Publications by authors named "Yiping Chen"

435 Publications

The subjective experience of family caregivers of people living with Parkinson's disease: a meta-ethnography of qualitative literature.

Aging Clin Exp Res 2021 Oct 14. Epub 2021 Oct 14.

School of Nursing, Shanxi Medical University, No.56, Xinjian South Road, Yingze District, Taiyuan, Shanxi, China.

Background And Aims: Parkinson's disease patients (PwPD) rely heavily on their family caregivers. However, there remains uncertainty regarding the subjective experience of the family caregivers of PwPD. This study aims to provide an in-depth summary of the current knowledge about the subjective experiences of family caregivers caring for PwPD, to understand the factors that influence this experience and to provide the evidence for healthcare services.

Methods: We conducted a systematic review and meta-ethnography using Noblit and Hare's approach. The search strategy used MeSH terms in combination with free-text searching of 10 databases (from their inception until July 2021). Titles and abstracts were reviewed by two reviewers and, for the studies that met the eligibility criteria, full-text articles were obtained. The Critical Appraisal Skills Program (CASP) checklist was employed to assess the quality of studies.

Results: A total of 3318 studies were screened and 29 qualitative studies were included in this review. These studies recorded the experience of 399 participants across 12 countries, most were females. Five themes emerged: (a) feelings related to PD; (b) challenges to family life; (c) external challenges; (d) adjustment and adaptation; (e) external support. We propose a new conceptual model that highlights that the experiences of caregivers for PwPD are dynamic and influenced by a variety of internal and external factors.

Conclusion: Our findings illustrate the complex and dynamic experiences of family caregivers for PwPD. It is necessary to explore how the influencing factors can be modified to improve the lived experience of family caregivers.
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http://dx.doi.org/10.1007/s40520-021-01995-9DOI Listing
October 2021

Gene Body Methylation Confers Transcription Robustness in Mangroves During Long-Term Stress Adaptation.

Front Plant Sci 2021 22;12:733846. Epub 2021 Sep 22.

State Key Laboratory of Biocontrol and Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Whether induced epigenetic changes contribute to long-term adaptation remains controversial. Recent studies indicate that environmentally cued changes in gene body methylation (gbM) can facilitate acclimatization. However, such changes are often associated with genetic variation and their contribution to long-term stress adaptation remains unclear. Using whole-genome bisulfite sequencing, we examined evolutionary gains and losses of gbM in mangroves that adapted to extreme intertidal environments. We treated mangrove seedlings with salt stress, and investigated expression changes in relation with stress-induced or evolutionarily-acquired gbM changes. Evolution and function of gbM was compared with that of genetic variation. Mangroves gained much more gbM than their terrestrial relatives, mainly through convergent evolution. Genes that convergently gained gbM during evolution are more likely to become methylated in response to salt stress in species where they are normally not marked. Stress-induced and evolutionarily convergent gains of gbM both correlate with reduction in expression variation, conferring genome-wide expression robustness under salt stress. Moreover, convergent gbM evolution is uncoupled with convergent sequence evolution. Our findings suggest that transgenerational inheritance of acquired gbM helps environmental canalization of gene expression, facilitating long-term stress adaptation of mangroves in the face of a severe reduction in genetic diversity.
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http://dx.doi.org/10.3389/fpls.2021.733846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493031PMC
September 2021

SEC61G overexpression and DNA amplification correlates with prognosis and immune cell infiltration in head and neck squamous cell carcinoma.

Cancer Med 2021 Sep 30. Epub 2021 Sep 30.

Department of Radiation Oncology, Jiangxi Cancer Hospital of Nanchang University, Nanchang, Jiangxi, China.

Background: The SEC61 translocon gamma subunit (SEC61G) is a component of the SEC61 complex, which import protein into the endoplasmic reticulum. However, the correlation between SEC61G and disease prognosis in head and neck squamous cell carcinoma (HNSCC) remains unclear.

Methods: SEC61G expression was analyzed using publicly available datasets. The association between SEC61G and disease prognosis was evaluated. SEC61G methylation and copy number variation were investigated and gene set enrichment analysis and gene ontology analyses identified SEC61G-associated functions. We also investigated the correlation between SEC61G and immune cell infiltration. Finally, immunohistochemistry was used to detect SEC61G expression in oropharyngeal carcinoma.

Results: SEC61G was overexpressed in pan-cancers, including HNSCC, and negatively correlated with overall survival (OS) (p < 0.001 for TCGA-HNSCC and p = 0.019 for GSE65858). Moreover, SEC61G was an independent prognostic factor for OS in TCGA and GSE65858 [hazard ratio (HR) = 1.80, 95% CI: 1.35-2.39, p < 0.001; HR = 1.87, 95% CI: 1.14-3.07, p = 0.013, respectively). SEC61G DNA amplification (9.66% of patients) was significantly associated with poor OS (p = 0.034). SEC61G overexpression and DNA amplification negatively correlated with B cell (p < 0.001), CD8 T cell (p < 0.001), CD4 T cell (p < 0.001), macrophage (p < 0.05), neutrophil (p < 0.001), and dendritic cell infiltration (p < 0.001). Among patients with metastatic urothelial cancer received atezolizumab, patients with high SEC61G expression had an inferior OS (p = 0.006). Furthermore, SEC61G protein expression was also an independent prognostic factor of OS (HR = 2.46, 95% CI: 1.15-5.28, p = 0.021) and progression-free survival (HR = 2.82, 95% CI: 1.36-5.85, p = 0.005) for oropharyngeal cancer.

Conclusions: SEC61G is overexpressed in HNSCC and is an independent prognostic factor for OS. SEC61G DNA amplification contributes to overexpression and poor outcome. Interestingly, SEC61G correlates with immune cell infiltration in HNSCC. These findings suggest that SEC61G is a potential broad-spectrum biomarker for prognosis in HNSCC.
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http://dx.doi.org/10.1002/cam4.4301DOI Listing
September 2021

The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.

