RESUMO
Sacral tumours encompass an extensive range of differential diagnosis. The clinical presentation is often non-specific, including neurological deficits and low back pain. Accurate diagnosis of sacral lesions is challenging and requires a comprehensive imaging strategy and robust knowledge on the imaging characteristics of different pathological processes. This review will provide an updated overview of the computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)-CT features of some common and rare sacral tumours and their mimics. Several clinical scenarios with specific diagnostic considerations and treatment implications will be described.
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Diagnóstico por Imagem/métodos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Medula Espinal/diagnóstico por imagemRESUMO
ABSTRACT: Objective To explore the characteristics of individuals with mental disorders suspected of road traffic offences and to find their differences from normal offenders, in order to regulate mental disorder patients' driving activities and prevent road traffic offences. Methods One hundred and twenty-three cases of forensic psychiatry testimony of individuals suspected of road traffic offences between 2014 and 2019 from the West China Forensic Center of Sichuan Province were collected. Fisher exact probability test was used to compare the differences between offenders with mental disorders and without mental disorders in terms of demographic characteristics, criminological characteristics, psychiatric characteristics and criminal responsibilities. Results There was no statistical significance in the differences of demographic characteristics, vehicles and kinds of alcohol between the two groups ï¼P>0.05ï¼. The main type of road traffic related crimes committed by offenders with mental disorders was risky driving and were mainly evaluated as partial criminal responsibility, whereas most offenders without mental disorders committed crime of causing traffic casualties and all were evaluated as full criminal responsibility. There was statistical significance in the differences of the types of crime and the criminal responsibility rating between the two groups ï¼P<0.05ï¼. Meanwhile, patients with mental disorders were characterized by long course of disease and irregular treatment, and individuals diagnosed as having mental disorders caused by psychoactive substances accounted for a large proportion. Conclusion There are differences in the characteristics of road traffic-related crimes between mental disorder patients and normal people. It is of great practical significance for reducing road traffic offences to evaluate whether the individuals with mental disorders are fit for driving.
Assuntos
Condução de Veículo , Criminosos , Transtornos Mentais , China/epidemiologia , Crime , Psiquiatria Legal , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologiaRESUMO
The KT/HAK/KUP family members encoding high-affinity potassium (K(+)) transporters mediate K(+) transport across the plasma membranes of plant cells to maintain plant normal growth and metabolic activities. In this paper, we identified 16 potassium transporter genes in the peach (Prunus persica) using the Hidden Markov model scanning strategy and searching the peach genome database. Utilizing the Arabidopsis KT/HAK/KUP family as a reference, phylogenetic analysis indicates that the KT/HAK/KUP family in the peach can be classified into 3 groups. Genomic localization indicated that 16 KT/HAK/KUP family genes were well distributed on 7 scaffolds. Gene structure analysis showed that the KT/HAK/KUP family genes have 6-9 introns. In addition, all of the KT/HAK/KUP family members were hydrophobic proteins; they exhibited similar secondary structure patterns and homologous tertiary structures. Putative cis-elements involved in abiotic stress adaption, Ca(2+) response, light and circadian rhythm regulation, and seed development were observed in the promoters of the KT/HAK/KUP family genes. Subcellular localization prediction indicated that the KT/HAK/KUP members were mainly located in the plasma membrane. Expression levels of the KT/HAK/ KUP family genes were much higher in the fruit and flower than those in the other 7 tissues examined, indicating that the KT/HAK/KUP family genes may have important roles in K(+) uptake and transport, which mainly contribute to flower formation and fruit development in the peach.
