Publications by authors named "Hong Xue"

345 Publications

Perspectives of research ethics committee members on human challenge studies in the development of vaccines against COVID-19: a mixed methods study.

Ann Palliat Med 2021 Jun 7. Epub 2021 Jun 7.

Ethics Committee for Medical Scientific Research, Peking University Third Hospital, Beijing, China; Department of Orthopedics, Peking University Third Hospital, Beijing, China.

Background: Vaccines are considered the most effective protection against the coronavirus disease 2019 (COVID-19). Human Challenge Studies can help to shorten the development process of vaccines. The reviewers' opinions from research ethics committees (REC) play an essential gate-keeping role in determining whether a clinical trial can be conducted or not.

Methods: A convergent mixed-methods study was conducted in a leading general hospital in China. A total of 58 REC members from the institution were invited to participate in an online questionnaire survey. According to the result of the quantitative survey, 15 of these REC members were purposefully selected to participate in qualitative interviews further. Quantitative data were analyzed using descriptive statistical techniques, and thematic analysis was used to analyze the qualitative data. Findings from the quantitative and qualitative analyses were synthesized to deeply illustrate the attitudes, views, and suggestions of REC members on human challenge studies to develop COVID-19 vaccination.

Results: The response rate of the online questionnaire was 62% (36/58), and 15 of the respondents were interviewed. All participants deemed that the human challenge study should provide compensation to its participants and that sufficiently informed consent is necessary. The human challenge study was disagreed with by 38.9% of participants. The key points of concern raised were representativeness and fairness of participant selection, benefit, and risk, vulnerable groups, compensation to participants, informed consent, and general view on human challenge studies.

Conclusions: Human challenge studies helped accelerate the development of vaccines for disease control to a certain extent, but the bottom line of medical ethics should not have been broken. At any time, the rights and interests of research participants should come first.
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http://dx.doi.org/10.21037/apm-20-2622DOI Listing
June 2021

Health policy and public health implications of obesity in China.

Lancet Diabetes Endocrinol 2021 Jun 4. Epub 2021 Jun 4.

Department of Health Administration and Policy, College of Health and Human Services, George Mason University, Fairfax, VA, USA.

China has experienced many drastic social and economic changes and shifts in people's lifestyles since the 1990s, in parallel with the fast rising prevalence of obesity. About half of adults and a fifth of children have overweight or obesity according to the Chinese criteria, making China the country with the highest number of people with overweight or obesity in the world. Assuming that observed time trends would continue in the future, we projected the prevalence of and the number of people affected by overweight and obesity by 2030, and the associated medical costs. The rising incidence of obesity and number of people affected, as well as the related health and economic consequences, place a huge burden on China's health-care system. China has made many efforts to tackle obesity, including the implementation of relevant national policies and programmes. However, these measures are inadequate for controlling the obesity epidemic. In the past decade, China has attached great importance to public health, and the Healthy China 2030 national strategy initiated in 2016 provides a historical opportunity to establish comprehensive national strategies for tackling obesity. China is well positioned to explore an effective model to overcome the obesity epidemic; however, strong commitment and leadership from central and local governments are needed, as well as active participation of all related society sectors and individual citizens. TRANSLATION: For the Chinese translation of the paper see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-8587(21)00118-2DOI Listing
June 2021

Revisiting the Relationship between WIC Participation and Breastfeeding among Low-Income Children in the U.S. after the 2009 WIC Food Package Revision.

Food Policy 2021 May 23;101. Epub 2021 Apr 23.

Fisher Institute of Health and Well-being, Department of Nutrition and Health Sciences, Ball State University, Muncie, Indiana, USA.

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides breastfeeding support and free formula to low-income participating infants in the U.S. Literature has consistently documented worse breastfeeding outcomes in WIC infants and children than in non-participants, although self-selection bias poses a challenge in examining the relationship between WIC participation and breastfeeding in low-income mother-child dyads. The WIC program adopted a comprehensive food package revision in 2009, the first one in four decades. Since that time, few national studies have examined the relationship between WIC participation and breastfeeding while controlling for the endogeneity of WIC participation with the propensity score method. This paper applied an instrumental variable (IV) approach on a large, nationally representative survey sample of children, the National Immunization Surveys (NIS), to examine the relationship between WIC participation and breastfeeding among children born between 2005 and 2014. We identified state Supplemental Nutrition Assistance Program (SNAP) enrollment rates and SNAP Policy Indices as valid IVs to address WIC participation endogeneity. Without the IVs, WIC participation had a significantly negative relationship with breastfeeding. After addressing endogeneity using the IVs, the relationship became insignificant in the whole sample and in the subpopulations across race/ethnicity and child gender. The neutrality of WIC participation on breastfeeding is important for policy makers to understand in seeking to improve breastfeeding among WIC participants.
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http://dx.doi.org/10.1016/j.foodpol.2021.102089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151795PMC
May 2021

Etanercept Protected Against Cigarette Smoke Extract-Induced Inflammation and Apoptosis of Human Pulmonary Artery Endothelial Cells via Regulating TNFR1.

Int J Chron Obstruct Pulmon Dis 2021 11;16:1329-1345. Epub 2021 May 11.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Purpose: Etanercept (ETN), a tumor necrosis factor-α (TNF-α) inhibitor, has been applied in the treatment of many diseases. However, whether it has effects on chronic obstructive pulmonary disease (COPD) and its interaction with tumor necrosis factor receptor 1 (TNFR1) remained unknown.

Methods: Histopathological analysis of lung tissues from non-smokers and smokers with or without COPD was conducted using hematoxylin-eosin (H&E) staining, Van Gieson (VG) staining, and terminal transferase-mediated biotin dUTP nick end labeling (TUNEL). TNF-α content was measured using Immunohistochemistry. Correlation analysis among apoptosis rate, smoke index, the FEV1/FVC ratio, and TNF-α-positive cells was performed. After ETN treatment and transfection of overexpressed or silenced TNFR1, levels of inflammatory cytokines, apoptosis and related genes expressions in cigarette smoke extract (CSE)-treated human pulmonary artery endothelial cells (HPAECs) were detected using enzyme-linked immunosorbent assay (ELISA), Hoechst 33342 staining, flow cytometry, quantitative real-time PCR (qRT-PCR) and Western blot.

