Publications by authors named "Tiejun Zhang"

173 Publications

Erratum: usDSM: a novel method for deleterious synonymous mutation prediction using undersampling scheme.

Brief Bioinform 2021 Jun 15. Epub 2021 Jun 15.

GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, China.

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http://dx.doi.org/10.1093/bib/bbab247DOI Listing
June 2021

Increasing prevalence of NAFLD/NASH among children, adolescents and young adults from 1990 to 2017: a population-based observational study.

BMJ Open 2021 05 4;11(5):e042843. Epub 2021 May 4.

Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China

Objective: To describe the prevalence and variations of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) among children and adolescents (CADs) and young adults (YADs).

Design: A population-based observational study.

Setting: Annual cases and prevalence of NAFLD/NASH from 1990 to 2017, by sex, region and country were collected from the Global Burden of Disease database.

Main Outcome Measures: The estimated annual percentage change, which was calculated by a regression line, was used to quantify the temporal trends in NAFLD/NASH burden among young people at the global, regional and national levels.

Results: Globally, NAFLD/NASH incidence increased from 19.34 million in 1990 to 29.49 million in 2017 among CADs, with an annual increase of 1.35%. Additionally, in YADs, the number of cases and NAFLD/NASH prevalence significantly increased during this period, independent of sex and region. The greatest NAFLD/NASH increase was in North Africa and the Middle East. Almost all countries showed an increasing trend from 1990 to 2017, with the most pronounced increase observed in the developed regions.

Conclusions: The epidemiology of NAFLD/NASH in young people has changed considerably over the last three decades. Both the prevalence and number of cases have increased irrespective of sex, age and region. This phenomenon can result in a predictable increase in chronic liver disease burden in the near future. Understanding the prevalence of NAFLD/NASH and its variations is of paramount importance to develop strategies to implement public health policy.
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http://dx.doi.org/10.1136/bmjopen-2020-042843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098935PMC
May 2021

usDSM: a novel method for deleterious synonymous mutation prediction using undersampling scheme.

Brief Bioinform 2021 Apr 19. Epub 2021 Apr 19.

GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, China.

Although synonymous mutations do not alter the encoded amino acids, they may impact protein function by interfering with the regulation of RNA splicing or altering transcript splicing. New progress on next-generation sequencing technologies has put the exploration of synonymous mutations at the forefront of precision medicine. Several approaches have been proposed for predicting the deleterious synonymous mutations specifically, but their performance is limited by imbalance of the positive and negative samples. In this study, we firstly expanded the number of samples greatly from various data sources and compared six undersampling strategies to solve the problem of the imbalanced datasets. The results suggested that cluster centroid is the most effective scheme. Secondly, we presented a computational model, undersampling scheme based method for deleterious synonymous mutation (usDSM) prediction, using 14-dimensional biology features and random forest classifier to detect the deleterious synonymous mutation. The results on the test datasets indicated that the proposed usDSM model can attain superior performance in comparison with other state-of-the-art machine learning methods. Lastly, we found that the deep learning model did not play a substantial role in deleterious synonymous mutation prediction through a lot of experiments, although it achieves superior results in other fields. In conclusion, we hope our work will contribute to the future development of computational methods for a more accurate prediction of the deleterious effect of human synonymous mutation. The web server of usDSM is freely accessible at http://usdsm.xialab.info/.
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http://dx.doi.org/10.1093/bib/bbab123DOI Listing
April 2021

Tumor infiltrating lymphocyte signature is associated with single nucleotide polymorphisms and predicts survival in esophageal squamous cell carcinoma patients.

Aging (Albany NY) 2021 04 4;13(7):10369-10386. Epub 2021 Apr 4.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Purpose: Esophageal cancer is the sixth leading cause of cancer-related death worldwide, and is associated with a poor prognosis. Stromal tumor infiltrating lymphocytes (sTIL) and certain single nucleotide polymorphisms (SNPs) have been found to be predictive of patient survival. In this study, we explored the association between SNPs and sTIL regarding the predictability of disease-free survival in patients with esophageal squamous cell carcinoma (ESCC).

Materials And Methods: We collected 969 pathologically confirmed ESCC patients from 2010 to 2013 and genotyped 101 SNPs from 59 genes. The number of sTIL for each patient was determined using an automatic algorithm. A Kruskal-Wallis test was used to determine the association between genotype and sTIL. The genotypes and clinical factors related to survival were analyzed using a Kaplan-Meier curve, Cox proportional hazards model, and log-rank test.

Results: The median age of the patients was 67 (42-85 years), there was a median follow-up of 851.5 days and 586 patients died. The univariable analysis showed that 10 of the 101 SNPs were associated with sTIL. Six SNPs were also associated with disease-free survival. A multivariable analysis revealed that sTIL, rs1801131, rs25487, and rs8030672 were independent prognostic markers for ESCC patients. The model combining SNPs, clinical characteristics and sTIL outperformed the model with clinical characteristics alone for predicting outcomes in ESCC patients.

Conclusion: We discovered 10 SNPs associated with sTIL in ESCC and we built a model of sTIL, SNPs and clinical characteristics with improved prediction of survival in ESCC patients.
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http://dx.doi.org/10.18632/aging.202798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064198PMC
April 2021

The gut microbiome in subclinical atherosclerosis: a population-based multi-phenotype analysis.

Rheumatology (Oxford) 2021 Mar 26. Epub 2021 Mar 26.

State Key Laboratory of Genetic Engineering and Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.

Background: The altered microbiota, considered as quantitative traits, has also been identified to play pivotal roles in the host vascular physiology and might contribute to diseases. To understand the role of gut microbiota on vascular physiology in the sub-clinical elderly population and how lifestyles affect the composition of host gut microbiota to further impact the pathogenesis of vascular diseases.

