Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
1.
Front Oncol ; 10: 217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219060

RESUMO

Background: Patients with metastatic radioiodine-refractory papillary thyroid carcinoma (PTC) have limited treatment options and a poor prognosis. There is an urgent need to develop new drugs targeting PTC for clinical application. Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is highly selective for vascular endothelial growth factor receptor-2 (VEGFR2) and exhibits antitumor effects in a variety of solid tumors. Although apatinib has been shown to be safe and efficacious in radioiodine-refractory differentiated thyroid cancer, the mechanism underlying its antitumor effect is unclear. In this report, we explored the effects of apatinib on PTC in vitro and in vivo. Methods: VEGFR2 expression levels were evaluated by immunohistochemistry (IHC), qPCR, and western blotting (WB). The effects of apatinib on cell viability, colony formation, and migration in the Transwell assay were assessed in vitro, and its effect on tumor growth rate was assessed in vivo. In addition, the levels of proteins in signaling pathways were determined by WB. Finally, the autophagy level was assessed by WB, immunofluorescence (IF), and transmission electron microscopy. Results: We found that high VEGFR2 expression is associated with tumor size, T stage, and lymph node metastasis in patients with PTC and that apatinib inhibits PTC cell growth, promotes apoptosis, and induces cell cycle arrest through the PI3K/Akt/mTOR signaling pathway. Moreover, apatinib induces autophagy, and pharmacological inhibition of autophagy or small interfering RNA (siRNA)-mediated targeting of autophagy-associated gene 5 (ATG5) can further increase PTC cell apoptosis. Conclusion: Our data suggest that apatinib can induce apoptosis and autophagy via the PI3K/Akt/mTOR signaling pathway for the treatment of PTC and that autophagy is a potential novel target for future therapy in resistant PTC.

2.
Sci Total Environ ; 709: 136227, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31927432

RESUMO

Vehicle emissions have become an increasingly important source to air pollution in China, thus an accurate estimate of vehicle emissions is essential but challenging for policy-making toward air quality improvement. Since vehicle emissions are episodic, roadway-based micro/meso-scale emissions are getting more and more attention for roadway exposure assessment and accuracy improvement of emission inventory. Hence, it is necessary to characterize the temporal and spatial distribution of vehicle emissions. However, due to the large number of vehicle population and managerial difficulties, it might not be practical to develop vehicle emission inventory based on all individual vehicles at a city level. This study aimed to develop an approach to use web-based real-time traffic data to estimate meso-scale vehicle emissions at a city level. Taking Chengdu as an example, traffic characteristics include driving modes, traffic flows, and fleet compositions under different traffic conditions were quantified using real-world measurements. Web-based traffic data was shown to have adequate accuracy for traffic characterization and thus emission estimation. Real-time traffic conditions of the study area derived from web-based traffic data were then matched with corresponding traffic characteristics. Combining with vehicle modal emission rates, roadway-based vehicle emissions were quantified both spatially and temporally. As expected, estimated roadway-based emissions correlated well with traffic conditions both temporally and spatially. Heavier traffic is usually associated with higher emissions. This study demonstrated that the web-based traffic data can be used in transportation and environment related research. Findings from this work can be used for hotspot identification in traffic and emissions and the associated risk analysis, traffic management, and many other applications.

3.
Gut ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818908

RESUMO

OBJECTIVE: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). DESIGN: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as 'positive' and 'less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. RESULTS: We initially identified 18 independent variants at 16 loci that were classified as 'positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as 'less-credible positive' SNPs; 72.2% of the 'positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to 'less-credible' positive (reducing the 'positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-analyses found no evidence to support their associations with CRC risk. CONCLUSION: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.

4.
PLoS Med ; 16(10): e1002937, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31626644

RESUMO

BACKGROUND: The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. METHODS AND FINDINGS: A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. CONCLUSION: In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities.


