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The application of silicon nanocrystals (Si-NC) is somewhat limited due to their low luminescence intensity. Therefore, it is of interest to investigate methods for enhancing the luminescence intensity of Si-NC. In this study, phosphorus (P)-doped Si-NC with two different doping methods were prepared by electron beam thermal evaporation: in-situ doping (during synthesis) and ex-situ doping (after synthesis). The photoluminescence (PL) intensity and crystallinity of Si-NC can be enhanced through phosphorus doping. Moreover, a comparison between two different methods of Si-NC doping reveals that the luminescence intensity of in-situ P-doped Si-NC is superior to that of ex-situ P-doped Si-NC, which is increased by an order of magnitude compared to the PL intensity of undoped Si-NC.
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An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
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Infecções por Caliciviridae/virologia , Gastroenterite/epidemiologia , Gastroenterite/virologia , Norovirus/classificação , Adulto , Idoso , Anticorpos Antivirais/sangue , Antígenos de Grupos Sanguíneos , Infecções por Caliciviridae/epidemiologia , China/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Surtos de Doenças , Hospitais , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Norovirus/genética , Filogenia , Ligação ProteicaRESUMO
Objective: To investigate the efficacy and safety of left bundle branch area pacing (LBBaP) with the new simplified approach (nine-partition method). Methods: A total of 118 patients with clinical indications and received pacemaker implantation from December 1, 2018 to December 31, 2019 in Beijing Anzhen Hospital were enrolled. LBBaP was performed with the nine-partition method (in the right anterior oblique 30° position, the ventriculogram was divided into nine partitions and the initial implant sites were located in the lower base 1/3 partitions). In X-ray image, the 3830 lead is located in the left bundle branch area, the unipolar pacing QRS wave is in the form of right bundle branch block, and the peak time from stimulation to left ventricular activation<90 ms is defined as successful operation. The clinical characters, such as the methods of venipuncture, electrode parameters, operation duration, fluoroscopy duration, the peak time from stimulation to left ventricular, pacemaker types, surgical success rate, complications, and immediate postoperative ECG parameters were collected. The patients were followed up after the operation, and the electrode parameters and postoperative complications were recorded. Results: This study is a retrospective study. There were 62 (52.5%) male patients in this cohort, the average age was (65.9±13.4) years old,and there were 49(41.5%) sick sinus syndrome, 6(5.1%) abnormal sinus node and atrioventricular node simultaneously, 63(53.4%) atrioventricular block, 26(22.0%) atrial fibrillation, 20(16.9%) cardiomyopathy; the baseline duration of QRS was (109.21±39.03) ms. Successful LBBaP was achieved in 109 patients with"nine-partition method"and the success rate was 92.4%; 104 patients (95.5%) were axillary vein puncture, 5 (4.6%) were subclavian vein puncture; the operation duration was (80.3±23.0) min, the fluoroscopy duration was (12.29±5.13) min; the QRS duration after LBBaP was (116.36±18.11) ms. The threshold of the left bundle branch (LBB) lead was (0.92±0.63) V, the R wave amplitude was (10.60±5.04) mV and the impedance was (798.71±194.90) Ω. In 1 V pacing, the peak time from stimulation to left ventricular activation was (67.91±12.15) ms, and in 5 V pacing was (67.52±12.45) ms; 1 case (0.9%) with a single-chamber pacemaker implanted, 106 cases (97.3%) with dual-chamber pacemaker and 2 cases (1.8%) with three-chamber pacemakers. There were no hematomas, pneumothorax, hemothorax, electrode dislocation, infection, and capsular hemorrhage and other serious surgery-related complications during the operation. A total of 97 patients (89.0%) were followed up for (6.21±2.90) months. The electrode parameters of all patients were stable and no complications observed. Conclusions: The LBBaP with nine-partition method is a simple, safe and effective physiological pacing approach. However, its long-term effect still needs to be further verified.
