RESUMO
BACKGROUND: In China, coronary artery abnormalities (CAAs) secondary to Kawasaki disease (KD) tend to have an increased occurrence. We hypothesize that Chinese children with KD may possess several unique CAA risks, and the predictive efficacy of multiple scoring systems in Chinese patients are still to be further studied. METHODS: Two hundred and three KD patients were recruited. Using multivariable analysis, independent predictors of CAAs were combined into a scoring system. Subsequently, CAA risks of our patients were evaluated by the newly established scoring system and eight other published scoring systems. RESULTS: Seventeen (8.37%) KD patients were identified as CAAs. The newly established scoring system contained the following 5 independent predictors: days of illness at initial treatment ≥7, redness and swelling of extremities, hematocrit ≤33%, percentage of monocytes ≥8.89%, and procalcitonin ≥0.5 ng/mL. The AUC value of newly established scoring system was 0.685 with a sensitivity of 41.18% and a specificity of 84.41%, higher than Harada score, Egami score, Kobayashi score, Sato score, San Diego score, Formosa score, and Tang score, whereas lower than Hua score. CONCLUSIONS: Days of illness at initial treatment ≥7 and procalcitonin are unique predictors of CAAs in newly established scoring system. Taking into account different identification criteria and analytical methodologies, there is still some heterogeneity among different scoring systems. IMPACT: The newly established scoring system contains the five independent predictors. Days of illness at initial treatment ≥7 and PCT are unique predictors of CAAs in our study, compared with 8 other systems. The AUC value of newly established scoring system is 0.685, similar to Hua score. There is some heterogeneity among different scoring systems.
Assuntos
Doença da Artéria Coronariana , Cardiopatias Congênitas , Síndrome de Linfonodos Mucocutâneos , Doença da Artéria Coronariana/complicações , Cardiopatias Congênitas/complicações , Humanos , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Pró-Calcitonina , Estudos RetrospectivosRESUMO
BACKGROUND: Abdominal wall endometriosisï¼AWEï¼is an unusual extra-pelvic endometriosis. Currently, multiple treatment modalities are available, but no clear guidelines exist for the management of large AWE. MATERIALS AND METHODS: We present a 36-year-old female patient with a large AWE lesion who underwent cesarean section due to abnormal fetal position 8 years ago. The mass lesion of AWE located in rectus muscle fascia and rectus muscle with a size of 61 × 25 × 49mm. RESULTS: HIFU treatment was completed in one session. One day post-HIFU MRI showed the mass was completely ablated. After HIFU treatment, the cyclical abdominal pain disappeared. The mass lesion shrank during follow-up period and disappeared in 1 year after HIFU. No complication was observed after HIFU. CONCLUSION: Surgical resection of AWE remains the standard of care. In patients with large AWE lesion located in rectus muscle fascia and rectus muscle where the muscle and fascia must be excised, HIFU treatment should be considered to avoid mesh implantation.
Assuntos
Parede Abdominal , Endometriose , Ablação por Ultrassom Focalizado de Alta Intensidade , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/cirurgia , Adulto , Cesárea , Endometriose/diagnóstico por imagem , Endometriose/patologia , Endometriose/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , GravidezRESUMO
PURPOSE: Glaucoma is a leading cause of global irreversible blindness, and characterized by the progressive loss of retinal ganglion cells (RGCs). Ligustrazine (TMP) is a natural product that has shown beneficial effects on various diseases. This study aimed to determine whether ligustrazine produces a therapeutic effect on glaucoma and to investigate its underlying mechanisms. METHODS: A rat chronic hypertensive glaucoma model was induced by episcleral vein cauterization (EVC). Adult Sprague-Dawley (SD) rats were intraperitoneally administered TMP at a dose of 80 mg/kg once a day, from two days before EVC to one month after EVC. To elucidate the role of the mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K), TMP-treated experimental rats were co-treated with the mTOR inhibitor rapamycin (5 mg/kg) or the PI3K inhibitor Ly294002 (10 mg/kg). The intraocular pressure (IOP) of the experimental and control rats was measured every six days. Retinal cells were examined by hematoxylin-eosin and terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling (TUNEL) staining, as well as transmission electron microscopy. Immunohistochemistry and western blot analysis were performed to measure proteins involved in apoptosis and autophagy. RESULTS: Ligustrazine protected retinal cells from death in experimental glaucoma rats, which was not due to the lowering of IOP, but could be attributable to direct suppression of retinal cell apoptosis. In glaucoma rats, autophagy was markedly activated in retina cells, as evidenced by increased numbers of autophagosomes and the expression of autophagy-related proteins (ATG5 and LC3-II/I). Notably, such alterations in glaucoma rats were almost completely reversed by ligustrazine. The suppressive effects of ligustrazine on apoptosis and autophagy of retina cells were markedly attenuated by the mTOR inhibitor rapamycin or the PI3K inhibitor Ly294002. Additionally, ligustrazine significantly increased the protein levels of phosphorylated PI3K (p-PI3K), protein kinase B (p-Akt), and mTOR (p-mTOR) in glaucoma rats, whereas such increases were attenuated by rapamycin or Ly294002. CONCLUSIONS: These results demonstrate that ligustrazine is protective in experimental glaucoma by inhibiting autophagy via the activation of the PI3K-Akt/mTOR pathway, providing compelling evidence that ligustrazine is potentially therapeutic for patients with glaucoma.