Results: Pulmonary arterial remodeling and increased apoptotic and TNF-α HPAECs were found in lung tissue of smokers with or without COPD, with higher degrees in smokers with COPD. The numbers of apoptotic and TNF-α HPAECs were positively correlated with smoke index, while the FEV1/FVC ratio was negatively correlated with apoptotic HPAECs. In HPAECs, ETN downregulated the expressions of proteins related to CSE-induced apoptosis and the TNF receptor family, decreased CSE-induced cell apoptosis and inflammatory cytokine levels, and inhibited TNFR1 expression and p65 phosphorylation. Overexpressed TNFR1 reversed the effects of ETN on CSE-treated HPAECs, whereas silencing TNFR1 did the opposite.

Conclusion: ETN protected HPAECs against CSE-induced inflammation and apoptosis via downregulating TNFR1, thus providing a potential therapy for smoking-induced COPD.
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http://dx.doi.org/10.2147/COPD.S295580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123949PMC
May 2021

Inequality of weight status in urban Cuba: 2001-2010.

Popul Health Metr 2021 May 4;19(1):24. Epub 2021 May 4.

Global Health Institute, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.

Background: Although understanding changes in the body weight distribution and trends in obesity inequality plays a key role in assessing the causes and persistence of obesity, limited research on this topic is available for Cuba. This study thus analyzed changes in body mass index (BMI) and waist circumference (WC) distributions and obesity inequality over a 9-year period among urban Cuban adults.

Methods: Kolmogorov-Smirnov tests were first applied to the data from the 2001 and 2010 National Survey on Risk Factors and Chronic Diseases to identify a rightward shift in both the BMI and WC distributions over the 2001-2010 period. A Shapley technique decomposed the increase in obesity prevalence into a mean-growth effect and a (re)distributional component. A univariate assessment of obesity inequality was then derived by calculating both the Gini and generalized entropy (GE) measures. Lastly, a GE-based decomposition partitioned overall obesity inequality into within-group and between-group values.

Results: Despite some relatively pronounced left-skewing, both the BMI and WC distributions exhibited a clear rightward shift to which the increases in general and central obesity can be mostly attributed. According to the Gini coefficients, both general and central obesity inequality increased over the 2001-2010 period, from 0.105 [95% confidence interval (CI) = 0.103-0.106] to 0.110 [95% CI = 0.107-0.112] and from 0.083 [95% CI = 0.082-0.084] to 0.085 [95% CI = 0.084-0.087], respectively. The GE-based decomposition further revealed that both types of inequality were accounted for primarily by within-group inequality (93.3%/89.6% and 87.5%/84.8% in 2001/2010 for general/central obesity, respectively).

Conclusions: Obesity inequality in urban Cuba worsened over the 2001-2010 time period, with within-group inequality in overall obesity dominant over between-group inequality. In general, the results also imply that the rise in obesity inequality is immune to health care system characteristics.
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http://dx.doi.org/10.1186/s12963-021-00251-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097838PMC
May 2021

Does Physical Activity Predict Obesity-A Machine Learning and Statistical Method-Based Analysis.

Int J Environ Res Public Health 2021 04 9;18(8). Epub 2021 Apr 9.

Department of Health Administration and Policy, George Mason University, Fairfax, VA 22030, USA.

Background: Obesity prevalence has become one of the most prominent issues in global public health. Physical activity has been recognized as a key player in the obesity epidemic.

Objectives: The objectives of this study are to (1) examine the relationship between physical activity and weight status and (2) assess the performance and predictive power of a set of popular machine learning and traditional statistical methods.

Methods: National Health and Nutrition Examination Survey (NHANES, 2003 to 2006) data were used. A total of 7162 participants met our inclusion criteria (3682 males and 3480 females), with average age ranging from 48.6 (normal weight) to 52.1 years old (overweight). Eleven classifying algorithms-including logistic regression, naïve Bayes, Radial Basis Function (RBF), local k-nearest neighbors (k-NN), classification via regression (CVR), random subspace, decision table, multiobjective evolutionary fuzzy classifier, random tree, J48, and multilayer perceptron-were implemented and evaluated, and they were compared with traditional logistic regression model estimates.

Results: With physical activity and basic demographic status, of all methods analyzed, the random subspace classifier algorithm achieved the highest overall accuracy and area under the receiver operating characteristic (ROC) curve (AUC). The duration of vigorous-intensity activity in one week and the duration of moderate-intensity activity in one week were important attributes. In general, most algorithms showed similar performance. Logistic regression was middle-ranking in terms of overall accuracy, sensitivity, specificity, and AUC among all methods.

Conclusions: Physical activity was an important factor in predicting weight status, with gender, age, and race/ethnicity being less but still essential factors associated with weight outcomes. Tailored intervention policies and programs should target the differences rooted in these demographic factors to curb the increase in the prevalence of obesity and reduce disparities among sub-demographic populations.
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http://dx.doi.org/10.3390/ijerph18083966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069304PMC
April 2021

Income-related health inequality among Chinese adults during the COVID-19 pandemic: evidence based on an online survey.

Int J Equity Health 2021 04 26;20(1):106. Epub 2021 Apr 26.

Global Health Institute, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.

Background: Partial- or full-lockdowns, among other interventions during the COVID-19 pandemic, may disproportionally affect people (their behaviors and health outcomes) with lower socioeconomic status (SES). This study examines income-related health inequalities and their main contributors in China during the pandemic.

Methods: The 2020 China COVID-19 Survey is an anonymous 74-item survey administered via social media in China. A national sample of 10,545 adults in all 31 provinces, municipalities, and autonomous regions in mainland China provided comprehensive data on sociodemographic characteristics, awareness and attitudes towards COVID-19, lifestyle factors, and health outcomes during the lockdown. Of them, 8448 subjects provided data for this analysis. Concentration Index (CI) and Corrected CI (CCI) were used to measure income-related inequalities in mental health and self-reported health (SRH), respectively. Wagstaff-type decomposition analysis was used to identify contributors to health inequalities.