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Bloqueio Atrioventricular , Estimulação Cardíaca Artificial , Idoso , Bloqueio de Ramo/terapia , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Objective: To explore the applicability of different exposure assessment methods in occupational health risk assessment of trichloroethylene (TCE) occupation posts in electroplating enterprise. Methods: In November 2018, the occupational health risk assessments are conducted in trichloroethylene (TCE) occupation posts of 6 metal plating enterprises in a street in Shenzhen by using the qualitative risk assessment, semi-quantitative risk assessment (including contact ratio method, contact index method and synthesis index method) and quantitative risk assessment method (including non-carcinogenic and carcinogenic risk assessment methods) , and the results of different methods are compared. Results: The results of qualitative assessment method are all level 4 (high risk) ; the results of contact ratio method show that the risk level is level 5 (very high risk) ; the results of contact index method and Synthesis index method show that the risk level is level 3 and level 4, 66.7% and 33.3% respectively; Non-carcinogenic risk assessment results show that TCE jobs are "unacceptable"; carcinogenic risk assessment results in carcinogenic inhalation excess risk of 50% each being "unacceptable" and "acceptable". The results of the six risk assessment methods showed that there were 3 "substantially consistent", 1 "partially consistent", and 2 "inconsistent" among the 6 companies. Conclusion: Synthesis index method and the carcinogenic risk assessment method are more suitable for occupational health risks of TCE occupation posts.
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Exposição Ocupacional , Saúde Ocupacional , Tricloroetileno , Galvanoplastia , Medição de RiscoRESUMO
Objective: To investigate the relationship between abnormal angiopoietin-2 (Ang-2) expression and invasion/metastasis of lung cancer. Methods: Totally 122 cases of postoperative primary lung cancer tissues and their paracancerous tissues from Jan. 2009 to Dec. 2010 were collected from Affiliated Hospital of Nantong University and Ang-2 expression was analyzed by immunohistochemistry. At the cellular level, the protein and mRNA levels of Ang-2 in lung epithelial cell line Beas-2B and four lung cancer cell lines (SPCA-1, NCI-1650, A549 and NCI-H1975) were observed. The most effective Ang-2-shRNA for Ang-2 transcription was screened and transfected into A 549 lung cancer cells. The Ang-2 expression, Ang-2 gene transcription, cell proliferation, invasion/metastasis, and epithelial-mesenchymal transition (EMT) abilities of lung cancer cells were analyzed by Western blotting, fluorescent quantitative reverse transcriptase PCR, Cell Counting Kit-8 assay, and Transwell cell models for exploring the relationship between Ang-2 expression and invasion/metastasis of lung cancer. Results: The higher Ang-2 expression levels in lung cancerous tissues were closely related to tumor diameter (P=0.008), differentiating degree (P=0.033), TNM stage (P=0.025) and 5-year survival rate (P<0.001). According to the Kaplan-Meier survival curves, the 5-year survival rate of patients with higher expression levels of Ang-2 (16.1%) was significantly poorer than that of patients with lower Ang-2 (80.0%, P<0.001). Significant difference of 5-year survival rate was found in patients with different Ang-2 levels at TNM stage â (P<0.001), but not at stage â ¡, â ¢ and â £. Among Beas-2B and four lung cancer cell lines, the protein and mRNA levels of Ang-2 in A549 cells were the highest. After Ang-2-shRNA-1 plasmid successfully transfected into A549 cells, cell proliferation rate was significantly lower than that in the shRNA-negative or blank group at a time-dependent manner. The significant decrease of the invasion, migration and EMT abilities were also found in A549 cells after transfection of Ang-2 shRNA. Conclusion: Abnormal expression of Ang-2 is closely related to invasion, migration and prognosis of lung cancer, and interfering the activation of Ang-2 would be a novel molecular-targeted therapy for lung cancer.
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Neoplasias Pulmonares , Angiopoietina-2 , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Prognóstico , RNA Interferente PequenoRESUMO
BACKGROUND/OBJECTIVES: We aim to (1) examine the influence of long-term adiposity status/short-term adiposity changes on asthma with high or low fractional exhaled nitric oxide (FeNO), and (2) to determine the differences in long-term adiposity status/short-term adiposity changes on atopy, airway inflammation and pulmonary function. SUBJECTS/METHODS: We recruited 2450 fourth- to sixth-grade children from the nationwide Taiwan Children Health Study. Data regarding various adiposity indicators, atopic status, pulmonary function tests and asthma outcomes were collected annually. New-onset asthma was stratified by airway inflammation status using FeNO. The generalized estimating equation was used for analyzing longitudinal relationships between long-term adiposity status/short-term adiposity changes and new-onset asthma. Individual adiposity growth slopes were obtained using a hierarchical linear model to establish the relationships between short-term adiposity changes and asthma among children with high airway inflammation. RESULTS: We found long-term adiposity status predicted childhood asthma with low FeNO, whereas short-term adiposity changes may increase risks of childhood asthma with high FeNO. Long-term adiposity status reduced pulmonary function, whereas short-term adiposity increase were associated with atopic diseases and airway inflammation. CONCLUSIONS: Obesity-induced asthma could be mediated by high or low airway inflammation, depending on the velocity of increase in adiposity. Rapid adiposity growth may increase risks of childhood asthma and airway inflammation.
