Publications by authors named "Yajun Liang"

87 Publications

Genome-Wide Association Analysis of Salt-Tolerant Traits in Terrestrial Cotton at Seedling Stage.

Plants (Basel) 2021 Dec 29;11(1). Epub 2021 Dec 29.

Economic Crops Research Institute, Xinjiang Academy of Agricultural Science (XAAS), Urumqi 830001, China.

Soil salinization is the main abiotic stress factor affecting agricultural production worldwide, and salt stress has a significant impact on plant growth and development. Cotton is one of the most salt-tolerant crops. Therefore, the selection and utilization of salt-tolerant germplasm resources and the excavation of salt resistance genes play important roles in improving cotton production in saline-alkali soils. In this study, we analysed the population structure and genetic diversity of a total 149 cotton plant materials including 137 elite cultivar accessions collected from China and 12 elite cultivar accessions collected from around the world. Illumina Cotton SNP 70 K was used to obtain genome-wide single-nucleotide polymorphism (SNP) data for 149 elite cultivar accessions, and 18,430 highly consistent SNP loci were obtained by filtering. It was assessed by using PCA principal component analysis so that the 149 elite cultivar accessions could be divided into two subgroups, including subgroup 1 with 78 materials and subgroup 2 with 71 materials. Using the obtained SNP and other marker genotype test results, under salt stress, the salt tolerance traits 3d Germination potential, 3d Radicle length drop rate, 7d Germination rate, 7d Radicle length drop rate, 7d Germination weight, 3d Radicle length, 7d Radicle length, Relative Germination potential, Relative Germination rate, 7d Radicle weight drop rate, Salt tolerance index 3d Germination potential index, 3d Radicle length index, 7d Radicle length index, 7d Radicle weight index and 7d Germination rate index were evaluated by GWAS (genome-wide association analysis). A total of 27 SNP markers closely related to the salt tolerance traits and 15 SNP markers closely related to the salt tolerance index were detected. At the SNP locus associated with phenotyping, , , , , and related to plant salt tolerance were detected, and they were found to be involved in intracellular transport, sucrose synthesis, osmotic pressure balance, transmembrane transport, N-glycosylation, auxin response and cell amplification. This study provides a theoretical basis for the selection and breeding of salt-tolerant upland cotton varieties.
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http://dx.doi.org/10.3390/plants11010097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747425PMC
December 2021

Exercise downregulates HIPK2 and HIPK2 inhibition protects against myocardial infarction.

EBioMedicine 2021 Dec 24;74:103713. Epub 2021 Nov 24.

Shanghai Engineering Research Center of Organ Repair, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, 200444, China. Electronic address:

Background: Exercise can protect myocardial infarction (MI) and downregulate cardiac Homeodomain-Interacting Protein Kinase 2 (HIPK2). However, the role of HIPK2 in MI is unclear.

Methods: HIPK2 mice and miR-222 rats, HIPK2 inhibitor (PKI1H) and adeno-associated virus serotype 9 (AAV9) carrying miR-222 were applied in the study. Animals were subjected to running, swimming, acute MI or post-MI remodeling. HIPK2 inhibition and P53 activator were used in neonatal rat cardiomyocytes (NRCMs) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to oxygen glucose deprivation/reperfusion (OGD/R). Serum miR-222 levels were analyzed in healthy people and MI patients that were survival or readmitted to the hospital and/or died.

Findings: Cardiac HIPK2 protein levels were reduced by exercise while increased in MI. In vitro, HIPK2 suppression by lentiviral vectors or inhibitor prevented apoptosis induced by OGD/R in NRCMs and hESC-CMs. HIPK2 inhibitor-treated mice and HIPK2 mice reduced infarct size after acute MI, and preserved cardiac function in MI remodeling. Mechanistically, protective effect against apoptosis by HIPK2 suppression was reversed by P53 activators. Furthermore, increasing levels of miR-222, targeting HIPK2, protected post-MI cardiac dysfunction, whereas cardiac dysfunction post-MI was aggravated in miR-222 rats. Moreover, serum miR-222 levels were significantly reduced in MI patients, as well as in MI patients that were readmitted to the hospital and/or died compared to those not.

Interpretation: Exercise-induced HIPK2 suppression attenuates cardiomyocytes apoptosis and protects MI by decreasing P-P53. Inhibition of HIPK2 represents a potential novel therapeutic intervention for MI.

Funding: This work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to JJ Xiao), National Natural Science Foundation of China (82020108002, 81722008, and 81911540486 to JJ Xiao, 81400647 to MJ Xu, 81800265 to YJ Liang), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to JJ Xiao), the grant from Science and Technology Commission of Shanghai Municipality (18410722200 and 17010500100 to JJ Xiao), the "Dawn" Program of Shanghai Education Commission (19SG34 to JJ Xiao), Shanghai Sailing Program (21YF1413200 to QL Zhou). JS is supported by Horizon2020 ERC-2016-COG EVICARE (725229).
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http://dx.doi.org/10.1016/j.ebiom.2021.103713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626841PMC
December 2021

Nanopore-Based Comparative Transcriptome Analysis Reveals the Potential Mechanism of High-Temperature Tolerance in Cotton ( L.).

Plants (Basel) 2021 Nov 19;10(11). Epub 2021 Nov 19.

Xinjiang Academy of Agricultural Science, Urumqi 830001, China.

Extreme high temperatures are threatening cotton production around the world due to the intensification of global warming. To cope with high-temperature stress, heat-tolerant cotton cultivars have been bred, but the heat-tolerant mechanism remains unclear. This study selected heat-tolerant ('Xinluzao36') and heat-sensitive ('Che61-72') cultivars of cotton treated with high-temperature stress as plant materials and performed comparative nanopore sequencing transcriptome analysis to reveal the potential heat-tolerant mechanism of cotton. Results showed that 120,605 nonredundant sequences were generated from the raw reads, and 78,601 genes were annotated. Differentially expressed gene (DEG) analysis showed that a total of 19,600 DEGs were screened; the DEGs involved in the ribosome, heat shock proteins, auxin and ethylene signaling transduction, and photosynthesis pathways may be attributed to the heat tolerance of the heat-tolerant cotton cultivar. This study also predicted a total of 5118 long non-coding RNAs (lncRNAs)and 24,462 corresponding target genes. Analysis of the target genes revealed that the expression of some ribosomal, heat shock, auxin and ethylene signaling transduction-related and photosynthetic proteins may be regulated by lncRNAs and further participate in the heat tolerance of cotton. This study deepens our understandings of the heat tolerance of cotton.
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http://dx.doi.org/10.3390/plants10112517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618236PMC
November 2021

CST6 protein and peptides inhibit breast cancer bone metastasis by suppressing CTSB activity and osteoclastogenesis.

