Platelet Microparticle-Derived MiR-320b Inhibits Hypertension with Atherosclerosis Development by Targeting ETFA.

Hypertension and atherosclerosis often occur simultaneously. This study aimed to explore the role and mechanism of platelet microparticle (PMP) -derived microRNA-320b (miR-320b) in patients with hypertension accompanied by atherosclerosis.We collected samples from 13 controls without hypertension and atherosclerosis and 20 patients who had hypertension accompanied by atherosclerosis. In vitro, platelets were activated by Thrombin receptor-activating peptide to produce PMPs. HUVECs were induced by CoCl2 to mimic a hypoxic environment in vitro. RT-qPCR was employed to detect the expression levels of CD61, miR-320b, and ETFA. The protein expression level of ETFA was evaluated via Western blotting. Furthermore, 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine, and wound healing assays were employed to assess the proliferation and migration of HUVECs. Enzyme-linked immunosorbent assay was used to measure the oxidative stress and inflammation-related factor expression.The expression of miR-320b was reduced in both platelets and PMPs but increased in plasma. MiR-320b promoted CoCl2-induced HUVEC viability, proliferation, and migration. The levels of the oxidative stress factors SOD and GSH as well as the inflammatory factor IL-10 were elevated in the CoCl2 + miR-320b mimics group compared with both the CoCl2 + mimics NC and CoCl2 groups. Conversely, the levels of the oxidative stress factors MDA and ROS as well as the inflammatory factors IL-6, TNF-α, and IL-1ß were decreased. These results were regulated by miR-320b targeting ETFA.PMP-derived miR-320b inhibits the development of hypertension accompanied by atherosclerosis by targeting ETFA.

Relationship between obesity severity, metabolic status and cardiovascular disease in obese adults.

BACKGROUND: Evidence about the associations between obesity severity, metabolic status and risk of incident cardiovascular disease (CVD) in adults with obesity remains limited. METHODS: The study included 109,301 adults with obesity free of prior CVD based on the UK Biobank cohort. Metabolic status was categorized into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes) and metabolically unhealthy obesity (MUO). Obesity severity was classified into three levels: class I (body mass index of 30.0-34.9 kg/m2 ), II (35.0-39.9) and III (≥40.0). Cox proportional hazards models were used for analyses. RESULTS: There were 8059 incident CVD events during a median follow-up of 8.1 years. MUO was significantly associated with a 74% increased CVD risk compared with MHO (HR = 1.74, 95% CI: 1.62-1.83). There was a significant interaction between obesity severity and metabolic status on an additive scale regarding CVD risk. When taking class I obesity as reference, class II was nonsignificantly associated with an increased risk of CVD in the MHO group (HR = 1.07, 95% CI: 0.90-1.27), while class III was significantly related to increased risks of CVD (HR = 1.48, 95% CI: 1.12-1.96). In the MUO group, both classes II and III were significantly related to increased risks of CVD. Significant subgroup effects of age (p = .009) and sex (p = .047) were observed among participants with MUO but not in the MHO group. CONCLUSIONS: Both elevated obesity severity and MUO were significantly associated with increased risks of CVD in adults with obesity, while metabolic status could modify the relationship between obesity severity and CVD risk. More research is needed to further clarify the relationship.

Association between metabolically healthy obesity and risk of atrial fibrillation: taking physical activity into consideration.

The modification of physical activity (PA) on the metabolic status in relation to atrial fibrillation (AF) in obesity remains unknown. We aimed to investigate the independent and joint associations of metabolic status and PA with the risk of AF in obese population. Based on the data from UK Biobank study, we used Cox proportional hazards models for analyses. Metabolic status was categorized into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). PA was categorized into four groups according to the level of moderate-to-vigorous PA (MVPA): none, low, medium, and high. A total of 119,424 obese participants were included for analyses. MHO was significantly associated with a 35% reduced AF risk compared with MUO (HR = 0.65, 95% CI: 0.57-0.73). No significant modification of PA on AF risk among individuals with MHO was found. Among the MUO participants, individuals with medium and high PA had significantly lower AF risk compared with no MVPA (HR = 0.84, 95% CI: 0.74-0.95, and HR = 0.87, 95% CI: 0.78-0.96 for medium and high PA, respectively). As the severity of MUO increased, the modification of PA on AF risk was elevated accordingly. To conclude, MHO was significantly associated with a reduced risk of AF when compared with MUO in obese participants. PA could significantly modify the relationship between metabolic status and risk of AF among MUO participants, with particular benefits of PA associated with the reduced AF risk as the MUO severity elevated.