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Adiposidade , Asma/fisiopatologia , Inflamação/fisiopatologia , Obesidade Infantil/fisiopatologia , Adiposidade/imunologia , Adolescente , Asma/prevenção & controle , Índice de Massa Corporal , Testes Respiratórios , Criança , Comorbidade , Exercício Físico , Expiração , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Inflamação/prevenção & controle , Comunicação Interdisciplinar , Estudos Longitudinais , Masculino , Óxido Nítrico/análise , Obesidade Infantil/complicações , Obesidade Infantil/prevenção & controle , Aptidão Física/fisiologia , Taiwan/epidemiologia , Redução de Peso/fisiologiaRESUMO
OBJECTIVES: Epidermal growth factor receptor (EGFR) gene amplification and the EGFRvIII mutation may have prognostic value in patients with glioblastoma. This meta-analysis was to determine whether EGFR gene amplification or the EGFRvIII mutation are predictors of survival in patients with glioblastoma and anaplastic astrocytoma. MATERIALS AND METHODS: Medline, the Cochrane Central Register of Controlled Trials, EMBASE, and Google Scholar databases were searched until July 31, 2014. Studies were selected for inclusion in the analysis if they included patients with anaplastic astrocytoma and/or glioblastoma, EGFR and/or EGFRvIII mutation status was reported, and overall survival (OS) data were reported. RESULTS: Of 113 articles initially identified, only eight contained data with respect to the outcome of interest and were included in the meta-analysis. The number of cases ranged from 14 to 268, and the majority of patients were 60 or more years of age. There was no significant difference in OS between EGFR amplification-positive and EGFR amplification-negative glioblastoma patients (pooled hazard ratio [HR] = 1.101, 95% confidence interval [CI] 0.845, 1.434, P = 0.475) or anaplastic astrocytoma patients (pooled HR = 1.455, 95% CI 0.852, 2.482, P = 0.169). There was no significant difference in OS between EGFRvIII-positive and EGFRvIII-negative glioblastoma patients (pooled HR = 1.321, 95% CI: 0.881-1.981, P = 0.178). Significant heterogeneity existed between the studies, and the significance changed when the analysis was performed with studies removed in turn. CONCLUSIONS: There is insufficient evidence that either EGFR amplification or the EGFRvIII mutation has prognostic value in patients with glioblastoma.
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Astrocitoma/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Glioblastoma/genética , Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Humanos , MutaçãoRESUMO
Basal ganglia-thalamocortical circuits are multistage loops critical to motor behavior, but the contributions of individual components to overall circuit function remain unclear. We addressed these issues in a songbird basal ganglia-thalamocortical circuit (the anterior forebrain pathway, AFP) specialized for singing and critical for vocal plasticity. The major known afferent to the AFP is the premotor cortical nucleus, HVC. Surprisingly, previous studies found that lesions of HVC alter song but do not eliminate the ability of the AFP to drive song production. We therefore used this AFP-driven song to investigate the role of basal ganglia and thalamus in vocal structure, tempo, and initiation. We found that lesions of the striatopallidal component (Area X) slowed song and simplified its acoustic structure. Elimination of the thalamic component (DLM) further simplified the acoustic structure of song and regularized its rhythm but also dramatically reduced song production. The acoustic structure changes imply that sequential stages of the AFP each add complexity to song, but the effects of DLM lesions on song initiation suggest that thalamus is a locus of additional inputs important to initiation. Together, our results highlight the cumulative contribution of stages of a basal ganglia-thalamocortical circuit to motor output along with distinct involvement of thalamus in song initiation or "gating."
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Gânglios da Base/fisiologia , Tálamo/fisiologia , Vocalização Animal , Animais , TentilhõesRESUMO
BACKGROUND: Excess reactive oxygen species generated by NADPH oxidase 2 (Nox2) in response to ethanol exposure mediate aspects of skeletal toxicity including increased osteoclast differentiation and activity. Because perturbation of chondrocyte differentiation in the growth plate by ethanol could be prevented by dietary antioxidants, we hypothesized that Nox2 in the growth plate was involved in ethanol-associated reductions in longitudinal bone growth. METHODS: Nox2 conditional knockout mice were generated, where the essential catalytic subunit of Nox2, cytochrome B-245 beta chain (Cybb), is deleted in chondrocytes using a Cre-Lox model with Cre expressed from the collagen 2a1 promoter (Col2a1-Cre). Wild-type and Cre-Lox mice were fed an ethanol Lieber-DeCarli-based diet or pair-fed a control diet for 8 weeks. RESULTS: Ethanol treatment significantly reduced the number of proliferating chondrocytes in the growth plate, enhanced bone marrow adiposity, shortened femurs, reduced body length, reduced cortical bone volume, and decreased mRNA levels of a number of osteoblast and chondrocyte genes. Conditional knockout of Nox2 enzymatic activity in chondrocytes did not consistently prevent any ethanol effects. Rather, knockout mice had fewer proliferating chondrocytes than wild-type mice in both the ethanol- and control-fed animals. Additional analysis of tibia samples from Nox4 knockout mice showed that loss of Nox4 activity also reduced the number of proliferating chondrocytes and altered chondrocyte size in the growth plate. CONCLUSIONS: Although Nox enzymatic activity regulates growth plate development, ethanol-associated disruption of the growth plate morphology is independent of ethanol-mediated increases in Nox2 activity.
