: Vascular failure (VF) and heart failure (HF) are extremely harmful and are the primary causes of hypoxia. Our previous results have shown that the sphingosine-1-phosphate (S1P) pathway was involved ...in regulating intermittent hypoxia–induced vascular defection, but the clinical role and molecular mechanism of the S1P pathway remain unclear.
: Normalized relative expression values and differentially expressed genes were downloaded in GSE145221 from the Gene Expression Omnibus dataset. WGCNA was used to construct a gene co-expression network. The Spearman correlation matrix was used to identify the top 500 highly correlated genes with the S1P pathway genes. R package clusterProfiler was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses on the WGCNA modules. Homer software was utilized to identify regulatory motifs in the promoter and gene body regions of S1P pathway genes. An intermittent hypoxic injury cell model was induced by chronic intermittent hypoxia (CIH). ROS and TUNEL staining and Western blot were used to detect cell apoptosis and reactive oxygen species.
: The transcriptional regulatory regions of S1P pathway genes were enriched with hypoxia-inducible factor 1-alpha, which indicated the close connection between the S1P pathway and the CIH process. In vitro, we confirmed that the endothelial cell apoptosis induced by CIH could be reversed by exogenous addition of S1P.
: This study elucidated the mechanism of the S1P pathway in regulating cardiovascular injury caused by CIH and provided a new strategy for early intervention in people with cardiovascular dysfunction induced by hypoxia.
The study aimed to explore the association between manganese concentration and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality in the general population of the United ...States.
We integrated the data from the National Health and Nutrition Examination Survey from 2011 to 2018. A total of 9,207 subjects were selected based on the inclusion and exclusion criteria. The relationship between manganese concentration and all-cause, CVD-related, and cancer-related mortality was analyzed by constructing a Cox proportional hazard regression model and a restricted cubic spline (RCS) plot. Additionally, subgroup analyses stratified by age, sex, race/ethnicity, hypertension, diabetes mellitus (DM), chronic heart disease, chronic heart failure, angina pectoris, heart attack, stroke, and BMI were further performed.
In the full adjusted model, compared with the lowest quartile, the adjusted hazard ratios with 95% confidence intervals (CIs) for all-cause, CVD-related, and cancer-related mortality across manganese quartiles were (1.11 (0.87,1.41), 0.96 (0.74, 1.23), and 1.23 (0.96, 1.59); P-value for trend =0.041), (0.86 (0.54, 1.37), 0.87 (0.55, 1.40), and 1.07 (0.67, 1.72); P-value for trend =0.906), and (1.45 (0.92, 2.29), 1.14 (0.70, 1.88), and 1.26 (0.75, 2.11); P-value for trend =0.526), respectively. The RCS curve shown a U-shaped association between manganese concentration and all-cause mortality and CVD-related mortality (P-value for nonlinear <0.05). However, there was an increase and then a decrease in the link between manganese concentration and cancer-related mortality (P-value for nonlinear <0.05). Manganese exposure was positively correlated with sex (correlation coefficient, r =0.19, P-value <0.001) and negatively correlated with age (correlation coefficient, r =-0.11, P-value <0.001) and serum creatinine (correlation coefficient, r =-0.12, P-value <0.001), respectively.
Our findings suggest that elevated serum manganese concentrations are associated with all-cause and CVD-related mortality in the U.S. population and that maintenance of serum manganese between 8.67-9.23 µg/L may promote public health.
Pulmonary rehabilitation (PR) has been recognized to be an effective therapy for chronic obstructive pulmonary disease (COPD). However, in China, the application of PR interventions is still less ...promoted. Therefore, this cross-sectional study aimed to understand COPD patients' intention to receive PR, capture the potential personal, social and environmental barriers preventing their willingness of receiving PR, and eventually identify demanding PR services with the highest priority from patients' point of view.
In total 237 COPD patients were recruited from 8 health care facilities in Zhejiang, China. A self-designed questionnaire was applied to investigate patients' intention to participate in PR and potentially associated factors, including personal dimension such as personal awareness, demographic factors, COPD status and health-related literacy/behaviors, as well as social policies and perceived environmental barriers. The demand questionnaire of PR interventions based on the Kano model was further adopted.