Results: Most participants reported their health status as "very good" (39.0%) or "excellent" (42.3%). CCI of SRH and mental health were - 0.09 (p < 0.01) and 0.04 (p < 0.01), respectively, indicating pro-poor inequality in ill SRH and pro-rich inequality in ill mental health. Income was the leading contributor to inequalities in SRH and mental health, accounting for 62.7% (p < 0.01) and 39.0% (p < 0.05) of income-related inequalities, respectively. The COVID-19 related variables, including self-reported family-member COVID-19 infection, job loss, experiences of food and medication shortage, engagement in physical activity, and five different-level pandemic regions of residence, explained substantial inequalities in ill SRH and ill mental health, accounting for 29.7% (p < 0.01) and 20.6% (p < 0.01), respectively. Self-reported family member COVID-19 infection, experiencing food and medication shortage, and engagement in physical activity explain 9.4% (p < 0.01), 2.6% (the summed contributions of experiencing food shortage (0.9%) and medication shortage (1.7%), p < 0.01), and 17.6% (p < 0.01) inequality in SRH, respectively (8.9% (p < 0.01), 24.1% (p < 0.01), and 15.1% (p < 0.01) for mental health).

Conclusions: Per capita household income last year, experiences of food and medication shortage, self-reported family member COVID-19 infection, and physical activity are important contributors to health inequalities, especially mental health in China during the COVID-19 pandemic. Intervention programs should be implemented to support vulnerable groups.
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http://dx.doi.org/10.1186/s12939-021-01448-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072088PMC
April 2021

Healthfulness Assessment of Recipes Shared on Pinterest: Natural Language Processing and Content Analysis.

J Med Internet Res 2021 Apr 20;23(4):e25757. Epub 2021 Apr 20.

Department of Health Administration and Policy, College of Health and Human Services, George Mason University, Fairfax, VA, United States.

Background: Although Pinterest has become a popular platform for distributing influential information that shapes users' behaviors, the role of recipes pinned on Pinterest in these behaviors is not well understood.

Objective: This study aims to explore the patterns of food ingredients and the nutritional content of recipes posted on Pinterest and to examine the factors associated with recipes that engage more users.

Methods: Data were collected from Pinterest between June 28 and July 12, 2020 (207 recipes and 2818 comments). All samples were collected via 2 new user accounts with no search history. A codebook was developed with a raw agreement rate of 0.97 across all variables. Content analysis and natural language processing sentiment analysis techniques were employed.

Results: Recipes using seafood or vegetables as the main ingredient had, on average, fewer calories and less sodium, sugar, and cholesterol than meat- or poultry-based recipes. For recipes using meat as the main ingredient, more than half of the energy was obtained from fat (277/490, 56.6%). Although the most followed pinners tended to post recipes containing more poultry or seafood and less meat, recipes with higher fat content or providing more calories per serving were more popular, having more shared photos or videos and comments. The natural language processing-based sentiment analysis suggested that Pinterest users weighted taste more heavily than complexity (225/2818, 8.0%) and health (84/2828, 2.9%).

Conclusions: Although popular pinners tended to post recipes with more seafood or poultry or vegetables and less meat, recipes with higher fat and sugar content were more user-engaging, with more photo or video shares and comments. Data on Pinterest behaviors can inform the development and implementation of nutrition health interventions to promote healthy recipe sharing on social media platforms.
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http://dx.doi.org/10.2196/25757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097524PMC
April 2021

Genetic Variants in and Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population.

Front Genet 2021 25;12:630310. Epub 2021 Mar 25.

Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: The tumor necrosis factor superfamily () and TNF receptor superfamily () play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population.

Methods: The -rs1234313, -rs7514229, -rs3181366, -rs2295800, -rs2298209, and -rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools.

Results: After adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), -rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2-4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles ( < 0.001). analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences.

Conclusion: -rs7514229, -rs3181366, and -rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.
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http://dx.doi.org/10.3389/fgene.2021.630310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027328PMC
March 2021

Pregnancy-related weight among immigrant and US-born mothers: The role of nativity, maternal duration of residence, and age at arrival.

Womens Health (Lond) 2021 Jan-Dec;17:17455065211003692

Department of Health Administration and Policy, College of Health and Human Sciences, George Mason University, Fairfax, VA, USA.

Objectives: The goals of this study were to examine the associations between nativity and pregnancy-related weight and to assess the associations between maternal duration of residence and age at arrival in the United States on pregnancy-related weight among immigrants.

Methods: Using logistic regression and data from the Early Childhood Longitudinal Study-Birth Cohort, we assessed differences in preconception weight and gestational weight gain between US-born and immigrant women (N = 7000). We then analyzed differences in both outcomes by duration of residence among immigrants (n = 1850) and examined whether the identified relationships varied by age at arrival in the United States.

Results: Compared to US-born mothers, immigrants were less likely to be classified as obese prior to pregnancy (odds ratio 0.435, 95% confidence interval, 0.321-0.590) or experience excessive gestational weight gain (odds ratio 0.757, 95% confidence interval, 0.614-0.978). Among the immigrant sub-sample, living in the United States for 10-15 years (odds ratio 2.737, 95% confidence interval, 1.459-5.134) or 16+ years was positively associated with both preconception obesity (odds ratio 2.918, 95% confidence interval, 1.322-6.439) and excessive gestational weight gain (odds ratio 1.683, 95% confidence interval, 1.012-2.797, 16+ years only). There was some evidence that the duration of residence was positively associated with preconception obesity, but only among women who had moved to the United States at age 18 years and older.

Conclusion: In sum, while immigrants are less likely than US-born mothers to experience preconception obesity or excessive gestational weight gain, these outcomes vary among the former group by duration of US residence.
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http://dx.doi.org/10.1177/17455065211003692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020768PMC
March 2021

Genetic-variant hotspots and hotspot clusters in the human genome facilitating adaptation while increasing instability.

Authors:
Xi Long Hong Xue

Hum Genomics 2021 Mar 19;15(1):19. Epub 2021 Mar 19.

Division of Life Science and Applied Genomics Centre, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

Background: Genetic variants, underlining phenotypic diversity, are known to distribute unevenly in the human genome. A comprehensive understanding of the distributions of different genetic variants is important for insights into genetic functions and disorders.

Methods: Herein, a sliding-window scan of regional densities of eight kinds of germline genetic variants, including single-nucleotide-polymorphisms (SNPs) and four size-classes of copy-number-variations (CNVs) in the human genome has been performed.

Results: The study has identified 44,379 hotspots with high genetic-variant densities, and 1135 hotspot clusters comprising more than one type of hotspots, accounting for 3.1% and 0.2% of the genome respectively. The hotspots and clusters are found to co-localize with different functional genomic features, as exemplified by the associations of hotspots of middle-size CNVs with histone-modification sites, work with balancing and positive selections to meet the need for diversity in immune proteins, and facilitate the development of sensory-perception and neuroactive ligand-receptor interaction pathways in the function-sparse late-replicating genomic sequences. Genetic variants of different lengths co-localize with retrotransposons of different ages on a "long-with-young" and "short-with-all" basis. Hotspots and clusters are highly associated with tumor suppressor genes and oncogenes (p < 10), and enriched with somatic tumor CNVs and the trait- and disease-associated SNPs identified by genome-wise association studies, exceeding tenfold enrichment in clusters comprising SNPs and extra-long CNVs.