Comparative effectiveness and safety of direct acting oral anticoagulants in nonvalvular atrial fibrillation for stroke prevention: a systematic review and meta-analysis.

PURPOSE: To systematically review available evidence of indirect comparisons from RCTs and direct comparisons from observational studies regarding the comparative effectiveness and safety of DOACs in patients with AF. METHODS: Electronic databases including EMBASE, MEDLINE, and PUBMED were searched up to June 5th, 2020. Primary endpoints included effectiveness (stroke or systemic embolism [SE]) and safety (major bleeding) outcomes. Bucher methods and random-effects models were conducted for indirect and direct comparisons among DOACs, respectively. Ranking probability analyses and the number needed to treat for net effect (NNTnet) were applied. RESULTS: A total of 36 studies, involving 7 RCTs (n = 60,292 patients) and 29 observational studies (n = 1,164,821 patients), were included for analyses. Regarding the risk of stroke/SE, no significant differences were found from indirect comparisons of RCTs among the DOACs. For major bleeding, apixaban tended to be safer than rivaroxaban and dabigatran based on both direct and indirect comparisons (all p < 0.05; evidence quality: very low to moderate). Ranking probability analysis showed that apixaban had a high probability of being the best treatment in decreased risk of stroke/SE and major bleeding (80.30% and 91.30%, respectively). Likewise, apixaban was found to have the highest net clinical benefit (0.02, 95% CI: 0.014-0.029) and smallest NNTnet (48, 95% CI: 35-74). CONCLUSIONS: Apixaban appeared to have a favorable effectiveness-safety profile compared with the other DOACs in AF for stroke prevention, based on evidence from both direct and indirect comparisons. However, additional high-quality evidence is needed to support firm recommendations on clinical decision-making.

Relationship between different particle size fractions and all-cause and cause-specific emergency ambulance dispatches.

BACKGROUND: Evidence on the relationship between different particle size fractions and emergency ambulance dispatches (EAD) remains limited and sparse. METHODS: We collected daily data of EAD, ambient air pollution and meteorological data from 2014 to 2018 in Guangzhou, China. We used a generalized additive model with covariate adjustments to estimate the associations between different particle size fractions and EAD related to all-cause, cardiovascular diseases, and respiratory diseases. Several subgroup and sensitivity analyses were also performed. RESULTS: Significant associations were observed between PM2.5, PM2.5-10, PM10 and EADs. A 10 µg/m3 increase of PM2.5, PM2.5-10, and PM10 was associated with an increase of 0.98% (95% CI: 0.67, 1.28%), 2.06% (95% CI: 1.44, 2.68%), and 0.75% (95%CI: 0.53, 0.96%) in all-cause EAD, with an increase of 0.69% (95% CI: 0.00, 1.39%), 2.04% (95% CI: 0.64, 3.45%), and 0.60% (95%CI: 0.11,1.10%) in cardiovascular-related EAD, and an increase of 1.14% (95% CI: 0.25, 2.04%), 2.52% (95% CI: 0.72, 4.35%), and 0.89% (95%CI: 0.25,1.52%) in respiratory-related EAD at lag03, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: This study revealed that PM2.5, PM2.5-10 and PM10 were significantly related with risks of all-cause and cause-specific EAD. More evidence of high quality may be needed to further support our results in this ecological study.

Association Between Remnant Cholesterol and Risk of Incident Atrial Fibrillation: Population-Based Evidence From a Large-Scale Prospective Cohort Study.

