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Objective: To use metagenomic sequencing to compare the differences in intestinal microbiota species and metabolic pathways in patients with hepatitis B cirrhosis with or without ascites and further explore the correlation between the differential microbiota and clinical indicators and metabolic pathways. Methods: 20 hepatitis B cirrhosis cases [10 without ascites (HBLC-WOA), 10 with ascites (HBLC-WA), and 5 healthy controls (HC)] were selected from the previously studied 16S rRNA samples. Metagenome sequencing was performed on the intestinal microbiota samples. The Kruskal-Wallis rank sum test and Spearman test were used to identify and analyse differential intestinal microbiota populations, metabolic pathways, and their correlations. Results: (1) The overall structure of the intestinal microbiota differed significantly among the three groups (R = 0.19, P = 0.018). The HC group had the largest abundance of Firmicutes and the lowest abundance of Proteobacteria at the genus level. Firmicutes abundance was significantly decreased (P(fdr) < 0.01), while Proteobacteria abundance was significantly increased (P(fdr) < 0.01) in patients with cirrhosis accompanied by ascites; (2) LEfSe analysis revealed that 29 intestinal microbiota (18 in the HBLC-WA group and 11 in the HBLC-WOA group) played a significant role in the disease group. The unclassified Enterobacteriaceae and Klebsiella species in the HBLC-WA group and Enterobacteriaceae in the HBLC-WOA group were positively correlated with the Child-Turcotte-Pugh (CTP) score, prothrombin time, and international normalized ratio score and negatively correlated with albumin and hemoglobin levels (P < 0.05). Escherichia and Shigella in the HBLC-WA group were positively correlated with CTP scores (P < 0.05); (3) The correlation analysis results between the KEGG pathway and 29 specific intestinal microbiota revealed that Enterobacteriaceae and arachidonic acid, α-linolenic acid, glycerolipid metabolism, and fatty acid degradation were positively correlated in the lipid metabolism pathway, while most Enterobacteriaceae were positively correlated with branched-chain amino acid degradation and negatively correlated with aromatic amino acid biosynthesis in the amino acid metabolic pathway. Conclusion: A significant increment of Enterobacteriaceae in the intestines of HBLC-WA patients influenced hepatic reserve function and was associated with amino acid and lipid metabolic pathways. Therefore, attention should be paid to controlling the intestinal microbiota to prevent complications and improve the prognosis in patients with hepatitis B cirrhosis, especially in those with ascites.
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Microbioma Gastrointestinal , Hepatitis B , Humanos , Ascitis/complicaciones , ARN Ribosómico 16S/genética , Cirrosis Hepática/complicaciones , Hepatitis B/complicaciones , AminoácidosRESUMEN
Objective: To investigate the changes of CTCs and the correlation between the changes of CTCs and the clinical efficacy of neoadjuvant immunotherapy for non-small cell lung cancer (NSCLC). Methods: A retrospective case-control study was conducted to collect the data of 23 patients with NSCLC who received neoadjuvant immunotherapy in the Third Xiangya Hospital from June 2018 to December 2019. They were 35-76 years old with a median age of 52 years old, including 13 male patients and 10 female patients. The CTCs value, evaluation results from response evaluation criteria in solid tumor (RECIST) and major pathological response were evaluated before treatment, after neoadjuvant immunotherapy and after operation. Mann Whitney U test was used for the comparison between the two groups, Wilcoxon test was used for the comparison of association samples, and Kruskal Wallis test was used for the comparison between multiple samples. Results: The CTCs value was positively correlated with tumor progression, that the CTCs value of â ¡B group, â ¢A group and â ¢B group was 10.69 (3.87) FU/3 ml, 12.90 (2.24) FU/3 ml and 16.04 (3.43) FU/3 ml, and the difference was statistically significant (χ2=7.829, P=0.020). Then CTCs decreased to 7.60(4.79) FU/3 ml significantly (Z=4.197,P=0.000), and decreased to 6.22(2.80) FU/3 ml significantly again after surgery(Z=-2.950,P=0.005). In RECIST results, the CTCs value of CR group, PR group and SD group was 12.90(3.79)FU/3 ml, 