Methods: Performed a population-based fecal metagenomic study over 569 elderly asymptomatic sub-clinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets.

Results: Carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were shown essentially in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of taking fresh fruits, fresh vegetables, and more exercise significantly reduces carotid arteries atherosclerosis in terms of IMT, PSV and EDV values the through the mediation of Alistepes, Oligella, and Prevotella. The gut microbes explained 16.5% of the mediation effect of lifestyles on the pathogenesis of carotid atherosclerosis. After adjusted, Faecalicatena (OR = 0.20∼0.30) was shown protective in the formation of carotid athersclerosis independently, while Libanicoccus (OR = 2.39∼2.43) were hazardous to carotid arterial IMTs. KEGG/KO analyses revealed a loss of anti-inflammation function in IMT subjects.

Conclusions: Our study provided a Chinese population-wide phenotype-metagenomic network, revealing association and mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at a therapeutic and preventive potential of microbiota in vascular diseases.
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http://dx.doi.org/10.1093/rheumatology/keab309DOI Listing
March 2021

Neuroprotection of Chikusetsu saponin V on transient focal cerebral ischemia/reperfusion and the underlying mechanism.

Phytomedicine 2021 Apr 17;84:153516. Epub 2021 Feb 17.

Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Background: Oxidative stress and frequently unwanted alterations in mitochondrial structure and function are key aspects of the pathological cascade in transient focal cerebral ischemia. Chikusetsu saponin V (CHS V), a major component of saponins from Panax japonicas, can attenuate HO-induced oxidative stress in SH-SY5Y cells.

Purpose: The aim of the present study was to investigate the neuroprotective effects and the possible underlying mechanism of CHS V on transient focal cerebral ischemia/reperfusion.

Methods: Mice with middle cerebral artery occlusion (MCAO) and cultured cortical neurons exposed to oxygen glucose deprivation (OGD) were used as in vivo and in vitro models of cerebral ischemia, respectively. The neurobehavioral scores, infarction volumes, H&E staining and some antioxidant levels in the brain were evaluated. The occurrence of neuronal death was estimated. Total and mitochondrial reactive oxygen species (ROS) levels, as well as mitochondrial potential were measured using flow cytometry analysis. Mitochondrial structure and respiratory activity were also examined. Protein levels were investigated by western blotting and immunohistochemistry.

Results: CHS V effectively attenuated cerebral ischemia/reperfusion (CI/R) injury, including improving neurological deficits, shrinking infarct volume and reducing the number of apoptotic cells. Furthermore, CHS V treatment remarkably increased antioxidant levels and reduced ROS levels and mitochondrial damage by enhancing the expression and deacetylation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by activating AMPK and SIRT-1, respectively.

Conclusion: Our data demonstrated that CHS V prevented CI/R injury by suppressing oxidative stress and mitochondrial damage through the modulation of PGC-1α with AMPK and SIRT-1.
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http://dx.doi.org/10.1016/j.phymed.2021.153516DOI Listing
April 2021

Spatiotemporal trends in stroke burden and mortality attributable to household air pollution from solid fuels in 204 countries and territories from 1990 to 2019.

Sci Total Environ 2021 Jun 13;775:145839. Epub 2021 Feb 13.

Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai 200438, China; Fudan University Taizhou Institute of Health Sciences, Taizhou 225312, Jiangsu, China. Electronic address:

Exposure to household air pollution from solid fuels (HAP) is associated with stroke. However, few studies have assessed stroke burden attributable to HAP globally and made comparisons across countries. We aimed to estimate the spatiotemporal trends in stroke burden and mortality attributable to household air pollution from solid fuels (HAP) in 204 countries and territories from 1990 to 2019. Data on stroke burden and mortality attributable to HAP from 1990 to 2019 were obtained from Global Burden of Disease Study 2019. We estimated the numbers and age-standardized rates (ASRs) of stroke disability-adjusted life years (DALYs) and mortality (ASDR and ASMR) by sex, age, and subtype, at global, regional, and national levels. Estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends in ASDR and ASMR from 1990 to 2019. In 2019, globally, 14.7 million DALYs and 0.6 million deaths were caused by stroke attributable to HAP. The corresponding ASDR and ASMR increased with age, were highest in males and for intracerebral hemorrhage, with highest ASRs in the low sociodemographic index (SDI) regions and Solomon Islands, and varied greatly at the national level. From 1990 to 2019, the corresponding EAPCs in ASDR and ASMR were -4.00 (95% confidence interval [CI]: -4.21 to -3.80) and -4.12 (95% CI: -4.37 to -3.87), respectively. Stroke burden attributable to HAP decreased in all age groups. Females had a lower decreasing trend in ASDR and ASMR, compared with males. The decline was more significant for subarachnoid hemorrhage, while proportions of ischemic stroke in the numbers of stroke burden increased worldwide and in all SDI regions. Although most of countries and territories were in a decreasing trend in ASRs over the past three decades, Zimbabwe and Philippines showed an undesirable increased trend. Stroke burden attributable to HAP is still pronounced in males, old-age populations, low-income countries, and for intracerebral hemorrhage. Despite its decreasing spatiotemporal trends in most countries, continued efforts on HAP control are needed to reduce related stroke burden, especially in those countries with increased trends.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145839DOI Listing
June 2021

Designing a next generation solar crystallizer for real seawater brine treatment with zero liquid discharge.

Nat Commun 2021 Feb 12;12(1):998. Epub 2021 Feb 12.

Water Desalination and Reuse Center, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.

