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1.
Fa Yi Xue Za Zhi ; 35(4): 448-454, 2019 Aug.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31532156

RESUMO

Abstract: Objective To analyze the genetic phenotypes of Y-chromosome STR and SNP in Han male population of Wujiang area, Suzhou City and explore the genetic structure of population of Wujiang area for further examination of regional-specific Y-SNP genetic markers ancestor haplogroups. Methods Blood samples of 472 Wujiang area Han males were randomly collected and genotyped by YfilerTM Plus PCR Amplification Kit. The allele frequencies and haplotype frequencies of each locus were obtained using the direct calculation method. Y-SNP haplogroups of each sample were estimated using Y-Predictor software and verified through experiments by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results A total of 453 haplotypes were found in the 27 Y-STR genetic markers in 472 Han males of Wujiang area. The haplotype diversity (HD) was 0.997 696 93, among which, the highest gene diversity (GD) value was DYF387S1a/b (GD=0.953 1) and the lowest was DYS438 (GD=0.321 8). Based on genotyping data of 27 Y-STRs and 472 samples, 132 haplogroups from C, D, N, O and Q, etc downstream Y-SNP haplogroups were estimated and then verified through experiments. Conclusion This study is based on Y-chromosome STR haplotypes, and predicts Y-SNP haplogroups by Y-Predictor software, then uses ARMS-PCR to verify. Y-SNP genetic markers were introduced to achieve precise analysis of the genetic structure of male families in population of three towns in Wujiang area.


Assuntos
Cromossomos Humanos Y/genética , Genética Populacional , China , Cidades , Frequência do Gene , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único
2.
Zhonghua Zhong Liu Za Zhi ; 41(8): 633-637, 2019 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-31434457

RESUMO

Objective: To investigate whether elevated levels of C-reactive protein (CRP) and neutrophil (NE) in the blood is associated with an increased risk of lung cancer incidence. Methods: From 2006 to 2007, all employees and retirees from Kailuan (Group) Limited liability Corporation were included in this Kailuan Cohort study. The last follow-up date was December 2015. Data on new cases of lung cancer were collected, and multivariable Cox proportional hazards regression models were used to the relationship between baseline CRP and NE at baseline and risk of lung cancer. Results: A total of 92 735 participants were enrolled in this study. During the follow-up, 850 new cases of lung cancer were identified. All subjects were divided into four groups according to the combination level of CRP and NE at baseline: CRP≤3 mg/L and NE≤4×10(9)/L(Group A), CRP≤3 mg/L and NE>4×10(9)/L(Group B), CRP>3 mg/L and NE≤4×10(9)/L(Group C), CRP>3 mg/L and NE>4×10(9)/L(Group D). The cumulative incidence of lung cancer were 950/100 000, 1 030/100 000, 1 081/100 000 and 1 596/100 000 in these four groups, respectively (P<0.001). Multivariate Cox proportional risk model showed that participants from Group D had an significantly increased 72% risks of lung cancer when compared to Group A (95% CI: 1.40~2.12, P<0.001). Stratified analyses gender showed that males in Group D had higher risk of lung cancer when compared with participants in Group A (HR=1.73, 95% CI: 1.40~2.15, P<0.001). Conclusion: Elevated levels of CRP and NE might increase the risk of lung cancer.


Assuntos
Neoplasias Pulmonares/epidemiologia , Proteína C-Reativa/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Masculino , Neutrófilos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
3.
Eur Rev Med Pharmacol Sci ; 23(13): 5851-5862, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31298336

