RESUMO
BACKGROUND: The use of Anti-PD-1 therapy has yielded promising outcomes in hepatocellular carcinoma (HCC). However, limited research has been conducted on the overall survival (OS) of patients with varying tumor responses and treatment duration. METHODS: This retrospective study analyzed HCC patients who received sintilimab between January 2019 and December 2020 at four centers in China. The evaluation of tumor progression was based on Response Evaluation Criteria in Solid Tumors version 1.1. The study investigated the correlation between tumor response and OS, and the impact of drug use on OS following progressive disease (PD). RESULTS: Out of 441 treated patients, 159 patients satisfied the inclusion criteria. Among them, 77 patients with disease control exhibited a significantly longer OS compared to the 82 patients with PD (median OS 26.0 vs. 11.3 months, P < 0.001). Additionally, the OS of patients with objective response (OR) was better than that of patients with stable disease (P = 0.002). Among the 47 patients with PD who continued taking sintilimab, the OS was better than the 35 patients who discontinued treatment (median OS 11.4 vs. 6.9 months, P = 0.042). CONCLUSIONS: In conclusion, the tumor response in HCC patients who received sintilimab affects OS, and patients with PD may benefit from continued use of sintilimab.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Critérios de Avaliação de Resposta em Tumores SólidosRESUMO
Only 6 to 8 % of the UK adults meet the daily recommendation for dietary fibre. Fava bean processing lead to vast amounts of high-fibre by-products such as hulls. Bean hull fortified bread was formulated to increase and diversify dietary fibre while reducing waste. This study assessed the bean hull: suitability as a source of dietary fibre; the systemic and microbial metabolism of its components and postprandial events following bean hull bread rolls. Nine healthy participants (53·9 ± 16·7 years) were recruited for a randomised controlled crossover study attending two 3 days intervention sessions, involving the consumption of two bread rolls per day (control or bean hull rolls). Blood and faecal samples were collected before and after each session and analysed for systemic and microbial metabolites of bread roll components using targeted LC-MS/MS and GC analysis. Satiety, gut hormones, glucose, insulin and gastric emptying biomarkers were also measured. Two bean hull rolls provided over 85 % of the daily recommendation for dietary fibre; but despite being a rich source of plant metabolites (P = 0·04 v. control bread), these had poor systemic bioavailability. Consumption of bean hull rolls for 3 days significantly increased plasma concentration of indole-3-propionic acid (P = 0·009) and decreased faecal concentration of putrescine (P = 0·035) and deoxycholic acid (P = 0·046). However, it had no effect on postprandial plasma gut hormones, bacterial composition and faecal short chain fatty acids amount. Therefore, bean hulls require further processing to improve their bioactives systemic availability and fibre fermentation.
Assuntos
Fabaceae , Hormônios Gastrointestinais , Adulto , Humanos , Voluntários Saudáveis , Putrescina , Pão/análise , Cromatografia Líquida , Estudos Cross-Over , Espectrometria de Massas em Tandem , Fibras na Dieta/análise , Fabaceae/metabolismo , Ácido Desoxicólico , Glicemia/análiseRESUMO
Advanced biliary tract cancer (BTC) has a poor prognosis, even after combined chemotherapy of gemcitabine and oxaliplatin (GEMOX). To investigate the efficacy and safety of GEMOX chemotherapy combining atezolizumab and bevacizumab in advanced BTC, the authors designed an open-label, single-arm, phase II clinical trial and will enroll patients with stage IV BTC. The participants will receive GEMOX chemotherapy combined with atezolizumab plus bevacizumab. The primary end point is objective response rate; the secondary end points are overall survival, disease control rate, progression-free survival, time to progression, duration of response and safety. The results of this trial are expected to provide novel, safe and effective treatment options for patients with advanced BTC, which could further improve their prognosis. Clinical Trial Registration: ChiCTR2100049830 (ChiCTR.org).
Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Gencitabina , Oxaliplatina/uso terapêutico , Cisplatino/uso terapêutico , Bevacizumab/efeitos adversos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
AIM: This study aimed to evaluate the effects of using the teach-back method among women with limited maternal health literacy (LMHL) on maternal health literacy(MHL), postpartum health behaviours and maternal-infant health outcomes. METHODS: A randomized controlled study was conducted in the obstetrics department of Anhui Provincial Hospital, China. A total of 258 pregnant women with LMHL were recruited at the point of admission to the hospital for birth and randomly assigned to the control group (n = 130), where women received routine education sessions, and the teach-back group (n = 128), where women received routine education sessions plus a teach-back intervention. The two groups were assessed in terms of MHL before and after the intervention, breastfeeding execution, uptake of 42-day postpartum check-ups, complete uptake of one-time recommended vaccines, and physical health outcomes. Statistical tests were employed for data analysis. RESULTS: There was no significant difference between the two groups in terms of MHL and other social, demographic, and medical status at baseline. After the intervention, the teach-back group had a higher level of MHL (p < 0.001), better postpartum health behaviours in terms of exclusive breastfeeding within 24 hours postpartum (x2 = 22.853, p<0.001), exclusive breastfeeding within 42 days postpartum (x2 = 47.735, p<0.001), uptake of 42-day postpartum check-ups (x2 = 9.050, p = 0.003) and vaccination (x2 = 5.586, p = 0.018) and better maternal-infant health outcomes in terms of the incidence of subinvolution of the uterus (x2 = 6.499, p = 0.011), acute mastitis (x2 = 4.884, p = 0.027), postpartum constipation (x2 = 5.986, p = 0.014), overweight (x2 = 4.531, p = 0.033) and diaper dermatitis (x2 = 10.896, p = 0.001). CONCLUSIONS: This study shows that the teach-back method is effective for enhancing MHL, leading to positive postpartum health behaviours, and improving postpartum maternal-infant health outcomes among women with LMHL. The teach-back method may play an important role in improving postpartum maternal-infant health and could be considered in maternal health education. TRIAL REGISTRATION NUMBER: Our trial has been prospectively registered at ClinicalTrials.gov (Ref. No.: NCT04858945) and the enrollment date was 26/04/2021.
Assuntos
Letramento em Saúde , Lactente , Gravidez , Feminino , Humanos , Saúde do Lactente , Período Pós-Parto , Sobrepeso , Aleitamento MaternoRESUMO
Recurrence and metastasis remain the major obstacles to successful treatment of hepatocellular carcinoma (HCC). Chromatin remodeling factor ARID2 is commonly mutated in HCC, indicating its important role in cancer development. However, its role in HCC metastasis is largely elusive. In this study, we find that ARID2 expression is significantly decreased in metastatic HCC tissues, showing negative correlation with pathological grade, organ metastasis and positive association with survival of HCC patients. ARID2 inhibits migration and invasion of HCC cells in vitro and metastasis in vivo. Moreover, ARID2 knockout promotes pulmonary metastasis in different HCC mouse models. Mechanistic study reveals that ARID2 represses epithelial-mesenchymal transition (EMT) of HCC cells by recruiting DNMT1 to Snail promoter, which increases promoter methylation and inhibits Snail transcription. In addition, we discover that ARID2 mutants with disrupted C2H2 domain lose the metastasis suppressor function, exhibiting a positive association with HCC metastasis and poor prognosis. In conclusion, our study reveals the metastasis suppressor role as well as the underlying mechanism of ARID2 in HCC and provides a potential therapeutic target for ARID2-deficient HCC.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Montagem e Desmontagem da Cromatina/fisiologia , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Fatores de Transcrição/metabolismo , Animais , Dedos de Zinco CYS2-HIS2 , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Knockout , Mutação , Metástase Neoplásica/patologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genéticaRESUMO