Proper disposal of industrial brine has been a critical environmental challenge. Zero liquid discharge (ZLD) brine treatment holds great promise to the brine disposal, but its application is limited by the intensive energy consumption of its crystallization process. Here we propose a new strategy that employs an advanced solar crystallizer coupled with a salt crystallization inhibitor to eliminate highly concentrated waste brine. The rationally designed solar crystallizer exhibited a high water evaporation rate of 2.42 kg m h under one sun illumination when treating real concentrated seawater reverse osmosis (SWRO) brine (21.6 wt%). The solar crystallizer array showed an even higher water evaporation rate of 48.0 kg m per day in the outdoor field test, suggesting a great potential for practical application. The solar crystallizer design and the salt crystallization inhibition strategy proposed and confirmed in this work provide a low-cost and sustainable solution for industrial brine disposal with ZLD.
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http://dx.doi.org/10.1038/s41467-021-21124-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881092PMC
February 2021

The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease-Related Genetic Variants.

Clin Gastroenterol Hepatol 2020 Dec 30. Epub 2020 Dec 30.

State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, China. Electronic address:

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed disease category that derived from non-alcoholic fatty liver disease. The impact of MAFLD on health events has not been investigated.

Methods: UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five genetic variants (PNPLA3 rs738409 C/G, TM6SF2 rs58542926 C/T, GCKR rs1260326 T/C, MBOAT7 rs641738 C/T, and HSD17B13 rs72613567 T/TA) were integrated into a genetic risk score (GRS). Cox proportional hazard model was used to examine the association of MAFLD with incident diseases.

Results: A total of 160 979 (38.0%, 95% confidence interval [CI] 37.9%, 38.2%) participants out of 423 252 were diagnosed as MAFLD. Compared with participants without MAFLD, MAFLD cases had multivariate adjusted hazard ratio (HR) for liver cancer of 1.59 (95% CI 1.28, 1.98), cirrhosis of 2.77 (2.29, 3.36), other liver diseases of 2.09 (1.95, 2.24), cardiovascular diseases of 1.39 (1.34, 1.44), renal diseases of 1.56 (1.48, 1.65), and cancers of 1.07 (1.05, 1.10). The impact of MAFLD, especially on hepatic events, was amplified by high GRS, of which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play the principal roles. MAFLD case with normal body weight is also associated with an increased risk of hepatic outcomes, but the genetic factor seems do not influence the risk in this subpopulation.

Conclusions: MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. Fatty liver disease related genetic variants amplify the effect of MAFLD on disease outcomes.
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http://dx.doi.org/10.1016/j.cgh.2020.12.033DOI Listing
December 2020

Effects of dexmedetomidine on immune response in patients undergoing radical and reconstructive surgery for oral cancer.

Oncol Lett 2021 Feb 10;21(2):106. Epub 2020 Dec 10.

Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

Oral cancer is one of the most common malignancies in the world. The present study aimed to investigate the effects of dexmedetomidine on immune response in patients undergoing radical and reconstructive surgery for oral cancer. Patients were randomly divided into the dexmedetomidine and control groups. Within 15 min before anesthesia induction, dexmedetomidine was infused with a 0.5 µg·kg loading dose followed by a maintenance dose of 0.4 µg·kg·h to the end of operation in the dexmedetomidine group, whereas the same volume of saline was administered in the control group. Blood samples were obtained at five time-points: 30 min Before induction (T), 1 h after induction (T), end of the operation (T) and 24 (T) and 48 h (T) after the operation. The T lymphocyte subsets (including CD3, CD4 and CD8 cells) and CD4/CD8 ratio, B lymphocytes, dendritic cells and myeloid-derived suppressor cells (MDSCs) were analyzed by flow cytometry. All immunological indicators, except CD8 cells, significantly decreased between the two groups at T compared with T (P<0.05). The percentages of CD3, CD4, dendritic cells and the CD4/CD8 ratios were significantly higher at T and the percentages of MDSCs were significantly lower at T in the dexmedetomidine group compared with the control group (all P<0.05). These findings suggested that dexmedetomidine can attenuate immunosuppression in patients undergoing radical and reconstructive surgery for oral cancer.
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http://dx.doi.org/10.3892/ol.2020.12367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751342PMC
February 2021

Global trend of aetiology-based primary liver cancer incidence from 1990 to 2030: a modelling study.

Int J Epidemiol 2021 03;50(1):128-142

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.

Background: Predictions of primary liver cancer (PLC) incidence rates and case numbers are critical to understand and plan for PLC disease burden.

Methods: Data on PLC incidence rates and case numbers from 1990 to 2017 were retrieved from the Global Burden of Disease database. The estimated average percentage change (EAPC) was calculated to quantify the trends of PLC age-standardized incidence rates (ASRs). Bayesian age-period-cohort models were constructed to project PLC incidence rates and case numbers through 2030.

Results: Globally, the PLC case number doubled from 472 300 in 1990 to 953 100 in 2017. The case number will further increase to 1 571 200 in 2030, and the ASR will increase from 11.80 per 100 000 in 2018 to 14.08 per 100 000 in 2030. The most pronounced increases are observed in people afflicted by non-alcoholic steatohepatitis (NASH) and in older people. The trends of PLC incidence rates between 1990 and 2030 are heterogeneous among countries and can be summarized as five scenarios: (i) 46 countries that have and will continue to experience a persistent increase (e.g. Australia); (ii) 21 countries that experienced an initial decrease (or remained stable) but are predicted to increase (e.g. China); (iii) 7 countries that experienced an initial increase but are predicted to remain stable (e.g. USA); (iv) 29 countries that experienced an initial increase but are predicted to decrease (e.g. Egypt); and (v) 82 countries that have and will continue to experience a persistent decrease (e.g. Japan).

Conclusion: PLC incidence rates and case numbers are anticipated to increase at the global level through 2030. The increases in people afflicted by NASH and among older people suggest a dearth of attention for these populations in current prevention strategies and highlight their priority in future schedules for global control of PLC.
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http://dx.doi.org/10.1093/ije/dyaa196DOI Listing
March 2021

Effects of Cryopreservation on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Assessing Drug Safety Response Profiles.

