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1.
  • 2019
  • Journal article (peer-reviewed)
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2.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Zhou, J. M., et al. (author)
  • Digoxin is associated with worse outcomes in patients with heart failure with reduced ejection fraction
  • 2020
  • In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:1, s. 139-147
  • Journal article (peer-reviewed)abstract
    • Aims The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline-recommended treatments in the real world in China. Methods and results Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN-HF) were enrolled to assess the all-cause mortality, HF mortality, all-cause re-hospitalization, and HF re-hospitalization associated with digoxin use. Eight hundred eighty-two eligible HFrEF patients in the CN-HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow-up of 28.6 months. Kaplan-Meier survival analysis showed that the all-cause mortality (P < 0.001) and all-cause re-hospitalization (P = 0.020) were significantly higher in digoxin group than non-digoxin group, while HF mortality (P = 0.232) and HF re-hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional-hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all-cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27-2.44; P = 0.001] and all-cause re-hospitalization (HR 1.27; 95% CI 1.03-1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all-cause mortality irrespective of rhythm or in combination with other guideline-recommended therapies. Conclusions Digoxin use is independently associated with increased risk of all-cause mortality and all-cause re-hospitalization in HFrEF patients.
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4.
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5.
  • Chiu, Ming-Jang, et al. (author)
  • Synergistic Association between Plasma Aβ1-42 and p-tau in Alzheimer's Disease but Not in Parkinson's Disease or Frontotemporal Dementia.
  • 2021
  • In: ACS chemical neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 12:8, s. 1376-1383
  • Journal article (peer-reviewed)abstract
    • Beta-amyloid (Aβ1-42) triggers the phosphorylation of tau protein in Alzheimer's disease (AD), but the relationship between phosphorylated tau (p-tau) and Aβ1-42 in the blood is not elucidated. We investigated the association in individuals with AD (n = 62, including amnesic mild cognitive impairment and dementia), Parkinson's disease (n = 30), frontotemporal dementia (n = 25), and cognitively unimpaired controls (n = 41) using immunomagnetic reduction assays to measure plasma Aβ1-42 and p-tau181 concentrations. Correlation and regression analyses were performed to examine the relation between plasma levels, demographic factors, and clinical severity. Both plasma Aβ1-42 and p-tau concentrations were significantly higher in AD and frontotemporal dementia than in the controls and Parkinson's disease. A significant positive association was found between plasma p-tau and Aβ1-42 in controls (r = 0.579, P < 0.001) and AD (r = 0.699, P < 0.001) but not in frontotemporal dementia or Parkinson's disease. Plasma p-tau was significantly associated with clinical severity in the AD in terms of scores of clinical dementia rating (r = 0.288, P = 0.025) and mini-mental state examination (r = -0.253, P = 0.049). Regression analysis showed that plasma Aβ1-42 levels explain approximately 47.7% of the plasma p-tau levels in the AD after controlling age, gender, and clinical severity. While in non-AD participants, the clinical dementia rating explained about 47.5% of the plasma p-tau levels. The disease-specific association between plasma Aβ1-42 and p-tau levels in AD implies a possible synergic effect in mechanisms involving these two pathological proteins' genesis.
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6.
  • Tang, R., et al. (author)
  • Increasing terrestrial ecosystem carbon release in response to autumn cooling and warming
  • 2022
  • In: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 12, s. 380-385
  • Journal article (peer-reviewed)abstract
    • Despite overall warming, many regions in the Northern Hemisphere have been cooling in autumn. This cooling resulted in an increasing release of net CO2 2004-2018 as primary production decreased more than respiration in cooling and respiration increased more than production in warming areas. Part of the Northern Hemisphere has experienced widespread autumn cooling during the most recent decades despite overall warming, but how this contrasting temperature change has influenced the ecosystem carbon exchange remains unclear. Here, we show that autumn cooling has occurred over about half of the area north of 25 degrees N since 2004, producing a weak cooling trend over the period 2004-2018. Multiple lines of evidence suggest an increasing net CO2 release in autumn during 2004-2018. In cooling areas, the increasing autumn CO2 release is due to the larger decrease of gross primary productivity (GPP) growth than total ecosystem respiration (TER) growth suppressed by cooling. In the warming areas, TER increased more than GPP because the warming and wetting conditions are more favourable for TER growth than GPP increase. Despite the opposite temperature trends, there has been a systematic increase in ecosystem carbon release across the Northern Hemisphere middle and high latitudes.
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7.
  • Wang, Fang, et al. (author)
  • Emerging contaminants: A One Health perspective
  • 2024
  • In: Innovation. - 2666-6758. ; 5
  • Research review (peer-reviewed)abstract
    • Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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8.
  • Zhong, Ziqian, 1995, et al. (author)
  • Disentangling the effects of vapor pressure deficit on northern terrestrial vegetation productivity
  • 2023
  • In: Science Advances. - 2375-2548. ; 9:32
  • Journal article (peer-reviewed)abstract
    • The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity's response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle's response to global warming.
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9.
  • Cao, J., et al. (author)
  • Prognostic value of N-terminal B-type natriuretic peptide on all-cause mortality in heart failure patients with preserved ejection fraction
  • 2019
  • In: Chinese Journal of Cardiology. Zhonghua xin xue guan bing za zhi. - 0253-3758. ; 47:11, s. 875-881
  • Journal article (peer-reviewed)abstract
    • Objective: To investigate the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) on all-cause mortality in heart failure patients with preserved ejection fraction (HFpEF) at real world scenarios. Methods: Patients who met the diagnostic criteria of HFpEF in the China National Heart Failure Registration Study (CN-HF) were divided into death and survival groups. The demographic data, physical examination, results of the first echocardiography, laboratory results at admission, complications, drug use and clinical outcomes were obtained from CN-HF. The univariate Cox proportional hazard model was used to screen the variates that might predict prognosis, and then the covariates with statistical significance were included in the multivariate Cox regression model to analyze the predictive value of baseline NT-proBNP on all-cause death. Spearman correlation analysis was used to evaluate the relationship between NT-proBNP and estimated glomerular filtration rate (eGFR), so as to further explore the predictive value of the interaction between renal dysfunction and NT-proBNP on death. Since NT-proBNP did not obey the binary normal distribution, it was expressed by the natural logarithm of NT-proBNP (LnNT-proBNP). Results: A total of 1 846 HFpEF patients were enrolled in this study, with an average age of 71.5 years, 1 017 males(55.1%), median NT-proBNP 860 ng/L, and median eGFR 73.9 ml·min-1·1.73m-2. After a median follow-up of 34 months, 213 (11.5%) patients died. Patients in the death group were older, with higher NYHA classification Ⅲ-Ⅳ ratio, longer