Correlation of Plasma Adiponectin Levels and Adiponectin Gene Polymorphisms with Idiopathic Atrial Fibrillation.

INTRODUCTION: Adiponectin is a cellular protein secreted by adipocytes, which is closely related to a variety of diseases, including atrial fibrillation (AF). Idiopathic atrial fibrillation (IAF) is defined as AF without hypertension, diabetes, and other underlying diseases. Genetic polymorphism of adiponectin affects serum adiponectin concentration. However, the association of serum adiponectin concentration and its genetic polymorphism with IAF has not been studied. This study investigated the relationship between serum levels of adiponectin, adiponectin gene polymorphisms, and the risk of developing IAF in a Chinese Han population. METHODS: Patients with IAF (n = 172, IAF group) and healthy individuals (n = 150, control group) were consecutively and randomly recruited and fasting peripheral blood samples were collected. All participants were examined for serum adiponectin concentrations and the polymorphisms SNP45T>G (SmaI locus, rs2241766) and SNP276G>T (BsmI locus, rs1501299) of the adiponectin gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Related clinical data from the two groups were also collected. RESULTS: Plasma adiponectin levels in the IAF group were significantly lower than those in the control group (9.9 ± 2.6 mg/L vs. 16.1 ± 7.0 mg/L, p = 0.006). There were no significant differences among the three genotypes (wild type, mutant heterozygote, and homozygote) of SNP45T>G or SNP276G>T in the prediction value of IAF. The frequency of the T allele of SNP45 T>G was 70.3% in the IAF group and significantly different from that of the control group (71.3%; p = 0.02). In the case of SNP276G>T, the frequency of the G allele was 68.61% in patients with IAF compared to 73.34% in the control group (p = 0.35). Furthermore, a comparison of the clinical data of individuals in the two groups revealed that the left atrial diameter (LAD) in patients in the IAF group was obviously higher than that in the control group (43.3 ± 6.7 mm vs. 37.9 ± 5.1 mm, respectively; p < 0.001). The left ventricular ejection fraction (LVEF) in the IAF group was obviously reduced than that in the control group (54.7 ± 11.9% vs. 60.2 ± 5.6%, respectively; p < 0.001). CONCLUSIONS: Low plasma adiponectin levels were significantly associated with IAF. Hypoadiponectinemia can thus serve as an important factor for the incidence of IAF. The genotypes of SNP45T>G and SNP276G>T in the adiponectin gene may not correlate with the occurrence of IAF. However, our results demonstrate that the T allele of SNP45T>G may be responsible for IAF development in the Chinese Han population.

Transcriptomic Analysis of Heat Stress Response in Brassica rapa L. ssp. pekinensis with Improved Thermotolerance through Exogenous Glycine Betaine.

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is sensitive to high temperature, which will cause the B. rapa to remain in a semi-dormancy state. Foliar spray of GB prior to heat stress was proven to enhance B. rapa thermotolerance. In order to understand the molecular mechanisms of GB-primed resistance or adaptation towards heat stress, we investigated the transcriptomes of GB-primed and non-primed heat-sensitive B. rapa 'Beijing No. 3' variety by RNA-Seq analysis. A total of 582 differentially expressed genes (DEGs) were identified from GB-primed plants exposed to heat stress relative to non-primed plants under heat stress and were assigned to 350 gene ontology (GO) pathways and 69 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. The analysis of the KEGG enrichment pathways revealed that the most abundantly up-regulated pathways were protein processing in endoplasmic reticulum (14 genes), followed by plant hormone signal transduction (12 genes), ribosome (8 genes), MAPK signaling pathway (8 genes), homologous recombination (7 genes), nucleotide excision repair metabolism (5 genes), glutathione metabolism (4 genes), and ascorbate and aldarate metabolism (4 genes). The most abundantly down-regulated pathways were plant-pathogen interaction (14 genes), followed by phenylpropanoid biosynthesis (7 genes); arginine and proline metabolism (6 genes); cutin, suberine, and wax biosynthesis (4 genes); and tryptophan metabolism (4 genes). Several calcium sensing/transducing proteins, as well as transcription factors associated with abscisic acid (ABA), salicylic acid (SA), auxin, and cytokinin hormones were either up- or down-regulated in GB-primed B. rapa plants under heat stress. In particular, expression of the genes for antioxidant defense, heat shock response, and DNA damage repair systems were highly increased by GB priming. On the other hand, many of the genes involved in the calcium sensors and cell surface receptors involved in plant innate immunity and the biosynthesis of secondary metabolites were down-regulated in the absence of pathogen elicitors in GB-primed B. rapa seedlings. Overall GB priming activated ABA and SA signaling pathways but deactivated auxin and cytokinin signaling pathways while suppressing the innate immunity in B. rapa seedlings exposed to heat stress. The present study provides a preliminary understanding of the thermotolerance mechanisms in GB-primed plants and is of great importance in developing thermotolerant B. rapa cultivars by using the identified DEGs through genetic modification.