RESUMO

OBJECTIVE: To explore the underlying mechanism of ncRNA (MIR22HG) in thyroid papillary carcinomas. PATIENTS AND METHODS: 40 pairs of thyroid papillary carcinomas tissues and adjacent normal tissues were collected from patients of the First Affiliated Hospital of Guangxi Medical University, who underwent oral surgery. qRT-PCR was applied to detect the expression of MIR22HG, miR-24-3p and p27kip1 in tissues and cells. Western blot was used to measure the protein level of p27kip1 in tissues and cells. Kaplan-Meier plot was used to analyze the overall survival rates in thyroid papillary carcinomas. Pearson's correlation analysis was used to analyze the correlation relationship among MIR22HG, miR-24-3p and p27kip1 expression. Flow cytometric assay was applied to measure cell apoptosis. Transwell assay was used to assess cell migration and invasion abilities. Luciferase reporter assay was applied to verify the molecular relationships among MIR22HG, miR-24-3p and p27kip1 in thyroid papillary carcinomas. RESULTS: LncRNA MIR22HG and p27kip expressed low while miR-24-3p expressed high in thyroid papillary carcinomas and cells. Overexpression of MIR22HG inhibited cell proliferation, migration and invasion, whereas promoted cell apoptosis in thyroid papillary carcinomas cells. However, these effects were reversed by upregulation of miR-24-3p. Further exploration showed that the promoted effects of miR-24-3p mimics on thyroid papillary carcinomas cells were suppressed by enhancing p27kip1 expression. Meanwhile, MIR22HG induced p27kip1 expression by binding miR-24-3p in thyroid papillary carcinomas. CONCLUSIONS: MIR22HG inhibited cell growth through modulating p27kip1 by decreasing miR-24-3p expression in thyroid papillary carcinomas, providing a new modulate mechanism and therapeutic targets in thyroid papillary carcinomas.

4.
Clin Genet ; 96(1): 35-42, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30883692

RESUMO

Genetic factors are considered to be important in the pathogenesis of diabetic nephropathy (DN). Despite several genome-wide association studies (GWASs) demonstrating that specific polymorphisms of candidate genes were associated with DN, there were some limitations in previous studies. We conducted a GWAS using customized DNA chips to identify novel susceptibility loci for DN in Korean. We analyzed a total of 414 DN cases and 474 normoalbuminuric diabetic hyper-controls across two stages using customized DNA chips containing 98 667 single nucleotide polymorphisms (SNPs). We explored the associations between SNPs and DN in samples from 87 DN cases, mostly confirmed by renal biopsy, and 104 diabetic hyper-controls, and replicated these associations in independent cohort samples with 327 DN cases and 370 diabetic hyper-controls. The top significant SNPs from the discovery samples were selected for replication in the independent cohort. rs3765156 in PIK3C2B was significantly associated with DN in the replication cohort after multiple test. The SNPs identified in our study provide new insights into the pathogenesis of DN in the Korean population. Additional studies are needed to determine biological effects and clinical utility of our findings.

5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(2): 218-226, 2019 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-30744276

RESUMO

Objective: From the economic point of view, this study was to systematically assess the status quo on lung cancer screening in the world and to provide reference for further research and implementation of the programs, in China. Methods: PubMed, EMbase, The Cochrane Library,CNKI and Wanfang Data were searched to gather papers on studies related to economic evaluation regarding lung cancer screening worldwide, from the inception of studies to June 30(th), 2018. Basic characteristics, methods and main results were extracted. Quality of studies was assessed. Cost were converted to Chinese Yuan under the exchange rates from the World Bank. The ratio of incremental cost-effectiveness ratio (ICER) to local GDP per capita were calculated. Results: A total of 23 studies (only 1 randomized controlled trial) were included and the overall quality was accepted. 22 studies were from the developed countries. Nearly half of the studies (11 studies) took 55 years old as the starting age of the screening program. Smoking history was widely applied for the selection of criteria on target populations (18). Low-dose computed tomography (LDCT) was involved in every study used to evaluate the economic effectiveness. Annual (17) and once-life time (7) screening were more common frequencies. 22 studies reported ICERs for LDCT screening, compared to no screening, of which 17 were less than 3 times local GDP per capita, and were considered as cost-effectiveness, according to the WHO's recommendation. 15 and 7 studies reported ICERs for annual and once-life time screening, of which 12 and 7 studies were in favor the results of their cost-effectiveness, respectively. Additionally, the cost-effectiveness of once-lifetime screening was likely to be superior to the annual screening. Differences of cost-effectiveness among the subgroups, by starting age or by the smoking history, might exist. Conclusions: Based on the studies, evidence from the developed countries demonstrated that LDCT screening programs on lung cancer, implemented among populations selected by age and smoking history, generally appeared more cost-effective. Combined with the local situation of health resource, the findings could provide direction for less developed regions/countries lacking of local evidence. Low frequency of LDCT screening for lung cancer could be adopted when budget was limited. Data on starting ages, smoking history and other important components related to the strategy of screening programs, needs to be precisely evaluated under the situation of local population.


