Causality of blood metabolites and metabolic pathways on peripheral arteriosclerosis: a Mendelian randomization study.

Background: Peripheral arteriosclerosis is caused by any atherosclerosis outside the heart and brain. However, the underlying biological mechanisms are not fully understood. This study aims to explore the causal relationship between blood metabolites and peripheral arteriosclerosis. Methods: A Mendelian randomization (MR) analysis was implemented to estimate the causality of blood metabolites on peripheral arteriosclerosis. A genome-wide association study (GWAS) of 1,400 metabolites was used as the exposure, whereas two different GWAS datasets of peripheral arteriosclerosis were the outcomes. Inverse-variance weighted (IVW) was the main analysis of causal analysis. MR-Egger, the simple mode, weighted median and weighted mode were used to increase the stability and robustness of the results. Cochran Q test, MR-Egger intercept test, the funnel plot, and MR-Pleiotropy RESidual Sum and Outlier were used for sensitivity analyses. Furthermore, metabolic pathway enrichment analysis was performed using MetaboAnalyst5.0. Results: In this MR study, eight blood metabolites have a strong causal relationship with peripheral arteriosclerosis, including 1-myristoyl-2-arachidonoyl-GPC (14:0/20:4), 1-palmitoyl-2-arachidonoyl-gpc (16:0/20:4n6), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE, 1-palmitoyl-2-dihomo-linolenoyl-GPC, Gamma-glutamylleucine, Deoxycholic acid glucuronide and two named X- (X-24546, X-26111). In addition, five important metabolic pathways in peripheral arteriosclerosis were identified through metabolic pathway analysis. Conclusion: This study provides evidence for the causal relationship between blood metabolites and peripheral arteriosclerosis, and these eight blood metabolites provide new perspectives for screening and prevention of peripheral arteriosclerosis in the future.

Microplastics are associated with elevated atherosclerotic risk and increased vascular complexity in acute coronary syndrome patients.

BACKGROUND: Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis-gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome. RESULTS: The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts. CONCLUSION: These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association. HIGHLIGHTS: 1 Blood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients. 2 Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP. 3 Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients.

Whole-genome sequence of Sclerotium delphinii, a pathogenic fungus of Dendrobium officinale southern blight.

Dendrobium officinale is a rare and precious medicinal plant. Southern blight is a destructive disease in the artificial cultivation of D. officinale, and one of its pathogens is Sclerotium delphinii. S. delphinii is a phytopathogenic fungus with a wide host range with extremely strong pathogenicity. In this study, S. delphinii was isolated from D. officinale with southern blight. Subsequently, this specific strain underwent thorough whole-genome sequencing using the PacBio Sequel II platform, which employed single-molecule real-time (SMRT) technology. Comprehensive annotations were obtained through functional annotation of protein sequences using various publicly available databases. The genome of S. delphinii measures 73.66 Mb, with an N90 contig size of 2,707,110 bp, and it contains 18,506 putative predictive genes. This study represents the first report on the genome size assembly and annotation of S. delphinii, making it the initial species within the Sclerotium genus to undergo whole-genome sequencing, which can provide solid data and a theoretical basis for further research on the pathogenesis, omics of S. delphinii.