OBJECTIVES: To explore downstream management and outcomes of machine learning (ML)-based CT derived fractional flow reserve (FFRCT) strategy compared with an anatomical coronary computed tomography angiography (CCTA) alone assessment in participants with intermediate coronary artery stenosis. METHODS: In this prospective study conducted from April 2018 to March 2019, participants were assigned to either the CCTA or FFRCT group. The primary endpoint was the rate of invasive coronary angiography (ICA) that demonstrated non-obstructive disease at 90 days. Secondary endpoints included coronary revascularization and major adverse cardiovascular events (MACE) at 1-year follow-up. RESULTS: In total, 567 participants were allocated to the CCTA group and 566 to the FFRCT group. At 90 days, the rate of ICA without obstructive disease was higher in the CCTA group (33.3%, 39/117) than that (19.8%, 19/96) in the FFRCT group (risk difference [RD] = 13.5%, 95% confidence interval [CI]: 8.4%, 18.6%; p = 0.03). The ICA referral rate was higher in the CCTA group (27.5%, 156/567) than in the FFRCT group (20.3%, 115/566) (RD = 7.2%, 95% CI: 2.3%, 12.1%; p = 0.003). The revascularization-to-ICA ratio was lower in the CCTA group than that in the FFRCT group (RD = 19.8%, 95% CI: 14.1%, 25.5%, p = 0.002). MACE was more common in the CCTA group than that in the FFRCT group at 1 year (HR: 1.73; 95% CI: 1.01, 2.95; p = 0.04). CONCLUSION: In patients with intermediate stenosis, the FFRCT strategy appears to be associated with a lower rate of referral for ICA, ICA without obstructive disease, and 1-year MACE when compared to the anatomical CCTA alone strategy. KEY POINTS: ⢠In stable patients with intermediate stenosis, ML-based FFRCT strategy was associated with a lower referral ICA rate, a lower normalcy rate of ICA, and higher revascularization-to-ICA ratio than the CCTA strategy. ⢠Compared with the CCTA strategy, ML-based FFRCTshows superior outcome prediction value which appears to be associated with a lower rate of 1-year MACE. ⢠ML-based FFRCT strategy as a non-invasive "one-stop-shop" modality may be the potential to change diagnostic workflows in patients with suspected coronary artery disease.
Assuntos
Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Angiografia por Tomografia Computadorizada/métodos , Constrição Patológica , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Valor Preditivo dos Testes , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
The therapeutic effect of transcatheter arterial chemoembolization (TACE) is limited for patients with hepatocellular carcinoma (HCC). Herein, we designed an open-label, single-arm phase II clinical trial to investigate the efficacy and safety of TACE combined with atezolizumab plus bevacizumab for patients with Barcelona Clinic Liver Cancer (BCLC) stage-B HCC. Patients will initially receive TACE. Atezolizumab and bevacizumab will be initiated 2-14 days after the first TACE session. TACE will be repeated on demand. The primary endpoint is the objective response rate. The secondary end points include overall survival, disease control rate, progression-free survival, time-to-progression and safety. The study results will provide evidence for establishing a novel therapeutic regimen for patients with unresectable HCC. Clinical Trial Registration: ChiCTR2100049829 (ChiCTR.org).