Assuntos
Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Neoplasias Pulmonares/economia , China , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/prevenção & controle , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Osteoporos Int ; 29(12): 2645-2658, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30306226

RESUMO

By integrating the multilevel biological evidence and bioinformatics analyses, the present study represents a systemic endeavor to identify BMD-associated genes and their roles in skeletal metabolism. INTRODUCTION: Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes. METHODS: BMD-associated genes were identified by combining the summary statistic P values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential bone mineral density (BMD)-associated variants were evaluated by estimating the correlation of the P values of the same single-nucleotide polymorphisms (SNPs)/genes between the two consecutive Genetic Factors for Osteoporosis Studies (GEFOS) with largely overlapping samples. RESULTS: Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, three novel genes (UBTF, AAAS, and C11orf58) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants. CONCLUSIONS: Gene-based analysis as a supplementary strategy to SNP-based genome-wide association studies, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes.


Assuntos
Densidade Óssea/genética , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/fisiologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(7): 909-913, 2018 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-30060303

RESUMO

Objective: To investigate the association between alcohol consumption and lung cancer risk in Chinese males. Methods: Information on alcohol consumption and outcomes were collected on a biennial basis among males in Kailuan Cohort (2006-2015). In addition, electronic databases of hospitals affiliated to Kailuan Community, Insurance Systems of Kailuan Community and Tangshan were also used for supplementary information retrieval. Cox proportional hazards regression models were used to evaluate the hazard ratio (HR) and 95%CI of baseline frequency and type of alcohol consumption associated with lung cancer risk in males. Non-drinkers were used as control group. Results: A total of 101 751 males were included and 913 new lung cancer cases were identified in the Kailuan male cohort study, with a total follow-up time of 808 146.56 person-years and a median follow-up time of 8.88 years by 31 December 2015. After adjusting for potential confounding factors, the HR of former drinkers, occasional drinkers (<1/day) and drinkers (≥1/day) were 1.30 (95%CI: 0.90-1.88), 0.80 (95%CI: 0.64-1.01) and 1.04 (95%CI: 0.85-1.27), respectively, compared with non-drinkers. In addition, drinking beer/red wine (HR=0.91, 95%CI: 0.69-1.20) and white wine (HR=0.99, 95%CI: 0.83-1.19) showed no significant association with lung cancer. The results were similar when stratified analysis were conducted. Conclusion: Our study results don't support the hypothesis that alcohol consumption is significantly associated with the risk of lung cancer in males.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , China/epidemiologia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(5): 604-608, 2018 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-29860802

RESUMO

Objective: To assess the association and intensity of baseline TC level with the incidence of lung cancer in men in China. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history, anthropometry and TC level were collected at the baseline interview, as well as the information of newly-diagnosed lung cancer cases during the follow-up period. According to guidelines for blood lipids in Chinese adults and the distribution in the population, TC level was classified into five groups as followed: <160, 160-, 180-, 200- and ≥240 mg/dl, with the second quintile group (160- mg/dl) serving as the referent category. Cox proportional hazards regression model and restricted cubic spline (RCS) model were used to evaluate the association and the nonlinear association between baseline TC level and the risk of lung cancer in the men. Results: By December 31, 2014, for the 109 884 men, a follow up of 763 819.25 person-years was made with a median follow-up period of 7.88 years. During the follow up, 808 lung cancer cases were identified. After adjustment for age, education level, income level, smoking status, alcohol consumption level, history of dust exposure, FPG level and BMI, HR (95%CI) of lung cancer for men with lower TC level (<160 mg/dl) and higher TC level (≥240 mg/dl) were 1.34 (1.04- 1.72) and 1.45 (1.09-1.92), respectively, compared with men with normal TC level (160- mg/dl). The results didn't change significantly after exclusion of newly diagnosed cancer cases within 2 years of follow up and subjects with the history of hyperlipidemia. Conclusion: Our results showed that TC might be associated with higher risk of lung cancer. Men with lower TC level or higher TC level had higher risk for lung cancer. Keep moderate TC level might be one of the effective precaution for the prevention of lung cancer.