12.52(3.96) FU/3 ml and 13.58(5.11) FU/3 ml,and no significant difference before treatment (χ²=1.806, P=0.405). After neoadjuvant immunotherapy, the CTCs of CR group decreased to 6.22(3.87) FU/3 ml significantly (Z=-4.950, P= 0.000), and also PR group to7.32(4.31) FU/3 ml (Z=-3.180, P=0.001) or SD group to (Z=-2.023, P=0.043). There was no significant difference between CR group and PR group (Z=-0.838, P=0.402), but significant difference between SD group and CR/PR group (Z=-1.922, P=0.050). After operation, the CTCs of CR, PR and SD group decreased to 6.09(3.43) FU/3 ml, 6.40(1.82) FU/3 ml and 9.20(5.16) FU/3 ml,and there was no significant difference to preparation in CR group and PR group, but significant difference in SD group (Z=-2.023, P=0.043). There was no significant difference between CR group and PR group (Z=-1.134, P=0.257), but significant difference between SD group and CR/PR group (Z=-1.624, P=0.014). Before treatment,CTCs of MPR group and non-MPR group were 11.98(4.14) FU/3 ml and 13.54(4.76) FU/3 ml,and there was no significant difference between them (Z=-1.354, P=0.176). After neoadjuvant immunotherapy, the CTCs of MPR group decreased to 6.36(2.65) FU/3 ml significantly (Z=-2.934, P=0.001) and also in non-MPR group to 10.88(2.80) FU/3 ml (Z=-2.840, P=0.003); but there was significant difference between MPR group and non-MPR group (Z=-3.693, P=0.000), and also the change of CTCs between two groups (Z=-2.770, P=0.006). After operation, the CTCs of MPR group decreased to 5.40(1.33) FU/3 ml insignificantly (Z=-0.533, P=0.594) but significantly to 7.05(3.80) FU/3 ml in non-MPR group (Z=-2.734, P=0.030), and significant difference between them (Z=-1.900, P=0.011). Conclusion: The value of CTCs is negatively correlated with the efficacy (RECIST and MPR) of neoadjuvant immunotherapy for NSCLC, which can be used for clinical efficacy evaluation of neoadjuvant immunotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/terapia , Estudios de Casos y Controles , Femenino , Humanos , Inmunoterapia , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios RetrospectivosRESUMEN
OBJECTIVE: To test the reliability and validity of the Chinese version of parenting sense of competence scale (PSOC) in Chinese mothers of preschool children, and to explore the perception of preschool children's mothers on their own parenting skills and their comfort of being a parent in Yanqing District of Beijing. METHODS: A cross-sectional survey was conducted using a convenience sample in 1 384 preschool children's mothers in Yanqing District of Beijing. SPSS 21.0 and Mplus 7.4 software were used for statistical analysis to test the structural validity, criterion related validity, internal consistency and split half reliability of the scale, and to analyze the score of the scale and its influencing factors. RESULTS: The PSOC had good reliability and validity. Exploratory factor analysis showed that each item of the PSOC had more than 0.4 factor loading in efficacy factor or satisfaction factor, and there was no double load phenomenon. Confirmatory factor analysis showed that the factor loadings ranged from 0.212 to 0.843 in efficacy factor and satisfaction factor, respectively. The goodness of fit test showed that all the fitting indexes were within the acceptable range, and the correlation between the effectiveness subscale and the satisfaction subscale was high. The Cronbach's α coefficient of the whole scale, the efficacy subscale and the satisfaction subscale were 0.872, 0.802, and 0.874, respectively. The Spearman-Brown coefficient of PSOC was 0.851. The average score of the whole scale, the efficacy subscale, and the satisfaction subscale were 72.33±11.31, 35.54±5.91, and 36.79±7.11, respectively, and the score of parenting competence in Chinese mothers of preschool children was influenced by the mother's educational level and the annual income of her family. CONCLUSION: The PSOC has satisfactory reliability and validity in Chinese mothers of preschool children. It can be used as an evaluation instrument for measuring the parenting competency, self perceived efficacy and satisfaction in the mainland Chinese mothers of preschool children. The competency of preschool children's mothers in Yanqing District of Beijing is very good, which may be related to the higher education level of the mothers and the higher annual income of their families in this study.