Assuntos
Glaucoma , Proteínas Proto-Oncogênicas c-akt , Pirazinas , Animais , Apoptose , Autofagia , Glaucoma/complicações , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Humanos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/farmacologia , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/metabolismo , Sirolimo/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Accurate classification of coronary artery abnormalities (CAAs) is essential for clinical decision-making and long-term management in Kawasaki disease (KD) patients. To date, there are several echocardiographic criteria of CAA assessment. MATERIALS AND METHODS: The Japanese Ministry of Health (JMH) criteria and the Z-score criteria from 2004 American Heart Association guidelines were adopted and their detective efficacies for CAAs were compared in 251 Chinese patients with KD Z scores were calculated by 6 published methods. RESULTS: According to the JMH criteria, 19 (7.57%) KD patients were classified as CAAs during the acute KD episode. However, the detective number of CAAs was highest and had a 0.68-fold increase by the Dallaire et al method with a Z-score cut point of ≥2.5 as compared with the JMH criteria; in contrast, more than 78.95% of patients with CAAs identified by the JMH criteria had a coronary artery Z score ≥2.5. All 6 different Z-score methods had satisfactory accuracies with a range from 93.23% to 97.61% in screening CAAs. For the 19 patients with CAAs identified by the JMH criteria, their Z scores presented the widest variation calculated by the McCrindle et al method. CONCLUSIONS: The JMH criteria underestimate the prevalence of CAAs as compared with the Z-score criteria. Quantitative assessment of coronary artery luminal dimensions, normalized as Z scores adjusted for body surface, should be recommended. The larger coronary artery luminal dimensions vary, the more heterogeneous Z scores calculated by different methods have.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Pré-Escolar , China , Doença da Artéria Coronariana/diagnóstico , Ecocardiografia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Guias de Prática Clínica como Assunto , Estudos RetrospectivosRESUMO
BACKGROUND: Kawasaki disease (KD) is an acute, self-limited vasculitis. Coronary artery aneurysm (CAA) serves as a major contributor to the long-term prognosis of KD. In addition, acute KD usually also leads to several kinds of noncoronary cardiac abnormalities (NCA) involving the pericardium, myocardium and endocardium. MATERIALS AND METHODS: A total of 142 Chinese children with KD were recruited from July 2015 to April 2018. Blood samples were collected at 24 hours pre-intravenous immunoglobulin (IVIG) therapy. Several inflammatory mediators and biomarkers for acute myocardial infarction were detected. Echocardiography and electrocardiography (ECG) were performed. RESULTS: Plasma white blood cell counts (WBC) were significantly increased in patients with IVIG-nonresponsive KD when compared with their IVIG-responsive counterparts. A total of 106 children (74.65%) suffered from NCA, including 8 patients (5.63%) with pericardial effusion, 23 patients (16.20%) with acute myocarditis, 101 patients (71.13%) with valvular regurgitation and 8 patients (5.63%) with abnormal ECG. No significant differences were observed in the distribution of clinical classification and the response to IVIG therapy regardless of NCA exhibited or not. CONCLUSIONS: Noncoronary cardiac abnormalities is almost universal in acute KD and mainly manifests as valvular regurgitation. However, it has no influence on clinical classification and the response to IVIG therapy.
