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PURPOSE: To investigate associations of five typical lifestyle-related behavioral risk factors (insufficient physical activity, prolonged screen viewing, deprived sleeping, consumption of fast food and sugar-sweetened beverage) with health-related quality of life (HRQoL) among school students in China. METHODS: Students aged 9-17 years (grades 4-12) were randomly selected from primary and high schools in Nanjing, China, to participate in this cross-sectional study in 2018. The outcome variable, HRQoL, was assessed using the Child Health Utility 9D (CHU9D) instrument and scored from 0 (worst) to 1 (best). Physical activity (including screen viewing and sleeping) and dietary intake were measured using a validated Physical Activity Scale and Food Frequency Questionnaire, respectively. Lifestyle-related behaviors were categorized as sufficient/insufficient or no/yes, and their associations with HRQoL were assessed using mixed-effects linear regression models. RESULTS: Overall, 4388 participants completed the questionnaire (response rate = 97.6%). Students with insufficient physical activity [mean difference (MD) = - 0.03; 95% confidence interval (CI) = - 0.04, - 0.01], prolonged screen time (MD = - 0.06; 95% CI = - 0.07, - 0.04), insufficient sleeping time (MD = - 0.04; 95% CI = - 0.07, - 0.02), consumption of sugar-sweetened beverage (MD = - 0.02; 95% CI = - 0.03, - 0.01) or fast food intake (MD = - 0.03; 95% CI = - 0.04, - 0.02) reported significantly lower HRQoL scores. When considered additively, each additional lifestyle-related risk factor was associated with an average decrease of 0.03 units (95% CI: - 0.03, - 0.02) CHU9D score. CONCLUSIONS: For Chinese students, HRQoL was positively associated with physical activity and sleep duration, but negatively with screen time and consumption of sugar-sweetened beverage and fast food. Moreover, lifestyle-related behaviors may have an additive effect on HRQoL.
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Conductas de Riesgo para la Salud , Estilo de Vida , Calidad de Vida , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Adolescente , Niño , China/epidemiología , Estudios Transversales , Ejercicio Físico , Comida Rápida , Femenino , Humanos , Masculino , Tiempo de Pantalla , Sueño , Bebidas Azucaradas , Encuestas y CuestionariosRESUMEN
Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20-30% of SRNS patients. Methods: We used whole exome sequencing to explore the genetic causes of SRNS in children. Totally, 101 patients with SRNS and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022. For the known monogenic causes analysis, we generated a known SRNS gene list of 71 genes through reviewing the OMIM database and literature. Results: Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4 (3/27), and ANLN (2/27). Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS. In total, 68.75% of variants we identified were novel and have not been previously reported in the literature. Conclusion: Comprehensive genetic analysis is key to realizing the clinical benefits of a genetic diagnosis. We suggest that all children with SRNS undergo genetic testing, especially those with early-onset and extrarenal phenotypes.
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BACKGROUND: Glomerulonephritis is a common urinary system disease among children. Growing evidence suggests that traditional Chinese medicine has potential in treating glomerulonephritis, such as Li-Da-Qian mixture. Although its anti-glomerulonephritis and alleviating hematuria effects have been reported, the exact mechanism of Li-Da-Qian mixture devoting to glomerulonephritis remains unexplored. It was necessary to explore the mechanism of Li-Da-Qian mixture against glomerulonephritis using modern technology, such as Chinese medicine database and molecular biological experiments. METHODS: Online databases were used to look up ingredients and predict targets of Li-Da-Qian mixture against glomerulonephritis. The intersecting targets of Li-Da-Qian mixture and glomerulonephritis were selected for enrichment analysis. Cytoscape software was applied to establish network and MCODE analysis. Molecular docking was used for the primary validation. Furthermore, we examined the function of the core compounds analyzed from Li-Da-Qian mixture to rescue LPS-induced inflammation in vivo and vitro. We also explored whether the core compounds can alleviate TGFß1-induced renal fibrosis in mouse proximal tubular cells. RESULTS: Network pharmacological analysis of Li-Da-Qian evaluated 20 active ingredients including baicalein, luteolin and quercetin. A total of 113 key targets were screened, including IL6, VEGFA, TP53, EGF, MMP2, etc, and they were enriched in AGE-RAGE signaling pathway in diabetic complications, TNF and IL-17 signaling pathways. Moreover, the core ingredients succeeded in binding to the main targets via molecular docking, further identifying the anti-glomerulonephritis effects and improvement of vascular injury. Western blotting and qPCR also suggested that baicalein and luteolin can improve inflammation and restore disturbance of mesangial cells or kidney induced by LPS. In addition, baicalein and luteolin inhibited renal fibrosis in vitro.