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BACKGROUND: Mucinous adenocarcinoma (MAC) is frequently reported to be associated with patients of young-age sporadic colorectal cancer (YSCC) and hereditary nonpolyposis colorectal cancer (HNPCC). This study is aimed to investigate whether the clinicopathological characteristics of MAC of HNPCC patients are distinct from those of YSCC patients. PATIENTS AND METHODS: Eighty-two HNPCC and 68 YSCC patients recorded in the colorectal cancer registry of Chang Gung Memorial Hospital at Linkou, Taiwan, between January 1, 1995 and December 31, 2001 were included in this study. Clinicopathological and molecular variables of MAC and non-MAC of HNPCC and YSCC patients were compared accordingly. RESULTS: Compared to non-MAC, MAC significantly showed higher frequencies of poor differentiation (32% vs. 8.2%, p = 0.001), advanced tumor stage (76% vs. 47%, p = 0.002), loss of mismatch repair protein (MMR) expression (74% vs. 44%, p = 0.023), and increased MUC2 expression (98% vs. 61%, p < 0.001). MAC of HNPCC patients showed predominant right-sided colon involvement, whereas MAC of YSCC patients displayed predominance in the left colon (79% vs. 22%, p = 0.001). Among the non-MAC counterparts, more differences were detectable including tumor stage, loss of MMR expression, and increased MUC1 expression. Furthermore, both MAC and non-MAC of YSCC patients showed higher frequencies of advanced tumor stage (81% vs. 62%, p = 0.072). In contrast, the incidence of loss of MMR expression in MAC and non-MAC of HNPCC patients is not significantly different (86% vs. 70%, p = 0.323). CONCLUSIONS: Significantly different tumor localization was observed between mucinous YSCC (left colon predominance) and mucinous HNPCC (right colon predominance).
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Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/patologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais Hereditárias sem Polipose/metabolismo , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucinas/metabolismo , Adulto JovemRESUMO
We studied the cytoarchitecture and dendritic arbors of the output neurons of the sensorimotor cortex of aged rats and found that although individual cortical layer became thinner, the overall cytoarchitecture and neuron densities remained comparable to those of young adults. To find out whether aging affects cortical outputs we studied the soma-dendritic arbors of layers III and V pyramidal neurons, main output neurons of the cerebral cortex, using brain slice intracellular dye injection technique. With a fluorescence microscope, selected neurons were filled with fluorescence dye under visual guidance. Injected slices were resectioned into thinner sections for converting the injected dye into non-fading material immunohistochemically. The long apical dendritic trunk and branches could be routinely revealed. This allowed us to reconstruct and study the dendritic arbors of these neurons in isolation in 300-microm-thick dimension. Analysis shows that their cell bodies did not shrink, but the densities of spines on dendrites and the total dendritic length significantly reduced. Among spines, those with long thin stalks thought to be involved in memory acquisition appeared to be reduced. These could underlie the compromise of sensorimotor functions following aging.
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Córtex Cerebral/citologia , Dendritos/ultraestrutura , Células Piramidais/ultraestrutura , Fatores Etários , Animais , Dendritos/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Feminino , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/metabolismo , Células Piramidais/metabolismo , Ratos , Ratos WistarRESUMO
Selenium concentrations in the serums of 17 acutely ill Legionnaires' disease patients were significantly lower than in their matching convalescent-phase serums. This trend was not observed in ten similarly paired samples of serum from control patients with pneumonia. There were no significant differences in the concentrations of nickel, copper, bromine, rubidium, lead, barium, or titanium in the serums of Legionnaires' disease and control patients.
