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Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.
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Niño , Preescolar , Femenino , Humanos , Masculino , Ceruloplasmina/metabolismo , Cobre/metabolismo , ATPasas Transportadoras de Cobre/genética , Degeneración Hepatolenticular/genética , Mutación , Fenotipo , Estudios RetrospectivosRESUMEN
Due to pediatric patients,there are the absence of clinical cases and the conflict between physicians and patients during teaching. Formative assessment(FA)is a teaching method to provide feedback and correctives at each stage in the teaching-learning process,which has been applied in clinical training for medical students and resident standardizing training recent years. Standardized patient(SP)is a simulated teaching tool,and when SPs are introduced in formative assessment by applied to history taking,patient education and counseling and communication skills. The combination not only solves the scarcity of clinical cases,but avoids doctor-patient contradiction. Therefore,SPs provide a broader application prospect for formative assessment. In fact,the combination offers new ideas for pediatric teaching.
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<p><b>OBJECTIVE</b>To explore risk factors of nonalcoholic fatty liver disease (NAFLD) in men in order to provide a theoretical basis for developing more effective NAFLD prevention and control strategies.</p><p><b>METHODS</b>One-hundred-and-two male patients (37.3+/-11.4 years old) hospitalized with NAFLD at the Dongnan Affiliated Hospital of Xiamen University between January 2009 and December 2010 were enrolled in the study, along with 23 age-matched healthy men (34.4+/-16.7 years old) to serve as the control group. The correlation(s) of body mass index (BMI; overweight defined as more than or equal to 22.717 kg/m2), waist circumference (WC), waist-to-hip ratio (WHR; central obesity defined as more than or equal to 0.866), fasting plasma glucose (FPG), triglyceride (TG), and total cholesterol (TC) with NAFLD was analyzed by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to select proper thresholds for classification.</p><p><b>RESULTS</b>BMI, WC, WHR, FPG, TG, and TC were significantly different between the cases and controls (P less than 0.01). BMI, WC, WHR, TG and TC were identified as risk factors of NAFLD in these male cases (P less than 0.01). Relative to WC, TG and TC, both BMI and WHR had significant predictive value for NAFLD (odds ratio (OR) = 10.819 and 10.588, respectively). In addition, BMI had the highest diagnostic value for the prediction of NAFLD (area under the curve (AUC) = 0.931) followed by WHR (AUC = 0.879).</p><p><b>CONCLUSION</b>BMI, WC, WHR, TG, and TC are risk factors of NAFLD in Chinese men. BMI and WHR are effective anthroposomatology indices of NAFLD and may be useful factors on which to base future prevention and early diagnosis strategies for NAFLD in males.</p>
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Humanos , Masculino , Índice de Masa Corporal , Enfermedad del Hígado Graso no Alcohólico , Factores de Riesgo , Circunferencia de la Cintura , Relación Cintura-CaderaRESUMEN
<p><b>OBJECTIVE</b>To determine the influences of Mannose binding protein (MBP) gene polymorphisms on HBV DNA loads and on the progression of liver disease in patients with chronic HBV infection.</p><p><b>METHOD</b>The Codons on 54 MBP gene polymorphisms and HBV DNA loads in a cohort of 395 patients with chronic HBV infection, including 244 with chronic hepatitis B (CHB), 151 with liver cirrhosis (LC) and 88 normal controls were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and fluorescent quantitative PCR (FQ-PCR).</p><p><b>RESULT</b>The MBP genotype frequencies of GGC/GAC and alleles genetic frequencies of GAC in CHB group showed no significant differences comparing to the normal control group (P > 0.05). The MBP genotype frequencies of GGC/GAC and alleles genetic frequencies of GAC on CHB group (severe), compensation phase of LC group and decompensation phase of LC group were higher than those in the normal control group (P < 0.05), the genetic polymorphism of decompensation of LC was 36.5%, highest of all. The MBP genotype frequencies of GGC/GAC and alleles genetic frequencies of GAC of patients with chronic HBV infection were not changed with the differences of HBV-DNA loads.</p><p><b>CONCLUSION</b>The codes on 54 MBP gene polymorphisms is not closely related to HBV DNA loads, but was associated with the progression of hepatitis B infection.</p>