The Value of Sacubitril/Valsartan in Acute Anterior Wall ST-Segment Elevation Myocardial Infarction before Emergency Percutaneous Coronary Intervention.

BACKGROUND: Many patients present with heart failure with reduced ejection fraction (HFrEF) after acute anterior wall ST-segment elevation myocardial infarction (STEMI). The purpose of this study was to evaluate the effect of preprocedural sacubitril/valsartan on N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and left ventricular ejection fraction (LVEF) in patients with acute anterior STEMI undergoing percutaneous coronary intervention (PCI). METHODS: We enrolled patients with acute anterior wall STEMI who underwent emergency PCI at The Affiliated Hospital of Putian University from January 2019 to January 2021. Prior to PCI, patients were randomized to receive sacubitril/valsartan or valsartan. Nonculprit lesion vessels that require PCI were excluded. The primary endpoints included changes in NT-pro-BNP, LVEF, and rehospitalization for heart failure (HF) during the follow-up period. RESULTS: Out of 109 patients who were randomized, 55 were assigned to receive sacubitril/valsartan and 54 were assigned to receive valsartan. The decrease in NT-pro-BNP concentrations and the increase in LVEF were significantly greater in the sacubitril/valsartan group than in the valsartan group. CONCLUSIONS: In patients with acute anterior wall STEMI undergoing emergency PCI, preprocedural initiation of sacubitril/valsartan therapy increased LVEF and lower NT-pro-BNP concentrations compared with valsartan therapy.

Predictive Value of Red Blood Cell Distribution Width and Atrial Diameter in Paroxysmal Atrial Fibrillation: A Cross-Sectional Study.

BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia and is associated with deleterious consequences. In addition to worsening a patient's quality of life, AF is associated with stroke, heart failure, and increased mortality. Red blood cell distribution width (RDW) has been associated with an increased risk of death and adverse cardiovascular outcomes, while left atrial enlargement has been linked to atrial fibrillation (AF). However, the relationship among RDW, atrial diameter (AD), and paroxysmal AF is uncertain. The aim of this study was to investigate the relationship among RDW, atrial diameter, and paroxysmal AF. MATERIAL AND METHODS A total of 22 patients with paroxysmal AF and 100 patients with non-AF were included in the study. The demographic variables and baseline clinical characteristics of both groups were analyzed. RESULTS The demographics and comorbidities were comparable between the paroxysmal AF and control groups, except for BMI (body mass index). RDW, high-sensitivity C-reactive protein (hs-CRP) levels, NT-pro-BNP levels, MPV/PLT (mean platelet volume/total platelet count), LAD, RAD, and CHA2DS2-VASc score were higher in the paroxysmal AF group versus the control group (P<0.05). Binary logistic regression analyses demonstrated that RDW (OR: 2.557, 95% CI: 1.481~4.414), Hs-CRP(OR: 1.445, 95% CI: 1.144~1.825), MPV/PLT (OR: 1.342, 95% CI: 1.047~1.720), LAD (OR: 1.068, 95% CI: 1.007~1.132), and CHA2DS2-VASc score (OR: 1.645, 95% CI: 1.042~2.597) were independent predictors for paroxysmal AF (P<0.05, respectively). The ROC analysis showed that the area under the curve for LAD was 0.692, the area under the curve for RAD was 0.566, the area under the curve for RDW was 0.811, and the area under the curve for MPV/PLT was 0.671. CONCLUSIONS LAD, RDW, and MPV/PLT were associated with paroxysmal AF.

