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1.
Pediatr Nephrol ; 39(6): 1927-1935, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38196017

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common in children with sepsis, chronic kidney disease, poisoning or other conditions. Wasp stings are recognized as an important etiology. Several retrospective studies have investigated AKI after wasp stings in adults, but research on children remains limited. METHODS: The study included 48 children with multiple organ dysfunction syndrome after wasp stings. Demographic data, clinical manifestations, laboratory findings, management and clinical outcomes were collected, and analyzed to identify early indicators or risk factors for AKI. RESULTS: 20 children (41.7%) developed AKI, and 28 (58.3%) did not. Serum creatine levels elevated mostly within 24 h from stings in children with AKI (16/20, 80%). Compared with non-AKI group, AKI group exhibited more cases with cola-colored urine, jaundice, and had higher sting numbers/body surface area (BSA) and higher revised sequential organ failure assessment scores (rSOFA) as well as higher levels of C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), lactate dehydrogenase (LDH), troponin (cTnI), creatine kinase (CK), and longer prothrombin time (PT). Both univariable and multivariable logistic regression analysis identified cola-colored urine as a potential early risk factor for AKI. CONCLUSIONS: The AKI group exhibited higher sting numbers/BSA, higher levels of CRP, ALT, AST, TBIL, LDH, cTnI, and CK, as well as longer PT (p < 0.05). Our findings also suggest that cola-colored urine may serve as an early indicator or potential risk factor for AKI after wasp stings in children, which is very easy to identify for first aiders or pediatricians.


Assuntos
Injúria Renal Aguda , Mordeduras e Picadas de Insetos , Vespas , Adulto , Criança , Animais , Humanos , Mordeduras e Picadas de Insetos/complicações , Estudos Retrospectivos , Injúria Renal Aguda/etiologia , Fatores de Risco
2.
BMC Med Educ ; 24(1): 787, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044219

RESUMO

BACKGROUND: Burnout is prevalent among pediatric residents. Self-efficacy and resilience, as concepts of positive psychology, may be protective factors for burnout. However, no current data demonstrates the mechanism of their interaction. OBJECTIVES: To investigate the pediatric residents' status of self-efficacy, resilience, and job burnout in a university-affiliated hospital in western China. To explore relationships among them, especially the mediating effects of resilience. METHODS: The study was conducted with 190 pediatric residents from an A-Class women's and children's hospital in western China. Data included demographic characteristics, status of pediatric residents, measures of burnout (using the Physicians' Career Burnout Questionnaire), self-efficacy (using the General Self-Efficacy Scale) and resilience (using the Connor-Davidson Resilience Scale). Multiple regression analysis and mediation analysis with bootstrapping were used to identify whether resilience mediates the relationship between self-efficacy and burnout. RESULTS: Female pediatric residents exhibited significantly lower self-efficacy (t = 2.53, p<0.05) and higher levels of job burnout (t=-2.64, p<0.01) compared to male residents. Residents in the standardized training stage experienced higher levels of job burnout compared to those who had completed the training, as indicated by t-values of -3.21, -2.13, and - 2.80 (p<0.05). Significant correlations (p ≤ 0.01) were found among self-efficacy, resilience, and burnout. Additionally, our findings indicated that pediatric residents' self-efficacy can positively predict job burnout and its three dimensions through a major mediating effect of resilience. CONCLUSIONS: The findings regarding the mediating effect of resilience on the influence of self-efficacy on burnout, and their association with gender and residency status, have practical implications for interventions aimed at reducing burnout and improving the well-being of pediatric residents.


