| 1. |
- Li, Wei, et al.
(författare)
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Non-lab and semi-lab algorithms for screening undiagnosed diabetes : A cross-sectional study
- 2018
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Ingår i: EBioMedicine. - : ELSEVIER SCIENCE BV. - 2352-3964. ; 35, s. 307-316
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Tidskriftsartikel (refereegranskat)abstract
- Background: The terrifying undiagnosed rate and high prevalence of diabetes have become a public emergency. A high efficiency and cost-effective early recognition method is urgently needed. We aimed to generate innovative, user-friendly nomograms that can be applied for diabetes screening in different ethnic groups in China using the non-lab or noninvasive semi-lab data. Methods: This multicenter, multi-ethnic, population-based, cross-sectional study was conducted in eight sites in China by enrolling subjects aged 20-70. Sociodemographic and anthropometric characteristics were collected. Blood and urine samples were obtained 2 h following a standard 75 g glucose solution. In the final analysis, 10,794 participants were included and randomized into model development (n - 8096) and model validation (n = 2698) group with a ratio of 3:1. Nomograms were developed by the stepwise binary logistic regression. The nomograms were validated internally by a bootstrap sampling method in the model development set and externally in the model validation set. The area under the receiver operating characteristic curve (AUC) was used to assess the screening performance of the nomograms. Decision curve analysis was applied to calculate the net benefit of the screening model. Results: The overall prevalence of undiagnosed diabetes was 9.8% (1059/10794) according to ADA criteria. The non-lab model revealed that gender, age, body mass index, waist circumference, hypertension, ethnicities, vegetable daily consumption and family history of diabetes were independent risk factors for diabetes. By adding 2 h post meal glycosuria qualitative to the non-lab model, the semi-lab model showed an improved Akaike information criterion (AIC: 4506 to 3580). The AUC of the semi-lab model was statistically larger than the non-lab model (0.868 vs 0.763, P < 0.001). The optimal cutoff probability in semi-lab and non-lab nomograms were 0.088 and 0.098, respectively. The sensitivity and specificity were 76.3% and 81.6%, respectively in semi-lab nomogram, and 72.1% and 673% in non-lab nomogram at the optimal cut off point. The decision curve analysis also revealed a bigger decrease of avoidable OGTT test (52 per 100 subjects) in the semi-lab model compared to the non-lab model (36 per 100 subjects) and the existed New Chinese Diabetes Risk Score (NCDRS, 35 per 100 subjects). Conclusion: The non-lab and semi-lab nomograms appear to be reliable tools for diabetes screening, especially in developing countries. However, the semi-lab model outperformed the non-lab model and NCDRS prediction systems and might be worth being adopted as decision support in diabetes screening in China.
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| 2. |
- Sun, Ryan, et al.
(författare)
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Integration of multiomic annotation data to prioritize and characterize inflammation and immune-related risk variants in squamous cell lung cancer
- 2021
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Ingår i: Genetic Epidemiology. - : John Wiley & Sons. - 0741-0395 .- 1098-2272. ; 45:1, s. 99-114
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Tidskriftsartikel (refereegranskat)abstract
- Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1 beta pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic level. While numerous genome-wide association studies (GWAS) have explored the genetic etiology of lung cancer, there remains a large gap between the type of information that may be gleaned from an association study and the depth of understanding necessary to explain and drive translational findings. Thus, in this study we jointly model and integrate extensive multiomics data sources, utilizing a total of 40 genome-wide functional annotations that augment previously published results from the International Lung Cancer Consortium (ILCCO) GWAS, to prioritize and characterize single nucleotide polymorphisms (SNPs) that increase risk of squamous cell lung cancer through the inflammatory and immune responses. Our work bridges the gap between correlative analysis and translational follow-up research, refining GWAS association measures in an interpretable and systematic manner. In particular, reanalysis of the ILCCO data highlights the impact of highly associated SNPs from nuclear factor-kappa B signaling pathway genes as well as major histocompatibility complex mediated variation in immune responses. One consequence of prioritizing likely functional SNPs is the pruning of variants that might be selected for follow-up work by over an order of magnitude, from potentially tens of thousands to hundreds. The strategies we introduce provide informative and interpretable approaches for incorporating extensive genome-wide annotation data in analysis of genetic association studies.