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X-linked hypophosphatemia (XLHR) is caused by loss-of-function mutations in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene. Considerable controversy exists regarding genotype-phenotype correlations in XLHR. The present study describes the clinical features and molecular genetic bases of 53 pediatric patients with XLHR. Overall, 47 different mutations were identified, of which 27 were not previously described in the literature or entered in the Human Gene Mutation Database (HGMD). A high prevalence (72.34%) of truncating variants was observed in XLHR patients. The clinical presentation and severity of XLHR did not show an evident correlation between the truncating and non-truncating mutation types in our cohort. To further delineate the characteristics of PHEX variants underlying this nonsignificant trend, we assessed the effects of 10 PHEX variants on protein expression, cellular trafficking, and endopeptidase activity. Our results showed that the nonsense mutations p.Arg567*, p.Gln714*, and p.Arg747* caused a reduction of protein molecular weight and a trafficking defect. Among seven non-truncating mutations, the p.Cys77Tyr, p.Cys85Ser, p.Ile281Lys, p.Ile333del, p.Ala514Pro, and p.Gly572Ser mutants were not secreted into the medium and remained trapped inside cells in an immature form, whereas the p.Gly553Glu mutant was terminally glycosylated and secreted into the medium. We further assessed the endopeptidase activity of the p.Gly553Glu mutant using a quenched fluorogenic peptide substrate and revealed that the activity of p.Gly553Glu significantly reduced to 13% compared with the wild type, which indicated disruption of catalytic function. These data not only support the clinical results showing no correlation between disease severity and the type of PHEX mutation but also provide helpful molecular insights into the pathogenesis of XLHR. © 2020 American Society for Bone and Mineral Research.
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Raquitismo Hipofosfatémico Familiar , Enfermedades Genéticas Ligadas al Cromosoma X , Niño , Codón sin Sentido , Raquitismo Hipofosfatémico Familiar/genética , Estudios de Asociación Genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Mutación/genética , Endopeptidasa Neutra Reguladora de Fosfato PHEX/genéticaRESUMEN
OBJECTIVES: The dysfunction of mitochondrial respiratory chain induced by cisplatin results in overproduction of reactive oxygen species (ROS) which contributes to kidney injury. The current study aimed to evaluate the effect of a mitochondrial electron transport inhibitors of rotenone (mitochondrial complex I inhibitor) and azoxystrobin (mitochondrial complex III inhibitor), in cisplatin-induced kidney injury. METHODS: In vivo, cisplatin was administered to male C57BL/6J mice by a single intraperitoneal (i.p.) injection (20 mg/kg). Then the mice were treated with or without 200 ppm rotenone in food. Mice were sacrificed after cisplatin administration for 72 h. The serum and the kidney tissues were collected for further analysis. In vitro, mouse proximal tubular cells (mPTCs) were treated with cisplatin (5 µg/mL) and rotenone/azoxystrobin for 24 h. Flow cytometry, Western blotting, and TUNEL staining were used to evaluate the cell injury. RESULTS: In vivo, rotenone treatment obviously ameliorated cisplatin-induced renal tubular injury evidenced by the improved histology and blocked NGAL upregulation. Meanwhile, cisplatin-induced renal dysfunction shown by the increased levels of serum creatinine (Scr), blood urea nitrogen (BUN), and cystatin C were significantly reduced by rotenone treatment. Moreover, the increments of cleaved caspase-3 and transferase dUTP nick-end labeling (TUNEL)-positive cells were markedly decreased in line with the attenuated mitochondrial dysfunction and oxidative stress after rotenone administration. In vitro, rotenone and azoxystrobin protected against mitochondrial dysfunction, oxidative stress, and renal tubular cell apoptosis induced by cisplatin. CONCLUSIONS: Our results demonstrated that inhibition of mitochondrial activity significantly attenuated cisplatin nephrotoxicity possibly by inhibiting mitochondrial oxidative stress.