Assuntos
Esgotamento Profissional , Internato e Residência , Pediatria , Resiliência Psicológica , Autoeficácia , Humanos , Esgotamento Profissional/psicologia , Feminino , China/epidemiologia , Estudos Transversais , Masculino , Adulto , Pediatria/educação , Inquéritos e Questionários
3.
BMC Nephrol ; 24(1): 36, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36792980

RESUMO

BACKGROUND: More attention has been put on the relationship between pediatric glomerular disease and respiratory tract virus infection. Children with glomerular illness, however, are uncommonly found to have biopsy-proven pathological evidence of viral infection. The purpose of this study is to determine whether and what kind of respiratory viruses are found in renal biopsy from glomerular disorders. METHODS: We used a multiplex PCR to identify a wide range of respiratory tract viruses in the renal biopsy samples (n = 45) from children with glomerular disorders and a specific PCR to verify their expression. RESULTS: These case series included 45 of 47 renal biopsy specimens, with 37.8% of male and 62.2% of female patients. Indications for a kidney biopsy were present in all of the individuals. In 80% of the samples, respiratory syncytial virus was discovered. Following that, the RSV subtypes in several pediatric renal disorders were found. There were 16 RSVA positives, 5 RSVB positives, and 15 RSVA/B positives, accounting for 44.4%, 13.9%, and 41.7%, respectively. Nephrotic syndrome samples made up 62.5% of RSVA positive specimens. The RSVA/B-positive was detected in all pathological histological types. CONCLUSIONS: Patients with glomerular disease exhibit respiratory tract viral expression in the renal tissues, especially respiratory syncytial virus. This research offers new information on the detection of respiratory tract viruses in renal tissue, which may facilitate the identification and treatment of pediatric glomerular diseases.


Assuntos
Nefropatias , Pneumonia , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Viroses , Criança , Humanos , Masculino , Feminino , Lactente , Estudos Retrospectivos , Viroses/diagnóstico , China/epidemiologia , Sistema Respiratório , Biópsia
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(4): 597-601, 2022 Jul.
Artigo em Zh | MEDLINE | ID: mdl-35871729

RESUMO

Objective: To discuss the characteristics of physician trainee outcomes after completion of the job-transfer subspecialty training in pediatrics, a program designed to increase the number of pediatricians, in Sichuan Province and to provide countermeasures for alleviating the shortage of pediatricians. Methods: We collected with questionnaire surveys information on changes in the workload and salaries experienced by physicians who completed the job-transfer subspecialty training program in pediatrics between February 2017 and May 2020 in Sichuan Province. Then, we compared the characteristics of physicians who successful became pediatricians and those who did no. Results: A total of 208 physicians completed the job-transfer subspecialty training program in pediatrics. Among them, 178, accounting for 85.6%, completed the questionnaire survey, and 120, accounting for 67.4%, had a background in other subspecialties than pediatrics. The majority (>90%) of physicians who participated in the training program came from secondary or lower levels of hospitals from the cities and prefectures all over Sichuan Province. In this study, we found that the rate of successful job transfer from being a physician to being a pediatrician in Sichuan Province in the past four years was 85.0% (102/120), with the year-by-year results being 88.2% (15/17) in 2017, 72.7% (16/22) in 2018, 86.7% (39/45) in 2019, and 94.% (32/34) in 2020. There was no significant difference between physicians who had successful job transfer and became pediatricians and those who failed to do so in terms of gender, age, hospital level, specialization prior to the job transfer, whether or not the hospital had a pediatrics department, amount of support for the pediatrics department, whether or not the physician was working at a new hospital after the job transfer, salaries, and changes of responsibilities during COVID-19 (all P>0.05). There was significant difference in the change of workload after completion of the training program between physicians who had successful job transfer and became pediatricians and those who failed to do so ( χ 2=9.037, P=0.003), and 78.4% of the trainees stated that their workload had increased after the job transfer. There was a moderate correlation between successful job transfer and changes in workload after the transfer (|Phi[ψ] |=0.729). Conclusions: The policy of government-supported job-transfer subspecialty training in pediatrics has played an active and important role in the swift resolution of the shortage of pediatricians. However, finding the root cause of and addressing the problem of the overwhelming workload of pediatricians remain challenging issues to be resolved.


