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Objective: To establish the normal reference for iQ200 urine component analyzer of healthy adults in Guangzhou area. Methods: Five hundreds and four normal urine samples were screened from the healthy population with the normal dry chemistry results of urine and normal biochemical results of plasma, and the RBC, WBC and epithelial cells were determined by iQ200 urine component analyzer. Then 1 ml urine was accurately collected from the samples by centrifugation and the RBC, WBC and epithelial cells were counted with neubauer counter by two inspectors. The samples were divided into 4 groups according to the age (18-45 years and >45 years old) and sex (male and female). The counts of RBC, WBC and epithelial cell of 4 groups with iQ200 urine component analyzer and neubauer counter were statistically analyzed. Results: The difference was not significant in RBC, WBC and epithelial cells between the results of iQ200 urine component analyzer and the results of neubauer counter(all P>0.05). There was not significant difference of RBC, WBC and epithelial cells of the same sex and different age groups (all P>0.05). There was significant difference of RBC, WBC and epithelial cells between the different gender groups(all P<0.05). The 95% confidence interval reference range of iQ200 urine component analyzer were as follows: RBC 0-7 cells/µl (male), 0-8 cells/µl (female); WBC 1-6 cells/µl (male), 1-8 cells/µl (female); epithelial cells 0-2 cells/µl (male), 0-8 cells/µl (female). Conclusion: The reference of this research of iQ200 urine component analyzer will be useful for the laboratory and clinic, but still need the verification experiment before using in the laboratory.
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Urinálise , Adolescente , Adulto , Contagem de Células , Centrifugação , Células Epiteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto JovemRESUMO
Objective: To investigate the relationship between the radioresistance of pancreatic cancer cell SW1990 and the induction of the Epithelial-Mesenchymal Transition (EMT). Methods: The radio-resistant pancreatic cancer cell SW1990-R were established by using the method of radiating pancreatic cancer cell SW1990 step by step and repeatedly. Then the changes of the morphology of the cell was observed by inverted phase contrast microscope, the radioresistance of SW1990-R was detected by colony-forming assay, and the apoptosis rate of the two cell lines after radiation were measured by flow cytometry. Then invasiveness and EMT-related genes was measured by trans-well test and qRT-PCR. Finally, the model of transplanted tumor on nude mouse was used to confirm the relationship between the radioresistance of pancreatic cancer cell SW1990 and the induction of EMT. Results: Compared with SW1990, SW1990-R had a lower radiosensitivity (survival fraction in 2 Gy, SF2: 0.326 3±0.007 3 vs 0.840 8±0.001 9, P<0.05) and lower apoptosis rate[(6.12±1.27) % vs (16.87±1.73)%, P<0.05]. Meanwhile, the invasive ability of SW1990-R were significant higher than that of SW1990 cell. According to the result of both in vivo and in vitro experiment, SW1990-R had a higher expression level of Vimentin and Snail, and lower expression level of E-cadherin when compared with SW1990. Conclusion: Compared with SW1990, the radio-resistant pancreatic cancer cell SW1990-R can induce the Epithelial-mesenchymal transition.
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Neoplasias Pancreáticas , Animais , Apoptose , Caderinas , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Camundongos , PâncreasRESUMO
Objective: To study the relationship between the changes of brain network and cognition in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) by using long term video electroencephalogram (VEEG) and resting-state functional magnetic resonance imaging (RS-fMRI) technology. Methods: Eleven patients with right-handed were recruited (from April 2015 to September 2016) from epilepsy specialist outpatients and functional department of neurosurgery of Tianjin Medical University General Hospital. They all underwent the long term VEEG monitoring (one sleep cycle was included at least). According to the spike-wave index (SWI) during slow ware sleep, they were divided into two groups: SWI<50% (5 cases) and SWI≥50% (6 cases). All the patients were assessed with cognitional test including language, execution, memory and attention. They also underwent the head MRI, RS-fMRI examinations. Then the results were comparatively analysed. Results: (1)There were no statisticaly significance in sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). The Full Intelligence Quotient (FIQ) (87±18), Verbal Intelligence Quotient (VIQ) (88±15) and Performance Intelligence Quotient (PIQ) (89±20) of SWI≥50% group were lower than SWI<50% group(118±8, 114±11, 119±5) and the differences were statistically significant(P<0.05). (2)There was a negative correlation between the FIQ (P=0.002), VIQ (P=0.006), PIQ (P=0.001) and SWI. The FIQ, VIQ and PIQ had no correlation with the sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). (3)Compared with SWI<50% group, SWI≥50% group showed increased regional homogeneity (ReHo) in the bilateral precentral gyrus, premotor area and the subcortical structure, the right temporal lobe and the bilateral insular lobe(P<0.05); while they showed decreased ReHo in the posterior cingulate gyrus, right posterior inferior temporal lobe and right occipital lobe(P<0.05). Conclusion: The change of the brain network which is caused by the paradoxical and constant discharge during slow ware sleep in patients with BECTS may affect the development of cognition.