Assuntos
Antiportadores de Potássio-Hidrogênio/genética , Potássio/metabolismo , Prunus persica/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/genética , Flores/crescimento & desenvolvimento , Frutas/genética , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Íntrons/genética , Filogenia , Antiportadores de Potássio-Hidrogênio/metabolismo , Prunus persica/metabolismoRESUMO
MicroRNA166 (miR166) is known to have highly conserved targets that encode proteins of the class III homeodomain-leucine zipper (HD-ZIP III) family, in a broad range of plant species. To further understand the relationship between HD-ZIP III genes and miR166, four HD-ZIP III family genes (PpHB14, PpHB15, PpHB8, and PpREV) were isolated from peach (Prunus persica) tissue and characterized. Spatio-temporal expression profiles of the genes were analyzed. Genes of the peach HD-ZIP III family were predicted to encode five conserved domains. Deduced amino acid sequences and tertiary structures of the four peach HD-ZIP III genes were highly conserved, with corresponding genes in Arabidopsis thaliana. The expression level of four targets displayed the opposite trend to that of miR166 throughout fruit development, with the exception of PpHB14 from 35 to 55 days after full bloom (DAFB). This finding indicates that miR166 may negatively regulate its four targets throughout fruit development. As for leaf and phloem, the same trend in expression level was observed between four targets and miR166 from 75 to 105 DAFB. However, the opposite trend was observed for the transcript level between four targets and miR166 from 35 to 55 DAFB. miRNA166 may negatively regulate four targets in some but not all developmental stages for a given tissue. The four genes studied were observed to have, exactly or generally, the same change tendency as individual tissue development, a finding that suggests genes of the HD-ZIP III family in peach may have complementary or cooperative functions in various tissues.
Assuntos
Genes de Plantas , Proteínas de Homeodomínio/genética , Zíper de Leucina , MicroRNAs/genética , Prunus persica/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/biossíntese , MicroRNAs/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Análise de Sequência de ProteínaRESUMO
The fruit peach originated in China and has a history of domestication of more than 4000 years. Numerous local cultivars were selected during the long course of cultivation, and a great morphological diversity exists. To study the diversity and genetic background of local peach cultivars in China, a set of 158 accessions from different ecological regions, together with 27 modern varieties and 10 wild accessions, were evaluated using 49 simple sequence repeats (SSRs) covering the peach genome. Broad diversity was also observed in local cultivars at the SSR level. A total of 648 alleles were amplified with an average of 13.22 observed alleles per locus. The number of genotypes detected ranged from 9 (UDP96015) to 58 (BPPCT008) with an average of 27.00 genotypes per marker. Eight subpopulations divided by STRUCTURE basically coincided with the dendrogram of genetic relationships and could be explained by the traditional groups. The 8 subpopulations were juicy honey peach, southwestern peach I, wild peach, Buddha peach + southwestern peach II, northern peach, southern crisp peach, ornamental peach, and Prunus davidiana + P. kansuensis. Most modern varieties carried the genetic backgrounds of juicy honey peach and southwestern peach I, while others carried diverse genetic backgrounds, indicating that local cultivars were partly used in modern breeding programs. Based on the traditional evolution pathway, a modified pathway for the development of local peach cultivars in China was proposed using the genetic background of subpopulations that were identified by SSRs. Current status and prospects of utilization of Chinese local peach cultivars were also discussed according to the SSR information.
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Evolução Biológica , Variação Genética , Repetições de Microssatélites/genética , Prunus persica/genética , Alelos , China , Ecótipo , Genética Populacional , Geografia , Heterozigoto , Linhagem , FilogeniaRESUMO
Zinc (Zn) is considered to be a major industrial pollutant because excessive amounts can impair plant growth. In this paper, we found that peach 'Yoshihime' seedlings are promising Zn tolerant plants. However, heavy Zn toxicity (2 mM) damaged plant performance by disrupting biochemical processes, including photosynthesis, proline production, and K(+) nutrition. Notably, elevated external K(+) supply (10 mM) alleviated peach seedlings from Zn toxicity, evidenced by enhanced photosynthesis, antioxidant defense systems, and plant K(+) nutritional status. Moreover, the transcript levels of KUP (K(+) uptake) genes involved in K(+) acquisition, transport, and homeostasis were significantly upregulated following supply of sufficient K(+) upon Zn toxicity. In general, K(+) favorably contributes to improvements in internal K(+) homeostasis, via the help of K(+) transporters, further protecting plant photosynthesis and the antioxidative defense system. Our findings further benefit the study of the mechanisms underpinning heavy metal tolerance in woody plants.