Theranostics 2021 11;11(20):9821-9832. Epub 2021 Oct 11.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Bone metastasis is a frequent symptom of breast cancer and current targeted therapy has limited efficacy. Osteoclasts play critical roles to drive osteolysis and metastatic outgrowth of tumor cells in bone. Previously we identified CST6 as a secretory protein significantly downregulated in bone-metastatic breast cancer cells. Functional analysis showed that CST6 suppresses breast-to-bone metastasis in animal models. However, the functional mechanism and therapeutic potential of CST6 in bone metastasis is unknown. Using osteoclastogenesis and metastasis assays, we studied the effect and mechanism of extracellular CST6 protein in suppressing osteoclastic niches and bone metastasis of breast cancer. A number of peptides containing the functional domain of CST6 were screened to inhibit bone metastasis. The efficacy, stability and toxicity of CST6 recombinant protein and peptides were evaluated in preclinical metastasis models. We show here that CST6 inhibits osteolytic bone metastasis by inhibiting osteoclastogenesis. Cancer cell-derived CST6 enters osteoclasts by endocytosis and suppresses the cysteine protease CTSB, leading to up-regulation of the CTSB hydrolytic substrate SPHK1. SPHK1 suppresses osteoclast maturation by inhibiting the RANKL-induced p38 activation. Importantly, recombinant CST6 protein effectively suppresses bone metastasis and . We further identified several peptides mimicking the function of CST6 to suppress cancer cell-induced osteoclastogenesis and bone metastasis. Pre-clinical analyses of CTS6 recombinant protein and peptides demonstrated their potentials in treatment of breast cancer bone metastasis. These findings reveal the CST6-CTSB-SPHK1 signaling axis in osteoclast differentiation and provide a promising approach to treat bone diseases with CST6-based peptides.
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http://dx.doi.org/10.7150/thno.62187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581426PMC
October 2021

Analysis of the genetic structure and diversity of upland cotton groups in different planting areas based on SNP markers.

Gene 2022 Jan 26;809:146042. Epub 2021 Oct 26.

Cash Crops Research Institute of Xinjiang Academy of Agricultural Science (XAAS), Urumqi 830001, Xinjiang, PR China. Electronic address:

Genetic diversity, kinship and population genetic structure analyses of Gossypium hirsutum germplasm can provide a better understanding of the origin and evolution of G. hirsutum biodiversity. In this study, adopt 273 elite upland cotton cultivar accessions collected from around the world, and especially from China to get 1,313,331 SNP molecular markers, it were used to construct a phylogenetic tree of each sample using MEGAX, to perform population structure analysis by ADMIXTURE software and principal component analysis (PCA) by EIGENSOFT software, and to estimate relatedness using SPAGeDi. ADMIXTURE software divided the experimental cotton population into 16 subgroups, and the Gossypium hirsutum samples could be roughly clustered according to source place, but there were some overlapping characteristics among samples. The experimental cotton population was divided into six groups according to source to calculate the genetic diversity index (H), and the obtained value (0.306) was close to that for germplasm collected by others in China. Cluster 4 had a relatively high genetic diversity level (0.390). The degrees of genetic differentiation within the experimental cotton population groups were low (the population differentiation indexes ranged from 0.02368 to 0.10664). The genetic distance among cotton accessions varied from 0.000332651 to 0.562664014, with an average of 0.25240429. The results of this study may provide a basis for mining elite alleles and using them for subsequent association analysis.
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http://dx.doi.org/10.1016/j.gene.2021.146042DOI Listing
January 2022

Author Correction: Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63.

Nat Commun 2021 Oct 7;12(1):5973. Epub 2021 Oct 7.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

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http://dx.doi.org/10.1038/s41467-021-26292-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497616PMC
October 2021

Global trends in the prevalence of secondhand smoke exposure among adolescents aged 12-16 years from 1999 to 2018: an analysis of repeated cross-sectional surveys.

Lancet Glob Health 2021 12 24;9(12):e1667-e1678. Epub 2021 Sep 24.

Department of Epidemiology, School of Public Health, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address:

Background: Secondhand smoke exposure can cause morbidity and premature mortality. However, the global prevalence of, and trends in, secondhand smoke exposure among adolescents are poorly documented. We aimed to assess the prevalence of, and trends in, secondhand smoke exposure among adolescents from 1999 to 2018.

Methods: We did an analysis of the most recent data from the Global Youth Tobacco Survey (GYTS), a nationally representative, self-administered, school-based cross-sectional survey of tobacco use and related factors among adolescents aged 12-16 years worldwide. Data from 142 countries and territories that had done a GYTS between 2010 and 2018, comprising 711 366 participants, were used to assess the prevalence of secondhand smoke exposure. Data from 131 countries and territories that had done two or more surveys between 1999 and 2018, comprising 1 405 458 participants, were used to assess trends in secondhand smoke exposure. The frequency of secondhand smoke exposure at home, in public places, or in any place was defined as follows, based on students' responses: 1 or more days, 3 or more days, 5 or more days, or daily during the past 7 days.

Findings: Based on the most recent surveys done in 142 countries between Jan 1, 2010, and Dec 31, 2018, the global prevalence of secondhand smoke exposure in any place was 62·9% (95% CI 61·7-64·1) on 1 or more days, 51·0% (49·8-52·1) on 3 or more days, 40·1% (38·9-41·2) on 5 or more days, and 32·5% (31·5-33·6) daily during the past 7 days. The prevalence of secondhand smoke exposure at home was 33·1% (95% CI 32·1-34·1) on 1 or more days, 20·1% (19·3-20·9) on 3 or more days, 14·9% (14·2-15·7) on 5 or more days, and 12·3% (11·7-13·0) daily during the past 7 days; and in public places the prevalence of secondhand smoke exposure was 57·6% (56·4-58·8) on 1 or more days, 43·4% (42·2-44·6) on 3 or more days, 30·3% (29·2-31·5) on 5 or more days, and 23·5% (22·5-24·5) daily during the past 7 days. Between Jan 1, 1999, and Dec 31, 2018, the prevalence of secondhand smoke exposure (on ≥1 day during the past 7 days) in any place decreased in 57 (43·5%) of 131 countries, increased in 27 (20·6%), and remained unchanged in 47 (35·9%). Although the prevalence of secondhand smoke exposure at home decreased in 86 (65·6%) countries, the prevalence in public places did not change in 46 (35·1%) countries and increased in 40 (30·5%).

Interpretation: Secondhand smoke exposure among adolescents remains a serious public health challenge worldwide. Although the prevalence of secondhand smoke exposure at home decreased in most countries, the prevalence in public places increased or remained unchanged in most countries between 1999 and 2018. These findings emphasise the need to strengthen smoke-free policies, especially in public places.

Funding: Youth Team of Humanistic and Social Science of Shandong University, Jinan, China.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2214-109X(21)00365-XDOI Listing
December 2021

Serglycin induces osteoclastogenesis and promotes tumor growth in giant cell tumor of bone.