Assuntos
Bancos de Espécimes Biológicos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Pleiotropia Genética , Ácido Úrico/sangue , Adulto , Idoso , Teorema de Bayes , Doenças Cardiovasculares/complicações , Estudos de Coortes , Comorbidade , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Reino Unido
5.
JMIR Med Inform ; 7(4): e14325, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31553307

RESUMO

BACKGROUND: The phecode system was built upon the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for phenome-wide association studies (PheWAS) using the electronic health record (EHR). OBJECTIVE: The goal of this paper was to develop and perform an initial evaluation of maps from the International Classification of Diseases, 10th Revision (ICD-10) and the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes to phecodes. METHODS: We mapped ICD-10 and ICD-10-CM codes to phecodes using a number of methods and resources, such as concept relationships and explicit mappings from the Centers for Medicare & Medicaid Services, the Unified Medical Language System, Observational Health Data Sciences and Informatics, Systematized Nomenclature of Medicine-Clinical Terms, and the National Library of Medicine. We assessed the coverage of the maps in two databases: Vanderbilt University Medical Center (VUMC) using ICD-10-CM and the UK Biobank (UKBB) using ICD-10. We assessed the fidelity of the ICD-10-CM map in comparison to the gold-standard ICD-9-CM phecode map by investigating phenotype reproducibility and conducting a PheWAS. RESULTS: We mapped >75% of ICD-10 and ICD-10-CM codes to phecodes. Of the unique codes observed in the UKBB (ICD-10) and VUMC (ICD-10-CM) cohorts, >90% were mapped to phecodes. We observed 70-75% reproducibility for chronic diseases and <10% for an acute disease for phenotypes sourced from the ICD-10-CM phecode map. Using the ICD-9-CM and ICD-10-CM maps, we conducted a PheWAS with a Lipoprotein(a) genetic variant, rs10455872, which replicated two known genotype-phenotype associations with similar effect sizes: coronary atherosclerosis (ICD-9-CM: P<.001; odds ratio (OR) 1.60 [95% CI 1.43-1.80] vs ICD-10-CM: P<.001; OR 1.60 [95% CI 1.43-1.80]) and chronic ischemic heart disease (ICD-9-CM: P<.001; OR 1.56 [95% CI 1.35-1.79] vs ICD-10-CM: P<.001; OR 1.47 [95% CI 1.22-1.77]). CONCLUSIONS: This study introduces the beta versions of ICD-10 and ICD-10-CM to phecode maps that enable researchers to leverage accumulated ICD-10 and ICD-10-CM data for PheWAS in the EHR.

6.
Int J Epidemiol ; 48(5): 1425-1434, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518429

RESUMO

BACKGROUND: Vitamin D deficiency is highly prevalent across the globe. Existing studies suggest that a low vitamin D level is associated with more than 130 outcomes. Exploring the causal role of vitamin D in health outcomes could support or question vitamin D supplementation. METHODS: We carried out a systematic literature review of previous Mendelian-randomization studies on vitamin D. We then implemented a Mendelian Randomization-Phenome Wide Association Study (MR-PheWAS) analysis on data from 339 256 individuals of White British origin from UK Biobank. We first ran a PheWAS analysis to test the associations between a 25(OH)D polygenic risk score and 920 disease outcomes, and then nine phenotypes (i.e. systolic blood pressure, diastolic blood pressure, risk of hypertension, T2D, ischaemic heart disease, body mass index, depression, non-vertebral fracture and all-cause mortality) that met the pre-defined inclusion criteria for further analysis were examined by multiple MR analytical approaches to explore causality. RESULTS: The PheWAS analysis did not identify any health outcome associated with the 25(OH)D polygenic risk score. Although a selection of nine outcomes were reported in previous Mendelian-randomization studies or umbrella reviews to be associated with vitamin D, our MR analysis, with substantial study power (>80% power to detect an association with an odds ratio >1.2 for per standard deviation increase of log-transformed 25[OH]D), was unable to support an interpretation of causal association. CONCLUSIONS: We investigated the putative causal effects of vitamin D on multiple health outcomes in a White population. We did not support a causal effect on any of the disease outcomes tested. However, we cannot exclude small causal effects or effects on outcomes that we did not have enough power to explore due to the small number of cases.

7.
Biomater Sci ; 7(10): 4174-4185, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31380882

RESUMO

The homeostasis process in the gut tissue of humans relies on intestinal bacteria. However, the intestine is a complex structural tissue with a huge superficial area, and thus the effective application of probiotics in the treatment of Crohn's disease (CD) is still challenging. Herein, we show the feasibility of probiotic target delivery and retention using magnetic iron oxide nanoparticle-internalized Roseburia intestinalis, which can be easily directed by a magnetic field in vitro and in vivo. Subsequently, the increased colonization of this core profitable flora not only resulted in a better therapy effect than traditional intragastric administration but also altered the bacterial composition, leading to a higher diversity in microbial taxa in rats with colitis. Our findings illustrate the exciting opportunities that nanotechnology offers for alternative strategies to modulate biological systems remotely and precisely, which represent a step towards the wireless magnetic manipulation of living biological entities in microbiology.