Among the 237 COPD patients, 75.1% of COPD patients were willing to participate in PR interventions, while only 62.9% of the investigated patients had heard of PR interventions. Over 90% of patients believed that the cost of PR services and the ratio of medical insurance reimbursement were potential obstacles hindering them from accepting PR services. The multiple linear regression analysis indicated that the PR skills of medical staff, knowledge promotion and public education levels of PR in the community, patients' transportation concerns and degree of support from family and friends were significantly associated with willingness of participation in PR interventions. By using the Kano model, the top 9 most-requisite PR services (i.e., one-dimensional qualities) were identified from patients' point of view, which are mainly diet guidance, education interventions, psychological interventions and lower limb exercise interventions. Subgroup analysis also revealed that patients' demographics, such as breathlessness level, age, education and income levels, could influence their choice of priorities for PR services, especially services related to exercise interventions, respiratory muscle training, oxygen therapy and expectoration.
This study suggested that PR-related knowledge education among patients and their family, as well as providing basic package of PR services with the most-requisite PR items to COPD patients, were considerable approaches to promote PR attendance in the future.
Several prospective studies have been conducted to examine the relationship between fruit juice intake and risk of incident type 2 diabetes, but results have been mixed. In the present study, we ...aimed to estimate the association between fruit juice intake and risk of type 2 diabetes.
PubMed and Embase databases were searched up to December 2013. All prospective cohort studies of fruit juice intake with risk of type 2 diabetes were included. The pooled relative risks (RRs) with 95% confidence intervals (CIs) for highest vs. lowest category of fruit juice intake were estimated using a random-effects model.
A total of four studies (191,686 participants, including 12,375 with type 2 diabetes) investigated the association between sugar-sweetened fruit juice and risk of incident type 2 diabetes, and four studies (137,663 participants and 4,906 cases) investigated the association between 100% fruit juice and risk of incident type 2 diabetes. A higher intake of sugar-sweetened fruit juice was significantly associated with risk of type 2 diabetes (RR = 1.28, 95%CI = 1.04-1.59, p = 0.02), while intake of 100% fruit juice was not associated with risk of developing type 2 diabetes (RR = 1.03, 95% CI = 0.91-1.18, p = 0.62).
Our findings support dietary recommendations to limit sugar-sweetened beverages, such as fruit juice with added sugar, to prevent the development of type 2 diabetes.
The aim of this study was to determine the effects of long-term Nicotinamide mononucleotide (NMN) treatment on modulating gut microbiota diversity and composition, as well as its association with ...intestinal barrier function. In this study, C57BL/6J mice were fed different concentrations of NMN, and their feces were collected for detection of 16S rDNA and non-targeted metabolites to explore the effects of NMN on intestinal microbiota and metabolites. The results revealed that NMN increased the abundance of butyric acid-producing bacteria (Ruminococcae_UCG-014 and Prevotellaceae_NK3B31_group) and other probiotics (Akkermansia muciniphila), while the abundance of several harmful bacteria (Bilophila and Oscillibacter) were decreased after NMN treatment. Meanwhile, the level of bile acid-related metabolites in feces from the G1 group (0.1 mg/ml) was significantly increased compared to the control group, including cholic acid, taurodeoxycholic acid, taurocholic acid, glycocholic acid, and tauro-β-muricholic acid. In addition, long-term NMN treatment affected the permeability of the intestinal mucosa. The number of goblet cells and mucus thickness increased, as well as expression of tight junction protein. These results demonstrate that NMN reduced intestinal mucosal permeability and exerts a protective effect on the intestinal tract. This study lays the foundation for exploring NMN's utility in clinical research.
Huizhou architecture is the most important Chinese ancient architecture. Being a traditional architecture, Huizhou architecture has always maintained a unique artistic style of elegance, simplicity, ...richness, and integration. Huizhou landscape is an essential embodiment of Huizhou culture. The landscape and pattern of Huizhou villages are the external manifestations of Huizhou culture symbols. This architecture needs to be preserved using multimedia technology and geographic information system. This paper uses these systems to extract the landscape image and develop three-dimensional Huizhou village’s modeling methods with automation, high efficiency, and low cost. It has realized the functions of landscape information query, high-dimensional measurement, terrain analysis, visibility analysis, and virtual roaming of Huipai village. This modeling has specific promotion effects on landscape spatial analysis, landscape planning, ecological protection, natural and cultural inheritance, and tourism development.
Despite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated.
In ...10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53–75 years during 1996–1998), we evaluated the associations of two key CKD measures - estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization discharge, or death records). Additionally, we performed a cross-sectional analysis for the CKD measures and ultrasound-based abdominal aortic diameter in 4258 participants during 2011–2013.
