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BACKGROUND: As comprehensive surgical management for gastric cancer becomes increasingly specialized and standardized, the precise differentiation between ≤T1 and ≥T2 gastric cancer before endoscopic intervention holds paramount clinical significance. OBJECTIVE: To evaluate the diagnostic efficacy of contrast-enhanced gastric ultrasonography in differentiating ≤T1 and ≥T2 gastric cancer. METHODS: PubMed, Web of Science, and Medline were searched to collect studies published from January 1, 2000 to March 16, 2023 on the efficacy of either double contrast-enhanced gastric ultrasonography (D-CEGUS) or oral contrast-enhanced gastric ultrasonography (O-CEGUS) in determining T-stage in gastric cancer. The articles were selected according to specified inclusion and exclusion criteria, and the quality of the included literature was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale. Meta-analysis was performed using Stata 12 software with data from the 2 × 2 crosslinked tables in the included literature. RESULTS: In total, 11 papers with 1124 patients were included in the O-CEGUS analysis, which revealed a combined sensitivity of 0.822 (95% confidence interval [CI] = 0.753-0.875), combined specificity of 0.964 (95% CI = 0.925-0.983), and area under the summary receiver operating characteristic (sROC) curve (AUC) of 0.92 (95% CI = 0.89-0.94). In addition, five studies involving 536 patients were included in the D-CEGUS analysis, which gave a combined sensitivity of 0.733 (95% CI = 0.550-0.860), combined specificity of 0.982 (95% CI = 0.936-0.995), and AUC of 0.93 (95% CI = 0.91-0.95). According to the I2 and P values ââof the forest plot, there was obvious heterogeneity in the combined specificities of the included papers. Therefore, the two studies with the lowest specificities were excluded from the O-CEGUS and D-CEGUS analyses, which eliminated the heterogeneity among the remaining literature. Consequently, the combined sensitivity and specificity of the remaining studies were 0.794 (95% CI = 0.710-0.859) and 0.976 (95% CI = 0.962-0.985), respectively, for the O-CEDUS studies and 0.765 (95% CI = 0.543-0.899) and 0.986 (95% CI = 0.967-0.994), respectively, for the D-CEGUS studies. The AUCs were 0.98 and 0.99 for O-CEGUS and D-CEGUS studies, respectively. CONCLUSION: Both O-CEGUS and D-CEGUS can differentiate ≤T1 gastric cancer from ≥T2 gastric cancer, thus assisting the formulation of clinical treatment strategies for patients with very early gastric cancer. Given its simplicity and cost-effectiveness, O-CEGUS is often favored as a staging method for gastric cancer prior to endoscopic intervention.
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Meios de Contraste , Estadiamento de Neoplasias , Neoplasias Gástricas , Ultrassonografia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Humanos , Ultrassonografia/métodos , Sensibilidade e Especificidade , Curva ROC , Estômago/diagnóstico por imagem , Estômago/patologiaRESUMO
In hepatic fibrosis (HF), hepatic stellate cells (HSCs) form the extracellular matrix (ECM), and the pathological accumulation of ECM in the liver leads to inflammation. Our previous research found that miR-324-3p was down-regulated in culture-activated human HSCs. However, the precise effect of miR-324-3p on HF has not been elucidated. In this study, the HF mouse models were induced through directly injecting carbon tetrachloride (CCl4) into mice; the HF cell models were constructed using TGF-ß1-treated LX-2 cells. Next, real-time-quantitative polymerase chain reaction (RT-qPCR), western blot (WB) and immunohistochemistry (IHC) were applied to assess the expression levels of miR-324-3p, α-smooth muscle actin (α-SMA), Vimentin or SMAD4; hematoxylin and eosin (H&E), Masson' s trichrome and Sirius red staining to evaluate the liver injury; luciferase reporter assay to verify the targeting relationship between miR-324-3p and SMAD4; enzyme-linked immunosorbent assay (ELISA) to determine the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and cell counting kit-8 (CCK-8) and flow cytometry to evaluate the effects of miR-324-3p on cell proliferation and cycle/apoptosis, respectively. The experimental results showed a reduction in miR-324-3p level in CCl4-induced HF mice as well as transforming growth factor (TGF)-ß1-activated HSCs. Interestingly, the miR-324-3p level was rescued following the HF recovery process. In HF mice induced by CCl4, miR-324-3p overexpression inhibited liver tissue damage, decreased serum ALT and AST levels, and inhibited fibrosis-related biomarkers (α-SMA, Vimentin) expression, thereby inhibiting HF. Similarly, miR-324-3p overexpression up-regulated α-SMA and Vimentin levels in HF cells, while knockdown of miR-324-3p had the opposite effect. Besides, miR-324-3p played an antifibrotic role through inhibiting the proliferation of hepatocytes. Further experiments confirmed that miR-324-3p targeted and down-regulated SMAD4 expression. SMAD4 was highly expressed in HF cells, and silencing SMAD4 significantly decreased the α-SMA and Vimentin levels in HF cells. Collectively, the miR-324-3p may suppress the activation of HSCs and HF by targeting SMAD4. Therefore, miR-324-3p is identified as a potential and novel therapeutic target for HF.