Stem Cell Reports 2021 01 17;16(1):168-181. Epub 2020 Dec 17.

Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

Burgeoning applications of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in disease modeling, regenerative medicine, and drug screening have broadened the usage of hiPSC-CMs and entailed their long-term storage. Cryopreservation is the most common approach to store hiPSC-CMs. However, the effects of cryopreservation and recovery on hiPSC-CMs remain poorly understood. Here, we characterized the transcriptome, electro-mechanical function, and drug response of fresh hiPSC-CMs without cryopreservation and recovered hiPSC-CMs from cryopreservation. We found that recovered hiPSC-CMs showed upregulation of cell cycle genes, similar or reduced contractility, Ca transients, and field potential duration. When subjected to treatment of drugs that affect electrophysiological properties, recovered hiPSC-CMs showed an altered drug response and enhanced propensity for drug-induced cardiac arrhythmic events. In conclusion, fresh and recovered hiPSC-CMs do not always show comparable molecular and physiological properties. When cryopreserved hiPSC-CMs are used for assessing drug-induced cardiac liabilities, the altered drug sensitivity needs to be considered.
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http://dx.doi.org/10.1016/j.stemcr.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897580PMC
January 2021

Heart Development and Regeneration in Non-mammalian Model Organisms.

Front Cell Dev Biol 2020 29;8:595488. Epub 2020 Oct 29.

GMU-GIBH Joint School of Life Sciences, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China.

Cardiovascular disease is a serious threat to human health and a leading cause of mortality worldwide. Recent years have witnessed exciting progress in the understanding of heart formation and development, enabling cardiac biologists to make significant advance in the field of therapeutic heart regeneration. Most of our understanding of heart development and regeneration, including the genes and signaling pathways, are driven by pioneering works in non-mammalian model organisms, such as fruit fly, fish, frog, and chicken. Compared to mammalian animal models, non-mammalian model organisms have special advantages in high-throughput applications such as disease modeling, drug discovery, and cardiotoxicity screening. Genetically engineered animals of cardiovascular diseases provide valuable tools to investigate the molecular and cellular mechanisms of pathogenesis and to evaluate therapeutic strategies. A large number of congenital heart diseases (CHDs) non-mammalian models have been established and tested for the genes and signaling pathways involved in the diseases. Here, we reviewed the mechanisms of heart development and regeneration revealed by these models, highlighting the advantages of non-mammalian models as tools for cardiac research. The knowledge from these animal models will facilitate therapeutic discoveries and ultimately serve to accelerate translational medicine.
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http://dx.doi.org/10.3389/fcell.2020.595488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673453PMC
October 2020

Construction of high-density genetic linkage map and mapping quantitative trait loci (QTL) for flowering time in autotetraploid alfalfa (Medicago sativa L.) using genotyping by sequencing.

Plant Genome 2020 11 26;13(3):e20045. Epub 2020 Sep 26.

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Flowering time is an important agronomic trait of alfalfa (Medicago sativa L.). Managing flowering time can produce economic benefits for farmers. To understand the genetic basis of this trait, quantitative trait loci (QTL) mapping was conducted in a full-sib population that consisted of 392 individuals segregating based on flowering time. High density linkage maps were constructed using single nucleotide polymorphism (SNP) markers generated by genotyping-by-sequencing (GBS). The linkage maps contained 3,818 SNP markers on 64 linkage groups in two parents. The average marker density was 4.33 cM for Parent 1 (P1) and 1.47 cM for Parent 2 (P2). Phenotypic data for flowering time was collected for three years at one location. Twenty-eight QTLs were identified associated with flowering time. Eleven QTLs explained more than 10% of the phenotypic variation. Among them, five main effect QTLs located on linkage group (LG) 7D of P1 and five main effect QTLs located on LG 6D of P2 were identified. Three QTLs were co-located with other QTLs. The identified linked markers to QTLs could be used for marker-assisted selection in breeding programs to develop new alfalfa varieties to modulate flowering time.
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http://dx.doi.org/10.1002/tpg2.20045DOI Listing
November 2020

Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription.

Acta Pharm Sin B 2020 Sep 27;10(9):1646-1657. Epub 2020 Jun 27.

Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.

Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising (CYH) and (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3. What's more, AD extract also exerted strongly inhibition to human transporters OATP1B1 and OATP1B3. It was also detected that IPT, ISP, and AD extract significantly downregulated the expression of , , and of liver in mice. The results show that the concentration of TDE in liver and kidney significantly decreased, while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT, ISP, and AD extract. These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney. That is to say, TDE with bitter taste could "flood up" into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD. This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3, OATP1B1, and OATP1B3, but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD. This study may offer a valuable clue to illustrate the mechanism of compatibility theory.
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http://dx.doi.org/10.1016/j.apsb.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564327PMC
September 2020

Early prediction of mortality risk among patients with severe COVID-19, using machine learning.

Int J Epidemiol 2021 01;49(6):1918-1929

State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, has been spreading globally. We aimed to develop a clinical model to predict the outcome of patients with severe COVID-19 infection early.

Methods: Demographic, clinical and first laboratory findings after admission of 183 patients with severe COVID-19 infection (115 survivors and 68 non-survivors from the Sino-French New City Branch of Tongji Hospital, Wuhan) were used to develop the predictive models. Machine learning approaches were used to select the features and predict the patients' outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models' performance. A total of 64 with severe COVID-19 infection from the Optical Valley Branch of Tongji Hospital, Wuhan, were used to externally validate the final predictive model.

Results: The baseline characteristics and laboratory tests were significantly different between the survivors and non-survivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the external validation sets were 0.881. The sensitivity and specificity were 0.839 and 0.794 for the validation set, when using a probability of death of 50% as the cutoff. Risk score based on the selected variables can be used to assess the mortality risk. The predictive model is available at [https://phenomics.fudan.edu.cn/risk_scores/].