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Madres , Responsabilidad Parental , Beijing , Preescolar , China , Estudios Transversales , Femenino , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Adaptive fluoride ceramic with glass forming layer (GCZBL-Er) used in laser anti-escaping has been prepared by one-step synthesis, and the thickness of glass layer is identified as ~0.41 mm. Blue, green and red emissions of Er3+/Yb3+ codoped fluoride ceramic (CZBL-Er) and glass layer (GZBL-Er) have been investigated under ~980 nm laser pumping. With the forming of thin glass layer on ceramic surface, the absorption intensities on diffuse reflection of GCZBL-Er at 974 nm and 1.53 µm increase by 48% and 53% than those of CZBL-Er. Excited by a 979 nm laser, the presence of the glass layer increases the absolute absorption rate in spectral power from 75% in CZBL-Er to 83% in GCZBL-Er, which is consistent with the improvement in the absorbed photon number. In addition, the quantum yield of GCZBL-Er complex is raised by 28.4% compared to the case of ceramic substrate by photon quantification. Intense absorption-conversion ability and efficient macroscopical anti-escaping effect confirm the superiority of ingenious structure in the fluoride ceramics with glass forming layer, which provides a new approach for developing the absorption-conversion materials of anti-NIR laser detection.
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Constipation has a significant influence on quality of life. Patients with constipation have slow waves in their gastrointestinal smooth muscles and less faecal water contents, which are closely associated with down-regulation of the interstitial cells of Cajal (ICC) in the gastrointestinal muscles and the aquaporin protein AQP3 expressed in colon epithelial cells. Recent studies supported that patients with constipation have altered intestinal microbial structures compared with healthy controls. Intestinal dysbiosis might be one possible pathophysiological mechanism causing constipation. Bacterial strains, such as Lactobacillus spp., have shown many beneficial effects on the amelioration of constipation. However, few studies reported the structural changes of intestinal microbiota post-intervention of probiotics. In this study, a bacterial mixture was administrated to rats with loperamide-induced constipation. Effects of the bacterial mixture on small intestine transit (SIT), faecal water content, and the intestinal microbiome in rats were evaluated. Meanwhile, we investigated several factors involved in signalling pathways that regulate function of ICC and expression of AQP3 to discuss the possible underlying molecular mechanisms. Intervention of the bacterial mixture improved SIT and faecal water content in constipated rats. The up-regulation of C-kit/SP signalling pathways in ICC and AQP3 significantly contributed to improvements. These changes were closely associated with the manipulation of intestinal dysbiosis in constipated rats. Furthermore, our results revealed the important role of intestinal microbiota in affecting gut motility through regulation of serotonin biosynthesis. This monoamine neurotransmitter, secreted from enterochromaffin cells, up-regulated both substance P/neurokinin 1 receptors pathway of ICC and the expression of AQP3 in intestinal epithelial cells. Our study suggested that the disrupted microbiome in patients could be a potential therapeutic target for the improvement of constipation.
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Estreñimiento/complicaciones , Disbiosis/terapia , Probióticos/administración & dosificación , Animales , Antidiarreicos/administración & dosificación , Antidiarreicos/farmacología , Estreñimiento/inducido químicamente , Heces/química , Microbioma Gastrointestinal , Tránsito Gastrointestinal , Intestino Delgado/fisiología , Loperamida/administración & dosificación , Loperamida/farmacología , Ratas , Resultado del Tratamiento , Agua/análisisRESUMEN
Transgene silencing, which is common in transgenic plants and animals, limits the generation and application of genetically modified organisms, and is associated with the exogenous gene copy number, the methylation status of its promoters, and histone modification abnormalities. Here, we analyzed the expression of the exogenous gene DsRed and the methylation status of its cytomegalovirus (CMV) promoter in six healthy transgenic cashmere goats and transgenic nuclear donor cells. The CMV promoter exhibited high methylation levels (74.4-88.2%) in four of the goats, a moderate methylation level (58.7%) in one, and a low methylation level (21.2%) in one, while the methylation level of the transgenic nuclear donor cells was comparatively low (14.3%). DsRed expression was negatively correlated with promoter methylation status. Transgenic cashmere goats carried one to three copies of the CMV promoter fragment and one to six copies of the DsRed fragment, but copy number showed no obvious correlation with DsRed expression. After treatment with the methylation inhibitor 5-azacytidine, DsRed expression in transgenic goat cells significantly increased and CMV promoter methylation significantly decreased; this indicated an inverse correlation between promoter methylation status and DsRed expression. After treatment with the histone deacetylase inhibitor trichostatin A, DsRed expression increased, indicating that an abnormal histone modification in transgenic goats is also involved in exogenous gene silencing. These findings indicate the potential of trichostatin A and 5-azacytidine to rescue the biological activity of silenced exogenous transgenes in adult-derived transgenic cells under culture conditions.