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Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Cohortes , ADN Viral , Progresión de la Enfermedad , Frecuencia de los Genes , Genotipo , Hepatitis B Crónica , Genética , Lectina de Unión a Manosa , Genética , Polimorfismo GenéticoRESUMEN
<p><b>OBJECTIVE</b>To study changes of glycolipid metabolism and adipocyte function in an catch-up growth intrauterine growth retardation (IUGR) rat model.</p><p><b>METHODS</b>IUGR rat model was established by maternal nutrition restriction during pregnancy. Newborn IUGR pups were used as IUGR group, and normal newborn pups were used as control group (appropriate for gestational age, AGA group). At age of 12 weeks, plasma samples were collected for the test of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), adiponectin and acylation stimulating protein (ASP). Oral glucose tolerance test (OGTT) was performed for the test of glucose and insulin levels, and insulin resistance index (IRI) was calculated. Expression of glucose transfer 4 (GLUT-4) in adipocytes was examined by confocal microscopy.</p><p><b>RESULTS</b>Body weight and BMI in the IUGR group were significantly higher than in the AGA group by 12 weeks (P<0.01), and plasma TC, TG and LDL-C levels in the IUGR group were higher than in the AGA group, but HDL-C was lower (P<0.05). In the OGTT test, blood glucose level and IRI score in the IUGR group were higher than in the AGA group (P<0.05). Compared with the AGA group, the IUGR group had a higher ASP level (P<0.05) and a lower adiponection level (P<0.05). GLUT4 expression in the adipocytes was significantly lower in the IUGR group than in the AGA group (P<0.05).</p><p><b>CONCLUSIONS</b>Catch-up growth may be obviously noted in IUGR rats after birth. Both hyperlipidaemia and insulin resistance occur at age of 12 weeks. Dysfunction of adipocytes decreased expression of GLUT-4 may be risk factors for insulin resistance in IUGR rats.</p>
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Animales , Femenino , Masculino , Ratas , Adipocitos , Fisiología , Glucemia , Índice de Masa Corporal , Peso Corporal , Metabolismo de los Hidratos de Carbono , Retardo del Crecimiento Fetal , Transportador de Glucosa de Tipo 4 , Metabolismo de los Lípidos , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To investigate the expression of RUNX3 mRNA and protein in hepatic cell carcinoma (HCC) and surrounding normal tissue, to analyze the relationship between RUNX3 expression and clinical pathological parameters.</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were performed to detect the expression of RUNX3 mRNA and protein in HCC and surrounding normal tissue respectively, and their relationship with clinical pathological parameters were analyzed.</p><p><b>RESULTS</b>The relative expression value of RUNX3 mRNA found in 51 cases HCC was 0.4509 +/- 0.0963, and that did in 51 cases surrounding normal tissue was 0.9147 +/- 0.0222. The difference of RUNX3 mRNA expression between two kinds of samples was statistically significant (t = 33.6087, P < 0.001). The positives rate of RUNX3 protein expression found in 51 cases HCC tissue was 49.02% (25/51) and that did in 51 cases surrounding normal tissue was 82.35% (42/51). The difference of RUNX3 protein expression between two kinds of samples was statistically significant (chi2 = 12.5706, P < 0.005). The difference of RUNX3 mRNA and protein expression in some clinical pathological parameters involving differentiation degree, invasion, cancer thrombus and diversion in liver were statistically significant (P < 0.05). However that were not in another clinical pathological parameters involving gender, cancer diameter, cancer location as well as hemorrhage and necrosis of cancer, histotype (P > 0.05).</p><p><b>CONCLUSION</b>The expression of RUNX3 mRNA and protein in HCC were significantly lower than that in surrounding normal tissue. The lower expression of runx3 protein in the HCC probably plays an important role in the tumorigenesis and development of HCC. The RUNX3 gene may be an anti-oncogene of HCC.</p>