Assuntos
COVID-19 , Criança , Humanos , Inquéritos e Questionários
5.
Lupus ; 30(3): 465-472, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33413003

RESUMO

BACKGROUND: Therapeutic plasma exchange (TPE) is an effective means of treating systemic lupus erythematosus in children and is safe for most pediatric patients with systemic lupus erythematosus, but severe complications such as toxic epidermal necrolysis (TEN) may occur, which is a life-threatening condition. METHODS: In this study, three systemic lupus erythematosus (SLE) children developed toxic epidermal necrolysis after TPE. We analyzed their medical history, clinical manifestations, SLEDAI scores, and immunological characteristics, compared to 117 cases of SLE patients without TEN after TPE, trying to find the possible risk factors. RESULTS: The three children with TEN after plasma exchange appeared to have a higher proportion of male (male: female = 2:1), fever (100% Vs 32.5%), erythema on the cheek (100% Vs 54.7%), itching rash (100% Vs 54.7%), ruptured rash (100% Vs 54.7%), oral ulcer (100% Vs 54.7%) and higher LDH level (1826.0 ± 1113.1 Vs 721.1 ± 799.5 U/L), but lower white blood cell count (5.5 ± 3.3 Vs 7.2 ± 4.2 × 109/L), neutrophil count (4.7 ± 3.7 Vs 5.2 ± 3.6 × 109/L), lymphocyte count (0.6 ± 0.5 Vs 1.5 ± 0.8 × 109/L), platelet count (133.7 ± 58.1 Vs 178.5 ± 103.1 × 109/L) and C-reactive protein (all normal Vs 47.9% elevated). Autoantibody spectrum revealed that positive anti-SSA seemed more common (100% Vs 42.7%) in the three children. Relative risk analysis revealed that male (OR 21.4, 95%CI 1.78-257.186), ruptured skin rash (OR 56.5, 95%CI 4.199-760.196) and rash with itching (OR 24, 95%CI 1.98-290.896) are the risk factors of SLE patients developing TEN after plasma exchange. CONCLUSIONS: We should pay particular attention to TEN after plasma exchange in SLE patients (3/120, 2.5%). This condition may be related to male, ruptured skin rash and rash with itching. For SLE patients with risk factors. We should arrange plasmapheresis more carefully.


Assuntos
Lúpus Eritematoso Sistêmico/terapia , Troca Plasmática/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Criança , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , Síndrome de Stevens-Johnson/patologia
6.
Inj Prev ; 27(6): 521-526, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33443032

RESUMO

OBJECTIVE: This study was designed to reveal the relationship between the use and type of eye protection and the occurrence of work-related corneal and conjunctival foreign body injuries. METHODS: This is a retrospective cohort study of patients with work-related corneal and/or conjunctival foreign body injuries between 1 August 2017 and 31 July 2018. They were all diagnosed and treated at Jia Ding Hospital affiliated to the Shanghai University of Medicine and Health Sciences in Shanghai, China. All patients received a comprehensive eye examination and a face-to-face interview using a structured questionnaire by ophthalmologists. RESULTS: A total of 426 consecutive patients were included in the study. The majority of work-related eye injuries occurred in men (94.17%). Summer was the season that had the highest incidence of eye injuries, especially in July and August (38.03%). There were 290 patients (68.08%) that were injured more than once. The ratio of eye protection use to non-protection was 1:7 at the first time of eye injury. The ratio improved to 1:3 on subsequent injury. A majority of employers (79.11%) provided eye protection to employees. However, 19.95% of the workers were injured despite wearing a pair of protective spectacles. The causes of work-related eye injury were as follows: no eye protections provided (20.89%); unawareness of work safety (30.99%); defect of spectacles (47.18%). CONCLUSIONS: Protection use at work effectively prevents work-related eye injuries. Both employers and employees require improved awareness of workplace hazards and personal protection. Eye protection should be selected appropriately according to the work environment.


Assuntos
Traumatismos Oculares , Corpos Estranhos , China/epidemiologia , Traumatismos Oculares/epidemiologia , Traumatismos Oculares/prevenção & controle , Dispositivos de Proteção dos Olhos , Humanos , Masculino , Estudos Retrospectivos
8.
Opt Express ; 25(15): 17393-17401, 2017 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-28789231

RESUMO

We present the combined configuration of dielectric helical cone and metallic granary-shaped nanotip to produce three -dimensional vector vortex nanofocused optical field. The intensity and phase of the electric fields, and Povnting vector of the optical field generated by the combined configuration with linearly polarized illumination are studied with three-dimensional finite difference time-domain method. The localized vector electric field near the apex of the metallic granary-shaped nanotip is strongly depended on the chirality of the dielectric helical cone and the bottom radius of the metallic granary-shaped nanotip. The localized vector electric field is wavelength selective with the maximum intensity enhancement up to 104 times and minimum size of about 900 nm2, and the maximum radial electric field rotates 67.0° along z axis. This indicates the vector vortex beam generated by the combined configuration can be applied in nanofabrication, nano-sensing and nano-manipulation.