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Transtornos Cognitivos/diagnóstico por imagem , Eletroencefalografia , Epilepsia Rolândica/complicações , Imageamento por Ressonância Magnética , Cognição , Transtornos Cognitivos/etiologia , Humanos , Descanso , Gravação em VídeoRESUMO
Recent evidence suggests that genetic variations in the IGFBP-3 gene may impact susceptibility to colorectal cancer, but individually published results are inconclusive. Our meta-analysis was aimed at providing a more precise estimation of these associations. An extensive literature search was conducted for appropriate articles published before May 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence interval (CI) were calculated. Eleven case-control studies were included with a total of 11,895 colorectal cancer patients and 17,147 healthy controls. Our meta-analysis indicated that the G variant of IGFBP-3 C2133G polymorphism may be associated with increased colorectal cancer risk. However, no statistically significant association was noted between IGFBP-3 A-202C polymorphism and colorectal cancer risk. No publication bias was detected in this meta-analysis. The current meta-analysis suggests that the IGFBP-3 C2133G polymorphism may confer susceptibility to colorectal cancer. The G variant of the IGFBP-3 C2133G polymorphism may serve as a useful biomarker for predicting the risk of colorectal cancer.
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Neoplasias Colorretais/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
AIM: Stoma reversal is frequently complicated by surgical site infection (SSI). To reduce SSI, several techniques for skin closure have been studied, with no agreement on which is best. The aim of this study was to identify the skin closure technique associated with the lowest rate of SSI following stoma reversal. METHOD: We systematically searched MEDLINE (PubMed and OvidSP), Scopus and clinical registries from 1 January 1980 to 24 March 2012, and included original reports on adult patients following stoma reversal. A network of treatments was created to map the comparisons between skin closure techniques, including primary closure, primary closure with a drain, secondary closure, delayed primary closure, loose primary closure and circular closure. Pairwise meta-analyses were performed for all available direct comparisons of closure types and heterogeneity was assessed. A multiple-treatments meta-analysis was conducted to estimate relative treatment effects between competing closure types (reported as an odds ratio with 95% credible interval, and a probability that each treatment is best). Several sensitivity analyses were performed. RESULTS: Fifteen studies were identified with a total of 2921 cases of stoma reversal. Overall, study quality was poor with observed low (one study), moderate (seven studies) and high (seven studies) risk of bias. Circular closure was associated with the lowest SSI risk (OR 0.12; 95% CI 0.02-0.40) and was the best of six skin closure techniques (probability of being best = 68.9%). Circular closure remained the best after sensitivity analyses. CONCLUSION: This study showed that circular closure is the best skin closure technique after stoma reversal in terms of SSI rate, but the quality of supporting evidence is limited, precluding definite conclusions.