8.
Mol Med Rep ; 20(2): 1007-1016, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173202

RESUMO

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), has a complex etiology that may be associated with dysbiosis of the microbiota. Previously, our study revealed significant loss of Roseburia intestinalis from the gut of untreated patients with CD, and that R. intestinalis exerted anti­inflammatory functions in TNBS­induced colitis; however, the function of R. intestinalis supernatant is unknown. Therefore, LPS­induced macrophages, including RAW264.7 macrophages and bone marrow­derived macrophages were treated with R. intestinalis supernatant. The results indicated that R. intestinalis supernatant suppressed expression of interleukin (IL)­6 and signal transducer and activator of transcription 3 (STAT3) by macrophages. Additionally, these findings were further verified in vivo in DSS­ and TNBS­induced mouse models of colitis. It was observed that R. intestinalis supernatant ameliorated IBD colitis by reducing the number of inflammatory macrophages and Th17 cells in the colon, and by downregulating the expression of IL­6 and STAT3. Finally, the non­protein components of R. intestinalis supernatant were examined using gas chromatography­mass spectrometry analysis and identified the presence of short­chain fatty acids. In conclusion, the results of the present study indicated that R. intestinalis supernatant may regulate immune responses and ameliorate colitis.


Assuntos
Clostridiales/fisiologia , Colite/terapia , Meios de Cultivo Condicionados/farmacologia , Imunidade Inata/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Animais , Clostridiales/química , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Meios de Cultivo Condicionados/química , Sulfato de Dextrana/administração & dosagem , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/isolamento & purificação , Regulação da Expressão Gênica , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células , Células RAW 264.7 , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Transdução de Sinais , Células Th17 , Ácido Trinitrobenzenossulfônico/administração & dosagem
10.
Scand J Gastroenterol ; 54(4): 432-440, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946611

RESUMO

Objective: Levels of oncostatin M (OSM) and the composition of gut microbiota predict responses to anti-TNF agents used for IBD therapy. Here, the aim was to investigate the effects of Roseburia intestinalis, a gut microbiota, on OSM and on intestinal barrier in colitis. Methods: In the murine model of 3% dextran sulfate sodium (DSS)-induced colitis, we tested disease activity index (DAI), colon length, histological score and expression of tight junction (TJ) proteins (ZO-1, occludin and claudin-1), OSM, TNF-α and TLR5. In addition, a cellular model was used to examine the role of R. intestinalis during secretion of OSM by lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and TLR5 knockout (TLR5 KO) mice. Furthermore, we evaluated the impact of OSM on expressions of TJ proteins by Caco-2 cells. Results: R. intestinalis in DSS-induced colitis decreased DAI score (p < .001), colon length shortening (6.46 ± 0.36 cm vs 5.65 ± 0.47 cm, p = .022), histological score (2.667 ± 1.15 vs 5.33 ± 1.14, p = .018) and increased expression of TJ proteins (p < .05). In addition, R. intestinalis reduced expression of OSM (p < .05) and TNF-α (p < .05), while increasing expression of TLR5 (p < .05). Furthermore, R. intestinalis reduced secretion of OSM (p < .05) by LPS-induced BMDMs isolated from WT and TLR5 KO mice. Moreover, OSM downregulated expression of TJ proteins (p < .05) by Caco-2 cells in a concentration-dependent manner. Conclusions: These results indicate that R. intestinalis attenuates inflammation in IBD by decreasing secretion of OSM and by promoting intestinal barrier function. Taken together, the data provide insight into the role of the gut microbiota in patients with IBD who are resistant to anti-TNF therapy.

11.
Biomed Pharmacother ; 114: 108800, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30921705

RESUMO

Chemoresistance is one of the major challenges for the breast cancer treatment. Owing to its heterogeneous nature, the chemoresistance mechanisms of breast cancer are complicated, and not been fully elucidated. The existing treatments fall short of offering adequate solution to drug resistance, so more effective approaches are desperately needed to improve existing therapeutic regimens. To overcome this hurdle, a number of strategies are being investigated, such as novel agents or drug carriers and combination treatment. In addition, some new therapeutics including gene therapy and immunotherapy may be promising for dealing with the resistance. In this article, we review the mechanisms of chemoresistance in breast cancer. Furthermore, the potential therapeutic methods to overcome the resistance were discussed.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Terapia Combinada/métodos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoterapia/métodos
12.
13.
BMC Med ; 16(1): 142, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30103784