Cell Death Dis 2021 09 23;12(10):868. Epub 2021 Sep 23.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Giant cell tumor of bone (GCTB) is an aggressive osteolytic bone tumor characterized by the within-tumor presence of osteoclast-like multinucleated giant cells (MGCs), which are induced by the neoplastic stromal cells and lead to extensive bone destruction. However, the underlying mechanism of the pathological process of osteoclastogenesis in GCTB is poorly understood. Here we show that the proteoglycan Serglycin (SRGN) secreted by neoplastic stromal cells plays a crucial role in the formation of MGCs and tumorigenesis in GCTB. Upregulated SRGN expression and secretion are observed in GCTB tumor cells and patients. Stromal-derived SRGN promotes osteoclast differentiation from monocytes. SRGN knockdown in stromal cells inhibits tumor growth and bone destruction in a patient-derived orthotopic xenograft model of mice. Mechanistically SRGN interacts with CD44 on the cell surface of monocytes and thus activates focal adhesion kinase (FAK), leading to osteoclast differentiation. Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.
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http://dx.doi.org/10.1038/s41419-021-04161-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460728PMC
September 2021

Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63.

Nat Commun 2021 09 2;12(1):5232. Epub 2021 Sep 2.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Disseminated tumor cells often fall into a long term of dormant stage, characterized by decreased proliferation but sustained survival, in distant organs before awakening for metastatic growth. However, the regulatory mechanism of metastatic dormancy and awakening is largely unknown. Here, we show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels of dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) NR2F1-AS1 (NAS1) is up-regulated in the dormant mesenchymal-like BCSCs, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanistically, NAS1 binds to NR2F1 mRNA and recruits the RNA-binding protein PTBP1 to promote internal ribosome entry site (IRES)-mediated NR2F1 translation, thus leading to suppression of ΔNp63 transcription by NR2F1. Furthermore, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs. Overall, the study links BCSC plasticity with metastatic dormancy, and reveals the lncRNA as an important regulator of both processes.
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http://dx.doi.org/10.1038/s41467-021-25552-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413371PMC
September 2021

Effect of high variation in transcript expression on identifying differentially expressed genes in RNA-seq analysis.

Ann Hum Genet 2021 11 3;85(6):235-244. Epub 2021 Aug 3.

Key Laboratory of Biomedical Engineering & Technology of Shandong High School, Qilu Medical University, Zibo, P. R. China.

Great efforts have been made on the algorithms that deal with RNA-seq data to enhance the accuracy and efficiency of differential expression (DE) analysis. However, no consensus has been reached on the proper threshold values of fold change and adjusted p-value for filtering differentially expressed genes (DEGs). It is generally believed that the more stringent the filtering threshold, the more reliable the result of a DE analysis. Nevertheless, by analyzing the impact of both adjusted p-value and fold change thresholds on DE analyses, with RNA-seq data obtained for three different cancer types from the Cancer Genome Atlas (TCGA) database, we found that, for a given sample size, the reproducibility of DE results became poorer when more stringent thresholds were applied. No matter which threshold level was applied, the overlap rates of DEGs were generally lower for small sample sizes than for large sample sizes. The raw read count analysis demonstrated that the transcript expression of the same gene in different samples, whether in tumor groups or in normal groups, showed high variations, which resulted in a drastic fluctuation in fold change values and adjustedp-values when different sets of samples were used. Overall, more stringent thresholds did not yield more reliable DEGs due to high variations in transcript expression; the reliability of DEGs obtained with small sample sizes was more susceptible to these variations. Therefore, less stringent thresholds are recommended for screening DEGs. Moreover, large sample sizes should be considered in RNA-seq experimental designs to reduce the interfering effect of variations in transcript expression on DEG identification.
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http://dx.doi.org/10.1111/ahg.12441DOI Listing
November 2021

Informal care and the impact on depression and anxiety among Swedish adults: a population-based cohort study.

BMC Public Health 2021 06 29;21(1):1263. Epub 2021 Jun 29.

Department of Global Public Health, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.

Background: As the population is ageing, the need for informal caregivers increases, and thus we need to know more about the effects on caregivers. This study aims to determine both cross-sectional and longitudinal associations between perceived limitation of informal caregiving and mental health of caregivers.

Methods: This population-based cohort study was based on the Swedish Psykisk hälsa, Arbete och RelaTioner (PART) study, and 9346 individuals aged 18-65 were included. Data were collected through questionnaires, interviews and Swedish registers. Informal care was defined as care given to a family member. Self-reported and diagnosed depression and anxiety were included as outcomes. Covariates included sex, age, social support and socio-economic position. Ordinal logistic regression and Cox regression were performed to determine the associations between caregiving and anxiety or depression.

Results: Self-reported depression and anxiety was only increased among those experiencing limitations (adjusted odds ratios [aOR] 2.00, 95% confidence intervals [CI] 1.63-2.47 for depression; aOR 2.07, 95% CI 1.57-2.74 for anxiety) compared to those not giving care, respectively. The adjusted hazard ratio (aHR) were increased for diagnosed depression (aHR 1.97, 95% CI 1.27-3.05) and for diagnosed anxiety (aHR 1.86, 95% CI 1.06-3.25) among those giving care and experiencing limitations, compared to those not giving care. No significant associations were found in caregivers without limitations.

Conclusion: Caregivers experiencing limitations showed a significant association with short- and long-term anxiety and depression. This study implies the importance of exploring the degree to which informal caregiving can be provided without adding burden to caregivers.
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http://dx.doi.org/10.1186/s12889-021-11246-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243546PMC
June 2021

Genome-Wide Comparative Analysis of Heat Shock Transcription Factors Provides Novel Insights for Evolutionary History and Expression Characterization in Cotton Diploid and Tetraploid Genomes.

Front Genet 2021 8;12:658847. Epub 2021 Jun 8.

Engineering Research Centre of Cotton of Ministry of Education, Xinjiang Agricultural University, Urumqi, China.

Heat shock transcription factors (HSFs) are involved in environmental stress response and plant development, such as heat stress and flowering development. According to the structural characteristics of the HSF gene family, HSF genes were classified into three major types (HSFA, HSFB, and HSFC) in plants. Using conserved domains of HSF genes, we identified 621 HSF genes among 13 cotton genomes, consisting of eight diploid and five tetraploid genomes. Phylogenetic analysis indicated that HSF genes among 13 cotton genomes were grouped into two different clusters: one cluster contained all HSF genes of HSFA and HSFC, and the other cluster contained all HSF genes of HSFB. Comparative analysis of HSF genes in , (A1), (A2), (D5), and (AD1) genomes demonstrated that four HSF genes were inherited from a common ancestor, A0, of all existing cotton A genomes. Members of the HSF gene family in (A1) genome indicated a significant loss compared with those in (A2) and (AD1) A genomes. However, HSF genes in (D5) showed relative loss compared with those in (AD1) D genome. Analysis of tandem duplication (TD) events of HSF genes revealed that protein-coding genes among different cotton genomes have experienced TD events, but only the two-gene tandem array was detected in (D1) genome. The expression analysis of HSF genes in (AD1) and (AD2) genomes indicated that the expressed HSF genes were divided into two different groups, respectively, and the expressed HSF orthologous genes between the two genomes showed totally different expression patterns despite the implementation of the same abiotic stresses. This work will provide novel insights for the study of evolutionary history and expression characterization of HSF genes in different cotton genomes and a widespread application model for the study of HSF gene families in plants.
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http://dx.doi.org/10.3389/fgene.2021.658847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217870PMC
June 2021

Health-related quality of life after first-ever acute ischemic stroke: associations with cardiovascular health metrics.