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| 3. |
- Zhou, Yunting, et al.
(författare)
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Lipotoxicity reduces beta cell survival through islet stellate cell activation regulated by lipid metabolism-related molecules
- 2019
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Ingår i: Experimental Cell Research. - : ELSEVIER INC. - 0014-4827 .- 1090-2422. ; 380:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Islet stellate cells (ISCs) activation is mainly associated with islet fibrosis, which contributes to the progression of type 2 diabetes. However, the molecular mechanism underlying this process is not fully understood.Methods: In order to investigate this process the current study examined ectopic fat accumulation in rats with high-fat diet (HFD) induced obesity. Levels of lipotoxicity-induced ISC activation and islet function were assessed via intraperitoneal glucose and insulin tolerance tests, and immunohistochemistry. The expression of lipid metabolism- and ISC activation-related markers was evaluated in cultured ISCs treated with palmitic acid (PA) using quantitative PCR and western blotting. We also overexpressed sterol regulatory element-binding protein (SREBP)-1c in ISCs by lentiviral transduction, and assessed the effects on insulin release in co-cultures with isolated rat islets.Results: HFD increased body weight and ectopic fat accumulation in pancreatic islets. Lipotoxicity caused progressive glucose intolerance and insulin resistance, upregulated a-smooth muscle actin, and stimulated the secretion of extracellular matrix. Lipotoxicity reduced the expression of lipid metabolism-related molecules in ISCs treated with PA, especially SREBP-1c. Overexpression of SREBP-1c in ISCs improved islet viability and insulin secretion in co-cultures.Conclucions: These results indicate that lipotoxicity-induced ISC activation alters islet function via regulation of lipid metabolism, suggesting that therapeutic strategies targeting activated ISC may be an effective treatment for prevention of ISC activation-associated islet dysfunction.
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| 4. |
- Li, Wei, et al.
(författare)
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A modified in vitro tool for isolation and characterization of rat quiescent islet stellate cells
- 2019
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Ingår i: Experimental Cell Research. - : ELSEVIER INC. - 0014-4827 .- 1090-2422. ; 384:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Islet stellate cells (ISCs) play a critical role in islet fibrosis, contributing to the progression of pancreatic diseases. Previous studies have focused on fibrosis-associated activated ISCs obtained by standard islet explant techniques. However, in vitro models of quiescent ISCs (qISCs) are lacking. This study aims to develop a method to isolate qISCs and analyze their phenotype during activation.Methods: Immunofluorescence staining was applied to localize ISCs in normal human, rat, and mouse islets. qISCs were isolated from rat islets using density gradient centrifugation (DGC) method. qRT-PCR, immunoblotting, proliferation, and migration assays were employed for their characterization.Results: Desmin-positive ISCs were detected in normal human, rat, and mouse islets. Freshly isolated qISCs, obtained by density gradient centrifugation, displayed a polygonal appearance with refringent cytoplasmic lipid droplets and expressed transcriptional markers indicating a low activation/quiescent state. With increasing culture time, the marker expression pattern changed, reflecting ISC activation. qISCs contained more lipid droplets and exhibited lower proliferation and migration abilities compared to spindle-shaped ISCs obtained by traditional explant techniques.Conclusions: This study describes a new method for efficient isolation of qISCs from rat islets, representing a useful in vitro tool to study the biology of ISCs in more physiological conditions.
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| 5. |
- Ma, Chuanwei, et al.
(författare)
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Global trends in the prevalence of secondhand smoke exposure among adolescents aged 12-16 years from 1999 to 2018 : an analysis of repeated cross-sectional surveys.