Enhanced Resistance to Sclerotinia sclerotiorum in Brassica rapa by Activating Host Immunity through Exogenous Verticillium dahliae Aspf2-like Protein (VDAL) Treatment.

Sclerotinia stem rot caused by Sclerotinia sclerotiorum is one of the most destructive diseases in Brassica rapa. Verticillium dahliae Aspf2-like protein (VDAL) is a secretory protein of V. dahliae which has been shown to enhance the resistance against fungal infections in several plants. Nonetheless, the molecular mechanisms of VDAL-primed disease resistance are still poorly understood. In this study, we performed physiological, biochemical, and transcriptomic analyses of Brassica rapa in order to understand how VDAL confers resistance to S. sclerotiorumn infections in plants. The results showed that foliar application of VDAL significantly reduced the plaque area on leaves inoculated with S. sclerotiorum. It also enhanced antioxidant capacity by increasing activities of superoxide dismutase (SOD), peroxidase (POD), peroxidase (APX), glutathione reductase (GR), protoporphyrinogen oxidase (PPO), and defense-related enzymes ß-1,3-glucanase and chitinase during the infection periods. This occurred in parallel with significantly reduced relative conductivity at different periods and lower malondialdehyde (MDA) content as compared to sole S. sclerotiorum inoculation. Transcriptomic analysis showed a total of 146 (81 up-regulated and 65 down-regulated) differentially expressed genes (DEGs) in VDAL-treated leaves compared to the control. The most enriched three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were the mitogen-activated protein kinase (MAPK) signaling pathway, plant hormone signal transduction, and plant-pathogen interaction, all of which were associated with plant immunity. DEGs associated with MAPK and hormone signal transduction pathways were ethylene response sensor ERS2, EIN3 (Ethylene Insensitive3)-binding F-box protein 2 (EBF2), ethylene-responsive transcription factor ERF94, MAPK 9 (MKK9), protein phosphatase 2C (PP2C37), auxin-responsive proteins (AUX/IAA1 and 19), serine/threonine-protein kinase CTR1, and abscisic acid receptors (PLY 4 and 5). Among the DEGs linked with the plant-pathogen interaction pathway were calmodulin-like proteins (CML5, 24, 27), PTI1-like tyrosine protein kinase 3 (Pti13) and transcription factor MYB30, all of which are known to play key roles in pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity (ETI) for hypersensitive response (HR), cell wall reinforcement, and stomatal closure in plants. Overall, VDLA treatment triggered repression of the auxin and ABA signaling pathways and de-repression of the ethylene signaling pathways in young B. rapa seedlings to increase plant innate immunity. Our results showed that VDAL holds great potential to enhance fungal disease resistance in B. rapa crop.

Glutamic Acid and Poly-γ-glutamic Acid Enhanced the Heat Resistance of Chinese Cabbage (Brassica rapa L. ssp. pekinensis) by Improving Carotenoid Biosynthesis, Photosynthesis, and ROS Signaling.