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Femenino , Humanos , Masculino , Carcinoma Hepatocelular , Química , Patología , Subunidad alfa 3 del Factor de Unión al Sitio Principal , Genética , Fisiología , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Química , Patología , ARN MensajeroRESUMEN
<p><b>OBJECTIVE</b>This study examined the effects of PI3K inhibitor LY294002 on the differentiation of mouse preadipocytes and the expression of CCAAT enhancer binding protein α (C/EBPα) and peroxisome proliferation activated receptor γ (PPARγ), in order to study the possible roles of insulin receptor substrate (IRSs)/PI3K signal pathway in the differentiation of preadipocytes.</p><p><b>METHODS</b>The mouse 3T3-L1 cells were cultured normally and divided into experimental and control groups. 3T3-L1 cells in the experimental group were treated with PI3K inhibitor LY294002 (25 μmol/L) and those in the control group were treated with DMSO culture medium. 3-isobutyl-1-methylxanthine (IBMX) (0.5 mmol/L), dexamethasone (10-6 mol/L) and insulin (5 μg/mL) were used to induce the differentiation of 3T3-L1 preadipocytes in both groups. Before culture, and 2, 4 and 8 days after culture, the cells were collected to detect the expression of C/EBPα and PPARγ by real-time PCR and Western blot assays. The lipid droplets of 3T3-L1 preadipocytes were observed by oil-red O staining.</p><p><b>RESULTS</b>PI3K inhibitor LY294002 did not affect the expression of C/EBPα and PPARγ in un-induced 3T3-L1 preadipocytes (P>0.05), but decreased the expression of C/EBPα and PPARγ during the in vitro induced differentiation of 3T3-L1 preadipocytes compared with the control group (P<0.05 or 0.01). The lipid droplets count was greatly reduced by LY294002.</p><p><b>CONCLUSIONS</b>PI3K inhibitor LY294002 can inhibit the differentiation of mouse 3T3-LI preadipocytes and the expression of C/EBPα and PPARγ in the differentiation of 3T3-LI preadipoeytes, suggesting that IRSs/PI3K signal pathway may play an important role in the differentiation of 3T3-L1 preadipocytes by regulating the expression of C/EBPα and PPARγ.</p>
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Animales , Ratones , Células 3T3-L1 , Adipocitos , Biología Celular , Proteína alfa Potenciadora de Unión a CCAAT , Genética , Diferenciación Celular , Cromonas , Farmacología , Regulación de la Expresión Génica , Morfolinas , Farmacología , PPAR gamma , Genética , Fosfatidilinositol 3-Quinasas , ARN MensajeroRESUMEN
<p><b>OBJECTIVE</b>To investigate the expression of RUNX3 protein in hepatic cell carcinoma (HCC) and its relationship with the clinicopathological factors of HCC.</p><p><b>METHODS</b>Immunohistochemistry was performed to detect the expression of RUNX3 protein in HCC and the surrounding normal tissues, and the relation of RUNX3 with the clinicopathological factors of HCC was analyzed.</p><p><b>RESULTS</b>The positivity rate of RUNX3 protein expression was 49.02% (25/51) in HCC tissues, significantly lower than that in the surrounding normal tissues [82.35% (42/51), Χ(2)=12.5706, P<0.01). RUNX3 protein expression varied significantly with such pathological factors as the differentiation degree, cancer-associated thrombosis in the portal vein and intrahepatic metastasis (P<0.05), but not with tumor diameter, location, tumoral hemorrhage, necrosis or histotypes of the tumor (P>0.05).</p><p><b>CONCLUSION</b>RUNX3 protein expression is lowered in HCC as compared with that in the surrounding normal tissue, suggesting an important role of RUNX3 in the tumorigenesis and development of HCC and the possible identity of RUNX3 gene as an anti-oncogene of HCC.</p>