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Azacitidina/farmacología , Cabras/genética , Histonas/genética , Ácidos Hidroxámicos/farmacología , Proteínas Luminiscentes/genética , Regiones Promotoras Genéticas/efectos de los fármacos , Animales , Animales Modificados Genéticamente , Citomegalovirus/genética , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN/efectos de los fármacos , Femenino , Dosificación de Gen , Expresión Génica , Silenciador del Gen/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Histonas/metabolismo , Proteínas Luminiscentes/agonistas , Proteínas Luminiscentes/antagonistas & inhibidores , Proteínas Luminiscentes/metabolismo , Masculino , TransgenesRESUMEN
Objective: To explore the clinical characteristics of single subcortical cerebral infarction of middle cerebral artery (MCA) territory and the possible pathogenesis. Methods: A total of 344 cases diagnosed as single subcortical cerebral infarction of MCA territory were enrolled in the study and divided into the parent artery disease (PAD) group and the non-PAD group according to whether the MCA stenosis was presented or not. A total of 312 cases diagnosed as single subcortical cerebral infarction of MCA territory were divided into the BAD group and the SVD group according to the relationship between the lesion sites and MCA. Differences in the clinical and imaging feature were compared between different groups. Results: A total of 32 patients were in the PAD group. Compared with the non-PAD group, patients in the PAD group were found with higher prevalence of asymptomatic cerebral arterial atherosclerosis [93.8%(30/32) vs 57.1%(178/312), P<0.001], higher prevalence of branch atheromatous disease[75.0%(24/32) vs 58.7%(183/312), P=0.072]. A total of 183 patients were in the BAD group. Compared with the BAD group, patients in the SVD group were older[(64.7±11.2) years vs (61.7±12.2) years, P=0.031], more with hypertension [65.9%(85/129) vs 53.0%(97/183), P=0.027] and smoking [41.9%(54/129) vs 57.9%(106/183), P=0.006] and more severe leukoaraiosis. Conclusions: Single subcortical cerebral infarction of MCA territory has different etiology and pathogenesis. Evidence of systemic atherosclerosis should be carefully searched in patients with branch atheromatous disease.
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Enfermedades Arteriales Cerebrales/patología , Imagen de Difusión por Resonancia Magnética , Infarto de la Arteria Cerebral Media/patología , Distribución por Edad , Anciano , Aterosclerosis , Investigación Biomédica , Enfermedades Arteriales Cerebrales/complicaciones , Infarto Cerebral , Femenino , Humanos , Hipertensión , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/fisiopatología , Arteria Vertebral/patologíaRESUMEN
This study was conducted to investigate the effects of stress on the absorption of glycylsarcosine in the jejunum of broilers, as well as the underlying mechanisms. A glucocorticoid analogue, dexamethasone (DEX), was chosen to simulate the effects of endogenous glucocorticoids. Two hundred 21-day-old male Arbor Acre broilers were randomly allotted to 4 groups with 5 replicates in each group and 10 birds per replicate by a completely randomized assignment involving a single factorial arrangement of injection dose DEX. The broilers were injected with 1-mL DEX (0.1-, 0.5-, and 2.5-mg/kg BW) or saline subcutaneously in the abdomen 1×/d for 7 d. The broilers were weighed, killed, and sampled at 28 days old. The results showed that DEX dose-dependently reduced growth and endogenous corticosterone content in the plasma of the broilers (P<0.05). DEX decreased absorption of glycylsarcosine by jejunum brush border membrane vesicles and gut sacs (P<0.05). DEX treatment increased the crypt depth of the jejunum, decreased the villus height, absorption area, and ratio of villus height to crypt depth (P<0.05). Effect of dexamethasone on villus width was not obvious (P>0.05). It was concluded that DEX reduced the absorption of glycylsarcosine in the jejunum of broilers.