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Lesión Renal Aguda , Cisplatino/farmacología , Mitocondrias , Pirimidinas/farmacología , Rotenona/farmacología , Estrobilurinas/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Lesión Renal Aguda/prevención & control , Animales , Complejo III de Transporte de Electrones/antagonistas & inhibidores , Riñón/metabolismo , Riñón/patología , Pruebas de Función Renal/métodos , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Resultado del Tratamiento , Desacopladores/farmacologíaRESUMEN
Acute kidney injury (AKI) has been widely recognized as an important risk factor leading to the occurrence and progression of chronic kidney disease (CKD). Thus, development of the strategies in retarding the transition of AKI to CKD is becoming a hot research field. Recently, accumulating evidence suggested a pathogenic role of mitochondrial dysfunction in both AKI and CKD. Therefore, in the present study, we evaluated the effect of mitochondrial complex 1 inhibition by rotenone on the chronic renal damage induced by acute ischemia-reperfusion. The mice were treated with 45 min unilateral renal ischemia and reperfusion (I/R) to induce an acute renal injury. After three days of I/R injury, rotenone at a dose of 200 ppm in food was administered to the mice. Strikingly, after three weeks treatment with rotenone, we found that the unilateral I/R-induced tubular damage, tubulointerstitial fibrosis were all attenuated by rotenone as determined by the tubular injury score, Masson staining, and the levels of collagen-I, collagen-III, fibronectin, PAI-1, and TGF-ß. Meanwhile, the enhanced inflammatory markers of TNF-α, IL-1ß, IL-6, and IL-18 and apoptotic markers of Bax and caspase-3 were all significantly blunted by inhibiting mitochondrial complex-1. Moreover, rotenone treatment also partially protected the mitochondria as shown by the restoration of mitochondrial SOD (SOD2), ATPB, and mitochondrial DNA copy number. These findings suggested that inhibition of mitochondrial complex-1 activity by rotenone could retard the progression of AKI to CKD probably via protecting the mitochondrial function to some extent.
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An eight-year-old girl, presenting with palpebral edema, gross hematuria, and foam in urine, was admitted to our hospital. Investigations indicated increased serum antistreptolysin O (ASO) and anti-mycoplasma antibody titers. Renal biopsy showed crescentic poststreptococcal acute glomerulonephritis (CPAGN) with isolated C3 deposition in the glomeruli. Electro-microscope examination showed subepithelial deposition of electron dense material. She received the double pulse therapies of methylprednisolone and cyclophosphamide as well as the treatment of oral prednisolone, angiotensin converting enzyme-II (ACE-II) inhibitor, dipyridamole and traditional Chinese medicine. The complete clinical remission was achieved after 9 months. No serious adverse effects were observed during the follow-up. Our findings indicated that CPAGN with isolated C3 deposition might have a favorable prognosis after aggressive immunosuppressive treatment. However, the influence of isolated C3 deposition on CPAGN prognosis remains to be clarified.
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Complemento C3/análisis , Glomerulonefritis/inmunología , Glomérulos Renales/inmunología , Infecciones Estreptocócicas/inmunología , Enfermedad Aguda , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Biomarcadores/análisis , Biopsia , Niño , Quimioterapia Combinada , Femenino , Técnica del Anticuerpo Fluorescente , Glomerulonefritis/diagnóstico , Glomerulonefritis/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/ultraestructura , Microscopía Electrónica , Inducción de Remisión , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/diagnóstico , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are similar syndromes. We aimed to determine whether the crescent formation/immunocomplex in glomeruli is associated with the differences of the biochemical indexes between HSPN and IgAN. METHODS: We investigated the medical records of 137 HSPN cases and 41 IgAN cases from January 2009 to April 2014 in Nanjing Children's Hospital of Nanjing Medical University. The clinical and pathological data were analyzed and compared between HSPN and IgAN. RESULTS: HSPN patients had markedly higher levels of blood white blood cell (WBC), hemoglobulin (Hb) and platelet (PLT), lower levels of hematuria, blood nitrogen (BUN) and C4 compared with IgAN cases. Crescents formation and C3 deposition in the kidney did not affect these differences. Significantly lower levels of hematuria, blood IgG, IgM and C4 in HSPN compared with IgAN cases were observed among patients with IgG deposition. Markedly higher levels of WBC and Hb, lower levels of hematuria, creatinine (Cr), C4 in HSPN compared with IgAN cases were observed among patients with IgM deposition. No marked differences of the biochemical indexes were noted between HSPN and IgAN cases among patients with C1q deposition. Markedly higher levels of WBC and Hb, lower level of blood C4 in HSPN compared with IgAN cases were observed among patients with fibrogen deposition. CONCLUSIONS: The different levels of biochemical indexes at presentation between HSPN and IgAN may be associated with the deposition of IgG, IgM, C1q and fibrogen in the kidney.