Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease.

BACKGROUND: Mitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored. METHODS: We extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality. RESULTS: 96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value < 8.21e - 07. The coding genes of these PTVs were mainly enriched in pathways related to lipid, fatty acid, amino acid, and carbohydrate metabolisms. The 866 PTVs were presented in 1.07% (4721) of participants. Compared with participants who did not carry any of the PTVs, the carriers had a 5.33-fold (95% CI 4.15-6.85), 2.82-fold (1.69-4.72), and 4.41-fold (3.04-6.41) increased risk for fibrosis and cirrhosis of liver, liver cancer, and liver disease-related mortality, respectively. These adverse effects were consistent across subgroups based on age, sex, body mass index, smoking status, and presence of hypertension, diabetes, dyslipidemia, and metabolic syndrome. CONCLUSIONS: Our findings revealed a significant impact of PTVs in MT-related genes on liver disease risk, highlighting the importance of these variants in identifying populations at risk of liver diseases and facilitating early clinical interventions.

Lipid metabolism mediates the association between body mass index change and bone mineral density: The Taizhou imaging study.

BACKGROUND: Limited research explores the impact of body mass index (BMI) change on osteoporosis, regarding the role of lipid metabolism. We aimed to cross-sectionally investigate these relationships in 820 Chinese participants aged 55-65 from the Taizhou Imaging Study. METHODS: We used the baseline data collected between 2013 and 2018. T-score was calculated by standardizing bone mineral density and was used for osteoporosis and osteopenia diagnosis. Multinomial logistic regression was used to examine the effect of BMI change on bone health status. Multivariable linear regression was employed to identify the metabolites corrected with BMI change and T-score. Exploratory factor analysis (EFA) and mediation analysis were conducted to ascertain the involvement of the metabolites. RESULTS: BMI increase served as a protective factor against osteoporosis (OR = 0.79[0.71-0.88], P-value<0.001) and osteopenia (OR = 0.88[0.82-0.95], P-value<0.001). Eighteen serum metabolites were associated with both BMI change and T-score. Specifically, high-density lipoprotein (HDL) substructures demonstrated negative correlations (ß = -0.08 to -0.06 and - 0.12 to -0.08, respectively), while very low-density lipoprotein (VLDL) substructions showed positive correlations (ß = 0.09 to 0.10 and 0.10 to 0.11, respectively). The two lipid factors (HDL and VLDL) extracted by EFA acted as mediators between BMI change and T-score (Prop. Mediated = 8.16% and 10.51%, all P-value<0.01). CONCLUSION: BMI gain among Chinese aged 55-65 is beneficial for reducing the risk of osteoporosis. The metabolism of HDL and VLDL partially mediates the effect of BMI change on bone loss. Our research offers novel insights into the prevention of osteoporosis, approached from the perspective of weight management and lipid metabolomics.

Disease trajectory of high neuroticism and the relevance to psychiatric disorders: A retro-prospective cohort study.

BACKGROUND: Neuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear. METHOD: Our study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome-wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism. RESULTS: The risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety-, depression-, and stress-related disorders. CONCLUSION: Neuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management.

Mobility-related brain regions linking carotid intima-media thickness to specific gait performances in old age.

BACKGROUND: Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations. METHODS: A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators. RESULTS: Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (ß = 0.129, p = 0.010) as well as gait performances related to pace (ß=-0.213, p < 0.001) and symmetry (ß = 0.096, p = 0.045). Besides, gait performances were correlated with mobility-related brain regions responsible for motor, visuospatial attention, executive control, memory, and balance (all FDR < 0.05). Notably, significant regions differed depending on the gait outcomes measured. The primary motor (41.9%), sensorimotor (29.3%), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules) (13.8%), entorhinal cortex (36.4%), and motor imagery (precuneus, parahippocampus, posterior cingulated cortex) (27.3%) mediated the association between increased carotid intima-media thickness and poorer Timed-Up-and-Go performance. For the pace domain, the primary motor (37.5%), sensorimotor (25.8%), visuospatial attention (12.3%), entorhinal cortex (20.7%), motor imagery (24.9%), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) (11.6%) acted as mediators. CONCLUSIONS: Carotid intima-media thickness is associated with gait performances, and mobility-related brain volume mediates these associations. Moreover, the distribution of brain regions regulating mobility varies in the different gait domains. Our study adds value in exploring the underlying mechanisms of gait disturbance in the aging population.