JAMA Psychiatry 2021 Sep 29. Epub 2021 Sep 29.

23andme, Inc, Sunnyvale, California.

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.

Objective: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression.

Design, Setting, And Participants: Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021.

Exposures: Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts.

Main Outcomes And Measures: Depression status was defined based on health records and self-report questionnaires.

Results: There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (β = -0.018, SE = 0.003, P = 4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (β = 0.028, SE = 0.005, P = 6.48x10-9 for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (β = -0.003, SE = 0.005, P = .53 for rs4656484 and β = -0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = -0.212, SE = 0.084), contrary to findings for individuals of European descent.

Conclusions And Relevance: These results support caution against generalizing findings about depression risk factors across populations and highlight the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.2099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482304PMC
September 2021

Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease.

Front Cell Infect Microbiol 2021 9;11:698852. Epub 2021 Sep 9.

Department of Pediatric Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.
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http://dx.doi.org/10.3389/fcimb.2021.698852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459332PMC
September 2021

Alcohol drinking and risks of liver cancer and non-neoplastic chronic liver diseases in China: a 10-year prospective study of 0.5 million adults.

BMC Med 2021 09 17;19(1):216. Epub 2021 Sep 17.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Alcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations.

Methods: The prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30-79 years recruited from ten areas during 2004-2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years' follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease.

Results: Overall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23-1.69) for liver cancer (n = 547), 1.83 (1.60-2.09) for liver cirrhosis (n = 388), 2.01 (1.77-2.28) for ALD (n = 200), 1.71 (1.35-2.16) for NAFLD (n = 198), and 1.52 (1.40-1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40-3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01-1.72), liver cirrhosis (1.37, 1.02-1.85), and ALD (1.60, 1.09-2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers.

Conclusions: In Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.
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http://dx.doi.org/10.1186/s12916-021-02079-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447782PMC
September 2021

Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study.

Elife 2021 Sep 13;10. Epub 2021 Sep 13.

Epidemiology and Biostatistics, Peking University, Beijing, China.

Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.

We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10-year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.

After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR <0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47% decrease to a 118% increase. Mediation analyses revealed 28.5% of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of gene (P for mediation effect = 0.036). Methylation level at the promoter region of was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7% (P = 0.003) via systolic blood pressure and 6.4% (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.

We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and BP-related pathways to CHD risk.

This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key and Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).
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http://dx.doi.org/10.7554/eLife.68671DOI Listing
September 2021

FGF8-mediated signaling regulates tooth developmental pace during odontogenesis.

J Genet Genomics 2021 Sep 6. Epub 2021 Sep 6.

Fujian Key Laboratory of Developmental and Neural Biology & Southern Center for Biomedical Research, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, 350117, P.R. China. Electronic address:

The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control since their teeth share highly conserved and well-characterized developmental processes and their developmental tempo varies notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrate that the dental mesenchyme dominates the tooth developmental tempo and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3K-Akt intracellular signaling, and impelled the transition of the cell cycle from G1- to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo and the dental mesenchymal FGF8 could be a pivotal factor in controlling the developmental pace in a non-cell-autonomous manner during mammalian odontogenesis.
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http://dx.doi.org/10.1016/j.jgg.2021.08.009DOI Listing
September 2021

N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma.

Sci Rep 2021 Sep 8;11(1):17844. Epub 2021 Sep 8.

Department of Hepatopancreatobiliary Surgery, Fujian Abdominal Surgery Research Institute, the First Affiliated Hospital of Fujian Medical University, Fujian, China.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, fatal tumor. N6-methylandenosine (m6A) methylation is the major epigenetic modification of RNA including lncRNAs. The roles of m6A-related lncRNAs in PDAC have not been fully clarified. This study aims to assess gene signatures and prognostic value of m6A-related lncRNAs in PDAC. The Cancer Genome Atlas (TCGA) dataset and the International Cancer Genome Consortium (ICGC) dataset were explored to identify m6A-related lncRNAs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were performed to construct the m6A-related lncRNAs prognostic riskscore (m6A-LPR) model to predict the overall survival (OS) in the TCGA training cohort. Kaplan-Meier curve with log-rank test and receiver operating characteristic (ROC) curve were used to evaluate the prognostic value of the m6A-LPR. Furthermore, the robustness of the m6A-LPR was further validated in the ICGC cohort. Tumor immunity was evaluated using ESTIMATE and CIBERSORT algorithms. A total of 262 m6A-related lncRNAs were identified in two datasets. In the TCGA training cohort, 28 prognostic m6A-related lncRNAs were identified and the m6A-LPR including four m6A-related lncRNAs was constructed. The m6A-LPR was able to identify high-risk patients with significantly poorer OS and accurately predict OS in both the TCGA training cohort and the ICGC validation cohort. Analysis of tumor immunity revealed that high-risk groups had remarkably lower stromal, immune, and ESTIMATE scores. Moreover, high-risk groups were associated with significantly higher levels of plasma B cells and resting NK cells infiltration, and lower levels of infiltrating resting memory CD4 T cells, monocytes, and resting mast cells. Our study proposed a robust m6A-related prognostic signature of lncRNAs for predicting OS in PDAC, which provides some clues for further studies focusing on the mechanism process underlying m6A modification of lncRNAs.
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http://dx.doi.org/10.1038/s41598-021-97362-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426490PMC
September 2021

Dietary patterns and cardiometabolic diseases in 0.5 million Chinese adults: a 10-year cohort study.

Nutr J 2021 09 3;20(1):74. Epub 2021 Sep 3.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Background: The effect of the overall diet quality on cardiometabolic diseases has been well studied in the Western population. However, evidence is still in need regarding dietary patterns depicting unique Chinese dietary habits and their associations with cardiometabolic diseases.