Conclusions: In conclusion, the genetic-variant hotspots and clusters represent two-edged swords that spearhead both positive and negative genomic changes. Their strong associations with complex traits and diseases also open up a potential "Common Disease-Hotspot Variant" approach to the missing heritability problem.
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http://dx.doi.org/10.1186/s40246-021-00318-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976700PMC
March 2021

Intrinsic and chemically-induced daughter number variations in cancer cell lines.

Cell Cycle 2021 Mar-Mar;20(5-6):537-549. Epub 2021 Feb 17.

Division of Life Science and Applied Genomics Center, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China.

Multipolar mitosis was observed in cancer cells under mechanical stress or drug treatment. However, a comprehensive understanding of its basic properties and significance to cancer cell biology is lacking. In the present study, live-cell imaging was employed to investigate the division and nucleation patterns in four different cell lines. Multi-daughter divisions were observed in the three cancer cell lines HepG2, HeLa and A549, but not in the transformed non-cancer cell line RPE1. Multi-daughter mother cells displayed multi-nucleation, enlarged cell area, and prolonged division time. Under acidic pH or treatment with the anti-cancer drug 5-fluorouracil (5-FU) or the phytochemical compound wogonin, multi-daughter mitoses were increased to different extents in all three cancer cell lines, reaching as high as 16% of all mitoses. While less than 0.4% of the bi-daughter mitosis were followed by cell fusion events under the various treatment conditions, 50% or more of the multi-daughter mitoses were followed by fusion events at neutral, acidic or alkaline pH. These findings revealed a "Daughter Number Variation" (DNV) process in the cancer cells, with multi-daughter divisions in Stage 1 and cell fusions leading to the formation of cells containing up to five nuclei in Stage 2. The Stage 2-fusions were inhibited by 5-FU in A549 and HeLa, and by wogonin in A549, HeLa and HepG2. The parallel relationship between DNV frequency and malignancy among the different cell lines suggests that the inclusion of anti-fusion agents exemplified by wogonin and 5-FU could be beneficial in combinatory cancer chemotherapies.
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http://dx.doi.org/10.1080/15384101.2021.1883363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018351PMC
February 2021

Fibrillin-1-enriched microenvironment drives endothelial injury and vascular rarefaction in chronic kidney disease.

Sci Adv 2021 Jan 27;7(5). Epub 2021 Jan 27.

State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Endothelial cell injury leading to microvascular rarefaction is a characteristic feature of chronic kidney disease (CKD). However, the mechanism underlying endothelial cell dropout is poorly defined. Here, we show a central role of the extracellular microenvironment in controlling endothelial cell survival and proliferation in CKD. When cultured on a decellularized kidney tissue scaffold (KTS) from fibrotic kidney, endothelial cells increased the expression of proapoptotic proteins. Proteomics profiling identified fibrillin-1 (FBN1) as a key component of the fibrotic KTS, which was up-regulated in animal models and patients with CKD. FBN1 induced apoptosis of endothelial cells and inhibited their proliferation in vitro. RNA sequencing uncovered activated integrin αβ/transforming growth factor-β signaling, and blocking this pathway abolished FBN1-triggered endothelial injury. In a mouse model of CKD, depletion of FBN1 ameliorated renal fibrotic lesions and mitigated vascular rarefaction. These studies illustrate that FBN1 plays a role in mediating vascular rarefaction by orchestrating a hostile microenvironment for endothelial cells.
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http://dx.doi.org/10.1126/sciadv.abc7170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840119PMC
January 2021

Eating-out behaviors, associated factors and associations with obesity in Chinese school children: findings from the childhood obesity study in China mega-cities.

Eur J Nutr 2021 Jan 13. Epub 2021 Jan 13.

Global Health Institute, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Purpose: Eating-out and prevalence of obesity/overweight have been rising rapidly in China in the past two decades due to social economic developments. This study examined Chinese school children's eating-out behaviors and associated factors, including their association with obesity during a 3-year follow.

Methods: Data were collected from 3313 primary and middle school children aged 7-16 years in five mega-cites across China in 2015, 2016 and 2017, in an open cohort study. Eating-out behaviors were assessed using questionnaire survey. The Chinese age-sex-specific body mass index (BMI) cutoffs were used defining child overweight/obesity (combined) and obesity; central obesity was defined as WHtR ≥ 0.48. Mixed effect models examined associations between child eating-out behaviors and BMI, overweight and obesity in this longitudinal data, adjusting for other covariates.

Results: About 80.1% of the children reported having eaten out ≥ 1 times/week over the past 3 months; 46.7% and 70.9% chose Western- and Chinese-style food when ate out, respectively. Meanwhile, 29.8% of them were overweight/obese, 12.7% were obese and 20.1% had central obesity. Child eating-out behaviors were positively associated with parents' eating-out behaviors (p < 0.05). Boys were more likely to choose Western-style food than girls (OR 1.27; 95% CI 1.09-1.48) when eating out. Compared to non-overweight/obese children, those being overweight/obese at baseline were less likely to eat out dining on Western-style food during the follow-up.

Conclusion: Eating-out is common among school children in major cities in China, but with considerable differences across groups. Children's weight status was associated with eating-out behaviors.
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http://dx.doi.org/10.1007/s00394-020-02475-yDOI Listing
January 2021

Matrix metalloproteinase-10 protects against acute kidney injury by augmenting epidermal growth factor receptor signaling.

Cell Death Dis 2021 01 12;12(1):70. Epub 2021 Jan 12.

