Physical frailty, genetic predisposition, and the risks of severe non-alcoholic fatty liver disease and cirrhosis: a cohort study.

BACKGROUND: Frailty, defined as a phenotype of decreased physiological reserves and diminished ability to respond to stressors, has been linked to the development of chronic diseases. Epidemiological evidence connecting frailty to non-alcoholic fatty liver disease (NAFLD) and cirrhosis risks remain sparse. We aimed to assess the longitudinal associations of frailty with the risks of severe NAFLD and cirrhosis in middle-aged to older adults and further explore the modification role of genetic risk on these associations. METHODS: This study included a total of 398 386 participants from the UK Biobank. Incident cases of severe NAFLD and cirrhosis were ascertained through linked hospital records and death registries. Frailty status was assessed by a modified version of the frailty phenotype, encompassing five key components: weight loss, tiredness, physical activity, gait speed, and grip strength. Participants were classified as pre-frailty if they met one or two of these criteria, and as frailty if they met three or more. Genetic predisposition to NAFLD and cirrhosis was estimated by genetic risk score (GRS) and further categorized into high, intermediate, and low genetic risk levels according to tertiles of GRSs. Cox proportional hazards regression model was employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for their associations. RESULTS: The mean (standard deviation) age of the study population was 56.6 (8.03) years. 214 408 (53.8%) of the participants was female; 14 924 (3.75%) of participants met the criteria for frailty, 170 498 (42.8%) for pre-frailty, and 212 964 (53.5%) for non-frailty. Over a median follow-up of 12.0 years, we documented 4439 incident severe NAFLD and 3323 incident cirrhosis cases, respectively. Compared with non-frailty, both pre-frailty (HR: 1.50; 95% CI: 1.40-1.60) and frailty (HR: 1.98; 95% CI: 1.77-2.21) were associated with increased risk of NAFLD. Similar associations were observed for cirrhosis, the corresponding HRs (95% CIs) for non-frailty, pre-frailty, and frailty were 1.00 (reference), 1.29 (1.20, 1.38), and 1.90 (1.66, 2.18). Such associations were consistent across all genetic risk levels, with no observed interactions between frailty and GRSs (all P for interactions ≥0.10). Compared with participants with frailty and a low level of genetic risk, the greatest risk increasement in developing severe NAFLD (HR: 3.36; 95% CI: 2.83-3.99) and cirrhosis (HR: 2.81; 95% CI: 2.29-3.44) was both observed in those with frailty and a high level of genetic risk. CONCLUSIONS: Our findings indicate that frailty is a significant predictor of severe NAFLD and cirrhosis, irrespective of genetic predisposition.

Sugar types, genetic predictors of the gut microbiome, and the risk of chronic kidney disease: a prospective cohort study.

Background: Emerging studies suggest that focusing on the intake of specific types or sources of sugars may yield greater benefits in preventing chronic kidney disease (CKD). Objective: We aimed to investigate the associations between free and non-free sugar intakes and CKD risk as well as the potential sugar type-gut microbiome interactions. Methods: A total of 138 064 participants from the UK Biobank were included in this prospective study. The free and non-free sugar intakes were assessed using repeated web-based 24-hour dietary recalls. A cause-specific competing risk model was used to estimate hazard ratios (HRs) and the corresponding confidence intervals (CIs) of incident CKD, treating deaths before incident CKD as competing events. Results: During a median follow-up of 10.5 years, 2,923 participants (2.1%) developed CKD. The free sugar intake was positively associated with the risk of CKD (HRquartile 4 vs. quartile 1 = 1.32, 95% CI = 1.18, 1.47), with a nonlinear relationship (P for nonlinearity = 0.01, the risk increased rapidly after free sugars made up 10% of the total energy). The non-free sugar intake was inversely associated with CKD risk (HRquartile 4 vs. quartile 1 = 0.68, 95% CI = 0.60, 0.77), with an L-shaped nonlinear curve (p for nonlinearity = 0.01, the turning point was at 13.5% of the total energy). We found that the associations between free sugar and non-free sugar intakes and CKD risk were more pronounced in participants with high genetically predicted gut microbial abundance. Furthermore, a significant interaction was observed between the genetically predicted gut microbial abundance and non-free sugar intake (P for interaction = 0.04). Conclusion: A higher intake of free sugars was associated with an elevated risk of CKD, whereas a higher intake of non-free sugars was associated with a reduced risk of CKD. The impact of free sugar intake and non-free sugar intake may be modified by the gut microbial abundance.

Meta-analysis of the relationship between Dietary Inflammatory Index and esophageal cancer risk.