Assuntos
Aneurisma Coronário/epidemiologia , Doenças das Valvas Cardíacas/epidemiologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Miocardite/epidemiologia , Derrame Pericárdico/epidemiologia , Adolescente , Insuficiência da Valva Aórtica/epidemiologia , Insuficiência da Valva Aórtica/etiologia , Criança , Pré-Escolar , China/epidemiologia , Aneurisma Coronário/etiologia , Creatina Quinase Forma MB/sangue , Ecocardiografia , Eletrocardiografia , Feminino , Doenças das Valvas Cardíacas/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Masculino , Insuficiência da Valva Mitral/epidemiologia , Insuficiência da Valva Mitral/etiologia , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/terapia , Miocardite/etiologia , Derrame Pericárdico/etiologia , Insuficiência da Valva Tricúspide/epidemiologia , Insuficiência da Valva Tricúspide/etiologia , Troponina T/sangueRESUMO
Hand, foot and mouth disease (HFMD) is a common infectious disease among children, caused primarily by human enterovirus-A71 (EV-A71) and coxsackievirus-A16 (CV-A16). To date, only two case reports mention that renal involvement can be secondary to or coexisting with CV-A16-associated HFMD. In the present report, we describe a 10-year-old girl who was infected with EV-A71 and subsequently developed a definite acute kidney injury (AKI), mainly based on the characteristic rash, virus isolation, eyelid edema, hypertension, decreased urine output, mild proteinuria and impaired renal function. She was treated with intravenous ribavirin, immunoglobulin, oral administration of nifedipine and ramipril. After 7 days of intensive observations, she recovered fully. Hypertension is a common feature in both HFMD and AKI. On one hand, hypertension serves as a risk factor for severe HFMD; on the other hand, hypertension induces AKI onset and is also deteriorated by AKI.
Assuntos
Injúria Renal Aguda/etiologia , Enterovirus Humano A , Doença de Mão, Pé e Boca/complicações , Hipertensão/etiologia , Criança , Feminino , Doença de Mão, Pé e Boca/virologia , HumanosRESUMO
Developing new polymer dielectrics with superior dielectric and energy storage properties is urgent to meet the demand for electronic devices in the field of microminiaturization or harsh environments. In this paper, two dipolar glass polymers based on polynorbornene main chain and flexible/rigid cyano side chain were synthesized by ring opening metathesis polymerization method: polymer PCEMT with flexible side chains and polymer PCPMT with rigid side chains. The backbone is built from two rigid five-membered rings, which not only avoids the narrow band gap caused by π-π conjugation of traditional aromatic main chains, but also maintains high thermal stability and high glass transition temperature (Tg). The introduced polar cyano groups on the side chain gave high dielectric constants (εr) for both polymers, where the εr of PCEMT and PCPMT reached 7.9 and 4.6 at room temperature and 1 kHz, respectively. Due to high polarization and high breakdown strength, the PCPMT obtains a maximum discharge energy density (Ud) of 4.47 J/cm3 at room temperature, which is 1.61 and 1.57 times of biaxially oriented polypropylene and polyimide (Kapton). The supernal Tg of 229 °C makes the energy storage performance of PCPMT almost unaffected at 100 °C. The charge-discharge efficiency (η) always keeps over 90% and an Ud of 5.2 J/cm3 at 480 MV/m is achieved, which is much better than Kapton (Ud = 1.77 J/cm3, η = 42.5%) under the same conditions. This work provides a new idea for preparing the high-performance polymer dielectrics via introducing rigid polar side chains.
RESUMO
The interaction between the terahertz wave propagating in free space and the sample is weak, which leads to the weak signal of the sample, which cannot meet the detection needs of trace samples. In order to meet the detection of trace samples, a kind of metamaterial absorber (the basic unit of the absorber is composed of gold-high resistance silicon-aluminum three-layer structure) is designed, and the monolayer graphene is transferred on the surface of the metamaterial absorber to construct the graphene-metamaterial absorber heterostructure. The transmission spectrum of the resonant cavity is simulated and measured by terahertz time domain spectroscopy system, and the obvious resonance frequency shift is observed. The results show that the graphene-metamaterial absorber heterostructure can detect josamycin antibiotic solution with concentration of 0.02 mg/L (the mass of josamycin is 0.2 ng). Compared with using the same structure metamaterial absorber to detect josamycin antibiotics, the sensitivity is increased by an order of magnitude. Using graphene-metamaterial heterostructure to detect the relative change of heterostructure reflectivity caused by josamycin antibiotics can reach 40%. The research in this paper provides a new technical means for accurate and rapid detection in terahertz band.