hospital stay, higher serum potassium and NT-proBNP level, prevalence of complications of diabetes mellitus, arrhythmia and atrial fibrillation, use of angiotensin receptor antagonist(ARB), mineralocorticoid receptor antagonists (MRA), diuretic and digoxin was significantly higher in death group than in survival group. Body mass index (BMI), diastolic blood pressure, left ventricular ejection fraction (LVEF), hemoglobin, serum cholesterol(TC), serum triglycerides (TG) and eGFR, and use of angiotensin converting enzyme inhibitors (ACEI), statins and aspirin were lower in death group than in survival group. Univariate Cox regression analysis showed that NT-proBNP was a predictor of all-cause death in HFpEF patients (HR=2.522, 95%CI 2.040-3.119, P<0.001). Multivariate Cox regression analysis showed that the elevated NT-proBNP remains as the independent predictor of all-cause death in patients with HFpEF (HR=1.230, 95%CI 1.049-1.442, P=0.011) after adjusting for age, BMI, diastolic blood pressure, LVEF, hemoglobin, serum potassium, serum sodium, TC, serum high-density lipoprotein cholesterol (HDL-C), TG, eGFR, atrial fibrillation, as well as the treatment of ACEI/ARB, MRA, diuretics and digoxin. Spearman correlation analysis showed that LnNT-proBNP was negatively correlated with eGFR (r=-0.361, P<0.001), but there was no interaction between NT-proBNP and renal dysfunction in predicting death in HFpEF patients (P>0.05). Conclusion: The elevated level of NT-proBNP at admission is an independent predictor of all-cause mortality in HFpEF patients. 目的： 探讨入院基线N末端B型利钠肽原（NT-proBNP）对射血分数保留的心力衰竭（HFpEF）患者全因死亡的预测价值。 方法： 入选中国住院患者心力衰竭注册研究（CN-HF）中符合HFpEF诊断标准的患者，根据随访期间是否死亡分为死亡组和存活组。从CN-HF中获得研究对象的人口学信息、入院时体格检查信息、入院首次超声心动图检查结果、实验室检查结果、合并症情况、用药情况和临床结局等资料。通过单因素Cox回归模型对可能预测预后的变量进行筛选，将单因素分析中与全因死亡有统计学意义的协变量纳入多因素Cox回归模型，进而分析基线NT-proBNP对全因死亡的预测价值。采用Spearman相关分析分析NT-proBNP与估算的肾小球滤过率（eGFR）的关系，并进一步探讨肾功能不全与NT-proBNP预测全因死亡的交互作用。鉴于NT-proBNP不服从二元正态分布，本研究中NT-proBNP作连续变量分析时均取自然对数（LnNT-proBNP）。 结果： 共1 846例患者纳入本研究，平均年龄71.5岁，男性1 017例（55.1%），NT-proBNP中位数860 ng/L，eGFR中位数73.9 ml·min-1·1.73m-2。本研究中位随访时间34（24~42）个月，随访期间全因死亡213例（11.5%）被纳入死亡组，存活1 633例（88.5%）被纳入存活组。与存活组比较，死亡组患者年龄较大，纽约心脏协会（NYHA）心功能Ⅲ~Ⅳ级者比例较高，住院时间较长，血钾、NT-proBNP较高，合并糖尿病、心律失常、心房颤动者较多，服用血管紧张Ⅱ受体阻滞剂（ARB）、盐皮质激素受体拮抗剂（MRA）、利尿剂和地高辛者较多（P均<0.05）。与存活组比较，死亡组患者体重指数（BMI）、舒张压、左心室射血分数（LVEF）较低，血红蛋白、血清总胆固醇（TC）、血清甘油三酯（TG）、eGFR较低，服用血管紧张素转化酶抑制剂（ACEI）、他汀类药物和阿司匹林者较少（P均<0.05）。单因素Cox回归分析结果显示NT-proBNP是HFpEF患者全因死亡的预测因素（HR=2.522，95%CI 2.040~3.119，P<0.001）。多因素Cox回归分析结果显示，校正了年龄、BMI、舒张压、LVEF、血红蛋白、血钾、血钠、TC、高密度脂蛋白胆固醇、TG、eGFR、心房颤动以及ACEI/ARB、MRA、利尿剂、地高辛使用情况后，NT-proBNP仍是HFpEF患者全因死亡的独立预测因素（HR=1.230，95%CI 1.049~1.442，P=0.011）。Spearman相关分析结果显示，LnNT-proBNP与eGFR呈负相关（r=-0.361，P<0.001）。而校正了混杂因素后，多因素Cox回归分析结果显示肾功能不全与NT-proBNP预测HFpEF患者全因死亡无交互作用（P>0.05）。 结论： 入院基线NT-proBNP是HFpEF患者全因死亡的独立预测因素。.
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10.
  • Jin, X., et al. (author)
  • Outcomes of patients with anemia and renal dysfunction in hospitalized heart failure with preserved ejection fraction (from the CN-HF registry)
  • 2019
  • In: IJC Heart and Vasculature. - : Elsevier BV. - 2352-9067. ; 25
  • Journal article (peer-reviewed)abstract
    • Background: Although a large number of studies on heart failure with reduced ejection fraction (HFrEF) have found that anemia and renal dysfunction (RD) independently predicted poor outcomes, there are still few reports on patients with heart failure with preserved ejection fraction (HFpEF). Methods: Clinical data of HFpEF patients registered in the China National Heart Failure Registration Study (CN-HF) were evaluated and the clinical features of patients with or without anemia/RD were compared to explore the impact of anemia and RD on all-cause mortality and all-cause re-hospitalization. Results: 1604 patients with HFpEF were enrolled, the prevalence of anemia was 51.0%. Although anemia was associated with increased risk of all-cause mortality and all-cause re-hospitalization in univariate COX regression (p < 0.05), multivariate COX model confirmed that anemia was not independently associated with all-cause mortality [hazard ratio (HR) 1.14, 95% confidence interval (CI) 0.85–1.52, p = 0.386] and all-cause re-hospitalization (HR 1.13, 95% CI 0.96–1.33, p = 0.152). Similarly, RD was not an independent predictor of all-cause mortality (HR 1.18, 95% CI 0.88–1.57, p = 0.269) and all-cause re-hospitalization (HR 0.94, 95% CI 0.79–1.12, p = 0.488) as assessed in the adjusted COX regression model. The interaction between RD and anemia on end-points events was also not statistically significant. However, anemia was associated with increased all-cause re-hospitalization in patients with New York Heart Association (NYHA) class III-IV. Conclusions: In patients with HFpEF from CN-HF registry, anemia was common, but was not an independent predictor of all-cause mortality and all-cause re-hospitalization, except for the all-cause re-hospitalization in patients with NYHA class III-IV. Clinical Trial Registration: http://www.clinicaltrials.gov/ct2/home; ID: NCT02079428. © 2019 The Authors
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11.
  • Klaric, Lucija, et al. (author)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Other publication (other academic/artistic)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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12.
  • Liao, Chuan, et al. (author)
  • Advancing landscape sustainability science: theoretical foundation and synergies with innovations in methodology, design, and application
  • 2020
  • In: Landscape Ecology. - : Springer Science and Business Media LLC. - 0921-2973 .- 1572-9761. ; 35, s. 1-9
  • Journal article (other academic/artistic)abstract
    • © 2020, Springer Nature B.V. Our society has entered in an era of Anthropocene, in which people and their activities dominate almost all ecosystems on the planet. In the context of growing uncertainties, landscape sustainability science (LSS), as a place-based, use-inspired science, aims to understand and improve the dynamic relationship between ecosystem services and human well-being. In this editorial, we identify the major theoretical foundations of LSS, discuss recent innovations in research methodology to advance LSS, summarize the extension of LSS through landscape design and geo-design, and examine the application of LSS for addressing sustainability challenges across multiple landscapes. We highlight that long-term regional sustainability can only be achieved by integrating context-based sustainability across agricultural, urban, and natural landscapes so as to minimize the regional ecological footprint and make advancement towards achieving the sustainable development goals.
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13.
  • Lin, C. G., et al. (author)
  • Impacts of wind stilling on solar radiation variability in China
  • 2015
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
  • Journal article (peer-reviewed)abstract
    • Solar dimming and wind stilling (slowdown) are two outstanding climate changes occurred in China over the last four decades. The wind stilling may have suppressed the dispersion of aerosols and amplified the impact of aerosol emission on solar dimming. However, there is a lack of long-term aerosol monitoring and associated study in China to confirm this hypothesis. Here, long-term meteorological data at weather stations combined with short-term aerosol data were used to assess this hypothesis. It was found that surface solar radiation (SSR) decreased considerably with wind stilling in heavily polluted regions at a daily scale, indicating that wind stilling can considerably amplify the aerosol extinction effect on SSR. A threshold value of 3.5 m/s for wind speed is required to effectively reduce aerosols concentration. From this SSR dependence on wind speed, we further derived proxies to quantify aerosol emission and wind stilling amplification effects on SSR variations at a decadal scale. The results show that aerosol emission accounted for approximately 20% of the typical solar dimming in China, which was amplified by approximately 20% by wind stilling.