Qual Life Res 2021 Oct 1;30(10):2907-2917. Epub 2021 May 1.

Department of Neurology, Shandong Provincial Hospital Affiliated To Shandong University, Jinan, Shandong, China.

Purpose: To investigate the associations between cardiovascular health (CVH) metrics and health-related quality of life (HRQL) among patients with ischemic stroke in China, and further explore the role of physical and cognitive function in their associations.

Methods: This hospital-based study included 1714 patients with first-ever acute ischemic stroke (age ≥ 40 years; 36.7% women) who were admitted to two university hospitals in Shandong, China. We collected information on seven CVH metrics (smoking, body mass index, diet, physical activity, blood pressure, total cholesterol, and fasting blood glucose) through interviews, clinical examinations, and laboratory tests. EQ-5D-3L was used to assess HRQL. Cognitive and physical functioning was assessed by the Montreal Cognitive Assessment test and Barthel index, respectively. Data were analyzed using the general linear regression models.

Results: The average score (SD) was 0.746 (0.23) for HRQL index and 72.7 (15.8) for self-rated health. Optimal levels of four individual CVH metric components (diet, physical activity, blood pressure, and blood glucose) and a higher composite CVH score were significantly associated with a greater HRQL index and better self-rated health (p < 0.05 for all). Physical dependence and cognitive impairment were associated with a lower HRQL index and poorer self-rated health status (p < 0.001). Furthermore, the relationships between CVH metrics and HRQL index varied by functional status, such that their associations were statistically significant only among people who had physical dependence or cognitive impairment.

Conclusion: Achieving a better cardiovascular health profile is associated with better quality of life among ischemic stroke survivors, primarily in those with physical or cognitive impairment.
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http://dx.doi.org/10.1007/s11136-021-02853-xDOI Listing
October 2021

Death of a parent during childhood and blood pressure in youth: a population-based cohort study of Swedish men.

BMJ Open 2021 04 26;11(4):e043657. Epub 2021 Apr 26.

Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.

Objective: Compelling evidence suggests that childhood adversities are associated with an increased risk of hypertension in middle age and old age. The link between childhood adversities and blood pressure in youth is less clear. In this cohort study, we examined the association between death of a parent during childhood and blood pressure in early adulthood in men.

Setting: Sweden.

Participants: We studied 48 624 men born in 1949-1951 who participated in the compulsory military conscription in 1969/1970 in Sweden. Information on death of a parent during childhood was obtained from population-based registers. Information on covariates was obtained from the questionnaire and the clinical examination completed at conscription and from population-based registers.

Outcome Measures: Blood pressure was measured at conscription according to standard procedures.

Results: The multivariable least square means of systolic and diastolic blood pressure did not differ between bereaved (128.25 (127.04-129.46) and 73.86 (72.89-74.84) mm Hg) and non-bereaved study participants (128.02 (126.86-129.18) and 73.99 (73.06-74.93) mm Hg). Results were similar when considering the cause of the parent's death, the gender of the deceased parent or the child's age at loss. Loss of a parent in childhood tended to be associated with an increased hypertension risk (OR and 95% CI: 1.10 (1 to 1.20)); the association was present only in case of natural deaths.

Conclusion: We found no strong support for the hypothesis that stress following the loss of a parent during childhood is associated with blood pressure or hypertension in youth in men.
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http://dx.doi.org/10.1136/bmjopen-2020-043657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076918PMC
April 2021

Geriatric Syndromes and Incident Chronic Health Conditions Among 9094 Older Community-Dwellers: Findings from the Lifelines Cohort Study.

J Am Med Dir Assoc 2022 Jan 30;23(1):54-59.e2. Epub 2021 Mar 30.

Department of Health Sciences, University of Groningen, University Medical Center Groningen, Community and Occupational Medicine, Groningen, The Netherlands.

Objectives: To determine the association between geriatric syndromes and any specific incident chronic health conditions among older community-dwellers.

Design: Population-based cohort study over a median follow-up period of 43 months.

Setting And Participants: Participants from the Lifelines Cohort Study aged 60 years and older without presence of the studied chronic health conditions at baseline (n = 9094).

Methods: Baseline assessment took place between November 2006 and December 2013 and included information on socioeconomic (age, sex, level of education and income), social contact, and health-related factors [eg, self-rated health, body mass index, chronic health conditions, and health behavior (alcohol consumption and smoking)]. Participants also reported the presence of geriatric syndromes (ie, included falls, incontinence, vision impairment, hearing impairment, depressive symptoms, and frailty at baseline). Three follow-up questionnaires were used to examine the incidence of any and specific chronic health conditions (ie, pulmonary and cardiovascular diseases, diabetes, cancer, and neurological diseases). Cox regression was used to analyze the longitudinal associations between geriatric syndromes and incident chronic health conditions.

Results: Older community-dwelling individuals with at least one geriatric syndrome (44.7%, n = 4038) had an increased risk of developing any new chronic health condition [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.21-1.51]. The association was attenuated but remained significant after adjustment for socioeconomic factors, social contact, health status, and health behavior (HR 1.27; 95% CI 1.12-1.43). Analyses for specific chronic health conditions showed that compared with older community-dwellers without geriatric syndromes, those with geriatric syndromes had an increased risk to develop a cardiovascular health condition (HR 1.42; 95% CI 1.13-1.79) or diabetes (HR 1.53; 95% CI 1.11-2.11). They had no increased risk to develop pulmonary conditions, cancer, or neurological conditions.

Conclusion And Implications: The presence of geriatric syndromes is associated with incident chronic health conditions, specifically cardiovascular conditions and diabetes. Increased awareness is needed among older people with geriatric syndromes and their physicians. Comprehensive assessments of geriatric syndromes may help to prevent or at least delay the development of chronic health conditions.
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http://dx.doi.org/10.1016/j.jamda.2021.02.030DOI Listing
January 2022

Latent class growth modelling for the evaluation of intervention outcomes: example from a physical activity intervention.

J Behav Med 2021 10 25;44(5):622-629. Epub 2021 Mar 25.

Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.