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Ensaios Clínicos Fase II como Assunto , Neoplasias Hepáticas/terapia , Terapia Combinada/efeitos adversosRESUMO
PURPOSE: To investigate whether the high-grade pivot-shift phenomenon is associated with asymmetry of the lateral and medial compartment anterior tibial translation (L-ATT and M-ATT) and lateral meniscus posterior horn (LMPH) tears in anterior cruciate ligament (ACL) injuries. METHODS: A retrospective analysis was performed on 192 consecutive patients who had complete ACL injuries between January 2019 and December 2020. Among these, 156 met the inclusion criteria. L-ATT and M-ATT were measured using preoperative weight-bearing magnetic resonance imaging (MRI), and the differences between L-ATT and M-ATT were calculated. Thirty-five patients who demonstrated excessive differences in L-ATT and M-ATT (> 6.0 mm) were regarded as asymmetric (study group), and 36 patients with minimal or no differences in L-ATT and M-ATT (< 3.0 mm) were allocated to the control group. Demographic data, grade of the pivot-shift test, integrality of LMPH, and medial meniscus posterior horn (MMPH) were compared between the groups. Moreover, predictors of high-grade pivot-shift phenomenon, including asymmetry of L-ATT and M-ATT, integrity of LMPH and MMPH, time from injury to surgery, sex, age, and body mass index (BMI) were assessed using multivariable logistic regression analysis. RESULTS: The difference between L-ATT and M-ATT in the study group was significantly higher than that in the control group (mean ± SD: 8.4 ± 2.1 mm vs. 1.5 ± 1.0 mm, P < 0.001). A higher proportion of patients with high-grade pivot-shift phenomenon (2 + and 3 +) and LMPH tears were identified in the study group (high-grade pivot-shift phenomenon: 25/35 vs. 13/36, P = 0.003; LMPH tears: 18/35 vs. 5/36, P = 0.001). Additionally, asymmetry of L-ATT, M-ATT (odds ratio 5.8; 95% CI 1.7-19.8; P = 0.005), and LMPH tears (odds ratio 3.8; 95% CI 1.3-11.6; P = 0.018) were found to be good predictors of the high-grade pivot-shift phenomenon after ACL injury, whereas MMPH tears, time from injury to surgery, sex, age, and BMI were not. CONCLUSION: In patients with ACL injury, the high-grade pivot-shift phenomenon is associated with asymmetry between L-ATT and M-ATT, and LMPH tears. LEVEL OF EVIDENCE: III.
Assuntos
Lesões do Ligamento Cruzado Anterior , Instabilidade Articular , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/cirurgia , Humanos , Instabilidade Articular/cirurgia , Articulação do Joelho , Meniscos Tibiais , Estudos Retrospectivos , Tíbia/cirurgiaRESUMO
PURPOSE: This study aimed to compare the difference in posterior tibial slope (PTS) measurements based on the full-length and half-length tibial anatomic axes of the same group of patients. It was hypothesized that the obtained PTS values would be affected by the length of tibia chosen during the measurements. METHODS: Full-length true lateral tibia radiographs were obtained for each patient who underwent anterior cruciate ligament reconstruction (ACLR) in our department. PTS measurements were obtained by measuring the angle between the full-length or half-length tibial anatomic axis and an average of the lateral and medial tibial plateau. The anatomic axis was defined as the center of the tibial diaphysis. The PTS measurements from the full-length and half-length true lateral tibia radiographs were obtained and compared. Additionally, the absolute difference and the relationship between the two PTS measurements were calculated and analyzed. RESULTS: A total of 200 ACL-injured patients were included in this study. The average PTS values using the anatomic axis were 15.9 ± 3.7° and 14.1 ± 3.7° on full-length and half-length true lateral tibial radiographs. There was a significant difference between the measurements with the full-length and half-length tibial radiographs (P < 0.01). Additionally, 49.5% (n = 99) of patients had ≥ 2.0° differences between the full-length and half-length anatomic axis PTS measurement techniques; meanwhile, a strong and significant linear relationship (r = 0.95; P < 0.001) was identified between the two PTS measurements. CONCLUSION: There were significant differences and linear relationships between PTS measurements that measured the anatomic axis from full-length and half-length true lateral tibia radiographs. Therefore, the obtained PTS values were strongly associated with the length of tibia chosen during the measurements. Surgeons should pay more attention to the measurement techniques and the tibial length when considering the role of PTS in ACL injury and ACLR failure. Knowledge of the association is very important for calculating potential closing wedge proximal tibial osteotomies to correct excessive PTS in the setting of ACLR failures. LEVEL OF EVIDENCE: IV.
Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteotomia , Tíbia/diagnóstico por imagem , Tíbia/cirurgiaRESUMO
OBJECTIVE: To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)-based coronary CT angiography (CCTA)-derived fractional flow reserve (CT-FFR) with FFR as a reference standard. METHODS: A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. RESULTS: Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. CONCLUSION: Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. KEY POINTS: ⢠CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. ⢠No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. ⢠No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , China , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Aprendizado de Máquina , Masculino , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 infection occurred in Wuhan, Hubei Province, China, and spread across China and beyond. On February 12, 2020, the World Health Organization officially named the disease caused by the novel coronavirus as coronavirus disease 2019 (COVID-19). Because most patients infected with COVID-19 had pneumonia and characteristic CT imaging patterns, radiologic examinations have become vital in early diagnosis and the assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19 while highlighting the role of chest CT in prevention and disease control.
Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , COVID-19 , Teste para COVID-19 , China/epidemiologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Diagnóstico Diferencial , Diagnóstico Precoce , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate the effect of image quality of coronary CT angiography (CCTA) on the diagnostic performance of a machine learning-based CT-derived fractional flow reserve (FFRCT). METHODS: This nationwide retrospective study enrolled participants from 10 individual centers across China. FFRCT analysis was performed in 570 vessels in 437 patients. Invasive FFR and FFRCT values ≤ 0.80 were considered ischemia-specific. Four-score subjective assessment based on image quality and objective measurement of vessel enhancement was performed on a per-vessel basis. The effects of body mass index (BMI), sex, heart rate, and coronary calcium score on the diagnostic performance of FFRCT were studied. RESULTS: Among 570 vessels, 216 were considered ischemia-specific by invasive FFR and 198 by FFRCT. Sensitivity and specificity of FFRCT for detecting lesion-specific ischemia were 0.82 and 0.93, respectively. Area under the curve (AUC) of high-quality images (0.93, n = 159) was found to be superior to low-quality images (0.80, n = 92, p = 0.02). Objective image quality and heart rate were also associated with diagnostic performance of FFRCT, whereas there was no statistical difference in diagnostic performance among different BMI, sex, and calcium score groups (all p > 0.05, Bonferroni correction). CONCLUSIONS: This retrospective multicenter study supported the FFRCT as a noninvasive test in evaluating lesion-specific ischemia. Subjective image quality, vessel enhancement, and heart rate affect the diagnostic performance of FFRCT. KEY POINTS: ⢠FFRCTcan be used to evaluate lesion-specific ischemia. ⢠Poor image quality negatively affects the diagnostic performance of FFRCT. ⢠CCTA with ≥ score 3, intracoronary enhancement degree of 300-400 HU, and heart rate below 70 bpm at scanning could be of great benefit to more accurate FFRCTanalysis.
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Aprendizado de Máquina , Idoso , Estenose Coronária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Comprehensive data on hepatitis C virus (HCV) genotypes distribution is critical for treatment regimen selection, vaccine design, and drug development. This study aimed to understand the dynamic distribution of HCV genotypes in Mainland China. Three hundred sixty-two studies published from January 1993 to December 2017 involving 64 891 samples (5133 injecting drug users, 2748 volunteer blood donors, 1509 former paid plasma donors, 160 sexually encounters, and 1992 human immunodeficiency virus (HIV)/HCV coinfection patients) were eligible for the quantitative synthesis estimation. Pooled proportion of HCV genotypes (and 95% confidence intervals [CIs]) was estimated through the Freeman-Tukey double arcsine transformation by period, region, and risk group. A sharp decline of the subtype 1b was observed in all regions except in northwestern and central regions. The genotypes 3 and 6 showed an obvious increase in southern and southwestern regions and have already spread nationwide. After 2010, subtype 1b was the most dominant variant in all regions and risk groups, accounting for 54.0% (95% CI, 51.9-56.1) of all national infections. Subtype 2a was the second most prevalent strain in all regions except in the south and southwest, with 15.4% (95% CI, 13.1-17.8) national infections. The subtype 6a in southern region and 3b and 3a in southwestern region had a higher proportion of infections than that in other regions. In addition, the genotypes 3 and 6 are already prevalent in almost all risk groups. The distribution of HCV genotypes were sharply shifting in China in the past three decades. The HCV subtype 1b posed a sharp decline, whereas genotypes 3 and 6 played an increasing role in the regional and populational HCV pandemic.