Assuntos
Colesterol/sangue , Neoplasias Pulmonares/epidemiologia , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Estudos de Coortes , Humanos , Incidência , Lipídeos , Neoplasias Pulmonares/etnologia , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
10.
Br J Dermatol ; 179(5): 1088-1094, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29723931

RESUMO

BACKGROUND: Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown. OBJECTIVES: To examine the association between AD use and cSCC risk among a cohort of non-Hispanic white individuals with hypertension enrolled in a comprehensive integrated healthcare delivery system in northern California (n = 28 357). METHODS: Electronic pharmacy data were used to determine exposure to ADs, which were classified as photosensitizing, nonphotosensitizing or unknown, based on published literature. We identified patients who developed a cSCC during follow-up (n = 3010). We used Cox modelling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Covariates included age, sex, smoking, comorbidities, history of cSCC and actinic keratosis, survey year, healthcare utilization, length of health plan membership and history of photosensitizing AD use. RESULTS: Compared with nonuse of ADs, risk of cSCC was increased with ever having used photosensitizing ADs (aHR = 1·17, 95% CI 1·07-1·28) and ever having used ADs of unknown photosensitizing potential (aHR = 1·11, 95% CI 1·02-1·20), whereas no association was seen with ever having used nonphotosensitizing ADs (aHR = 0·99; 95% CI 0·91-1·07). Additionally, there was a modest increased risk with an increased number of prescriptions for photosensitizing ADs (aHR = 1·12, 95% CI 1·02-1·24; aHR = 1·19, 95% CI 1·06-1·34; aHR = 1·41, 95% CI 1·20-1·67 for one to seven, eight to 15 and ≥ 16 fills, respectively). CONCLUSIONS: These findings provide moderate support for an increased cSCC risk among individuals treated with photosensitizing ADs.


Assuntos
Anti-Hipertensivos/efeitos adversos , Carcinoma de Células Escamosas/epidemiologia , Hipertensão/tratamento farmacológico , Fármacos Fotossensibilizantes/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Luz Solar/efeitos adversos , Idoso , California/epidemiologia , Carcinoma de Células Escamosas/etiologia , Prescrições de Medicamentos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/etiologia
11.
Zhonghua Yu Fang Yi Xue Za Zhi ; 52(5): 511-516, 2018 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-29747343

RESUMO

Objective: To investigate the association between tea consumption and lung cancer risk in Chinese males. Methods: Tea consumption and incident lung cancer cases were collected on a biennial basis among males in Kailuan Cohort during 2006-2015. Up to 31st December 2015, a total of 103 010 male candidates from the Chinese Kailuan Male Cohort Study were enrolled in the present study. Cox proportional hazards regression model was used to evaluate the association between tea consumption and risk of lung cancer in males. Results: The age of male candidates was (51.3±13.4)years old. There were 828 810.74 person-years of follow-up and 8.91 years of median follow-up period. During the follow-up, 964 lung cancer cases were identified. In male, the rate of never cosumers, tea drinkers (<4/week) and tea drinkers (≥4/week) were 58.17%(n=59 926), 24.04%(n=24 765) and 17.78%(n=18 319), respectively. After adjustment for potential confounding factors, HR (95%CI) of lung cancer for subjects with tea drinkers (<4/week) and tea drinkers (≥4/week) were 0.80 (0.63-1.02) and 1.02 (0.80-1.30), respectively, as compared with never cosumers. The results showed no significant association with lung cancer. Stratification analysis and sensitivity analysis showed no significant changes. Conclusion: Our study has not found that tea consumption is significantly associated with the risk of male lung cancer.