Intervention studies often assume that changes in an outcome are homogenous across the population, however this assumption might not always hold. This article describes how latent class growth modelling (LCGM) can be performed in intervention studies, using an empirical example, and discusses the challenges and potential implications of this method. The analysis included 110 young adults with mobility disability that had participated in a parallel randomized controlled trial and received either a mobile app program (n = 55) or a supervised health program (n = 55) for 12 weeks. The primary outcome was accelerometer measured moderate to vigorous physical activity (MVPA) levels in min/day assessed at baseline, 6 weeks, 12 weeks, and 1-year post intervention. The mean change of MVPA from baseline to 1-year was estimated using paired t-test. LCGM was performed to determine the trajectories of MVPA. Logistic regression models were used to identify potential predictors of trajectories. There was no significant difference between baseline and 1-year MVPA levels (4.8 min/day, 95% CI: -1.4, 10.9). Four MVPA trajectories, 'Normal/Decrease', 'Normal/Increase', 'Normal/Rapid increase', and 'High/Increase', were identified through LCGM. Individuals with younger age and higher baseline MVPA were more likely to have increasing trajectories of MVPA. LCGM uncovered hidden trajectories of physical activity that were not represented by the average pattern. This approach could provide significant insights when included in intervention studies. For higher accuracy it is recommended to include larger sample sizes.
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http://dx.doi.org/10.1007/s10865-021-00216-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484241PMC
October 2021

A combination of genome-wide and transcriptome-wide association studies reveals genetic elements leading to male sterility during high temperature stress in cotton.

New Phytol 2021 07 2;231(1):165-181. Epub 2021 May 2.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Global warming has reduced the productivity of many field-grown crops, as the effects of high temperatures can lead to male sterility in such plants. Genetic regulation of the high temperature (HT) response in the major crop cotton is poorly understood. We determined the functionality and transcriptomes of the anthers of 218 cotton accessions grown under HT stress. By analyzing transcriptome divergence and implementing a genome-wide association study (GWAS), we identified three thermal tolerance associated loci which contained 75 protein coding genes and 27 long noncoding RNAs, and provided expression quantitative trait loci (eQTLs) for 13 132 transcripts. A transcriptome-wide association study (TWAS) confirmed six causal elements for the HT response (three genes overlapped with the GWAS results) which are involved in protein kinase activity. The most susceptible gene, GhHRK1, was confirmed to be a previously uncharacterized negative regulator of the HT response in both cotton and Arabidopsis. These functional variants provide a new understanding of the genetic basis for HT tolerance in male reproductive organs.
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http://dx.doi.org/10.1111/nph.17325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252431PMC
July 2021

Sex disparities in cardiovascular health metrics among rural-dwelling older adults in China: a population-based study.

BMC Geriatr 2021 03 4;21(1):158. Epub 2021 Mar 4.

Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324 Jingwuweiqi Road, Jinan, 250021, Shandong, People's Republic of China.

Background: Cardiovascular health (CVH) metrics among Chinese older adults are poorly understood. We investigated sex disparities in CVH metrics and their management among rural-dwelling older adults in China.

Methods: This community-based study included 5026 participants (age ≥ 65 years; 57.2% women) in the baseline survey of a multimodal intervention study in rural China. In March-September 2018, data were collected through face-to-face interviews, clinical examinations, and laboratory tests. We defined six CVH metrics (three behavioral factors-smoking, body mass index, and physical activity; three biological factors-blood pressure, total cholesterol, and blood glucose) following the modified American Heart Association's recommendations. We performed descriptive analysis separately for men and women.

Results: Of all participants, only 0.8% achieved ideal levels in all six CVH metrics. Men were more likely than women to have ideal levels in all CVH metrics but smoking. Women had higher prevalence of ideal global (9.7% vs. 7.8%) and behavioral (18.3% vs. 9.5%) CVH metrics (p < 0.001), whereas men had higher prevalence of ideal biological CVH metrics (5.4% vs. 3.5%, p < 0.001). The prevalence of ideal global and behavioral CVH metrics increased with age in both women and men (p for trend< 0.001). Women were more likely to be aware of their hypertension and diabetes, and to receive antihypertensive treatment, while men were more likely to achieve the goal of high cholesterol treatment (p < 0.05).

Conclusions: The CVH metrics among older adults living in the rural communities in China are characterized by an extremely low proportion of optimal global CVH metrics and distinct sex differences, alongside poor management of major biological risk factors.

Trial Registration: ChiCTR1800017758 (Aug 13, 2018).
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http://dx.doi.org/10.1186/s12877-021-02116-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934439PMC
March 2021

Prevalence and trends in tobacco use among adolescents aged 13-15 years in 143 countries, 1999-2018: findings from the Global Youth Tobacco Surveys.

Lancet Child Adolesc Health 2021 04 2;5(4):245-255. Epub 2021 Feb 2.

Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Background: Tobacco use is a leading preventable cause of morbidity and mortality worldwide. Little is known about recent prevalence and trends in tobacco use among adolescents globally. We aimed to assess the recent global prevalence of tobacco use in young adolescents and the secular trends in prevalence between 1999 and 2018.

Methods: We used the most recent Global Youth Tobacco Surveys data on adolescents aged 13-15 years from 143 countries or territories that had done at least one survey between Jan 1, 2010, and Dec 31, 2018, to assess the recent prevalence of tobacco use; and data from 140 countries that had done two or more surveys between Jan 1, 1999, and Dec 31, 2018, to assess the trends in the prevalence of tobacco use.

Findings: 530 234 adolescents were included from the 143 countries that had done at least one survey between 2010 and 2018. 1 192 312 adolescents were included from the 140 countries that had done two or more surveys between 1999 and 2018. The most recent global prevalence of cigarette smoking was 11·3% (95% CI 10·3-12·3) in boys and 6·1% (5·6-6·6) in girls, based on cigarette smoking on at least 1 day during the past 30 days, 6·0% (5·5-6·6) and 2·6% (2·4-2·9) based on smoking on at least 3 days, and 4·2% (3·8-4·6) and 1·6% (1·4-1·8) based on smoking on at least 6 days. The most recent prevalence of the use of tobacco products other than cigarettes (eg, chewing tobacco, snuff, dip, cigars, cigarillos, pipe, electronic cigarettes) on at least 1 day during the past 30 days was 11·2% (9·9-12·6) in boys and 7·0% (6·4-7·7) in girls. The most recent prevalence of any tobacco use on at least 1 day during the past 30 days was 17·9% (16·1-19·6) in boys and 11·5% (10·5-12·4) in girls. The prevalence of cigarette smoking on at least 1 day during the past 30 days decreased between the first and last surveys in 80 (57·1%) of 140 countries, was unchanged in 39 countries (27·9%), and increased in 21 countries (15·0%). However, the prevalence of the use of tobacco products other than cigarettes was unchanged or increased in 81 (59·1%) of 137 countries.

Interpretation: The global prevalence of tobacco use among adolescents aged 13-15 years was substantial. Although the prevalence of cigarette smoking decreased over time in the majority of countries, the prevalence of the use of other tobacco products increased or did not change in the majority of countries during the past two decades. These findings re-emphasise the need to strengthen tobacco control efforts among young adolescents globally.