Assuntos
Variação Genética , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/virologia , China/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Evolução Molecular , Genótipo , Infecções por HIV/epidemiologia , Hepacivirus/classificação , Humanos , Filogenia , Prevalência , Análise de Sequência de DNA , Proteínas do Envelope Viral/genéticaRESUMO
BACKGROUND The aim of this study was to identify biomarkers closely related to the pathogenesis and prognosis of oral squamous cell carcinoma (OSCC) by using weighted gene co-expression network analysis (WGCNA) based on integrative transcriptome datasets. MATERIAL AND METHODS Gene expression profiles of OSCC were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained and we then performed with Gene ontology (GO) and pathway enrichment analysis as well as protein-protein interactions (PPI) network analysis. WGCNA was used to construct the co-expression network. Multipart results were intersected to acquire the candidate genes, and survival analysis was used to identify the hub genes. RESULTS A total of 568 DEGs, including 272 upregulated genes and 296 downregulated genes, were identified. GO and pathway analyses revealed that these DEGs were mainly enriched in extracellular matrix (ECM), ECM organization, structural constituent of muscle, and ECM-receptor interaction. The PPI network of DEGs was established, comprising 428 nodes and 1944 edges. In the co-expression network, pink module was the key module, in which 34 genes with high connectivity were identified. After the intersection of multipart results, 24 common genes were chosen as the candidate genes, among which 7 hub genes (PLAU, SERPINE1, LAMC2, ITGA5, TGFBI, FSCN1, and HLF) were identified using survival analysis. CONCLUSIONS Seven potential biomarkers were identified as being closely related with the initiation and prognosis of OSCC and might serve as potential targets for early diagnosis and personalized therapy of OSCC.
Assuntos
Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biomarcadores Tumorais/sangue , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , Neoplasias Bucais/sangue , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , TranscriptomaRESUMO
Using nanocrystals as "artificial atoms" to construct supercrystals is an interesting process to explore the stacking style of nanoscale building blocks and corresponding collective properties. Various types of semiconducting supercrystals have been constructed via the assembly of nanocrystals driven by the entropic, electrostatic, or van der Waals interactions. We report a new type of metal halide perovskite supercrystals via the gold-bromide complex triggered assembly of newly emerged attractive CsPbBr3 nanocubes. Through introducing gold-bromide (Au-Br) complexes into CsPbBr3 nanocubes suspension, the self-assembly process of CsPbBr3 nanocubes to form supercrystals was investigated with the different amount of Au-Br complexes added to the suspensions, which indicates that the driven force of the formation of CsPbBr3 supercrystals included the van der Waals interactions among carbon chains and electrostatic interactions between Au-Br complexes and surfactants. Accordingly, the optical properties change with the assembly of CsPbBr3 nanocubes and the variation of mesoscale structures of supercrystals with heating treatment was revealed as well, demonstrating the ionic characteristics of CsPbBr3 nanocrystals. The fabricated CsPbBr3 supercrystal presents a novel type of semiconducting supercrystals that will open an avenue for the assembly of ionic nanocrystals.
RESUMO
Purpose To assess the accuracy of computed tomographic (CT) angiography for diagnosis of cerebral aneurysms 5 mm or smaller, with digital subtraction angiography (DSA) as the reference standard, in a large patient cohort Materials and Methods This retrospective study was approved by the local institutional review board with a waiver of written informed consent. A total of 1366 patients who underwent cerebral CT angiography followed by DSA were included. The performance of CT angiography for depiction of aneurysms was evaluated by two readers on a per-patient and per-aneurysm basis and based on size of aneurysm, location, and status of rupture. The performance of CT angiography for diagnosis of aneurysms of different size, location, and rupture status was compared by using χ2 test. κ statistic was used to assess interreader agreement for diagnosis of aneurysms. Results Of 1366 patients, 579 patients had 711 small aneurysms at DSA. By using DSA as the reference standard, the respective sensitivity, specificity, and accuracy of CT angiography for readers 1 and 2 for detection of small aneurysms on a per-patient basis were 97.1% (562 of 579) and 97.4% (564 of 579), 98.5% (451 of 458) and 99.1% (454 of 458), and 97.7% (1013 of 1037) and 98.2% (1018 of 1037) and those on a per-aneurysm basis were 95.2% (677 of 711) and 95.4% (678 of 711), 96.6% (451 of 467) and 97.0% (454 of 468), and 95.8% (1128 of 1178) and 96.0% (1132 of 1179). The sensitivities of CT angiography were lower for detection of aneurysms smaller than 3 mm and unruptured compared with aneurysms that were 3-5 mm and ruptured (P < .001). No difference existed for the sensitivities of CT angiography for diagnosis of aneurysms in the anterior versus posterior circulation (P > .0167). Excellent or good interreader agreement was found for detection of intracranial aneurysms on a per-patient (κ = 0.982) and per-aneurysm (κ = 0.748) basis. Conclusion This large cohort study demonstrated that CT angiography had high accuracy for detection of small cerebral aneurysms, including those smaller than 3 mm. © RSNA, 2017 Online supplemental material is available for this article.