Conclusions: Age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level of COVID-19 patients at admission are informative for the patients' outcomes.
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http://dx.doi.org/10.1093/ije/dyaa171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543461PMC
January 2021

Non-invasive fibrosis markers are associated with mortality risk in both general populations and non-alcoholic fatty liver disease patients.

Hepatol Res 2021 Jan 8;51(1):90-101. Epub 2020 Oct 8.

State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.

Aim: We assessed the correlations between non-invasive fibrosis scores and mortality in both the general population and non-alcoholic fatty liver disease (NAFLD) patients.

Methods: We used data from the US National Health and Nutrition Examination Survey 1988-2014. The NAFLD fibrosis score (NFS), Fibrosis-4 index (FIB-4) score, aspartate aminotransferase to platelet ratio index (APRI) score, and Forns index score were calculated at baseline. The associations of these scores with the risk of mortality were determined using additive Cox proportional hazard models. The area under the receiver operating characteristic curve (AUROC) was used to study the predictive capacity of each scoring system.

Results: A total of 44 508 participants were included; among them, 9721 deaths occurred during a mean follow-up of 12.5 years. A "J"-shaped correlation pattern was observed for both the FIB-4 and APRI scores. A "U"-shaped correlation pattern was observed for both the Forns index and NFS. Similar correlation patterns were observed in 1955 NAFLD patients. For overall mortality, the AUROC values of the selected fibrosis scores were comparable between general population and NAFLD patients. The superior predictive capacity was found for FIB-4, with AUROC of 75.03% (95% confidence interval, 70.91% to 79.82%) in general population and 75.32% (95% confidence interval, 69.43% to 80.11%) in NAFLD patients, respectively.

Conclusions: Non-linear associations were shown between the fibrosis scoring systems and mortality risk. These scores could serve as indicators for mortality in people with or without NAFLD.
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http://dx.doi.org/10.1111/hepr.13570DOI Listing
January 2021

Global trends in the incidence and mortality of esophageal cancer from 1990 to 2017.

Cancer Med 2020 09 4;9(18):6875-6887. Epub 2020 Aug 4.

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.

Background: The incidence and mortality of esophageal cancer are high, with 5.90 new cases and 5.48 deaths per 100 000 people worldwide in 2017. The prognosis of esophageal cancer is poor, with an overall 5-year survival rate of less than 20%. Esophageal cancer in different geographical locations has different etiologies, and the incidence and mortality of esophageal cancer continue to rise in some regions.

Methods: We collected incidence and mortality data by age and gender for 195 countries and territories from 1990 to 2017 in the Global Burden of Disease (GBD) database. And we used these data to calculate the estimated annual percentage change (EAPC) to quantify trends in morbidity and mortality. Then we analyzed the gender- and age-specific incidence and mortality in esophageal cancer to targeted high-risk populations. Finally, we analyzed the correlation between the age-standardized mortality rate (ASMR) and both the EAPC and social-demographic index (SDI), and we calculated the Pearson correlation coefficient.

Results: We found that Malawi, East Asia, and high-middle SDI regions had the highest age-standardized incidence rate (ASIR) and ASMR, and the ASIR and ASMR in western Sub-Saharan Africa showed an upward trend. Our study also showed that the incidence and mortality in esophageal cancer were highest in men and in the 70+ years age group, and they presented a decreasing trend in most regions, but the 15-49 years age groups in Australasia, Caribbean, and Oceania and the 70+ years age group in High-Income North America, Oceania and high-SDI regions presented an increasing trend. There were significant negative associations between ASMR at baseline and EAPC and between ASMR and SDI in 2017.

Conclusion: By analyzing the global distribution of incidence and mortality in esophageal cancer, trends over time, and gender and age specificity, we can understand the heterogeneity of its global trends. This heterogeneity can help us to identify high-risk groupsand to provide clues for the exploration of the etiology and early prevention of the disease.
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http://dx.doi.org/10.1002/cam4.3338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520289PMC
September 2020

Disease burden of viral hepatitis A, B, C and E: A systematic analysis.

J Viral Hepat 2020 12 18;27(12):1284-1296. Epub 2020 Aug 18.

State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.

Viral hepatitis has been recognized as a leading cause of deaths worldwide. We aimed to analyse the disease burden of viral hepatitis at the global, regional and national levels. We collected the data of death number, mortality rate, and disability-adjusted life years (DALYs) of viral hepatitis by sex, age, geography and type of disease from the Global Health Data Exchange platform. Estimated average percentage change (EAPC) was used to quantify the age-standardized mortality rate (ASMR) of viral hepatitis between 1990 and 2017. Globally, the number of deaths from viral hepatitis increased from 980.9 thousand in 1990 to 1412.3 thousand in 2017, accompanying by the DALYs increased from 35.2 million to 43.1 million in the same period. Hepatitis B and C accounted for 97.6% of total viral hepatitis-related deaths worldwide in 2017. While the death number and DALYs were decreased in acute hepatitis A, B, C and E, a significant increase was found in liver cancer and cirrhosis due to hepatitis B and C. The ASMRs of liver cancer and cirrhosis caused by hepatitis B and C were decreased at the global level and in most regions. However, a significant increase was observed in several developed countries, such as the USA and the UK. The disease burden of viral hepatitis continues to increase worldwide, which was driven by the increase in burden of chronic hepatitis B and C.
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http://dx.doi.org/10.1111/jvh.13371DOI Listing
December 2020

Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.

Nat Commun 2020 07 21;11(1):3475. Epub 2020 Jul 21.

Department of Bioengineering, University of California at San Diego, La Jolla, CA, 92093, USA.

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
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http://dx.doi.org/10.1038/s41467-020-17316-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374162PMC
July 2020

Cohort profile: protocol and baseline survey for the Shanghai Suburban Adult Cohort and Biobank (SSACB) study.