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Procedimentos Cirúrgicos Dermatológicos/métodos , Estomas Cirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Técnicas de Fechamento de Ferimentos , Saúde Global , Humanos , Incidência , Reoperação/métodosRESUMO
Many existing studies have demonstrated that common polymorphisms in the hypoxia inducible factor-1α (HIF-1A) may contribute to the development of digestive tract cancers, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a precise estimation of the relationships between HIF1A Pro582Ser polymorphism and the risk of digestive tract cancers. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through May 1, 2013. Meta-analysis was performed using the STATA 12.0 software. We assessed 6 case-control studies that included a total of 911 digestive tract cancer patients and 2774 healthy controls. Our meta-analysis indicated that HIF1A Pro582Ser polymorphism was associated with an increased risk of digestive tract cancer. Subgroup analysis by ethnicity suggested that HIF1A Pro582Ser polymorphism might increase an individual's susceptibility to digestive tract cancer in Asian populations. However, similar association was not observed in Caucasian populations. In conclusion, our findings suggest that HIF1A Pro582Ser polymorphism may contribute to the risk of digestive tract cancers, especially in Asian populations.
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Substituição de Aminoácidos , Neoplasias do Sistema Digestório/genética , Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Polimorfismo Genético , Alelos , Estudos de Casos e Controles , Códon , Genótipo , Humanos , Razão de ChancesRESUMO
A set of 120 simple sequence repeats (SSRs) was developed from the newly assembled pear sequence and evaluated for polymorphisms in seven genotypes of pear from different genetic backgrounds. Of these, 67 (55.8 %) primer pairs produced polymorphic amplifications. Together, the 67 SSRs detected 277 alleles with an average of 4.13 per locus. Sequencing of the amplification products from randomly picked loci NAUPy31a and NAUpy53a verified the presence of the SSR loci. When the 67 primer pairs were tested on 96 individual members of eight species in the Rosaceae family, 61.2 % (41/67) of the tested SSRs successfully amplified a PCR product in at least one of the Rosaceae genera. The transferability from pear to different species varied from 58.2 % (apple) to 11.9 % (cherry). The ratio of transferability also reflected the closer relationships within Maloideae over Prunoideae. Two pear SSR markers, NAUpy43c and NAUpy55k, could distinguish the 20 different apple genotypes thoroughly, and UPGMA cluster analysis grouped them into three groups at the similarity level of 0.56. The high level of polymorphism and good transferability of pear SSRs to Rosaceae species indicate their promise for application to future molecular screening, map construction, and comparative genomic studies among pears and other Rosaceae species.
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Classical laws of friction suggest that friction force is proportional to the normal load and independent of the nominal contact area. As a great improvement in this subject, it is now widely accepted that friction force is proportional to the real contact area, and much work has been conducted based on this hypothesis. In present study, this hypothesis will be carefully revisited by measuring the friction force and real contact area in-site and real-time at both normal loading and unloading stages. Our experiments reveal that the linear relation always holds between friction force and normal load. However, for the relation between friction force and real contact area, the linearity holds only at the loading stage while fails at the unloading stage. This study may improve our understanding of the origin of friction.
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Sera from 28 patients with renal cancer were tested for reactivity with surface antigens of cultured autologous renal cancer cells. Four serological assays were used to survey sera for autologous antibody. Immune adherence, protein A, and C3-mixed hemadsorption assays detected reactivity in a high percentage of patients (80-100%), whereas mixed hemadsorption assays were negative with sera from all but one patient. Reactive sera from six patients were analyzed by absorption tests with autologous, allogeneic, and restricted to autologous renal cancer cells; class 2 antigens, present on certain allogeneic renal and nonrenal cancer cells; and class 3 antigens, found on a wide variety of normal and malignant cell types. The sera of one patient detected class 1, 2, and 3 antigens, the sera of three patients detected class 2 antigens, and the sera of two patients detected class 3 antigens. This analysis of renal cancer, with the recognition of three classes of surface antigens recognized by autologous sera, resembles the results of autologous typing of three other human malignancies: malignant melanoma, acute leukemia, and astrocytoma. Evidence provided by autologous typing of these cancers indicates that class 1 and class 2 antigens are tumor-restricted and that under certain circumstances these antigens are immunogenic for the autologous host.