9.
Pediatr Nephrol ; 32(12): 2351-2360, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28755073

RESUMO

BACKGROUND: Several novel biomarkers that predict acute kidney injury (AKI) have recently been proposed. We have evaluated the sequential patterns of biomarker elevation after pediatric cardiopulmonary bypass (CPB) and determined their diagnostic accuracy. METHODS: We measured the ability of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver type fatty-acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein 7 (IGFBP7), to predict AKI (≥50% increase in serum creatinine from baseline). Areas under the receiver-operator characteristic curves (AUCs) were calculated for each biomarker and for various biomarker combinations at multiple time points after CPB. RESULTS: Of 150 patients examined, AKI had developed in 50 patients by 24 h after CPB, with an elevated NGAL concentration first noted at 2 h post-CPB, increases in IL-18, L-FABP, and the product of TIMP-2 and IGFBP7 first noted at 6 h, and an elevated KIM-1 level noted at 12 h. At each time point, urine NGAL remained the marker with the highest predictive ability (AUC > 0.9). The addition of any other biomarker did not increase the predictive accuracy of NGAL alone at 2 and 6 h. At 12 h, when compared to NGAL alone, the combination of NGAL, IL-18, and TIMP2 improved the AUC for AKI prediction (from 0.938 to 0.973). CONCLUSIONS: While urine NGAL remains a superior stand-alone test at the 2 and 6 h time points after pediatric CPB, a panel of carefully selected biomarkers may prove optimal at later time points.


Assuntos
Injúria Renal Aguda/diagnóstico , Biomarcadores/urina , Ponte Cardiopulmonar/efeitos adversos , Pontos de Checagem do Ciclo Celular , Injúria Renal Aguda/etiologia , Área Sob a Curva , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/sangue , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação a Ácido Graxo/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Humanos , Lactente , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Interleucina-18/urina , Lipocalina-2/urina , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Inibidor Tecidual de Metaloproteinase-2/urina
10.
Am J Pathol ; 183(5): 1461-73, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24160323

RESUMO

The expression of the bone morphogenetic protein antagonist, Gremlin 1, was recently shown to be increased in the lungs of pulmonary arterial hypertension patients, and in response to hypoxia. Gremlin 1 released from the vascular endothelium may inhibit endogenous bone morphogenetic protein signaling and contribute to the development of pulmonary arterial hypertension. Here, we investigate the impact of Gremlin 1 inhibition in disease after exposure to chronic hypoxia/SU5416 in mice. We investigated the effects of an anti-Gremlin 1 monoclonal antibody in the chronic hypoxia/SU5416 murine model of pulmonary arterial hypertension. Chronic hypoxic/SU5416 exposure of mice induced upregulation of Gremlin 1 mRNA in lung and right ventricle tissue compared with normoxic controls. Prophylactic treatment with an anti-Gremlin 1 neutralizing mAb reduced the hypoxic/SU5416-dependent increase in pulmonary vascular remodeling and right ventricular hypertrophy. Importantly, therapeutic treatment with an anti-Gremlin 1 antibody also reduced pulmonary vascular remodeling and right ventricular hypertrophy indicating a role for Gremlin 1 in the progression of the disease. We conclude that Gremlin 1 plays a role in the development and progression of pulmonary arterial hypertension in the murine hypoxia/SU5416 model, and that Gremlin 1 is a potential therapeutic target for pulmonary arterial hypertension.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/prevenção & controle , Hipóxia/complicações , Indóis/efeitos adversos , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Pirróis/efeitos adversos , Animais , Anticorpos Monoclonais/farmacologia , Proteínas Morfogenéticas Ósseas/metabolismo , Doença Crônica , Hipertensão Pulmonar Primária Familiar , Células HEK293 , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipóxia/patologia , Hipóxia/fisiopatologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Camundongos , Transdução de Sinais/efeitos dos fármacos
11.
Arch Esp Urol ; 76(2): 123-131, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37139617