Methods: A prospective cohort recruited around 0.5 million Chinese residents aged 30-79 years from 10 diverse survey sites during 2004-08. Dietary patterns were obtained using factor analysis based on the habitual consumption of 12 food groups collected at baseline. Among 477,465 eligible participants free of prior heart disease, stroke and cancer, linkages to multiple registries and health insurance database recorded 137,715 cardiovascular diseases (CVD) and 17,412 diabetes cases (among 451,846 non-diabetic participants) until 31 December 2017. Adjusted hazard ratios (HRs) were estimated to compare the risks of cardiometabolic diseases across quintiles of dietary pattern scores using the Cox regression.

Results: Two dietary patterns were derived: the traditional northern pattern, characterised by wheat, other staples, egg and dairy products; and the modern pattern, featured with fresh fruit, meat, poultry, fish, dairy products and soybean. Adherence to either dietary pattern was associated with lower risks of major cardiometabolic diseases in a dose-response relationship way. After multivariate adjustment, participants adhering to the traditional northern pattern the most had an 8% (95%CI: 5-11%) lower risk of CVD in comparison with those adhering the least. Corresponding risk reductions were 12% (11-32%) for haemorrhagic stroke (HS), 14% (8-19%) for ischaemic stroke (IS), and 15% (6-24%) for diabetes, respectively. When comparing extreme quintiles of the modern pattern, the adjusted HR of HS was 0.67 (95%CI: 0.59-0.77). Corresponding HRs were 0.89 (0.86-0.92) for CVD, 0.88 (0.77-0.99) for MCE, 0.85 (0.80-0.89) for IS, and 0.89 (0.81, 0.97) for diabetes.

Conclusion: Among Chinese adults, both traditional northern and modern dietary patterns were associated with lower risks of cardiovascular disease and diabetes beyond other risk factors.
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http://dx.doi.org/10.1186/s12937-021-00730-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418004PMC
September 2021

Utility of single versus sequential measurements of risk factors for prediction of stroke in Chinese adults.

Sci Rep 2021 09 2;11(1):17575. Epub 2021 Sep 2.

Clinical Trial Service Unit and Epidemiological Studies, Nuffield Department of Population Health, University of Oxford, Big Data Institute, Old Road Campus, Oxford, OX 7LF, UK.

Absolute risks of stroke are typically estimated using measurements of cardiovascular disease risk factors recorded at a single visit. However, the comparative utility of single versus sequential risk factor measurements for stroke prediction is unclear. Risk factors were recorded on three separate visits on 13,753 individuals in the prospective China Kadoorie Biobank. All participants were stroke-free at baseline (2004-2008), first resurvey (2008), and second resurvey (2013-2014), and were followed-up for incident cases of first stroke in the 3 years following the second resurvey. To reflect the models currently used in clinical practice, sex-specific Cox models were developed to estimate 3-year risks of stroke using single measurements recorded at second resurvey and were retrospectively applied to risk factor data from previous visits. Temporal trends in the Cox-generated risk estimates from 2004 to 2014 were analyzed using linear mixed effects models. To assess the value of more flexible machine learning approaches and the incorporation of longitudinal data, we developed gradient boosted tree (GBT) models for 3-year prediction of stroke using both single measurements and sequential measurements of risk factor inputs. Overall, Cox-generated estimates for 3-year stroke risk increased by 0.3% per annum in men and 0.2% per annum in women, but varied substantially between individuals. The risk estimates at second resurvey were highly correlated with the annual increase of risk for each individual (men: r = 0.91, women: r = 0.89), and performance of the longitudinal GBT models was comparable with both Cox and GBT models that considered measurements from only a single visit (AUCs: 0.779-0.811 in men, 0.724-0.756 in women). These results provide support for current clinical guidelines, which recommend using risk factor measurements recorded at a single visit for stroke prediction.
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http://dx.doi.org/10.1038/s41598-021-95244-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413314PMC
September 2021

Scene Recognition Using Deep Softpool Capsule Network Based on Residual Diverse Branch Block.

Sensors (Basel) 2021 Aug 19;21(16). Epub 2021 Aug 19.

School of Electronic and Electrical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China.

With the improvement of the quality and resolution of remote sensing (RS) images, scene recognition tasks have played an important role in the RS community. However, due to the special bird's eye view image acquisition mode of imaging sensors, it is still challenging to construct a discriminate representation of diverse and complex scenes to improve RS image recognition performance. Capsule networks that can learn the spatial relationship between the features in an image has a good image classification performance. However, the original capsule network is not suitable for images with a complex background. To address the above issues, this paper proposes a novel end-to-end capsule network termed DS-CapsNet, in which a new multi-scale feature enhancement module and a new Caps-SoftPool method are advanced by aggregating the advantageous attributes of the residual convolution architecture, Diverse Branch Block (DBB), Squeeze and Excitation (SE) block, and the Caps-SoftPool method. By using the residual DBB, multiscale features can be extracted and fused to recover a semantic strong feature representation. By adopting SE, the informative features are emphasized, and the less salient features are weakened. The new Caps-SoftPool method can reduce the number of parameters that are needed in order to prevent an over-fitting problem. The novel DS-CapsNet achieves a competitive and promising performance for RS image recognition by using high-quality and robust capsule representation. The extensive experiments on two challenging datasets, AID and NWPU-RESISC45, demonstrate the robustness and superiority of the proposed DS-CapsNet in scene recognition tasks.
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http://dx.doi.org/10.3390/s21165575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402264PMC
August 2021

A systematic dissection of human primary osteoblasts at single-cell resolution.

Aging (Albany NY) 2021 08 24;13(16):20629-20650. Epub 2021 Aug 24.

Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA.

