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BACKGROUND: Prior researches have highlighted inverse associations between levels of circulating very-long chain saturated fatty acids (VLCSFAs) and coronary heart disease (CHD). However, the intricate links involving VLCSFAs, gut microbiota, and bile acids remain underexplored. OBJECTIVE: This study examined the association of erythrocyte VLCSFAs with CHD incidence, focusing on the mediating role of gut microbiota and fecal bile acids. METHODS: This 10-year prospective study included 2383 participants without CHD at baseline. Erythrocyte VLCSFAs (arachidic acid [C20:0], behenic acid [C22:0], and lignoceric acid [C24:0]) were measured using gas chromatography at baseline and 274 CHD incidents were documented in triennial follow-ups. Gut microbiota in 1744 participants and fecal bile acid metabolites in 945 participants were analyzed using 16S rRNA sequencing and UPLC-MS/MS at middle-term. RESULTS: The multivariable-adjusted HRs (95%CI) for CHD incidence in highest vs. lowest quartiles were 0.87 (0.61, 1.25) for C20:0, 0.63 (0.42,0.96) for C22:0, 0.59 (0.41,0.85) for C24:0, and 0.57 (0.39, 0.83) for total VLCSFAs. Participants with higher total VLCSFA levels exhibited increased abundances of Holdemanella, Coriobacteriales Incertae Sedis spp., Ruminococcaceae UCG-005 and UCG-010, and Lachnospiraceae ND3007 group. These five genera generated microbial score (ODMS) that accounted for 11.52% of the total VLCSFAs-CHD association (Pmediation =0.018). Bile acids tauro_α_ and tauro_ß_muricholic acid (T_α_ and T_ß_MCA) were inversely associated with ODMS and positively associated with incident CHD. Opposite associations were found for glycolithocholic acid (GLCA), glycodeoxycholic acid (GDCA). Mediation analyses indicated that GLCA, GDCA, and T_α_ and T_ß_MCA explained 56.40%, 35.19%, and 26.17% of the ODMS-CHD association, respectively (Pmediation =0.002, 0.008, and 0.020). CONCLUSIONS: Elevated erythrocyte VLCSFAs are inversely associated with CHD risk in the Chinese population, with gut microbiota and fecal bile acid profiles potentially mediating this association. The identified microbiota and bile acid metabolites may serve as potential intervention targets in future studies. CLINICAL TRIAL REGISTRY NUMBER: NCT03179657.
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BACKGROUND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and risk of MASLD and its severity. APPROACH RESULTS: This prospective multi-cohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1,137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. Additionally, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3,010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6,454 person-years of follow-up, and the UK Biobank 1,350 developed MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR=0.87, 95% CI: 0.78, 0.96; GNHS: HR=0.79, 95% CI: 0.64, 0.98; UK Biobank: HR=0.73, 95% CI: 0.63, 0.85). Moreover, liver controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß=-5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with risk of MASLD as well as its severity.
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The impact of milk on bone health in rural preschoolers is under-researched. This study, through a clinical trial and a meta-analysis, finds that milk supplementation enhances forearm and calcaneus bone acquisition in children, supporting the benefits of daily milk consumption. PURPOSE: This study evaluated the impact of dairy supplementation on bone acquisition in children's limbs through a cluster-randomized controlled trial and a meta-analysis. METHODS: The trial involved 315 children (4-6 year) from Northwest China, randomized to receive either 390 ml of milk daily (n = 215) or 20-30 g of bread (n = 100) over 12 months. We primarily assessed bone mineral density (BMD) and content (BMC) changes at the limbs, alongside bone-related biomarkers, measured at baseline, the 6th and 12th months. The meta-analysis aggregated BMD or BMC changes in the forearm/legs/calcaneus from published randomized trials involving children aged 3-18 years supplemented with dairy foods (vs. control group). RESULTS: Of 278 completed the trial, intention-to-treat analysis revealed significant increases in BMD (4.05% and 7.31%) and BMC (4.69% and 7.34%) in the left forearm at the 6th and 12th months in the milk group compared to controls (P < 0.001). The calcaneus showed notable improvements in BMD (2.01%) and BMC (1.87%) at 6 months but not at 12 months. Additionally, milk supplementation was associated with beneficial changes in bone resorption markers, parathyroid hormone (- 12.70%), insulin-like growth factor 1 (6.69%), and the calcium-to-phosphorus ratio (2.22%) (all P < 0.05). The meta-analysis, encompassing 894 children, indicated that dairy supplementation significantly increased BMD (SMD, 0.629; 95%CI: 0.275, 0.983) and BMC (SMD, 0.616; 95%CI: 0.380, 0.851) (P < 0.05) in the arms, but not in the legs (P > 0.05). CONCLUSION: Milk supplementation significantly improves bone health in children's forearms, underscoring its potential as a strategic dietary intervention for bone development. Trial registration NCT05074836.