RESUMO

INTRODUCTION: Lupus nephritis (LN) is still a great burden for patients with systemic lupus erythematosus, and also one of the most severe complications of SLE. Radix Paeoniae Alba (white peony, WP) is proved with potential efficacy in treating LN. This study was to explore the effective ingredients, potential targets, and pathways of WP in treating LN based on network pharmacology and molecular docking. METHODS: The active ingredients and potential protein targets of WP were gathered on Traditional Chinese Medicine Systematic Pharmacology Database and predicted by Swiss Target Prediction. LN-related therapeutic targets were acquired from multiple databases including Genecards, DisGeNET, OMIM, Drugbank, and PharmGKB. The intersection targets of WP and LN were acquired through Veeny 2.1.0. Protein-Protein Interaction (PPI) network was established by STRING. The results were then visualized by Cytoscape version 3.7.1. to study the mechanisms of WP on LN, gene ontology and functional enrichment analysis were carried out. Finally, molecular docking presented with the binding ability of key targets and major active components. RESULTS: We acquired a total of 13 active ingredients and 260 potential targets of WP. Among them, the intersection with targets of LN were 82 proteins. These targets were regarded as potential therapeutic targets. Through PPI network, we found that the top three proteins were RAC-alpha serine/threonine protein kinase (AKT1), vascular endothelial growth factor A (VEGFA), and transcription factor Jun (JUN), and their corresponding components were kaempferol, paeoniflorin, lactiflorin, paeoniflorgenone, etc. The results of enrichment analysis suggested that WP treatment for LN mainly involves in signaling pathways in cancer, lipid and atherosclerosis, advanced glycation end product (AGE)-receptor of AGE (RAGE) pathways, C-type lectin receptor and nuclear factor (NF)-kappa B signaling pathways. Molecular docking predicted that the above components have excellent affinity to AKT1, VEGFA, and JUN. CONCLUSIONS: This study gave an insight into the key target proteins and potential underlying pharmacological mechanism of WP in treating LN, which provided evidence for further researches on the mechanism of WP on LN.


Assuntos
Nefrite Lúpica , Paeonia , Humanos , Nefrite Lúpica/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator A de Crescimento do Endotélio Vascular
12.
Proc Natl Acad Sci U S A ; 106(11): 4337-42, 2009 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-19246393

RESUMO

For more than 2 centuries active immunotherapy has been at the forefront of efforts to prevent infectious disease [Waldmann TA (2003) Nat Med 9:269-277]. However, the decreased ability of the immune system to mount a robust immune response to self-antigens has made it more difficult to generate therapeutic vaccines against cancer or chronic degenerative diseases. Recently, we showed that the site-specific incorporation of an immunogenic unnatural amino acid into an autologous protein offers a simple and effective approach to overcome self-tolerance. Here, we characterize the nature and durability of the polyclonal IgG antibody response and begin to establish the generality of p-nitrophenylalanine (pNO(2)Phe)-induced loss of self-tolerance. Mutation of several surface residues of murine tumor necrosis factor-alpha (mTNF-alpha) independently to pNO(2)Phe leads to a T cell-dependent polyclonal and sustainable anti-mTNF-alpha IgG autoantibody response that lasts for at least 40 weeks. The antibodies bind multiple epitopes on mTNF-alpha and protect mice from severe endotoxemia induced by lipopolysaccharide (LPS) challenge. Immunization of mice with a pNO(2)Phe(43) mutant of murine retinol-binding protein (RBP4) also elicited a high titer IgG antibody response, which was cross-reactive with wild-type mRBP4. These findings suggest that this may be a relatively general approach to generate effective immunotherapeutics against cancer-associated or other weakly immunogenic antigens.