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14.
  • Menkveld, Albert J., et al. (author)
  • Nonstandard Errors
  • 2024
  • In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Journal article (peer-reviewed)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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15.
  • Razavi-Shearer, Devin M., et al. (author)
  • Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
  • 2024
  • In: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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16.
  • Speliotes, Elizabeth K., et al. (author)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Journal article (peer-reviewed)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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17.
  • Yan, G., et al. (author)
  • Silencing RhoA inhibits migration and invasion through Wnt/β-catenin pathway and growth through cell cycle regulation in human tongue cancer
  • 2014
  • In: Acta Biochimica et Biophysica Sinica. - : China Science Publishing & Media Ltd.. - 1672-9145 .- 1745-7270. ; 46:8, s. 682-690
  • Journal article (peer-reviewed)abstract
    • Ras homolog gene family member A (RhoA) has been identified as a critical regulator of tumor aggressive behavior. In this study, we assessed the role of RhoA in the mechanisms underlying growth, migration, and invasion of squamous cell carcinoma of tongue (TSCC). Stable RhoA knockdown of TSCC cell lines SCC-4 and CAL27 were achieved using Lentiviral transfection. The effects of RhoA depletion on cell migration, invasion, and cell proliferation were determined. The possible underlying mechanism of RhoA depletion on TSCC cell line was also evaluated by determining the expression of Galectin-3 (Gal-3), β-catenin, and matrix metalloproteinase-9 (MMP-9) in vivo. Meanwhile, the underlying mechanism of TSCC growth was studied by analysis of cyclin D1/2, p21 CIP1/WAF1, and p27Kip1 protein levels. Immunohistochemical assessments were performed to further prove the alteration of Gal-3 and β-catenin expression. We found that, in mice injected with human TSCC cells in the tongue, RhoA levels were higher in primary tumors and metastasized lymph nodes compared with those in the normal tissues. Silencing of RhoA significantly reduced the tumor growth, decreased the levels of Gal-3, β-catenin, MMP-9, and cyclin D1/2, and increased the levels of p21 CIP1/WAF1 and p27Kip1. In vitro, RhoA knockdown also led to inhibition of cell migration, invasion, and proliferation. Our data suggest that RhoA plays a significant role in TSCC progression by regulating cell migration and invasion through Wnt/β-catenin signaling pathway and cell proliferation through cell cycle regulation, respectively. RhoA might be a novel therapeutic target of TSCC. © 2014 The Author .
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18.
  • Bergstrom, K, et al. (author)
  • Core 1- and 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice.
  • 2017
  • In: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 10, s. 91-103
  • Journal article (peer-reviewed)abstract
    • Core 1- and 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1(-/-)) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and 3-derived O-glycans (DKO) developed spontaneous colitis in both the distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1(-/-) mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than wild-type mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients.Mucosal Immunology advance online publication, 4 May 2016; doi:10.1038/mi.2016.45.
  •  
19.
  • Buchanan, E. M., et al. (author)
  • The Psychological Science Accelerator's COVID-19 rapid-response dataset
  • 2023
  • In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 10:1
  • Journal article (peer-reviewed)abstract
    • In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
  •  
20.
  • Buvall, Lisa, 1976, et al. (author)
  • Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human beta-adrenergic receptor
  • 2006
  • In: Clin Exp Immunol. - : Oxford University Press (OUP). - 0009-9104. ; 143:2, s. 209-15
  • Journal article (peer-reviewed)abstract
    • In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been suggested that the beta1-adrenergic receptor (beta1AR) is a potential pathogenic autoantigen. The aim of the present study was to investigate whether immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the beta1AR (beta1AR EC(II)) was able to induce the early stage of cardiomyopathy and also to investigate immunological and receptor functional parameters at a transcriptional level to permit insights into the autoimmune mechanism in cardiomyopathy. Eleven Whistar Fur rats were immunized with a beta1AR EC(II) peptide (H26R) once a month during 12 months and seven control rats were injected with vehicle according to the same procedure used for the immunized group. Cardiac function, beta1AR autoantibodies and their functional effects on cardiomyocytes were analysed. beta1AR receptor signalling, immunological and cardiomyocyte stretch markers were determined on transcriptional level. In H26R immunized rats, beta1AR autoantibodies were shown to be present and functionally active, cardiac functions in terms of fractional shortening were decreased and beta1-adrenergic receptor kinase (GRK2) mRNA were increased compared with the control group. These data have shown that immunization of rats with a putative antigenic peptide was able to induce an early stage phenotype of cardiomyopathy in the form of cardiac dysfunction and up-regulation of GRK2 as the first step in the desensitization process of the beta1AR, implying the pathological importance of the beta1AR autoantibody.
  •  
21.
  • Chang, W, et al. (author)
  • Parathyroid Ca(2+)-conducting currents are modulated by muscarinic receptor agonists and antagonists.
  • 1997
  • In: The American journal of physiology. - 0002-9513. ; 273:5 Pt 1
  • Journal article (peer-reviewed)abstract
    • Parathyroid cells express Ca(2+)-conducting cation currents, which are activated by raising the extracellular Ca2+ concentration ([Ca2+]o) and blocked by dihydropyridines. We found that acetylcholine (ACh) inhibited these currents in a reversible, dose-dependent manner (50% inhibitory concentration approximately equal to 10(-8) M). The inhibitory effects could be mimicked by the agonist (+)-muscarine. The effects of ACh were blunted by the antagonist atropine and reversed by removing ATP from the pipette solution (+)-Muscarine enhanced the adenosine 3',5'-cyclic monophosphate (cAMP) production by 30% but had no effect on inositol phosphate accumulation in parathyroid cells. Oligonucleotide primers, based on sequences of known muscarinic receptors (M1-M5), were used in reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify receptor cDNA from parathyroid poly (A)+ RNA. RT-PCR products displayed > 90% nucleotide sequence identity to human M2- and M4-receptor cDNAs. Expression of M2-receptor protein was further confirmed by immunoblotting and immunocytochemistry. Thus parathyroid cells express muscarinic receptors of M2 and possibly M4 subtypes. These receptors may couple to dihydropyridine-sensitive, cation-selective currents through the activation of adenylate cyclase and ATP-dependent pathways in these cells.
  •  
22.
  • Chen, Jie, et al. (author)
  • Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes
  • 2006
  • In: The European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 8:5, s. 460-467
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Immunoadsorption has been shown to improve cardiac performance and reduce mortality in patients with dilated cardiomyopathy. In this study, the underlying mechanism for these beneficial effects was investigated in cultured rat cardiomyocytes. METHODS AND RESULTS: Immunoadsorption was performed in patients with dilated cardiomyopathy (n=7). Antibody-induced complement-dependent cytotoxicity was investigated by colorimetric MTT. Autoantibodies against the beta(1)-adrenoceptor were detected by ELISA and purified. Column eluent from six patients exhibited a cytotoxic effect, three patients were positive for the beta(1)-adrenoceptor autoantibodies. The purified autoantibodies were able to visualize the beta(1)-adrenoceptors by immunocytofluorescence on rat cardiomyocytes, and also displayed partial agonist properties and induced a positive chronotropic effect, which were blocked by the beta(1)-selective antagonist bisoprolol and the peptide corresponding to the beta(1)-adrenoceptor. Column eluent from one patient induced apoptosis in nick end labelling test (8.1+/-1.7% vs. 2.9+/-1.2% in control, p<0.05). CONCLUSION: Autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy have a pathophysiological role, as shown by the complement-dependent cytotoxicity and chronotropic action on rat cardiomyocytes. This implies that removal of circulating autoantibodies might be part of the underlying mechanism for improved cardiac function.