BMJ Open 2020 07 8;10(7):e035430. Epub 2020 Jul 8.

Department of Health Economic, School of Public Health, Fudan University, Shanghai, China.

Purpose: The Shanghai Suburban Adult Cohort and Biobank (SSACB) was established to identify environmental, lifestyle and genetic risk factors for non-communicable chronic diseases (NCDs) in adults (20-74 years old) living in a suburban area of Shanghai with rapid urbanisation.

Participants: Two of eight suburban district were purposely selected according to participant willingness, health service facilities, population, geographic region and electronic medical record system. From these suburban districts, four communities were selected based on economic level and population size. At stage three, one-third of the committees/villages were randomly selected from each community. All residents aged 20-74 years old were invited as study participants.

Findings To Date: The baseline data on demographics, lifestyle and physical health-related factors were collected using a face-to-face questionnaire interview. All participants completed physical examinations and had blood and urine tests. Blood and urine samples from these tests were stored in a biobank. From 6 April 2016 through 31 October 2017, we conducted face-to-face interviews and clinical examinations in 44 887 participants: 35 727 from Songjiang District and 9160 from Jiading District. The average age of participants was 56.4±11.2 years in Songjiang and 56.6±10.5 years in Jiading. The prevalence of hypertension, diabetes and dyslipidaemia was 34.0%, 8.2% and 11.1%, respectively.

Future Plans: In-person surveys will be conducted every 5 years. For annual tracking, baseline data was linked to the local health information system, which was composed of an electronic medical record system, a chronic disease management system, a cancer registry system, an infectious disease report system and a death registry system. The data of the SSACB cohort is located in the School of Public Health, Fudan University. International and domestic collaborative research projects are encouraged and inherent in the project.
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http://dx.doi.org/10.1136/bmjopen-2019-035430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348462PMC
July 2020

Empowering microfluidics by micro-3D printing and solution-based mineral coating.

Soft Matter 2020 Jul;16(29):6841-6849

Department of Mechanical Engineering, Masdar Institute, Khalifa University of Science and Technology, P. O. Box 54224, Abu Dhabi, United Arab Emirates.

Fluid-solid interaction in porous materials is of tremendous importance to earth, space, energy, environment, biological, and medical applications. High-resolution 3D printing enables efficient fabrication of porous microfluidic devices with complicated pore-throat morphology, but lacking desired surface functionality. In this work, we propose a novel approach to additively fabricate functional porous devices by integrating micro-3D printing and solution-based internal coating. This approach is successfully applied to create energy/environment-orientated porous micromodels that replicate the μCT-captured porous geometry and natural mineralogy of carbonate rock. The functional mineral coating in a 3D-printed porous scaffold is achieved by seeding calcite nanoparticles along the inner surface and enabling in situ growth of calcite crystals. For conformal and stable coating in confined pore spaces, we manage to control the wetting and capillarity effects during fabrication: (i) capillarity-enhanced nanoparticle immobilization for forming an adhered seeding layer; (ii) capillary pore-throat blockage mitigation for uniform crystal growth. These transparent micromodels are then used to directly image and characterize microscopic fluid dynamics including wettability-dependent fluid propagation and capillarity-held phase transition processes. The proposed approach can be readily tailored with on-demand-designed scaffold geometry and appropriate coating recipe to fit in many other emerging applications.
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http://dx.doi.org/10.1039/d0sm00958jDOI Listing
July 2020

Comparison in Sedative Effects between Dexmedetomidine and Midazolam in Dental Implantation: A Randomized Clinical Trial.

Biomed Res Int 2020 2;2020:6130162. Epub 2020 Jun 2.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, China.

Dexmedetomidine refers to an -adrenergic receptor agonist causing potent sedative, analgesic, and minimal respiratory depression compared with alternative drugs. The present study was aimed at comparing the efficaciousness and safety of midazolam and dexmedetomidine as sedatives for dental implantation. We recruited 60 patients belonging to group I or II of the American Society of Anesthesiologists (ASA) and treated them with either midazolam or dexmedetomidine in a random manner. Patients' duration of analgesia after surgery, surgeon and patient degrees of satisfaction, Observer's Assessment of Alertness/Sedation Scale (OAAS) scores after drug administration, visual analogue scale (VAS) pain scores, and vital signs were recorded variables. Patients administered dexmedetomidine had significantly lower OAAS scores than those administered midazolam ( < 0.05). Patients administrated dexmedetomidine had a significantly longer analgesia duration after the surgical procedure than those administered midazolam, and the difference was statistically significant ( < 0.05). Dexmedetomidine had a significantly larger number of surgeons satisfied with the level of sedation/analgesia than midazolam ( < 0.05). Accordingly, it is considered that dexmedetomidine can achieve better postoperative analgesia, surgeon satisfaction, and sedation than midazolam.
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http://dx.doi.org/10.1155/2020/6130162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288223PMC
March 2021

Comparison of Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Dental Patients under General Anesthesia: A Randomised Clinical Trial.

Biomed Res Int 2020 24;2020:5142913. Epub 2020 Apr 24.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laoratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, Hubei 430079, China.