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Anticorpos Antineoplásicos , Antígenos de Neoplasias , Antígenos de Superfície , Neoplasias Renais/imunologia , Adulto , Idoso , Técnicas de Cultura , Feminino , Testes de Inibição da Hemadsorção , Humanos , Rim/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Experimentais/imunologia , Formação de RosetaRESUMO
AH antigen, initially defined by an antibody present in a melanoma patient, is a cell surface antigen found on approximately 65% of melanoma cell lines. Absorption analysis indicates that AH is a differentiation antigen marking normal and malignant cells of neuroectodermal origin. The AH determinant has been found to be related to GD2 ganglioside.
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Antígenos de Neoplasias/análise , Antígenos/análise , Autoantígenos/análise , Gangliosídeo G(M2)/imunologia , Gangliosídeos/imunologia , Melanoma/imunologia , Antígenos de Neoplasias/imunologia , Ligação Competitiva , Linhagem Celular , Gangliosídeo G(M2)/farmacologia , Humanos , FenótipoRESUMO
OBJECTIVE: To investigate the clinical and pathological characteristics of thyroid nodules, as well as to evaluate the significance of ultrasonographically detected thyroid calcification in the diagnosis of thyroid carcinomas. METHODS: Retrospective data were studied from 1,051 consecutive patients who underwent a thyroidectomy in the Provincial Hospital of Fujian Medical University in South China between January 2003 and July 2006 for nodular thyroid disease. Complete sonographical information before surgery was only collected from 758 of the 1,051 patients. RESULTS: Among the 1,051 patients, benign lesions were found in 857 (81.54%) patients, of whom 612 (71.41%) were nodular goiter; malignant lesions were found in 194 (18.46%) patients, in whom benign thyroid lesions were also found in 85 (43.81%) patients. A total of 48 patients suffered from microcarcinomas, of whom 37 patients had benign lesions; these 37 accounted for 43.53 and 77.08%, respectively, of the 85 malignant cases with benign lesions and the 48 cases with microcarcinomas. In the 758 patients who underwent thyroid ultrasonography before surgery, intrathyroidal calcifications were apparent in 243 patients (32.06%). The incidence of calcification was significantly higher in patients with thyroid carcinoma (54.17%) than in those with benign lesions (26.87%; p < 0.005). Detection of calcification in thyroid lesions by ultrasound had a sensitivity of 32.38% and a specificity of 87.35%, with an OR of 3.31 (95% CI, 2.24-4.63), positive likelihood ratio of 2.56, negative likelihood ratio of 0.77 and a kappa value of 0.23. CONCLUSION: Thyroid carcinoma, especially microcarcinoma, often coexists with benign thyroid disease. Calcification detected by thyroid ultrasound represents a risk factor for malignancy, but is of limited use as a sole marker of malignancy.
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Calcinose/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Criança , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia , Ultrassonografia , Adulto JovemRESUMO
AIMS: Considering the effect of natural fermentation on the textural improvement of fermented rice noodles in China and South Asia, and given the lack of reports concerning microbial populations and structure in the fermentation process, this study aims to determine the number of viable micro-organisms and identify the species isolated from the local factories, and to assess their potential use as a starter culture from their enzymatic profiles. METHODS AND RESULTS: Fourteen samples from three local factories were analysed for the presence of micro-organisms. A total of 170 lactic acid bacteria (LAB) and 96 yeasts were isolated from the factories. The isolates were phenotypically characterized by using API 50 CHL kits, API 20 Strep kits, API ID 32 C kits and by performing additional biochemical tests. The enzymatic profiles of isolates were assessed by using API ZYM kits. Lactobacillus plantarum and Saccharomyces cerevisiae were identified as predominant species in the fermented supernatants. A majority of the isolates of LAB and yeasts displayed activities of alpha-glucosidase, beta-glucosidase, lipase and trypsin. CONCLUSIONS: The microbial composition and strain characteristics present in the fermentation supernatant demonstrate that a majority of micro-organisms have the ability to digest starch, sugar, protein or lipid. It supports our previous work in which the rice starch was modified and purified by fermentation and thus improves the texture of rice noodles. SIGNIFICANCE AND IMPACT OF THE STUDY: The dominant strains would be important in developing a starter culture. The results can form the basis for the improvement of product quality and consistency.