Development of a Microwave Sensor for Real-Time Monitoring of a Micro Direct Methanol Fuel Cell.

Micro direct methanol fuel cells (µDMFCs) are a promising power source for microelectronic devices and systems. As the operating state and performance of a µDMFC is generally determined by both electrochemical polarization and methanol crossover, it is important to monitor the methanol concentration in µDMFCs. Here, we design and fabricate a microwave sensor and integrate it with a µDMFC for the online detection of methanol concentration in a nonintrusive way. The sensing area is set at the bottom of the anode chamber of a µDMFC which exhibits a maximum output power density of 28.8 mW cm-2 at 30 °C. With a square ring structure, the dual-mode microwave sensor shows a sensitivity of 9.5 MHz mol-1 L. Furthermore, the importance of methanol concentration monitoring is demonstrated in the long term. A relatively smooth methanol decline curve was obtained, which indicated a normal and stable operating status of the µDMFC. Derived from real-time recording data, fuel utilization was additionally calculated as 28.5%.

Motivating factors of farmers' adaptation behaviors to climate change in China: A meta-analysis.

Adapting to climate change is critical to building sustainable and resilient agricultural systems. Understanding farmers' perceptions of climate change has become the key to the effective implementation of climate change adaptation policies. This research draws multidisciplinary attention to how farmers participate in decision-making on adaptation behaviors and provides useful insights for realizing synergies between environmental change and agricultural production. In this work, we conducted a meta-analysis of 63 quantitative studies on Chinese farmers' adaptation to climate change to assess the relationship between motivational factors and adaptation behavior. Our analysis highlights that farmers' perceptions of precipitation changes are often inaccurate; however, other psychological factors, such as perception, experience, and risk attitude, significantly positively impact their adaptation behavior. In addition, different climate regions are the main source of high heterogeneity in inter-study comparisons of climate change perception, and the effect of climate regions may therefore constitute a moderating factor that weakens the positive relationship between climate change perception and adaptive behavior. Furthermore, this study highlights the need to intervene at the household level to enhance farmers' adaptability to climate change, which includes providing support through income diversification, early warning information services, training, assistance, credit, subsidies, and other resources. In the future, research on how perception, experience, and risk interact to affect adaptive behavior should be strengthened.

Metagenomic association analysis of cognitive impairment in community-dwelling older adults.

The gut microbiota is reportedly involved in neurodegenerative disorders, and exploration of differences in the gut microbiota in different cognitive status could provide clues for early detection and intervention in cognitive impairment. Here, we used data from the Taizhou Imaging Study (N = 516), a community-based cohort, to compare the overall structure of the gut microbiota at the species level through metagenomic sequencing, and to explore associations with cognition. Interestingly, bacteria capable of producing short-chain fatty acids (SCFAs), such as Bacteroides massiliensis, Bifidobacterium pseudocatenulatum, Fusicatenibacter saccharivorans and Eggerthella lenta, that can biotransform polyphenols, were positively associated with better cognitive performance (p < 0.05). Although Diallister invisus and Streptococcus gordonii were not obviously related to cognition, the former was dominant in individuals with mild cognitive impairment (MCI), while the later was more abundant in cognitively normal (CN) than MCI groups, and positively associated with cognitive performance (p < 0.05). Functional analysis further supported a potential role of SCFAs and lactic acid in the association between the gut microbiota and cognition. The significant associations persisted after accounting for dietary patterns. Collectively, our results demonstrate an association between the gut microbiota and cognition in the general population, indicating a potential role in cognitive impairment. The findings provide clues for microbiome biomarkers of dementia, and insight for the prevention and treatment of dementia.