Heat stress is one of the most common agrometeorological risks in crop production in the middle and lower reaches of the Yangtze River in China. This study aimed to investigate whether glutamic acid (Glu) or poly-γ-glutamic acid (γ-PGA) biostimulants can improve the thermotolerance of a cool-season Chinese cabbage (Brassica rapa L. ssp. pekinensis) crop. Priming with Glu (2.0 mM) or γ-PGA (20 mg·L-1) was conducted at the third leaf stage by applying as daily foliar sprays for 5 days before 5 days of heat stress (45 °C in 16-h light/35 °C in 8-h dark). Coupled with morpho-physiological and biochemical analyses, transcriptomes of Glu or γ-PGA-primed Chinese cabbage under heat stress were examined by RNA-seq analysis. The results showed that the thermotolerance conferred by Glu and γ-PGA priming was associated with the increased parameters of vegetative growth, gas exchange, and chlorophyll fluorescence. Compared with the control, the dry weights of plants treated with Glu and γ-PGA increased by 51.52% and 39.39%, respectively. Glu and γ-PGA application also significantly increased the contents of total chlorophyll by 42.21% and 23.12%, and carotenoid by 32.00% and 24.00%, respectively. In addition, Glu- and γ-PGA-primed plants markedly inhibited the levels of malondialdehyde, electrolyte leakage, and super-oxide anion radical, which was accompanied by enhanced activity levels of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD). Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) categories within the differentially expressed genes (DEGs) functional clusters of RNA-seq data indicated that the expression levels of the genes for DNA replication, DNA repair system, linoleic acid metabolism, cysteine and methionine metabolism, glutathione metabolism, purine and pyrimidine metabolism, carotenoid biosynthesis, and plant-pathogen interaction were commonly up-regulated by both Glu and γ-PGA priming. Glu treatment enhanced the expression levels of the genes involved in aliphatic glucosinolate and 2-oxocarboxylic acid, while γ-PGA treatment activated carotenoid cleavage reaction to synthesize abscisic acid. Taken together, both Glu and γ-PGA have great potential for the preadaptation of Chinese cabbage seedlings to heat stress, with Glu being more effective than γ-PGA.

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities.

Wikstroemia nutans Champ. ex Benth., a traditional herbal medicine collected at the Lingnan region of China, was chemically investigated. A new biscoumarin glucoside, wikstronutin (1), along with three known bis- and tricoumarin glucosides (2-4), two flavonoid glycosides (5-6), and eleven lignan glucosides (7-17) were isolated from the stems and roots of W. nutans. The new structure including its absolute configuration was elucidated based on a combination of 1D and 2D NMR, UV, IR, HRESIMS spectroscopic data, as well as chemical transformation. Compounds 1-17 were first isolated from the plant species W. nutans, while compounds 1-3, 8, and 11 were reported from the genus Wikstroemia for the first time. All co-isolates were evaluated for their in vitro inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells. The antibacterial activity of the selected compounds was also tested. Our work enriches the structure diversity of the secondary metabolites from the genus Wikstroemia.

Protective Effects of 1,25 Dihydroxyvitamin D3 against High-Glucose-Induced Damage in Human Umbilical Vein Endothelial Cells Involve Activation of Nrf2 Antioxidant Signaling.

AIM: To explore the protective effects and related mech-anisms of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) on en-dothelial dysfunction under hyperglycemic conditions. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were treated with normal glucose (glucose concentration of 5.5 mmol/L), high glucose (glucose concentration of 33 mmol/L), and high glucose plus 1,25(OH)2D3, respectively. Cell viability and apoptosis, intracellular reactive oxygen species (ROS) and nitric oxide (NO) contents, antioxidant enzyme activities, proinflammatory cytokine mRNA levels, and expression levels of proteins involved were measured. RESULTS: High glucose decreased HUVEC viability, promoted ROS production and apoptosis, and reduced NO generation, which was associated with decreased activities of antioxidant enzymes and increased levels of proinflam-matory cytokines. 1,25(OH)2D3 treatment enhanced HUVEC viability, attenuated ROS generation and apoptosis, and -increased NO production, which was accompanied by -enhanced antioxidant enzyme activities and reduced -proinflammatory factors. Mechanically, 1,25(OH)2D3 promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in a vitamin D receptor (VDR)-dependent manner, and Nrf2 siRNA abolished the antioxidative and -anti-inflammatory effects of 1,25(OH)2D3. CONCLUSIONS: 1,25(OH)2D3 attenuates high-glucose-induced endothelial oxidative injury through upregulation of the Nrf2 antioxidant pathway in a VDR-dependent manner.

Regioisomers Salviprolin A and B, Unprecedented Rosmarinic Acid Conjugated Dinorditerpenoids from Salvia przewalskii Maxim.