The aim of this study was to compare the effects of preoperative intranasal dexmedetomidine and oral midazolam on preoperative sedation and postoperative agitation in pediatric dentistry. A total of 60 children (ASA grade I, aged 3-6 years) scheduled for elective pediatric dental treatment were randomly divided into the dexmedetomidine (DEX) and midazolam (MID) groups. Ramsay sedation score, parental separation anxiety scale, mask acceptance scale, pediatric anesthesia emergence delirium scale, and hemodynamic parameters were recorded. The Ramsay sedation scale and hemodynamic parameters of the children were observed and recorded immediately before administration and 10, 20, and 30 min after administration. A satisfactory mask acceptance scale rate was 93.33% in both MID and DEX groups, and there was no significant difference between the two groups ( > 0.05). The proportions of children that "successfully separated from their parents" were 93.33% (MID) and 96.67% (DEX). No significant difference was found between the two groups ( > 0.05). The incidence of agitation was 20% in the MID group and 0% in the DEX group, and the difference was statistically significant ( < 0.05). Intranasal dexmedetomidine and oral midazolam provided satisfactory sedation. No significant difference between the two groups was found in terms of parental separation anxiety and mask acceptance ( > 0.05). The incidence of postoperative pediatrics emergence delirium was significantly lower in the DEX group ( < 0.05).
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http://dx.doi.org/10.1155/2020/5142913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196136PMC
February 2021

Comparison between Dexmedetomidine and Midazolam for Sedation in Patients with Intubation after Oral and Maxillofacial Surgery.

Biomed Res Int 2020 8;2020:7082597. Epub 2020 Apr 8.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, China.

The aim of the investigation is to clarify the beneficial sedative effects for patients with postoperative intubation in the intensive care unit (ICU) after oral and maxillofacial surgery. Forty patients with postoperative intubation were divided into two groups in method of random number table: midazolam group and dexmedetomidine group. The Ramsay score, the behavioral pain scale (BPS) score, SpO, HR, MAP, and RR were recorded before sedation (T0), 30 minutes (T1), 1 hour (T2), 2 hours (T3), 6 hours (T4), and 12 hours (T5) after dexmedetomidine or midazolam initiation in intensive care unit, and 10 minutes after extubation (T6). The rate of incidences of side effects was calculated. Sedation with midazolam was as good as standard sedation with dexmedetomidine in maintaining target sedation level. The BPS score in the midazolam group was higher than that in the dexmedetomidine group. The time of tracheal catheter extraction in the dexmedetomidine group was shorter than that in the midazolam group ( ≤ 0.001). The incidence of bradycardia in the dexmedetomidine group was higher than that in the midazolam group ( = 0.028). There was no statistically significant difference in the incidence of hypotension between the two groups ( = 0.732). The incidence of respiratory depression of group midazolam was higher than that of group dexmedetomidine ( = 0.018). The incidence of delirium in the dexmedetomidine group was significantly lower than that in the midazolam group, and the difference was statistically significant ( = 0.003). Dexmedetomidine and midazolam can meet the needs for sedation in ICU patients. And dexmedetomidine can improve patients' ability to communicate pain compared with midazolam.
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http://dx.doi.org/10.1155/2020/7082597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168695PMC
January 2021

Condensation of Satellite Droplets on Lubricant-Cloaked Droplets.

ACS Appl Mater Interfaces 2020 May 29;12(19):22246-22255. Epub 2020 Apr 29.

Department of Mechanical Engineering, Masdar Institute, Khalifa University of Science and Technology, P.O. Box 54224, Abu Dhabi, UAE.

Condensation on lubricant-infused micro- or nanotextured superhydrophobic surfaces exhibits remarkable heat transfer performance owing to the high condensation nucleation density and efficient condensate droplet removal. When a low surface tension lubricant is used, it can spread on the condensed droplet and "cloak" it. Here, we describe a previously unobserved condensation phenomenon of satellite droplet formation on lubricant-cloaked water droplets using environmental scanning electron microscopy. The presence of satellite droplets confirms the cloaking behavior of common lubricants on water such as Krytox oils. More interestingly, we have observed satellite droplets on BMIm ionic liquid-infused surfaces, which is unexpected because BMIm was used in previous reports as a lubricant to eliminate cloaking during water condensation. Our studies reveal that the cloaking of BMIm on water droplets is theoretically favorable due to the fast timescale spreading during initial condensation when compared to the long timescale required for dissolution of the lubricant in water. We utilize a novel characterization approach based on Raman spectroscopy to confirm the existence of cloaking lubricant films on water droplets residing on lubricant-infused surfaces. The selected lubricants include Krytox oil, ionic liquid, and dodecane, which have drastically different surface tensions and polarities. In addition, spreading dynamics of cloaking and noncloaking lubricants on water droplets show that ionic liquid has the capability to mobilize water droplets spontaneously owing to cloaking and its relatively high surface tension. Our studies not only elucidate the physics governing cloaking and satellite droplet condensation phenomena at micro- and macroscales but also reveal a subset of previously unobserved lubricant-water interfacial interactions for a large variety of applications.
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http://dx.doi.org/10.1021/acsami.9b22417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304831PMC
May 2020

Expression of a Gene from Delays Flowering Time and Enhances Stress Tolerance.

Int J Mol Sci 2020 Mar 30;21(7). Epub 2020 Mar 30.

College of Grassland Science, Beijing Forestry University, Beijing 100083, China.

Shoot branching is one of the most variable determinants of crop yield, and the signaling pathways of plant branches have become a hot research topic. As an important transcription factor in the B3 family, NGATHA1 (NGA1), plays an important role in regulating plant lateral organ development and hormone synthesis and transport, but few studies of the role of this gene in the regulation of plant growth and stress tolerance have been reported. In this study, the gene was isolated from and its function was characterized. The cis-acting elements upstream of the 5' end of and the expression pattern of were analyzed, and the results indicated that the gene may act as a regulator of stress resistance. A plant expression vector was constructed and transgenic Arabidopsis plants were obtained. Transgenic Arabidopsis showed delayed flowering time and reduced branching phenotypes. Genes involved in the regulation of branching and flowering were differentially expressed in transgenic plants compared with wild-type plants. Furthermore, transgenic plants demonstrated strong tolerances to salt- and mannitol-induced stresses, which may be due to the upregulated expression of () by the gene. These results provide useful information for the exploration and genetic modification use of in the future.
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http://dx.doi.org/10.3390/ijms21072384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177866PMC
March 2020

Global incidence trends in primary liver cancer by age at diagnosis, sex, region, and etiology, 1990-2017.