Subject(s)
Bone Density , Dietary Supplements , Child , Child, Preschool , Female , Humans , Male , Bone Density/drug effects , Bone Development/physiology , Calcaneus/diagnostic imaging , China , Forearm , Milk , AdolescentABSTRACT
BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.
Subject(s)
Body Fat Distribution , Methylamines , Humans , Methylamines/blood , Female , Middle Aged , Male , Prospective Studies , Aged , Body Fat Distribution/methods , Adult , Absorptiometry, Photon/methods , Body Composition , Cohort Studies , ChinaABSTRACT
BACKGROUND & AIMS: Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults. METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism. RESULTS: A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn't reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058). CONCLUSION: SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.
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BACKGROUND AND AIMS: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure. METHODS: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes. RESULTS: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 µg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01). CONCLUSIONS: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome.
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BACKGROUND: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. METHODS: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. FINDINGS: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. INTERPRETATION: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. FUNDING: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.
Subject(s)
Gastrointestinal Microbiome , Metabolic Syndrome , Metabolome , Metabolomics , Humans , Male , Female , Aged , Metabolomics/methods , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Proteomics/methods , Metagenomics/methods , Middle Aged , Biomarkers/blood , Feces/microbiology , MultiomicsABSTRACT
Background: The escalating prevalence of hyperuricemia is emerging as a significant public health concern. The association between dietary lignans and hyperuricemia is yet to be fully elucidated. Our study aims to evaluate the relationships between dietary lignan intake and hyperuricemia among middle-aged and elderly Chinese individuals, with an additional focus on investigating the underlying mechanisms. Methods: Dietary lignan intake was measured using a validated Food Frequency Questionnaire in 3801 participants at the baseline. Among them, 2552 participants were included in the longitudinal study with a median follow-up of 10.5 years. The gut microbiota was analyzed by shotgun metagenome sequencing in 1789 participants, and the targeted fecal metabolome was determined in 987 participants using UPLC-MS/MS at the midpoint of follow-up. Results: The multivariable-adjusted HRs (95% CIs) for hyperuricemia incidence in the highest quartile (vs. the lowest quartile) of dietary intake of total lignans, matairesinol, pinoresinol, and secoisolariciresinol were 0.93 (0.78-1.10), 0.77 (0.66-0.90), 0.83 (0.70-0.97), and 0.85 (0.73-1.00), respectively. The gut microbial and fecal metabolic compositions were significantly different across the dietary lignan groups and the hyperuricemia groups. The beneficial associations between dietary lignans and hyperuricemia might be mediated by several gut microbes (e.g., Fusobacterium mortiferum and Blautia sp. CAG-257) and the downstream bile acid products (e.g., NorCA, glycochenodeoxycholic acid, and glycoursodeoxycholic acid). Conclusion: We found that dietary lignans were inversely associated with hyperuricemia incidence, and the gut microbiota-bile acid axis might mediate this association. Our findings provide new perspectives on precise therapeutic targets and underlying mechanisms for conditions associated with elevated uric acid.
Subject(s)
Bile Acids and Salts , Gastrointestinal Microbiome , Hyperuricemia , Lignans , Gastrointestinal Microbiome/drug effects , Humans , Lignans/administration & dosage , Middle Aged , Male , Female , Prospective Studies , Aged , Bile Acids and Salts/metabolism , Longitudinal Studies , Feces/microbiology , Diet , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , China , AdultABSTRACT
OBJECTIVE: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. METHODS: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). CONCLUSIONS: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.
