| 1. |
- Wang, Chao-Jie, et al.
(författare)
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Prognostic value of nuclear FBI-1 in patients with rectal cancer with or without preoperative radiotherapy
- 2019
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 18:5, s. 5301-5309
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Tidskriftsartikel (refereegranskat)abstract
- Factor that binds to the inducer of short transcripts of the human immunodeficiency virus-1 (FBI-1) represents as a crucial gene regulator in colorectal cancer; however, the correlation between FBI-1 and preoperative radiotherapy (RT) in rectal cancer (RC) has not yet been reported. The aim was to detect FBI-1 expression in patients with RC with or without RT, by immunohistochemistry and quantitative polymerase chain reaction, and to analyze its association with clinicopathological features and response to RT. The results from immunohistochemistry analysis (n=139) and reverse transcription-quantitative polymerase chain reaction (n=55) demonstrated that FBI-1 was overexpressed in patients with RC, whether they had received preoperative RT or not. Subsequently, the association between FBI-1 expression, and the clinicopathological features and response to RT in patients with RC was analyzed. Cytoplasmic FBI-1 was upregulated in non-RT (n=77) and RT (n=62) groups (17.7 vs. 74.0%, P<0.001; 41.1 vs. 69.4%, P=0.002, respectively) of patients with RC compared with normal mucosa. However, nuclear FBI-1 was downregulated (75.8 vs. 22.1%, P<0.001; 83.9 vs. 35.5%, P<0.001, respectively) in both groups. RT had no significant effect on FBI-1 expression in RC tissues. Furthermore, nuclear FBI-1 was positively associated with tumor-node-metastasis stage and distant recurrence (P=0.003 and P=0.010, respectively). In patients with stage I, II or III RC, higher nuclear FBI-1 expression was associated with poorer disease-free survival [hazard ratio (HR)=1.934, 95% confidence interval (CI): 1.055-3.579, P=0.033] and overall survival (HR=2.174, 95% CI: 1.102-4.290, P=0.025), independently of sex, age, growth pattern, differentiation and RT. In addition, FBI-1 was positively correlated with numerous biological factors, including p73 [Spearman's correlation coefficient (rs)=0.332, P=0.007], lysyl oxidase (rs=0.234, P=0.043), Wrap53 (rs=-0.425, P=0.0002) and peroxisome proliferator-activated receptor δ (rs=-0.294, P=0.026). In conclusion, the present study demonstrated that nuclear FBI-1 was an independent prognostic factor in patients with RC and correlated with numerous biological factors, which indicated that it may have multiple roles in RC.
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| 2. |
- Zhao, Sen, et al.
(författare)
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Expanding the mutation and phenotype spectrum of MYH3-associated skeletal disorders
- 2022
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Ingår i: NPJ genomic medicine. - : Nature Publishing Group. - 2056-7944. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic variants in MYH3 cause distal arthrogryposis type 2A and type 2B3 as well as contractures, pterygia and spondylocarpotarsal fusion syndromes types 1A and 1B. These disorders are ultra-rare and their natural course and phenotypic variability are not well described. In this study, we summarize the clinical features and genetic findings of 17 patients from 10 unrelated families with vertebral malformations caused by dominant or recessive pathogenic variants in MYH3. Twelve novel pathogenic variants in MYH3 (NM_002470.4) were identified: three of them were de novo or inherited in autosomal dominant way and nine were inherited in autosomal recessive way. The patients had vertebral segmentation anomalies accompanied with variable joint contractures, short stature and dysmorphic facial features. There was a significant phenotypic overlap between dominant and recessive MYH3-associated conditions regarding the degree of short stature as well as the number of vertebral fusions. All monoallelic variants caused significantly decreased SMAD3 phosphorylation, which is consistent with the previously proposed pathogenic mechanism of impaired canonical TGF-β signaling. Most of the biallelic variants were predicted to be protein-truncating, while one missense variant c.4244T>G,p.(Leu1415Arg), which was inherited in an autosomal recessive way, was found to alter the phosphorylation level of p38, suggesting an inhibition of the non-canonical pathway of TGF-β signaling. In conclusion, the identification of 12 novel pathogenic variants and overlapping phenotypes in 17 affected individuals from 10 unrelated families expands the mutation and phenotype spectrum of MYH3-associated skeletal disorders. We show that disturbances of canonical or non-canonical TGF-β signaling pathways are involved in pathogenesis of MYH3-associated skeletal fusion (MASF) syndrome.