Human osteoblasts are multifunctional bone cells, which play essential roles in bone formation, angiogenesis regulation, as well as maintenance of hematopoiesis. However, the categorization of primary osteoblast subtypes in humans has not yet been achieved. Here, we used single-cell RNA sequencing (scRNA-seq) to perform a systematic cellular taxonomy dissection of freshly isolated human osteoblasts from one 31-year-old male with osteoarthritis and osteopenia after hip replacement. Based on the gene expression patterns and cell lineage reconstruction, we identified three distinct cell clusters including preosteoblasts, mature osteoblasts, and an undetermined rare osteoblast subpopulation. This novel subtype was found to be the major source of the nuclear receptor subfamily 4 group A member 1 and 2 (NR4A1 and NR4A2) in primary osteoblasts, and the expression of NR4A1 was confirmed by immunofluorescence staining on mouse osteoblasts . Trajectory inference analysis suggested that the undetermined cluster, together with the preosteoblasts, are involved in the regulation of osteoblastogenesis and also give rise to mature osteoblasts. Investigation of the biological processes and signaling pathways enriched in each subpopulation revealed that in addition to bone formation, preosteoblasts and undetermined osteoblasts may also regulate both angiogenesis and hemopoiesis. Finally, we demonstrated that there are systematic differences between the transcriptional profiles of human and mouse osteoblasts, highlighting the necessity for studying bone physiological processes in humans rather than solely relying on mouse models. Our findings provide novel insights into the cellular heterogeneity and potential biological functions of human primary osteoblasts at the single-cell level.
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http://dx.doi.org/10.18632/aging.203452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436943PMC
August 2021

Lifestyle, cardiometabolic disease, and multimorbidity in a prospective Chinese study.

Eur Heart J 2021 09;42(34):3374-3384

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Xueyuan Road, Haidian District, Beijing 100191, China.

Aims: The potential difference in the impacts of lifestyle factors (LFs) on progression from healthy to first cardiometabolic disease (FCMD), subsequently to cardiometabolic multimorbidity (CMM), and further to death is unclear.

Methods And Results: We used data from the China Kadoorie Biobank of 461 047 adults aged 30-79 free of heart disease, stroke, and diabetes at baseline. Cardiometabolic multimorbidity was defined as the coexistence of two or three CMDs, including ischaemic heart disease (IHD), stroke, and type 2 diabetes (T2D). We used multi-state model to analyse the impacts of high-risk LFs (current smoking or quitting because of illness, current excessive alcohol drinking or quitting, poor diet, physical inactivity, and unhealthy body shape) on the progression of CMD. During a median follow-up of 11.2 years, 87 687 participants developed at least one CMD, 14 164 developed CMM, and 17 541 died afterwards. Five high-risk LFs played crucial but different roles in all transitions from healthy to FCMD, to CMM, and then to death. The hazard ratios (95% confidence intervals) per one-factor increase were 1.20 (1.19, 1.21) and 1.14 (1.11, 1.16) for transitions from healthy to FCMD, and from FCMD to CMM, and 1.21 (1.19, 1.23), 1.12 (1.10, 1.15), and 1.10 (1.06, 1.15) for mortality risk from healthy, FCMD, and CMM, respectively. When we further divided FCMDs into IHD, ischaemic stroke, haemorrhagic stroke, and T2D, we found that LFs played different roles in disease-specific transitions even within the same transition stage.

Conclusion: Assuming causality exists, our findings emphasize the significance of integrating comprehensive lifestyle interventions into both health management and CMD management.
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http://dx.doi.org/10.1093/eurheartj/ehab413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423468PMC
September 2021

Adherence to healthy lifestyle and attenuation of biological aging in middle-aged and older Chinese adults.

J Gerontol A Biol Sci Med Sci 2021 Jul 30. Epub 2021 Jul 30.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China.

Background: Little is known about the effects of lifestyle modification on biological aging in population-based studies of middle-aged and older adults.

Methods: We examined the individual and joint associations of multiple lifestyle factors with accelerated biological aging measured by change in frailty index (FI) over 8 years in a prospective study of Chinese adults. Data were obtained on 24,813 participants in the China Kadoorie Biobank (CKB) on lifestyle factors and frailty status at baseline and at 8 years after baseline. Adherence to healthy lifestyle factors included non-smoking or quitting smoking for reasons other than illness, avoidance of heavy alcohol consumption, daily intake of fruit and vegetables, being physically active, body mass index (BMI) of 18.5-23.9 kg/m 2, and waist-to-hip ratio (WHR) <0.90 (men)/0.85 (women). FI was constructed separately at baseline and resurvey using 25 age- and health-related items.

Results: Overall, 8,760 (35.3%) individuals had a worsening frailty status. In multivariable-adjusted logistic regression analyses, adherence to healthy lifestyle was associated with a lower risk of worsening frailty status. Compared with robust participants maintaining 0-1 healthy lifestyle factors, the corresponding OR (95% CI) was 0.93 (0.83-1.03), 0.75 (0.67-0.84), 0.68 (0.60-0.77), and 0.55 (0.46-0.65) for robust participants with 2, 3, 4, and 5-6 healthy lifestyle factors. The decreased risk of frailty status worsening by adherence to healthy lifestyle factors was similar in both middle-aged and older adults, and in both robust and prefrail participants at baseline.

Conclusions: Adherence to a healthy lifestyle may attenuate the rate of change in biological aging in middle-aged and older Chinese adults.
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http://dx.doi.org/10.1093/gerona/glab213DOI Listing
July 2021

Association between blood pressure categories and cardiovascular disease mortality in China.

PLoS One 2021 30;16(7):e0255373. Epub 2021 Jul 30.

Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing, China.

Background: Blood pressure (BP) categories are useful to simplify preventions in public health, and diagnostic and treatment approaches in clinical practice. Updated evidence about the associations of BP categories with cardiovascular diseases (CVDs) and its subtypes is warranted.