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OBJECTIVE: Abdominal ultrasonography after transrectal filling with contrast agent (AU-TFCA) was retrospectively evaluated with respect to determination of T stage and lesion length in patients with colorectal cancer (CRC) who had previously failed colonoscopy because of severe intestinal stenosis. METHODS: The population comprised 83 patients with CRC with intestinal stenosis and previously failed colonoscopy who underwent AU-TFCA, and in addition contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI), 2 wk before surgery. The diagnostic performance of AU-TFCA and CECT/MRI was evaluated relative to the post-operative pathological results (PPRs) by paired sample t-test, receiver operator characteristic (ROC) curve, Pearson's χ2-test and κ and intraclass correlation coefficients. RESULTS: The T staging identified via AU-TFCA, but not CECT/MRI, was relatively consistent with that of the PPRs (linearly weighted κ coefficient: 0.558, p < 0.001, and linearly weighted κ coefficient: 0.237, p < 0.001, respectively). The overall diagnostic accuracy of T staging based on AU-TFCA (83.1%) was significantly higher than that based on CECT/MRI (50.6%). Regarding lesion length, the results of AU-TFCA and PPRs were comparable (t = 1.852, p = 0.068), but those of CECT/MRI and PPRs were significantly different (t = 8.450, p < 0.001). CONCLUSION: AU-TFCA is effective in evaluation of lesion length and T stage in patients with severely stenotic CRC lesions who previously failed colonoscopy. The diagnostic accuracy of AU-TFCA is significantly better compared with that of CECT/MRI.
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Neoplasias Colorretais , Meios de Contraste , Humanos , Estudos Retrospectivos , Constrição Patológica/diagnóstico por imagem , Ultrassonografia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
Objective: To explore the effects of fecal microbiota transplantation (FMT) on neurobehavior and gut microbiota of arsenic-exposed offspring rats. Methods: In April 2021, Thirty-six SPF SD rats aged 8 weeks were seleted, rats were ranked by weight and divided into four groups according to randomized block design, namely control group, arsenic exposure group (As group) , arsenic+normal saline group (As+NaCl group) and As+FMT group, 6 females and 3 males in each group. Fecal microbiota fluid were provided by feces of rats in control group. Rats drank tap water containing 75 mg/L sodium arsenite for one week and then were caged together. The arsenic exposure was terminated until the pups were born. Female rats with vaginal plug were treated with fecal microbiota fluid via gavage during neurodevelopmental teratogenic window period. The volume of gavage was 1 ml/100 g with once every two days, for a total of three times. Weight alterations of offspring rats were recorded every week after weaning, and when offspring rats grew up for 6 weeks, Morris test and open field experiment was used to observe learning and memory abilities, as well as neurobehavioral performance of autonomous exploration and tension, respectively. 16S rDNA sequencing technology was used to detect microbiota diversities in fecal samples of rats in As group and As+FMT group. Results: Compared with the control group, the ratio of swimming distance and staying time in the target quadrant and the times of crossing the platform of rats in As group decreased significantly, and the motor distance, times entering central zone and the number of grid crossing of rats decreased significantly (P<0.05) . Compared with As group, the ratio of swimming distance in target quadrant, the motor distance in central zone and times entering central zone of rats in As+FMT group were evidently increased (P<0.05) . The analysis of fecal microbiota diversities showed that, at the phyla level, the relative abundance of Bacteroidetes in feces of rats in As+FMT group was higher than that in As group (68.34% vs 60.55%) , while the relative abundance of Firmicutes was lower than that in As group (28.02% vs 33.48%) . At the genus level, the relative abundance of Prevotella in As+FMT group was significantly higher than that in As group, becoming the dominant genus (42.08% vs 21.78%) . Additionally, compared with As group, a total of 22 genus were increased with 21 decreased genus in As+FMT group (P<0.05) . LEfSe analysis showed that dominant genuses in As+FMT group were Prevotella and UCG_005, and their relative abundance was significantly higher than that of As group (P<0.05) . Conclusion: FMT may alleviate the impaired learning and memory ability and anxiety like behavior of the offspring rats exposed to arsenic, and improve the disrupted gut microbiota.