Assuntos
Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/epidemiologia , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/epidemiologia , Adulto , Causalidade , Angiografia Cerebral/estatística & dados numéricos , China/epidemiologia , Comorbidade , Angiografia por Tomografia Computadorizada/estatística & dados numéricos , Feminino , Humanos , Aneurisma Intracraniano/patologia , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To evaluate image quality and diagnostic accuracy for acute infarct detection and radiation dose of 70 kVp whole brain CT perfusion (CTP) and CT angiography (CTA) reconstructed from CTP source data. METHODS: Patients were divided into three groups (n = 50 each): group A, 80 kVp, 21 scanning time points; groups B, 70 kVp, 21 scanning time points; group C, 70 kVp, 17 scanning time points. Objective and subjective image quality of CTP and CTA were compared. Diagnostic accuracy for detecting acute infarct and cerebral artery stenosis ≥ 50 % was calculated for CTP and CTA with diffusion weighted imaging and digital subtraction angiography as reference standards. Effective radiation dose was compared. RESULTS: There were no differences in any perfusion parameter value between three groups (P > 0.05). No difference was found in subjective image quality between three groups (P > 0.05). Diagnostic accuracy for detecting acute infarct and vascular stenosis showed no difference between three groups (P > 0.05). Compared with group A, radiation doses of groups B and C were decreased by 28 % and 37 % (both P < 0.001), respectively. CONCLUSION: Compared with 80 kVp protocol, 70 kVp brain CTP allows comparable vascular and perfusion assessment and lower radiation dose while maintaining high diagnostic accuracy in detecting acute infarct. KEY POINTS: ⢠70 kVp whole brain CTP can provide diagnostic image quality. ⢠70 kVp CTP diagnostic accuracy was maintained vs. 80 kVp protocol. ⢠70 kVp CTP radiation doses were lower than 80 kVp protocol.
Assuntos
Doenças Arteriais Cerebrais/diagnóstico , Infarto Cerebral/diagnóstico , Encéfalo/irrigação sanguínea , Angiografia por Tomografia Computadorizada/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Constrição Patológica/diagnóstico , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada Espiral/métodosRESUMO
The core-shell structure Fe3 O4 /SiO2 magnetic microspheres were prepared by a sol-gel method, and immobiled with iminodiacetic acid (IDA) as metal ion affinity ligands for protein adsorption. The size, morphology, magnetic properties and surface modification of magnetic silica nanospheres were characterized by various modern analytical instruments. It was shown that the magnetic silica nanospheres exhibited superparamagnetism with saturation magnetization values of up to 58.1 emu/g. Three divalent metal ions, Cu(2+) , Ni(2+) and Zn(2+) , were chelated on the Fe3 O4 @SiO2 -IDA magnetic microspheres to adsorb lysozyme. The results indicated that Ni(2+) -chelating magnetic microspheres had the maximum adsorption capacity for lysozyme of 51.0 mg/g, adsorption equilibrium could be achieved within 60 min and the adsorbed protein could be easily eluted. Furthermore, the synthesized Fe3 O4 @SiO2 -IDA-Ni(2+) magnetic microspheres were successfully applied for selective enrichment lysozyme from egg white and His-tag recombinant Homer 1a from the inclusion extraction expressed in Escherichia coli. The result indicated that the magnetic microspheres showed unique characteristics of high selective separation behavior of protein mixture, low nonspecific adsorption, and easy handling. This demonstrates that the magnetic silica microspheres can be used efficiently in protein separation or purification and show great potential in the pretreatment of the biological sample.