RESUMO

BACKGROUND: Whilst observational studies establish that lower plasma 25-hydroxyvitamin D (25-OHD) levels are associated with higher risk of colorectal cancer (CRC), establishing causality has proven challenging. Since vitamin D is modifiable, these observations have substantial clinical and public health implications. Indeed, many health agencies already recommend supplemental vitamin D. Here, we explore causality in a large Mendelian randomisation (MR) study using an improved genetic instrument for circulating 25-OHD. METHODS: We developed a weighted genetic score for circulating 25-OHD using six genetic variants that we recently reported to be associated with circulating 25-OHD in a large genome-wide association study (GWAS) meta-analysis. Using this score as instrumental variable in MR analyses, we sought to determine whether circulating 25-OHD is causally linked with CRC risk. We conducted MR analysis using individual-level data from 10,725 CRC cases and 30,794 controls (Scotland, UK Biobank and Croatia). We then applied estimates from meta-analysis of 11 GWAS of CRC risk (18,967 cases; 48,168 controls) in a summary statistics MR approach. RESULTS: The new genetic score for 25-OHD was strongly associated with measured plasma 25-OHD levels in 2821 healthy Scottish controls (P = 1.47 × 10- 11), improving upon previous genetic instruments (F-statistic 46.0 vs. 13.0). However, individual-level MR revealed no association between 25-OHD score and CRC risk (OR 1.03/unit log-transformed circulating 25-OHD, 95% CI 0.51-2.07, P = 0.93). Similarly, we found no evidence for a causal relationship between 25-OHD and CRC risk using summary statistics MR analysis (OR 0.91, 95% CI 0.69-1.19, P = 0.48). CONCLUSIONS: Despite the scale of this study and employing an improved score capturing more of the genetic contribution to circulating 25-OHD, we found no evidence for a causal relationship between circulating 25-OHD and CRC risk. Although the magnitude of effect for vitamin D suggested by observational studies can confidently be excluded, smaller effects sizes and non-linear relationships remain plausible. Circulating vitamin D may be a CRC biomarker, but a causal effect on CRC risk remains unproven.


Assuntos
Neoplasias Colorretais/etiologia , Análise da Randomização Mendeliana/métodos , Vitamina D/análogos & derivados , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Vitamina D/efeitos adversos
14.
15.
Talanta ; 186: 299-305, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29784365

RESUMO

Mycotoxins threaten human health seriously because they usually exist in food, fodder and commodities. In this study, a rapid and sensitive immunoassay system for commonly encountered mycotoxins was established based on microfluidics and protein microarrays. Four mycotoxins (T-2 toxin, aflatoxin B1, ochratoxin A, and zearalenone) can be automatically detected in a custom-made microdevice within 30 min under the assistance of a prototype of the instrument with a fluid control system and an imaging system. Once the microdevices are fabricated, they are small-sized and user-friendly. Standard curves for each of the studied mycotoxins were generated with a good logistic correlation (R2 > 0.98). Working ranges from 0.1 to 20 ng/ml were employed in the immunoassay being the limit of detection achieved between 0.03 and 1.24 ng/ml. These values were calculated when the four mycotoxins were present in samples at the same time. Samples of spiked water and field corn were tested to assess the performance of our microfluidic-based detection technique for the mycotoxins. Recovery rates of mycotoxins from spiked water and corn samples were accessed and the results ranged from 80% to 110%, where the intra-assay coefficients of variation were under 15%. In summary, the system can realize rapid and reliable detection of multiple contaminants in actual samples automatically.


Assuntos
Análise de Alimentos , Contaminação de Alimentos/análise , Imunoensaio , Técnicas Analíticas Microfluídicas , Micotoxinas/análise , Zea mays/química
16.
Nutr Metab (Lond) ; 15: 34, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755575