Reliability and validity of the Chinese version of the coronary artery disease empowerment scale (CADES) in patients with coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Empowerment is a comprehensive concept involving intrapersonal, interactional, and behavioral aspects. However, there is a lack of a specific empowerment scale for Coronary artery disease (CAD) related to knowledge and skills in China. The reliability and validity of the Coronary Artery Disease Empowerment Scale (CADES) need to be tested. This study aimed to assess the reliability and validity of the Chinese version of CADES among patients with CAD in China. METHODS: The study adopted a cross-sectional design. After obtaining the copyright by contacting the author, the original English CADES was developed into Chinese by forward translation, back-translation, cross-cultural adaptation, and a pretest (30 patients). The Chinese version of CADES was administered to 391 CAD patients between September 2022 and June 2023, with the reliability and validity of the version evaluated. Exploratory factor analysis and confirmatory factor analysis were performed to examine the underlying factor structure of the translated questionnaire. The Cronbach's α coefficient, Guttman's split-half coefficient, and McDonald's omega coefficient were calculated to verify the scale's reliability. RESULTS: For the Chinese version of CADES, the scale-content validity index was 0.972, with the item-content validity index ranging from 0.86 to 1.00. The questionnaire comprised 25 items, and exploratory factor analysis extracted four factors with loadings > 0.40, explaining 62.382% of the total variance. An acceptable model fit was achieved (χ2/df = 1.764, RMSEA = 0.060, TLI = 0.901, CFI = 0.912, IFI = 0.913). The Cronbach's α coefficient of the total questionnaire was 0.928, with coefficients for the four factors ranging from 0.683 to 0.913. The split-half reliability coefficient was 0.777, and the McDonald's omega reliability coefficient was 0.926. CONCLUSIONS: The Chinese version of CADES is reliable and valid among CAD patients in China. This instrument can serve as a valuable reference for guiding the implementation of targeted intervention strategies tailored to the empowerment status of CAD patients in clinical practice.

Lithium carbonate-induced giant goiter and subclinical hyperthyroidism in a patient with schizophrenia: A case report and review of literature.

BACKGROUND: Lithium carbonate is used to manage various mood disorders, but it can cause thyroid abnormalities, including goiter, hypothyroidism, and hyperthyroidism. In rare cases, it can lead to giant goiter and subclinical hyperthyroidism, which may require surgical intervention in severe cases. CASE SUMMARY: This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment. The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve, which led to respiratory distress, hoarseness, and dysphagia. The immediate danger of suffocation required urgent surgical intervention. In this report, we describe the case of a 41-year-old Chinese woman. This sheds light on the etiology and challenges associated with managing a giant goiter. The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion. Prior to the procedure, the patient was given iodine to prepare. Concurrently, changes were made to the psychiatric medication regimen. Following surgery, the patient's respiratory function and vocal cord functionality improved significantly, and her mental state remained stable. CONCLUSION: It is essential to monitor thyroid function, test thyroid antibody levels, and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment. This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.

Embodied Conversational Agents for Chronic Diseases: Scoping Review.

BACKGROUND: Embodied conversational agents (ECAs) are computer-generated animated humanlike characters that interact with users through verbal and nonverbal behavioral cues. They are increasingly used in a range of fields, including health care. OBJECTIVE: This scoping review aims to identify the current practice in the development and evaluation of ECAs for chronic diseases. METHODS: We applied a methodological framework in this review. A total of 6 databases (ie, PubMed, Embase, CINAHL, ACM Digital Library, IEEE Xplore Digital Library, and Web of Science) were searched using a combination of terms related to ECAs and health in October 2023. Two independent reviewers selected the studies and extracted the data. This review followed the PRISMA-ScR (Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. RESULTS: The literature search found 6332 papers, of which 36 (0.57%) met the inclusion criteria. Among the 36 studies, 27 (75%) originated from the United States, and 28 (78%) were published from 2020 onward. The reported ECAs covered a wide range of chronic diseases, with a focus on cancers, atrial fibrillation, and type 2 diabetes, primarily to promote screening and self-management. Most ECAs were depicted as middle-aged women based on screenshots and communicated with users through voice and nonverbal behavior. The most frequently reported evaluation outcomes were acceptability and effectiveness. CONCLUSIONS: This scoping review provides valuable insights for technology developers and health care professionals regarding the development and implementation of ECAs. It emphasizes the importance of technological advances in the embodiment, personalized strategy, and communication modality and requires in-depth knowledge of user preferences regarding appearance, animation, and intervention content. Future studies should incorporate measures of cost, efficiency, and productivity to provide a comprehensive evaluation of the benefits of using ECAs in health care.