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Microbiologia de Alimentos , Microbiologia Industrial , Lactobacillus/isolamento & purificação , Oryza/microbiologia , Saccharomyces cerevisiae/isolamento & purificação , Ácido Acético/análise , China , Contagem de Colônia Microbiana , Fermentação , Manipulação de Alimentos/métodos , Concentração de Íons de Hidrogênio , Ácido Láctico/análise , Lactobacillus/enzimologia , Oryza/química , Saccharomyces cerevisiae/enzimologiaRESUMO
In this study, a thermostable recombinant xylanase B (XynB) from Thermotoga maritima MSB8 was immobilized on nickel-chelated Eupergit C 250L. This immobilized XynB was then used to hydrolyze the autohydrolysis explosion liquor of corncob (AELC) in a packed-bed enzyme reactor for continuous production of xylooligosaccharides, especially xylobiose. When tested in batch hydrolysis of AELC, the immobilized XynB still retained its relative activity of 92.5% after 10 cycles of hydrolysis at 90 degrees C. The immobilized XynB retained 83.6% of its initial hydrolysis activity even after 168 h of hydrolysis reaction at 90 degrees C and demonstrated a half-life time of 577.6 h (24 days) for continuous hydrolysis. HPLC showed that xylobiose (49.8%) and xylose (22.6%) were the main hydrolysis products yielded during continuous hydrolysis. Xylobiose was adsorbed on an activated charcoal column and eluted with a linear gradient of 15% (v/v) ethanol to yield xylobiose with 84.7% of recovery. Also, the purity of xylobiose was up to 97.2% as determined by HPLC. Therefore, the immobilized XynB was suitable for the efficient production of xylobiose from AELC. This is the first report on the immobilization of xylanase for xylobiose production.
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Dissacarídeos/biossíntese , Endo-1,4-beta-Xilanases/química , Níquel/química , Polímeros/química , Thermotoga maritima/enzimologia , Zea mays/química , Reatores Biológicos/microbiologia , Quelantes/química , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Dissacarídeos/isolamento & purificação , Estabilidade Enzimática , Enzimas Imobilizadas/química , Genes Bacterianos , Meia-Vida , Hidrólise , Proteínas Recombinantes de Fusão/metabolismo , Temperatura , Thermotoga maritima/genética , Fatores de Tempo , Xilose/química , Zea mays/microbiologiaRESUMO
An extracellular beta-xylosidase from the thermophilic fungus Paecilomyces thermophila J18 was purified 31.9-fold to homogeneity with a recovery yield of 2.27% from the cell-free culture supernatant. It appeared as a single protein band on SDS-PAGE with a molecular mass of approx 53.5 kDa. The molecular mass of beta-xylosidase was 51.8 kDa determined by Superdex 75 gel filtration. The enzyme was a glycoprotein with a carbohydrate content of 61.5%. It exhibited an optimal activity at 55 degrees C and pH 6.5, respectively. The enzyme was stable in the range of pH 6.0-9.0 and at 55 degrees C. The purified enzyme hydrolyzed xylobiose and higher xylooligosaccharides but was inactive against xylan substrates. It released xylose from xylooligosaccharides with a degree of polymerization ranging between 2 and 5. The rate of xylose released from xylooligosaccharides by the purified enzyme increased with increasing chain length. It had a K(m) of 4.3mM for p-nitrophenol-beta-d-xylopyranoside and was competitively inhibited by xylose with a K(i) value of 139 mM. Release of reducing sugars from xylans by a purified xylanase produced by the same organism increased markedly in the presence of beta-xylosidase. During 24-hour hydrolysis, the amounts of reducing sugar released in the presence of added beta-xylosidase were about 1.5-1.73 times that of the reaction employing the xylanase alone. This is the first report on the purification and characterization of a beta-xylosidase from Paecilomyces thermophila.