Funding: Shandong University.
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http://dx.doi.org/10.1016/S2352-4642(20)30390-4DOI Listing
April 2021

Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation.

Cancer Cell 2021 03 14;39(3):423-437.e7. Epub 2021 Jan 14.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. Electronic address:

Lung metastasis is the major cause of breast cancer-related mortality. The neutrophil-associated inflammatory microenvironment aids tumor cells in metastatic colonization in lungs. Here, we show that tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating recruitment of neutrophils and formation of neutrophil extracellular traps (NETs). CTSC enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to facilitate interleukin-1β (IL-1β) processing and nuclear factor κB activation, thus upregulating IL-6 and CCL3 for neutrophil recruitment. In addition, the CTSC-PR3-IL-1β axis induces neutrophil reactive oxygen species production and formation of NETs, which degrade thrombospondin-1 and support metastatic growth of cancer cells in the lungs. CTSC expression and secretion are associated with NET formation and lung metastasis in human breast tumors. Importantly, targeting CTSC with compound AZD7986 effectively suppresses lung metastasis of breast cancer in a mouse model. Overall, our findings reveal a mechanism of how tumor cells regulate neutrophils in metastatic niches and support CTSC-targeting approaches for cancer treatment.
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http://dx.doi.org/10.1016/j.ccell.2020.12.012DOI Listing
March 2021

Cardiovascular health metrics from mid- to late-life and risk of dementia: A population-based cohort study in Finland.

PLoS Med 2020 12 15;17(12):e1003474. Epub 2020 Dec 15.

Aging Research Center & Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Stockholm University, Stockholm, Sweden.

Background: Very few studies have explored the patterns of cardiovascular health (CVH) metrics in midlife and late life in relation to risk of dementia. We examined the associations of composite CVH metrics from midlife to late life with risk of incident dementia.

Methods And Findings: This cohort study included 1,449 participants from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, who were followed from midlife (baseline from1972 to 1987; mean age 50.4 years; 62.1% female) to late life (1998), and then 744 dementia-free survivors were followed further into late life (2005 to 2008). We defined and scored global CVH metrics based on 6 of the 7 components (i.e., smoking, physical activity, and body mass index [BMI] as behavioral CVH metrics; fasting plasma glucose, total cholesterol, and blood pressure as biological CVH metrics) following the modified American Heart Association (AHA)'s recommendations. Then, the composite global, behavioral, and biological CVH metrics were categorized into poor, intermediate, and ideal levels. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data were analyzed with Cox proportional hazards and the Fine and Gray competing risk regression models. During the follow-up examinations, dementia was diagnosed in 61 persons in 1998 and additional 47 persons in 2005 to 2008. The fully adjusted hazard ratio (HR) of dementia was 0.71 (95% confidence interval [CI]: 0.43, 1.16; p = 0.174) and 0.52 (0.29, 0.93; p = 0.027) for midlife intermediate and ideal levels (versus poor level) of global CVH metrics, respectively; the corresponding figures for late-life global CVH metrics were 0.60 (0.22, 1.69; p = 0.338) and 0.91 (0.34, 2.41; p = 0.850). Compared with poor global CVH metrics in both midlife and late life, the fully adjusted HR of dementia was 0.25 (95% CI: 0.08, 0.86; p = 0.028) for people with intermediate global CVH metrics in both midlife and late life and 0.14 (0.02, 0.76; p = 0.024) for those with midlife ideal and late-life intermediate global CVH metrics. Having an intermediate or ideal level of behavioral CVH in both midlife and late life (versus poor level in both midlife and late life) was significantly associated with a lower dementia risk (HR range: 0.03 to 0.26; p < 0.05), whereas people with midlife intermediate and late-life ideal biological CVH metrics had a significantly increased risk of dementia (p = 0.031). Major limitations of this study include the lack of data on diet and midlife plasma glucose, high rate of attrition, as well as the limited power for certain subgroup analyses.

Conclusions: In this study, we observed that having the ideal CVH metrics, and ideal behavioral CVH metrics in particular, from midlife onwards is associated with a reduced risk of dementia as compared with people having poor CVH metrics. Maintaining life-long health behaviors may be crucial to reduce late-life risk of dementia.
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http://dx.doi.org/10.1371/journal.pmed.1003474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737898PMC
December 2020

Maternal age at birth and neonatal mortality: Associations from 67 low-income and middle-income countries.

Paediatr Perinat Epidemiol 2021 05 16;35(3):318-327. Epub 2020 Nov 16.

Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Both young and advanced maternal age have been associated with higher risks of neonatal mortality, but most studies are from high-income countries and the evidence from low- and middle-income countries (LMICs) is scarce.

Objective: To investigate the association between maternal age at delivery and neonatal mortality in LMICs.

Methods: This is a cross-sectional study using data from 159 Demographic and Health Surveys in 67 LMICs between 2000 and 2018. Maternal age at the time of the birth was the exposure variable, and neonatal mortality was the outcome. Multivariable logistic regression model taking into consideration complex survey design was performed with adjustments for maternal education level, paternal education level, rural/urban residence, country, and survey year. Subgroup analyses were performed by time of death, sex, the country's World Bank income classification, the World Health Organization region, and survey year.

Results: A total of 1 395 746 mother-neonate pairs were included. Overall, compared with neonates born to mothers aged 25-29 years, those born to younger mothers aged 20-24, 16-19 and 12-15 years were at an increased risk of mortality (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 1.17, 1.30; OR 1.81, 95% CI 1.71, 1.93; OR 2.29, 95% CI 1.96, 2.67, respectively). Neonates born to mothers aged 30-34, 35-39, 40-44, and ≥45 years were also at an increased risk of mortality (OR 1.09, 95% CI 1.03, 1.15; OR 1.30, 95% CI 1.21, 1.39; OR 1.50, 95% CI 1.38, 1.64; OR 1.84, 95% CI 1.54, 2.20, respectively). The results were consistent across most subgroup analyses.

Conclusions: Neonates born to younger (<25 years) and older mothers (≥30 years) are at increased risk of neonatal death in LMICs.
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http://dx.doi.org/10.1111/ppe.12734DOI Listing
May 2021

Life-course blood pressure trajectories and cardiovascular diseases: A population-based cohort study in China.

PLoS One 2020 21;15(10):e0240804. Epub 2020 Oct 21.

Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.

Background: The patterns of blood pressure trajectory (i.e., change over time) over life-course remain to be explored. In this study, we aim to determine the trajectories of systolic blood pressure (SBP) from adulthood to late life and to assess its impact on the risk of cardiovascular diseases (CVDs).

Methods: Based on the China Health and Nutrition Survey, a total of 3566 participants aged 20-50 years at baseline (1989) with at least three SBP measurements during 1989-2011 were included. SBP was measured through physical examination, and socio-demographic factors, lifestyles, medications, and CVDs were based on self-reported questionnaire. Latent class growth modeling was performed to examine SBP trajectory. Odds ratio (OR) and 95% confidence interval (CI) from logistic regression was used to determine the association between SBP trajectory and CVDs.