The Use of Gamification in the Self-Management of Patients With Chronic Diseases: Scoping Review.

BACKGROUND: Chronic disease self-management is a public health issue of worldwide concern, and gamification is an emerging strategy to improve patients' participation in chronic disease self-management. Some studies have summarized designs for the gamification of chronic disease self-management from the perspective of eHealth technology, but they have not mentioned differences in design methods, functions, and evaluation methods of gamified designs for self-management in different chronic diseases. OBJECTIVE: This scoping review aims to synthesize the characteristics of realization forms, functions, and evaluation methods in chronic disease self-management gamification to improve self-management among the chronic disease population. METHODS: We applied a methodological framework for scoping reviews and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist. As of January 7, 2023, we systematically searched 9 databases for relevant studies from January 2012 to December 2022. Related data were extracted based on the research questions. We calculated the frequencies, charted the quantitative data, and coded the extracted material for qualitative content analysis. RESULTS: We retrieved 16,221 records, of which 70 (0.43%) met the eligibility criteria. In the included research, the target populations for gamified designs for self-management of chronic diseases included patients with stroke, cancer, diabetes, chronic obstructive pulmonary disease, coronary heart disease, obesity, and hypertension. Almost all studies mentioned technical support for gamification (68/70, 97%), mainly in the form of active video games (58/70, 83%); however, less than half of the studies mentioned the theoretical basis for gamification (31/70, 44%). There were 37 concepts or theories relevant to gamification design, most of which were in the field of psychology or were cross-disciplinary (n=33, 89%). Gamification for the self-management of chronic diseases has been widely recognized, including for promoting physical exercise and rehabilitation training (48/99, 48%), increasing initiative for symptom management (18/99, 18%), providing psychological support (14/99, 14%), improving cognitive function (12/99, 12%), and improving medication adherence (7/99, 7%). A total of 39 studies mentioned the gamification effect; however, we did not find a unified evaluation standard. CONCLUSIONS: This scoping review focuses on gamification designs for chronic disease self-management and summarizes the realization forms and functions of gamification in self-management for different patient populations. With practice in a gamified internet-based environment, patients can not only master the knowledge and skills of self-management in fascinating scenarios but also benefit from gaming experience and make better health-related decisions in real life. It is worth noting that a comprehensive evaluation of the users as well as a personalized and targeted intervention should be developed before gamification.

KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Lysine butyrylation of HSP90 regulated by KAT8 and HDAC11 confers chemoresistance.

Posttranslational modification dramatically enhances protein complexity, but the function and precise mechanism of novel lysine acylation modifications remain unknown. Chemoresistance remains a daunting challenge to successful treatment. We found that lysine butyrylation (Kbu) is specifically upregulated in chemoresistant tumor cells and tissues. By integrating butyrylome profiling and gain/loss-of-function experiments, lysine 754 in HSP90 (HSP90 K754) was identified as a substrate for Kbu. Kbu modification leads to overexpression of HSP90 in esophageal squamous cell carcinoma (ESCC) and its further increase in relapse samples. Upregulation of HSP90 contributes to 5-FU resistance and can predict poor prognosis in cancer patients. Mechanistically, HSP90 K754 is regulated by the cooperation of KAT8 and HDAC11 as the writer and eraser, respectively; SDCBP increases the Kbu level and stability of HSP90 by binding competitively to HDAC11. Furthermore, SDCBP blockade with the lead compound V020-9974 can target HSP90 K754 to overcome 5-FU resistance, constituting a potential therapeutic strategy.

Generative Deep Learning-Based Thermographic Inspection of Artwork.