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Masculino , Ratos , Animais , Feminino , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Arsênio , Ratos Sprague-Dawley , FezesRESUMO
OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome,featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
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Ratos , Animais , Arsênio/toxicidade , Fluoretos , RNA Ribossômico 16S/genética , Ratos Sprague-Dawley , Metaboloma , MicrobiotaRESUMO
BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder that is characterized by severely increased low-density lipoprotein (LDL) cholesterol levels. At the same time, elevated LDL levels accelerated the development of coronary heart disease. Several classes of drugs are currently in use to treat FH. Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is novel one of these. CASE SUMMARY: This manuscript reports a case of FH that responded modestly after treatment with PCSK9i and statin drugs. Of even more concern is that the patient frequently admitted to the hospital during a 12-year follow-up period. Subsequently, we identified a heterozygous mutation, 1448G>A (W483X) of the LDL receptor (LDLR) in this patient. The serum levels of PCSK9 (proprotein convertase subtilisin/kexin type 9) in the patient was 71.30 ± 26.66 ng/mL, which is close the average level reported in the literature. This LDLR mutation affects LDLR metabolism or structure, which may make it unsuitable for use of PCSK9i. CONCLUSION: Our outcome demonstrates that LDLR-W483X represents a partial loss-of-function LDLR and may contribute to PCSK9i ineffective. In the meanwhile, additional measures are therefore required (particularly with gene sequencing or change the treatment plan) must be initiated as early as possible. Genetic testing for clinically challenging cases who do not respond to PCSK9i therapy is very helpful.
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Objective@#Long-term seroprotection the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection.@*Methods@#Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.@*Results@#A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.@*Conclusions@#Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children induction of memory B cells to provide stable and durable immune protection.
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , China , Hepatite A , Alergia e Imunologia , Anticorpos Anti-Hepatite A , Sangue , Vacinas contra Hepatite A , Imunidade Ativa , Modelos Estatísticos , VacinaçãoRESUMO
@#【Objective】To investigate the expression and clinical significance of programmed death- 1(PD- 1),programmed death-ligand 1(PD-L1)and CD4+ CD25+ Foxp3+ regulatory T cells(Treg)and CD4+/CD8+ ratios in JAK2V617F mutation positive myeloroliferative neoplasms patients(MPN).【Methods】45 cases of JAK2 V617F positive MPN patients were selected including 17 cases of essential thrombocythemia(ET),13 cases of polycythemia vera(PV)and 15 cases of primary myelofibrosis(ET). 30 cases of the newly diagnosed group and 15 cases of treatment group were from them. 15 cases of healthy volunteers were selected as control group. The ratio of mutant and wild type of JAK2 was detected by fluorescence quantitative polymerase chain reaction(FQ-PCR). The expression levels of p-JAK2,PD-1 and PD- L1 in pathological tissues of bone marrow were detected by immunohistochemistry. The changes of treg cells and lymphocyte subsets in peripheral blood of MPN patients and controls were detected by flow cytometry. 【Results】 The expression levels of p-JAK2,PD-1,PD-L1,and Treg in the newly diagnosed group were significantly higher than that of treatment group and control group(P<0.05),while the expression levels of CD4 +/CD8 + ratio were significantly lower than treatment group and control group(P<0.05). JAK2 V617F mutation burden was positive correlation with PD-1 and PD- L1,and was negative correlation with CD4 +/CD8 + ,the correlation coefficients were r=0.593,P<0.01;r=0.723,P<0.01;r=-0.771,P<0.01,respectively.【Conclusion】p-JAK2,PD-1,PD-L1,Treg,CD4+/CD8+ and JAK2 V617F were involved in the pathogenesis of myeloroliferative neoplasms.