Methods And Findings: About 0.5 million adults aged 30 to 79 years were recruited from 10 areas in China during 2004-2008. The present study included 430 977 participants without antihypertension treatment, cancer, or CVD at baseline. BP was measured at least twice in a single visit at baseline and CVD deaths during follow-up were collected via registries and the national health insurance databases. Multivariable Cox regression was used to estimate the associations between BP categories and CVD mortality. Overall, 16.3% had prehypertension-low, 25.1% had prehypertension-high, 14.1% had isolated systolic hypertension (ISH), 1.9% had isolated diastolic hypertension (IDH), and 9.1% had systolic-diastolic hypertension (SDH). During a median 10-year follow-up, 9660 CVD deaths were documented. Compared with normal, the hazard ratios (95% CI) of prehypertension-low, prehypertension-high, ISH, IDH, SDH for CVD were 1.10 (1.01-1.19), 1.32 (1.23-1.42), 2.04 (1.91-2.19), 2.20 (1.85-2.61), and 3.81 (3.54-4.09), respectively. All hypertension subtypes were related to the increased risk of CVD subtypes, with a stronger association for hemorrhagic stroke than for ischemic heart disease. The associations were stronger in younger than older adults.

Conclusions: Prehypertension-high should be considered in CVD primary prevention given its high prevalence and increased CVD risk. All hypertension subtypes were independently associated with CVD and its subtypes mortality, though the strength of associations varied substantially.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255373PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323908PMC
July 2021

Blood pressure and cardiovascular diseases in Chinese adults with type 2 diabetes: A prospective cohort study.

Lancet Reg Health West Pac 2021 Feb 23;7:100085. Epub 2021 Jan 23.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK.

Background: Controversy persists about the relationship of blood pressure with cardiovascular diseases (CVD) in diabetes and associated disease burden. We assessed these associations among Chinese adults with type 2 diabetes (T2D).

Methods: In 2004-08, the China Kadoorie Biobank recruited >512,000 adults aged 30-79 years from 10 localities across China, including 26,315 with T2D (based on self-report or plasma glucose measurement) but no prior CVD, followed-up for ~9 years. Cox regression yielded adjusted HR for major CVD and all-cause mortality associated with 10 mmHg higher usual (longer-term average) SBP. Attributable fractions were estimated to assess cardiovascular mortality burden due to uncontrolled hypertension (SBP ≥130 mmHg or DBP ≥80 mmHg).

Findings: Overall, 75.7% of participants had self-reported (24.8%) or screen-detected (50.9%) (SBP ≥130 mmHg or DBP ≥80 mmHg) hypertension. Among individuals with self-reported hypertension, 82.3% were treated, of whom 9.3% achieved control. There were positive log-linear associations of blood pressure with CVD, with no evidence of a threshold down to ~120 mmHg for usual SBP. Each 10 mmHg higher usual SBP was associated with HR of 1.28 (95% CI 1.25-1.30), 1.18 (1.15-1.21), 1.17 (1.15-1.19) and 1.45 (1.38-1.52) for cardiovascular death (=1807), major coronary event (=1190), ischaemic stroke (=4362) and intracerebral haemorrhage (=469), respectively. There was an apparent J-shaped association with all-cause mortality (=4503). In this diabetes population, uncontrolled hypertension accounted for 39% of cardiovascular deaths.

Interpretation: Uncontrolled hypertension is common in Chinese adults with T2D, resulting in substantial excess risks of CVD. Improved hypertension management could avoid a large number of cardiovascular-related deaths.

Funding: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315364PMC
February 2021

Long-term solid fuel use and risks of major eye diseases in China: A population-based cohort study of 486,532 adults.

PLoS Med 2021 07 29;18(7):e1003716. Epub 2021 Jul 29.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom.

Background: Over 3.5 billion individuals worldwide are exposed to household air pollution from solid fuel use. There is limited evidence from cohort studies on associations of solid fuel use with risks of major eye diseases, which cause substantial disease and economic burden globally.

Methods And Findings: The China Kadoorie Biobank recruited 512,715 adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Cooking frequency and primary fuel types in the 3 most recent residences were assessed by a questionnaire. During median (IQR) 10.1 (9.2 to 11.1) years of follow-up, electronic linkages to national health insurance databases identified 4,877 incident conjunctiva disorders, 13,408 cataracts, 1,583 disorders of sclera, cornea, iris, and ciliary body (DSCIC), and 1,534 cases of glaucoma. Logistic regression yielded odds ratios (ORs) for each disease associated with long-term use of solid fuels (i.e., coal or wood) compared to clean fuels (i.e., gas or electricity) for cooking, with adjustment for age at baseline, birth cohort, sex, study area, education, occupation, alcohol intake, smoking, environmental tobacco smoke, cookstove ventilation, heating fuel exposure, body mass index, prevalent diabetes, self-reported general health, and length of recall period. After excluding participants with missing or unreliable exposure data, 486,532 participants (mean baseline age 52.0 [SD 10.7] years; 59.1% women) were analysed. Overall, 71% of participants cooked regularly throughout the recall period, of whom 48% used solid fuels consistently. Compared with clean fuel users, solid fuel users had adjusted ORs of 1.32 (1.07 to 1.37, p < 0.001) for conjunctiva disorders, 1.17 (1.08 to 1.26, p < 0.001) for cataracts, 1.35 (1.10 to 1.66, p = 0.0046) for DSCIC, and 0.95 (0.76 to 1.18, p = 0.62) for glaucoma. Switching from solid to clean fuels was associated with smaller elevated risks (over long-term clean fuel users) than nonswitching, with adjusted ORs of 1.21 (1.07 to 1.37, p < 0.001), 1.05 (0.98 to 1.12, p = 0.17), and 1.21 (0.97 to 1.50, p = 0.088) for conjunctiva disorders, cataracts, and DSCIC, respectively. The adjusted ORs for the eye diseases were broadly similar in solid fuel users regardless of ventilation status. The main limitations of this study include the lack of baseline eye disease assessment, the use of self-reported cooking frequency and fuel types for exposure assessment, the risk of bias from delayed diagnosis (particularly for cataracts), and potential residual confounding from unmeasured factors (e.g., sunlight exposure).