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Pollos/metabolismo , Dexametasona/metabolismo , Dipéptidos/metabolismo , Glucocorticoides/metabolismo , Yeyuno/fisiología , Estrés Fisiológico , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Animales , Dexametasona/farmacología , Glucocorticoides/farmacología , Yeyuno/efectos de los fármacos , Masculino , Distribución AleatoriaRESUMEN
Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.
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Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.
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HeLa cells were exposed to formaldehyde and its metabolic derivatives, methanol, formic acid, and acetaldehyde, to investigate that the toxicity of formaldehyde is not caused by the chemical group. After 1 h of treatment with formaldehyde, mitochondrial assays showed that low concentrations (e.g. 10 µmol/L) of formaldehyde promoted growth of the HeLa cells, while higher concentrations (e.g. ≥62.5 µmol/L) inhibited cell growth; while all four chemicals at a concentration of 125 µmol/L affected cell growth, formaldehyde affected the largest. Reactive oxygen species concentration increased with the concentration of the exposure chemical. The endogenous formaldehyde content increased the most in the formaldehyde group, but in other three groups, it did not increase as the exposure concentration increased. Expression of dehydrogenase (formaldehyde dehydrogenase (FDH)) in the formaldehyde (10.40) and methanol (10.60) groups increased significantly compared with the control (1), while it was similar to the control in formic acid (0.90) and acetaldehyde (1.10) groups. Our results suggest that formaldehyde could affect cell activity and even enter cells. Exposure to formaldehyde changes the endogenous formaldehyde concentration in cells within 24 h, and this induces expression of FDH for formaldehyde degradation to maintain the formaldehyde balance. The toxicity of formaldehyde is not caused by the carbon atoms in the aldehyde, hydroxyl, or carboxyl groups. Formaldehyde is hypothesized to be an important signaling molecule in the regulation of cell growth and maintenance of the endogenous formaldehyde level.
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Acetaldehído/toxicidad , Formaldehído/toxicidad , Formiatos/toxicidad , Metanol/toxicidad , Acetaldehído/metabolismo , Aldehído Oxidorreductasas/genética , Aldehído Oxidorreductasas/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Formaldehído/metabolismo , Formiatos/metabolismo , Células HeLa , Humanos , Metanol/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factores de TiempoRESUMEN
OBJECTIVES: The objective of this study is to determine the prevalence of antibiotic resistance factors, including the production of extended-spectrum beta-lactamases (ESBLs) and the presence of class 1 integrons among Escherichia coli isolated from clinical specimens. MATERIALS AND METHODS: Bacterial species identification was performed using a VITEK-2 system (VITEK2 GN-card; bioMérieux, France). Antimicrobial susceptibility testing was determined using the disk diffusion method according to the 2010 Clinical and Laboratory Standards Institute guidelines. Polymerase chain reaction (PCR) was used to detect integrons and amplify variable regions of the bla TEM, bla SHV and bla CTX-M genes. Gene cassettes were detected by deoxyribonucleic acid sequencing. RESULTS: In this study, 58% (100/172) of clinical E. coli isolates were identified as ESBL producers. We found that 90% of the ESBL-producing E. coli isolates harbored the blaCTX-M gene, whereas only 59% and 32% possessed the blaTEM and blaSHV genes respectively. The presence of class 1 integrons was based on the detection of the integrase gene by PCR. A total of 69% of the ESBL-producing isolates were integron-positive. Resistance to 10 antibiotics, including quinolones, sulfonamides and ß-lactam/enzyme inhibitors, was significantly higher in the class 1 integron-positive isolates (P < 0.05). The occurrence of class 1 integrons in blaTEM , blaSHV and blaCTX-M gene carriers was 72.9%, 84.4% and 68.9%, respectively. Class 1 integrons were detected in 61.5% of the isolates with only one ESBL genotype, but in 69.0% and 92.3% of the isolates with two or three different ESBL genotypes, respectively. CONCLUSIONS: Our findings indicate that clinical strains of bacteria with multiple ESBL genotypes may have greater opportunities to carry class 1 integrons.