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Doença dos Legionários/sangue , Selênio/sangue , Humanos , Metais/sangue , Níquel/sangueRESUMO
Nickel concentrations in lung tissues of nine deceased Legionnaire victims average nine times that of controls. There is a significant correlation between the nickel levels in the lungs of the Legionnaire victims and the weights of the lung specimens. No similar correlation is evident in the study of the victims' kidney tissues or tissues from the controls.
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Doença dos Legionários/metabolismo , Pulmão/metabolismo , Níquel/metabolismo , Humanos , Rim/análise , Níquel/intoxicação , PennsylvaniaRESUMO
Phytophthora capsici Leonion was first identified on pepper (Capsicum annuum L) in Taiwan in 1976. At that time, only the A1 mating type was present (2). In 2007, the A2 mating type of P. capsici was identified on tomato and eggplant in the central part of the country (1). During an excessively rainy period in mid-2008, many chili and sweet pepper fields in Taiwan suffered severe losses due to P. capsici. Symptoms included a foliar blight and stem, root, and fruit rot. Plants eventually wilted and died. Symptomatic plants were collected from chili- and sweet pepper-production areas in central, southern, and eastern Taiwan. Fifty-three isolates from single zoospores were identified by PCR using species-specific primers CAPFW/CAPRV2 (4). Mating type was determined by co-inoculating rape seed agar plates (3) with mycelial plugs of the tester and a known isolate. Pc134, maintained by the mycology unit at The World Vegetable Center, and 27220, provided by P. J. Ann at the Taiwan Agricultural Research Institute, were used as reference isolates of A1 and A2 mating types, respectively. Plates were examined microscopically for oospores after 5 to 7 days of incubation at 24°C in the dark. Of the 53 isolates, 15 were identified as the A2 mating type and the remaining 38 isolates were identified as A1. The A2 mating type was found in the central and southern regions while the A1 mating type was widely distributed across all three regions. The sporangia of the A2 mating type were 60.4 to 73.4 × 40.9 to 51.8 µm (average 69.2 × 44.7 µm), whereas sporangia of the A1 mating type were 50.1 to 73.9 × 37.9 to 48.1 µm (average 61.4 × 44.1 µm). In general, the A2 mating type produced longer sporangia and only a few isolates produced chlamydospores in V8 broth and on agar. To our knowledge, this is the first report of the A2 mating type of P. capsici infecting peppers in Taiwan. The presence of both mating types in the same field has been observed. References: (1) P. J. Ann et al. Plant Pathol. Bull. 17:69, 2008. (2) L. S. Leu and C. W. Kao. Plant Prot. Bull. (Taiwan) 23:59, 1981. (3) M. M. Sautor. Mycologia 59:161, 1967. (4) C. Silvar et al. Eur. J. Plant Pathol. 112:43, 2005.
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BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is characterized genetically by germline mutations in DNA mismatch repair (MMR) genes. Immunohistochemistry (IHC) has high sensitivity and specificity for identifying MMR-deficient tumours. This study investigated the clinical presentations and frequency of HNPCC in Taiwan by combined Amsterdam II criteria (AC-II) and IHC. METHODS: In 1995-2003, 7108 patients with primary colorectal cancer registered in Chang Gung Memorial Hospital's Colorectal Cancer Registry were screened using AC-II. Tumour specimens were analysed for MMR protein expression by IHC, and relevant clinicopathological details were documented. RESULTS: Some 83 patients fulfilled the AC-II. Clinicopathologically, 43 patients (52 per cent) had proximal tumours, ten (12 per cent) had poorly differentiated cancers, 17 (20 per cent) had mucinous adenocarcinoma and 51 (61 per cent) had stage I-II tumours. Seventeen patients developed second primary colonic and extracolonic cancers over a mean 7.2-year follow-up. Immunohistochemically, 58 patients were MMR protein deficient. They had a significantly earlier age of onset (P < 0.001), more proximal tumour location (P = 0.002), less advanced tumour stage (P = 0.008) and more second primary cancers (P = 0.017) compared with MMR-competent patients. CONCLUSION: These data show significant differences in clinical features between MMR protein-deficient and MMR competent subgroups.
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Neoplasias Colorretais Hereditárias sem Polipose/metabolismo , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/deficiência , Proteínas de Neoplasias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina Trifosfatases/deficiência , Adenosina Trifosfatases/genética , Adulto , Idoso , Estudos de Coortes , Pólipos do Colo/epidemiologia , Pólipos do Colo/genética , Pólipos do Colo/metabolismo , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Enzimas Reparadoras do DNA/deficiência , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/deficiência , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/metabolismo , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prevalência , Taiwan/epidemiologiaRESUMO
Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.