Conclusions: Among Chinese adults, long-term solid fuel use for cooking was associated with higher risks of not only conjunctiva disorders but also cataracts and other more severe eye diseases. Switching to clean fuels appeared to mitigate the risks, underscoring the global health importance of promoting universal access to clean fuels.
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http://dx.doi.org/10.1371/journal.pmed.1003716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321372PMC
July 2021

Horseradish peroxidase-catalyzed formation of polydopamine for ultra-sensitive magnetic relaxation sensing of aflatoxin B.

J Hazard Mater 2021 10 12;419:126403. Epub 2021 Jun 12.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China. Electronic address:

Aflatoxin B as one of the most toxic mycotoxins poses a major health risk to humans and animals. Highly sensitive detection methods of aflatoxin B are urgently required because of its low abundance in biological samples. In this work, we developed a magnetic relaxation sensing strategy using enzyme-catalyzed formation of polydopamine for signal amplification. Horseradish peroxidase can catalyze the reaction to generate polydopamine that assembles magnetic nanoparticles for magnetic relaxation sensing with a high signal-to-noise ratio. Combined with the specific antigen-antibody interaction, this magnetic sensor enables fast and ultra-sensitive detection of aflatoxin B by using transverse relaxation time (T) as a readout. Under optimized conditions, the linear range of this magnetic sensor for detecting aflatoxin B is from 10 pg/mL to 10 ng/mL, and the limit of detection is 0.35 pg/mL. This sensor has been challenged for the quantitative analysis of aflatoxin B in animal feed samples that is promising for real-world applications.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126403DOI Listing
October 2021

Highly sensitive magnetic relaxation sensing method for aflatoxin B1 detection based on Au NP-assisted triple self-assembly cascade signal amplification.

Biosens Bioelectron 2021 Nov 9;192:113489. Epub 2021 Jul 9.

Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Science/Key Laboratory of Agro-Products Quality and Safety of MOA, Beijing, 100081, PR China. Electronic address:

Highly sensitive detection of aflatoxin B (AFB) is of great significance because of its high toxicity and carcinogenesis. We propose a magnetic relaxation sensing method based on gold nanoparticles (Au NPs)-assisted triple self-assembly cascade signal amplification for highly sensitive detection of AFB. Both AFB antibody and initiator DNA (iDNA) are labeled on Au NPs to form Ab-Au-iDNA probe. iDNA is enriched by Au NPs to achieve first signal amplification. Different amounts of Ab-Au-iDNA were bound with AFB antigen by indirect competitive immunoassay, and then hybridization chain reaction event was initiated by iDNA to produce long hybridization chain reaction products to enrich more horseradish peroxidase-streptavidin for the second signal amplification. Dopamine could be rapidly converted to polydopamine by HRP catalysis, which is used as the third signal amplification. The Fe solution, providing paramagnetic ions with a strong magnetic signal, could be adsorbed by the polydopamine due to the formation of coordination bonds of phenolic hydroxyl groups with Fe. This effective interaction between polydopamine and Fe significantly changes the transverse relaxation time signal of Fe supernatant solution, which can be used as a magnetic probe for highly sensitive detection of AFB. The sensor exhibited high specificity and sensitivity with a detection limit of 0.453 pg/mL owing to the Au NP-assisted triple self-assembly cascade signal amplification strategy. It has been successfully employed for AFB detection in animal feed samples with consistent results of enzyme linked immune sorbent assay and high-performance liquid chromatography.
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http://dx.doi.org/10.1016/j.bios.2021.113489DOI Listing
November 2021

Re-utilization of Chinese medicinal herbal residues improved soil fertility and maintained maize yield under chemical fertilizer reduction.

Chemosphere 2021 Nov 19;283:131262. Epub 2021 Jun 19.

Institute of Ecology and Environmental Governance, College of Life Sciences, Hebei University, Baoding, 071002, China.

Excessive utilization of chemical fertilizers (CF) is not a sustainable agricultural development strategy due to adverse effects on soil health. In contrast, a combination of organic and mineral fertilizers has a positive effect on both soil health and productivity. Chinese medicinal herbal residues (CMHR) is the plant material wastes remaining after drug extraction but has not been extensively used as fertilizer. We evaluated application of CMHR to maize fields over 3 consecutive growing seasons in the presence and absence of standard CF to assess improvements in soil fertility, maize yields and sustainable development. CMHR fertilization increased soil organic matter and total N and K when mixed with chemical fertilizer at 50 and 75% the standard application rate. Soil organic matter increased by 27.0-51.4% and available -N, -P and -K levels and grain yields as well as N and P use efficiency in the presence of CMHR mixes were similar to levels obtained with chemical fertilizer only. These increases in production were due to increased leaf areas, photosynthetic rates, grain number and 1000-grain weights. The addition of CMHR to fields posed a slightly risk of toxic-metal pollution. Overall, we found that (1) CMHR can be used as an effective organic fertilizer and replace up to 50% of the amount of chemical fertilizer normally applied to fields without hampering maize grain yields and (2) CMHR application to agricultural fields is an effective recycling strategy and nutrient management practice to improve soil fertility under CF usage reduction.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131262DOI Listing
November 2021

Correction to: Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons.

Cell Mol Life Sci 2021 Jul 22;78(14):5665-5666. Epub 2021 Jun 22.

Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children, University of California at Davis, School of Medicine, 2425 Stockton Blvd., Sacramento, CA, 95817, USA.

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http://dx.doi.org/10.1007/s00018-021-03870-2DOI Listing
July 2021

Associations of toothbrushing behaviour with risks of vascular and nonvascular diseases in Chinese adults.