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| 3. |
- Fu, Jianjie, et al.
(författare)
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Elevated levels of perfluoroalkyl acids in family members of occupationally exposed workers : the importance of dust transfer
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The exposure pathways of perfluoroalkyl acids (PFAAs) to humans are still not clear because of the complex living environment, and few studies have simultaneously investigated the bioaccumulative behaviour of different PFAAs in humans. In this study, serum, dust, duplicate diet, and other matrices were collected around a manufacturing plant in China, and homologous series of PFAAs were analysed. PFAA levels in dust and serum of local residents in this area were considerably higher than those in non-polluted area. Although dietary intake was the major exposure pathway in the present study, dust ingestion played an important role in this case. Serum PFAAs in local residents was significantly correlated with dust PFAAs levels in their living or working microenvironment. Serum PFAAs and dust PFAAs were significantly higher in family members of occupational workers (FM) than in ordinary residents (OR) (p<0.01). After a careful analysis of the PFAAs exposure pathway, a potential pathway in addition to direct dust ingestion was suggested: PFAAs might transferred from occupational worker's clothes to dinners via cooking processes. The bioaccumulative potential of PFHxS and PFOS were higher than other PFAAs, which suggested a substantial difference between the bioaccumulative ability of perfluorinated sulfonic acids and perfluorinated carboxylic acids.
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| 4. |
- Gao, Yan, et al.
(författare)
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Differential accumulation and elimination behavior of perfluoroalkyl acid isomers in occupational workers in a manufactory in China
- 2015
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:11, s. 6953-6962
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Tidskriftsartikel (refereegranskat)abstract
- In this study, serum and urine samples were collected from 36 occupational workers in a fluorochemical manufacturing plant in China from 2008 to 2012 to evaluate the body burden and possible elimination of linear and branched perfluoroalkyl acids (PFAAs). Indoor dust, total suspended particles (TSP), diet, and drinking water samples were also collected to trace the occupational exposure pathway to PFAA isomers. The geometric mean concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) isomers in the serum were 1386, 371, and 863 ng mL(-1), respectively. The linear isomer of PFOS, PFOA, and PFHxS was the most predominant PFAA in the serum, with mean proportions of 63.3, 91.1, and 92.7% respectively, which were higher than the proportions in urine. The most important exposure routes to PFAA isomers in the occupational workers were considered to be the intake of indoor dust and TSP. A renal clearance estimation indicated that branched PFAA isomers had a higher renal clearance rate than did the corresponding linear isomers. Molecular docking modeling implied that linear PFOS (n-PFOS) had a stronger interaction with human serum albumin (HSA) than branched isomers did, which could decrease the proportion of n-PFOS in the blood of humans via the transport of HSA.
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| 5. |
- Hay, S. I., et al.
(författare)
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Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016 : A systematic analysis for the Global Burden of Disease Study 2016
- 2017
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Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1260-1344
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Tidskriftsartikel (refereegranskat)abstract
- Background: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE difered from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs ofset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the fve lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs ofset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention eforts, and development assistance for health, including fnancial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 6. |
- Ma, Ping, et al.
(författare)
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Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200â mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-Crossed D sign°[ and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50â mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects.
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| 7. |
- Pan, Yitao, et al.