BMI trajectory of rapid and excessive weight gain during adulthood is associated with bone loss: a cross-sectional study from NHANES 2005-2018.

BACKGROUND: Studies have examined the effect of weight change on osteoporosis, but the results were controversial. Among them, few had looked at weight change over the life span. This study aimed to fill this gap and investigate the association between lifetime body mass index (BMI) trajectories and bone loss. METHODS: In this cross-sectional study, participants at age 50 and above were selected from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Dual-energy X-ray Absorptiometry was used to measure the bone mineral density at the femoral neck and lumbar spine. Standard BMI criteria were used, with < 25 kg/m2 for normal, 25-29.9 kg/m2 for overweight, and ≥ 30 kg/m2 for obesity. The latent class trajectory model (LCTM) was used to identify BMI trajectories. Multinomial logistic regression models were fitted to evaluate the association between different BMI trajectories and osteoporosis or osteopenia. RESULTS: For the 9,706 eligible participants, we identified four BMI trajectories, including stable (n = 7,681, 70.14%), slight increase (n = 1253, 12.91%), increase to decrease (n = 195, 2.01%), and rapid increase (n = 577, 5.94%). Compared with individuals in the stable trajectory, individuals in the rapid increase trajectory had higher odds of osteoporosis (OR = 2.25, 95% CI 1.19-4.23) and osteopenia (OR = 1.49, 95% CI 1.02-2.17). This association was only found in the lumbar spine (OR = 2.11, 95% CI 1.06-4.2) but not in the femoral neck. In early-stage (age 25-10 years ago) weight change, staying an obesity and stable weight seemed to have protective effects on osteoporosis (OR = 0.26, 95% CI 0.08-0.77) and osteopenia (OR = 0.46, 95% CI 0.25-0.84). Meanwhile, keeping an early-stage stable and overweight was related to lower odds of osteopenia (OR = 0.53, 95% CI 0.34-0.83). No statistically significant association between recent (10 years ago to baseline) weight change and osteoporosis was found. CONCLUSIONS: Rapid and excess weight gain during adulthood is associated with a higher risk of osteoporosis. But this association varies by skeletal sites. Maintaining stable overweight and obesity at an early stage may have potentially beneficial effects on bone health.

Education, neighborhood environment, and cognitive decline: Findings from two prospective cohort studies of older adults in China.

INTRODUCTION: The impacts of education on cognitive decline across different neighborhood environments (NEs) have rarely been studied. METHODS: We investigated and compared the associations between educational attainment and cognitive decline using data of 1286 participants from the Taizhou Imaging Study (TIS) and the Shanghai Aging Study (SAS). RESULTS: Compared with low-educated participants, in TIS with disadvantaged NE, high-educated participants manifested a significantly slower decline in global cognition (.062 Z score per year, P < .001), memory (.054 Z score per year, P < .05), and attention (.065 Z score per year, P < .01), whereas in SAS with advanced NE, highly educated individuals exhibited a slower decline only in attention (.028 Z score per year, P < .05). DISCUSSION: We observed the additive effect of educational attainment and NE on cognitive decline in older adults. Education is especially important for maintaining cognitive health in a disadvantaged environment.

Association between oral health and cognitive function among Chinese older adults: the Taizhou imaging study.

BACKGROUND: We aimed to investigate the association between oral health and cognitive function in a sample of older adults from a Chinese rural community. METHODS: The cross-sectional cognitive function of 677 individuals were assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). A comprehensive profile of the oral health status was evaluated by questionnaire and clinical examination. RESULTS: Multiple covariates-adjusted regression models demonstrated decayed teeth (DT) and decayed/missing/filled teeth (DMFT) were negatively associated with MoCA score (all p < 0.05). Calculus index (CI) and clinical attachment loss (CAL) were significantly associated with the lower MoCA, short-term memory and executive function score, respectively (all p < 0.05). Additionally, participants with missing teeth unrestored tend to get lower MMSE and MoCA scores (p < 0.05). The results also showed that increased DT and CI were modestly associated with higher odds of cognitive impairment (p < 0.05). CONCLUSIONS: There is an association between oral health and global cognition. Poor periodontal status was strongly associated with worse global cognition performance, especially in the short-term memory and executive domain for the aging population.