Eur J Clin Invest 2021 Jun 21:e13634. Epub 2021 Jun 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Accumulating evidence has shown that poor oral hygiene is associated with increased risk of cardiometabolic diseases in Western populations. However, its relevance about the relationships in Chinese adults remains unclear. The China Kadoorie Biobank enrolled 512 715 adults aged 30-79 years in China during 2004-2008. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with measures of oral hygiene. Overall 9.3% of the participants reported rarely or never brushing teeth at baseline. Participants who rarely or never brushed teeth had adjusted HR of 1.12 (95% CI: 1.09, 1.15) for MVE, with similar HRs for stroke (1.08, 1.05-1.12), intracerebral haemorrhage (1.18, 1.11-1.26) and pulmonary heart disease (1.22, 1.13-1.32) compared with those who brushed teeth regularly. Those who did not brush teeth also had increased risk of cancer (1.09, 1.04-1.14), chronic obstructive pulmonary disease (COPD) (1.12, 1.05-1.20), liver cirrhosis (1.25, 1.09-1.44) and all-cause death (1.25, 1.21-1.28) but not type 2 diabetes (0.94, 0.86-1.03) and chronic kidney disease (0.98, 0.81-1.18). Among Chinese adults, we found that poor oral hygiene is associated with higher risks of major vascular disease, cancer, COPD, liver cirrhosis and all-cause deaths, but not type 2 diabetes and chronic kidney disease.
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http://dx.doi.org/10.1111/eci.13634DOI Listing
June 2021

Establishing and Validating Cellular Functional Target Engagement Assay for Selective IRAK4 Inhibitor Discovery.

SLAS Discov 2021 Sep 16;26(8):1040-1054. Epub 2021 Jun 16.

Department of Quantitative Bioscience, Merck & Co., Inc., Boston, MA, USA.

One of the main reasons for the lack of drug efficacy in late-stage clinical trials is the lack of specific and selective target engagement. To increase the likelihood of success of new therapeutics, one approach is to conduct proximal target engagement testing during the early phases of preclinical drug discovery. To identify and optimize selective IRAK4 inhibitors, a kinase that has been implicated in multiple inflammatory and autoimmune diseases, we established an electrochemiluminescence (ECL)-based cellular endogenous IRAK1 activation assay as the most proximal functional evaluation of IRAK4 engagement to support structure-activity relationship (SAR) studies. Since IRAK1 activation is dependent on both the IRAK4 scaffolding function in Myddosome formation and IRAK4 kinase activity for signal transduction, this assay potentially captures inhibitors with different mechanisms of action. Data from this IRAK1 assay with compounds representing different structural classes showed statistically significant correlations when compared with results from both IRAK4 biochemical kinase activity and functional peripheral blood mononuclear cell (PBMC)-derived tumor necrosis factor α (TNFα) secretion assays, validating the biological relevancy of the IRAK1 target engagement as a biomarker of the IRAK4 activity. Plate uniformity and potency reproducibility evaluations demonstrated that this assay is amenable to high throughput. Using Bland-Altman assay agreement analysis, we demonstrated that incorporating such proximal pharmacological assessment of cellular target engagement to an in vitro screening funnel for SAR studies can prevent compound optimization toward off-target activity.
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http://dx.doi.org/10.1177/24725552211021074DOI Listing
September 2021

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses.

Nutr Metab Cardiovasc Dis 2021 07 27;31(8):2328-2337. Epub 2021 Apr 27.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China. Electronic address:

Background And Aims: Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.

Methods And Results: The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).

Conclusions: This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.
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http://dx.doi.org/10.1016/j.numecd.2021.04.015DOI Listing
July 2021

Development and external validation of a breast cancer absolute risk prediction model in Chinese population.

Breast Cancer Res 2021 05 29;23(1):62. Epub 2021 May 29.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Backgrounds: In contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. However, there is no validated risk prediction model in China to aid early detection yet.

Methods: A large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004-2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women's Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy.

Results: During a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed (E/O) ratios of 1.01 (95% confidence interval (CI), 0.94-1.09) and 0.94 (95% CI, 0.89-0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608-0.661) and 0.585 (95% CI, 0.564-0.605) in the CKB and the SWHS, respectively.

Conclusions: Based only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals' awareness and aid risk-stratified screening and prevention strategies.
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http://dx.doi.org/10.1186/s13058-021-01439-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164768PMC
May 2021

Gender differences in use of invasive diagnostic and therapeutic procedures for acute ischaemic heart disease in Chinese adults.

Heart 2021 May 27. Epub 2021 May 27.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK

Objective: To investigate gender differences in the use of diagnostic and therapeutic procedures for acute ischaemic heart disease (IHD) in Chinese adults and assess whether socioeconomic or health system factors contribute to such differences.

Methods: In 2004-2008, the China Kadoorie Biobank recruited 512 726 adults from 10 diverse areas in China. Data for 38 928 first hospitalisations with IHD (2911 acute myocardial infarction (AMI), 9817 angina and 26 200 other IHD) were obtained by electronic linkage to health insurance records until 31 December 2016. Multivariate Poisson regression models were used to estimate women-to-men rate ratios (RRs) of having cardiac enzyme tests, coronary angiography and coronary revascularisation.

Results: Among the 38 928 individuals (61% women) with IHD admissions, women were less likely to have AMI (5% vs 12%), but more likely to have angina (26% vs 24%) or other IHD (69% vs 64%). For admissions with AMI, there were no differences in the use of cardiac enzymes between women and men (RR=1.00; 95% CI, 0.97 to 1.03), but women had lower use of coronary angiography (0.80, 0.68 to 0.93) and coronary revascularisation (0.85, 0.74 to 0.99). For angina, the corresponding RRs were: 0.97 (0.94 to 1.00), 0.66 (0.59 to 0.74) and 0.56 (0.47 to 0.67), respectively; while for other IHD, they were 0.97 (0.94 to 1.00), 0.87 (0.76 to 0.99) and 0.61 (0.51 to 0.73), respectively. Adjusting for socioeconomic and health system factors did not significantly alter the women-to-men RRs.