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Farmacorresistencia Bacteriana , Infecciones por Escherichia coli/microbiología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Integrones , beta-Lactamasas/metabolismo , Antibacterianos/farmacología , ADN Bacteriano/genética , Escherichia coli/enzimología , Escherichia coli/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
Few studies to date have reported on the development and application of a nanobiosensor based on localized surface plasmon resonance (LSPR) for detecting gene mutations. This study aimed to develop a novel LSPR biosensor used for detecting p53 mutation. Nanosphere lithography was used to fabricate the silver nanoparticles. The DNA probe was designed to recognize the target sequence and immobilized on the chip surface by a covalent-coupling method using amine-group ligands. Synthetic oligonucleotides or PCR products were amplified from genomic DNA taken from blood samples and hybridized with the immobilized probe. Wild-type and mutant p53 was detected by measuring shifts in peak of LSPR extinction spectra. The low detection limit of the sensor for target sequence was 10 nM, and detection occurred over a wide dynamic range (10 nM - 10 µM). Importantly, the differences in measuring signal between wild-type and mismatched p53 DNA was significant, allowing for this sensor to effectively discriminate against single base mutations. In conclusion, we developed a biosensor with potential as a rapid, label-free, sensitive, and low-cost method for detecting p53 mutation. Our results suggest that such an LSPR-based biosensor provides an attractive alternative for clinical detection of genetic mutation.
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Técnicas Biosensibles , Sondas de ADN/química , Nanopartículas del Metal/química , Mutación/genética , Nanopartículas , Resonancia por Plasmón de Superficie , Proteína p53 Supresora de Tumor/genética , Humanos , Hibridación de Ácido Nucleico , Plata/química , Proteína p53 Supresora de Tumor/sangreRESUMEN
This study aimed to assess the efficiency and effects of insulin-like growth factor receptor-1 (IGF-IR) siRNA knockdown during bovine preimplantation embryonic development. In oocytes injected with IGF-IR siRNA, the relative IGF-IR mRNA levels compared to controls were 28% and 46% at 6 and 24 h after injection, respectively. With respect to the injection of IGF-IR siRNA in zygotes, 24 h after injection the relative levels of IGF-IR mRNA and protein in the two-cell embryos were 74% and 78% of those in the controls, respectively. IGF-IR siRNA reduced blastocyst formation (23.2%) compared to siRNA controls (33.0%) and uninjected oocytes (35.4%; P < 0.05) and the number of viable cells per IGF-IR siRNA-treated blastocyst (64 ± 3) was significantly reduced, compared to control siRNA and uninjected blastocysts (81 ± 3 and 116 ± 4; P < 0.01). In conclusion, IGF-IR siRNA knockdown reduces the development of bovine embryos, and microinjection in zygotes can decrease blastocyst cell number.
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INTRODUCTION: Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model. MATERIAL AND METHODS: Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR. RESULTS: Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen. CONCLUSION: ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity.