Assuntos
Aminoácidos/genética , Imunoterapia/métodos , Engenharia de Proteínas/métodos , Tolerância a Antígenos Próprios/imunologia , Aminoácidos/imunologia , Animais , Formação de Anticorpos , Autoanticorpos , Autoantígenos/genética , Imunoglobulina G , Camundongos , Fenilalanina/análogos & derivados , Fenilalanina/genética , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/genética
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 43(3): 344-7, 377, 2012 May.
Artigo em Zh | MEDLINE | ID: mdl-22812234

RESUMO

OBJECTIVE: To determine the susceptibility of primary human trophoblastic cells (HTCs) to human cytomegalovirus (HCMV) infection. METHODS: 30 villus of healthy pregnant women were digested with a mixture of 0.25% trypsin and 0.2% DNase. The digestion was then filtered by a 200 mesh stainless steel sieve. HTCs were purified by Percoll gradient centrifugation and repeat purification with trypsin during cell passage. HTCs were identified by cell morphology and immunofluorescence. PCR, Western blot and immunofluorescent staining were performed to detect HCMV gene and protein 72 hours post infection of HCMV. RESULTS: The combination of 0.25% trypsin and 0.2% DNase with Percoll gradient centrifugation isolated and purified primary HTCs. More than 90 percent cells expressed CK-7 related antigen. The results of PCR, western blot and immunofluorescence showed positive expressions of CMV gB and virus proteins. CONCLUSION: HTCs is susceptible to HCMV infection, which suggests a possible route of HCMV infection at the fetal-maternal interface.


Assuntos
Citomegalovirus/fisiologia , Trofoblastos/citologia , Trofoblastos/virologia , Citomegalovirus/crescimento & desenvolvimento , Infecções por Citomegalovirus/virologia , Suscetibilidade a Doenças , Feminino , Humanos , Gravidez , Cultura Primária de Células
14.
Front Immunol ; 13: 999491, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311786

RESUMO

This study aimed to develop and validate a nomogram to forecast severe kidney disease (SKD) outcomes for hospitalized Henoch-Schönlein purpura (HSP) children. The predictive model was built based on a primary cohort that included 2,019 patients with HSP who were diagnosed between January 2009 and December 2013. Another cohort consisting of 461 patients between January 2014 and December 2016 was recruited for independent validation. Patients were followed up for 24 months in development/training and validation cohorts. The data were gathered at multiple time points after HSP (at 3, 6, 12, and 24 months) covering severe kidney disease as the severe outcome after HSP. The least absolute shrinkage and selection operator (LASSO) regression model was utilized to decrease data dimension and choose potentially relevant features, which included socioeconomic factors, clinical features, and treatments. Multivariate Cox proportional hazards analysis was employed to establish a novel nomogram. The performance of the nomogram was assessed on the aspects of its calibration, discrimination, and clinical usefulness. The nomogram comprised serious skin rash or digestive tract purpura, severe gastrointestinal (GI) manifestations, recurrent symptoms, and renal involvement as predictors of SKD, providing favorable calibration and discrimination in the training dataset with a C-index of 0.751 (95% CI, 0.734-0.769). Furthermore, it demonstrated receivable discrimination in the validation cohort, with a C-index of 0.714 (95% CI, 0.678-0.750). With the use of decision curve analysis, the nomogram was proven to be clinically useful. The nomogram independently predicted SKD in HSP and displayed favorable discrimination and calibration values. It could be convenient to promote the individualized prediction of SKD in patients with HSP.


Assuntos
Vasculite por IgA , Nefropatias , Criança , Humanos , Vasculite por IgA/complicações , Nomogramas , Nefropatias/diagnóstico , Nefropatias/etiologia , Rim
15.
Front Genet ; 13: 985217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685820