Salvia przewalskii Maxim is a perennial plant from the genus Salvia (family Lamiaceae). The roots of S. przewalskii were long used as a traditional herb to treat blood circulation related illnesses in China. As part of our continuing interest in polycyclic natural products from medicinal plants, two unprecedented adducts comprised of a dinor-diterpenoid and a 9'-nor-rosmarinic acid derivative, linked by a 1,4-benzodioxane motif (1 and 2), were isolated from the roots of S. przewalskii. Their structures were established by extensive spectroscopic approaches including 1D, 2D NMR, and HRFABMS. Their cytotoxic activities against five human tumor cell lines were evaluated.

Effects of body mass index and gender on left atrial size in Chinese hypertensive patients.

BACKGROUND: Left atrial enlargement (LAE) is a common cardiac structural change in patients with hypertension, and obesity could further promote LAE. However, little is known about the effect of overweight on left atrial size, and if there is a gender difference of the effect. The aim of this study was to analyze the effects of different body mass index (BMI) grades (normal weight, overweight, and obesity) on left atrial size in both male and female patients with hypertension. METHODS: A total of 710 patients with hypertension were divided into 3 study groups: normal weight group (BMI < 24 g/m2, n = 302), overweight group (24 kg/m2 ≤ BMI < 28 kg2, n = 318), and obesity group (BMI ≥28 kg/m2, n = 90). The clinical data, echocardiographic indexes and left atrial size were obtained from all the subjects. Pearson correlation analysis was used to analyze the correlation between clinical variables and left atrial diameter (LAD)/left atrial diameter index (LADI), and stepwise regression evaluation was used to study the relevant factors affecting LAD/LADI among all patients, male and female patients for possible gender difference. RESULTS: The significant difference in LADI was noted in the three study groups with obesity group of 23.96 ± 2.90 mm/m, overweight group of 22.50 ± 3.02 mm/m and normal weight group of 21.08 ± 2.80 mm/m, respectively (P < . 05). After adjusting for age and gender, there was still significant difference in LADI among the three groups (P < . 05). The correlation between BMI and LADI was higher than that between systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r = 0.348 vs 0.092 and -0.068, respectively, P < .05). After adjusting for other influencing factors, there was still a significant correlation between BMI and LADI (ß = 0.326, P < .001), but no correlation was found between SBP and DBP (P > .05). For each additional unit of BMI, LAD increased by 0.034 mm and LADI increased by 0.305 mm/m. Multiple linear regression analysis showed that BMI, left ventricular mass index (LVMI), age and female gender were independently correlated with LADI (P < .05). And BMI was the most significant influencing factor of LADI in male patients (ß = 0.350, P < .001), followed by LVMI (ß = 0.343, P < .001). While in female patients, LVMI was the most significant (ß = 0.353, P < .001), followed by BMI (ß = 0.302, P < .001). CONCLUSION: Overweight and obesity were significantly associated with LAE in hypertensive patients, with obesity more significant than overweight. While BMI had the greatest correlation with LAE in male, LVMI was the most important determinant of LAE in female. Therefore, in addition to weight loss, more attention should be paid to early inhibition of left ventricular remodeling in female with hypertension.

Deep Sea Water Improves Abnormalities in Lipid Metabolism through Lipolysis and Fatty Acid Oxidation in High-Fat Diet-Induced Obese Rats.

Deep sea water (DSW) is a natural marine resource that has been utilized for food, agriculture, cosmetics, and medicine. The aim of this study was to investigate whether DSW has beneficial lipid metabolic effects in an animal model. Our previous in vitro study indicated that DSW significantly decreased the intracellular triglyceride and glycerol-3-phosphate dehydrogenase activity in 3T3-L1 adipocytes. DSW also inhibited the gene levels of adipocyte differentiation, lipogenesis, and adipocytokines, and up-regulated gene levels of lipolysis and fatty acid oxidation. In the present study, the results showed that body weight, liver, adipose tissue, hepatic triglycerides and cholesterol, and serum parameters in the high-fat diet (HFD) + DSW groups were significantly lower compared to the HFD group. Moreover, the fecal output of total lipids, triglycerides, and cholesterol in the HFD + DSW groups was significantly higher than that of the HFD group. Regarding gene expression, DSW significantly increased the gene levels of lipolysis and fatty acid oxidation, and decreased the gene levels of adipocytokine in the adipose tissue of rats with HFD-induced obesity. These results indicate a potential molecular mechanism by which DSW can suppress obesity in rats with HFD-induced obesity through lipolysis and fatty acid oxidation.