- 2021
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 9:12, s. E1667-E1678
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Secondhand smoke exposure can cause morbidity and premature mortality. However, the global prevalence of, and trends in, secondhand smoke exposure among adolescents are poorly documented. We aimed to assess the prevalence of, and trends in, secondhand smoke exposure among adolescents from 1999 to 2018.METHODS: We did an analysis of the most recent data from the Global Youth Tobacco Survey (GYTS), a nationally representative, self-administered, school-based cross-sectional survey of tobacco use and related factors among adolescents aged 12-16 years worldwide. Data from 142 countries and territories that had done a GYTS between 2010 and 2018, comprising 711 366 participants, were used to assess the prevalence of secondhand smoke exposure. Data from 131 countries and territories that had done two or more surveys between 1999 and 2018, comprising 1 405 458 participants, were used to assess trends in secondhand smoke exposure. The frequency of secondhand smoke exposure at home, in public places, or in any place was defined as follows, based on students' responses: 1 or more days, 3 or more days, 5 or more days, or daily during the past 7 days.FINDINGS: Based on the most recent surveys done in 142 countries between Jan 1, 2010, and Dec 31, 2018, the global prevalence of secondhand smoke exposure in any place was 62·9% (95% CI 61·7-64·1) on 1 or more days, 51·0% (49·8-52·1) on 3 or more days, 40·1% (38·9-41·2) on 5 or more days, and 32·5% (31·5-33·6) daily during the past 7 days. The prevalence of secondhand smoke exposure at home was 33·1% (95% CI 32·1-34·1) on 1 or more days, 20·1% (19·3-20·9) on 3 or more days, 14·9% (14·2-15·7) on 5 or more days, and 12·3% (11·7-13·0) daily during the past 7 days; and in public places the prevalence of secondhand smoke exposure was 57·6% (56·4-58·8) on 1 or more days, 43·4% (42·2-44·6) on 3 or more days, 30·3% (29·2-31·5) on 5 or more days, and 23·5% (22·5-24·5) daily during the past 7 days. Between Jan 1, 1999, and Dec 31, 2018, the prevalence of secondhand smoke exposure (on ≥1 day during the past 7 days) in any place decreased in 57 (43·5%) of 131 countries, increased in 27 (20·6%), and remained unchanged in 47 (35·9%). Although the prevalence of secondhand smoke exposure at home decreased in 86 (65·6%) countries, the prevalence in public places did not change in 46 (35·1%) countries and increased in 40 (30·5%).INTERPRETATION: Secondhand smoke exposure among adolescents remains a serious public health challenge worldwide. Although the prevalence of secondhand smoke exposure at home decreased in most countries, the prevalence in public places increased or remained unchanged in most countries between 1999 and 2018. These findings emphasise the need to strengthen smoke-free policies, especially in public places.FUNDING: Youth Team of Humanistic and Social Science of Shandong University, Jinan, China.TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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| 6. |
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| 7. |
- Shi, Ruifeng, et al.
(författare)
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Protective effects of Clec11a in islets against lipotoxicity via modulation of proliferation and lipid metabolism in mice
- 2019
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Ingår i: Experimental Cell Research. - : ELSEVIER INC. - 0014-4827 .- 1090-2422. ; 384:1
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Tidskriftsartikel (refereegranskat)abstract
- The lipotoxicity is considered as one of the risk for diabetes. Here we report C-type lectin domain family 11, member A (Clec11a) as a new regulator in islet playing a protective role in lipotoxicity induced dysfunction. Islet transcriptome sequencing was performed using the high-fat diet induced obesity (DIO) mice model. We found a significant decrease of Clec11a expression in islets of DIO mice compared to normal control mice, which was further confirmed by real-time PCR. Immunostaining demonstrated the localization of the Clec11a protein in mouse islets. Administration of recombinant human Clec11a (rClec11a) protein promoted the proliferation of islet cells and rescued the inhibition of fatty acid on cell proliferation, which involved the activation of Erk signaling pathway. We also found that the rClec11a altered the expression of genes involved in lipid metabolism.
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