Subject(s)
Metabolic Syndrome , Vitamin D , Humans , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Vitamin D/blood , Vitamin D/analogs & derivatives , Male , Female , Longitudinal Studies , Middle Aged , China/epidemiology , Adult , Cross-Sectional Studies , Risk Factors , Obesity, Abdominal/blood , Obesity, Abdominal/epidemiology , Asian People , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/blood , Aged , Odds Ratio , East Asian PeopleABSTRACT
BACKGROUND: The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD. METHODS: The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites. RESULTS: Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD. CONCLUSIONS: We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.
Subject(s)
Gastrointestinal Microbiome , Microbiota , Non-alcoholic Fatty Liver Disease , Middle Aged , Humans , Animals , Mice , Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/metabolism , Liver/metabolism , Independent LivingABSTRACT
The relationship between PM2.5 and metabolic diseases, including type 2 diabetes (T2D), has become increasingly prominent, but the molecular mechanism needs to be further clarified. To help understand the mechanistic association between PM2.5 exposure and human health, we investigated short-term PM2.5 exposure trajectory-related multi-omics characteristics from stool metagenome and metabolome and serum proteome and metabolome in a cohort of 3267 participants (age: 64.4 ± 5.8 years) living in Southern China. And then integrate these features to examine their relationship with T2D. We observed significant differences in overall structure in each omics and 193 individual biomarkers between the high- and low-PM2.5 groups. PM2.5-related features included the disturbance of microbes (carbohydrate metabolism-associated Bacteroides thetaiotaomicron), gut metabolites of amino acids and carbohydrates, serum biomarkers related to lipid metabolism and reducing n-3 fatty acids. The patterns of overall network relationships among the biomarkers differed between T2D and normal participants. The subnetwork membership centered on the hub nodes (fecal rhamnose and glycylproline, serum hippuric acid, and protein TB182) related to high-PM2.5, which well predicted higher T2D prevalence and incidence and a higher level of fasting blood glucose, HbA1C, insulin, and HOMA-IR. Our findings underline crucial PM2.5-related multi-omics biomarkers linking PM2.5 exposure and T2D in humans.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Middle Aged , Aged , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Multiomics , China/epidemiology , Biomarkers , Particulate MatterABSTRACT
The role of circulatory proteomics in osteoporosis is unclear. Proteome-wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, and the 2nd, and 3rd follow-ups (7704 person-tests) in the prospective Chinese cohorts with 9.8 follow-up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at follow-ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the osteoporosis (OP)-related proteomic features. The relationships between serum proteins and BMD in the two cohorts were estimated by linear mixed-effects model (LMM). Meta-analysis was then performed to explore the combined associations. We identified 53 proteins associated with osteoporosis using LightGBM, and a meta-analysis showed that 22 of these proteins illuminated a significant correlation with BMD (p < 0.05). The most common proteins among them were PHLD, SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified proteins were used to generate the biological age (BA) of bone. Each 1 SD-year increase in KDM-Proage was associated with higher risk of LS-OP (hazard ratio [HR], 1.25; 95% CI, 1.14-1.36, p = 4.96 × 10-06 ), and FN-OP (HR, 1.13; 95% CI, 1.02-1.23, p = 9.71 × 10-03 ). The findings uncovered that the apolipoproteins, zymoproteins, complements, and binding proteins presented new mechanistic insights into osteoporosis. Serum proteomics could be a crucial indicator for evaluating bone aging.
Subject(s)
Osteoporosis , Proteome , Humans , Prospective Studies , Proteomics , Chromatography, Liquid , Tandem Mass Spectrometry , Osteoporosis/genetics , AgingABSTRACT
BACKGROUND: The optimal multimorbidity measures for predicting disability trajectories are not universally agreed upon. We developed a multimorbidity index among middle-aged and older community-dwelling Chinese adults and compare its predictive ability of disability trajectories with other multimorbidity measures. METHODS: This study included 17,649 participants aged ≥50 years from the China Health and Retirement Longitudinal Survey 2011-2018. Two disability trajectory groups were estimated using the total disability score differences calculated between each follow-up visit and baseline. A weighted index was constructed using logistic regression models for disability trajectories based on the training set (70 %). The index and the condition count were used, along with the pattern identified by the latent class analysis to measure multimorbidity at baseline. Logistic regression models were used in the training set to examine associations between each multimorbidity measure and disability trajectories. C-statistics, integrated discrimination improvements, and net reclassification indices were applied to compare the performance of different multimorbidity measures in predicting disability trajectories in the testing set (30 %). RESULTS: In the newly developed multimorbidity index, the weights of the chronic conditions varied from 1.04 to 2.55. The multimorbidity index had a higher predictive performance than the condition count. The condition count performed better than the multimorbidity pattern in predicting disability trajectories. LIMITATION: Self-reported chronic conditions. CONCLUSIONS: The multimorbidity index may be considered an ideal measurement in predicting disability trajectories among middle-aged and older community-dwelling Chinese adults. The condition count is also suggested due to its simplicity and superior predictive performance.