Results: Five trajectory groups of SBP were identified: Class 1: rapid increase (n = 113, 3.2%); Class 2: slight increase (n = 1958, 54.9%); Class 3: stable (n = 614, 17.2%); Class 4: increase (n = 800, 22.4%); Class 5: fluctuant (n = 81, 2.3%). After adjustment of demographic factors, baseline SBP, and lifestyles, compared with the "slight increase" group, the OR (95% CI) of CVDs was 0.65 (0.32, 1.28) for "stable" group, 2.24 (1.40, 3.58) for "increase" group, 3.95 (1.81, 8.62) for "rapid increase" group, and 4.32 (1.76, 10.57) for "fluctuant" group. After stratified by use of antihypertensive drugs, the association was only significant for "rapid increase" group among those using antihypertensive drugs with OR (95% CI) of 2.81 (1.01, 7.77).

Conclusions: Having a rapidly increasing SBP over life-course is associated with a higher risk of CVDs. This implies the importance of monitoring lifetime change of blood pressure for the prevention of CVDs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240804PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577482PMC
December 2020

Evaluation of stability of deep venous thrombosis of the lower extremities using Doppler ultrasound.

J Int Med Res 2020 Aug;48(8):300060520942098

Department of Clinical Pharmacy, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang City, Henan Province, China.

Objective: This study aimed to assess using Doppler ultrasound for analyzing stability of deep venous thrombosis (DVT) of the lower extremities.

Methods: Patients with DVT of the lower extremities who were treated from August 2017 to December 2019 were selected. The patients were divided into stable and unstable groups according to whether thrombus was collected in a filter. Related ultrasound and blood test results were analyzed and compared.

Results: A total of 126 patients with DVT of the lower extremities were included, of whom 74 were in the stable group and 52 were in the unstable group. There were significant differences in the prothrombin time (PT), and lipoprotein alpha, D-dimer, and triglyceride levels between the groups. D-dimer levels >2800 ug/L, smoking, history of venous thrombosis, PT >13.15 s, and body mass index >24.45 kg/m were independent risk factors for stability of DVT of the lower extremities. The area under the curve with combined detection of DVT was significantly higher than that for body mass index, PT, and D-dimer alone.

Conclusion: Doppler ultrasound may be reliable for analyzing the stability of DVT of the lower extremities. Related strategies targeting risk factors are required for reducing DVT of the lower extremities.
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http://dx.doi.org/10.1177/0300060520942098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526051PMC
August 2020

Association between paternal age and offspring's under-5 mortality: Data from 159 surveys in 67 low- to middle-income countries.

J Paediatr Child Health 2020 Oct 17;56(10):1577-1583. Epub 2020 Aug 17.

Department of Epidemiology, School of Public Health, Shandong University, Jinan, China.

Aim: To investigat the association between paternal age at birth and offspring's under-5 mortality in low- and middle-income countries (LIMCs).

Methods: Data from 159 population-based surveys in 67 LIMCs between 2000 and 2018 were obtained from the Demographic and Health Surveys. Cox proportional hazard regression models in consideration of complex survey design were performed to examine the associations.

Results: In the pooled analysis, compared with children born to fathers aged 25-29 years, those born to younger fathers aged 20-24, 16-19 and 12-15 years, respectively, were at increased risk of under-5 mortality (hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.06-1.13; HR = 1.48, 95% CI = 1.42-1.55; HR = 1.70, 95% CI = 1.56-1.84, respectively). In addition, children born to older fathers aged 40-44 and ≥ 45 years, also had increased risk of under-5 mortality (HR = 1.08, 95% CI = 1.03-1.15; HR = 1.12, 95% CI = 1.07-1.18, respectively).

Conclusions: Our findings show that children born to both younger and older fathers are at higher risk of offspring's under-5 mortality in LIMCs.
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http://dx.doi.org/10.1111/jpc.15029DOI Listing
October 2020

Elevated blood pressure in childhood and hypertension risk in adulthood: a systematic review and meta-analysis.

J Hypertens 2020 12;38(12):2346-2355

Department of Epidemiology.

Objective: Several longitudinal studies have investigated the association between elevated blood pressure (BP) in childhood and hypertension in adulthood but the strength of the association has not been always consistent. This study aimed at quantitatively assessing the strength of the association between elevated BP in childhood and hypertension in adulthood based on both a meta-analysis and a systematic review.

Methods: We identified eligible studies using PubMed and Embase databases up to 1 November, 2019 and by manually searching the reference lists of all identified studies. All longitudinal studies on the association between elevated BP in childhood and hypertension in adulthood were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model in this meta-analysis.

Results: Eleven articles (N = 39 714) were included in our meta-analysis and five additional articles were used for systematic review (two providing ORs without 95% CIs, one not using standard cut-offs for elevated BP in childhood, and two not using standard criteria for adult hypertension). Elevated BP in childhood (3--18 years in the included studies) was significantly associated with hypertension in adulthood (18--57 years in the included studies), with a summary OR of 2.02 (95% CI 1.62--2.53). We also found that an increase of 1 standard deviation in systolic BP and diastolic BP, respectively, in childhood (3--19 years in the included studies) was associated with hypertension in adulthood (21--49 years in the included studies), with summary ORs of 1.71 (1.50-1.95) and 1.57 (1.37-1.81). Our systematic review of the five additional articles not eligible for meta-analysis also suggested a significant association between elevated BP in childhood and hypertension in adulthood.

Conclusion: This meta-analysis and systematic review demonstrated a significant association between elevated BP in childhood and hypertension in adulthood. The findings support measures to promote healthy BP during childhood to reduce the risk of hypertension later in life.
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http://dx.doi.org/10.1097/HJH.0000000000002550DOI Listing
December 2020

Smoking, heavy drinking, physical inactivity, and obesity among middle-aged and older adults in China: cross-sectional findings from the baseline survey of CHARLS 2011-2012.

BMC Public Health 2020 Jul 6;20(1):1062. Epub 2020 Jul 6.

Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.

Background: Prevention and control of cardiometabolic conditions and cardiovascular disease (CVD) in China may contribute to sustainable CVD reduction globally, given the fact that one-fifth of the worldwide population is in China. Knowing the distribution of behavioral risk factors (e.g., smoking and physical inactivity), especially at a national level in China, would be extremely relevant to the field of public health and CVD prevention. The objectives of this study were to investigate the nationwide prevalence of obesity, smoking, heavy drinking, and physical inactivity in Chinese adults, and further explore whether cardiometabolic conditions would modify the distribution of behavioral risk factors.

Methods: This population-based study is based on the China Health and Retirement Longitudinal Study (2011-2012), including 17,302 adults (≥45 years, mean age 59.67 years, female 51.66%) from 25 provinces in China. Data on demographics, lifestyle factors, health status and history of diseases were collected via structured interviews and laboratory tests. Smoking, heavy drinking, obesity, and physical inactivity were defined following standard guidelines. We performed descriptive analysis and logistic regressions in this study.