RESUMO

Background: Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease whose etiology remains unknown. This study aims to explore diagnostic biomarkers and pathways involved in IPF using bioinformatics analysis. Methods: IPF-related gene expression datasets were retrieved and downloaded from the NCBI Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, and weighted correlation network analysis (WGCNA) was performed to identify key module and genes. Functional enrichment analysis was performed on genes in the clinically significant module. Then least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were run to screen candidate biomarkers. The expression and diagnostic value of the biomarkers in IPF were further validated in external test datasets (GSE110147). Results: 292 samples and 1,163 DEGs were screened to construct WGCNA. In WGCNA, the blue module was identified as the key module, and 59 genes in this module correlated highly with IPF. Functional enrichment analysis of blue module genes revealed the importance of extracellular matrix-associated pathways in IPF. IL13RA2, CDH3, and COMP were identified as diagnostic markers of IPF via LASSO and SVM-RFE. These genes showed good diagnostic value for IPF and were significantly upregulated in IPF. Conclusion: This study indicates that IL13RA2, CDH3, and COMP could serve as diagnostic signature for IPF and might offer new insights in the underlying diagnosis of IPF.

16.
Proc Natl Acad Sci U S A ; 105(32): 11276-80, 2008 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-18685087

RESUMO

The ability to selectively induce a strong immune response against self-proteins, or increase the immunogenicity of specific epitopes in foreign antigens, would have a significant impact on the production of vaccines for cancer, protein-misfolding diseases, and infectious diseases. Here, we show that site-specific incorporation of an immunogenic unnatural amino acid into a protein of interest produces high-titer antibodies that cross-react with WT protein. Specifically, mutation of a single tyrosine residue (Tyr(86)) of murine tumor necrosis factor-alpha (mTNF-alpha) to p-nitrophenylalanine (pNO(2)Phe) induced a high-titer antibody response in mice, whereas no significant antibody response was observed for a Tyr(86) --> Phe mutant. The antibodies generated against the pNO(2)Phe are highly cross-reactive with native mTNF-alpha and protect mice against lipopolysaccharide (LPS)-induced death. This approach may provide a general method for inducing an antibody response to specific epitopes of self- and foreign antigens that lead to a neutralizing immune response.


Assuntos
Substituição de Aminoácidos , Formação de Anticorpos/efeitos dos fármacos , Mutação de Sentido Incorreto , Tolerância a Antígenos Próprios/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Animais , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Doenças Transmissíveis/genética , Doenças Transmissíveis/imunologia , Endotoxemia/induzido quimicamente , Endotoxemia/tratamento farmacológico , Endotoxemia/genética , Endotoxemia/imunologia , Epitopos/genética , Epitopos/imunologia , Epitopos/farmacologia , Imunoquímica , Lipopolissacarídeos/toxicidade , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/imunologia , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Nitrofenóis/imunologia , Nitrofenóis/farmacologia , Tolerância a Antígenos Próprios/genética , Tolerância a Antígenos Próprios/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Vacinas/genética , Vacinas/imunologia
17.
World J Clin Cases ; 9(13): 3056-3062, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33969091

RESUMO

BACKGROUND: Crumbs homolog 2 (CRB2) is a recently discovered gene that is closely related to the maintenance of normal polarity in podocytes; mutations can directly lead to steroid-resistant nephrotic syndrome (SRNS). However, the characteristics of nephrotic syndrome (NS) caused by CRB2 mutations have not been described. CASE SUMMARY: We report a novel compound heterozygous mutation of the CRB2 gene in two siblings with SRNS. The two siblings had edema, proteinuria, hypoproteinemia and hyperlipidemia. Both their father and mother had normal phenotypes (no history of NS). Whole exon sequencing (WES) of the family showed a novel compound heterozygous mutation, c.2290 (exon 8) C > T and c.3613 (exon 12) G > A. Glucocorticoid therapy (methylprednisolone pulse therapy or oral prednisone) and immunosuppressive agents (tacrolimus) had no effect. During a 3-year follow-up after genetic diagnosis by WES, proteinuria persisted, but the patient was healthy. CONCLUSION: CRB2 mutations related to SRNS often occur in exons 7, 10, and 12. Clinical manifestations of SRNS caused by CRB2 mutations are often less severe than in other forms of SRNS.