Infrared thermography is a widely utilized nondestructive testing technique in the field of artwork inspection. However, raw thermograms often suffer from problems, such as limited quantity and high background noise, due to limitations inherent in the acquisition equipment and experimental environment. To overcome these challenges, there is a growing interest in developing thermographic data enhancement methods. In this study, a defect inspection method for artwork based on principal component analysis is proposed, incorporating two distinct deep learning approaches for thermographic data enhancement: spectral normalized generative adversarial network (SNGAN) and convolutional autoencoder (CAE). The SNGAN strategy focuses on augmenting the thermal images, while the CAE strategy emphasizes enhancing their quality. Subsequently, principal component thermography (PCT) is employed to analyze the processed data and improve the detectability of defects. Comparing the results to using PCT alone, the integration of the SNGAN strategy led to a 1.08% enhancement in the signal-to-noise ratio, while the utilization of the CAE strategy resulted in an 8.73% improvement.

N4-acetylcytidine modification of lncRNA CTC-490G23.2 promotes cancer metastasis through interacting with PTBP1 to increase CD44 alternative splicing.

Although N4-acetylcytidine (ac4C) modification affects the stability and translation of mRNA, it is unknown whether it exists in noncoding RNAs, and its biological function is unclear. Here, nucleotide-resolution method for profiling CTC-490G23.2 ac4C sites and gain- and loss-of-function experiments revealed that N-acetyltransferase 10 (NAT10) is responsible for ac4C modification of long noncoding RNAs (lncRNAs). NAT10-mediated ac4C modification leads to the stabilization and overexpression of lncRNA CTC-490G23.2 in primary esophageal squamous cell carcinoma (ESCC) and its further upregulation in metastatic tissues. CTC-490G23.2 significantly promotes cancer invasion and metastasis in vitro and in vivo. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the binding of CD44 pre-mRNA to polypyrimidine tract-binding protein 1 (PTBP1), resulting in a oncogenic splicing switch from the standard isoform CD44s to the variant isoform CD44v(8-10). CD44v(8-10), but not CD44s, binds to and increases the protein stability of vimentin. Expression levels of CTC-490G23.2 and CD44v(8-10) can predict poor prognosis in cancer patients. Furthermore, the antisense oligonucleotide (ASO)/SV40-LAH4-L1 peptide self-assembled nanocomplexes targeting CTC490G23.2 exerts a significantly suppressive effect on cancer metastasis. The outcome of this study will provide new mechanistic insight into the ac4C modification of lncRNAs and useful clues for the development of novel systemic therapies and prognostic biomarkers.

Deciphering the Underlying Mechanism of Eucommiae Cortex against Osteoporotic Fracture by Network Pharmacology.

BACKGROUND: Du Zhong (DZ), or Eucommiae Cortex, a traditional Chinese herbal medicine, has been used to treat osteoporosis. Although it has been reported that DZ can improve bone mass in ovariectomized rats, its pharmacological mechanisms in treating osteoporotic fractures (OPF) remain unclear. METHODS: In this study, we used a network pharmacological manner to explore its potential complicated mechanism in treating OPF. We obtained DZ compounds from TCMSP and BATMAN-TCM databases and collected potential targets of these compounds through target fishing based on TCMSP and BATMAN-TCM databases. Next, we collected the OPF targets by using CTD, GeneCards, OMIM, HPO, and GenCLiP 3 databases. And then the overlapping genes between DZ potential targets and OPF targets were used to build up the protein-protein interaction (PPI) network and to analyze their interactions and find out the big hub genes in this network. Subsequently, clusterProfiler package in R language was utilized to conduct the enrichment of Gene Ontology biological process and KEGG pathways. RESULTS: There were totally 93 active compounds and 916 related targets in DZ. After the enrichment analysis, we collected top 25 cellular biological processes and top 25 pathways based on the adjusted P value and found that the DZ anti-OPF effect was mainly associated with the regulation of ROS and inflammatory response. Furthermore, 64 hub genes in PPI network, such as MAPK1 (degree = 41), SRC (degree = 39), PIK3R1 (degree = 36), VEGFA (degree = 31), TP53 (degree = 29), EGFR (degree = 29), JUN (degree = 29), AGT (degree = 29), MAPK1, SRC, PIK3R1, VEGFA, and TP53, were considered as potential therapeutic targets, implying the underlying mechanisms of DZ acting on OPF. CONCLUSION: We investigated the possible therapeutic mechanisms of DZ from a systemic perspective. These key targets and pathways provided promising directions for the future research to reveal the exact regulating mechanisms of DZ in treating OPF.