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23.
  • Chen, Xiaojing, et al. (author)
  • Age-dependent differences in clinical phenotype and prognosis in heart failure with mid-range ejection compared with heart failure with reduced or preserved ejection fraction
  • 2019
  • In: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 108:12, s. 1394-1405
  • Journal article (peer-reviewed)abstract
    • Background: HFmrEF has been recently proposed as a distinct HF phenotype. How HFmrEF differs from HFrEF and HFpEF according to age remains poorly defined. We aimed to investigate age-dependent differences in heart failure with mid-range (HFmrEF) vs. preserved (HFpEF) and reduced (HFrEF) ejection fraction. Methods and results: 42,987 patients, 23% with HFpEF, 22% with HFmrEF and 55% with HFrEF, enrolled in the Swedish heart failure registry were studied. HFpEF prevalence strongly increased, whereas that of HFrEF strongly decreased with higher age. All cardiac comorbidities and most non-cardiac comorbidities increased with aging, regardless of the HF phenotype. Notably, HFmrEF resembled HFrEF for ischemic heart disease prevalence in all age groups, whereas regarding hypertension it was more similar to HFpEF in age ≥ 80years, to HFrEF in age < 65years and intermediate in age 65–80years. All-cause mortality risk was higher in HFrEF vs. HFmrEF for all age categories, whereas HFmrEF vs. HFpEF reported similar risk in ≥ 80years old patients and lower risk in < 65 and 65–80years old patients. Predictors of mortality were more likely cardiac comorbidities in HFrEF but more likely non-cardiac comorbidities in HFpEF and HFmrEF with < 65years. Differences among HF phenotypes for comorbidities were less pronounced in the other age categories. Conclusion: HFmrEF appeared as an intermediate phenotype between HFpEF and HFrEF, but for some characteristics such as ischemic heart disease more similar to HFrEF. With aging, HFmrEF resembled more HFpEF. Prognosis was similar in HFmrEF vs. HFpEF and better than in HFrEF. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
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24.
  • Chen, Xiaojing, et al. (author)
  • Guideline-directed medical therapy in real-world heart failure patients with low blood pressure and renal dysfunction
  • 2021
  • In: Clinical Research in Cardiology. - : SPRINGER HEIDELBERG. - 1861-0684 .- 1861-0692. ; 110, s. 1051-1062
  • Journal article (peer-reviewed)abstract
    • Background Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), beta-blockers (BB) and mineralocorticoid receptor antagonist (MRA) are known as guideline-directed medical therapy to improve prognosis. However, low blood pressure (BP) and renal dysfunction are often challenges prevent clinical implementation, so we investigated the association of different combinations of GDMT treatments with all-cause mortality in HFrEF population with low BP and renal dysfunction. Methods This study initially included 51, 060 HF patients from the Swedish Heart Failure Registry, and finally 1464 HFrEF patients with low BP (systolic BP <= 100 mmHg) and renal dysfunction (estimated glomerular filtration rate (eGFR) <= 60 ml/min/1.73m(2)) were ultimately enrolled. Patients were receiving oral medication for HF at study enrollment, and divided into four groups (group 1-4: ACEI/ARB + BB + MRA, ACEI/ARB + BB, ACEI/ARB + MRA or ACEI/ARB only, and other). The outcome is time to all-cause mortality. Results Among the study patients, 485 (33.1%), 672 (45.9%), 109 (7.4%) and 198 (13.5%) patients were in group 1-4. Patients in group 1 were younger, had highest hemoglobin, and most with EF < 30%. During a median of 1.33 years follow-up, 937 (64%) patients died. After adjustment for age, gender, LVEF, eGFR, hemoglobin when compared with the group 1, the hazard ratio for all-cause mortality in group 2 was 1.04 (0.89-1.21) (p = 0.62), group 3 1.40 (1.09-1.79) (p = 0.009), and group 4 1.71 (1.39-2.09) (p < 0.001). Conclusions In real-world HFrEF patients with low BP and renal dysfunction, full medication of guideline-directed medical therapy is associated with improved survival. The benefit was larger close to the index date and decreased with follow-up time.
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25.
  • Chen, Xiaojing, et al. (author)
  • High-normal blood pressure conferred higher risk of cardiovascular disease in a random population sample of 50-year-old men: A 21-year follow-up.
  • 2020
  • In: Medicine. - 1536-5964. ; 99:17
  • Journal article (peer-reviewed)abstract
    • The relationship between various categories of blood pressure (BP), subtypes of hypertension, and development of cardiovascular disease (CVD) have not been extensively studied. Therefore, our study aimed to explore this relationship in a random population sample of men born in 1943, living in Sweden and followed over a 21-year period.Participants were examined for the first time in 1993 (age 50 years), where data on medical history, concomitant diseases, and general health were collected. The examination was repeated in 2003 and with additional echocardiography also in 2014. Classification of participants according to their BP at the age of 50 years was as follows: optimal-normal BP (systolic blood pressure [SBP] <130 and diastolic BP [DBP] <85mmHg), high-normal BP (130≤SBP<140, 85≤DBP<90mmHg), isolated systolic-diastolic hypertension (ISH-IDH) (SBP ≥140 and DBP <90 or SBP <140 and DBP ≥90mmHg), and systolic-diastolic hypertension (SDH) (SBP ≥140 and DBP ≥90mmHg).During the follow-up, the incidence of heart failure (HF), CVD, and coronary heart disease were all lowest for those with optimal-normal BP. Participants with high-normal BP showed greater wall thickness and left ventricular mass index, larger LV size and larger left atrial size when compared with the optimal-normal BP group. Furthermore, those with high-normal BP, ISH-IDH, and SDH had a higher risk of CVD than those with optimal-normal BP. The adjusted relative risk of CVD was highest for SDH (hazard ratio [HR] 1.95; 95% confidence interval [95% CI] 1.37-2.79), followed by ISH-IDH (HR 1.34; 95% CI 0.93-1.95) and high-normal BP (HR 1.31; 95% CI 0.91-1.89).Over a 21-year follow-up, the participants with high-normal BP or ISH-IDH had a higher relative risk of CVD than those with optimal-normal BP.
  •  
26.
  • Chen, Xiaojing, et al. (author)
  • High prevalence of cardiac dysfunction or overt heart failure in 71-year-old men: A 21-year follow-up of "The Study of men born in 1943"
  • 2020
  • In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:7, s. 717-725
  • Journal article (peer-reviewed)abstract
    • Background: Knowledge about long-term risk factors and the prevalence of heart failure stages in general population is limited. We aimed to study the prevalence of cardiac dysfunction and heart failure in 71-year-old men and potential risk factors in the past two decades. Design: This research was based on a randomized selected population study with longitudinal follow-up. Methods: A random sample of men born in 1943 in Gothenburg, Sweden were examined in 1993 (at 50 years of age) and re-examined 21 years later in 2014 (at 71 years of age). Cardiac dysfunction or heart failure was classified into four stages (A-D) according to American Heart Association/American College of Cardiology guidelines on heart failure. Results:Of the 798 men examined in 1993 (overall cohort), 535 (67%) were re-examined in 2014 (echo cohort). In the echo cohort 122 (23%) men had normal cardiac function, 135 (25%) were at stage A, 207 (39%) men were at stage B, 66 (12%) men were at stage C, and five (1%) men were at stage D. Multivariable logistic regression demonstrated that elevated body mass index at 50 years old was the only independent risk factor for developing heart failure/cardiac dysfunction during the subsequent 21 years. For each unit (1 kg/m(2)) of increased body mass index, the odds ratio for stages C/D heart failure vs no heart failure/stage A increased by 1.20 (95% confidence interval, 1.11-1.31, p < 0.001), after adjustment for smoking, sedentary life style, systolic blood pressure, diabetes, and hyperlipidemia. Conclusion: In a random sample of men at 71 years of age, half presented with either cardiac dysfunction or clinical heart failure. High body mass index was associated with an increased risk for developing cardiac dysfunction or heart failure over a 21-year period.