18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 41(4): 600-3, 625, 2010 Jul.
Artigo em Zh | MEDLINE | ID: mdl-20848777

RESUMO

OBJECTIVE: To explore the activation of toll-like receptor 3 (TLR3) pathway on the process of respiratory syncytial virus (RSV) induced nephropathy. METHODS: SD rats were inoculated intranasally and intraperitoneally with 6 X 10(6) plaque forming unit(PFU) RSV and sacrificed on days 4, 14, 30 postinoculation (RSV4, RSV14 and RSV30). The normal rats without intervention were set as control. Renal tissues were obtained, and the morphological changes were studied. The expressions of TLR3, NF-kappaB and IL-13 in the rats' kidney were measured with real-time quantitative RT-PCR, and indirect IF staining. RESULTS: After the inoculation of RSV, the rats had proteinuria and the fusion of foot processes of glomerular epithelial cells, resembling human minimal changed nephrotic syndrome (MCNS). The expressions of TLR3, NF-kappaB and IL-13 in renal tissues increased obviously at Day 4 and Day 14 postinoculation, the differences were significant when compared with normal control rats (P < 0.05). The expressions of these three factors decreased at Day 30, which were not significantly different to those of normal control group (P > 0.05). CONCLUSION: TLR3 signal pathway may play an important role in early stage of RSV nephropathy.


Assuntos
Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/fisiologia , Receptor 3 Toll-Like/metabolismo , Animais , Masculino , Síndrome Nefrótica/etiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Infecções por Vírus Respiratório Sincicial/metabolismo , Transdução de Sinais , Receptor 3 Toll-Like/genética
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 41(3): 424-7, 2010 May.
Artigo em Zh | MEDLINE | ID: mdl-20629313

RESUMO

OBJECTIVE: To detect whether the primary culture of human umbilical vein endothelial cells (HUVEC) is susceptible to human cytomegalovirus (HCMV) infection so as to explain how virus from mothers traverses the placenta to fetus. METHODS: Thirty umbilical cords of healthy parturient were used in this study. The HUVEC were harvested with 0.1% collagenase for 15 minutes. The cells were identified by morphology and immunofluorescence. Then the HUVEC were infected with HCMV in vitro. The DNA of cytomegalovirus and protein of infected cells were detected 72 hours later. RESULTS: The HUVEC with adequate quality were harvested, which expressed VIII related antigen. Positive expressions of CMV gB gene and virus proteins were identified in all of the HUVEC infected with HCMV. CONCLUSION: HUVEC is susceptible to HCMV infection, which suggests a possible route of HCMV infection through the fetal-maternal interface.


Assuntos
Citomegalovirus/patogenicidade , Células Endoteliais/virologia , Veias Umbilicais/virologia , Células Cultivadas , Infecções por Citomegalovirus/transmissão , Células Endoteliais/citologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Veias Umbilicais/citologia
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 40(1): 55-8, 2009 Jan.
Artigo em Zh | MEDLINE | ID: mdl-19292045

RESUMO

OBJECTIVES: To investigate the expression of glomerular heparin sulfate (HS) in paediatric patients with minimal change nephritic syndrome (MCNS). METHODS: The kidyney tissues were collected by biopsy from 13 paediatric patients with MCNS, while 5 normal renal biopsy samples were used as control. HS in glomeruli was analysed by indirect immunofluorescence staining using four different monoclonal antibodies, Hepss1, 3G10, JM403 and 10E4, which all recognize distinct HS species and each interacts with a specific HS domain. The concentrations of urine heparan sulfate also were measured by enzyme-linked immunosorbent assay (Elisa). RESULTS: Expression of HS fine domains was aberrant in paediatric patients compared with control subjects. Children with MCNS in replase showed a decreased glomerular expression of 10E4, JM403 and Hepss1 (P < 0.05). The level of urinary HS was significantly increased in peadiatric patients with MCNS when compared with that in control subjects (P < 0.01). CONCLUSION: These results suggest that loss of heparan sulphate in renal tissue may play a role in the pathogenesis of MCNS proteinuria.


Assuntos
Heparitina Sulfato/metabolismo , Glomérulos Renais/metabolismo , Síndrome Nefrótica/metabolismo , Anticorpos Monoclonais , Estudos de Casos e Controles , Criança , Feminino , Heparitina Sulfato/urina , Humanos , Masculino
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