High-dose nitrate therapy recovers the expression of subtypes α1 and ß-adrenoceptors and Ang II receptors of the renal cortex in rats with myocardial infarction-induced heart failures.

BACKGROUND: Few studies examined the effect of long-acting nitrates on renal function in chronic heart failure (CHF). Thus, we aimed to investigate the effect of long-acting nitrate on the expression of adrenoceptors (AR) and angiotensin II receptor (ATR) subtypes of the renal cortex, in rats with myocardial infarction-induced CHF. METHODS: Rats were randomly divided into the following groups: control, sham-operated, CHF, low- and high-dose nitrate, positive drug control (olmesartan), and high-dose of long-acting nitrate + olmesartan. Ultrasound echocardiography markers were compared, and the levels of AR subtypes, AT1R, and AT2R were measured using reverse transcription-polymerase chain reaction and western blot analysis. Histopathology of the kidney was determined on hematoxylin and eosin-stained sections. RESULTS: CHF significantly increased plasma renin activity (PRA) and angiotensin II levels, upregulated AT1R expression and downregulated α1A-, ß1-, ß2-AR, and AT2R expression compared to the sham control. High-dose nitrate or olmesartan alone, and especially in combination, decreased the levels of PRA and angiotensin II and downregulated the CHF-induced expression of AT1R, α1A-, ß1-, and ß2-AR, and AT2R. CHF resulted in significant impairment of the renal tissue, including inflammatory cells infiltration to the tubular interstitium and surrounding the renal glomerulus, and tubular necrosis, which was alleviated in all treatment groups to different degrees. CONCLUSIONS: Long-acting nitrates could reverse CHF-induced changes in AR and ATR subtypes in the kidney, and improve cardiac function to protect renal function. Compared with monotherapy, the combination of nitrates and olmesartan shows more significant benefits in regulating AR and ATR subtypes.

Comparison of Secondary Prevention Status between Percutaneous Coronary Intervention and Coronary Artery Bypass Patients.

BACKGROUND: Data are scarce regarding disparities in cardiovascular risk factor management between patients treated with percutaneous coronary intervention (PCI) and those treated with coronary artery bypass grafting (CABG). OBJECTIVE: Whether the goal achievement rates of cardiovascular risk factors were different between PCI and CABG patients. METHODS: We retrospectively reviewed the data retrieved from a clinical record database of patients admitted to Beijing Anzhen Hospital between January 1, 2014, and December 31, 2014, who underwent PCI or CABG. RESULTS: Compared with the CABG group, low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L (28.6% vs. 24.7%; p < 0.01), LDL-C < 2.07 mmol/L (43.5% vs. 39.4%; p < 0.01) and blood pressure (BP) < 140/90 mm Hg (85.6% vs. 77.7%; p < 0.01) goal achievement rates were significantly higher in the PCI group. Compared with patients ≥ 60 years old: patients < 60 years old had better BP < 140/90 mm Hg goal achievement rates (87.7% vs. 84.4%; p < 0.01) in the PCI group, and better fasting blood-glucose (FBG) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) and HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) goal achievement rates in the CABG group. Compared with females: males had better LDL-C < 2.07 mmol/L (24.7% vs. 28.5%; p < 0.01), FBG < 7 mmol/L (71.8% vs.75.2%; p < 0.01) and HbA1c < 7% (70.4% vs. 74.1%; p < 0.01) goal achievement rates in the PCI group. CONCLUSION: Patients in the PCI group were generally more likely than those in the CABG group to achieve LDL-C < 1.8 mmol/L and BP goals. The control of cardiovascular risk factors differed between patients ≥ 60 years old and < 60 years old. Female patients were less likely to achieve LDL-C, FBG and HbA1c goals.