Assuntos
Técnicas Biossensoriais , Grafite , Antibacterianos , Simulação por Computador , Grafite/química , Josamicina , Manufaturas , Modelos Teóricos , Refratometria/métodos , Espalhamento de RadiaçãoRESUMO
Ligustrazine, an alkaloid monomer extracted from Chuanxiong Rhizoma, has the function of protecting nerve cells. However, the effect and mechanism of ligustrazine on retinal ischemia/reperfusion (I/R) injury still need to be clarified. In our study, retinal ganglion cells (RGC-5) were used to establish a retinal I/R injury model by anaerobic cultivation. Cell viability, autophagy, and apoptosis were evaluated by cell counting kit 8 assay, transmission electron microscopy, and TUNEL staining after treatment with ligustrazine, PI3K inhibitor Ly294002, and/or mTOR inhibitor rapamycin, respectively. Besides, the levels of PI3K/Akt/mTOR pathway and autophagy-related proteins were determined by western blot. Moreover, one-way ANOVA was adopted for inter-group comparisons of measurement data. Our results demonstrated that low-concentration ligustrazine significantly enhanced cell viability and suppressed cell autophagy and apoptosis of RGC-5 cells after I/R injury, suggesting the protective effect of low-concentration ligustrazine on retinal I/R injury. Moreover, the alleviating effect of ligustrazine on RGC-5 with retinal I/R injury was mechanistically associated with the activation of the PI3K/Akt/mTOR pathway. In conclusion, low-concentration ligustrazine has a significant protective effect on RGC-5 cells with retinal I/R injury by activating the PI3K/Akt/mTOR pathway.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Pirazinas/farmacologia , Traumatismo por Reperfusão/metabolismo , Células Ganglionares da Retina , Animais , Sobrevivência Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
PURPOSE: Several studies have demonstrated that C-type natriuretic peptide (CNP) stimulates osteoblastic proliferation seemly via antagonizing the expression of fibroblast growth factor (FGF)-23 in vitro. The main aim of the present study is to probe whether the post-receptor pathways of FGF-23 participate in osteogenesis caused by CNP. METHODS: Osteoblasts were cultured in the absence or presence of CNP: 0, 10, and 100 âpmol/L, for 24 âh, 48 âh and 72 âh, respectively. RESULTS: The findings of the present study indicated that osteoblastic proliferation was directly promoted by exogenous CNP in a dose-dependent manner; osteoblastic FGF-23 was significantly down-regulated by CNP at 24 âh post-treatment; RAF-1, extracellular signal-regulated kinases (ERK), and P38 were substantially suppressed by CNP in a dose- and time-dependent manner; and signal transducer and activator of transcription (STAT)-1 was not changed on the premise of the down-regulated FGF-23 in osteoblasts treated with CNP. CONCLUSION: CNP may promote osteogenesis via inhibiting ERK and P38, rather than STAT-1, in the downstream of FGF-23/RAF-1 pathway.
Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Natriuréticos/farmacologia , Peptídeo Natriurético Tipo C/farmacologia , Osteoblastos/citologia , Osteogênese , Proteínas Proto-Oncogênicas c-raf/metabolismo , Animais , Fatores de Crescimento de Fibroblastos/genética , Masculino , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
BACKGROUND: Although the specific etiology of Henoch-Schonlein purpura (HSP) is still unknown, several kinds of infectious triggers have been proved to participate in its pathogenesis. The objectives of present study were to analyze the association of the infectious triggers with childhood HSP in Anhui province, China. METHODS: 1200 HSP children were recruited from January 2015 to December 2017. Serum antistreptolysin O titer, TORCH, Epstein-Barr virus, helicobacter pylori (HP), Mycoplasma antibodies (MP-Ab), tubercle bacillus antibody (TB-Ab), respiratory pathogens (legionella pneumophila, chlamydia pneumoniae, adenovirus, respiratory syncytial virus, influenza A virus, influenza B virus, rickettsia, parainfluenza virus) were determined. Patients' histories were obtained by interviews and questionnaires. RESULTS: The annual incidence of HSP was 8.13-9.17 per 100,000. HSP occurred more commonly in spring and winter than in summer with an obvious west-to-east gradient. On admission, several potential infections were identified in 611 cases (50.92%). The infectious agents including streptococcus, HP, MP, parainfluenza, respiratory syncytial virus, TB and toxoplasma gondii were identified in 205 cases (17.08%), 71 cases (5.92%), 58 cases (4.83%), 6 cases (0.5%), 1 case (0.08%), 1 case (0.08%) and 1 case (0.08%) respectively. 123 cases (10.25%) relapsed or recurred more than one time; the mean number was 2.92, and the mean interval was 11.4 weeks. The infection was the most frequent trigger regardless of clinical phenotypes and relapse/recurrence. Symptomatic treatment plus adjunctive anti-infectious agents could significantly improve the remission rate of purpura in the infectious cases (x2=24.60, p<0.01). CONCLUSIONS: Streptococcus is the most frequent infectious agent in HSP children regardless of clinical phenotype or relapse/recurrence. The complete elimination of infectious triggers may help relieve cutaneous purpura.
