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BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The KaplanâMeier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).
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BACKGROUND: Acute kidney injury (AKI) is a major complication of acute myocardial infarction(AMI), which can significantly increase mortality. This study is to analyze the related risk factors and establish a prediction score of acute kidney injury in order to take early measurement for prevention. METHODS: The medical records of 6014 hospitalized patients with AMI in Beijing Anzhen Hospital from January 2010 to December 2016 were retrospectively analyzed. These patients were randomly assigned into two cohorts: one was for the derivation of prediction score (n = 4252) and another for validation (n = 1762). The criterion for AKI was defined as an increase in serum creatinine of ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h. On the basis of odds ratio obtained from multivariate logistic regression analysis, a prediction score of acute kidney injury after AMI was built up. RESULTS: In this prediction score, risk score 1 point included hypertension history, heart rate > 100 bpm on admission, peak serum troponin I ≥ 100 µg/L, and time from admission to coronary reperfusion > 120 min; risks score 2 points included Killip classification ≥ class 3 on admission; and maximum dosage of intravenous furosemide ≥ 60 mg/d; risks score 3 points only included shock during hospitalization. In addition, when baseline estimated glomerular filtration rate (eGFR) was less than 90 ml/min·1.73 m2, every 10 ml/min·1.73 m2 reduction of eGFR increased risk score 1 point. Youden index showed that the best cut-off value for prediction of AKI was 3 points with a sensitivity of 71.1% and specificity 74.2%. The datasets of derivation and validation both displayed adequate discrimination (an area under the ROC curve, 0.79 and 0.81, respectively) and satisfactory calibration (Hosmer-Lemeshow statistic test, P = 0.63 and P = 0.60, respectively). CONCLUSIONS: In conclusion, a prediction score for AKI secondary to AMI in Chinese patients was established, which may help to prevent AKI early.
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Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Povo Asiático , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Idoso , Estudos de Coortes , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Valor Preditivo dos Testes , Distribuição Aleatória , Reprodutibilidade dos Testes , Estudos Retrospectivos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversosRESUMO
OBJECTIVE: To investigate the inhibitory effect of plasmid-based survivin-specific short hairpin RNA and GRIM-19 on the growth of Hep-2 laryngeal cancer cells. METHODS: The plasmid expressing survivin-specific short hairpin RNA (shRNA) and GRIM-19 (p-siRNA survivin/GRIM-19) was prepared and transfected into Hep-2 cells with Lipofectamine 2000. The mRNA and protein expression of surviving and GRIM-19 were measured with RT-PCR and western blot assay, respectively. MTT assay was employed to detect the proliferation of Hep-2 cells, and flow cytometry and AO/EB assay were done to determine the apoptosis of Hep-2 cells. RESULTS: In the p-siRNA survivin/GRIM-19, the mRNA and protein expression of survivin was markedly reduced by 54.4% and 42.2%, and the reduction in protein expression of surviving was more obvious than that in the p-siRNA survivin group (37%) (P<0.05). The protein expression of GRIM-19 was markedly enhanced when compared with the control group (P<0.01). MTT assay revealed the proliferation of Hep-2 cells undergoing transfection with p-siRNA survivin/GRIM-19 was markedly inhibited, and the inhibition rate was as high as 79%, which was higher than that in the psi-survivin group (45%) and p-GRIM-19 group (35%). AO/EB assay and flow cytometry indicated that the apoptotic cells in the p-siRNA survivin/GRIM-19 group were dramatically increased as compared to the psi-survivin group and p-GRIM-19 group. CONCLUSION: The p-siRNA survivin/GRIM-19 has marked decrease in survivin expression and dramatic increase in GRIM-19 expression. Moreover, silencing of survivin and over-expression of GRIM-19 can significantly inhibit the growth and induce the apoptosis of Hep-2 in vitro and in vivo.
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Proteínas Reguladoras de Apoptose/genética , Proliferação de Células , Proteínas Inibidoras de Apoptose/genética , Neoplasias Laríngeas/genética , NADH NADPH Oxirredutases/genética , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Terapia Genética , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Masculino , Camundongos , Camundongos Nus , NADH NADPH Oxirredutases/metabolismo , Interferência de RNA , RNA Interferente Pequeno , SurvivinaRESUMO
OBJECTIVE: To study the effect of silencing survivin on the growth of Hep-2 human laryngeal cancer cells in vitro and in vivo. METHODS: Hep-2 cells were transfected with pGCsilencer-siRNA-survivin (psi-survivin)by Lipofectamine 2000. The mRNA and protein expressions of survivin were detected by semi-quantitative RT-PCR and Western blot, respectively. Cell proliferation activity was measured by MTT assay. Apoptosis was assessed by flow cytometry. The implanted tumors were formed from injected Hep-2 cells in nude mice. After the tumor formation, psi-survivin was injected into peritumor tissues. The growth of tumor were observed. The tumor volume was calculated and the tumor growth curve was plotted. The expression of survivin in tumor tissues was detected by Western blot. The tumor cell apoptosis was observed by Tunel staining. RESULTS: The sequence-specific siRNA of survivin inhibited the expressions of survivin mRNA and protein. The inhibition rates of survivin mRNA and protein expression were 54.4% and 37.0% respectively. Also the growth of Hep-2 cells was inhibited significantly, with a decrease by 71.7%. By the day 32 of tumor growth, the mean tumor volumes were (1443.9 ± 230.5) mm(3) (x(-) ± s) in saline control group, (1348.5 ± 198.4) mm(3) in plasmid-negative control group, and (624.6 ± 188.4) mm(3) in psi-survivin group, respectively (t = -5.917, P < 0.01). In the implanted tumors injected with psi-survivin, survivin protein expression was down-regulated significantly, with a inhibition rate of 41.8%. Tunel staining showed the apoptosis occurred in the implanted tumors. CONCLUSION: Silencing survivin could significantly inhibit the growth of Hep-2 human laryngeal cancer cells in vitro and in vivo.