RESUMO

Background: The meta-analyses of genome-wide association studies identified several waist-hip ratio (WHR) related loci in individuals of European ancestry. Since the pattern of fat distribution and the relationship between fat distribution and glucose metabolism disturbance in Chinese are different from those in Europeans, the present study aimed to explore the individual and cumulative effects of WHR-related loci on glycemic phenotypes in Chinese children. Methods: A total of 2030 children were recruited from two independent studies. Eleven single nucleotide polymorphisms (SNPs) were selected and genotyped using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Logistic regression and linear regression model were used to examine the association of 11 SNPs and genetic risk score (GRS) with impaired fasting glucose (IFG) and fasting plasma glucose (FPG), respectively. Results: Three SNPs (rs6795735, rs984222 and rs1011731) were nominally associated with IFG (all P < 0.05). Each WHR-increasing (C) allele of rs6795735 (ADAMTS9) was associated with a 40.1% increased risk of IFG (OR = 1.401, 95% CI = 1.131-1.735, P = 0.002), which remained significant after Bonferroni correction. We observed no association of both weighted and unweighted GRS with FPG and IFG (all P > 0.05). Conclusions: We identified individual effects of rs6795735 (ADAMTS9), rs984222 (TBX15-WARS2), and rs1011731 (DNM3-PIGC) on glycemic phenotypes in Chinese children for the first time. The study suggests that genetic predisposition to central obesity is associated with impaired fasting glucose, providing more evidence for the pathogenesis of diabetes.

17.
Zhongguo Fei Ai Za Zhi ; 21(3): 206-211, 2018 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-29587943

RESUMO

BACKGROUND: Da Vinci Surgical System is one of the greatest inventions of the 20th century, which represents the development direction of the precise minimally invasive surgical techniques, the aim of this study was to comparing the short-term outcomes between da Vinci robot-assisted lobectomy and video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer. METHODS: 45 pairs of non-small cell lung cancer patients underwent pulmonary lobectomy with da Vinci Robotic assisted thoracoscopic (RATS) and VATS approach during the same period from January 2014 to January 2017. The operative time, estimated blood loss (EBL), total number and total groups of dissected lymph nodes, postoperative duration of drainage, the first day volume of drainage, total volume of drainage were compared. RESULTS: No perioperative death and convertion to thoracotomy occured in both groups. There were significant difference between RATS group and VATS group in EBL [(50.30±32.33) mL vs (208.60±132.63) mL], the first day volume of drainage [(275.00±145.42) mL vs (347.60±125.80) mL], the dissected total number [(22.67±9.67) vs (15.51±5.41)] and total team [(6.31±1.43) vs (4.91±1.04)] of lymph node. There were no significant difference in other outcomes. CONCLUSIONS: RATS is safe and effective and took better short-outcomes than VATS in non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Robótica/métodos , Cirurgia Torácica Vídeoassistida/métodos , Toracoscopia/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Duração da Cirurgia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/instrumentação , Toracoscopia/instrumentação
18.
Int J Clin Oncol ; 23(4): 783-789, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29558001

RESUMO

BACKGROUND: Leptomeningeal metastasis is an uncommon but devastating complication. The incidence of non-Hodgkin's lymphoma has been increasing in recent decades, due to the poor central nervous system penetration of drugs and the prolonged overall survival of patients, leptomeningeal metastases has gradually increased over time. Patients with leptomeningeal metastases have short survival durations and poor quality of life; there are few studies about non-Hodgkin's lymphoma with leptomeningeal metastases. We investigated characteristics and outcomes of non-Hodgkin's lymphoma patients with leptomeningeal metastases. METHODS: This study included 27 non-Hodgkin's lymphoma patients with leptomeningeal metastases diagnosed at Tianjin Medical University Cancer Institute and Hospital between 2013 and 2016. Statistical analysis was performed to investigate the overall survival of non-Hodgkin's lymphoma with leptomeningeal metastases. RESULTS: Diffuse large B cell lymphoma was the most common cancer subtype (21/27, 78%), and more than half of the patients showed extranodal involvement (18/27, 67%). Survival analysis has shown extranodal involvement (P = 0.0205), International Prognostic Index (P = 0.0112), performance status (P < 0.0001), parenchymal involvement (P = 0.0330) and received radiotherapy (P = 0.0056) were predictive factors of prognosis for these patients with leptomeningeal metastases. Cox regression analysis has shown patients with concurrent parenchymal involvement and received radiotherapy are correlated with good prognosis. CONCLUSIONS: Given the small number of patients who were included, this study exhibited limitations with respect to analytical power and the random selection of patients. Nevertheless, this investigation revealed characteristics of non-Hodgkin's lymphoma patients with leptomeningeal metastases and suggested that such patients could benefit from multimodal therapy.


Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Carcinomatose Meníngea/mortalidade , Qualidade de Vida , Adolescente , Adulto , Terapia Combinada , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Carcinomatose Meníngea/secundário , Carcinomatose Meníngea/terapia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
19.
Ann Rheum Dis ; 77(7): 1039-1047, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29437585

RESUMO

OBJECTIVES: We aimed to investigate the role of serum uric acid (SUA) level in a broad spectrum of disease outcomes using data for 120 091 individuals from UK Biobank. METHODS: We performed a phenome-wide association study (PheWAS) to identify disease outcomes associated with SUA genetic risk loci. We then implemented conventional Mendelianrandomisation (MR) analysis to investigate the causal relevance between SUA level and disease outcomes identified from PheWAS. We next applied MR Egger analysis to detect and account for potential pleiotropy, which conventional MR analysis might mistake for causality, and used the HEIDI (heterogeneity in dependent instruments) test to remove cross-phenotype associations that were likely due to genetic linkage. RESULTS: Our PheWAS identified 25 disease groups/outcomes associated with SUA genetic risk loci after multiple testing correction (P<8.57e-05). Our conventional MR analysis implicated a causal role of SUA level in three disease groups: inflammatory polyarthropathies (OR=1.22, 95% CI 1.11 to 1.34), hypertensive disease (OR=1.08, 95% CI 1.03 to 1.14) and disorders of metabolism (OR=1.07, 95% CI 1.01 to 1.14); and four disease outcomes: gout (OR=4.88, 95% CI 3.91 to 6.09), essential hypertension (OR=1.08, 95% CI 1.03 to 1.14), myocardial infarction (OR=1.16, 95% CI 1.03 to 1.30) and coeliac disease (OR=1.41, 95% CI 1.05 to 1.89). After balancing pleiotropic effects in MR Egger analysis, only gout and its encompassing disease group of inflammatory polyarthropathies were considered to be causally associated with SUA level. Our analysis highlighted a locus (ATXN2/S2HB3) that may influence SUA level and multiple cardiovascular and autoimmune diseases via pleiotropy. CONCLUSIONS: Elevated SUA level is convincing to cause gout and inflammatory polyarthropathies, and might act as a marker for the wider range of diseases with which it associates. Our findings support further investigation on the clinical relevance of SUA level with cardiovascular, metabolic, autoimmune and respiratory diseases.


Assuntos
Predisposição Genética para Doença/epidemiologia , Estudo de Associação Genômica Ampla , Gota/genética , Multimorbidade , Infarto do Miocárdio/genética , Ácido Úrico/sangue , Adulto , Artrite/sangue , Artrite/epidemiologia , Artrite/genética , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Bancos de Espécimes Biológicos , Doença Celíaca/sangue , Doença Celíaca/epidemiologia , Doença Celíaca/genética , Feminino , Gota/sangue , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/genética , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Prognóstico , Medição de Risco , Reino Unido
20.
PLoS One ; 13(2): e0192470, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29447180

RESUMO

We study the structural instability mechanism and effect of a multi-echelon support in very-deep roadways. We conduct a scale model test for analysing the structural failure mechanism and the effect of multi-echelon support of roadways under high horizontal stress. Mechanical bearing structures are classified according to their secondary stress distribution and the strength degradation of the surrounding rock after roadway excavation. A new method is proposed by partitioning the mechanical bearing structure of the surrounding rock into weak, key and main coupling bearing stratums. In the surrounding rock, the main bearing stratum is the plastic reshaping and flowing area. The weak bearing stratum is the peeling layer or the caving part. And the key bearing stratum is the shearing and yielding area. The structural fracture mechanism of roadways is considered in analysing the bearing structure instability of the surrounding rock, and multi-echelon support that considers the structural characteristics of roadway bearings is proposed. Results of the experimental study indicate that horizontal pressure seriously influences the stability of the surrounding rock, as indicated by extension of the weak bearing area and the transfer of the main and key bearing zones. The falling roof, rib spalling, and floor heave indicate the decline of the bearing capacity of surrounding rock, thereby causing roadway structural instability. Multi-echelon support is proposed according to the mechanical bearing structure of the surrounding rock without support. The redesigned support can reduce the scope of the weak bearing area and limit the transfer of the main and key bearing areas. Consequently, kilometre-deep roadway disasters, such as wedge roof caving, floor heave, and rib spalling, can be avoided to a certain degree, and plastic flow in the surrounding rock is relieved. The adverse effect of horizontal stress on the vault, spandrel and arch foot decreases. The stability of the soft rock surrounding the roadways is maintained.


Assuntos
Estresse Mecânico , Transportes , Modelos Teóricos , Pressão
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA