Abstract
Background
Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations ...reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer’s disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ).
Methods
A two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively.
Results
We found suggestive associations of host-genetic-driven increase in
Blautia
(OR, 0.88; 95%CI, 0.79–0.99;
P
= 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92–1.00;
P
= 0.034), a downstream product of
Blautia
-dependent arginine metabolism, with a lower risk of AD. Genetically increased
Enterobacteriaceae family
and
Enterobacteriales order
were potentially associated with a higher risk of SCZ (1.09; 1.00–1.18;
P
= 0.048), while
Gammaproteobacteria class
(0.90; 0.83–0.98;
P
= 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00–1.15;
P
= 0.047). Furthermore, genetically increased
Bacilli class
was related to a higher risk of MDD (1.07; 1.02–1.12;
P
= 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition.
Conclusions
These data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.
Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to ...what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories.
The China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval CI 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification.
Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.
Observational studies have shown that moderate-to-vigorous physical activity (MVPA), vigorous physical activity (VPA), sedentary behaviours, and sleep duration were associated with cardiovascular ...diseases (CVDs) and lipid levels. However, whether such observations reflect causality remain largely unknown. We aimed to investigate the causal associations of physical activity, sedentary behaviours, and sleep duration with coronary artery disease (CAD), myocardial infarction (MI), stroke and lipid levels.
We conducted a Mendelian randomization (MR) study using genetic variants as instruments which are associated with physical activity, sedentary behaviours, and sleep duration to examine the causal effects on CVDs and lipid levels. This study included analyses of 4 potentially modifiable factors and 7 outcomes. Thus, the threshold of statistical significance is P = 1.8 × 10
(0.05/4 × 7) after Bonferroni correction.
In the present study, there was suggestive evidence for associations of genetically predicted VPA with CAD (odds ratio, 0.65; 95% confidence intervals, 0.47-0.90; P = 0.009) and MI (0.74; 0.59-0.93; P = 0.010). However, genetically predicted VPA, MVPA, sleep duration and sedentary behaviours did not show significant associations with stroke and any lipid levels.
Our findings from the MR approach provided suggestive evidence that vigorous exercise decreased risk of CAD and MI, but not stroke. However, there was no evidence to support causal associations of MVPA,sleep duration or sedentary behaviours with cardiovascular risk and lipid levels.
The findings of this study did not point out specific recommendations on increasing physical activity required to deliver significant health benefits. Nevertheless, the findings allowed clinicians and public health practitioners to provide advice about increasing the total amount of excising time by demonstrating that such advice can be effective. Reliable assessment of the association of physical activity levels with different subtypes of CVDs is needed to provide the basis for a comprehensive clinical approach on CVDs prevention, which can be achieved through lifestyle interventions in addition to drug therapy.
Previous evidence yielded contradictory findings on the relationship between metformin and anemia. This study aims to assess whether metformin use is associated with iron-deficiency anemia (IDA) risk ...in patients with type 2 diabetes (T2D) in Beijing, China.
Overall, 60,327 newly diagnosed T2D patients were included based on a historical cohort study design. The information pertaining to these patients was gathered from the Beijing Medical Claim Data for Employees Database. These patients were then categorized into the metformin and non-metformin groups and matched on a 1:1 propensity score based on their initial antidiabetic prescription. The Cox proportional hazards models were utilized to calculate the incidences and the hazard ratios (HRs).
The study enrolled 27,960 patients with type 2 diabetes, with 13,980 patients in each of the initial glucose-lowering prescription groups: metformin and non-metformin. During a median follow-up period of 4.84 years, 4832 patients developed IDA. The incidence of IDA was significantly lower in the metformin group (26.08/1000 person-years) than in the non-metformin group (43.20/1000 person-years). Among the three groups divided by the proportion of days covered by metformin, we found a negative correlation between the proportion of days covered by metformin and the risk of IDA. The risk of IDA in patients with a proportion of days covered by metformin of <20%, 20-79%, and ≥80% was 0.43 (0.38, 0.48), 0.37 (0.34, 0.42), and 0.91 (0.85, 0.98), respectively, compared to the non-metformin group. We also performed subgroup analyses and sensitivity analyses: the incidence of IDA in the metformin group was lower than that in the non-metformin group in all subgroups, and the protective effect was more significant in subgroups of patients aged ≥65, with Charlson comorbidity index (CCI) ≥2, and with gastric acid inhibitor use.
In Chinese patients with T2DM, metformin treatment was associated with a decreased risk of IDA admission, and this risk responded positively to the proportion of days covered by metformin. These findings suggest that metformin may have a pleiotropic effect on IDA in patients with type 2 diabetes. Our study has important clinical implications for the management of patients with diabetes and other conditions that increase the risk of IDA.
Improving the effectiveness of harvesting robots requires quick and accurate apple detection in natural environments. The colour and shape features of apples are corrupted due to the reflected light ...and the incomplete coverage of the fruit bag, bringing difficulties to apple detection. To address this issue, the Coordinate Attention You Only Look Once version 5 (CA-YOLOv5) is designed to simultaneously detect bagged and unbagged apples in the natural environment. Firstly, 1525 apple images are collected from apple orchards to build a dataset. Secondly, to solve the reflected light problem, all C3 modules in the Backbone are substituted for Coordinate Attention modules which can improve the feature representation of objects. Finally, to solve the incomplete bagging problem, the Path Aggregation Network in the Neck is replaced by a Bidirectional Feature Pyramid Network which can better fuse the features of various sizes. The CA-YOLOv5 network reaches 82.7%, 89.8%, 48.6%, and 87.0% for recall, mAP@0.5, mAP@0.5:0.95, and F1 score, respectively, which is 2.3%,1.2%,1.9%, and 2.9% higher than the YOLOv5. The results reveal that CA-YOLOv5 has much superior detection performance than the original YOLOv5, and it can serve as a technical benchmark for the development of automatic orchard-picking robots.
Evidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to ...investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented.
This study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern.
There were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5-6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (p
< 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011.
Adherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives.
Evidence for the health effects of ambient PM1 (particulate matter with an aerodynamic diameter ≤ 1 µm) pollution is limited, and it remains unclear whether a smaller particulate matter has a greater ...impact on human health. We conducted a time-series study in 184 major cities by extracting daily hospital data on admissions for ischemic heart disease, heart failure, heart rhythm disturbances, and stroke between 2014 and 2017 from a medical insurance claims database of 0.28 billion beneficiaries. City-specific associations were estimated with over-dispersed generalized additive models. A random-effects meta-analysis was used to estimate regional and national average associations. We conducted stratified and meta-regression analyses to explore potential effect modifiers of the association. We recorded 8.83 million cardiovascular admissions during the study period. At the national-average level, a 10-μg/m3 increase in same-day PM1, PM2.5(particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10(particulate matter with an aerodynamic diameter ≤ 10 µm) concentrations corresponded to a 1.14% (95% confidence interval 0.88–1.41%), 0.55% (0.40–0.70%), and 0.45% (0.36–0.55%) increase in cardiovascular admissions, respectively. PM1 exposure was also positively associated with all cardiovascular disease subtypes, including ischemic heart disease (1.28% change; 0.99–1.56%), heart failure (1.30% change; 0.70–1.91%), heart rhythm disturbances (1.11% change; 0.65–1.58%), and ischemic stroke (1.29% change; 0.88–1.71%). The associations between PM1 and cardiovascular admissions were stronger in cities with lower PM1 levels, higher air temperatures and relative humidity, as well as in subgroups with elder age (all P < 0.05). This study provides robust evidence of short-term associations between PM1 concentrations and increased hospital admissions for all major cardiovascular diseases in China. Our findings suggest a greater short-term impact on cardiovascular risk from PM1 in comparison to PM2.5 and PM10.
•Short-term impact on cardiovascular risk from PM1 is greater than PM2.5 and PM10.•First nationwide study of association between PM1 and cardiovascular morbidity.•PM1 is associated with all major cardiovascular diseases.
Accurate semantic segmentation of disease spots is critical in the evaluation and treatment of cucumber leaf damage. To solve the problem of poor segmentation accuracy caused by the imbalanced ...feature fusion of SegFormer, the Efficient Channel Attention SegFormer (ECA-SegFormer) is proposed to handle the semantic segmentation of cucumber leaf disease spots under natural acquisition conditions. First, the decoder of SegFormer is modified by inserting the Efficient Channel Attention and adopting the Feature Pyramid Network to increase the scale robustness of the feature representation. Then, a cucumber leaf disease dataset is built with 1558 images collected from the outdoor experimental vegetable base, including downy mildew, powdery mildew, target leaf spot, and angular leaf spot. Tested on the dataset, the Mean Pixel Accuracy of ECA-SegFormer is 38.03%, and the mean Intersection over Union is 60.86%, which is 14.55% and 1.47% higher than SegFormer, respectively. These findings demonstrate the superiority of ECA-SegFormer over the original SegFormer, offering enhanced suitability for precise segmentation of cucumber leaf disease spots in the natural environment.
Background and Objectives: Observational studies have associated lifestyle, dietary, adiposity, biochemical and clinical measures with heart failure. Whether the associations are causal remains ...unclear. We aimed to determine the causal associations between modifiable risk factors and incidence or mortality of heart failure. Methods and Study Design: Using single-nucleotide polymorphism (SNP) as genetic instruments, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal effects of 27 modifiable risk factors on incident heart failure (2526 cases; 20926 participants) and mortality of heart failure (1798 deaths; 2828 patients). Results: None of 27 modifiable risk factors were significantly associated with incidence or mortality of heart failure after the Bonferroni correction (p<0.0019). However, there was suggestive evidence for genetically predicted educational attainment (odds ratio OR per educational year increase: 0.57, 95% CI 0.33-0.99, p=0.049), circulating mono-unsaturated fatty acid concentrations (OR per 1-SD increase ORSD : 1.50, 1.10-2.04, p=0.011), C-reactive protein (CRP) (1.53, 1.04-2.25, p=0.031), high-density lipoprotein (HDL) (0.84, 0.72-0.99, p=0.036), triglycerides (1.24, 1.00-1.52, p=0.045), and systolic blood pressure (SBP) (1.06, 1.01-1.11, p=0.017) with incident heart failure. Conclusions: Our findings provide supporting evidence for prioritizing certain modifiable risk factors such as education, lipids, and blood pressure for primary prevention of heart failure, suggesting important clues for further mechanism research.
Metformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic ...peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China.
All patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.
Among 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0 g and >2.0 g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69).
In Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.
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