Conclusions: Among Chinese adults hospitalised with acute IHD, women were less likely than men to have coronary angiography and revascularisation, but socioeconomic and health system factors did not contribute to these differences.
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http://dx.doi.org/10.1136/heartjnl-2021-318988DOI Listing
May 2021

Age-Specific Associations Between Habitual Snoring and Cardiovascular Diseases in China: A 10-Year Cohort Study.

Chest 2021 Sep 21;160(3):1053-1063. Epub 2021 May 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China. Electronic address:

Background: Limited convincing evidence is available of the relationship between habitual snoring and cardiovascular diseases (CVDs).

Research Question: Is habitual snoring associated with total CVD and CVD subtypes in different age groups of Chinese adults?

Study Design And Methods: The China Kadoorie Biobank study enrolled more than 0.5 million adults aged 30 to 79 years from 10 regions in China. Snoring status and other baseline characteristics were collected from 2004 to 2008, using an interviewer-administered laptop-based questionnaire. The current analysis included 489,583 participants without stroke or coronary heart disease at baseline. Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs) and 95% CIs of cardiovascular diseases (CVDs) for habitual snoring vs nonhabitual snoring.

Results: During a median follow-up of 9.6 years, 130,935 participants developed CVDs. Associations between habitual snoring and CVDs varied with age. Among participants aged younger than 50 years at baseline, habitual snoring was associated with an increased risk of total CVD (HR, 1.11; 95% CI, 1.07-1.14) after adjustment for known CVD risk factors, including systolic BP. The corresponding HRs (95% CIs) for ischemic heart disease, ischemic stroke, and hemorrhagic stroke were 1.18 (1.12-1.24), 1.12 (1.05-1.19), and 1.05 (0.92-1.19), respectively. However, such associations in adults aged 50 to 64 years were much weaker, and no statistically significant association was observed among individuals aged ≥65 years. Age-specific risk estimates were generally similar across sex and obesity subgroups.

Interpretation: Habitual snoring was associated with increased risks of total CVD, ischemic heart disease, ischemic stroke, but not hemorrhagic stroke in Chinese, and these associations were mainly limited to those aged <50 years. Clinicians in China are encouraged to identify snoring, particularly in younger adults.
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http://dx.doi.org/10.1016/j.chest.2021.04.070DOI Listing
September 2021

KRN7000 Reduces Airway Inflammation via Natural Killer T Cells in Obese Asthmatic Mice.

Inflammation 2021 Oct 22;44(5):1982-1992. Epub 2021 May 22.

The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530001, People's Republic of China.

Although natural killer T cells (NKT cells) are altered in obese asthmatic mice, their function remains completely unclear. To further explore the potential mechanism of NKT cells in airway inflammation of obesity-associated asthma, we examined the effects of α-galactosylceramide (KRN7000) on airway inflammation in obese asthmatic mice. Male C57BL/6J mice were divided into five groups: (1) control; (2) asthma; (3) A + KRN, asthma with KRN7000; (4) obese asthma; and (5) OA + KRN, obese asthma with KRN7000. Cytometric bead array (CBA) was used to detect interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the serum. Flow cytometry was used to detect NKT cells and CD69 NKT cells. Airway inflammation was observed in pathological sections, and calmodulin (CaM) expression was observed by immunohistochemistry in lung tissues. Airway inflammation in the obese asthma group was more severe than that of the asthma group. Airway inflammation of the OA + KRN group was reduced more than that of the A + KRN group. CD69+ NKT cells were only significantly reduced in the OA + KRN group. The levels of serum IFN-γ and TNF-α increased more in the OA + KRN group than in the A + KRN group. CaM is widely expressed in the cytoplasm of the lung tissues and was sharply decreased in the OA + KRN group. KRN7000 can significantly reduce airway inflammation in obesity-associated asthma by regulating NKT cell cytokine secretion and intracellular calcium. These results may contribute to the development of novel therapeutic approaches.
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http://dx.doi.org/10.1007/s10753-021-01475-2DOI Listing
October 2021

Stroke risk prediction using machine learning: a prospective cohort study of 0.5 million Chinese adults.

J Am Med Inform Assoc 2021 07;28(8):1719-1727

Department of Engineering Science, University of Oxford, Oxford, UK.

Objective: To compare Cox models, machine learning (ML), and ensemble models combining both approaches, for prediction of stroke risk in a prospective study of Chinese adults.

Materials And Methods: We evaluated models for stroke risk at varying intervals of follow-up (<9 years, 0-3 years, 3-6 years, 6-9 years) in 503 842 adults without prior history of stroke recruited from 10 areas in China in 2004-2008. Inputs included sociodemographic factors, diet, medical history, physical activity, and physical measurements. We compared discrimination and calibration of Cox regression, logistic regression, support vector machines, random survival forests, gradient boosted trees (GBT), and multilayer perceptrons, benchmarking performance against the 2017 Framingham Stroke Risk Profile. We then developed an ensemble approach to identify individuals at high risk of stroke (>10% predicted 9-yr stroke risk) by selectively applying either a GBT or Cox model based on individual-level characteristics.

Results: For 9-yr stroke risk prediction, GBT provided the best discrimination (AUROC: 0.833 in men, 0.836 in women) and calibration, with consistent results in each interval of follow-up. The ensemble approach yielded incrementally higher accuracy (men: 76%, women: 80%), specificity (men: 76%, women: 81%), and positive predictive value (men: 26%, women: 24%) compared to any of the single-model approaches.

Discussion And Conclusion: Among several approaches, an ensemble model combining both GBT and Cox models achieved the best performance for identifying individuals at high risk of stroke in a contemporary study of Chinese adults. The results highlight the potential value of expanding the use of ML in clinical practice.
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http://dx.doi.org/10.1093/jamia/ocab068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324240PMC
July 2021
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