Assuntos
Neoplasias Pulmonares/epidemiologia , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Fatores de Risco , Chá
12.
Zhonghua Xue Ye Xue Za Zhi ; 39(5): 408-413, 2018 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-29779352

RESUMO

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.


Assuntos
Bortezomib/uso terapêutico , Aberrações Cromossômicas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
13.
Artigo em Chinês | MEDLINE | ID: mdl-29798289

RESUMO

Objective:To investigate the effectiveness of balloon catheter dilation (BCD) in the treatment of chronic rhinosinusitis, and to analyse the possible factors which lead to BCD failure, as well as to provide basic reference for BCD clinical usage.Method:Forty-six sinuses of 32 patients with chronic rhinosinusitis were underwent "Balloon-only" BCD or "FESS assisted" BCD at our institution between September 2014 and December 2016. By recording details of the operation of all the subjects in this study and following up the clinical symptoms, nasal endoscopy, computed tomography of the sinuses, and postoperative complications six months after operation, to evaluate the difficulty, safety, effectiveness and especially, the failing reasons of BCD.Result:BCD was approached in 46 sinuses (19 maxillary sinus, 22 frontal and 5 sphenoid), and succeeded in 13 maxillary sinuses, 19 frontal sinuses, and 4 sphenoid sinuses. Of the 13 maxillary sinuses, there were 9 sinuses underwent "Balloon-only" procedure, other 4 cases underwent "FESS assisted" procedure. There were 3 cases of frontal sinus failed, because of the frontal recess anatomical complexity and the twisted drainage. Of the 5 sphenoid sinuses, 4 cases succeeded, including fungal sphenoiditis cases, in which the mould was completely cleared through the dilated ostia, and 1 case failed. All the patients were followed up for 1, 3 and 6 months of patient's quality of life, nasal endoscope, computed tomography of the sinuses. The results showed that the SNOT-20 scores of the quality of life in significant relief of symptoms, nasal mucosa status improved significantly compared with the preoperative, dilated ostium remains open, no obvious scar formation, no severe operative complications.Conclusion:Balloon catheter dilation in the treatment of chronic rhinosinusitis is safe and effective. But the operation indications is limited, and many factors influence the success rate of BCD, so, preoperatively gaining the information of nasal cavity and anatomical structure around ostium according to patients' nasal endoscopy and sinus CT is critical to success of BCD.


Assuntos
Cateterismo , Rinite/terapia , Sinusite/terapia , Doença Crônica , Dilatação , Endoscopia , Humanos , Qualidade de Vida , Resultado do Tratamento
14.
Inflamm Bowel Dis ; 24(7): 1520-1530, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29668982

RESUMO

Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.


Assuntos
Colectomia/estatística & dados numéricos , Colite Ulcerativa/terapia , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Criança , Pré-Escolar , Colectomia/efeitos adversos , Colite Ulcerativa/epidemiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Reino Unido/epidemiologia
15.
Allergy ; 73(3): 627-634, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28944471

RESUMO

BACKGROUND: Aberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma. METHODS: Ten exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases. RESULTS: Exhaled LTB4 , LTE4 , PGE2, and LXA4 showed significant difference between asthmatics (N = 60) and controls (N = 20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls was partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver operating characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB4 , LXA4 , together with FeNO and FEV1 , distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as "asthma classification ratio" was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively. CONCLUSIONS: In a pediatric study population in Taiwan, the levels of exhaled LTB4 , LTE4 , LXA4, and PGE2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB4 and LXA4 , together with FeNO and FEV1 , best characterized childhood asthma.