Assuntos
Infecções Bacterianas/epidemiologia , Vasculite por IgA/epidemiologia , Vasculite por IgA/etiologia , Viroses/epidemiologia , Adolescente , Infecções Bacterianas/complicações , Criança , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Recidiva , Inquéritos e Questionários , Viroses/complicaçõesRESUMO
BACKGROUND: The effects of C-type natriuretic peptide (CNP) and fibroblast growth factor (FGF)-23 appear to oppose each other during the process of bone formation, whereas few studies exist on the interaction between CNP and FGF-23. The main objective of the present study is to probe whether CNP is directly responsible for the regulation of osteoblast or via antagonizing FGF-23. METHODS: Osteoblasts were cultured in the absence or presence of CNP (0, 10, and 100 pmol/L) for 24 h, 48 h and 72 h, respectively. RESULTS: The findings of the present study indicated that: (1) CNP significantly stimulated osteoblastic proliferation and collagen (Col)-X expression; (2) both osteoblastic (osteocalcin, procollagen type I carboxy-terminal propeptide, total alkaline phosphatase and bone-specific alkaline phosphatase) and osteolytic (tartrate-resistant acid phosphatase and cross-linked carboxyterminal telopeptide of type I collagen) bone turnover biomarkers were up-regulated by CNP in osteoblasts; (3) FGF-23 mRNA and protein were significantly down-regulated at 24 h by CNP in osteoblasts, but the expression of FGF receptor-1/Klotho had no significant change. CONCLUSIONS: CNP stimulates osteoblastic proliferation and Col-X expression via the down-regulation of FGF-23 possibly in vitro. However, the specific mechanisms of the interaction between CNP and FGF-23 in osteoblasts are still unclear according to our findings. A further study on osteoblasts cultured with CNP and FGF-23 inhibitor will be undertaken in our laboratory.
Assuntos
Proliferação de Células/genética , Fatores de Crescimento de Fibroblastos/genética , Peptídeo Natriurético Tipo C/metabolismo , Osteoblastos/metabolismo , Fosfatase Alcalina/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Western Blotting , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/genética , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo X/efeitos dos fármacos , Colágeno Tipo X/genética , Colágeno Tipo X/metabolismo , Ensaio de Imunoadsorção Enzimática , Fatores de Crescimento de Fibroblastos/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/metabolismo , Imunofluorescência , Expressão Gênica , Regulação da Expressão Gênica , Glucuronidase/efeitos dos fármacos , Glucuronidase/genética , Glucuronidase/metabolismo , Técnicas In Vitro , Proteínas Klotho , Peptídeo Natriurético Tipo C/farmacologia , Osteoblastos/efeitos dos fármacos , Osteocalcina/efeitos dos fármacos , Osteocalcina/metabolismo , Osteogênese/genética , Fragmentos de Peptídeos/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Cultura Primária de Células , Pró-Colágeno/efeitos dos fármacos , Pró-Colágeno/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/efeitos dos fármacos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Fosfatase Ácida Resistente a Tartarato/efeitos dos fármacos , Fosfatase Ácida Resistente a Tartarato/metabolismoRESUMO
