Anxiety, home blood pressure monitoring, and cardiovascular events among older hypertension patients during the COVID-19 pandemic.

The global coronavirus disease 2019 (COVID-19) pandemic has led to a health crisis. It remains unclear how anxiety affects blood pressure (BP) and cardiovascular risk among older patients with hypertension. In this study, we extracted longitudinal data on home BP monitored via a smartphone-based application in 3724 elderly patients with hypertension from a clinical trial (60-80 years; 240 in Wuhan and 3484 in non-Wuhan areas) to examine changes in morning BP during the COVID-19 outbreak in China. Anxiety was evaluated using Generalized Anxiety Disorder-7 item scores. Changes in morning systolic BP (SBP) were analyzed for five 30-day periods during the pandemic (October 21, 2019 to March 21, 2020), including the pre-epidemic, incubation, developing, outbreak, and plateau periods. Data on cardiovascular events were prospectively collected for one year. A total of 262 individuals (7.0%) reported an increased level of anxiety, and 3462 individuals (93.0%) did not. Patients with anxiety showed higher morning SBP than patients without anxiety, and the between-group differences in SBP change were +1.2 mmHg and +1.7 mmHg during the outbreak and plateau periods (P < 0.05), respectively. The seasonal BP variation in winter among patients with anxiety was suppressed during the pandemic. Anxious patients had higher rates of uncontrolled BP. During the 1-year follow-up period, patients with anxiety had an increased risk of cardiovascular events with a hazard ratio of 2.47 (95% confidence interval, 1.10-5.58; P = 0.03). In summary, COVID-19-related anxiety was associated with a short-term increase in morning SBP among older patients and led to a greater risk of cardiovascular events. (ClinicalTrials. gov number, NCT03015311).

Intervention Effect of Probiotics in Gastric Cancer Patients with Complications of Coronary Heart Disease and Heart Failure.

OBJECTIVE: To investigate the characteristics of intestinal flora in patients with gastric cancer complicated by coronary heart disease and heart failure and the guiding value of probiotics intervention for clinical treatment. METHODS: (1) One hundred and sixty-eight gastric cancer patients with complications of coronary heart disease and heart failure from August 2017 to December 2020 were selected as the observation group. A total of 125 patients with coronary heart disease treated at the same time were selected as control group 1, and 89 healthy subjects were selected as control group 2. Fecal samples were retained to extract the total RNA, and high-throughput sequencing was applied to complete the analysis of microbial diversity and structure differences, so as to obtain the biological species information of the specimens. (2) Patients in the observation group were randomly divided into two equal groups of 84 patients, namely, group A and group B. Group A was treated with conventional methods, and group B was combined with probiotics intervention on the basis of group A; then, the differences in the intestinal mucosal barrier between the two groups were compared. RESULTS: The Chao, ACE, and Simpson index in the observation group were lower than those in control group 1 (P < 0.05), and the Shannon index was higher than that in control group 1 (P < 0.05). The Chao, ACE, and Shannon index in control group 1 were lower than those in control group 2 (P < 0.05), whereas the Simpson index was higher than in control group 2 (P < 0.05). The abundance of Bacteroidetes in the observation group was lower than that in control group 1 and control group 2 (P < 0.05). The abundance of Firmicutes was higher than that of control group 1 and control group 2 (P < 0.05). Four weeks after treatment, the levels of ET, D-lactic acid, and PCT in the group B were (0.10 ± 0.01), (3.99 ± 0.32), and (0.41 ± 0.10), respectively, which were lower than those in group A (0.19 ± 0.03), (4.51 ± 0.46), and (0.81 0.13). CONCLUSION: Gastric cancer patients with complications of coronary heart disease and heart failure are associated with intestinal flora disorder, which may be involved in the occurrence and development of the disease. Probiotics intervention is helpful to repair the intestinal mucosal barrier in patients, which is worthy of popularization and application.

Protective Effect of Ginsenoside Rb1 Nanoparticles Against Contrast-Induced Nephropathy by Inhibiting High Mobility Group Box 1 Gene/Toll-Like Receptor 4/NF-κB Signaling Pathway.