BACKGROUND: Evidence for the relationship between remnant cholesterol (RC) and incident atrial fibrillation (AF) risk remains sparse and limited. METHODS AND RESULTS: Participants were enrolled between 2006 and 2010 and followed up to 2021. The multivariable Cox proportional hazards model was used to examine the relationship between RC quartiles and risk of incident AF. Subgroup analyses and sensitivity analyses were performed to explore the potential modification of the association and the robustness of the main findings. A total of 422 316 participants (mean age, 56 years; 54% women) were included for analyses. During a median follow-up of 11.9 years (first quartile-third quartile, 11.6-13.2 years), there were 24 774 AF events documented with an incidence of 4.92 events per 1000 person-years (95% CI, 4.86-4.98). Participants in higher RC quartiles had a lower risk of incident AF than those in the lowest quartile (first quartile): hazard ratio (HR)=0.96 (95% CI, 0.91-1.00) for second quartile; HR=0.92 (95% CI, 0.88-0.96) for third quartile; and HR=0.85 (95% CI, 0.81-0.89) for fourth quartile (P for trend <0.001). The association between RC quartiles and risk of incident AF was stronger in participants aged ≥65 years, in men, and in participants without history of diabetes when compared with control groups (P<0.001 for interaction). CONCLUSIONS: On the basis of data from this large-scale prospective cohort study, elevated RC was associated with a lower risk of incident AF.

Relationship between short-term exposure to sulfur dioxide and emergency ambulance dispatches due to cardiovascular disease.

Background: The relationship between sulfur dioxide (SO2) and cardiovascular disease (CVD) remains inconclusive. We aimed to clarify the association between short-term exposure to SO2 and emergency ambulance dispatches (EADs) due to CVD. Methods: We collected daily data on the number of EADs due to CVD, air pollutants, and meteorological factors between October 2013 and June 2018 in Guangzhou, China. We used the quasi-Poisson generalized additive model combined with a distributed lag nonlinear model to estimate the short-term effect of SO2 on EADs due to CVD in multivariable models. Subgroup and sensitivity analyses were also performed. Results: A total of 37,889 EADs due to CVD were documented during the study period. The average daily SO2 concentration was 12.5 µg/m3. A significant relationship between SO2 and EADs due to CVD was found, with a relative risk of 1.04 (95% confidence interval: 1.02, 1.06) with each 10 µg/m3 increment of SO2 at lag 0-1. The relationship was stronger in males, for participants aged ≥65 years, and in the cold season; however, no significant modification by subgroup was found in the association between SO2 and EADs due to CVD. Similar results from sensitivity analyses to the main findings were observed. Conclusions: Short-term exposure to SO2 was significantly associated with increased EADs due to CVD.

Relationship between remnant cholesterol and risk of heart failure in participants with diabetes mellitus.

BACKGROUND: Evidence about the association between calculated remnant cholesterol (RC) and risk of heart failure (HF) in participants with diabetes mellitus (DM) remains sparse and limited. METHODS: We included a total of 22 230 participants with DM from the UK Biobank for analyses. Participants were categorized into three groups based on their baseline RC measures: low (with a mean RC of 0.41 mmol/L), moderate (0.66 mmol/L), and high (1.04 mmol/L). Cox proportional hazards models were used to evaluate the relationship between RC groups and HF risk. We performed discordance analysis to evaluate whether RC was associated with HF risk independently of low-density lipoprotein cholesterol (LDL-C). RESULTS: During a mean follow-up period of 11.5 years, there were a total of 2232 HF events observed. The moderate RC group was significantly related with a 15% increased risk of HF when compared with low RC group (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.01-1.32), while the high RC group with a 23% higher HF risk (HR = 1.23, 95% CI: 1.05-1.43). There was significant relationship between RC as a continuous measure and the increased HF risk (P < 0.01). The association between RC and risk of HF was stronger in participants with HbA1c level ≥ 53 mmol/mol when compared with HbA1c < 53 mmol/mol (P for interaction = 0.02). Results from discordance analyses showed that RC was significantly related to HF risk independent of LDL-C measures. CONCLUSIONS: Elevated RC was significantly associated with risk of HF in patients with DM. Moreover, RC was significantly related to HF risk independent of LDL-C measures. These findings may highlight the importance of RC management to HF risk in patients with DM.

Relationship between diurnal temperature range and emergency ambulance dispatches due to stroke in Guangzhou, China.