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Endo-1,4-beta-Xilanases/metabolismo , Paecilomyces/enzimologia , Xilose/metabolismo , Xilosidases/metabolismo , Eletroforese em Gel de Poliacrilamida , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Cinética , Peso Molecular , Paecilomyces/crescimento & desenvolvimento , Especificidade por Substrato , Triticum , Xilosidases/isolamento & purificaçãoRESUMO
Objective: To explore the relationship between genotype and phenotype of ABCB11 deficiency. Methods: Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene' or 'bile salt export pump', 'cholestasis' and 'child' as key words. Results: The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after ursodeoxycholic acid therapy and/or partial external biliary diversion, 5 received orthotopic liver transplantation, 2 developed hepatocellular carcinoma and 4 cases died in childhood. Conclusions: The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings. Patients should be managed in individualized maner.
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Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Colestase Intra-Hepática , Fenótipo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/deficiência , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP , Criança , Genótipo , Humanos , Lactente , Masculino , Estudos Retrospectivos , IrmãosRESUMO
Many cancers are chemotherapy-resistant. Chemotherapy combined with immunotherapy offers a potential avenue for the treatment of chemotherapy-resistant cancers. In this study, we investigated the apoptotic pathways induced by combined interferon-gamma/adriamycin treatment in Hep G2 cells. Our data showed that Hep G2 cells treated with combined interferon-gamma/adriamycin enhanced cell apoptosis in comparison with that of cells treated with adriamycin. Interferon-y increased TNFR-1, CSE1L/CAS (cellular apoptosis susceptibility protein), Bax, and Bad levels. Adriamycin increased p53 and Bax, but not TNFR- 1 and CAS levels. Interferon-y did not increase p53 accumulation; nevertheless it enhanced adriamycin-induced p53 accumulation. Overexpression of IRF-1 augmented the combined interferon-gamma/adriamycin-induced p53 accumulation. Interferon-gamma co-treatment increased the stability of p53 protein induced by adriamycin. Our data suggest that TNF-gamma may greatly enhance the combined interferon-gamma/chemotherapeutic drug-induced apoptosis of cancers. Our findings also indicate that CAS, TN-FR-1, p53, Bax, and Bad may be the targets for the interferon-y-based chemo-immunotherapy of the chemotherapy-resistant cancers.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Proteína de Suscetibilidade a Apoptose Celular/metabolismo , Doxorrubicina/farmacologia , Interferon gama/farmacologia , Neoplasias Hepáticas/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Etoposídeo/farmacologia , Humanos , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Neoplasias Hepáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Transfecção , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
BACKGROUND: Rabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response. METHODS: We conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses. RESULTS: Both the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p=0.411) and 16.7% in control vaccine classic regimen (p=0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42. CONCLUSION: The investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults. Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.
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Adjuvantes Imunológicos/farmacologia , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Linfócitos T CD4-Positivos/efeitos dos fármacos , Vacina Antirrábica/administração & dosagem , Receptor 3 Toll-Like/agonistas , Adulto , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Chlorocebus aethiops , Expressão Gênica , Voluntários Saudáveis , Humanos , Esquemas de Imunização , Imunogenicidade da Vacina , Masculino , Testes de Neutralização , Segurança do Paciente , Profilaxia Pós-Exposição/métodos , Raiva/prevenção & controle , Vírus da Raiva/química , Vírus da Raiva/imunologia , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Vacinação , Células VeroRESUMO
The production of extracellular xylanase by a newly isolated thermophilic fungus, Paecilomyces themophila J18, on the lignocellulosic materials was studied in solid-state fermentation (SSF). The strain grew well at 50 degrees C and produced a high-level of xylanase activity using the selected lignocellulosic materials, especially wheat straw. Production of xylanase by P. themophila J18 on wheat straw was enhanced by optimizing the particle size of wheat straw, nitrogen source, initial moisture level, growth temperature and initial pH of the culture medium. Under the optimized conditions, yield as high as 18,580 Ug(-1) of carbon source of xylanase was achieved. No CMCase activity was observed. The xylanase exhibited remarkable stability and retained more than 50% of its original activity at 70 degrees C for 4h at pH 7.0-8.0. Therefore, P. themophila J18 could to be a promising microorganism for thermostable, cellulase-free xylanase production in SSF.