Subject(s)
Disabled Persons , Multimorbidity , Middle Aged , Humans , Aged , Longitudinal Studies , Independent Living , Chronic DiseaseABSTRACT
BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Prenatal Exposure Delayed Effects , Starvation , Adult , Humans , Middle Aged , China , Cohort Studies , Diabetes Mellitus, Type 2/complications , East Asian People , Famine , Microbiota , Starvation/complications , Adolescent , Young Adult , Aged , Aged, 80 and overABSTRACT
STUDY DESIGN: A meta-analysis of randomized controlled trials. OBJECTIVE: Our meta-analysis was conducted to investigate whether interspinous spacer (IS) results in better performance for patients with lumbar spinal stenosis (LSS) when compared with decompressive surgery (DS). BACKGROUND DATA: DS and IS are common surgeries for the treatment of LSS. However, controversy remains as to whether the IS is superior to DS. METHODS: We comprehensively searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for prospective randomized controlled trials that compared IS versus DS for LSS. The retrieved results were last updated on July 30, 2023. RESULTS: Eight studies involving 852 individuals were included in the meta-analysis. The pooled data indicated that IS was superior to DS considering shorter operation time (P = .003), lower dural violation rate (P = .002), better Zurich Claudication Questionnaire Physical function score (P = .03), and smaller foraminal height decrease (P = .004), but inferior to DS considering the higher rate of reoperation (P < .0001). There was no significant difference between the 2 groups regarding hospital stay (P = .26), blood loss (P = .23), spinous process fracture (P = .09), disc height decrease (P = .87), VAS leg pain score (P = .43), VAS back pain score (P = .26), Oswestry Disability Index score (P = .08), and Zurich Claudication Questionnaire symptom severity (P = .50). CONCLUSIONS: In summary, we considered that IS had similar effects with DS in hospital stay, blood loss, spinous process fracture, disc height decrease, VAS score, Oswestry Disability Index score, and Zurich Claudication Questionnaire Symptom severity, and was better in some indices such as operation time, dural violation, Zurich Claudication Questionnaire Physical function, and foraminal height decrease than DS. However, due to the higher rate of reoperation in the IS group, we considered that both IS and DS were acceptable strategies for treating LSS. As a novel technique, further well-designed studies with longer-term follow-up are needed to evaluate the effectiveness and safety of IS.
Subject(s)
Spinal Stenosis , Humans , Spinal Stenosis/surgery , Decompression, Surgical/adverse effects , Decompression, Surgical/methods , Prospective Studies , Lumbar Vertebrae/surgery , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.
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Long-standing administration of disease-modifying antirheumatic drugs confirms their clinical value for managing rheumatoid arthritis (RA). Nevertheless, there are emergent worries over unwanted adverse risks of systemic drug administration. Hence, a novel strategy that can be used in a drug-free manner while diminishing side effects is immediately needed, but challenges persist in the therapy for RA. To this end, herein we conjugated tyramine (TYR) with alginate (ALG) to form ALG-TYR and then treated it for 5 min with oxygen plasma (ALG-TYR + P/5 min). It was shown that the ALG-TYR + P/5 min hydrogel exhibited favorable viscoelastic, morphological, mechanical, biocompatible, and cellular heat-shock protein amplification behaviors. A thorough physical and structural analysis was conducted on the ALG-TYR + P/5 min hydrogel, revealing favorable physical characteristics and uniform porous structural features within the hydrogel. Moreover, ALG-TYR + P/5 min not only effectively inhibited inflammation of RA but also potentially regulated lesion immunity. Once ALG-TYR + P/5 min was intra-articularly administered to joints of rats with zymosan-induced arthritis, we observed that ALG-TYR + P/5 min could ameliorate syndromes of RA joint. This bioinspired and self-restorable ALG-TYR + P/5 min hydrogel can thus serve as a promising system to provide prospective outcomes to potentiate RA therapy.