Assuntos
Asma/classificação , Asma/diagnóstico , Biomarcadores/análise , Algoritmos , Área Sob a Curva , Testes Respiratórios , Criança , Pré-Escolar , Dinoprostona/análise , Eicosanoides/análise , Feminino , Volume Expiratório Forçado , Humanos , Leucotrieno B4/análise , Leucotrieno E4/análise , Lipoxinas/análise , Masculino , Óxido Nítrico/análise , Curva ROC , Sensibilidade e Especificidade
16.
Zhonghua Yi Xue Za Zhi ; 97(40): 3158-3161, 2017 Oct 31.
Artigo em Chinês | MEDLINE | ID: mdl-29081162

RESUMO

Objective: To investigate whether elevated levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) at baseline are associated with an increased risk of colorectal cancer in Kailuan male cohort. Methods: Since May 2006, males from Kailuan cohort were included in this study. Information on demographics, medical history, anthropometry, hsCRP and NE were collectedat baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) of association between baseline hsCRP and NE and colorectal cancer risk. Results: By December 31, 2015, a total of 73 869 participants were enrolled in this study. During the follow-up, 336 incident colorectal cancer cases were identified. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of colorectal cancer were 456/10(5,) 510/10(5) and 746/10(5) in these 3 groups, respectively (χ(2)=10.79, P=0.005). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significant increased risks of colorectal cancer (HR=1.38, 95%CI: 1.05-1.81, P=0.020)after adjusting for age, gender, smoking, drinking, BMI, diabetes and income. Furthermore, subjects were divided into two groups according to the level of NE (≤ 4.08×10(9)/L and > 4.08×10(9)/L). Multivariable Cox proportional hazards regression models indicated that there is no statistical significance of association between NE and colorectal cancer. Conclusions: Elevated levels of hsCRP at baseline might increase the risk of colorectal cancer in males.


Assuntos
Biomarcadores Tumorais/análise , Proteína C-Reativa/análise , Neoplasias Colorretais/diagnóstico , Neoplasias do Colo , Humanos , Incidência , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
17.
Cancer Res ; 77(21): 5989-6000, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28923858

RESUMO

CD137 (4-1BB) is a T-cell costimulatory molecule, and agonstic CD137 antibodies are currently being evaluated in the clinic as cancer immunotherapy. Recently, it was found that CD137-/- mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here, we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results. Specifically, CD137L suppressed intratumoral differentiation of IL12-producing CD103+ DC and type 1 tumor-associated macrophages (TAM). Differentiation of these cell types is important because they are required to generate IFNγ-producing CD8+ cytotoxic T lymphocytes (Tc1). Notably, CD137L blockade increased levels of IL12 and IFNγ, which promoted intratumoral differentiation of IFNγ-producing Tc1, IL12-producing CD103+ DC, and type 1 TAM within tumors. Our results offer an explanation for the paradoxical effects of CD137 blockade, based on differential immunomodulatory effects of CD137 signaling and reverse signaling in T cells and DC, respectively. Further, they show how CD137L blockade can seed a forward-feedback loop for activation of CD103+ DC/type 1 TAM and Tc1 that can create a self-perpetuating cycle of highly effective immunosurveillance. Cancer Res; 77(21); 5989-6000. ©2017 AACR.


Assuntos
Ligante 4-1BB/imunologia , Anticorpos Monoclonais/farmacologia , Neoplasias/imunologia , Transdução de Sinais/efeitos dos fármacos , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Ligante 4-1BB/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neoplasias/genética , Neoplasias/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
18.
Opt Express ; 25(7): 7627-7636, 2017 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-28380882

RESUMO

Broad expansion of optical frequency comb (OFC) by the self-Raman scattering is numerically analyzed and experimentally accomplished in a coupled-cavity self-mode-locked (SML) monolithic Yb:KGW laser. The gain medium is coated to achieve the monolithic SML operation and a partially reflective mirror is further exploited to form the coupled cavity and to multiply the repetition rate up to 128.9 GHz. With a coupled reflectivity of 95%, it is experimentally found that not only the first-order but also second-order stimulated Raman scattering (SRS) can be efficiently generated. The mode-locked OFC can be consequently expanded to reach approximately 8.4 THz, leading the pulse width to be as narrow as 53 fs. At the pump power of 8.7 W, the total output power for the fundamental and the first- and second-Stokes waves can be maintained at 1.6 W. The present exploration provides a promising way to generate the ultrahigh-repetition-rate broadband OFC via the simultaneous SML and SRS processes.