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The technical review for clinical trials of implantable sacral nerve stimulation system needs to focus on the basic principles of trials, clinical institutition and design elements of clinical trial protocols.
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OBJECTIVE@#To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes.@*METHODS@#The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived. Simulation studies were conducted to evaluate the derived power functions.@*RESULTS@#Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed. The intra-correlation showed a positive correlation with the power of the bioequivalence test. When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval. If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power. Sample size can be calculated through numerical iteration with the derived power functions.@*CONCLUSION@#The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.
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Humanos , Administração Tópica , Ensaios Clínicos como Assunto , Métodos , Estudos Cross-Over , Modelos Teóricos , Soluções Oftálmicas , Farmacocinética , Tamanho da Amostra , Equivalência TerapêuticaRESUMO
BACKGROUND: Restrictive cardiomyopathy (RCM) is the least common cardiomyopathy in which the walls are rigid and the heart is restricted from stretching and filling properly. Cardiac troponin I (cTnI) mutation-caused myofibril Ca2+ hypersensitivity has been shown to be associated with impaired diastolic function. This study aimed to investigate the linkage between the genotype and clinical therapy of RCM. METHODS: Five sporadic pediatric RCM patients confirmed by echocardiography were enrolled in this study. Whole-exome sequencing (WES) was performed for the cohort to find out candidate causative gene variants. Sanger sequencing confirmed the WES-identified variants. RESULTS: TNNI3 variants were found in all of the five patients. R192H mutation was shared in four patients while R204H mutation was found only in one patient. Structure investigation showed that the C terminus of TNNI3 was flexible and mutation on the C terminus was possible to cause the RCM. Catechins were prescribed for the five patients once genotype was confirmed. Ventricular diastolic function was improved in three patients during the follow-up. CONCLUSIONS: Our data demonstrated that TNNI3 mutation-induced RCM1 is the most common type of pediatric RCM in this study. In addition, WES is a reliable approach to identify likely pathogenic genes of RCM and might be useful for the guidance of clinical treatment scheme.
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Cardiomiopatia Restritiva/genética , Exoma/genética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mutação/genética , Linhagem , Fenótipo , Troponina I/genéticaRESUMO
Objective To explore the efficacy and toxicities of gemcitabine combined with S-1 in treating locally advanced and metastatic pancreatic ductal adenocarcinoma and prognostic factors. Methods We retrospectively analyzed the clinical data of patients with locally advanced and metastatic pancreatic cancer receiving gemcitabine and S-1 as first-line therapy in the Department of Medical Oncology,Peking Union Medical College Hospital from January 2014 to January 2017.Gemcitabine was administered at a dose of 1000 mg/mover 30 min-utes on days 1 and 8,and oral S-1 at a dose of 40-60 mg twice daily from days 1 to 14,repeated every 3 weeks.All patients received at least two cycles of chemotherapy. Results A total of 60 patients were included,13(22%) achieved partial remission,37(61%) had stable disease,and 10(17%) experienced progressive disease.The median progression-free survival was 7 months(95% CI=6-10 months) and the median overall survival was 12 months(95% CI=9-20 months).Both univariate and multivariate analyses of prognostic factors showed primary resection was significant in predicting shorter progression-free survival and lung metastasis was significant for shorter overall survival.The most common grade 3-4 toxicities were neutropenia(27%) and leukopenia(18%). Conclusion Gemcitabine combined with S-1 is an effective regimen with manageable toxicities in the treatment of advanced pancreatic cancer and can be used as first-line therapy.