Comparison of Secondary Prevention Status between Percutaneous Coronary Intervention and Coronary Artery Bypass Patients / Comparação de Prevenção Secundária em Intervenção Coronária Percutânea e Cirurgia de Revascularização Miocárdica

Abstract Background: Data are scarce regarding disparities in cardiovascular risk factor management between patients treated with percutaneous coronary intervention (PCI) and those treated with coronary artery bypass grafting (CABG). Objective: Whether the goal achievement rates of cardiovascular risk factors were different between PCI and CABG patients. Methods: We retrospectively reviewed the data retrieved from a clinical record database of patients admitted to Beijing Anzhen Hospital between January 1, 2014, and December 31, 2014, who underwent PCI or CABG. Results: Compared with the CABG group, low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L (28.6% vs. 24.7%; p < 0.01), LDL-C < 2.07 mmol/L (43.5% vs. 39.4%; p < 0.01) and blood pressure (BP) < 140/90 mm Hg (85.6% vs. 77.7%; p < 0.01) goal achievement rates were significantly higher in the PCI group. Compared with patients ≥ 60 years old: patients < 60 years old had better BP < 140/90 mm Hg goal achievement rates (87.7% vs. 84.4%; p < 0.01) in the PCI group, and better fasting blood-glucose (FBG) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) and HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) goal achievement rates in the CABG group. Compared with females: males had better LDL-C < 2.07 mmol/L (24.7% vs. 28.5%; p < 0.01), FBG < 7 mmol/L (71.8% vs.75.2%; p < 0.01) and HbA1c < 7% (70.4% vs. 74.1%; p < 0.01) goal achievement rates in the PCI group. Conclusion: Patients in the PCI group were generally more likely than those in the CABG group to achieve LDL-C < 1.8 mmol/L and BP goals. The control of cardiovascular risk factors differed between patients ≥ 60 years old and < 60 years old. Female patients were less likely to achieve LDL-C, FBG and HbA1c goals.

Resumo Fundamento: Há poucos dados referentes às disparidades no manejo de fatores de risco cardiovascular entre pacientes tratados com intervenção coronária percutânea (ICP) e aqueles tratados com cirurgia de revascularização miocárdica (CRM). Objetivo: Avaliar se as taxas de cumprimento de metas de fatores de risco cardiovascular diferiram entre pacientes submetidos a ICP ou a CRM. Métodos: Revisão retrospectiva de banco de dados de prontuários médicos de pacientes admitidos no Hospital Beijing Anzhen entre 1 de janeiro de 2014 e 31 de dezembro de 2014, submetidos a ICP ou a CRM. Resultados: Comparado ao grupo CRM, o grupo ICP apresentou taxas significativamente maiores de cumprimento de meta de colesterol da lipoproteína de baixa densidade (LDL-C) < 1,8 mmol/L (28,6% vs. 24,7%; p < 0,01), LDL-C < 2,07 mmol/L (43,5% vs. 39,4%; p < 0,01) e pressão arterial (PA) <140/90 mmHg (85,6% vs. 77,7%; p < 0,01). Comparados aos pacientes ≥ 60 anos de idade, aqueles < 60 anos de idade apresentaram melhor taxa de cumprimento de meta de PA < 140/90 mmHg (87,7% vs. 84,4%; p < 0,01) no grupo ICP, e melhores taxas de cumprimento de meta de glicemia de jejum (GJ) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) e HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) no grupo CRM. Comparados às mulheres, os homens apresentaram melhores taxas de cumprimento de meta de LDL-C < 2,07 mmol/L (24,7% vs. 28,5%; p < 0,01), GJ < 7 mmol/L (71,8% vs. 75,2%; p < 0,01) e HbA1c < 7% (70,4% vs. 74,1%; p < 0,01) no grupo ICP. Conclusão: Em geral, o grupo ICP apresentou maior probabilidade do que o grupo CRM de cumprir as metas de LDL-C < 1,8 mmol/L e PA. O controle dos fatores de risco cardiovascular diferiu entre pacientes ≥ 60 e < 60 anos de idade. As mulheres apresentaram menor probabilidade de cumprir as metas de LDL-C, GJ e HbA1c.