  •  
27.
  • Chen, Xiaojing, et al. (author)
  • Impact of adherence to guideline-directed therapy on risk of death in HF patients across an ejection fraction spectrum
  • 2023
  • In: Esc Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 10:6, s. 3656-3666
  • Journal article (peer-reviewed)abstract
    • Aims How different degrees of adherence to guideline-directed medical therapy (GDMT) affect mortality risk in patients with heart failure (HF) in a real-world clinical setting is poorly understood. This study sought to investigate how different levels of adherence to GDMT were associated with the risk of all-cause mortality in patients with HF across a spectrum of left ventricular ejection fractions (LVEFs) in a real-world clinical setting.Methods and results A total of 64 610 HF patients with no missing value of LVEF from the Swedish Heart Failure Registry were included in the study. Patients were divided according to different LVEFs (<30%, 30-39%, 40-49%, and >= 50%) and stratified by an adherence score (good, moderate, or poor) according to the triple, double, and single one usage of GDMT: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists. The outcome is time to all-cause mortality. The mean age of the whole cohort was 73.9 +/- 12.1 years, and the proportion of patients in LVEF < 30%, 30-39%, 40-49%, and >= 50% groups was 27.6%, 26.9%, 22.1%, and 23.3%, respectively. Patients with LVEF < 30% had the highest mortality rate, almost 20% higher than those with LVEF >= 50% {hazard ratio [HR] [95% confidence interval (CI)]: 0.80 [0.71-0.90], P < 0.001}. After treatment of GDMT with good adherence, patients with LVEF < 30% had similar mortality to those with LVEF >= 50% [HR (95% CI): 0.97 (0.86-1.10), P = 0.664]. However, the percentage of moderate or poor GDMT was alarmingly high, with good adherence only in 20% of the patients.Conclusions Good adherence to GDMT works best in patients with LVEF < 50%, whereas moderate adherence to GDMT varies in efficacy depending on the components of the drug combinations.
  •  
28.
  • Chen, Xiaojing, et al. (author)
  • Impact of changes in heart rate with age on all-cause death and cardiovascular events in 50-year-old men from the general population
  • 2019
  • In: Open Heart. - : BMJ. - 2053-3624. ; 6:1
  • Journal article (peer-reviewed)abstract
    • Background Resting heart rate (RHR), a known cardiovascular risk factor, changes with age. However, little is known about the association between changes in RHR and the risk of cardiovascular events. The purpose of this study was therefore to assess the impact of RHR at baseline, and the change in RHR over time, on the risk of all-cause death and cardiovascular events. Design A random population sample of men born in 1943 who were living in Gothenburg, Sweden was prospectively followed for a 21-year period. Methods Participants were examined three times: first in 1993 and then re-examined in 2003 and 2014. At each visit, a clinical examination, an ECG and laboratory analyses were performed. Change in RHR between 1993 and 2003 was defined as a decrease if RHR decreased by 5 beats per minute (bpm), an increase if RHR increased by 5 bpm or stable if the RHR change was <4bpm). Results Participants with a baseline RHR of >75 bpm in 1993 had about a twofold higher risk of all-cause death (HR 2.3, CI 1.2 to 4.7, p=0.018), cardiovascular disease (CVD) (HR 1.8, CI 1.1 to 3.0, p=0.014) and coronary heart disease (CHD) (HR 2.2, CI 1.1 to 4.5, p=0.025) compared with those with <55 bpm in 1993. Participants with a stable RHR between 1993 and 2003 had a 44% decreased risk of CVD (HR 0.56, CI 0.35 to 0.87, p=0.011) compared with participants with an increasing RHR. Furthermore, every beat increase in heart rate from 1993 was associated with a 3% higher risk for all-cause death, 1% higher risk for CVD and 2% higher risk for CHD. Conclusion High RHR was associated with an increased risk of death and cardiovascular events in men from the general population. Moreover, individuals with an increase in RHR between 50 and 60 years of age had worse outcome. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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29.
  • Chen, Xiaojing, et al. (author)
  • Improved short and long term survival associated with percutaneous coronary intervention in the elderly patients with acute coronary syndrome
  • 2018
  • In: BMC Geriatr. - : Springer Science and Business Media LLC. - 1471-2318. ; 18:1
  • Journal article (peer-reviewed)abstract
    • Background: Percutaneous coronary intervention (PCI) are increasingly used in daily clinical practice in elderly patients with acute coronary syndrome (ACS) despite limited evidence. The purpose of this study was to assess the impact of PCI on short and long term survivals in a large cohort of elderly patients with ACS from a "real world". Methods: We enrolled 491 patients aged >= 70 years admitted to our institution with ACS from 2006 to 2012. Effect of PCI on short and long term survival was evaluated in both overall and a propensity score-matched cohort. Results: The mean age of the overall cohort is 83 +/- 6 years. Among them, 285 were treated with PCI, whereas 206 were not. Patients treated with PCI were younger (82 +/- 5 vs. 85 +/- 6), more males (67% vs. 46%), with lower heart rate (77 +/- 22 vs. 84 +/- 21), higher eGFR (58 +/- 20 vs. 47 +/- 23), and less with heart failure (29% vs. 15%) (all p < 0.001). In both overall and propensity-matched population, improved survival was associated with PCI-treatment at 1 and 3 years (p < 0.001 for all comparisons). Furthermore, by using multivariate Cox proportional-hazards regression model following factors were identified as independent predictors of 3-year all-cause mortality: age (HR 1.08, 95% CI 1.00-1.16), heart rate (HR 1.02, 95% CI 1.01-1.03), eGFR (HR 3.07, 95% CI 1.63-5.77), malignancy (HR 2.03, 95% CI 1.27-4.57), prior CABG (HR 2.033, 95% CI 1.27-4.57), medication with statin (HR 0.40, 95% CI 0.19-0.86) in PCI group, whereas age (HR 1.08, 95% CI 1.03-1.13), heart rate (HR 1.01, 95% CI 1.01-1.02), hypertension (HR 1.87, 95% CI 1.01-3.49) and using of ACEI/ARB (HR 0.46, 95% CI 0.28-0.76) in non-PCI group. Conclusions: In elderly ACS patients, PCI-treatment was associated with improved 1 and 3-year survival and PCI-treated patients had different prognostic profile compared to those without PCI treatment.
  •  
30.
  • Chen, Xiaojing, et al. (author)
  • Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population
  • 2021
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
  • Journal article (peer-reviewed)abstract
    • The QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50-60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. Delta QRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: Delta QRS < 4 ms, group 2: 4 ms <= Delta QRS < 8 ms, group 3: Delta QRS >= 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (Delta QRS < 4 ms), men with Delta QRS >= 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07-2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.
  •  
31.
  • Chen, Xiaojing, et al. (author)
  • The eligible population of the PARADIGM-HF trial in a real-world outpatient clinic and its cardiovascular risk between 2005 and 2016.