Assuntos
Cromatografia de Afinidade/métodos , Histidina/isolamento & purificação , Iminoácidos/química , Nanopartículas de Magnetita/química , Muramidase/isolamento & purificação , Dióxido de Silício/química , Adsorção , Animais , Proteínas de Transporte/química , Proteínas de Transporte/isolamento & purificação , Galinhas , Histidina/química , Proteínas de Arcabouço Homer , Muramidase/química , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificaçãoRESUMO
Human NKX2.5 (NK2 homeobox 5) premature stop codon (PTC) mutations cause congenital heart diseases such as atrial septal defect and atrioventricular block. At present, eight NKX2.5 PTC mutations were reported as E109X, Q149X, Q170X, Q187X, Q198X, Y256X, Y259X and C264X. To observe the ability of tRNA suppressors to read through NKX2.5 PTC mutations and produce functional full-length proteins, eight NKX2.5 PTC mutations were cloned into pcDNA3.1(-) vectors and four fragments (wild-type NKX2.5, E109X, Q149X and C264X) were cloned in pEGFP-N1 vectors to acquire NKX2.5-EGFP fusing plasmids. After transfection of NKX2.5-EGFP with or without corresponding tRNA suppressor into HeLa cells, the quantity of EGFP was measured to confirm the readthrough ability of the PTCs. NKX2.5 full-length and truncated protein expression levels were examined by Western blotting and the readthrough efficiency of tRNA suppressors on the PTCs was calculated respectively. The activity of NKX2.5 full-length and truncated protein was confirmed on NKX2.5 target gene-Cx43 mRNA level measured by Real-time PCR. Three tRNA suppressors were used: tRNA am, tRNA oc and tRNA op. tRNA am could suppress UAG-containing PTCs Q149X, Q170X, Q187X, Q198X and the readthrough efficiency for the latter three was above 50%. tRNA op could suppress UGA-containing PTC C264X with ~50% readthrough efficiency. tRNA oc failed to read through NKX2.5 PTC mutations. The relative Cx43 mRNA level in all readthrough samples was increased to 7%-41.7%. In conclusion, tRNA am and tRNA op could suppress NKX2.5 PTCs and induce functional protein expression. However, the effects of tRNA suppressors on cellular function are not clear yet, warranting further researches.
Assuntos
Códon de Terminação/genética , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Terminação Traducional da Cadeia Peptídica , RNA de Transferência/genética , Fatores de Transcrição/genética , Códon de Terminação/metabolismo , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/metabolismo , Humanos , RNA de Transferência/metabolismo , Fatores de Transcrição/metabolismoRESUMO
ß/γ-Crystallins are the major structural proteins in mammalian lens. The N-terminal truncation of ßB1-crystallin has been associated with the regulation of ß-crystallin size distributions in human lens. Herein we studied the roles of ßB1 N-terminal extension in protein structure and folding by constructing five N-terminal truncated forms. The truncations did not affect the secondary and tertiary structures of the main body as well as stability against denaturation. Truncations with more than 28 residues off the N-terminus promoted the dissociation of the dimeric ßB1 into monomers in diluted solutions. Interestingly, the N-terminal extension facilitated ßB1 to adopt the correct folding pathway, while truncated proteins were prone to undergo the misfolding/aggregation pathway during kinetic refolding. The N-terminal extension of ßB1 acted as an intramolecular chaperone (IMC) to regulate the kinetic partitioning between folding and misfolding. The IMC function of the N-terminal extension was also critical to the correct refolding of ß-crystallin heteromer and the action of the lens-specific molecular chaperone αA-crystallin. The cooperation between IMC and molecular chaperones produced a much stronger chaperoning effect than if they acted separately. To our knowledge, this is the first report showing the cooperation between IMC and molecular chaperones.