Coronary artery abnormalities (CAAs) are prominent during the acute Kawasaki disease (KD) episode and represent the major contributors to the long-term prognosis. Several meta-analysis and published scoring systems have identified hepatic dysfunction as an independent predictor of CAA risks. The medical records of 210 KD children were reviewed. Blood samples were collected from all subjects at 24 h pre-therapy and 48 h post-therapy, respectively. Liver function test (LFT) and inflammatory mediators were detected. Multivariate logistic regression analysis was conducted to identify the reliable biomarkers predicting whether CAAs existed or not in KD patients. 90.95% of KD patients had at least 1 abnormal LFT. Hypoalbuminemia was the most prevalent type of hepatic dysfunction, followed by elevated aspartate aminotransferase, low TP, low A/G and hyperbilirubinemia, respectively. The elevated inflammatory mediators (procalcitonin and C-reactive protein) and moderate dose of aspirin played a synthetic role in hepatic dysfunction secondary to KD. However, LFT presented no significant differences between infectious and noninfectious conditions. By a multivariate analysis, a lower albumin/globulin ratio (A/G, OR 13.50, 95% CI 3.944-46.23) served as an independent predictor of CAAs and had a sensitivity of 56.25%, and a specificity of 61.11% at a cutoff value of < 1.48. In conclusion, hepatic dysfunction is a common complication during the acute KD episode, characterized by elevated serum liver enzymes, hypoalbuminemia and hyperbilirubinemia. Systemic inflammation and aspirin, rather than infectious agents, are both the major contributors of hepatic dysfunction secondary to KD. A lower A/G serves as an independent predictor of CAAs.
Assuntos
Biomarcadores/sangue , Hepatopatias/diagnóstico , Síndrome de Linfonodos Mucocutâneos/complicações , Aspartato Aminotransferases/sangue , Aspirina/sangue , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Hepatopatias/sangue , Hepatopatias/etiologia , Hepatopatias/fisiopatologia , Testes de Função Hepática , Modelos Logísticos , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Pró-Calcitonina/sangue , Estudos RetrospectivosRESUMO
BACKGROUND: In the last decade, incomplete Kawasaki disease (KD), intravenous immunoglobulin (IVIG) non-response and coronary artery abnormalities (CAA) have experienced the increasing trends in China. In addition, the enhancement of pediatricians' awareness may also raise the diagnostic rate of incomplete KD and stimulate more aggressive initial therapy in the acute episode of KD. Given this background, we hypothesize that the time option of IVIG treatment should be in parallel with peak time of systemic inflammation; either earlier or later IVIG treatment may affect the clinical classification, therapeutic responsiveness and CAA occurrence in KD patients. Therefore, the major objective of the present study is to identify whether the time option of IVIG treatment could be associated with the clinical classification, therapeutic responsiveness and CAA occurrence in the acute episode of KD. MATERIALS AND METHODS: A total of 153 children with KD were recruited between July 2015 and May 2018. All patients received the standard therapy of KD, including a single infusion of IVIG (2 g/kg) and aspirin (30-50 mg/kg/d). Blood samples were collected from all subjects within 24 h pre-IVIG treatment, respectively. Echocardiography was performed during the period from 2 days to 14 days after IVIG treatment. RESULTS: (1) The clinical classification presented no significant heterogenicity among different treatment time (x2 = 1.59, p > 0.05) (2) Eleven KD patients resisted to IVIG treatment and 7 of them (63.60%) received the initial IVIG dose on day 5 and 6. (3) The distribution of CAA onset was subjected to a significant difference according to timing option of IVIG treatment (x2 = 11.94, p < 0.05). CONCLUSIONS: The time option of IVIG treatment is associated with therapeutic responsiveness and CAA but not with clinical classification in the acute episode of KD.