19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 38(2): 137-141, 2017 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-28231654

RESUMO

Objective: To investigate the association between waist circumference and risk of male lung cancer incidence. Methods: Since May 1, 2006, all the male employees including the retirees in Kailuan Group had been recruited into a Chinese Kailuan Male Cohort study. Information on anthropometries including body weight, height and waist circumference were collected at the baseline investigation, as well as information on newly-diagnosed lung cancer cases during the follow-up period. Waist circumference was grouped by quintiles of the population waist circumference distribution and categorized into the following five groups: <80, 80-, 85-, 90- and ≥95 cm, with the relevant normal group, the second quintile group (80-cm), serving as the referent category. Multivariable Cox proportional hazards regression models were used to evaluate the association between levels of waist circumference and risk of lung cancer. Results: A total of 105 386 males were recruited in the study, with 739 651.13 person-years of follow-up and an average follow-up period of 7.00 years. By the end of 2014, a total of 707 lung cancer cases were identified in the cohort study. Compared with males having the 80-cm of waist circumference, the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer were 1.17(0.90-1.52), 0.96(0.74-1.23), 0.94(0.72-1.21) and 0.80(0.63-1.03) for the <80, 85-, 90- and ≥95 cm of waist circumference, after adjustment for potential confounding factors including age, education level, smoking status and pack-year amount, alcohol consumption, physical activities, environment for working place and the prevalence on diabetes. The inverse association existed in smokers (≥95 cm compared to 80-cm of waist circumference: HR=0.69, 95%CI: 0.48-0.99) and alcohol drinkers (≥95 cm compared to 80-cm of waist circumference: HR=0.65, 95%CI: 0.45-0.94) when analysis was conducted in subgroups stratified by smoking or alcohol drinking status. Conclusion: Waist circumference might be inversely associated with male lung cancer risk.


Assuntos
Neoplasias Pulmonares/epidemiologia , Fumar/efeitos adversos , Circunferência da Cintura , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Antropometria , Índice de Massa Corporal , Peso Corporal , Exercício , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia
20.
Transl Psychiatry ; 7(2): e1026, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28170005

RESUMO

Interferon alpha (IFN-α)-treated patients commonly develop depression during the therapy period. Although most IFN-α-induced depressive disorders achieve remission after IFN-α therapy, no studies have examined the long-term mood effects of IFN-α treatment. We conducted a 12-year population-based cohort study of hepatitis C virus (HCV)-infected patients who were older than 20 years and had received IFN-α therapy. The sample was obtained from the Taiwan National Health Insurance Research Database. The cohort included patients with and without IFN-α-induced depression, matched randomly by age, sex and depression history, at a ratio of 1:10. The follow-up started after the last administration of IFN-α and was designed to determine the incidence of recurrent depressive disorder after IFN-α therapy. A total of 156 subjects were identified as having IFN-α-induced depression and achieving full remission after IFN-α therapy. The overall incidence of recurrent depressive disorders among patients with and without IFN-α-induced depression was 56.8 (95% confidence interval (CI), 42.4-76.1) and 4.1 (95% CI, 2.9-5.8) cases, respectively, per 100 000 person-years, P<0.001. The adjusted hazard ratios for recurrent depressive disorder were 13.5 (95% CI, 9.9-18.3) in the IFN-α-treated cohort and 22.2 (95% CI, 11.2-44.2) in the matched cohort for IFN-α-induced depression patients after adjusting for age, sex, income, urbanization and comorbid diseases. IFN-α-induced depression was associated with a high risk of recurrent depression. It was not a transient disease and might be considered an episode of depressive disorder. Continuation therapy might be considered, and further research is needed.


Assuntos
Antivirais/efeitos adversos , Transtorno Depressivo Maior/induzido quimicamente , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Transtorno Depressivo/induzido quimicamente , Transtorno Depressivo/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Taiwan/epidemiologia
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