IMPACT OF PENETRATION AND IMAGE ANALYSIS IN OPTICAL COHERENCE TOMOGRAPHY ON THE MEASUREMENT OF CHOROIDAL VASCULARITY PARAMETERS.

PURPOSE: To investigate the impact of penetration and image analysis in different optical coherence tomography (OCT) instruments on the measurement of choroidal vascularity parameters. METHODS: Twenty-three healthy volunteers were imaged using two swept-source OCTs and one spectral-domain OCT. A fully automatic segmentation method based on ResNet-UNet and Niblack local threshold binarization was performed to quantify the relevant choroidal vascular parameters, including choroidal vascularity index, total choroidal volume, and luminal volume. The intraclass correlation coefficient (ICC) and coefficient of repeatability (COR) were used to analyze the repeatability and consistency of automatic and manual segmentation, respectively. RESULTS: Both swept-source OCT devices showed good consistency of luminal volume and total choroidal volume measurements (all ICC value >0.98 with COR% < 8.53%) based on manual segmentation, whereas the consistency of the spectral-domain OCT was lower (ICC value <0.60 with COR% > 40%), which was greatly improved after using the automatic algorithm (ICC value >0.99 with COR% < 4%). The repeatability of choroidal vascularity index obtained from different OCT images using manual or automatic segmentation showed good agreement (all ICC values >0.85), whereas the choroidal vascularity index measurement from the spectral-domain OCT was larger than the other two swept-source OCT devices (ICC value <0.65). CONCLUSION: For healthy youngsters, the penetration of OCT plays a role in the measurement precision for choroidal vascularity parameters, and automatic segmentation can improve the ability of choroidal boundary identification with deficient penetration, suggesting these factors need to be considered in clinical work.

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

OBJECTIVES: An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. METHODS: We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical 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: By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects. CONCLUSION: Our study revealed a Chinese population-wide phenotype-metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.

MRI-Based Investigation of Association Between Cerebrovascular Structural Alteration and White Matter Hyperintensity Induced by High Blood Pressure.

BACKGROUND: High blood pressure (BP) is a common risk factor for cerebral small vessel disease including white matter hyperintensity (WMH). Whether increased BP exacerbates WMH by impacting cerebral vascular morphologies remains poorly studied. PURPOSE: To determine the relationships among high BP, cerebrovascular morphologies, and WMH in elderly individuals. STUDY TYPE: Cohort. SUBJECTS: Eight hundred sixty-three participants (54.2% female) from the Taizhou Imaging Study without clinical evidence of neurologic disorders were included in the analyses. FIELD STRENGTH/SEQUENCE: 3.0 T; time-of-flight magnetic resonance angiography (TOF MRA); T2 fluid-attenuated inversion recovery (FLAIR); T1 magnetization-prepared rapid gradient-echo; gradient echo T2*-weighted; diffusion tensor imaging; pulsed arterial spin labeling. ASSESSMENT: Cerebrovascular morphologic measurements were quantified based on the TOF MRA images, including vessel density, radius, tortuosity, and branch number. WMH lesion volumes (WMHV) and WMH lesion counts (WMHC) were calculated automatically based on the T2 FLAIR images. STATISTICAL TESTS: Multivariable linear regression analysis and path analysis with a linear single-mediator model were employed. A P value <0.05 was considered statistically significant. RESULTS: Higher BP, especially diastolic BP, was significantly correlated with lower cerebrovascular density (ß = -104) and lower branch numbers (ß = -0.02). Although decreased tortuosity (ß = -1.25) and increased radius (ß = 93.8) were correlated with BP, no significant relationship of tortuosity (ß = -4.6 × 10-4 , P = 0.58) or radius (ß = 0.03, P = 0.08) with BP in small vessels was found. The proportion of small vessels decreased as BP increased (SBP: ß = -6.6 × 10-4 ; DBP: ß = -9.0 × 10-4 ). Similarly, increased WMHV and WMHC were associated with decreased vessel density (volumes: ß = -24, counts: ß = -127), decreased tortuosity (volumes: ß = -0.08, counts: ß = -0.53), and increased radius (volumes: ß = 12.6, counts: ß = 86.6). Path analyses suggested an association between high BP and WMHs that were mediated by cerebrovascular morphologic changes. DATA CONCLUSION: Structural alterations of cerebral vessels induced by high BP are correlated with WMH. This result suggested that elevated BP might be one of the pathophysiological mechanisms involving in the co-occurrence of cerebrovascular alteration and small vessel disease. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1.