Assuntos
Arterite/tratamento farmacológico , Doença da Artéria Coronariana/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Mediadores da Inflamação/metabolismo , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Henoch-Schönlein purpura (HSP) is a common autoimmune vasculitis in childhood. The detailed pathogenesis of HSP is still unclear, whereas several types of predisposing factors have been proved to be the initial step. The objectives of present study were to analyze the distribution of predisposing factors, association of the predisposing factors with clinical manifestations and HSP relapse/recurrence. 1200 children with HSP were recruited between January 2015 and December 2017. We reviewed their laboratory tests and medical histories associated with HSP onset. The annual incidence of HSP was 8.13-9.17 per 100 000 in Anhui province. HSP occurred more commonly in spring and winter than in summer with an obvious west-to-east gradient. Cutaneous purpura was the most prevalent manifestation (100%), followed by arthritis/arthralgias (43.67%), abdominal pain (40.17%) and renal involvement (18.17%). On admission, series of potential infections were identified in 611 patients (50.92%). The histories of allergy, injury, surgery, vaccination and tick bite were declared by 231 patients (19.25%), 15 patients (1.25%), 12 patients (1.00%), 4 patients (0.33%) and 3 patients (0.25%), respectively. However, predisposing factors could not be identified in 521 children with HSP (43.42%) yet. 123 cases (10.25%) relapsed or recurred more than one time; the mean number was 2.92, and the mean interval was 11.4 weeks. The infection is the most frequent predisposing factor regardless of clinical phenotypes and relapse/recurrence, whereas the clinical manifestations exhibit an obvious heterogenicity according to different predisposing factors.
Assuntos
Vasculite por IgA/etiologia , Criança , China , Feminino , Humanos , Masculino , Admissão do Paciente , Recidiva , Fatores de RiscoRESUMO
The purpose of the present study was to determine whether fibroblast growth factor (FGF)23 could serve as a novel biomarker for renal osteodystrophy (ROD) progression. A rat model of ROD was induced by left nephrectomy plus intravenous injection of Adriamycin. Serum FGF23 was determined using an enzymelinked immunosorbent assay. Serum level and bone expression of FGF23 were both significantly elevated in the ROD group at 24 h postsurgery. Serum FGF23 was negatively correlated with calcium, phosphate, 25hydroxyvitamin D, conventional bone biomarkers and bone collagen X. More importantly, serum FGF23 was significantly associated with abnormalities in bone formation rate, osteoblasts, osteoclasts, trabecular volume thickness and osteoid volume. Therefore, FGF23 may serve as a novel biomarker for ROD.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Progressão da Doença , Fatores de Crescimento de Fibroblastos/metabolismo , Animais , Biomarcadores/metabolismo , Osso e Ossos/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Colágeno Tipo X/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/metabolismo , Rim/patologia , Rim/fisiopatologia , Testes de Função Renal , Proteínas Klotho , Masculino , Ratos Sprague-Dawley , Receptores de Fatores de Crescimento de Fibroblastos/metabolismoRESUMO
Kawasaki disease (KD) is an acute, systemic vasculitis and occurs mainly in childhood. Interleukin-6 (IL-6) is a pleiotropic cytokine synthesized predominantly by neutrophils and monocytes/macrophages and plays an important role in systemic inflammatory disease. However, a little information is currently available on the relationship of serum IL-6 with conventional inflammatory mediators, clinical classification, IVIG response and coronary artery aneurysm (CAA). 165 Chinese children with KD were enrolled and divided into six subgroups, including complete KD, incomplete KD, IVIG-responsive KD, IVIG-nonresponsive KD, coronary artery noninvolvement KD and coronary artery involvement KD. Blood samples were collected from all subjects within 24-h pre- and 48-h post-IVIG therapy, respectively. Serum IL-6 and conventional inflammatory mediators were detected. (1) Serum IL-6 markedly increased in the acute phase of KD, whereas declined to normal after IVIG therapy; it was positively correlated with C-reactive protein and erythrocyte sedimentation rate. (2) Serum IL-6 was significantly elevated in patients with incomplete KD when compared with their complete counterparts. The area under receiver operating characteristic curve (AUC) value for serum IL-6 in prediction of incomplete KD was 0.596, and the estimated sensitivity and specificity were 77.80% and 54.40% with a cutoff of IL-6 > 13.25 pg/ml, respectively. (3) Serum IL-6 was significantly elevated in patients with IVIG-nonresponsive KD when compared with their IVIG-responsive counterparts; the AUC value for serum IL-6 in prediction of IVIG-nonresponsive KD was 0.580, and the estimated sensitivity and specificity were 60.00% and 66.30% with a cutoff of IL-6 > 26.40 pg/ml, respectively. (4) No significant differences in IL-6 were found between KD patients with and without CAA. IL-6 is prone to be a candidate biomarker for predicting incomplete and IVIG nonresponsive KD rather than CAA.