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Antioxidantes/metabolismo , Potássio/metabolismo , Plântula/metabolismo , Estresse Fisiológico/genética , Intoxicação por Metais Pesados , Fotossíntese , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Intoxicação , Prunus persica/efeitos dos fármacos , Prunus persica/metabolismo , Plântula/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Zinco/toxicidadeRESUMO
AIM: To investigate the recovery of thiazolidinedione-induced body weight gain and haematopoietic changes after stopping pioglitazone treatment in patients with Type 2 diabetes. METHODS: This retrospective cohort study included 214 patients divided into three groups according to pioglitazone treatment status. The first study arm included patients who received pioglitazone for 38 months then interrupted this for 10 months (pioglitazone-interruption group). The second arm consisted of patients who received pioglitazone throughout the 48 months (pioglitazone-continuous group); the third arm included patients who had never received pioglitazone therapy (control group). RESULTS: Red blood cell count and haematocrit and haemoglobin levels decreased significantly, while body weight increased in the two pioglitazone-treated groups as compared with the control group at 38 months. Multivariate regression analysis showed that the reductions in red blood cell count/haemoglobin levels were associated with pioglitazone use. In the pioglitazone-interruption group, no recoveries of red blood cells, or haematocrit or haemoglobin levels were observed after stopping pioglitazone for 10 months compared with the pioglitazone-continuous group, but body weight gain decreased to a level that was significantly lower than that in the pioglitazone-continuous group and did not differ significantly from the control group. CONCLUSION: In this study, we observed a reversal of body weight gain but no recoveries in red blood cells or haematocrit or haemoglobin levels after stopping pioglitazone for 10 months in patients treated with pioglitazone for 38 months. This finding should prompt a reconsideration of the sustained effect of thiazolidinediones on the haematopoietic system in patients with Type 2 diabetes.
Assuntos
Anemia/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Monitoramento de Medicamentos , Hematopoese/efeitos dos fármacos , Hipoglicemiantes/efeitos adversos , Tiazolidinedionas/efeitos adversos , Idoso , Anemia/complicações , Anemia/epidemiologia , Anemia/prevenção & controle , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Contagem de Eritrócitos , Feminino , Seguimentos , Hematócrito , Hemoglobinas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Sobrepeso/induzido quimicamente , Sobrepeso/complicações , Sobrepeso/epidemiologia , Sobrepeso/prevenção & controle , Pioglitazona , Estudos Retrospectivos , Risco , Taiwan/epidemiologia , Tiazolidinedionas/uso terapêutico , Aumento de Peso/efeitos dos fármacosRESUMO
Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatite C/transmissão , Viremia , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Masculino , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Doadores de Tecidos , Carga ViralRESUMO
In this study, 33 homeodomain-leucine zipper (HD-ZIP) genes were identified in peach using the HD-ZIP amino acid sequences of Arabidopsis thaliana as a probe. Based on the phylogenetic analysis and the individual gene or protein characteristics, the HD-ZIP gene family in peach can be classified into 4 subfamilies, HD-ZIP I, II, III, and IV, containing 14, 7, 4, and 8 members, respectively. The most closely related peach HD-ZIP members within the same subfamilies shared very similar gene structure in terms of either intron/exon numbers or lengths. Almost all members of the same subfamily shared common motif compositions, thereby implying that the HD-ZIP proteins within the same subfamily may have functional similarity. The 33 peach HD-ZIP genes were distributed across scaffolds 1 to 7. Although the primary structure varied among HD-ZIP family proteins, their tertiary structures were similar. The results from this study will be useful in selecting candidate genes from specific subfamilies for functional analysis.