Efficacy and biomarker exploration of camrelizumab combined with apatinib in the treatment of advanced primary liver cancer: a retrospective study.

This study was to explore the efficacy and safety of camrelizumab combined with apatinib in patients with advanced liver cancer. Moreover, the relationship between peripheral blood parameters and tumor response rate was also investigated. Patients with unresectable or recurrent primary liver cancer (PLC) who received treatment from July 2019 to July 2020 in the First Affiliated Hospital of Guangxi Medical University were included in this single-center retrospective study. The patients were treated with camrelizumab (200 mg, intravenous q2w) plus apatinib (250 mg, oral qd) until the occurrence of disease progression or unbearable toxicity. All the patients underwent blood routine test and detection of lactate dehydrogenase and serum albumin levels before treatment. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). This study included a total of 45 patients. The overall ORR was 33.3% [95% confidence interval (CI),19.0-47.7] and the overall DCR was 57.8% (95% CI, 42.8-72.8). The ORR and DCR were higher in the first-line treatment than those in the second-line treatment (ORR: 45.5% vs. 21.7%, DCR: 63.6% vs. 52.3%). Median progression-free survival in the second-line treatment was 10.5 months (95% CI, 7.9-13.1, P = 0.022). Adverse events occurred in 39 (86.7%) patients. Grade 3/4 adverse reactions occurred in 7 (15.6%) patients. One patient (4.3%) was terminated from treatment due to adverse events. One patient (4.3%) died, which was potentially associated with adverse events. Subgroup analysis indicated that the remission rate in patients with high lymphocyte to monocyte ratio (H-LMR) was higher than that in patients with low lymphocyte to monocyte ratio (L-LMR) (56.25% vs. 25.93%, P = 0.047), and the remission rate in patients with high Prognostic Nutritional Index (H-PNI) was higher than that in patients with low Prognostic Nutritional Index (L-PNI) (66.7% vs. 26.5%, P = 0.046). Camrelizumab combined with apatinib in the treatment of PLC showed encouraging clinical efficacy, with tolerable toxicities. Levels of PNI and LMR may serve as predictors of the prognosis of advanced PLC patients who receive immunotherapy combined with targeted therapy.

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

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.

Lifestyle, multi-omics features, and preclinical dementia among Chinese: The Taizhou Imaging Study.

China has the largest number of patients with dementia in the world. However, dementia in the Chinese population is still poorly understood and under-researched. Given the differences in genetic, demographic, sociocultural, lifestyle, and health profiles among Chinese and other ethnic/racial groups, it is crucial to build appropriate infrastructure for long-term longitudinal studies to advance Chinese cognitive aging and dementia research. We initiated a community-based prospective cohort-the Taizhou Imaging Study (TIS)-to accelerate the understanding of dementia and cerebrovascular diseases in Chinese. This article presents the rationale, aims, study design, and organization of TIS. In addition, we described some examples of the types of studies such a resource might support. The TIS provides a new framework for facilitating Chinese dementia research, encompassing invaluable resources including detailed epidemiological, sociocultural, neuroimaging, and omics data.