With the progress made in the widespread application of interventional radiology procedures, there has been an increasing number of patients who suffer from cardiovascular diseases and go through imaging and interventional treatment with iodine contrast medium (ICM) year by year. In turn, there has been an increasing amount of concern over acute kidney injury (AKI) brought about by ICM. As evidenced by numerous studies, the initiation of inflammatory response plays a critical role in the development of ICM-induced AKI. Correspondingly, the strategy of targeting renal inflammatory response and cytokine release could provide an effective solution to mitigating the ICM-induced AKI. Moreover, Ginsenoside Rb1 (GRb1) constitutes one of the major active components of ginseng and features a wide range of vital biological functions. Judging from the research findings, GRb1 could impose antioxidant and anti-inflammatory effects on cardiovascular diseases, in addition to lung, liver and kidney diseases. However, reports on whether GRb1 could impose a protective effect against contrast-induced nephropathy (CIN) are absent. In this study, we have examined the therapeutic effects imposed by GRb1 as well as the potential molecular mechanism by establishing an in vivo and in vitro model of CIN. In addition, we have set up a mouse model of CIN through sequential intravenous injection of indomethacin, N(ω)-nitro-Larginine methyl ester (L-NAME), and iopromide. To further enhance the bioavailability of GRb1, we have encapsulated GRb1 with polyethylene glycol (PEG)/poly lactic-co-glycolic acid (PLGA) nanocarriers to generate GRb1 nanoparticles (NPs) conducting the in vivo experiments. During the in vitro experiments, we have adopted GRb1 to treat NRK-52E cells or cells transfected with the high mobility group box 1 gene (HMGB1) overexpression plasmid. As shown by the in vivo experimental results, GRb1 NPs could evidently improve the renal dysfunction in CIN, diminish the extent of apoptosis of tubular epithelial cells, and reduce the expression of high mobility group box 1 (HMGB1) and cytokines (tumor necrosis factor (TNF-α), interleukin (IL) 6 and IL-1ß). In addition, GRb1 NPs are found to be capable of preventing the activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway triggered by contrast medium. The in vitro experimental results have exactly confirmed the findings of the in vivo experiments. In the meantime, through the observation of the in vitro assays, overexpression of HMGB1 can partially counteract the beneficial effects imposed by GRb1. Judging from our research data, GRb1 could impose a protective effect against CIN by inhibiting inflammatory response via HMGB1/TLR4/NF-κB pathway, whereas HMGB1 constitutes a critical molecular target of GRb1.

Patients with Dipper and Nondipper High-Normal Blood Pressure Were Associated with Left Ventricular Mass.

PURPOSE: High-normal blood pressure has been suggested to associate with target organ damage and higher left ventricular mass index (LVMI). Our aim is to find the association between people with high-normal blood pressure and their left ventricular mass index. MATERIALS AND METHODS: Given a total of 181 people with office blood pressure, 24-hour ambulatory blood pressure monitoring, 35 of them are normotensive (BP < 130/85 mm Hg), and 146 people with high-normal blood pressure (BP 130-139/85-89 mm Hg), divide the high-normal blood pressure group into dipper and nondipper according to their ABPM in 24 hours. All of them were performed with echocardiography to calculate LVMI. RESULTS: After adjusting for potential confounding factors, mean systolic blood pressure (BP) of the nondipper group is (119 + 9) mmHg in 24 h, which is significantly higher (p < 0.05) than in the dipper group (116 + 11) mmHg, indicating the mean systolic BP is associated with the dipper type (p < 0.05); furthermore, the higher nocturnal blood pressure is associated with the nondipper group significantly (p < 0.05), and LVMI ((121 ± 11) g/m2) of the nondipper group is also significantly higher than in the dipper group's LVMI ((108 ± 12) g/m2) (p < 0.05). The multivariate linear regression analyses revealed significant and independent associations of LVMI with these factors: triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and coefficient of variation of systolic and diastolic blood pressure in 24 hours. CONCLUSION: After multiple relevant clinical confounding factors were adjusted, patients with dipper and nondipper high-normal blood pressure had higher LVMI. Abnormalities in circadian blood pressure variability may be associated with the left ventricular hypertrophy.

Preoperative Prognostic Nutritional Index is a Significant Predictor of Survival in Esophageal Squamous Cell Carcinoma Patients.

Background: Preoperative assessment of patients is meaningful to predict survival in patients with malignant tumors. The prognostic nutritional index (PNI) is one of the most significant factors related to the prognosis in various types of cancer; however, its role in esophageal cancer is still inconclusive. The aim of this study was to identify the prognostic value of PNI in predicting overall survival (OS) in esophageal squamous cell carcinoma (ESCC).Methods: This retrospective study included 4146 ESCC patients, 3812 who underwent esophagectomy for ESCC. Other 334 had no surgery. The Preoperative PNI was measured before any therapies and calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). We classified the patients into three categories according to the PNI, >50, 45-50, and <45.Results: Our study showed that PNI was associated with age (P<0.0001), gender(P<0.001),tumor length (P<0.0001), T grade (P = 0.001), N staging (P = 0.017),and M staging (P<0.0001). Multivariate analysis showed that PNI was a significant predictor of overall survival Lower PNI vs. Higher PNI group had significantly increased the hazard ratio of ESCC survival (OR = 1.2, 95% CI= 1.05-1.5, p = 0.01). The Kaplan-Meier curve suggested that high PNI group will significantly increase the OS in both surgical and non-surgical group.Conclusion: PNI is a useful predictive factor for long-term survival in ESCC. The survival rate of ESCC can be discriminated between three groups, PNI, >50, 45-50, and <45. The prognostic value of PNI can be applied for both surgical and non-surgical ESCC patients.

Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Protective Effect of miR-204 on Doxorubicin-Induced Cardiomyocyte Injury via HMGB1.

The toxicity of doxorubicin (DOX) limits its clinical application. Nevertheless, at present, there is no effective drug to prevent DOX-induced cardiac injury. miR-204 is a newly discovered miRNA with many protective effects on cardiovascular diseases. However, little research has been done on the effects of miR-204 on DOX-induced cardiac injury. Our study is aimed at investigating the effect of miR-204 on DOX-induced myocardial injury. An adenoassociated virus system was used to achieve cardiac-specific overexpression of miR-204. Two weeks later, the mice were intraperitoneally injected with DOX (15 mg/kg) to induce cardiac injury. H9c2 myocardial cells were used to validate the role of miR-204 in vitro. Our study showed that miR-204 expression was decreased in DOX-treated hearts. miR-204 overexpression improved cardiac function and alleviated cardiac inflammation, apoptosis, and autophagy induced by DOX. In addition, our results showed that miR-204 prevented DOX-induced injury in cardiomyocytes by directly decreasing HMGB1 expression. Moreover, the overexpression of HMGB1 could offset the protective effects of miR-204 against DOX-induced cardiac injury. In summary, our study showed that miR-204 protected against DOX-induced cardiac injury via the inhibition of HMGB1, and increasing miR-204 expression may be a new treatment option for patients with DOX-induced cardiac injury.

Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424-5p/IGF2 axis.

BACKGROUND: Circular RNAs (circRNAs) have been identified to be critical mediators in the progression of atherosclerosis (AS). However, the exact roles and molecular mechanism of circ_0029589 in AS are far from understood. METHODS: Vascular smooth muscle cells (VSMCs) stimulated by oxidized low-density lipoprotein (ox-LDL) were served as a cellular model of AS. The expression levels of circ_0029589, microRNA (miR)-424-5p, and insulin-like growth factor 2 (IGF2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot analysis. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell apoptosis, migration and invasion were examined by flow cytometry and transwell assay. The relationship between miR-424-5p and circ_0029589 or IGF2 was predicted by starbase and verified by dual-luciferase reporter assay. RESULTS: Circ_0029589 and IGF2 were upregulated and miR-424-5p was downregulated in VSMCs treated with ox-LDL. Silence of circ_0029589 inhibited proliferation, migration and invasion but induced apoptosis in ox-LDL-treated VSMCs. MiR-424-5p was a target of circ_0029589 and its knockdown reversed the effects of circ_0029589 interference on proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs. IGF2 was a target of miR-424-5p and miR-424-5p overexpression suppressed proliferation, migration and invasion while promoted apoptosis in ox-LDL-treated VSMCs by downregulating IGF2. Circ_0029589 positively modulated IGF2 expression by sponging miR-424-5p. CONCLUSION: Circ_0029589 silence might inhibit the progression of AS by regulating miR-424-5p/IGF2 axis, providing a novel mechanism for pathogenesis of AS.

TBC1D25 Regulates Cardiac Remodeling Through TAK1 Signaling Pathway.

Cardiac remodeling is a major early event of heart failure, which is regulated by multiple signaling pathways. Here, we demonstrate that TBC1D25 is upregulated during pathological cardiac remodeling. The aim of this study is to determine the role of TBC1D25 in cardiac remodeling and to illustrate the underlying molecular mechanism. Specifically, cardiac remodeling was induced in TBC1D25-KO mice and their wild-type control mice through partial transverse aortic constriction (TAC) of aortic arch. Knockout TBC1D25 exacerbated cardiac hypertrophy, fibrosis and dysfunction. Meanwhile, TBC1D25 overexpression in both H9C2 cells and NRCMs alleviate Angiotensin II-induced cardiomyocyte hypertrophy in vitro. Moreover, TBC1D25 deficiency increases the phosphorylation levels of TAK1 and its downstream molecular (JNK and p38), whereas overexpressed TBC1D25 inhibits phosphorylation of TAK1, JNK and p38. And TAK1 is the key molecule in this process. Furthermore, we demonstrated that TBC1D25 could directly interacts with TAK1 by immunoprecipitation assay and GST pull-down assay, and the interaction needs the amino acids from at least 138 to 226 in the C-terminal region of TBC1D25 and from 1 to 300 in the C-terminal region of TAK1. We conclude that TBC1D25 suppresses pathological cardiac remodeling via regulating TAK1-JNK/p38 signaling pathway, which suggests that TBC1D25 will likely become a promising therapeutic target for heart failure.