ß3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells.

OBJECTIVE: The aim of this study was to explore the effects of ß3-adrenoceptor (ß3-AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. MATERIALS AND METHODS: HepG2 cells were cultured and treated with the ß3-AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and ß3-AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol content of the foam cells was also measured, and the cholesterol efflux from the macrophages was examined by determining 3H-labeled cholesterol levels. Expression of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam cells was also assessed. RESULTS: ß3-AR activation increased ApoA-I expression in both the HepG2 cells and the supernatants; PPARγ expression was upregulated, but PPARα expression was not. Treatment with GW9662 abolished the increased expression of ApoA-I induced by the ß3-AR agonist. The HepG2 cell supernatants decreased the lipid accumulation and increased the cholesterol efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1 expression, increased in the macrophage foam cells treated with BRL37344-treated HepG2 cell supernatants. CONCLUSION: Activation of ß3-AR in HepG2 cells upregulates ApoA-I expression, which might further promote cholesterol efflux from macrophage foam cells. PPARγ might be required for the induction of ApoA-I expression.

Positive correlation between plasma PCSK9 and tissue factors levels in patients with angiographically diagnosed coronary artery disease and diabetes mellitus.

BACKGROUND: Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C). Both oxidized LDL and tissue factor (TF) contributed to the development of prothrombotic state. The present study aims to explore the relationship between plasma level of PCSK9 and that of TF in patient with coronary artery disease (CAD). METHODS: From July 2013 to March 2014, we enrolled 197 consecutive patients who underwent coronary angiography because of suspected CAD at Beijing Anzhen Hospital in this study. All patients had no history of using lipid-lowering medication. Of these 197 patients (131 male and 66 female, mean age 56.9 ± 11.8 years), 81 had angiographically diagnosed CAD. Clinical data were collected. Plasma PCSK9 and TF were measured using enzyme-linked immunosorbent assay (ELISA). Levels of plasma PCSK9 and TF were compared and their correlation analyzed among different patient groups. RESULTS: Both plasma levels of PCSK9 (279.8 ± 60.4 µg/L vs. 216.5 ± 45.3 µg/L, P < 0.01) and TF (156.4 ± 26.6 µg/mL vs. 112.1 ± 38.3 µg/L, P < 0.01) were significantly higher in patients with CAD, as compared with those without CAD. Correlation analysis showed plasma level of PCSK9 was significantly correlated with that of TF in both patients with and without CAD. However, multivariate regression analysis after adjustment for age, gender, smoking, alcohol, hypertension and hyperlipidemia showed that only in CAD patients with type 2 diabetes mellitus, there was significant positive correlation between plasma levels of PCSK9 and TF (ß = 0.353, P < 0.01). CONCLUSIONS: The plasma level of PCSK9 is independently and positively associated with that of TF in CAD patients with diabetes mellitus, but not in those without diabetes mellitus. Further study is needed to investigate the underlying mechanism.

Impact of statins on ALI/ARDS: A meta-analysis.