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Femenino , Humanos , Masculino , Carcinoma Hepatocelular , Genética , Metabolismo , Patología , Subunidad alfa 3 del Factor de Unión al Sitio Principal , Genética , Metabolismo , Regulación hacia Abajo , Genes Supresores de Tumor , Neoplasias Hepáticas , Genética , Metabolismo , Patología , Proteínas Supresoras de Tumor , Genética , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the correlation between nonalcoholic fatty liver disease (NAFLD) and three anthropometric indices, namely waist to hip ratio (WHR), body mass index (BMI) and waist to height ratio (WHtR).</p><p><b>METHODS</b>This retrospective case-control study involved 77 NAFLD patients and 50 patients without such disease, and their data of the 3 anthropometric indices were collected. Risk correlation analysis and Mantel-Haenszel chi-square test were used for correlation analysis.</p><p><b>RESULTS</b>NAFLD was significantly correlated to WHR (chi(2)(MH)=59.609, P<0.001; odds ratio=30.522, 95% CI 12.815-72.695), WHtR (chi(2)(MH)=45.316, P<0.001; odds ratio=21.037, 95% CI 8.665-51.072) and showed a dose-response relationship with BMI (chi(2)=25.017, P<0.001).</p><p><b>CONCLUSION</b>These results support a close correlation between NAFLD and the 3 anthropometric indices, indicating that BMI, WHR and WHtR can be significant predictors of NAFLD and have potential value for evaluating and predicting NAFLD.</p>
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Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antropometría , Constitución Corporal , Estatura , Índice de Masa Corporal , Estudios de Casos y Controles , Hígado Graso , Diagnóstico , Enfermedad del Hígado Graso no Alcohólico , Estudios Retrospectivos , Circunferencia de la Cintura , Relación Cintura-CaderaRESUMEN
<p><b>OBJECTIVE</b>Preparing rat model of non-alcoholic fatty liver disease by fat-rich diet to observe the expression and the role of LXR-alpha in rat nonalcoholic fatty liver disease.</p><p><b>METHODS</b>Thirty-six SD rats were randonmized into basic diet-control group and high-fat diet group. Each of the two groups was subdivided into 3 subgroups (4, 8, 12 weeks). Changes in animal weight, liver exponent and the level of TG and TC in serum and liver were observed dynamically. Meanwhile,the expression of hepatocyte LXR-alpha and SREBP-1c were assayed by Reverse transcript-polymerase chain reaction at 4, 8, 12 weeks. The level of steatosis was observed under light microscope after haematoxylon-eosin (HE) staening.</p><p><b>RESULTS</b>Compared with control group, body weight, liver exponent, TG and Tc in serum and liver were increased dynamically in model groups. Compared with control group, the mRNA of LXR-a and SREBP-1c were obviously increased dynamically in model groups (P < 0.05) .</p><p><b>CONCLUSION</b>The increase of LXR-alpha and SREBP-1c in liver may be concered with energy disorder and closely associated with the activity of inflammation and the severity of the liver damage in NAFLD rats.</p>
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Animales , Humanos , Masculino , Ratas , Modelos Animales de Enfermedad , Hígado Graso , Genética , Metabolismo , Receptores X del Hígado , Receptores Nucleares Huérfanos , Genética , Metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Genética , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of interferon -alpha1b (IFN-alpha1b) on hepatic intercellular adhesion molecule-1 (ICAM-1) expression and serum HBV DNA in patients with chronic hepatitis B.</p><p><b>METHODS</b>Before and 6 months after IFN-alpha1b treatment, liver biopsy was performed in patients with chronic hepatitis B to detect the expression of ICAM-1 in the liver tissues using immunohistochemistry. Serum HBV load was detected with real-time fluorescence polymerase chain reaction.</p><p><b>RESULT</b>CAM-1 expression in the liver tissue was significantly down-regulated after IFN treatment in patients with severe and moderate chronic hepatitis B (P<0.05). No significant variation was noted in the expression of ICAM-1 in the livers of patients with mild chronic hepatitis B after the treatment (P>0.05). In the patients weakly positive for ICAM-1 expression (+), serum HBV DNA varied scarcely after the treatment (P>0.05), while in the patients with strong ICAM-1 positivity (++, +++, or ++++), significant variation of serum HBV DNA occurred after the treatment (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>The therapeutic effect of IFN-alpha1b is associated with the expression of ICAM-1 in the hepatocytes, and its expression might enhance the effects of IFN on HBV DNA in patients with chronic hepatitis B.</p>
