1.65-3.11). Therefore, our results suggested that regulatory polymorphism -609T/G and the haplotype TAGAA may be related to increased susceptibility to KD in Chinese individuals.
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Síndrome de Linfonodos Mucocutâneos/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Ativação Transcricional , Criança , Pré-Escolar , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Sequências Reguladoras de Ácido Nucleico/genética , Ativação Transcricional/genéticaRESUMO
OBJECTIVE: To investigate the alteration of immune function and possible immunopathogenesis in the children with 2009 influenza A (H1N1) infection. METHOD: Sixty patients with 2009 influenza A (H1N1) infection hospitalized in Shenzhen Children's Hospital between November 1, 2009 and January 10, 2010 and 20 age-matched healthy children were enrolled in this study. The patients were divided into two groups according to the severity of influenza A infection: 35 mild cases (mild pneumonia) and 25 severe cases (severe pneumonia, acute encephalopathy associated with influenza A, and 3 died from acute necrotizing encephalopathy with influenza A infection). Real-time PCR was used to evaluate the expression levels of pattern recognition receptor (PRRs), retinoic acid induced gene I/melanoma differentiation associated gene 5 (RIG/MDA5), Toll-like receptors (TLRs) and TLRs signaling molecules, and negative-regulator. Three color fluorescent and flow cytometry were used to investigate the apoptosis of CD3(+), CD4(+), CD8(+) and CD19(+) cells. Plasma cytokines (IL-1ß, IL-6, TNF-α, IFN-γ, IFN-α, IL-10) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). RESULT: (1) The expression levels of RIG/MDA5, TLR2, 4 were much higher in the patients with influenza A infection, especially severe cases [TLR2 (9.69 ± 3.15) × 10(-2) vs. (3.96 ± 0.83) × 10(-2), t = 10.16, P < 0.05; TLR4 (10.23 ± 2.85) × 10(-2) vs. (7.46 ± 2.18) × 10(-2), t = 3.76, P < 0.05]. The expression levels of TLRs signal transduction molecules like MyD88 and TRAM also increased. (2) The cell counts of CD3(+), CD4(+), CD8(+) T cells and NK cells were markedly lower in the patients with influenza A infection compared to the NC group [CD3(+)(1.22 ± 0.38) × 10(9)/L vs.(3.59 ± 1.10) × 10(9)/L, t = 9.21, P < 0.05]. (3) Plasma concentrations and the mRNA expression of TNF-α, IL-6, and IL-1ß were elevated in mild cases, while declined in severe cases [TNF-α (6.42 ± 1.76) × 10(-2) vs. (9.05 ± 2.51) × 10(-2), t = 4.55, P < 0.05]. Plasma concentrations of IFN-α/IFN-ß were up-regulated gradually with the aggravation of the disease, especially in severe cases. Compared with healthy controls, the expression of IFN-I inducible gene IP-10, RANTES, or iNOS was significantly higher in children with mild [IP-10 (20.52 ± 6.09) × 10(-2) vs.(1.18 ± 0.34) × 10(-2), t = 18.74, P < 0.05], and relatively lower in severe cases. (4) The apoptosis of CD3(+), CD4(+), CD8(+) and NK cells significantly increased in the patients with influenza A infection than those in NC group [CD3(+)(32.90 ± 7.66)% vs. (20.21 ± 6.58)%, t = 6.21, P < 0.05]. Compared with healthy controls, the expression levels of apoptosis-related gene like TRAIL and CASPASE-3 significantly increased in the patients with influenza A infection. (5) The expression levels of negative regulator of SOCS1, SOCS3, IRAK-M, TRAF4 and FLN29 were significantly increased in the patients with influenza A, especially in severe cases than those in NC group (P < 0.05). CONCLUSION: Immune function changed with the severity of the disease. The mild cases presented systemic immune activation status, while critically ill cases presented mixed immune activation and immunosuppression status.