Assuntos
Genoma de Planta , Proteínas de Homeodomínio/genética , Zíper de Leucina/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica/genética , Filogenia , Prunus , Fatores de TranscriçãoRESUMO
One of the most important uses of DNA markers is cultivar identification. However, no DNA fingerprint analysis strategy is available for making DNA markers helpful in practical plant cultivar identification, especially for the identification of a large number of cultivars. We developed a manual cultivar identification diagram strategy for efficient identification of plant cultivars, from which a cultivar identification diagram (CID) of genotyped plant individuals can be constructed manually. This CID could be used as a reference for quick identification of plant cultivars of interest. We used 11-mer RAPD primers to amplify DNA samples of 32 ornamental peach genotypes; all the cultivars were well distinguished by fingerprints from 6 primers. The utility of this CID was verified by identification of three randomly chosen groups of cultivars among the 32 ones that we selected. This CID generated will be useful for the identification of commercially important ornamental peach cultivars.
Assuntos
Prunus/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos , Impressões Digitais de DNA/métodos , Marcadores Genéticos , Genoma de PlantaRESUMO
BACKGROUND: Children's hand skills when performing in real-life contexts have been commonly thought as a possible determinant of their self-care function; however, there is a paucity of research investigating this potential predictive relationship. The purpose of this study was to provide evidence regarding whether children's real-life hand skill performance is contributive to or predictive of their self-care function by considering other child and cultural factors. METHODS: A total of 139 typically developing children and 114 with disabilities, ages 2-12 years from Australia and Taiwan, participated in the study. The outcome measures used were the Assessment of Children's Hand Skills (a measure of real-life hand skill performance) and the Personal Living Skills subscale of the Vineland Adaptive Behavior Scales - Classroom Edition (a measure of self-care function). RESULTS: Hierarchical regression analysis revealed that the children's demographic variables (age, gender, disability status, handedness and cultural context) accounted for 43% of the variance of the self-care function in the combined group of children with and without disabilities. Age, presence of disability and cultural context were the statistically significant independent factors. However, after the entry of the real-life hand skill performance factor, the contributing values of age and disability status decreased and the age factor became non-significant. The hand skill performance factor was found to be the strongest, and its addition led to significant increments of 24.6% of the explained variance for children's self-care function. Similar results were also found in the regression analyses based on separate groups of typically developing children or those with disabilities. CONCLUSIONS: The findings provide evidence that children's real-life hand skill performance is a contributing factor of their self-care function. The assessment of children's hand skill performance in real-life contexts is therefore needed.
Assuntos
Atividades Cotidianas , Crianças com Deficiência , Destreza Motora , Autocuidado , Fatores Etários , Austrália/epidemiologia , Criança , Pré-Escolar , Comparação Transcultural , Avaliação da Deficiência , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , Taiwan/epidemiologia , Análise e Desempenho de TarefasRESUMO
DNA markers have useful applications in cultivar identification. A novel analysis approach called cultivar identification diagram (CID) was developed using DNA markers in the separation of plant individuals. This new strategy is less time- and cost-consuming, has reliable results, and was constructed for fingerprinting. Ten 11-mer primers were used to amplify the genotypes; all 95 peach genotypes (from the National Peach Germplasm Repository, in Nanjing, China) were distinguished by a combination of 54 primers. The utilization of the CID among these 95 peach cultivars was also verified by the identification of three randomly chosen groups of cultivars. This identification showed some advantages including the use of fewer primers and easy separation of all cultivars by the corresponding primers marked in the right position on the CID. This peach CID could provide the information to separate any peach cultivars of these 95, which may be of help to the peach industry in China and for the utilization of DNA markers to identify other plant species.