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Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , ADN Viral , Sangre , Virus de la Hepatitis B , Genética , Hepatitis B Crónica , Sangre , Quimioterapia , Virología , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular , Interferón-alfa , Usos Terapéuticos , Hígado , Metabolismo , Virología , Reacción en Cadena de la Polimerasa , Métodos , Carga ViralRESUMEN
<p><b>OBJECTIVE</b>To study the pathological and clinical features of nonalcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>Grades and stages of liver lesions in 41 patients with NAFLD were analyzed. The relationships between pathohistological features of the livers, serum biochemical parameters, ultrasound examination and other clinical data of the patients were studied.</p><p><b>RESULTS</b>Among the 41 patients with NAFLD (there were 21 with their liver fatty degeneration in grade 1, 15 in grade 2, and 5 in grade 3). There were 2 of grade 0, grade 1 had 25, grade 2 had 10, grade 3 had 3, and grade 4 had 1. Stage 0 of fibrosis was 20, stage 1 was 14, stage 2 was 4, stage 3 was 2, and stage 4 was 1. Degree of fatty degeneration was not positively associated with the body mass index (BMI) of the patients and the ultrasound findings in their livers. Grading of the inflammation was positively related to the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the blood and ultrasound findings in their livers, but negatively to the platelet counts. Staging of fibrosis of the livers was positively related to the blood ALT, AST, GGT, and ALP, and negatively to triglyceride levels and platelet counts.</p><p><b>CONCLUSIONS</b>Degree of liver fatty degeneration was not associated with grades of inflammation and staging of fibrosis of the liver. BMI, ALT and AST level, platelet counts, and ultrasound grades of fatty liver were associated with the liver histopathological changes of NAFLD patients. Liver biopsy is the essential way to make a diagnosis of NAFLD.</p>
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Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biopsia con Aguja , Hígado Graso , Diagnóstico , Diagnóstico por Imagen , Patología , Hígado , Diagnóstico por Imagen , Patología , UltrasonografíaRESUMEN
<p><b>OBJECTIVE</b>To investigate the clinicopathological features of nonalcoholic steatohepatitis (NASH) and elucidate its diagnosis and differential diagnosis.</p><p><b>METHODS</b>Liver biopsy tissues and clinical data of 32 patients with NASH were collected and the clinicopathological findings by HE and Masson staining were evaluated for NASH grading.</p><p><b>RESULTS</b>Ballooning degeneration of the liver cells and fibrosis around hepatic sinusoid was scarce in mild NASH cases and increased in moderate to severe cases. Steatotic and inflammatory cells in the liver lobes decrease in liver cirrhosis related to seatohepatitis.</p><p><b>CONCLUSION</b>Ballooning degeneration of the liver cells and fibrosis around the hepatic sinusoid have important value in differential diagnosis of mild from moderate to severe NASH, and correct histological grading benefits clinical intervention and prognostic evaluation of NASH.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biopsia con Aguja , Diagnóstico Diferencial , Hígado Graso , Diagnóstico , Patología , Interpretación de Imagen Asistida por Computador , Hígado , Patología , PronósticoRESUMEN
<p><b>OBJECTIVE</b>To study histological changes of the livers in patients with chronic viral hepatitis B treated with bicyclol tablets.</p><p><b>METHODS</b>Thirty one patients with chronic viral hepatitis B were divided into two groups and were treated with bicyclol orally at doses of 150 mg daily or 75 mg daily for 36 weeds. The histological changes of the livers were observed before and after the treatment.</p><p><b>RESULTS</b>Compared with pre-treatment findings, there were significant differences in histological activity index in each group (P < 0.01, P < 0.05), there were also significant differences between the two groups (P < 0.05). Decreased inflammatory reaction was also seen (P < 0.05).</p><p><b>CONCLUSION</b>Daily use of 150 mg and 75 mg bicyclol tablets are effective in improving liver histological changes in chronic hepatitis B patients. Bicyclol 150 mg daily was better.</p>