Effect and Mechanism of QiShenYiQi Pill on Experimental Autoimmune Myocarditis Rats.

BACKGROUND: To observe the effect of QiShenYiQi pill (QSYQ) on experimental autoimmune myocarditis rats, and to explore its mechanism of action. MATERIAL/METHODS: Lewis rats underwent the injection of myocardial myosin mixed with Freund's complete adjuvant were randomized into 3 groups: model, valsartan, and QSYQ groups. Rats injected with phosphate-buffered saline (PBS) mixed with Freund's complete adjuvant were used as the control group. Rats were euthanized at 4 and 8 weeks, and we weighed rat body mass, heart mass, and left ventricular mass. Myocardium sections were stained with hematoxylin and eosin (H&E) and Masson trichrome. Myocardial TGF-ß1 and CTGF protein expression was detected by immunohistochemistry, and myocardial TGF-ß1 and CTGF mRNA expression was detected by real-time qPCR. RESULTS: QSYQ reduced HMI and LVMI, as well as the histological score of hearts and CVF, which further decreased over time, and its effect was significantly greater than that of valsartan at 4 and 8 weeks. After 4 weeks, QSYQ inhibited the protein and mRNA expression of TGF-ß1 and CTGF, and its effect on lowering CTGF was significantly greater than that of valsartan. In addition, after 8 weeks, QSYQ also inhibited the protein and mRNA expression of CTGF, whereas there was no significant difference in the expression of myocardial TGF-ß1. CONCLUSIONS: This study provides evidence that QSYQ can improve cardiac remodeling of experimental autoimmune myocarditis rats. It also effectively improved the degree of myocardial fibrosis, which is related to the mechanism of regulation of TGF-ß1 CTGF.

Anti-ß2GPI antibodies stimulate endothelial cell microparticle release via a nonmuscle myosin II motor protein-dependent pathway.

The antiphospholipid syndrome is characterized by thrombosis and recurrent fetal loss in patients with antiphospholipid antibodies (APLAs). Most pathogenic APLAs are directed against ß2-glycoprotein I (ß2GPI), a plasma phospholipid binding protein. One mechanism by which circulating antiphospholipid/anti-ß2GPI antibodies may promote thrombosis is by inducing the release of procoagulant microparticles from endothelial cells. However, there is no information available concerning the mechanisms by which anti-ß2GPI antibodies induce microparticle release. In seeking to identify proteins phosphorylated during anti-ß2GPI antibody-induced endothelial activation, we observed phosphorylation of nonmuscle myosin II regulatory light chain (RLC), which regulates cytoskeletal assembly. In parallel, we observed a dramatic increase in the formation of filamentous actin, a two- to fivefold increase in the release of endothelial cell microparticles, and a 10- to 15-fold increase in the expression of E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and tissue factor messenger RNA. Microparticle release, but not endothelial cell surface E-selectin expression, was blocked by inhibiting RLC phosphorylation or nonmuscle myosin II motor activity. These results suggest that distinct pathways, some of which mediate cytoskeletal assembly, regulate the endothelial cell response to anti-ß2GPI antibodies. Inhibition of nonmuscle myosin II activation may provide a novel approach for inhibiting microparticle release by endothelial cells in response to anti-ß2GPI antibodies.

Advances in device-based treatment of heart failure with preserved ejection fraction: evidence from clinical trials.

Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society. Recent research indicates that certain device-based therapies may serve as valuable adjuncts to drug therapy in patients with specific phenotypes of HFpEF, effectively improving symptoms and quality of life while reducing the risk of readmission for heart failure. These include inter-atrial shunt and greater splanchnic nerve ablation to reduce left ventricular filling pressure, implantable heart failure monitor to guide diuresis, left atrial pacing to correct interatrial dyssynchrony, cardiac contractility modulation to enhance cardiac calcium handling, as well as renal denervation, baroreflex activation therapy, and vagus nerve stimulation to restore the autonomic imbalance. In this review, we provide a comprehensive overview of the mechanisms and clinical evidence pertaining to these devices, with the aim of enhancing therapeutic strategies for HFpEF.