BACKGROUND: The evidence between diurnal temperature range (DTR) and stroke remains controversial and sparse. We aimed to assess the relationship between DTR and emergency ambulance dispatches (EADs) due to stroke, and to explore whether there were effect modifications to the relationship. METHODS: A Quasi-Poisson generalized linear regression combined with a distributed lag non-linear model was used to examine the relationship between DTR and EADs for stroke between January 1st 2011 and June 30th 2018 in Guangzhou, China. We estimated the effects of the low DTR and high DTR (defined as DTR below and above 10 °C respectively) on EADs. The effects of minimum, maximum, 5th, 25th, 50th, 75th, and 95th percentiles of DTR compared with the DTR of 10 °C were also analyzed. RESULTS: A total of 20,275 EADs for stroke were included for analyses, among which 17,556 EADs were used in the model further adjusted for age and sex. A quasi-U-shaped relationship between DTR and EADs over lag0-2 days was observed. For the low DTR, per 1 °C decrease in DTR was significantly associated with an increase of 2.64% (RR = 1.03, 95% CI: 1.01-1.04) for EADs, while per 1 °C increase for the high DTR was non-significantly related with an increased risk of EADs (RR = 1.01, 95% CI: 0.90-1.13). Significant effects of the 5th and 25th percentiles of DTR on EADs were found when compared with the DTR of 10 °C. No significant effect modifications by age, sex or season were found to the association between DTR and EADs. CONCLUSIONS: We found a quasi-U-shaped relationship between DTR and EADs due to stroke in this study, while age, sex or season did not significantly modify the association between DTR and EADs. More high-quality evidence is needed to further explore and validate the relationship between DTR and stroke.

Construction and Analysis of the lncRNA-miRNA-mRNA Network Based on Competing Endogenous RNA in Atrial Fibrillation.

BACKGROUND: Accumulated studies have revealed that long non-coding RNAs (lncRNAs) play critical roles in human diseases by acting as competing endogenous RNAs (ceRNAs). However, functional roles and regulatory mechanisms of lncRNA-mediated ceRNA in atrial fibrillation (AF) remain unknown. In the present study, we aimed to construct the lncRNA-miRNA-mRNA network based on ceRNA theory in AF by using bioinformatic analyses of public datasets. METHODS: Microarray data sets of GSE115574 and GSE79768 from the Gene Expression Omnibus database were downloaded. Twenty-one AF right atrial appendage (RAA) samples and 22 sinus rhythm (SR) subjects RAA samples were selected for subsequent analyses. After merging all microarray data and adjusting for batch effect, differentially expressed genes were identified. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. A ceRNA network was constructed. RESULT: A total of 8 lncRNAs and 43 mRNAs were significantly differentially expressed with fold change >1.5 (p < 0.05) in RAA samples of AF patients when compared with SR. GO and KEGG pathway analysis showed that cardiac muscle contraction pathway were involved in AF development. The ceRNA was predicted by co-expressing LOC101928304/ LRRC2 from the constructional network analysis, which was competitively combined with miR-490-3p. The expression of LOC101928304 and LRRC were up-regulated in myocardial tissue of patients with AF, while miR-490-3p was down-regulated. CONCLUSION: We constructed the LOC101928304/miR-490-3p/LRRC2 network based on ceRNA theory in AF in the bioinformatic analyses of public datasets. The ceRNA network found from this study may help improve our understanding of lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of AF.

circRNA-miRNA Complex Participates in the Apoptosis of Myocardial Cells in Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion (I/R) injury is a common condition. This study aimed to investigate the potential mechanisms of circ_Ddx60 in the mouse model of I/R injury. Cardiac tissues were used to extract RNA for subsequent RNA sequencing analysis. Bioinformatic analysis was performed and circ_Ddx60 and Bcl2a1a (B cell leukemia/lymphoma 2 related protein A1a) were selected for further validation. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect the gene expression level. The effect of circ_Ddx60 on cardiac cell apoptosis was examined. The function of miR-302a-3p in cell apoptosis was further explored in circ_Ddx60-overexpressed HL-1 cells under hypoxia/reoxygenation (H/R) treatment. We have revealed a number of differentially expressed circRNAs and mRNAs between the I/R group and sham groups, with circ_Ddx60 being among them. Treatment of HL-1 cells with hypoxia/reoxygenation (H/R) led to an overexpression of circ_Ddx60, which then inhibited apoptosis and promoted the Bcl2a1a expression. Furthermore, circ_Ddx60 directly binds with miR-302a-3p, which could reverse the effect of circ_Ddx60 overexpression on cellular apoptosis and Bcl2a1a expression. Our study revealed that circ_Ddx60 inhibits apoptosis in myocardial cells by regulating the miR-302a-3p/Bcl2a1a axis, which provides novel insights into the prevention of myocardial I/R injury.