Construction and utilization of human genetic resources in large population cohorts.

In the era of big data and precision medicine, large population cohort studies are one of the preferred designs for studying the etiology of chronic diseases, and cohort genetic resources have become important strategic resources of China. Promoting the standardized construction and utilization of cohort genetic resources can effectively promote the original innovation of research and technological development in the field of biomedicine, and make full use of the rich genetic resources of China. To provide a reference for the construction and utilization of genetic resources in the cohort research in China, we took the Taizhou Longitudinal Study (TZL) as an example and introduced the principles, methods, standard system, and practical experience of the collection, preservation, and shared utilization of genetic resources in the process of the cohort construction.

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

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.

The progress of gut microbiome research related to brain disorders.

There is increasing evidence showing that the dynamic changes in the gut microbiota can alter brain physiology and behavior. Cognition was originally thought to be regulated only by the central nervous system. However, it is now becoming clear that many non-nervous system factors, including the gut-resident bacteria of the gastrointestinal tract, regulate and influence cognitive dysfunction as well as the process of neurodegeneration and cerebrovascular diseases. Extrinsic and intrinsic factors including dietary habits can regulate the composition of the microbiota. Microbes release metabolites and microbiota-derived molecules to further trigger host-derived cytokines and inflammation in the central nervous system, which contribute greatly to the pathogenesis of host brain disorders such as pain, depression, anxiety, autism, Alzheimer's diseases, Parkinson's disease, and stroke. Change of blood-brain barrier permeability, brain vascular physiology, and brain structure are among the most critical causes of the development of downstream neurological dysfunction. In this review, we will discuss the following parts: Overview of technical approaches used in gut microbiome studiesMicrobiota and immunityGut microbiota and metabolitesMicrobiota-induced blood-brain barrier dysfunctionNeuropsychiatric diseases ■ Stress and depression■ Pain and migraine■ Autism spectrum disordersNeurodegenerative diseases ■ Parkinson's disease■ Alzheimer's disease■ Amyotrophic lateral sclerosis■ Multiple sclerosisCerebrovascular disease ■ Atherosclerosis■ Stroke■ Arteriovenous malformationConclusions and perspectives.

Temporal trends in the mortality rate of Alzheimer's disease and other dementias attributable to smoking, 1990-2017.

BACKGROUND: Smoking is a well-defined modifiable risk factor for dementia. Understanding national temporal trends of dementia deaths due to smoking is critical for prioritizing action for the global prevention of dementia, as well as smoking prevention. We aimed to estimate the patterns and temporal trends of smoking-attributable dementia-related deaths for 195 countries from 1990 to 2017. METHODS: Detailed data on dementia deaths attributable to smoking were obtained from the Global Burden of Disease Study 2017. The estimated annual percentage change (EAPC) was used to quantify the temporal trends in the age-standardized mortality rate (ASMR) of dementia attributable to smoking by age, sex, region, and country. RESULTS: In 2017, approximately 2.51 million deaths attributable to dementia occurred globally; among them, 317,747 dementia-related deaths were attributable to smoking. The corresponding ASMR decreased by 31.1% from 6.33 per 100,000 population in 1990 to 4.36 per 100,000 population in 2017, with an EAPC of -1.43 (95% CI -1.48, -1.37). The reduction in the ASMR in women (EAPC = -2.13; 95% CI -2.18, -2.08) was more pronounced than that in men (EAPC = -1.26; 95% CI -1.32, -1.20). Most geographic region have achieved significant declines in ASMRs since 1990; however, Central Asia and 24 countries and territories showed increased trends in ASMRs over the same period. CONCLUSIONS: Despite large reductions in the ASMRs of dementia attributable to smoking over the past three decades, the corresponding number of deaths has steadily increased due to population growth and aging. The ASMR trend patterns were heterogeneous across countries, and there were undesirable increases in the dementia ASMR in some countries. Strengthened efforts for tobacco prevention are still needed to reduce the disease burden due to smoking, particularly in countries where the dementia ASMR is increasing.