Cancer 2020 05 23;126(10):2267-2278. Epub 2020 Mar 23.

State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.

Background: The incidence of primary liver cancer (PLC) continues to increase worldwide. The incidence trends and patterns of PLC associated with different age at diagnosis remain unknown.

Methods: We collected detailed information on PLC between 1990 and 2017 from Global Burden of Disease Study 2017. Estimated annual percentage changes in the PLC age-standardized incidence rate (ASR) diagnosed by age, sex, region, and etiology were calculated to quantify the temporal trends in PLC ASR.

Results: Globally, the number of PLC cases for which the age at diagnosis was <30 years decreased from 17,381 in 1990 to 14,661 in 2017, whereas the number of PLC cases diagnosed at age 30 to 59 and ≥60 years old increased from 216,561 and 241,189 in 1990 to 359,770 and 578,344 in 2017, respectively. The ASR of PLC cases with age at diagnosis <30 years and between 30 and 59 years decreased in both sexes, whereas the ASR of PLC with age at diagnosis ≥60 years increased in males and remained stable in females at the global level. Males had a more dramatic increase in PLC diagnosed at age ≥60 years but a milder decrease in PLC diagnosed between 30 and 59 years of age. This decrease was attributed largely to the reduction in PLC caused by hepatitis B and hepatitis C and was consistent in most regions except for developed countries, in which the ASR of PLC increased irrespective of sex and age. The ASR of PLC due to nonalcoholic steatohepatitis (NASH) increased by the greatest magnitude in most regions.

Conclusion: PLC in highly endemic regions has been partly alleviated due to the potent control of hepatitis, especially among young and middle-aged people. However, an unfavorable trend was observed in most developed countries and in elderly populations. As such, PLC prevention schedules should give more attention to NASH and elderly patients.
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http://dx.doi.org/10.1002/cncr.32789DOI Listing
May 2020

Stroke burden and mortality attributable to ambient fine particulate matter pollution in 195 countries and territories and trend analysis from 1990 to 2017.

Environ Res 2020 05 29;184:109327. Epub 2020 Feb 29.

State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, 200438, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, 225312, Jiangsu, China. Electronic address:

Background: Fine particulate matter (PM) exposure is associated with stroke incidence and mortality. However, the global distribution and trends of stroke burden and mortality attributable to PM are rarely studied. We estimated the spatial patterns and temporal trends of PM-attributable stroke burden in 195 countries and territories from 1990 to 2017.

Methods: Detailed data on stroke burden attributable to PM were extracted from the Global Burden of Disease Study (GBD) 2017. The numbers and age-standardized rates of stroke disability-adjusted life years (DALYs) and mortality (ASDR and ASMR) were estimated by age, sex, subtype, region, and country. Temporal trends in ASDR and ASMR were analyzed using estimated annual percentage change (EAPC).

Results: Globally, in 2017, 10.5 million DALYs and 0.4 million deaths related to stroke were attributable to PM. The corresponding ASDR and ASMR increased with age, were highest in males and for intracerebral hemorrhage, and varied greatly across countries, with the largest burden in high-middle sociodemographic index (SDI) regions and East Asia. The global ASDR and ASMR decreased by 7.2% and 12.2% from 1990 to 2017, with EAPCs of -0.42 (95% confidence interval [CI]: -0.55, -0.28) and -0.57 (95% CI: -0.72, -0.42), respectively. Age-specific stroke burden rates declined significantly, except in the middle-aged population. The decrease was more pronounced in women and for subarachnoid hemorrhage, while proportions of ischemic stroke burden increased globally and in all SDI regions. Most geographic regions achieved significant declines in ASDR and ASMR since 1990; however, Asia and approximately 30% of countries and territories, especially in low-income countries, showed undesirable increasing trends.

Conclusions: The patterns and trends were heterogeneous across countries. Strengthened and tailored approaches for stroke prevention and air pollution management are still needed to reduce the disease burden associated with PM, particularly in males, middle-age populations, and low-income countries and for ischemic stroke.
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http://dx.doi.org/10.1016/j.envres.2020.109327DOI Listing
May 2020

Construction of High-Density Linkage Maps and Identification of Quantitative Trait Loci Associated with Verticillium Wilt Resistance in Autotetraploid Alfalfa ( L.).

Plant Dis 2020 May 9;104(5):1439-1444. Epub 2020 Mar 9.

United States Department of Agriculture-Agricultural Research Service, Plant Germplasm Introduction and Testing Research, 24106 N Bunn Road, Prosser, WA, U.S.A.

Verticillium wilt (VW) of alfalfa is a devastating disease that causes forage yield reductions of up to 50% in the northern United States and Canada. The most effective method for controlling the disease is through the development and use of resistant varieties. To identify quantitative trait loci (QTL) for VW resistance in alfalfa, we used a full-sib population segregating for VW resistance. High-density linkage maps for both resistant and susceptible parents were constructed using single-dose alleles of single-nucleotide polymorphism markers generated by genotyping-by-sequencing. Five QTL associated with VW resistance were identified and they were in four linkage groups (4D, 6B, 6D, and 8C). Of those, three QTL (, and ) had higher logarithm of odds. Two putative candidates of nucleotide-binding site leucine-rich repeat disease resistance genes were identified in the QTL intervals of and , respectively. The result agreed with our previous studies, in which similar resistance loci were identified in an association panel using genome-wide association. The results provide insight into the quantitative resistance to VW in alfalfa. The resistance loci and closely linked markers identified in the present study can be used in developing new alfalfa varieties with enhanced resistance to VW.
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http://dx.doi.org/10.1094/PDIS-08-19-1718-REDOI Listing
May 2020