Relationship between Serum 25-Hydroxyvitamin D Level and Risk of Recurrent Stroke.

Evidence for the association between vitamin D and risk of recurrent stroke remains sparse and limited. We aimed to assess the relationship between serum circulating 25-hydroxyvitamin D (25(OH)D) level and risk of recurrent stroke in patients with a stroke history, and to identify the optimal 25(OH)D level in relation to lowest recurrent stroke risk. Data from the nationwide prospective United Kingdom Biobank were used for analyses. Primary outcome was time to first stroke recurrence requiring a hospital visit during follow-up. We used Cox proportional hazards regression model with restricted cubic splines to explore 25(OH)D level in relation to recurrent stroke. The dose-response relationship between 25(OH)D and recurrent stroke risk was also estimated, taking the level of 10 nmol/L as reference. A total of 6824 participants (mean age: 60.6 years, 40.8% females) with a baseline stroke were included for analyses. There were 388 (5.7%) recurrent stroke events documented during a mean follow-up of 7.6 years. Using Cox proportional hazards regression model with restricted cubic splines, a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke was found, where the lowest recurrent stroke risk lay at the 25(OH)D level of approximate 60 nmol/L. When compared with 10 nmol/L, a 25(OH)D level of 60 nmol/L was related with a 48% reduction in the recurrent stroke risk (hazard ratio = 0.52, 95% confidence interval: 0.33-0.83). Based on data from a large-scale prospective cohort, we found a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke in patients with a stroke history. Given a lack of exploring the cause-effect relationship in this observational study, more high-quality evidence is needed to further clarify the vitamin D status in relation to recurrent stroke risk.

Rare and potential pathogenic mutations of LMNA and LAMA4 associated with familial arrhythmogenic right ventricular cardiomyopathy/dysplasia with right ventricular heart failure, cerebral thromboembolism and hereditary electrocardiogram abnormality.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with ventricular arrhythmia, heart failure (HF), and sudden death. Thromboembolism is also an important and serious complication of ARVC/D. However, the etiology of ARVC/D and thromboembolism and their association with genetic mutations are unclear. METHODS: Genomic DNA samples of peripheral blood were conducted for whole-exome sequencing (WES) and Sanger sequencing in the ARVC/D family. Then, we performed bioinformatics analysis for genes susceptible to cardiomyopathies and arrhythmias. Further, we analyzed how the potential pathogenic mutations were affecting the hydrophobicity and phosphorylation of amino acids and their joint pathogenicity by ProtScale, NetPhos and ORVAL algorisms. RESULTS: We discovered a Chinese Han family of ARVC/D with right ventricular HF (RVHF), cerebral thromboembolism, arrhythmias (atrial fibrillation, atrial standstill, multifocal ventricular premature, complete right bundle block and third-degree atrioventricular block) and sudden death. Based on the WES data, the variants of LMNA p.A242V, LAMA4 p.A225P and RYR2 p.T858M are highly conserved and predicated as "deleterious" by SIFT and MetaSVM algorithms. Their CADD predicting scores are 33, 27.4 and 25.8, respectively. These variants increase the hydrophobicity of their corresponding amino acid residues and their nearby sequences by 0.378, 0.266 and 0.289, respectively. The LAMA4 and RYR2 variants lead to changes in protein phosphorylation at or near their corresponding amino acid sites. There were high risks of joint pathogenicity for cardiomyopathy among these three variants. Cosegregation analysis indicated that LMNA p.A242V might be an important risk factor for ARVC/D, electrocardiogram abnormality and cerebral thromboembolism, while LAMA4 p.A225P may be a pathogenic etiology of ARVC/D and hereditary electrocardiogram abnormality. CONCLUSIONS: The LMNA p.A242V may participate in the pathogenesis of familial ARVC/D with RVHF and cerebral thromboembolism, while LAMA4 p.A225P may be associated with ARVC/D and hereditary electrocardiogram abnormality.

Histone Deacetylases in the Pathogenesis of Diabetic Cardiomyopathy.

The global burden of diabetes mellitus and its complications are currently increasing. Diabetic cardiomyopathy (DCM) is the main cause of diabetes mellitus associated morbidity and mortality; therefore, a comprehensive understanding of DCM development is required for more effective treatment. A disorder of epigenetic posttranscriptional modification of histones in chromatin has been reported to be associated with the pathology of DCM. Recent studies have implicated that histone deacetylases could regulate cardiovascular and metabolic diseases in cellular processes including cardiac fibrosis, hypertrophy, oxidative stress and inflammation. Therefore in this review, we summarized the roles of histone deacetylases in the pathogenesis of DCM, aiming to provide insights into exploring potential preventative and therapeutic strategies of DCM.