State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase involved in regulating a wide range of biologic processes, such as apoptosis, cell proliferation, and tissue remodeling. However, the role of MMP-10 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we show that MMP-10 was upregulated in the kidneys and predominantly localized in the tubular epithelium in various models of AKI induced by ischemia/reperfusion (IR) or cisplatin. Overexpression of exogenous MMP-10 ameliorated AKI, manifested by decreased serum creatinine, blood urea nitrogen, tubular injury and apoptosis, and increased tubular regeneration. Conversely, knockdown of endogenous MMP-10 expression aggravated kidney injury. Interestingly, alleviation of AKI by MMP-10 in vivo was associated with the activation of epidermal growth factor receptor (EGFR) and its downstream AKT and extracellular signal-regulated kinase-1 and 2 (ERK1/2) signaling. Blockade of EGFR signaling by erlotinib abolished the MMP-10-mediated renal protection after AKI. In vitro, MMP-10 potentiated EGFR activation and protected kidney tubular cells against apoptosis induced by hypoxia/reoxygenation or cisplatin. MMP-10 was colocalized with heparin-binding EGF-like growth factor (HB-EGF) in vivo and activated it by a process of proteolytical cleavage in vitro. These studies identify HB-EGF as a previously unrecognized substrate of MMP-10. Our findings also underscore that MMP-10 can protect against AKI by augmenting EGFR signaling, leading to promotion of tubular cell survival and proliferation after injury.
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http://dx.doi.org/10.1038/s41419-020-03301-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803968PMC
January 2021

Racial-Ethnic Disparities in Obesity and Biological, Behavioral, and Sociocultural Influences in the United States: A Systematic Review.

Adv Nutr 2021 Jan 11. Epub 2021 Jan 11.

Systems-Oriented Global Childhood Obesity Intervention Program, Fisher Institute of Health and Well-being, College of Health, Ball State University, Muncie, IN, USA.

For a comprehensive understanding of high-level obesity in the USA, we studied the trends of obesity prevalence since 2007, and related biological, behavioral, and sociocultural factors in obesity racial/ethnic disparities. We searched PubMed, Embase, and national data archives for the studies using national survey data and published in English from January 1, 2007 to September 11, 2020. Forty-seven studies met the inclusion criteria and were systematically reviewed. After a short leveling-off during 2009-2012, the US national prevalence of obesity has steadily increased. Although women had higher racial/ethnic disparities in obesity and severe obesity than men, it decreased due to the significant drop in non-Hispanic black (NHB) women in the last 10 y. However, obesity and severe obesity prevalence increased in Mexican-American (MA) men, MA boys, and MA girls and became similar to or surpassing NHB groups. Substantial racial/ethnic disparities remained in the past decade. Even at the same level of BMI, MAs and non-Hispanic Asians had a higher percent of body fat and metabolic syndrome than other ethnic/racial groups. NHB's cultural preference for a large body significantly associated weight misperception and lower weight control practices. In addition to socioeconomic status, health behaviors, neighborhood environments, and early childhood health factors explained substantial racial/ethnic differences in obesity. Differences in biological, behavioral, and sociocultural characteristics should be considered in future public health intervention efforts to combat obesity in the USA.
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http://dx.doi.org/10.1093/advances/nmaa162DOI Listing
January 2021

Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Patients With Previous Direct-Acting Antiviral Therapy Failures: A Meta-Analysis.

Front Med (Lausanne) 2020 3;7:592472. Epub 2020 Dec 3.

Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Since a greater number of hepatitis C virus (HCV) patients have access to direct-acting antiviral (DAA) based therapies, the number of patients not properly responding to prior DAA regimens is increasing. The objective of this comprehensive analysis was to assess the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in HCV patients who experienced previous DAA therapy failures. Bibliographic databases were systematically searched for relevant articles published by November 2020. The main endpoints were sustained viral response after 12 weeks (SVR12), adverse events (AEs; any grade) and severe adverse events (SAEs). Publication bias assessment was performed using funnel plots and the Egger's test. Fourteen studies consisting of a total of 1,294 subjects were included in this study and the pooled estimate of SVR12, AEs and SAEs rates were 96.8% (95%CI: 95.1-98.2), 47.1% (95%CI: 26.0-69.3), and 1.8% (95%CI: 0.7-3.4), respectively. Subgroup analysis showed that pooled SVR12 rates were 97.9% (95%CI: 96.7-98.9) for Japan and 91.1% (95%CI: 87.3-94.3) for the United States; 95.8% (95%CI: 93.9-97.4) for genotype (GT)1 and 100.0% (95%CI: 99.6-100.0) for GT2; 95.3% (95%CI: 92.4-97.2) for cirrhosis and 96.3% (95%CI: 94.2-97.7) for non-cirrhosis cases. There was no publication bias included this study. This comprehensive analysis revealed that GLE/PIB is an effective and secure retreatment option for patients who did not optimally respond to DAA treatment, especially the Asian population with GT1-2.
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http://dx.doi.org/10.3389/fmed.2020.592472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793883PMC
December 2020

Early truncation of the N-terminal variable region of EYA4 gene causes dominant hearing loss without cardiac phenotype.

Mol Genet Genomic Med 2021 01 10;9(1):e1569. Epub 2020 Dec 10.

Precision Medicine Center, Academy of Medical Science, Zhengzhou University, Zhengzhou, China.

Background: Autosomal dominant hearing loss (ADHL) accounts for about 20% of all hereditary non-syndromic HL. Truncating mutations of the EYA4 gene can cause either non-syndromic ADHL or syndromic ADHL with cardiac abnormalities. It has been proposed that truncations of the C-terminal Eya domain lead to non-syndromic HL, whereas early truncations of the N-terminal variable region cause syndromic HL with cardiac phenotype.

Methods: The proband and all the other hearing impaired members of the family underwent a thorough clinical and audiological evaluation. The cardiac phenotype was examined by ECG and echocardiography. Their DNA was subjected to target exome sequencing of 129 known deafness genes. The sequencing data were analyzed and the candidate variants were interpreted following the ACMG guidelines for clinical sequence interpretation. The effect of candidate variant on EYA4 gene expression was assessed by quantitative PCR and western blot of gene production in blood.

Results: We report a Chinese family cosegregating post-lingual onset, progressive ADHL with a novel nonsense mutation NM_004100.4:c.543C>G (p.Tyr181Ter) of EYA4. Two affected members show no cardiac abnormalities at least until now revealed by electrocardiography and echocardiography. The overall expression level of the EYA4 gene in the proband was lower than that in his unaffected relative.

Conclusion: This report expands the mutational spectrum of the EYA4 gene and highlights the fact that more data are needed to elucidate the complex genotype-phenotype correlation of EYA4 mutations.
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http://dx.doi.org/10.1002/mgg3.1569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963430PMC
January 2021

A 3-year Longitudinal Study of Pocket Money, Eating Behavior, Weight Status: The Childhood Obesity Study in China Mega-Cities.

Int J Environ Res Public Health 2020 12 7;17(23). Epub 2020 Dec 7.

Global Health Institute, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710000, China.

The associations between children's pocket money and their eating behaviors and weight status have not been examined using longitudinal data in China. Examined child and parental factors associated with children's pocket money, and longitudinal effects of pocket money on children's eating behaviors and weight status. Data were collected in 2015, 2016, and 2017 from 3261 school-age children and their parents in mega-cities across China (Beijing, Shanghai, Nanjing, Xi'an, Chengdu). Children's weight, height, and waist circumference were measured; pocket money and eating behaviors were self-reported. Mixed effect models were used. Older children received more pocket money than younger children (incident rate ratio (IRR) = 1.21, 95% confidence interval (CI): 1.15, 1.26). Fathers gave their children more pocket money than mothers did (IRR = 1.22, 95% CI: 1.16, 1.30). Children with fathers having ≥ college education received more pocket money than the others did (IRR = 1.20, 95% CI: 1.04, 1.40). Some nutrition-related parenting behaviors and attitude were also associated with children's pocket money. Compared with children receiving no weekly pocket money, those having 1-10 or 10-30 or >30-yuan weekly pocket money were 12.0-136% more likely to consume unhealthy foods and were 66-132% more likely to be overweight or obese. Some child and parental factors were associated with children's pocket money, which increased risks of having unhealthy eating behaviors and being overweight and obese.
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http://dx.doi.org/10.3390/ijerph17239139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729809PMC
December 2020

A 3-year longitudinal study of the association of physical activity and sedentary behaviours with childhood obesity in China: The childhood obesity study in China mega-cities.

Pediatr Obes 2021 Jun 22;16(6):e12753. Epub 2020 Nov 22.

Department of Health Administration and Policy, College of Health and Human Services, George Mason University, Fairfax, Virginia, USA.

Objectives: Examine school children's physical activity (PA) and sedentary behaviours (SB) during 2015 to 2017 in China, and study their associations with children's weight status and relevant gender differences.

Methods: This open cohort study included students from five major cities (Beijing, Shanghai, Xi'an, Nanjing, and Chengdu) across China. Data were collected from students in 2015, 2016, and 2017 (n = 5535) and from their parents and school personnel. Children's weight, height, and waist circumference were measured. SB and PA factors were evaluated using questionnaires. Mixed-effects models examined the relationship between weight status and PA-/SB-associated factors using this longitudinal data.

Results: These children had high rates of obesity (12.4%, 95% CI 11.6%-13.3%) and central obesity (28.1%, 95% CI 26.9%-29.3%) during 2015 to 2017. Boys were more likely to have obesity than girls (16.5% vs 8.4%, respectively) as well as centrally obesity (36.3% vs 19.8%, respectively) and spent more time in screen viewing than girls (hours/week ± SD: 2015, 1.8 ± 2.5 vs 1.5 ± 2.0; 2016, 2.0 ± 2.4 vs 1.8 ± 2.5; 2017, 1.7 ± 2.3 vs 1.4 ± 2.1 hours/week). Those who walked <5 minutes on their average daily walk to school were more likely to have obesity (OR: 1.96, 95% CI 1.03-3.73) than those who spent ≥15 minutes on walking to school. When stratified by gender, this higher risk was only observed in girls (OR: 3.01, 95% CI 1.09-8.35). Children who spent more time in screen viewing were more likely to have obesity (OR: 1.13, 95% CI 1.06-1.21) and have central obesity (OR: 1.05, 95% CI 1.02-1.09). The association for obesity was consistent in boys and girls (boys, OR: 1.15, 95% CI 1.05-1.25; girls, OR: 1.12, 95% CI 1.00-1.24).

Conclusions: More screen time and less walking time were risk factors for developing obesity in urban Chinese children. The associations varied by gender.
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http://dx.doi.org/10.1111/ijpo.12753DOI Listing
June 2021

Linking Challenge-Hindrance Stressors to Safety Outcomes and Performance: A Dual Mediation Model for Construction Workers.

Int J Environ Res Public Health 2020 10 27;17(21). Epub 2020 Oct 27.

Faculty of Management and Economics, Kunming University of Science and Technology, Kunming 650500, China.

Occupational stressors have long been recognized as an important risk factor for injury accidents. The mechanisms underlying the relationships among challenge stressors, hindrance stressors, safety outcomes (occupational injuries), emotional experiences (attentiveness), and job performance (task performance) were investigated from the perspectives of the challenge-hindrance stress model and the conservation of resources theory. This study collected multi-source data over two timepoints for 105 safety supervisors and 379 construction workers in China. Results revealed that both challenge and hindrance stressors were positively related to occupational injuries, but only challenge stressors were positively associated with attentiveness. In addition, occupational injuries mediated the relationship between both challenge and hindrance stressors and task performance, while attentiveness mediated only the relationship between challenge stressors and task performance. These findings contribute to our knowledge of stress management in the construction project context and provide recommendations for stress management for front-line workers at construction sites.
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http://dx.doi.org/10.3390/ijerph17217867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663220PMC
October 2020

Hydroxysafflor Yellow A Exerts Anti-Inflammatory Effects Mediated by SIRT1 in Lipopolysaccharide-Induced Microglia Activation.

Front Pharmacol 2020 11;11:1315. Epub 2020 Sep 11.

Encephalopathy Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

Abnormal microglia activation causes sever neuroinflammation, contributing to the development of many diseases, yet the mechanism remains incompletely unknown. In current study, we identified that Hydroxysafflor yellow A (HYA), a chalcone glycoside derived from effectively attenuates LPS-induced inflammation response in primary microglia regulating the expression of inflammatory genes and remodeling the polarization of microglia. We also reported the effects of HYA on improving lipopolysaccharide (LPS)-stimulated mitochondrial dysfunction and oxidative stress for the first time. Interestingly, we found that HYA could serves as an effective SIRT1 activator. Deficiency of SIRT1 abrogates the protective effects of HYA against LPS-induced response. Overall, our data suggest HYA, a novel SIRT1 activator, could serve as an effective approach to treat LPS-induced neurodegenerative diseases.
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http://dx.doi.org/10.3389/fphar.2020.01315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517830PMC
September 2020

Characteristics of HIV-1 env genes from Chinese chronically infected donors with highly broad cross-neutralizing activity.

Virology 2020 12 28;551:16-25. Epub 2020 Sep 28.