BACKGROUND: Statins may be beneficial in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), but their application remains controversial. OBJECTIVES: This meta-analysis of published studies investigated their potential benefit in ALI/ARDS treatment. METHODS: PubMed, EMBASE, Google Scholar and Cochrane databases were searched and all randomized controlled trials (RCT) and cohort studies with head-to-head comparison between statin and standard care were included. RESULTS: Three RCTs and six cohort studies were included. Overall, statins treatment had no significant effect on mortality compared with placebo (RCTs: OR = 0.99, 95% CI = 0.72, 1.37; cohorts: OR = 0.99, 95% CI = 0.71, 1.37). In addition, ventilator-free days were comparable between the two groups (RCTs: SMD = 0.08, 95% CI = -0.03, 0.19; cohorts: SMD = 0.06, 95% CI = -0.17, 0.29). The one-way sensitivity analysis confirmed the stability of results. CONCLUSION: The results did not show that statins had effects on mortality and ventilator-free days among ALI/ARDS patients. However, this meta-analysis is limited by the number of RCTs included.

Effects of beta3-adrenoceptor activation on the interaction between adrenoceptors and angiotensin II receptors in apolipoprotein E knockout mouse lung.

Hyperlipidemia can be harmful to the lung and ß3-adrenoceptor agonist can improve lipid metabolism disorders. In this study, we aim to investigate the effects of ß3-adrenoceptor activation on the interactions of adrenoceptors and angiotensin II receptors in aged apolipoprotein E gene knockout (ApoE(-/-)) mouse lung. Ten wild type C57BL/6J mice were included as normal control, 40 ApoE(-/-) mice were randomly divided into hyperlipidemia model (saline), low dose and high dose ß3-adrenoceptor agonist and ß3-adrenoceptor antagonist groups. After 26 weeks of high-fat diet, treatments were given for 12 weeks. Total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were examined by an automatic biochemical analyzer. Quantitative real-time PCR and Western blot were used to analyze the mRNA and protein expression of α1A-, α1B-, α2A-, ß1-, ß2-, ß3-adrenoceptors and angiotensin II type 1 and type 2 receptors in lung. We found that ß3-adrenoceptor agonist could decrease TG, TC and LDL-C in aged ApoE(-/-) mice (P<0.01) and down-regulate the expressions of α1A-, α2A-adrenoceptors and angiotensin II type 1 receptor which were significantly increased in model mice (P<0.01, P<0.05). Compared with model mice, α1B-, ß1-, ß2-, ß3-adrenoceptors and angiotensin II type 2 receptor expressions were increased in ß3-adrenoceptor agonist-treat mice (P<0.01, P<0.05). These findings suggest that the expressions of adrenoceptors and angiotensin II receptors in lung are regulated towards adverse directions after taking ß3-adrenoceptor agonist, which shows there are interactions between ß3-adrenoceptor and other adrenoceptor subtypes and angiotensin II receptors. These interactions may play a protective role in lung under condition of hyperlipidemia.

Fumigant activity of eleven essential oil compounds and their selected binary mixtures against Culex pipiens pallens (Diptera: Culicidae).

To seek natural products for the development of environment friendly mosquito control agents, fumigant activity of eleven essential oil compounds and the joint action of the active compounds were evaluated against Culex pipiens pallens adults. Fumigant bioassay demonstrated that carvacrol exhibited the highest fumigant activity followed by thymol and l-perillaldehyde, with LC50 values of 0.26, 0.28, and 0.34 mg/L air, respectively. Among the binary mixtures of four compounds with preferable performance, only the binary mixture of carvacrol and thymol (1:1, w/w) displayed a synergistic effect with the co-toxicity coefficient (CTC) value of 174.1 and LC50 value of 0.16 mg/L air. Furthermore, the actual efficacy of the binary mixture at 300 mg/mat (KT50 = 7.9, 15.8, and 22.0 min after 0, 2, and 4 h of preliminary heating, respectively) was comparable with that of d-allethrin at 30 mg/mat (KT50 = 8.7, 17.9, and 21.2 min after 0, 2, and 4 h of preliminary heating, respectively) tested in vaporizing mats by the glass chamber method (70 × 70 × 70 cm). These results revealed that carvacrol, thymol, and their binary mixture have potential for the development of natural fumigants for adult mosquito control.