ABSTRACT
Metabolic syndrome (MetS) is a complex metabolic disorder with a global prevalence of 20%-25%. Early identification and intervention would help minimize the global burden on healthcare systems. Here, we measured over 400 proteins from â¼20,000 proteomes using data-independent acquisition mass spectrometry for 7,890 serum samples from a longitudinal cohort of 3,840 participants with two follow-up time points over 10 years. We then built a machine-learning model for predicting the risk of developing MetS within 10 years. Our model, composed of 11 proteins and the age of the individuals, achieved an area under the curve of 0.774 in the validation cohort (n = 242). Using linear mixed models, we found that apolipoproteins, immune-related proteins, and coagulation-related proteins best correlated with MetS development. This population-scale proteomics study broadens our understanding of MetS and may guide the development of prevention and targeted therapies for MetS.
Subject(s)
Metabolic Syndrome , Humans , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Prognosis , Proteomics , Proteome , Machine LearningABSTRACT
BACKGROUND: Furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a strong biomarker of fish and n-3 polyunsaturated fatty acid (PUFA) intake. The relationship of CMPF with human health has been controversial, especially for type 2 diabetes and chronic kidney disease. OBJECTIVE: We performed a prospective cohort study to examine the association of serum CMPF with incident type 2 diabetes and chronic kidney disease. METHODS: In the Guangzhou Nutrition and Health Study, during a median follow-up of 8.8 y, we used a multivariable-adjusted Poisson regression model to investigate the association of baseline serum CMPF with the incidence of type 2 diabetes (1470 participants and 170 incident cases) and chronic kidney disease (1436 participants and 112 incident cases). We also examined the association of serial measures of serum CMPF with glycemic and renal function biomarkers. Mediation analysis was also performed to examine the contribution of CMPF in the association between marine n-3 PUFAs and risk of type 2 diabetes or chronic kidney disease. RESULTS: Each standard deviation increase in baseline serum CMPF was associated with an 18% lower risk of type 2 diabetes (relative risk: 0.82, 95% confidence interval [CI]: 0.68, 0.99) but was not associated with chronic kidney disease (relative risk: 0.95; 95% CI: 0.77-1.16). Correlation analyses of CMPF with glycemic and renal function biomarkers showed similar results. Mediation analysis suggested that serum CMPF contributed to the inverse association between erythrocyte marine n-3 PUFAs and incident type 2 diabetes (proportion mediated 37%, P-mediation = 0.022). CONCLUSIONS: Our findings suggest that serum CMPF was associated with a lower risk of type 2 diabetes but not chronic kidney disease. This study also suggests that CMPF may be a functional metabolite underlying the protective relationship between marine n-3 PUFA intake and type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Fatty Acids, Omega-3 , Kidney Diseases , Animals , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Fatty Acids , Cohort Studies , Risk , Prospective Studies , Fatty Acids, Unsaturated , Biomarkers , FuransABSTRACT
Introduction: Post-stroke depression (PSD) is a serious mental disorder after ischemic stroke. Early detection is important for clinical practice. This research aims to develop machine learning models to predict new-onset PSD using real-world data. Methods: We collected data for ischemic stroke patients from multiple medical institutions in Taiwan between 2001 and 2019. We developed models from 61,460 patients and used 15,366 independent patients to test the models' performance by evaluating their specificities and sensitivities. The predicted targets were whether PSD occurred at 30, 90, 180, and 365 days post-stroke. We ranked the important clinical features in these models. Results: In the study's database sample, 1.3% of patients were diagnosed with PSD. The average specificity and sensitivity of these four models were 0.83-0.91 and 0.30-0.48, respectively. Ten features were listed as important features related to PSD at different time points, namely old age, high height, low weight post-stroke, higher diastolic blood pressure after stroke, no pre-stroke hypertension but post-stroke hypertension (new-onset hypertension), post-stroke sleep-wake disorders, post-stroke anxiety disorders, post-stroke hemiplegia, and lower blood urea nitrogen during stroke. Discussion: Machine learning models can provide as potential predictive tools for PSD and important factors are identified to alert clinicians for early detection of depression in high-risk stroke patients.