Results: The overall prevalence of heavy drinking, obesity, current smoking, and physical inactivity among middle-aged and older adults was 7.23% (95% confidence interval 6.53-7.29%), 11.53% (10.43-12.62%), 27.46% (26.30-28.62%), and 44.06% (41.19-46.92%), respectively. The prevalence varied between rural and urban areas as well as among geographic areas, with higher prevalence in the Northern and Northeastern regions. Heavy drinking and obesity were significantly associated with incident hypertension, diabetes, and high cholesterol; while current smoking was significantly associated with incident hypertension. Compared with healthy individuals, participants who self-reported a diagnosis of hypertension, high cholesterol, or diabetes were less likely to smoke currently and drink alcohol heavily, but more likely to be physically inactive and obese.

Conclusions: Among Chinese middle-aged and older adults, the prevalence of behavioral risk factors varies by geographic region. Further effort is required to improve physical activity and fitness for Chinese adults, especially those with cardiometabolic conditions.
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http://dx.doi.org/10.1186/s12889-020-08625-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336642PMC
July 2020

Maternal body mass index and risks of neonatal mortality and offspring overweight and obesity: Findings from 0.5 million samples in 61 low- and middle-income countries.

Pediatr Obes 2020 11 15;15(11):e12665. Epub 2020 Jun 15.

Department of Epidemiology, School of Public Health, Shandong University, Jinan, China.

Background: Evidence on associations of maternal overweight and obesity with risks of offspring mortality and obesity is limited in low- and middle-income countries (LMICs).

Objective: We aimed to assess the associations of maternal overweight and obesity with neonatal mortality, and offspring overweight and obesity in LMICs.

Methods: Data were from the Demographic and Health Surveys in 61 LMICs. A total of 507 203 pairs of mother and offspring were included in the analysis for neonatal mortality, and 455 534 pairs in the analysis for overweight and obesity in offspring aged 3 to 59 months. Survey logistic regression models were used to examine the associations of maternal overweight and obesity with neonatal mortality, and offspring overweight and obesity in consideration of complex survey design with adjustment for potential covariates.

Results: Compared with mothers having normal weight, neonatal mortality risks were increased in mothers having overweight, modest obesity and severe obesity, with ORs (95% CIs) of 1.32 (1.17-1.49), 1.50 (1.27-1.77) and 1.56 (1.22-1.98), respectively. In addition, offspring with mothers having overweight, modest obesity and severe obesity were at increased risks of overweight (with ORs [95% CIs] of 1.32 [1.24-1.40], 1.61 [1.48-1.74] and 1.69 [1.52-1.88], respectively) and obesity (with ORs [95% CIs] of 1.23 [1.13-1.34], 1.22 [1.10-1.35] and 1.42 [1.21-1.66], respectively).

Conclusions: Our results suggest that maternal overweight and obesity increased the risks of neonatal mortality, and offspring overweight and obesity in LMICs. Maternal weight control should be considered as the highest priority goal for preventing offspring's adverse health outcomes in LMICs.
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http://dx.doi.org/10.1111/ijpo.12665DOI Listing
November 2020

Breastfeeding and Mortality Under 2 Years of Age in Sub-Saharan Africa.

Pediatrics 2020 05 22;145(5). Epub 2020 Apr 22.

Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China;

Background: Several studies have investigated the association of breastfeeding status with offspring mortality in Africa, but most studies were from one center only or had limited statistical power to draw robust conclusions.

Methods: Data came from 75 nationally representative cross-sectional Demographic and Health Surveys in 35 countries in sub-Saharan Africa conducted between 2000 and 2016. Our study relied on 217 112 individuals aged 4 days to 23 months for breastfeeding pattern analysis, 161 322 individuals aged 6 to 23 months for breastfeeding history analysis, and 104 427 individuals aged 12 to 23 months for breastfeeding duration analysis.

Results: Compared with children aged 4 days to 23 months exclusively breastfed in the first 3 days of life, those not breastfed had a high risk of mortality at <2 years of age (odds ratio [OR] = 13.45; 95% confidence interval [CI] = 11.43-15.83). Young children who were predominantly breastfed or partially breastfed had moderately increased risk of mortality at <2 years of age (OR = 1.11, 95% CI = 1.03-1.21 for predominant pattern; OR = 1.12, 95% CI = 0.99-1.27 for partial pattern). Compared with children aged 6 to 23 months who were breastfed within the first 6 months of life, those not breastfed had a high risk of mortality (OR = 5.65; 95% CI = 4.27-7.47). Compared with children aged 12 to 23 months who were breastfed for ≥6 months, those who were breastfed for shorter periods had a higher risk of mortality (OR = 2.78, 95% CI = 1.45-5.32 for duration of <3 months; OR = 5.28, 95% CI = 3.24-8.61 for those who were not breastfed).

Conclusions: Our findings support exclusive breastfeeding during the first 6 months of life and continued breastfeeding up to 2 years of age recommended by the World Health Organization for reducing mortality of children <2 years old in sub-Saharan Africa.
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http://dx.doi.org/10.1542/peds.2019-2209DOI Listing
May 2020

Impact of the 2017 American Academy of Pediatrics Guideline on Hypertension Prevalence Compared With the Fourth Report in an International Cohort.

Hypertension 2019 12 21;74(6):1343-1348. Epub 2019 Oct 21.

From the Department of Epidemiology, School of Public Health, Shandong University, Jinan, China (L.Y., B.X.).

In 2017, the American Academy of Pediatrics (AAP) updated the clinical practice guideline for high blood pressure (BP) in the pediatric population. In this study, we compared the difference in prevalence of elevated and hypertensive BP values defined by the 2017 AAP guideline and the 2004 Fourth Report and estimated the cardiovascular risk associated with the reclassification of BP status defined by the AAP guideline. A total of 47 200 children and adolescents aged 6 to 17 years from 6 countries (China, India, Iran, Korea, Poland, and Tunisia) were included in this study. Elevated BP and hypertension were defined according to 2 guidelines. In addition, 1606 children from China, Iran, and Korea who were reclassified upward by the AAP guideline compared with the Fourth Report and for whom laboratory data were available were 1:1 matched with children from the same countries who were normotensive by both guidelines. Compared with the Fourth Report, the prevalence of elevated BP defined by the AAP guideline was lower (14.9% versus 8.6%), whereas the prevalence of stages 1 and 2 hypertension was higher (stage 1, 6.6% versus 14.5%; stage 2, 0.4% versus 1.7%). Additionally, comparison of laboratory data in the case-control study showed that children who were reclassified upward were more likely to have adverse lipid profiles and high fasting blood glucose compared with normotensive children. In conclusion, the prevalence of elevated BP and hypertension varied significantly between both guidelines. Applying the new AAP guideline could identify more children with hypertension who are at increased cardiovascular risk.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13807DOI Listing
December 2019
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