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<p><b>BACKGROUND</b>The primary cause of ischemic heart failure (HF) is myocardial infarction (MI) resulting in left ventricle (LV) wall motion abnormality secondary to ventricular remodeling. A prospective, nonrandomized study conducted in China was designed to assess safety and efficacy of the percutaneous ventricular restoration therapy using Parachute device (CardioKinetix, Inc., CA, USA) in ischemic HF patients as a result of LV remodeling after anterior wall MI.</p><p><b>METHODS</b>Thirty-one patients with New York Heart Association (NYHA) Class II, III ischemic HF, ejection fraction between 15% and 40%, and dilated akinetic or dyskinetic anterior-apical wall without the need to be revascularized were enrolled from seven sites in China from October to December 2014. The Parachute device was implanted through femoral artery. All patients received low-dose aspirin and anticoagulation with warfarin for at least 12 months postdevice implantation. The primary end-point was the assessment of efficacy as measured by the reduction in LV end-systolic volume index (LVESVI) against baseline LVESVI at 3 months postdevice implantation, determined by the echocardiography and measured by echocardiography core laboratory. Quality of life was assessed using EQ-5D and visual analog scale (VAS). For quantitative data comparison, paired t-test (normality data) and signed-rank test (abnormality data) were used; application of signed-rank test was for the ranked data comparison.</p><p><b>RESULTS</b>A change in LVESVI as measured by echocardiography from the preimplant baseline to 3-month postdevice implantation revealed a statistically significant reduction from 77.5 ± 20.0 ml/m2 to 53.1 ± 17.0 ml/m2 (P < 0.0001). The trial met its primary end-point. Of the 31 patients, the procedural success was 96.8%. Overall, NYHA HF class assessment results showed an improvement of more than half a class at 3 months (P < 0.001). Quality of life assessed by the VAS value increased 11.5 points (P < 0.01), demonstrating improvement at 3 months.</p><p><b>CONCLUSION</b>The favorable outcomes observed in the high-risk patients provide reassuring safety and efficacy data to support adoption of this technology as a therapeutic option for ischemic HF patients.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT02240940; https://clinicaltrials.gov/ct2/show/NCT02240940.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China , Insuficiência Cardíaca , Cirurgia Geral , Ventrículos do Coração , Cirurgia Geral , Estudos Prospectivos , Implantação de Prótese , Métodos , Volume Sistólico , Fisiologia , Resultado do Tratamento , Remodelação Ventricular , FisiologiaRESUMO
BACKGROUND: Transcatheter occlusion has been applied to treat ostium secundum atrial septal defect (OS ASD) since 1997. During the clinical practice, several postoperative complications including arrhythmia have been reported. This study aimed to evaluate the value of the ratio of atrial septal occluder (ASO) versus atrial septal length (ASL) for predicting arrhythmia occurrence after transcatheter closure in children with OS ASD. METHODS: Six hundred and fifty-one children diagnosed with OS ASD underwent occlusion procedures after completing routine examinations. The onsets and types of arrhythmia both during and after the occlusion procedures were monitored. Treatments were given based on the individual types of arrhythmia. The binary logistic regression analysis and receiver-operating characteristic (ROC) curve were used in the analysis of value of the ratio of ASO/ASL for predicting postoperative arrhythmia occurrence. RESULTS: Transcather occlusions were conducted in 651 children, among whom 7 children had different types and degrees of arrhythmia, with an incidence of 1.1%. The types of arrhythmia included sinus bradycardia, atrial premature beats, bundle branch block, and different degrees of atrioventricular block. Normal electrocardiograph findings were resumed in these 7 patients following active therapies such as corticoids, nutrition, and surgeries. The binary logistic regression and ROC analysis suggested that the ratio of ASO/ASL exhibited an intermediate predictive value for predicting arrhythmia occurrence after occlusion procedures. A cut-off value of 0.576 in the ratio provided a sensitivity of 87.5% and a specificity of 76.2% with an area under the ROC curve of 0.791 (95% confidence intervals, 0.655-0.926; P < 0.05) in predicting arrhythmia occurrence after the closure procedures. CONCLUSIONS: The ratio of ASO/ASL might be a useful index for predicting arrhythmia occurrence after closure procedures in children with OS ASD.