  • 2020
  • In: Journal of cardiovascular medicine. - 1558-2035. ; 21:1, s. 6-12
  • Journal article (peer-reviewed)abstract
    • The PARADIGM-HF trial showed that sacubitril-valsartan - an angiotensin receptor-neprilysin inhibitor (ARNI) - is more effective than enalapril for some patients with heart failure. However, the eligibility of the PARADIGM-HF study to a real-world heart failure population was not well established.We made secondary analysis of patients (n=4872) with heart failure prospectively enrolled in the Swedish Heart Failure Registry from Sahlgrenska University Hospital/Östra Hospital, Sweden during 2005-2016. The eligibility of the PARADIGM-HF trial in the real world was studied based on patients whether they were either fully or partially compatible with the PARADIGM-HF population. Patients were judged to be fully eligible for the PARADIGM-HF trial if they completely met the inclusion and exclusion criteria, and partially eligible if they did not stay on target dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), despite their having been treated with ACEI/ARB for at least 6 months.Among patients who had heart failure with reduced left ventricular ejection fraction (≤40%) (HFrEF) (n=2165), 653 (30%) and 958 (44%) patients were fully and partially compatible with PARADIGM-HF criteria, respectively. In both fully and partially eligible groups, patients were more male. Despite those fully eligible patients being younger (77.6±12.7 vs. 84.0±13.7 years) than noneligible patients, they were much older than in the PARADIGM-HF trial. Moreover, those fully eligible patients had lower all-cause mortality compared with both partially and noneligible patients. However, both fully and partially eligible patients had higher all-cause mortality than that in the PARADIGM-HF trial.In a real-world outpatient clinical setting, around 1/3-1/2 of HFrEF were eligible for treatment of Sac/Val except that they are older, sicker, and carry higher risk for all-cause mortality than the PARADIGM-HF trial population.
  •  
32.
  • Chen, Yun, 1966, et al. (author)
  • Characterization of VCAM-1-Binding Peptide-Functionalized Quantum Dots for Molecular Imaging of Inflamed Endothelium
  • 2013
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
  • Journal article (peer-reviewed)abstract
    • Inflammation-induced activation of endothelium constitutes one of the earliest changes during atherogenesis. New imaging techniques that allow detecting activated endothelial cells can improve the identification of persons at high cardiovascular risk in early stages. Quantum dots (QDs) have attractive optical properties such as bright fluorescence and high photostability, and have been increasingly studied and developed for bio-imaging and bio-targeting applications. We report here the development of vascular cell adhesion molecule-1 binding peptide (VCAM-1 binding peptide) functionalized QDs (VQDs) from amino QDs. It was found that the QD fluorescence signal in tumor necrosis factor alpha (TNF-alpha) treated endothelial cells in vitro was significantly higher when these cells were labeled with VQDs than amino QDs. The VQD labeling of TNF-alpha-treated endothelial cells was VCAM-1 specific since pre-incubation with recombinant VCAM-1 blocked cells' uptake of VQDs. Our ex vivo and in vivo experiments showed that in the inflamed endothelium, QD fluorescence signal from VQDs was also much stronger than that of amino QDs. Moreover, we observed that the QD fluorescence peak was significantly blue-shifted after VQDs interacted with aortic endothelial cells in vivo and in vitro. A similar blue-shift was observed after VQDs were incubated with recombinant VCAM-1 in tube. We anticipate that the specific interaction between VQDs and VCAM-1 and the blue-shift of the QD fluorescence peak can be very useful for VCAM-1 detection in vivo.
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33.
  • Chiang, Yueh-Tao, et al. (author)
  • Developing the "Healthcare CEO App" for patients with type 1 diabetes transitioning from adolescence to young adulthood: A mixed-methods study.
  • 2023
  • In: Nursing open. - : Wiley. - 2054-1058. ; 10:3
  • Journal article (peer-reviewed)abstract
    • To develop and test a mobile application that supports the disease self-management of adolescents with type 1 diabetes during their transition to early adulthood.A sequential mixed-methods design was employed.The application content was designed according to previously identified care needs and expectations, followed by application development on the Android operating system. From the outpatient clinic of the Department of Paediatric Endocrinology and Metabolism at a medical centre in northern Taiwan, 35 individuals aged between 16-25years participated in application testing.The overall median score of the QUIS was 4-5, most of the 25% quartile was 4-5, and all of the 75% quartile was 5, indicating adequate user interaction satisfaction.
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34.
  • Chiang, Yueh-Tao, et al. (author)
  • Emergence of a butterfly: the life experiences of type 1 diabetes Taiwanese patients during the 16-25 years old transition period.
  • 2020
  • In: International journal of qualitative studies on health and well-being. - : Informa UK Limited. - 1748-2631. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Purpose: To explore the life experiences of patients with type 1 diabetes transition from adolescence into adulthood in Taiwan.Methods: Descriptive phenomenological design was used. Fourteen participants were individually interviewed using a semi-structured interview.Results: The life experiences of patients with type 1 diabetes transition from adolescence into adulthood experience a metamorphosis from awareness of responsibility to figuring out a way to care for themselves. Six themes emerged: (1) hibernation: awareness of responsibility; (2) emergence: attempts to take responsibility; (3) perseverance: encountering difficulties; (4)anxiety: multiple worries; (5) hesitation: back-and-forth," and (6) exit: finding a way out."Conclusions: During the transition phase, the participants experienced the trials of various situations. Regardless of whether they are able to independently bear the responsibilities of self-management, they all hope to turn around the challenges of disease control and take ownership of their disease. Like a butterfly that emerges from a cocoon, they hoped to overcome the dangers of taking flight through trial and error and navigating the world. The results of this study can serve as a reference for clinical care and developing localized intervention strategies targeted to the transition period between adolescence and young adulthood.
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35.
  • Choy, Manting, et al. (author)
  • Phenotypes of heart failure with preserved ejection fraction and effect of spironolactone treatment.
  • 2022
  • In: ESC heart failure. - : Wiley. - 2055-5822. ; 9:4, s. 2567-2575
  • Journal article (peer-reviewed)abstract
    • The aims of this study were to explore phenotypes of heart failure with preserved ejection fraction (HFpEF) and evaluate differential effects of spironolactone treatment.A swap-stepwise algorithm was used for variable selection. Latent class analysis based on 10 selected variables was employed in a derivative set of 1540 patients from the TOPCAT trial. Cox proportional hazard models were used to evaluate the prognoses and effects of spironolactone treatment. Three phenotypes of HFpEF were identified. Phenotype 1 was the youngest with low burden of co-morbidities. Phenotype 2 was the oldest with high prevalence of atrial fibrillation, pacemaker implantation, and hypothyroidism. Phenotype 3 was mostly obese and diabetic with high burden of other co-morbidities. Compared with phenotype 1, phenotypes 2 (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.14-1.89; P = 0.003) and 3 (HR: 2.35; 95% CI: 1.80-3.07; P < 0.001) were associated with higher risks of the primary composite outcome. Spironolactone treatment was associated with a reduced risk of the primary outcome only in phenotype 1 (HR: 0.63; 95% CI: 0.40-0.98; P = 0.042).Three distinct HFpEF phenotypes were identified. Spironolactone treatment could improve clinical outcome in a phenotype of relatively young patients with low burden of co-morbidities.
  •  
36.