(författare)
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First Report on the Occurrence and Bioaccumulation of Hexafluoropropylene Oxide Trimer Acid : An Emerging Concern
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:17, s. 9553-9560
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Tidskriftsartikel (refereegranskat)abstract
- Here, we report on the occurrence of a novel perfluoroalkyl ether carboxylic acid, ammonium perfluoro-2-[(propoxy)propoxy]-1-propanoate (HFPO-TA), in surface water and common carp (Cyprinus carpio) collected from the Xiaoqing River and in 'residents residing near a fluoropolymer production plant in Huantai County, China. Compared with the levels upstream of the Xiaoqing River, HFPO-TA concentrations (5200-68500 ng/L) were approximately 120-1600-times higher downstream after receiving fluoropolymer plant effluent from a tributary. The riverine discharge' of HFPO-TA was estimated to be 4.6 t/yr, accounting for 22% of total PFAS discharge. In the wild common carp collected downstream from the point source, HFPO-TA was detected in the blood (median: 1510 ng/mL), liver (587 ng/g ww), and muscle (118 ng/g ww). The log BCFbiood of HFPO-TA (2.18) was significantly higher than that of PFOA (1.93). Detectable levels of HFPO-TA were also found in the sera of residents (median: 2.93 ng/mL). This is the first report on the environmental occurrence and bioaccumulation of this novel chemical. Our results indicate an emerging usage of HFPO-TA in the fluoropolymer manufacturing industry and raise concerns about the toxicity and potential health risks of HFPO-TA to aquatic organisms and humans.
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| 8. |
- Pan, Yitao, et al.
(författare)
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Worldwide Distribution of Novel Perfluoroether Carboxylic and Sulfonic Acids in Surface Water
- 2018
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 52:14, s. 7621-7629
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Tidskriftsartikel (refereegranskat)abstract
- Driven by increasingly stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), novel fluorinated compounds have emerged on the market. Here we report on the occurrences of several perfluoroalkyl ether carboxylic and sulfonic acids (PFECAs and PFESAs), including hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA), ammonium 4,8-dioxa-3 H-perfluorononanoate (ADONA), chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), and its hydrogen-substituted analogue (6:2 H-PFESA) in surface waters from China ( n = 106), the United States ( n = 12), the United Kingdom ( n = 6), Sweden ( n = 10), Germany ( n = 14), The Netherlands ( n = 6), and Korea ( n = 6). Results showed that HFPO-DA, HFPO-TA, and 6:2 Cl-PFESA (median = 0.95, 0.21, and 0.31 ng/L, respectively) were frequently detected in all countries, indicating ubiquitous dispersal and distribution in global surface waters. The presence of 6:2 H-PFESA was widely detected in China (detection rate > 95%) but not in any other country. Only trace levels of ADONA (0.013-1.5 ng/L) were detected in the Rhine River flowing through Germany. The estimated total riverine mass discharges of HFPO-DA, HFPO-TA, and ΣPFESAs reached 2.6, 6.0, and 4.3 ton/year in five of the major river systems in China. Our results indicated that novel PFECAs and PFESAs might become global contaminants, and future investigations are warranted.
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| 9. |
- Vos, T., et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
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Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 10. |
- Zhang, Haiyan, et al.
(författare)
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Levels and distributions of hexachlorobutadiene and three chlorobenzenes in biosolids from wastewater treatment plants and in soils within and surrounding a chemical plant in China.
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:3, s. 1525-1531
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Tidskriftsartikel (refereegranskat)abstract
- Although hexachlorobutadiene (HCBD) was recently proposed as a candidate persistent organic pollutant (POP) under the Stockholm Convention, information about its environmental levels and distributions is still very limited. In this work, HCBD was determined in the sewage sludge from 37 wastewater treatment plants (WWTPs) in 23 cities and 17 soils near a chemical plant in China. Three chlorobenzenes (CBs) (1,2,4-trichlorobenzene, 1,2,4,5-tetrachlorobenzene, and hexachlorobenzene) were simultaneously studied to help better understand the environmental behavior of HCBD. Concentrations of HCBD in sludge samples ranged from <0.03 to 74.3 ng/g dry weight (dw) with a median value of 0.30 ng/g dw, which was lower than those of the three CBs. Levels of HCBD were not correlated with capacity of the WWTPs and total organic carbon. For soils, high level of HCBD was found in the sample within the plant, with a rapid decreasing concentration trend with the increase of distance from the plant. It was suspected that releasing as a byproduct during manufacturing of chlorinated chemicals was the primary source of HCBD in the studied location. Further risk assessment indicated that the environmental risk of HCBD to soil organisms and the health risk to employees were very low through soil exposure within the plant.
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