INTRODUCTION: Diet is closely related to the occurrence of esophageal cancer (EC). Dietary Inflammatory Index (DII), as a novel index that describes the inflammatory potential of diet, was widely used in many diseases. OBJECTIVE: To systematically analyze the relationship between DII and the risk of esophageal cancer. METHODS: We mainly searched relative studies in PubMed, Cochrane library, Web of Science, and other literature database. The random-effect model was used for meta-analysis, and subgroup analysis and sensitivity analysis were used to detect the origin of heterogeneity. RESULTS: We finally obtained 6 articles (8 studies). All studies were case-control studies which consisted of 1961 cases and 3577 controls. In this study, compared with the lowest DII category, the highest DII category had a higher risk of esophageal cancer, and the pooled odds ratio (OR) of the 8 studies were 2.54 (95% confidence interval (CI): 1.90-3.40; I = 65.7%, P = .005). Furthermore, regardless of the differences in published year, DII components, geographic location, and study quality, there was still an increased risk of esophageal cancer in the highest DII category compared with the lowest DII category. CONCLUSIONS: Our results inferred that DII was positively correlated with esophageal cancer risk and it could be used as a tool to predict the esophageal cancer risk and evaluate human health.

Association between biomass fuel use and risk of hypertension among Chinese older people: A cohort study.

BACKGROUNDS: Previous studies linking biomass fuel use to hypertension have been inconsistent. We investigated the association between biomass fuel use and the risk of hypertension and blood pressure measures in older Chinese people. METHODS: The prospective cohort study of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) included participants aged 65 years and older in 2011/2012 who were followed up until 2014 in 23 provinces in China. We explored the association between biomass fuel use and hypertension using the Cox proportional hazards model and examined the relationship of biomass fuel use with blood pressure measures using the generalized estimating equation. Additionally, we examined the effect of switching cooking fuels on hypertension during the follow-up. RESULTS: Among 3754 participants who were without hypertension at baseline, the mean age was 86 years old, and 47.5% of participants were men. Reported use of biomass fuel for cooking (50.2%) was associated with a higher risk of hypertension (incidence rate (IR) per 100 person-years: 13.15 versus 12.99, hazard ratio (HR) = 1.15, 95% confidence interval (CI) = 1.01-1.31). Biomass fuel use was related to systolic blood pressure (SBP) (ß 1.10 mmHg, 95% CI: 0.48-1.72), diastolic blood pressure (DBP) (ß 1.02 mmHg, 95% CI: 0.61-1.43) and mean arterial pressure (MAP) (ß 1.03 mmHg, 95% CI: 0.63-1.43) elevation. Compared with persistent clean fuel users, participants who reported switching from clean to biomass fuels for cooking had a noticeably higher risk of hypertension (IR per 100 person-years: 14.27 versus 12.81, HR 1.49, 95% CI: 1.16-1.90) and higher SBP (3.71 mmHg), DBP (2.44 mmHg) and MAP (2.86 mmHg). Interaction and stratified analyses showed greater effect estimates of SBP and MAP in the oldest oldpeople (≥85). CONCLUSIONS: The use of biomass fuel for cooking was associated with greater hypertension risk, and the risk may be higher among those who switched from clean fuels to biomass fuels in the Chinese elderly population. Biomass fuel use was associated with a statistically significant but small absolute increase in blood pressure measures.

Interaction between CYP1A1/CYP17A1 polymorphisms and parental risk factors in the risk of hypospadias in a Chinese population.

Hypospadias (HS) is a common congenital malformation of the genitourinary tract in males and its etiology is viewed as multifactorial, and studies about gene-environment interaction in the etiology of HS are rare. A total of 152 cases and 151 controls were selected in the present study. Information before and during pregnancy from questionnaires finished by mothers of subjects were extracted, and the relating data were analyzed to determine the risk factors of HS. Meanwhile, maternal genomic DNA was genotyped for the single nucleotide polymorphisms (SNPs) of CYP1A1 rs1048943 and CYP17A1 rs4919686. Results of multivariable logistic regression analyses showed that several factors were associated with hypospadias risk. Analysis of the distributions of SNPs in CYP1A1 and CYP17A1 genes showed that the mutant genotype CC (OR = 4.87) of CYP1A1 rs1048943, and mutant genotype CC (OR = 5.82), recessive genotype AC + CC (OR = 2.17) and allele C (OR = 1.77) of CYP17A1 rs4919686 significantly increased the risk of HS. In addition, the additive gene-environment interactions were also found in several models. Several maternal risk factors that are associated with HS risk can interact with CYP1A1/CYP17A1 polymorphisms, which lead to infants vulnerable to occurrence of HS in Chinese populations.

Acute corticosterone treatment elicits antidepressant-like actions on the hippocampal 5-HT and the immobility phenotype.