  • Chu, S. Y., et al. (author)
  • Intra-aortic balloon pump on in-hospital outcomes of cardiogenic shock: findings from a nationwide registry, China
  • 2021
  • In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:4, s. 3286-3294
  • Journal article (peer-reviewed)abstract
    • Aims The real-world usage of intra-aortic balloon pump (IABP) in various cardiogenic shocks (CS) and the association with outcomes are lacking. We aimed to investigate IABP adoption in CS in a nationwide registry in China. Methods and results We retrospectively retrieved data of 30 106 CS patients (age 67.1 +/- 14.6 years, 37.6% female patients) in the Hospital Quality Monitoring System registry from 2013 to 2016. Ischaemic heart disease was the leading cause of CS (73.9%). Hypertension, cardiomyopathy, myocarditis, valvular, and congenital heart disease were seen in 36.0%, 7.5%, 2.6%, 7.3%, and 2.4% of the population. IABP was employed in 2320 (7.7%) subjects. The association between IABP usage and primary outcome of in-hospital mortality and secondary outcomes of expenses and lengths of stay were investigated. The patients with IABP support had similar in-hospital mortality to those without IABP (39.6% vs. 38.3%, P = 0.226), but longer hospital-stay [8.0 (2.0-16.0) vs. 6.0 (2.0-13.0) days, P < 0.001] and higher expenses [7.1(4.4-11.1) vs. 2.3 (0.8-5.5) 10 000RMB, P < 0.001]. IABP support was not associated with reduced mortality in the overall CS population in multivariate regression analysis [odds ratio (OR) 1.05, 95% confidence interval (CI) 0.95-1.17], except for subgroups with myocarditis (OR 0.61, 95% Cl 0.39-0.95, P for interaction = 0.010) and those who did not receive the early percutaneous coronary intervention (PCI) (OR 0.86, 95% CI 0.75-0.97, P for interaction < 0.001). Similar results were further confirmed in the propensityscore-matched population. Conclusions In this nationwide registry of CS patients, IABP was not noted with improved survival but increased healthcare consumption. However, IABP appears protective in those with myocarditis or who failed to receive early PCI.
  •  
37.
  • Fan, Lijun, et al. (author)
  • Comparison between two statistical downscaling methods for summer daily rainfall in Chongqing, China
  • 2015
  • In: International Journal of Climatology. - : Wiley. - 0899-8418 .- 1097-0088. ; 35:13, s. 3781-3797
  • Journal article (peer-reviewed)abstract
    • Two circulation index-based methods were applied to downscale summer daily rainfall at four meteorological stations in Chongqing, China. One is a regression method (CIM) and the other a hybrid circulation classification plus regression method (CPM). Both methods used the same three circulation indices and surface specific humidity as predictors. In the first method (CIM), the indices and humidity were used directly as predictors and only one model was developed at each station. In the second method (CPM), the indices were further used to define circulation patterns using the objective Lamb-Jenkinson classification scheme, and one model was built using humidity as the sole predictor for each pattern. Logistic regression was used to define rainfall probability, and a gamma distribution was fit using observations to randomly generate daily rainfall amounts. The two downscaling methods were validated and compared. The results suggest that (1) both methods yield consistently reasonable results with respect to occurrence and amount of daily rainfall, although they perform poorly in reproducing interannual and interdecadal variability, (2) specific humidity should be used as a predictor. Both methods were forced by two future scenarios of a global climate model (GCM) to demonstrate the added value with two methods. The downscaled scenarios show a shift towards larger rainfall values, accompanied by more frequent dry days. This shift is mainly attributed to a change in specific humidity. Despite the similar performances of the two methods, CPM gives a higher frequency of dry days than CIM, whereas CIM produces stronger intensity of rainfall than CPM. This provides additional information about the uncertainty in the projections.
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38.
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39.
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40.
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41.
  • Fan, Lijun, et al. (author)
  • Statistical downscaling of summer temperature extremes in northern China
  • 2013
  • In: Advances in Atmospheric Sciences. - : Springer Science and Business Media LLC. - 0256-1530 .- 1861-9533. ; 30:4, s. 1085-1095
  • Journal article (peer-reviewed)abstract
    • Two approaches of statistical downscaling were applied to indices of temperature extremes based on percentiles of daily maximum and minimum temperature observations at Beijing station in summer during 1960-2008. One was to downscale daily maximum and minimum temperatures by using EOF analysis and stepwise linear regression at first, then to calculate the indices of extremes; the other was to directly downscale the percentile-based indices by using seasonal large-scale temperature and geo-potential height records. The cross-validation results showed that the latter approach has a better performance than the former. Then, the latter approach was applied to 48 meteorological stations in northern China. The cross-validation results for all 48 stations showed close correlation between the percentile-based indices and the seasonal large-scale variables. Finally, future scenarios of indices of temperature extremes in northern China were projected by applying the statistical downscaling to Hadley Centre Coupled Model Version 3 (HadCM3) simulations under the Representative Concentration Pathways 4.5 (RCP 4.5) scenario of the Fifth Coupled Model Inter-comparison Project (CMIP5). The results showed that the 90th percentile of daily maximum temperatures will increase by about 1.5A degrees C, and the 10th of daily minimum temperatures will increase by about 2A degrees C during the period 2011-35 relative to 1980-99.
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42.
  • Feng, Y. Z., et al. (author)
  • Patient-level comparison of heart failure patients in clinical phenotype and prognosis from China and Sweden
  • 2022
  • In: Bmc Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 22:1
  • Journal article (peer-reviewed)abstract
    • Background Clinical phenotype and prognosis of heart failure (HF) may be variable among different racial populations. Therefore, a patient-level comparison of hospitalized HF patients in two university hospitals from China and Sweden was performed. Methods and results This study was a pooled data analysis of the patients prospectively enrolled in two single-center studies in China (n = 949) and Sweden (n = 1639) from 2011 to 2015. Clinical characteristics and 6-month all-cause mortality were collected. Higher systolic blood pressure (126.1 +/- 20.3 vs. 114.2 +/- 15.4 mmHg, p < 0.001) and NT-proBNP level (4540 vs. 3251 pg/mL, p = 0.013) were found in the Swedish cohort, also more patients with ischemic heart disease (32.0% vs. 19.2%), hypertension (64.2% vs. 36.8%), valvular heart disease (40.9% vs.31.6%) and atrial fibrillation (55.3% vs. 39.6%) (all p < 0.001). The use of ACEIs/ARBs (48.8% vs. 80.8%) or beta-blockers (58.8% vs. 86.5%) (both p < 0.001) was lower in Chinese cohort. Given younger age in Chinese cohort (61.6 vs. 76.4 years, p < 0.001), age-stratified analyses were conducted, as there were similar patient numbers in 50-74 years in Chinese (n = 550) and Swedish (n = 554) cohorts, therefore baseline characteristics and prognosis were further compared. The age- and sex-adjusted outcome (HR 0.80 [95% CI 0.55-1.19], p = 0.273) was comparable between the two populations. The NT-proBNP and eGFR independently predicted 6-month mortality in both Chinese (HR [95% CI] 1.006 [1.003-1.008], 0.986 [0.976-0.999]) and Swedish cohort (1.003 [1.000-1.007], 0.988 [0.976-0.999]). Conclusions Patient-level comparison of real-world HF populations from China and Sweden demonstrated different clinical phenotypes and therapy but similar prognosis and their predictors.
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43.
  • Folkersen, Lasse, et al. (author)
  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
  • 2020
  • In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
  • Journal article (peer-reviewed)abstract
    • Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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44.