State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. Electronic address:

Knowledge about the special characteristics of HIV-1 envelope (env) glycoproteins in rare individuals developing >90% neutralization breadth in Chinese subtype B' slow progressors may provide insights for vaccine design against local viruses. We performed a cross-sectional analysis on 7 samples. We tested the neutralization breadth and geometric mean ID50 titers (GMTs) of these samples, and divided them into hBCN+ and hBCN- group according to whether their neutralization breadth >90%. We obtained env sequences in these samples through single genome amplification (SGA) assay. By comparing with hBCN-, subtype B chronically infected group (B-SP), and Chinese subtype B group (B-Database), we analyzed the characteristics of the env sequences of hBCN+ group. Longer V1 and V4 regions with more glycosylation sites were found in hBCN+ samples compared to hBCN- samples. Further analysis compared to B-SP and B-Database showed that hBCN+ group exhibited unique extra-long V1 region containing higher proportion of N-glycan sites and additional cysteines.
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http://dx.doi.org/10.1016/j.virol.2020.08.012DOI Listing
December 2020

PARK2 promotes mitochondrial pathway of apoptosis and antimicrotubule drugs chemosensitivity degradation of phospho-BCL-2.

Theranostics 2020 8;10(22):9984-10000. Epub 2020 Aug 8.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Neoadjuvant chemotherapy has become the standard treatment of locally advanced breast cancer. Antimicrotubule drugs and DNA-damaging drugs are the most popular medicines used for neoadjuvant chemotherapy. However, we are unable to predict which chemotherapeutic drug will benefit to an individual patient. PARK2 as a tumor suppressor in breast cancer has been reported. While the role of PARK2 in chemotherapy response remains unknown. In this study, we explore the impact of PARK2 on chemosensitivity in breast cancer. PARK2 expression in breast cancer patients with different neoadjuvant chemotherapeutic regimens was studied using immunohistochemistry. Data was correlated to disease-free survival (DFS), overall survival and pathologic complete response (pCR). The functional roles of PARK2 were demonstrated by a series of and experiments. Including mass spectrometry, Co-immunoprecipitation, isolation of subcellular fractionation, fluorescence microscopy, ubiquitination assay and luciferase analyses. Highly expressed PARK2 predicted better response to antimicrotubule drugs-containing regimen associated with higher rate of pathologic complete response (pCR). In contrast, PARK2 expression did not predict response to the DNA-damaging drugs regimen. Following antimicrotubule drugs treatment, levels of PARK2 was upregulated due to the repression of STAT3-mediated transcriptional inhibition of PARK2. Moreover, overexpression of PARK2 specifically rendered cells more sensitive to antimicrotubule drugs, but not to DNA-damaging drugs. Depletion of PARK2 enhanced resistance to antimicrotubule drugs. Mechanistically, PARK2 markedly activated the mitochondrial pathway of apoptosis after exposure to antimicrotubule drugs. This occurred through downregulating the antiapoptotic protein, phospho-BCL-2. BCL-2 phosphorylation can be specifically induced by antimicrotubule drugs, whereas DNA-damaging drugs do not. Notably, PARK2 interacted with phospho-BCL-2 (Ser70) and promoted ubiquitination of BCL-2 in an E3 ligase-dependent manner. Hence, PARK2 significantly enhanced the chemosensitivity of antimicrotubule drugs both , while loss-of-function PARK2 mutants did not. Our findings explained why PARK2 selectively confers chemosensitivity to antimicrotubule drugs, but not to DNA-damaging drugs. In addition, we identified PARK2 as a novel mediator of antimicrotubule drugs sensitivity, which can predict response of breast cancer patients to antimicrotubule drugs-containing regime.
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http://dx.doi.org/10.7150/thno.47044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481404PMC
May 2021

Mucosal-associated invariant T cells in hepatitis B virus-related liver failure.

World J Gastroenterol 2020 Aug;26(31):4703-4717

Nantong Institute of Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong 226006, Jiangsu Province, China.

Background: Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear.

Aim: To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure.

Methods: We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People's Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay.

Results: Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 5.19 ± 1.27%, 0.0001; number: 5.47 ± 4.93 84.43 ± 19.59, 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 2.04 ± 0.95%, 0.0001) and in cell count (17.24 ± 8.56 7.41 ± 4.99, 0.0001). The proportion (2.29 ± 1.01 1.58 ± 1.38%, 0.05) and number (7.30 ± 5.70 2.94 ± 1.47, 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan-Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival ( 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL 17.76 ± 2.79 pg/mL, 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL 362.99 ± 109.64 pg/mL, 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs.

Conclusion: Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.
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http://dx.doi.org/10.3748/wjg.v26.i31.4703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445862PMC
August 2020

Lactose-Induced Chronic Diarrhea Results From Abnormal Luminal Microbial Fermentation and Disorder of Ion Transport in the Colon.

Front Physiol 2020 29;11:877. Epub 2020 Jul 29.

Digestive Laboratory of Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Diarrhea is one of the major abdominal symptoms in lactose-intolerant subjects. The changes in the large intestinal luminal environment and disorder of the epithelial ion transport in lactose-induced diarrhea remain unclear. The present study aimed to investigate the effect of an incremental high-lactose diet (IHLD, 30%/40%/50%) on luminal microbiota, microbiota-derived metabolite concentrations and colonic ion transport. Gut microbiota were analyzed by 16S rRNA amplicon sequencing and the concentration of SCFAs by gas chromatography, galactose, lactose and lactic acid through assay kit; Ussing chamber was performed to detect basal and stimulated ion transport; The expression and location of SCFA transporters, the Na-H exchanger 3(NHE3), cystic fibrosis transporter regulater (CFTR) and NKCC1 in the colon mucosa were analyzed by western and immunostaining. The concentrations of lactose, galactose and lactic acid of the cecal content were markedly increased ( < 0.01) and SCFA concentration was significantly decreased ( < 0.01). This was associated with depletion of the Lachnospiraceae NK4A136 group and Ruminococcaceae UCG-005 and increased relative abundance of Lactobacillus, escherichia-shigella and megamonas in the cecal microbiota. The expression of monocarboxylate transporter 1 was decreased in the colonic mucosa of the IHLD group. Low NHE3 expression and phosphorylation levels, and decreases in delta basal short circuit current after apical Na removal in the colonic mucosa of the IHLD group contributed to Na accumulation in the lumen and decrease stimulated Cl secretion with low CFTR and NKCC1 expression would compensate for water and electrolyte loss during the diarrhea process. These results indicated that the persistence of the diarrhea state was maintained by abnormal colonic microbiota fermentation leading to high concentrations of lactose, galactose and lactic acid and low SCFAs in the lumen, and decreased Na absorption with the low NHE3 expression and phosphorylation levels.
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http://dx.doi.org/10.3389/fphys.2020.00877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403511PMC
July 2020

Effects of 'yam gruel' on the cognitive function of diabetic rats with focal cerebral ischemia-reperfusion injury via the gut-brain axis.