Corticosterone (CORT) has long been shown to modulate 5-HT system, and to alter hippocampal functions in various physiological and pathological conditions. However, CORT-elicited changes in the hippocampal 5-HT transmission and the immobility phenotype had not been fully addressed. The current study sought to explore effects of acute CORT subcutaneously injected at 10, 20, 40 mg/kg on the extracellular 5-HT in the hippocampus and the immobility time in male CD-1 mice. Following an injection of CORT or vehicle, time course of the extracellular 5-HT in the hippocampal CA3 was determined using in vivo microdialysis. The immobility time was measured at 0 min, 60 min, 120 min, 180 min in the forced swimming test (FST) and the tail suspension test (TST), respectively. Results showed that the vehicle, used to dissolve CORT, did not affect the dialysate 5-HT, nor the immobility time, by comparing the pre- and post-injection. CORT was found to dose-dependently increase the dialysate 5-HT and decrease the immobility time when compared to their vehicle-treated controls. The peak increase in the dialysate 5-HT and the decrease in the immobility time were both obtained at the 120 min following the CORT injection. Furthermore, a negative correlation was detected between the immobility time and the peak increase in the dialysate 5-HT. Our results indicated that acute CORT injection elicits antidepressant-like actions on the hippocampal 5-HT and the immobility time. The study suggested that hippocampal 5-HT responses may be one of the neurochemical bases for the immobility phenotype following CORT injection.

Effect of low income on health-related quality of life: a cross-sectional study in northeast China.

Following the dramatic socioeconomic transition since the 1980s in China, some people became unemployed and experienced a significant drop in income. The aim of this study was to assess the effects of low income on health-related quality of life (HRQOL) among the population in northeast China. A total of 5100 individuals in northeast China were randomly sampled and investigated using the 36-item Short-Form Health Survey (SF-36) from November 2005 to October 2006. According to the monthly per capita income level, the population was divided into different groups for analysis. Multiple linear regressions showed that low income, older age, disease, and unemployment were the important factors that could lead to worse HRQOL. Covariance analysis showed that there were significant differences in HRQOL scores among the subgroups of the low-income population. When the income level increased, HRQOL scores improved. This study could provide valuable information for planning integrated economic and public health policies to improve the health of people living in poverty.

An urban neo-poverty population-based quality of life and related social characteristics investigation from northeast China.

OBJECTIVE: To investigate quality of life (QOL) and related characteristics among an urban neo-poverty population in northeast China, and to compare this population with a traditional poverty cohort. DESIGN: The research was a cross-sectional survey executed from June 2005 to October 2007, with a sample of 2940 individuals ages 36 to 55 in three different industrial cities of northeast China. Data were collected on QOL status and sociodemographic characteristics. QOL was assessed using the 36-item Short Form Health Survey (Chinese version). Multiple regression analysis was employed to analyze association between sociodemographic variables and QOL. RESULTS: The scores for QOL in the neo-poverty group were higher than those in the traditional poverty group, but lower than those in the general population. When the neo-poverty population was divided into two subgroups by age, 36-45 years and 46-55 years, the differences in QOL scores were not significant. However, there were significant differences in several dimensions between two subgroups according to unemployment time (<5 years and >5 years). Additionally, stepwise regression analysis indicated that disease burden, including disease and medical expenditures, was a common risk factor for declining QOL in the neo-poverty group. CONCLUSIONS: Despite some limitations, this study provides initial evidence that the QOL of the urban neo-poverty population lies between that of the general population and traditional poverty. QOL of the neo-poverty group approached QOL of the traditional poverty group with increased unemployment years. In addition to decreased income, disease burden is the most important factor influencing QOL status in urban neo-poverty.

Pyruvate prevents the inhibition of the long-term potentiation induced by amyloid-ß through protein phosphatase 2A inactivation.

Amyloid-ß (Aß) oligomers are derived from proteolytic cleavage of amyloid-ß protein precursor and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. Pyruvate has a protective effect against Aß-induced neuronal cell death in hippocampal slice cultures. However, whether pyruvate also has a protective effect against the inhibition of neuronal plasticity induced by Aß remains to be elucidated. This study examined the effect of pyruvate on the Aß-induced inhibition of LTP in the rat hippocampus. We found that pyruvate prevented the Aß-induced inhibition of LTP as strong as fostriecin, a specific protein phosphatase 2A (PP2A) inhibitor. Pyruvate prevented the Aß block of Ca(2+)/calmodulin dependent protein kinase 2 (CaMK2) autophosphorylation and the Aß-induced PP2A activation. Pyruvate, but not lactate, decreased reactive oxygen species levels in CA1 slices exposed to Aß. We propose that pyruvate could prevent the Aß-induced inhibition of LTP by the re-autophosphorylation of CaMK2 through PP2A inactivation. The reduction of reactive oxygen species production is considered to be the upstream mechanism of this observed pyruvate protection.