Association Between GJA1 rs13216675 T>C Polymorphism and Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Rs13216675 T>C polymorphism, an SNP (single-nucleotide polymorphism) close to the gap junction protein alpha 1 (GJA1) gene, has been reported to be associated with risk of atrial fibrillation (AF); however, the results remained inconclusive. We aimed to perform a systematic review to clarify the relationship between rs13216675 and risk of AF. Materials and methods: We systematically searched the databases of PubMed, EMBASE, Web of Science, and the Chinese National Knowledge Infrastructure up to July 15, 2020. Data were synthesized using the random-effects model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the relationship between rs13216675 and risk of AF. Results: Seven studies involving 39,827 cases and 458,466 controls were analyzed in the meta-analysis. The overall pooled OR of rs13216675 polymorphism for AF was significant (OR = 1.10, 95% CI = 1.07-1.12, P < 0.001) under the additive genetic model. Subgroup analyses revealed that rs13216675 polymorphism was significantly associated with AF in both Asians (OR = 1.12, 95% CI = 1.07-1.17, P < 0.001) and Europeans (OR = 1.09, 95% CI = 1.06-1.12, P < 0.001). When data were stratified by control sources, rs13216675 polymorphism was significantly related to AF in studies with both population-based controls (OR = 1.09, 95% CI = 1.07-1.12) and hospital-based controls (OR = 1.12, 95% CI = 1.07-1.17). No evidence of publication bias was detected. Conclusion: Our meta-analysis suggested that rs13216675 was significantly related to risk of AF and, therefore, might serve as a potential biological marker of AF.

Identification of potential crucial genes in atrial fibrillation: a bioinformatic analysis.

BACKGROUND: Atrial fibrillation (AF) is at least partially heritable, affecting 2-3% of the population in Europe and the USA. However, a substantial proportion of heritability is still lacking. In the present study, we aim to identify potential crucial genes associated with AF through bioinformatic analyses of public datasets. METHODS: Microarray data sets of GSE115574, GSE31821, GSE79768, GSE41177 and GSE14975 from the Gene Expression Omnibus (GEO) database were retrieved. After merging all microarray data and adjusting batch effect, differentially expressed genes (DEGs) were identified. Functional enrichment analyses based on Gene Ontology (GO) resource, Kyoto Encyclopedia of Genes and Genomes (KEGG) resource, Gene Set Enrichment Analysis (GSEA), Reactome Pathway Database and Disease Ontology (DO) were carried out. Protein-protein interaction (PPI) network was constructed using the STRING database. Combined with aforementioned significant bioinformatics information, potential crucial genes were subsequently selected. The comparative toxicogenomics database (CTD) was used to explore the interaction between potential crucial genes and AF. RESULT: We identified 27 of DEGs with gene expression fold change (FC) ≥ 1.5 or ≤ 2/3 (|log2 FC| ≥ 0.58) and 5 with FC ≥ 2 or ≤ 0.5 (|log2 FC| ≥ 1) of AF patients compared with sinus rhythm controls. The most significantly enriched pathway was regulation of insulin-like growth factor transport and uptake by insulin-like growth factor binding proteins. IGFBP2, C1orf105, FHL2, CHGB, ATP1B4, IGFBP3, SLC26A9, CXCR4 and HTR2B were considered the potential crucial genes. CTD showed CXCR4, IGFBP2, IGFBP3 and FHL2 had higher scores with AF. CONCLUSIONS: The 9 potential crucial genes, especially CXCR4, IGFBP2, IGFBP3 and FHL2, may be associated with risk of AF. Our study provided new insights of AF into genetics, molecular pathogenesis and new therapeutic targets.

Real-time fluorescence Loop-Mediated Isothermal Amplification (LAMP) for rapid and reliable diagnosis of pulmonary tuberculosis.