J Integr Neurosci 2020 Jun;19(2):273-283

School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, 350122, P. R. China.

Focal cerebral ischemia-reperfusion injury is closely related to hyperglycemia and gut microbiota imbalance, while gut microbiota contributes to the regulation of brain function through the gut-brain axis. Previous studies in patients with diabetes have found that 'yam gruel' is a classic medicated diet made from , increases the content of , regulates oxidative stress, and reduces fasting blood glucose levels. The research reported here investigated the effects of 'yam gruel' on the cognitive function of streptozotocin-induced diabetic rats with focal cerebral ischemia-reperfusion injury and explored the mechanism underlying the role of the gut-brain axis in this process. 'Yam gruel' was shown to improve cognitive function as indicated by increased relative content of probiotic bacteria, and short-chain fatty acids in the intestinal tract and cerebral cortex reduced oxidative stress and inflammatory response and promotion of the expression of neurotransmitters and brain-derived neurotrophic factor. Thus, it is concluded that 'yam gruel' has a protective effect on cognitive function via a mechanism related to the gut-brain axis.
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http://dx.doi.org/10.31083/j.jin.2020.02.69DOI Listing
June 2020

Highly Recurrent Copy Number Variations in Associated With Schizophrenia and Premenstrual Dysphoric Disorder.

Front Psychiatry 2020 30;11:572. Epub 2020 Jun 30.

Applied Genomics Center and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Division of Life Science, Hong Kong, Hong Kong.

Objective: Although single-nucleotide polymorphisms in , the gene encoding for GABA receptors β2 subunit, have been associated with schizophrenia (SCZ), it is unknown whether there is any association of copy number variations (CNVs) in this gene with either SCZ or premenstrual dysphoric disorder (PMDD).

Methods: In this study, the occurrences of the recurrent CNVs esv2730987 in Intron 6 and nsv1177513 in Exon 11 of in Chinese and German SCZ, and Chinese PMDD patients were compared to controls of same ethnicity and gender by quantitative PCR (qPCR).

Results: The results demonstrated that copy-number-gains were enriched in both SCZ and PMDD patients with significant odds ratios (OR). For combined-gender SCZ patients versus controls, about two-fold increases were observed in both ethnic groups at both esv2730987 (OR = 2.15, 5.32E-4 in Chinese group; OR = 2.79, 8.84E-3 in German group) and nsv1177513 (OR = 3.29, 1.28E-11 in Chinese group; OR = 2.44, 6.17E-5 in German group). The most significant copy-number-gains were observed in Chinese females at nsv1177513 (OR = 3.41), and German females at esv2730987 (OR=3.96). Copy-number-gains were also enriched in Chinese PMDD patients versus controls at esv2730987 (OR = 10.53, 4.34E-26) and nsv1177513 (OR = 2.39, 3.19E-5).

Conclusion: These findings established for the first time the association of highly recurrent CNVs with SCZ and PMDD, suggesting the presence of an overlapping genetic basis with shared biomarkers for these two common psychiatric disorders.
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http://dx.doi.org/10.3389/fpsyt.2020.00572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338560PMC
June 2020

Descent of Bacteria and Eukarya From an Archaeal Root of Life.

Evol Bioinform Online 2020 23;16:1176934320908267. Epub 2020 Jun 23.

Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.

The 3 biological domains delineated based on small subunit ribosomal RNAs (SSU rRNAs) are confronted by uncertainties regarding the relationship between Archaea and Bacteria, and the origin of Eukarya. The similarities between the paralogous valyl-tRNA and isoleucyl-tRNA synthetases in 5398 species estimated by BLASTP, which decreased from Archaea to Bacteria and further to Eukarya, were consistent with vertical gene transmission from an archaeal root of life close to through a Primitive Archaea Cluster to an Ancestral Bacteria Cluster, and to Eukarya. The predominant similarities of the ribosomal proteins (rProts) of eukaryotes toward archaeal rProts relative to bacterial rProts established that an archaeal parent rather than a bacterial parent underwent genome merger with bacteria to generate eukaryotes with mitochondria. Eukaryogenesis benefited from the predominantly archaeal (AGA) phenotype pertaining to horizontally transferred genes from other prokaryotes and expedited genome evolution via both gene-content mutations and nucleotidyl mutations. Archaeons endowed with substantial AGA activity were accordingly favored as candidate archaeal parents. Based on the top similarity bitscores displayed by their proteomes toward the eukaryotic proteomes of and , and high AGA activity, the archaea were identified as leading candidates of the archaeal parent. The archaeons and a number of bacterial species were among the foremost potential contributors of eukaryotic-like proteins to Eukarya.
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http://dx.doi.org/10.1177/1176934320908267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313328PMC
June 2020

The Diffusion of Discrete Event Simulation Approaches in Health Care Management in the Past Four Decades: A Comprehensive Review.

MDM Policy Pract 2020 Jan-Jun;5(1):2381468320915242. Epub 2020 Jun 6.

Fisher Institute of Health and Well-Being, Ball State University, Muncie, Indiana.

This study systematically examines the diffusion of the discrete event simulation (DES) approach in health services and health care management by examining relevant factors such as research areas, channels with the objective of promoting the application of DES in the health field. We examined 483 journal papers referencing this approach that were published in 230 journals during 1981 to 2014. The application of DES has extended from health service operational research evaluation to the assessment of interventions in diverse health arenas. The increase in the number of adopters (paper authors) of DES and the increase in number of related channels (journals publishing DES-related articles) are highly correlated, which suggests an increase of DES-related publications in health research. The same conclusion is reached, that is, an increased diffusion of DES in health research, when we focus on the temporal trends of the channels and adopters. The applications of DES in health research cover 22 major areas based on our categorization. The expansion in the health areas also suggests to a certain extent the rapid diffusion of DES in health research.
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http://dx.doi.org/10.1177/2381468320915242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278318PMC
June 2020