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Resistencia a Antineoplásicos/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , ARN Mensajero/metabolismo , Antagonistas de Andrógenos/uso terapéutico , Flutamida/análogos & derivados , Flutamida/uso terapéutico , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Masculino , Co-Represor 1 de Receptor Nuclear/genética , Coactivador 2 del Receptor Nuclear/genética , Coactivadores de Receptor Nuclear/genética , Neoplasias de la Próstata/tratamiento farmacológico , Células Tumorales CultivadasRESUMEN
With increased use of intensity-modulated radiation therapy (IMRT) for head and neck treatment questions have arisen as to selection of an optimum treatment approach when either superficial sparing or treatment is desired. Other work has pointed out the increased superficial dose resulting from obliquity effects when multiple tangential beams are applied to head and neck treatment, as is the general case in IMRT planning. Helical tomotherapy might be expected to result in even further enhanced superficial dose compared with conventional bilateral field treatment. We have designed a typical right oropharynx target volume in an anthropomorphic head and neck phantom. Three different treatment techniques have been used to optimally treat this target, including bilateral static fields, eight-field IMRT and helical tomotherapy. The phantom was immobilized in a standard treatment position and treated on a Varian 2300cd linear accelerator and on a Hi-Art Helical Tomotherapy unit. 1 mm3 lithium-fluoride thermoluminescent dosimeters (TLDs) were placed on the surface of the phantom at a number of axial test positions. Film strips (Kodak EDR2) were either wrapped around the surface or sandwiched within the phantom. Measured doses at the surface and as a function of depth are compared with the planning system predictions for each treatment technique. The maximum surface doses on the proximal treatment side, averaged from TLDs and films, were measured to be 69-82% of the target dose with the bilateral fields yielding the lowest surface doses (69%), tomotherapy about 2% more than that (71%) and IMRT 13% more (82%). Anterior to the target volume, doses are always low for bilateral treatment. In this case the minimum anterior surface dose (chin area) was 6% of the prescription dose from that technique as compared with 26% and 35% from the IMRT and tomotherapy methods, respectively. The Eclipse and Tomotherapy planning systems both modelled deep and superficial doses well. Surface doses were better modelled by Eclipse at the test points, while the tomotherapy plans consistently overestimated the measured doses by 10% or more. Depth dose measurements, extracted from embedded films, indicated the depth of dose build-up to >99% to be the shallowest for IMRT (2-5 mm) followed by tomotherapy (5-8 mm) and bilateral fields (10-15 mm). The amount of surface dose is clearly technique dependent and should be taken into account in the planning stage.
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Neoplasias de Cabeza y Cuello/radioterapia , Aceleradores de Partículas , Planificación de la Radioterapia Asistida por Computador/métodos , Dosimetría Termoluminiscente/métodos , Protocolos Antineoplásicos , Calibración , Fluoruros/química , Neoplasias de Cabeza y Cuello/patología , Humanos , Compuestos de Litio/química , Fantasmas de Imagen , Traumatismos por Radiación , Protección Radiológica , Dosificación Radioterapéutica/normasRESUMEN
We introduce a statistically based methodology for the design of neural networks when the dimension d of the network input is comparable to the size n of the training set. If one proceeds straightforwardly, then one is committed to a network of complexity exceeding n. The result will be good performance on the training set but poor generalization performance when the network is presented with new data. To avoid this we need to select carefully the network architecture, including control over the input variables. Our approach to selecting a network architecture first selects a subset of input variables (features) using the nonparametric statistical process of difference-based variance estimation and then selects a simple network architecture using projection pursuit regression (PPR) ideas combined with the statistical idea of slicing inverse regression (SIR). The resulting network, which is then retrained without regard to the PPR/SIR determined parameters, is one of moderate complexity (number of parameters significantly less than n) whose performance on the training set can be expected to generalize well. The application of this methodology is illustrated in detail in the context of short-term forecasting of the demand for electric power from an electric utility.
RESUMEN
To study the escaping behavior of 1030 schizophrenic in-patients, "Brief Rating Scale for Dangerous Behavior of In-patient" was used to asses them within their first week hospitalization from May 1994 to March 1996. The result showed that 276 (26.8%) patients had escaping behavior. The patients with paranoid schizophrenia had higher rate of escaping behavior. There was no correlation being found between sex, age, duration of illness, and escaping behavior. The patients with the history of such behavior were more likely to escape from ward (41.9%). The suggestion for preventing such behavior were discussed.
Asunto(s)
Reacción de Fuga , Psicología del Esquizofrénico , Adolescente , Adulto , Anciano , Escalas de Valoración Psiquiátrica Breve , Femenino , Humanos , Pacientes Internos/psicología , Masculino , Persona de Mediana EdadRESUMEN
One terpenoids has been isolated from the MeOH extract of Sagittaria sagittifolia by repeated chromatography on silica gel. Its structure was identified as sandaracopimaric acid on the basis of spectral and physical data. Sandaracopimaric acid has good immunosuppression action.