A Rare Case of Esophageal Carcinoma Cuniculatum Palliated by Esophageal and Endobronchial Stenting.

Carcinoma cuniculatum is a rare variant of well-differentiated squamous cell carcinoma. To date, there are less than 30 cases of esophageal carcinoma cuniculatum reported. It is frequently a diagnostic challenge: A definitive diagnosis typically cannot be made before esophagectomy. We present a uniquely aggressive case of esophageal carcinoma cuniculatum complicated by a bronchoesophageal fistula and successfully palliated with dual esophageal and endobronchial stenting.

Effects of low-level hexabromocyclododecane (HBCD) exposure on cardiac development in zebrafish embryos.

Hexabromocyclododecane (HBCD) is one of the most widely used brominated flame retardants. In the present study, zebrafish embryos were exposed to HBCD at the low concentrations of 0, 2, 20 and 200 nM. The results showed HBCD exposure resulted in an increase in heart rate and cardiac arrhythmia after exposure for 72 h, though the survival rate and the whole malformation rate were not significantly affected. These results demonstrated that the heart might be a target of HBCD. Low-level HBCD exposure may not share the same mechanisms as exposure to high concentrations, since no obvious increase of apoptotic cells around the heart was observed in the HBCD-treated groups. It was observed that the expression of Tbx5 and Nkx2.5 was significantly elevated by HBCD treatment in a dose-dependent manner using real-time quantitative PCR, which may be mainly responsible for the alteration of heart rate, given that Tbx5 and Nkx2.5 are two factors regulating ventricle conduction. The mRNA expression of RyR2 and Atp2a2b (SERCA2a) was up-regulated in the exposure group, which may be one of reasons to affect the normal heart rate, since SERCA2a and RyR2 play an important role in calcium ion transport of cadiomyocytes. However, HBCD exposure did not significantly change the expression of Actc1l, Tnnt2, and Myh6, which are mainly muscle contractile genes that play key roles in the formation of cardiac structure. These results were consistent with the lack of effect seen on the other measurements of cardiac function, end diastolic volume, end-systolic volume, stroke volume, and cardiac output.

Heart failure with recovered ejection fraction: Current understanding and future prospects.

Heart failure with reduced ejection fraction (HFrEF) is a prevalent kind of heart failure in which a significant amount of the ejection fraction can be repaired, and left ventricular remodeling and dysfunction can be reversed or even restored completely. However, a considerable number of patients still present clinical signs and biochemical features of incomplete recovery from the pathophysiology of heart failure and are at risk for adverse outcomes such as re-deterioration of systolic function and recurrence of HFrEF. Furthermore, it is revealed from a microscopic perspective that even if partial or complete reverse remodeling occurs, the morphological changes of cardiomyocytes, extracellular matrix deposition, and abnormal transcription and expression of pathological genes still exist. Patients with "recovered ejection fraction" have milder clinical symptoms and better outcomes than those with continued reduction of ejection fraction. Based on the unique characteristics of this subgroup and the existence of many unknowns, the academic community defines it as a new category-heart failure with recovered ejection fraction (HFrecEF). Because there is a shortage of natural history data for this population as well as high-quality clinical and basic research data, it is difficult to accurately evaluate clinical risk and manage this population. This review will present the current understanding of HFrecEF from the limited literature.

Icariin induces developmental toxicity via thyroid hormone disruption in zebrafish larvae.