  • Fontana, J. M., et al. (author)
  • Transport and release of colloidal 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots in human umbilical vein endothelial cells
  • 2017
  • In: International Journal of Nanomedicine. - : Informa UK Limited. - 1178-2013. ; 12, s. 8615-8629
  • Journal article (peer-reviewed)abstract
    • Colloidal semiconductor quantum dots (QDs) have been extensively researched and developed for biomedical applications, including drug delivery and biosensing assays. Hence, it is pivotal to understand their behavior in terms of intracellular transport and toxicological effects. In this study, we focused on 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots (3MPA-QDs) converted from the as-grown octadecylamine-coated quantum dots (ODA-QDs) and their direct and dynamic interactions with human umbilical vein endothelial cells (HUVECs). Live cell imaging using confocal fluorescence microscopy showed that 3MPAQDs first attached to and subsequently aggregated on HUVEC plasma membrane similar to 25 min after QD deposition. The aggregated QDs started being internalized at similar to 2 h and reached their highest internalization degree at similar to 24 h. They were released from HUVECs after similar to 48 h. During the 48 h period, the HUVECs responded normally to external stimulations, grew, proliferated and wound healed without any perceptible apoptosis. Furthermore, 1) 3MPA-QDs were internalized in newly formed LysoTracker-stained early endosomes; 2) adenosine 5'-triphosphateinduced [Ca2+](i) modulation caused a transient decrease in the fluorescence of 3MPA-QDs that were attached to the plasma membrane but a transient increase in the internalized 3MPA-QDs; and 3) fluorescence signal modulations of co-stained LysoTracker and QDs induced by the lysosomotropic agent Gly-Phe-beta-naphthylamide were spatially co-localized and temporally synchronized. Our findings suggest that 3MPA-QDs converted from ODA-QDs are a potential nontoxic fluorescent probe for future use in clinical applications. Moreover, the photophysical strategy and techniques reported in this work are easily applicable to study of direct interactions between other nanoparticles and live cells; contributing to awareness and implementation of the safe applications of nanoparticles.
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45.
  • Fu, Jianxin, et al. (author)
  • Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice.
  • 2011
  • In: The Journal of clinical investigation. - 1558-8238. ; 121:4, s. 1657-66
  • Journal article (peer-reviewed)abstract
    • Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that mice with intestinal epithelial cell-specific deficiency of core 1-derived O-glycans, the predominant form of O-glycans, developed spontaneous colitis that resembled human UC, including massive myeloid infiltrates and crypt abscesses. The colitis manifested in these mice was also characterized by TNF-producing myeloid infiltrates in colon mucosa in the absence of lymphocytes, supporting an essential role for myeloid cells in colitis initiation. Furthermore, induced deletion of intestinal core 1-derived O-glycans caused spontaneous colitis in adult mice. These data indicate a causal role for the loss of core 1-derived O-glycans in colitis. Finally, we detected a biosynthetic intermediate typically exposed in the absence of core 1 O-glycan, Tn antigen, in the colon epithelium of a subset of UC patients. Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase-specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia. These data suggest what we believe to be a new molecular mechanism for the pathogenesis of UC.
  •  
46.
  • Fu, J., et al. (author)
  • Trends in graded precipitation in China from 1961 to 2000
  • 2008
  • In: Advances in atmospheric Sciences. - : Springer Science and Business Media LLC. - 1861-9533 .- 0256-1530. ; 25:2, s. 267-278
  • Journal article (peer-reviewed)abstract
    • Daily precipitation rates observed at 576 stations in China from 1961 to 2000 were classified into six grades of intensity, including trace (no amount), slight (<= 1 mm d(-1)), small, large, heavy, and very heavy. The last four grades together constitute the so called effective precipitation (> 1 mm d(-)1). The spatial distribution and temporal trend of the graded precipitation days are examined. A decreasing trend in trace precipitation days is observed for the whole of China, except at several sites in the south of the middle section of the Yangtze River, while a decreasing trend in slight precipitation days only appears in eastern China. The decreasing trend and interannual variability of trace precipitation days is consistent with the warming trend and corresponding temperature variability in China for the same period, indicating a possible role played by increased surface air temperature in cloud formation processes. For the effective precipitation days, a decreasing trend is observed along the Yellow River valley and for the middle reaches of the Yangtze River and Southwest China, while an increasing trend is found for Xinjiang, the eastern Tibetan Plateau, Northeast China and Southeast China. The decreasing trend of effective precipitation days for the middle-lower Yellow River valley and the increasing trend for the lower Yangtze River valley are most likely linked to anomalous monsoon circulation in East China. The most important contributor to the trend in effective precipitation depends upon the region concerned.
  •  
47.
  • Fu, Li, et al. (author)
  • Effects of long-term exposure to ambient fine particulate matter and its specific components on blood pressure and hypertension incidence
  • 2024
  • In: Environment International. - 0160-4120 .- 1873-6750. ; 184
  • Journal article (peer-reviewed)abstract
    • Background: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) and its specific components with hypertension and blood pressure is limited. Methods: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007–2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. Results: Each interquartile range (IQR = 16.80 μg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR μg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42−, NO3−, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. Conclusions: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.
  •  
48.
  • Fu, Ying, 1964-, et al. (author)
  • Endocytic pathway of vascular cell adhesion molecule 1 in human umbilical vein endothelial cell identified in vitro by using functionalized nontoxic fluorescent quantum dots
  • 2019
  • In: Sensors and actuators. B, Chemical. - : Elsevier B.V.. - 0925-4005 .- 1873-3077. ; 297
  • Journal article (peer-reviewed)abstract
    • Studies about vascular cell adhesion molecule 1 (VCAM1) in tumor growth, metastasis, and angiogenesis suggest that targeting VCAM1 expression is an attractive strategy for diagnosis and anti-tumor therapy. However, the endocytic pathway of VCAM1 in vascular cells has not been well characterized. In this study we visualize the endocytic pathway of tumor necrosis factor α (TNFα) induced VCAM1 in human umbilical vein endothelial cell (HUVEC) in vitro using 5-carboxyfluorescein labeled VCAM1 binding peptides and fluorescent water-dispersible 3-mercaptopropionic acid (3MPA)-coated CdSe-CdS/Cd0.5Zn0.5S/ZnS core–multishell nontoxic quantum dots (3MPA-QDs) functionalized with VCAM1 binding peptides. Clear key in vitro observations are as follows: (a) 3MPA-QDs functionalized with VCAM1 binding peptides, denoted as VQDs, adhered and aggregated cumulatively to cell membrane around 2 h after VQD deposition to cell culture medium and were found in lysosomes in TNFα-treated HUVECs approximately 24 h after VQD deposition; (b) VQDs remained in TNFα-treated HUVECs for the whole 16 days of the experimental observation period; (c) quite differently, 3MPA-QDs were endocytosed then exocytosed by HUVECs via endosomes in about 24–48 h after 3MPA-QD deposition. Our study suggests that VCAM1 molecules, initially expressed on cell membrane induced by TNFα treatment, are internalized into lysosomes. This provides a novel means to deliver materials to lysosomes such as enzyme replacement therapy. Moreover, our meticulous sensing methodology of devising fluorescent nontoxic QDs advances biosensing technique for studying cellular activities in vitro and in vivo. © 2019 The Authors
  •  
49.
  • Fu, Z. J., et al. (author)
  • Dietary omega-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin
  • 2015
  • In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 101:4, s. 879-888
  • Journal article (peer-reviewed)abstract
    • Background: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary omega-3 (n-3) long-chain polyunsaturated fatty acids (omega-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. Objective: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary omega-3 LCPUFAs to mediate the protective effect in ROP. Design: Serum APN concentrations were correlated with ROP development and serum omega-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether omega-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. Results: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum omega-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by omega-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. omega-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary omega-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. Conclusion: Our findings suggest that increasing APN by omega-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.
  •  
50.
  • Fu, Z. J., et al. (author)
  • Dyslipidemia in retinal metabolic disorders
  • 2019
  • In: Embo Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 11:10
  • Journal article (peer-reviewed)abstract
    • The light-sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid-rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.
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