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Arritmias Cardíacas/diagnóstico , Comunicação Interatrial/cirurgia , Adolescente , Septo Interatrial/cirurgia , Cateterismo Cardíaco , Criança , Pré-Escolar , Ecocardiografia Transesofagiana , Feminino , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/diagnóstico , Dispositivo para Oclusão SeptalRESUMO
Acute kidney injury (AKI) is a potential complication following cardiopulmonary bypass (CPB) surgery in infants and young children with congenital heart disease (CHD). The current pilot study evaluates the predictive value of serum cystatin C (CysC) for AKI after pediatric CPB surgery. We prospectively enrolled 43 children with CHD (30 males and 13 females) who underwent CPB surgery. They were aged 3 years or younger. Serum CysC was measured at baseline and at 6 hours, 12 hours, 24 hours, and 48 hours after initiating CBP. Twenty-one (48.8%) patients developed AKI after cardiac surgery. Children who developed AKI had more complex cardiac surgical procedures (based on the Risk Adjustment for Congenital Heart Surgery 1 [RACHS-1] category), a longer CPB duration, and a longer aortic clamping time (ACT). Serum concentrations of CysC postoperatively demonstrated an initial decline at 6 hours, a subsequent increase at 12 hours, and stabilized at 24-48 hours. The best predictive performance was achieved 6 hours after CPB with an area under receiver operating characteristic curve (AUC) value of 0.69. The optimal cut-off value was 0.47 mg/L (sensitivity, 85.7%; specificity, 50%). By contrast, the RACHS-1 category, CPB duration, and ACT had higher AUC values at 0.735, 0.791, and 0.731, respectively. In conclusion, serum CysC had limited predictive capacity and was not superior to clinical risk factors for the early detection of AKI after CPB surgery in this pilot study, which focused on infants and young children.
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Injúria Renal Aguda/sangue , Ponte de Artéria Coronária/efeitos adversos , Cistatina C/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
UNLABELLED: Emerging evidence suggests that significant left ventricular dysfunction may arise in right-sided septal or paraseptal accessory pathways (APs) with Wolff-Parkinson-White syndrome, even in the absence of recurrent or incessant tachycardia. During 1 year and 9 months, we identified four consecutive female children with median age of 8 years diagnosed as having dilated cardiomyopathy (DCM) combined with overt right-sided APs several years ago. Incessant or recurrent tachycardia as the cause of DCM could be excluded. Anti-heart failure chemotherapy did not produce satisfactory effects. The patients underwent radiofrequency ablations (RFCAs). This report describes the clinical and echocardiographic characteristics of the cases before and after the ablation. Dyssynchronous ventricular contraction was observed in all patients. The locations of the APs were the right-sided anteroseptum and the free wall (n = 2 each). All patients received successful RFCAs. Their physical activities and growth improved greatly, and the echocardiographic data demonstrated that their left ventricular (LV) contraction recovered to synchrony shortly after the ablation and that their LV function recovered to normal gradually during the follow-up. CONCLUSIONS: A causal relationship between overt ventricular preexcitation and the development of DCM is supported by the complete recovery of LV function and reversed LV remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was probably the crucial mechanism. Not only right-sided septal or paraseptal but also free wall overt APs may induce LV dysfunction and even DCM. AP-induced DCM is an indication for ablation with a good prognosis.
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Cardiomiopatia Dilatada/etiologia , Disfunção Ventricular Esquerda/etiologia , Síndrome de Wolff-Parkinson-White/complicações , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Ablação por Cateter , Criança , Eletrocardiografia , Feminino , Humanos , Fatores de Risco , Resultado do Tratamento , Ultrassonografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/cirurgia , Síndrome de Wolff-Parkinson-White/diagnóstico por imagem , Síndrome de Wolff-Parkinson-White/fisiopatologia , Síndrome de Wolff-Parkinson-White/cirurgiaRESUMO
Aurora-B as an important kinase to adjust the cell normal mitosis is a potent target for cancer treatment. Aurora-B is overexpressed in a broad range of tumor and tumor cells are more sensitive while Aurora-B is inhibited. Due to the key role of the Aurora-B in cell mitosis, the development of its inhibitors is becoming more and more important. Several small molecules inhibit with a similar efficacy both Aurora-A and Aurora-B, however, in most cases the effects resemble Aurora-B disruption by genetic methods, indicating that Aurora-B represents an effective therapeutic target. There were several Aurora-B kinase inhibitors which had entered the clinics and displayed good antitumor activity. In this review, we will outline the functions of Aurora kinase B in normal cell division and in malignancy. We will focus on recent preclinical and clinical studies that have explored the mechanism of action and clinical effect of Aurora-B inhibitors in cancer treatment.