Icariin (ICA) is a natural flavonoid isolated from the traditional Chinese medicinal herb, Epimedium brevicornu Maxim. Although previous studies have reported that ICA exhibits various pharmacological activities, little is known about its toxicology. Herein, zebrafish embryos were exposed to ICA at 0, 2.5, 10, and 40 µM. In developmental analysis, reduced hatching rates, decreased body length, and abnormal swim bladder were found after treatment with 10 and 40 µM ICA. In addition, the ability of locomotor behavior was impaired by ICA. Two important thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), were tested. The exposure resulted in a remarkable alteration of T4 level and a significant decrease of the T3/T4 ratio in the 40 µM, indicating thyroid endocrine disruption. Furthermore, gene transcription analysis showed that genes involved in thyroid development (nkx2.1) and THs synthesis (tg) were up-regulated after ICA exposure. Significant down-regulation of iodothyronine deiodinase (dio1) was also observed in the 10 and 40 µM groups compared to the control. Taken together, our study first demonstrated that ICA caused developmental toxicity possibly through disrupting thyroid development and hormone synthesis. These results show that it is necessary to perform risk assessments of ICA in clinical practice.

Analysis of cognitive dysfunction and its risk factors in patients with hypertension.

ABSTRACT: To observe whether obstructive sleep apnea syndrome (OSAS) can aggravate the cognitive dysfunction of patients with hypertension (HTN), and to explore other risk factors.One hundred one hypertensive patients were selected for information collection. After the polysomnography test, they were divided into HTN-obstructive sleep apnea (OSA) and HTN groups. The Montreal cognitive assessment and the mini-mental state examination scales were used to appraise the patients' cognitive function. Logistic regressive analysis was used to determine the risk factors of cognitive dysfunction in patients with HTN.Compared with the HTN patients, HTN-OSA patients performed worse in mini-mental state examination (25.5 ±â€Š2.9 vs 23.5 ±â€Š3.2; P = .01) and Montreal cognitive assessment (28 ±â€Š1.58 vs 21.2 ±â€Š3.96; P = .003), and patients in the HTN-OSA group seemed more likely to suffer from dementia (31% vs 66%; P < .01). The apnea-hypopnea index (AHI) in the HTN group was lower than HTN-OSA group. Through multivariate logistic regression analysis, we can found that alcohol drinking, body mass index, long-term medication, diabetes, hypercholesterolemia, coronary heart disease, and OSAS were the independent risk factors of cognitive dysfunction in patients with HTN.OSAS can aggravate the cognitive dysfunction of hypertensive patients, besides, drinking, high-body mass index, long-term medication, diabetes, hypercholesterolemia, and coronary heart disease were also the risk factors of cognitive dysfunction in patients with hypertension. The cognitive dysfunction of patients with HTN can benefit from sleep apnea treatment.

Carbohydrate antigen 125 combined with N-terminal pro-B-type natriuretic peptide in the prediction of acute heart failure following ST-elevation myocardial infarction.

The value of serum carbohydrate antigen 125 (CA125) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the evaluation of acute heart failure (AHF) after ST-segment elevation myocardial infarction (STEMI) remains unclear. The aim of this study was to evaluate the efficacy of CA125 combined with NT-proBNP in predicting AHF following STEMI. A total of 233 patients with STEMI were evaluated, including 39 patients with Killip II-IV and 194 patients with Killip I. The optimal cutoff point for predicting AHF was determined by receiver operating characteristic (ROC) curve, and the independent predictors of AHF were evaluated by multiple logistic regression. According to the cutoff value, it was divided into three groups: C1 = CA125 < 13.20 and NT-proBNP < 2300 (n = 138); C2 = CA125 ≥ 13.20 or NT-proBNP ≥ 2300 (n = 59); C3 = CA125 ≥ 13.20 and NT-proBNP ≥ 2300 (n = 36). Differences between groups were compared by odds ratio (OR). The levels of CA125 and NT-proBNP in AHF group were higher than those in non-AHF group (19.90 vs 10.00, P < .001; 2980.00 vs 1029.50, P < .001, respectively). The optimal cutoff values of CA125 and NT-proBNP for predicting AHF were 13.20 and 2300, both of which were independent predictors of AHF. The incidence of AHF during hospitalization was highest in C3 (69.44%), middle in C2 (20.34%) and lowest in C1 (1.45%). After adjustment for clinical confounding variables, compared with C1: C2 (OR = 6.41, 95% CI: 1.22-33.84, P = .029), C3 (OR = 19.27, 95% CI: 3.12-118.92, P = .001). Elevated CA125 and NT-proBNP are independent predictors of AHF in STEMI patients, and their combination can improve the recognition efficiency.