A reliable, simple and rapid diagnostic method that can be helpful in pulmonary tuberculosis diagnosis is urgently needed. Loop-mediated Isothermal Amplification (LAMP) allows DNA to be amplified rapidly at a constant temperature. In this study, real-time fluorescence LAMP was evaluated to rapidly detect Mycobacterium tuberculosis in sputum and was compared to the performance of real-time fluorescence quantitative PCR (Q-PCR). All the standard MTB strains were successfully detected and limit of detection (LOD) was 10(2)CFU/mL by real-time fluorescence LAMP within 20min. In light of MTB in sputum, the real-time fluorescence LAMP method yielded a sensitivity of 98.0% and a specificity of 78.3%, compared to Q-PCR assay, which yielded a sensitivity of 96.0% and a specificity of 82.6% for PTB diagnosis. There was an excellent overall agreement between LAMP and Q-PCR for PTB (κ=0.315) and non-PTB (κ=0.862). Therefore, the real-time fluorescence LAMP assay is a rapid, sensitive, and specific method to detect pulmonary tuberculosis.

[Consciousness and abilities on health emergency and the roles of emergency response among public at the communities].

OBJECTIVE: To evaluate the consciousness of health emergency and the abilities on self- and mutual medical aids among the public at the community level, as well as the community responses on health-related emergencies and other factors. METHODS: Random equidistant sampling method was used to extract 617 households before choosing a family member sampled by Kish Grid method. All the members were investigated face to face on a questionnaire-"Health emergency and related ability regarding self and mutual medical aids of the residents". Data were entered into computer database by using software Epi Data 3.1 and were analyzed by SPSS 21.0. RESULTS: Among the 617 households under survey, 47.84% of the public had general awareness on health-related emergencies. Regarding the following items as:prevention and isolation strategies of infectious disease, on safely procedures of earthquake and fires, on prevention of food poisoning, on prevention and first aid of emerging infectious diseases etc., the rates of awareness were 65.04%, 62.92%, 43.62% and 18.79% respectively. Proportions of households which had the first aid supplies were:first aid medicine box as 56.08%; fire extinguisher as 43.60%; spare water and food as 39.40%; having facilities as ropes, whistles and smoke masks for escape were all less than 15%. Rates of awareness on the following items as: correct use of gas switch as 81.52%, knowing the location of the circuit with gear and the fire hydrant as 74.39% and 35.98% , respectively. The correct disposal rates of the residents on the following items were:electric shock and falls (89.63%), patients of infectious diseases (83.31%), gas poisoning (82.98%), suspected symptoms on infectious diseases(82.66%), explosion and burns (66.78%), scald (62.72%)and sprain (57.05%). Scores on the related abilities were as follows: emergency(7.65, out of 10 points), escape(3.55, out of 5 points), self- and mutual medical aids (10.71, out of 16 points). Proportions of having learned and applied of first aid techniques among residents on the following items were:artificial breathing, chest compressions and cardiopulmonary resuscitation were all less than 10%. Level of knowing the first aid techniques was correlated with age and culture of the residents (P < 0.05). CONCLUSION: Both consciousness on health emergency and the abilities on self- and mutual medical aids were low among the community public, suggesting that both the government and pubic should pay more attention to the role of the abilities on self- and mutual medical aids.

[Effect of rosiglitazone on tumor necrosis factor-alpha-induced nuclear factor-kappaB and coupling factor 6 expressions in human umbilical vein endothelial cells].

OBJECTIVE: To investigate the effect of rosiglitazone on the expression of nuclear factor-kappaB (NF-kappaB) and coupling factor 6 (CF6) induced by tumor necrosis factor-alpha (TNF-alpha) in cultured human umbilical vein endothelial cells (HUVEC). METHODS: Cultured HUVEC of passage 3-5 were stimulated with TNF-alpha and then cultured in the presence of rosiglitazone. The expression of CF6 and NF-kappaB subunit p65 were evaluated by immunocytochemistical method. RESULTS: Pretreatment of HUVECs with rosiglitazone inhibited TNF-alpha-induced expression of CF6 in a dose-dependent manner. The activation of CF6 stimulated by TNF-alpha was suppressed by ROS in a dose-dependent manner. CONCLUSION: TNF-alpha-induced enhancement of the gene expression and release of CF6 is mediated by activation of NF-kappaB signaling pathway. ROS can inhibit the activation of IKK, block NF-kappaB signaling pathway and inhibit the expression of CF6, which may be the mechanism underlying the action of TZDs on hypertension.