During a median follow-up of 13.9 years, 347 participants developed AAA. The demographically-adjusted hazard ratio (HR) was 4.44 (95% CI 1.58–12.49) for eGFR <30, 3.29 (1.89–5.72) for 30–44, 2.03 (1.29–3.19) for 45–59, and 1.62 (1.11–2.35) for 60–74 compared to eGFR ≥90 mL/min/1.73 m2 and was 2.49 (1.28–4.87) for ACR ≥300, 1.99 (1.40–2.83) for 30–299, and 1.46 (1.08–1.97) for 10–29 compared to ACR <10 mg/g. The associations were generally similar after accounting for additional confounders, such as smoking (although attenuated), or after stratifying by subgroups, including diabetes. The cross-sectional analysis also showed continuous positive associations of these CKD measures with aortic diameter, particularly at the distal aortic segment assessed.
Reduced eGFR and elevated albuminuria were independently associated with greater incidence of AAA and greater abdominal aortic diameter. Our results suggest the potential usefulness of CKD measures to identify persons at high risk of AAA and the need to investigate pathophysiological pathways linking CKD to AAA.
•Chronic kidney disease was positively related to incident clinical abdominal aortic aneurysm.•Both kidney function and damage showed independent associations.•We also confirmed greater ultrasound-based aortic diameter related to chronic kidney disease.
Most strategies for prevention of venous thromboembolism focus on preventing recurrent events. Yet, primary prevention might be possible through approaches targeting the whole population or high-risk ...patients. To inform possible prevention strategies, population-based information on the ability of genetic risk scores to identify risk of incident venous thromboembolism is needed.
We used proportional hazards regression to relate two published genetic risk scores (273-variants versus 5-variants) with venous thromboembolism incidence in the Atherosclerosis Risk in Communities Study (ARIC) cohort (n = 11,292), aged 45-64 at baseline, drawn from 4 US communities.
Over a median of 28 years, ARIC identified 788 incident venous thromboembolism events. Incidence rates rose more than two-fold across quartiles of the 273-variant genetic risk score: 1.7, 2.7, 3.4 and 4.0 per 1,000 person-years. For White participants, age, sex, and ancestry-adjusted hazard ratios (95% confidence intervals) across quartiles were strong 1 (reference), 1.30 (0.99,1.70), 1.85 (1.43,2.40), and 2.58 (2.04,3.28) but weaker for Black participants 1, 1.05 (0.63,1.75), 1.37 (0.84,2.22), and 1.32 (0.80,2.20). The 5-variant genetic risk score showed a less steep gradient, with hazard ratios in Whites of 1, 1.17 (0.89,1.54), 1.48 (1.14,1.92), and 2.18 (1.71,2.79). Models including the 273-variant genetic risk score plus lifestyle and clinical factors had a c-statistic of 0.67.
In the general population, middle-aged adults in the highest quartile of either genetic risk score studied have approximately two-fold higher risk of an incident venous thromboembolism compared with the lowest quartile. The genetic risk scores show a weaker association with venous thromboembolism for Black people.
Gastric ulcers significantly impact the quality of life of patients, the pathogenesis of which is closely associated with Helicobacter pylori (HP) infection. Oxidative stress is involved in the ...pathological mechanism of gastric ulcers. Recently, adenosine A2B Receptor (A2BR) was reported to activate the p38MAPK pathway. However, the role of A2BR in gastric ulcers remains unknown. In the present study, the biological function of A2BR in HP-induced gastric ulcers was investigated to explore novel targets for gastric ulcers. GES-1 cells were infected with HP, followed by incubation with 10 μM BAY60-6583 (A2BR agonist) and 25 nM PSB1115 (A2BR antagonist). In HP-infected GES-1 cells, an increased apoptotic rate, enhanced migration ability, excessive release of reactive oxygen species (ROS), increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity were observed, accompanied by the activation of p38MAPK signaling, which were dramatically aggravated by BAY60-6583 and alleviated by PSB1115. In animal experiments, rats were treated with 2 mg/kg BAY60-6583 and 10 mg/kg PSB1115, followed by gastric ulcer modeling 30 min later. In HP-infected rats, increased ulcer area, elevated pepsin activity, increased hematoxylin and eosin (HE) pathological scores, increased MDA levels, and decreased SOD activity were observed, which were further aggravated by BAY60-6583 and ameliorated by PSB1115. Finally, the effects of A2BR activation on apoptosis, migration, oxidative stress, and p38MAPK signaling in HP-infected GES-1 cells were reversed by an inhibitor of the p38MAPK pathway. Collectively, A2BR facilitated the pathogenesis of HP-induced gastric ulcers by inducing oxidative stress through p38MAPK activation.
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