Assuntos
DNA de Plantas/genética , Marcadores Genéticos , Prunus/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Sequência de Bases , Primers do DNARESUMO
We identified 131 AP2/ERF (APETALA2/ethylene-responsive factor) genes in material from peach using the gene sequences of AP2/ERF amino acids of Arabidopsis thaliana (Brassicaceae) as probes. Based on the number of AP2/ERF domains and individual gene characteristics, the AP2/ERF superfamily gene in peach can be classified broadly into three families, ERF (ethylene-responsive factor), RAV (related to ABI3/VP1), and AP2 (APETALA2), containing 104, 5, and 21 members, respectively, along with a solo gene (ppa005376m). The 104 genes in the ERF family were further divided into 11 groups based on the group classification made for Arabidopsis. The scaffold localizations of the AP2/ERF genes indicated that 129 AP2/ERF genes were all located on scaffolds 1 to 8, except for two genes, which were on scaffolds 17 and 10. Although the primary structure varied among AP2/ERF superfamily proteins, their tertiary structures were similar. Most ERF family genes have no introns, while members of the AP2 family have more introns than genes in the ERF and RAV families. All sequences of AP2 family genes were disrupted by introns into several segments of varying sizes. The expression of the AP2/ERF superfamily genes was highest in the mesocarp; it was far higher than in the other seven tissues that we examined, implying that AP2/ERF superfamily genes play an important role in fruit growth and development in the peach. These results will be useful for selecting candidate genes from specific subgroups for functional analysis.
Assuntos
Genoma de Planta , Família Multigênica , Proteínas de Plantas/metabolismo , Prunus/genética , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Expressão Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Íntrons , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Estrutura Terciária de Proteína , Fatores de Transcrição/química , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). RESULTS: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. CONCLUSIONS: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antígeno B7-H1/metabolismo , Fatores de Transcrição Forkhead , Microambiente TumoralRESUMO
Chronic hepatitis B virus (HBV)-infected patients with liver failure have a poor prognosis, and no satisfactory biomarkers are available for diagnosis before the end-stage. We explored serum peptide profiling for diagnosis and prediction of progression to liver failure in HBV-infected patients. Serum samples (164) from healthy subjects (n = 20), or subjects with chronic hepatitis B without cirrhosis and liver failure [chronic hepatitis B subjects without cirrhosis and liver failure (CHB); n = 33], with compensated liver cirrhosis (compensated liver cirrhosis (LC); n = 35), with acute-on-chronic liver failure [acute-on-chronic liver failure (ACLF); n = 38] or with chronic liver failure [chronic liver failure (CLF), n = 38] were applied to ClinProt magnetic beads, and bound peptides/proteins were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Our classification diagnostic models of liver disease were generated based on the Genetic Algorithm (GA) and Quick Classifier Algorithm (QC). Differentially expressed peptides were found among all test groups, with patterns of difference that readily distinguished between healthy and various HBV-associated liver disease samples. The model generated seven characteristic peptide peaks at 4053 m/z, 3506 m/z, 4963 m/z, 9289 m/z, 2628 m/z, 3193 m/z and 6432 m/z, giving overall predictive capability of 54.27%. Two-way comparisons of LC, ACLF or CLF vs CHB had predictive capabilities of 79.8%, 91.41% and 97.99%, respectively. Comparisons of ACLF or CLF vs LC were predictive at 87.72% and 82.18%, respectively and ACLF vs CLF was predictive at 75.05%. These classification diagnostic models generated by different peptide peaks were further validated in blinded tests with 67-100% accuracy. Serum peptide patterns vary during progression of chronic HBV infection to liver failure and may be used to distinguish different stages of the disease.