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Aurora Quinase B/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Aurora Quinase B/genética , Aurora Quinase B/metabolismo , Ativação Enzimática , Humanos , Mitose , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To understand the incidence of acute kidney injury (AKI) in infants and toddlers and evaluate the possibility of predicting AKI with urine neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-beta-D-glucosaminidase (NAG), microalbumin (MA) and α1-microglobulin (α1-MG) after surgeries for congenital heart diseases with cardiopulmonary bypass (CPB). METHOD: Fifty-eight children (ages ≤ 3 years) who had undergone surgery for congenital heart diseases with CPB were enrolled. Urinary samples were collected before and 4 h, 6 h, 12 h, 24 h post CPB to detect the concentration of NGAL, IL-18, NAG, MA and α1-MG. RESULT: The AKI group had 29 cases, none AKI group also had 29 cases. Urinary concentration of NGAL 4, 6, and 12 h post CPB were significantly higher in AKI group (2820 µg/g, 905.7 µg/g, 76.1 µg/g separately) than in none AKI group (27.6 µg/g, 19.5 µg/g, 16.0 µg/g separately, P < 0.01). Urinary concentration of IL-18 4, 6, 12 and 24 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of NAG 4 h and 6 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.01). Urinary concentration of MA/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of α1-MG/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.01). All the five biomarkers had predictive abilities at 4-hour after surgery. CONCLUSION: Urine biomarkers NGAL, IL-18, NAG, MA and α1-MG were valuable early predictors of AKI after CPB surgery.
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Injúria Renal Aguda/urina , Biomarcadores/urina , Ponte Cardiopulmonar/efeitos adversos , Cardiopatias Congênitas/cirurgia , Injúria Renal Aguda/etiologia , Proteínas de Fase Aguda/urina , alfa-Globulinas/urina , Pré-Escolar , Creatinina/urina , Feminino , Humanos , Lactente , Interleucina-18/urina , Lipocalina-2 , Lipocalinas/urina , Masculino , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas/urina , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To summarize and analyze the effects of treatment and prognosis of infants with endocardial fibroelastosis (EFE) in different states of the illness undergone relevant therapies, and to understand the roles of different treatments for improving the prognosis of the disease. METHODS: Data of 75 cases with EFE admitted into Anzhen Hospital Affiliated to Capital Medical University from August 1984 to June 2006 were analyzed retrospectively. RESULTS: (1) Of the 75 cases with EFE (40 males and 35 females), with the onset age ranged from 20-days to two years and eight months, 69 cases were treated normally and followed up in the Outpatient Department of the Hospital after discharge, the follow-up rate was 92%, with the follow-up span from six months to 23 years (5.7 years in average). During the follow-up, six cases (8.7%) died. (2) The total curative rate of EFE patients was 46.4% (32/69), while the improvement rate was 40.6% (28/69), the total rate of the cure and improvement was 87%. (3) The average value of ejection fraction (EF) of left ventricle of all the patients returned to normal two years after treatment (EF value was 55.86 ± 2.85), the percentage of patients with normal left ventricle EF at 1 year, 3 years, 5 years and 10 years after treatment was 42.6% (26/61), 64.4% (29/45), 70.7% (29/41) and 84.6% (22/26), respectively. The average value of cardiothoracic (C/T) ratio became normal three years after treatment through X ray examination (0.50 ± 0.01), however the average value of the LVDD had not been returned to normal 3 years after treatment. At 1 year, 3 years, 5 years and 10 years after treatment, the proportion of patients with normal LVDD was 0% (0/61), 13.3% (6/45), 53.7% (22/41) and 84.6% (22/26), respectively. (4) The average value of EF became normal one year after treatment in the glucocorticoid group (EF value 58.44 ± 5.10) in 37 cases scored < 22 at the first visit, while the average value of C/T normalized two years after treatment (0.50 ± 0.00); The average value of EF became normal three years after treatment in the glucocorticoid plus cyclophosphamide group (EF 57.33 ± 3.43) in 29 cases scored < 22 at the first visit, however the average value of the C/T and the LVDD did not return to normal 3 years after treatment. (5) Use of IVIG reduced the percentage of patients who received cyclophos-phamide. (6) The recovery of intimal thickness was slow in EFE patients, the span was four years on the average (1 - 8 years), the percentage of patients whose endocardium became normal 1 year, 3 years, 5 years and 10 years after treatment was 9.85% (6/61), 22.2% (10/45), 51.2% (21/41), 100% (29/29). CONCLUSION: The long-term continuous normal treatment of patients with EFE showed good therapeutic effects. For severe and refractory cases, immunotherapy must be strengthened and maintained for longer time. For those who clinically recovered, the quantity of activity should be restricted after the treatment is discontinued, and the re-examination should be done timely for further management.