Assuntos
Biomarcadores/sangue , Aneurisma Coronário/diagnóstico , Testes Diagnósticos de Rotina/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interleucina-6/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Adolescente , Povo Asiático , Proteína C-Reativa/análise , Criança , Pré-Escolar , Aneurisma Coronário/patologia , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/patologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Falha de TratamentoRESUMO
Renal osteodystrophy (ROD) occurs as early as chronic kidney disease (CKD) stage 2 and seems ubiquitous in almost all pediatric patients with CKD stage 5. Fibroblast growth factor (FGF)-23, a bone-derived endocrine regulator of phosphate homeostasis, is overexpressed in CKD and disturbs osteoblast differentiation and matrix mineralization. In contrast, C-type natriuretic peptide (CNP) acts as a potent positive regulator of bone growth. In the present study, we infused CNP into uremic rats and observed whether CNP could attenuate ROD through the inhibition of FGF-23 cascades. In uremic rats, CNP administration significantly alleviated renal dysfunction, calcium phosphate metabolic disorders, hypovitaminosis D, secondary hyperparathyroidism, the decrease in bone turnover markers and retarded bone pathological progression. More importantly, within FGF-23/mitogen-activated protein kinase (MAPK) signaling, the fibroblast growth factor receptor-1, Klotho and alternative (STAT-1/phospho-STAT-1) elements were upregulated by CNP, whereas FGF-23, RAF-1/phospho-RAF-1, and downstream (ERK/phospho-ERK and P38/phospho-P38) elements were paradoxically underexpressed in bone tissue. Therefore, CNP exerts a therapeutic effect on ROD through inhibition of FGF-23/MAPK signaling at the RAF-1 level.
Assuntos
Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Peptídeo Natriurético Tipo C/administração & dosagem , Animais , Osso e Ossos/patologia , Cálcio/sangue , Diferenciação Celular/efeitos dos fármacos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Modelos Animais de Doenças , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica , Humanos , Rim/patologia , Masculino , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima , UremiaRESUMO
C-type natriuretic peptide (CNP) is believed to be produced locally in the kidneys and possess several renoprotective properties. In contrast, fibroblast growth factor (FGF) -23 elevates in the early stage of chronic kidney disease and predicts its outcomes. Currently, several studies have demonstrated that CNP and FGF-23 act through a close pathway, and moreover, FGF-23/mitogen-activated protein kinase (MAPK) can be obviously suppressed by CNP. In the present study, human mesangial cells (MCs) were incubated in serum-containing medium in the absence or presence of CNP (0, 10 and 100 pM) for 24, 48 and 72 h, respectively. CNP administration significantly suppresses MCs proliferation in a time- and dose-dependent manner. As a down-stream signaling of CNP activation, the expressions of natriuretic peptide receptor (NPR)-B, cyclic guanosine monophosphate-dependent protein kinases II and NPR-C were obviously augmented, whereas neutral endopeptidase expression was significantly decreased after CNP treatment in MCs. FGF-23, FGF receptor-1 and RAF-1 experienced a pronounced down-regulation in MCs with different doses of CNP throughout the whole observational period. CNP may dampen FGF-23 expression via MAPK signaling pathway in MCs.
Assuntos
Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células Mesangiais/efeitos dos fármacos , Peptídeo Natriurético Tipo C/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Células Mesangiais/metabolismo , Peptídeo Natriurético Tipo C/administração & dosagem , Relação Estrutura-Atividade , Fatores de TempoRESUMO
C-type natriuretic peptide (CNP) is regarded as a local, paracrine hormone to regulate vascular tone and cell proliferation. Although several in vivo studies have documented that CNP exerts the inhibitory effects on mesangial cells (MCs) proliferation and collagen production, a limited number of studies exist about the resistance of CNP to MCs proliferation in vitro. Besides, whether its receptor signaling and neutral endopeptidase (NEP) are involved remains unclear. In the present study, human MCs were incubated in serum-containing medium in the absence or presence of CNP (0, 10 and 100 pM) for 24, 48 and 72 hours, respectively. CNP administration significantly suppresses MCs proliferation and collagen-IV (Col-IV) expression in a time-dependent and dose-dependent manner. As a down-stream signal molecule of CNP activation, the expressions of natriuretic peptide receptor (NPR)-B, cyclic guanosine monophosphate-dependent protein kinases II and NPR-C were obviously augmented, whereas NEP expression was significantly decreased after CNP treatment. In conclusion, receptor signaling and NEP are involved in the resistance of CNP to human mesangial proliferation and Col-IV expression.