Assuntos
Biomarcadores/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Falência Hepática/diagnóstico , Falência Hepática/patologia , Peptídeos/sangue , Adulto , Idoso , Feminino , Hepatite B Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Soro/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto JovemRESUMO
AIM: The development of Type 2 diabetes mellitus (T2DM) has been recognized to be associated with a combination of pancreatic beta-cell dysfunction and insulin resistance. Nuclear factor-kappaB (NF-kappaB) has been recognized as one central mediator in the reaction of inflammation and proapoptotic event in beta-cells. A functional polymorphism at the codon 55 (methionine to valine; A163G) of the small ubiquitin- like modifier-4 (SUMO4) gene may result in higher NF-kappaB activity. This study investigates whether this SUMO4 Met55Val polymorphism also contributes to the development of T2DM. MATERIALS AND METHODS: The study was performed using genomic DNA samples from 574 Type 2 diabetic patients and 323 healthy controls. The SUMO4 Met55Val polymorphism was genotyped using allele-specific real-time PCR. RESULTS: The frequency of the G allele (encoding Val55) was significantly higher in Type 2 diabetic patients and Type 2 diabetic patients with the GG genotype had higher hemoglobin A1c level. Multivariate logistic regression analysis revealed the genotype of GG and GA was an independent risk factor contributing to the development of T2DM. CONCLUSION: This study suggests that in Taiwan the SUMO4 Met 55Val polymorphism is associated with susceptibility to T2DM and Type 2 diabetic patients with GG genotype have worse glycemic control.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , TaiwanRESUMO
BACKGROUND: Metabolic syndrome (MS) is considered a cause of abnormal deposition of fat into hepatocytes, which might be associated with hepatic steatosis or abnormal liver function. OBJECTIVE: The aim of this study was to explore the factors associated with MS and the relationship between MS and abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels in Taiwanese subjects without chronic hepatitis B (CHB) or C (CHC). SUBJECTS: We enrolled 2539 Taiwanese adults without CHB or CHC (age range: 16-88 years old) and investigated the factors related to MS using the NCEP-ATP (National Cholesterol Education Program-Adult Treatment Panel) III criteria; body mass index (BMI) was measured using Asia-Pacific criteria. RESULTS: The prevalence rate of MS in Taiwanese adults without CHB or CHC was 16.9% using the modified ATP III criteria and 15.4% using the International Diabetes Federation criteria. Males had a significantly higher prevalence rate than females (P<0.001), and subjects with MS were significantly older and had significantly higher BMI values and AST, ALT and GGT levels (all P<0.001). In univariate analyses, the abnormality of liver function test results were related to gender, level of fasting sugar, systolic blood pressure, triglyceride, high-density lipoprotein, BMI and MS (all P<0.05). Multivariate analysis showed that the male gender, a higher BMI value and MS were related to abnormal liver function test results. The cutoff value for ALT in relation to MS is 31 IU l(-1) for male and 18 IU l(-1) for female. CONCLUSION: The prevalence of MS in Taiwanese adults without hepatitis B or C was found to be high, and MS and BMI were identified as being related to abnormal liver function test results in these adults.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepatopatias/enzimologia , Síndrome Metabólica/enzimologia , Obesidade/enzimologia , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Hepatite B Crônica , Hepatite C Crônica , Humanos , Hepatopatias/epidemiologia , Testes de Função Hepática , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Taiwan/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Hepatite B/tratamento farmacológico , Hepatite B/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Ásia/epidemiologia , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Uso Indevido de Medicamentos/estatística & dados numéricos , Feminino , Mau Uso de Serviços de Saúde/estatística & dados numéricos , Hepatite B/complicações , Vírus da Hepatite B/fisiologia , Humanos , Prescrição Inadequada/estatística & dados numéricos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The long-term benefits of interferon-based therapy on preventing cirrhosis at non-cirrhotic stage in chronic hepatitis C patients are not fully clarified. AIM: To evaluate the effectiveness of interferon-based therapy regarding to cirrhosis prevention in non-cirrhotic chronic hepatitis C patients. METHODS: A total of 1386 biopsy-proven, non-cirrhotic chronic hepatitis C patients (892 received interferon-based therapy and 494 untreated) were enrolled. RESULTS: Fifty-six untreated and 51 treated (24 sustained virologic responders and 27 non-responders) patients developed cirrhosis during a mean follow-up period of 5.0 (1-16) and 5.1 (1-15.3) years, respectively. The annual incidences of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non-responders: 1.99%, sustained responders: 0.74%), respectively. The 15-year cumulative incidence of cirrhosis was significantly lower in treated (9.9%) than untreated patients (39.8%, P = 0.0008, log-rank test). The 14.5-year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) compared with non-responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001). The difference was not significant between non-responders and untreated controls. Cox proportional hazards regression showed sustained virologic responders and younger age were independent negative factors for cirrhosis development. CONCLUSION: A sustained virologic response secondary to IFN-based therapy could reduce cirrhosis development in chronic hepatitis C patients.