Rationale and design of the Henan ST elevation myocardial infarction (STEMI) registry: a regional STEMI project in predominantly rural central China.

BACKGROUND: Cardiovascular disease including ST elevation myocardial infarction (STEMI) is increasing and the leading cause of death in China. There has been limited data available to characterize STEMI management and outcomes in rural areas of China. The Henan STEMI Registry is a regional STEMI project with the objectives to timely obtain real-world knowledge about STEMI patients in secondary and tertiary hospitals and to provide a platform for care quality improvement efforts in predominantly rural central China. METHODS: The Henan STEMI Registry is a multicentre, prospective and observational study for STEMI patients. The registry includes 66 participating hospitals (50 secondary hospitals; 16 tertiary hospitals) that cover 15 prefectures and one city direct-controlled by the province in Henan province. Patients were consecutively enrolled with a primary diagnosis of STEMI within 30 days of symptom onset. Clinical treatments, outcomes and cost are collected by local investigators and captured electronically, with a standardized set of variables and standard definitions, and rigorous data quality control. Post-discharge patient follow-up to 1 year is planned. As of August 2018, the Henan STEMI Registry has enrolled 5479 patients of STEMI. DISCUSSION: The Henan STEMI Registry represents the largest Chinese regional platform for clinical research and care quality improvement for STEMI. The board inclusion of secondary hospitals in Henan province will allow for the exploration of STEMI in predominantly rural central China. TRIAL REGISTRATION: [NCT02641262] [29 December, 2015].

miR-34b/c regulates doxorubicin-induced myocardial cell injury through ITCH.

Objective: To determine the underlying mechanism of miR-34b/c in regulating doxorubicin (Dox)-induced myocardial cell injury.Methods: The viability of mouse myocardial cells HL-1 was detected by MTT assay. The apoptosis of HL-1 cells was detected by TUNEL assay. mRNA expressions of ITCH, TNF-α and IL-6 were measured by qRT-PCR. Protein levels of ITCH, NF-κB, TNF-α and IL-6 were measured by western blot. Dual luciferase assay was performed to detect the regulation of miR-34b/c on ITCH. Mouse model of cardiomyopathy was induced by intraperitoneal injection of Dox.Results: Dox reduced HL-1 cell viability and activated NF-κB pathway in HL-1 cells. miR-34b/c expressions were gradually up-regulated and ITCH expression was gradually down-regulated in Dox-treated HL-1 cells. miR-34b/c expression had negative correlation with the mRNA expression of ITCH. Besides, ITCH was a target of miR-34b/c. miR-34b/c mimic reduced cell viability, suppressed ITCH expression, increased TNF-α and IL-6 level, and promoted NF-κB expression in nucleus and cytoplasm of HL-1 cells. Whereas silencing miR-34 protected HL-1 cells through regulating ITCH. Finally, we demonstrated miR-34 antagomir-protected myocardial cells in mouse model of cardiomyopathy.Conclusion: miR-34b/c decreased HL-1 cell viability and promoted the secretion of proinflammatory cytokines in Dox-induced myocardial cells through ITCH/NF-κB pathway.

No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study.

BACKGROUND: Reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient. METHODS: In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of "compound reserpine and triamterene tablets (CRTTs)" for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected. RESULTS: From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users (P = 0.7). The majority of study subject had a depression score < 53 (87.6% in reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users. CONCLUSIONS: There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered; and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

China STudy of valsartan/amlodipine fixed-dose combination-bAsed long-Term blood pressUre management in HypertenSive patients: a one-year registry (China STATUS III).

Objective: The present observational study evaluated long-term management of hypertension in patients who received treatment with valsartan and amlodipine in a single-pill combination (Val/Aml SPC) in a real-world setting in China (Chinese Clinical Trial Registry number ChiCTR1900021324). Methods: This was a prospective, observational, multicenter, real-world registry study wherein patients with hypertension who had already received Val/Aml SPC (80/5 mg) for at least 4 weeks before study enrollment were observed for 1 year. Investigators recorded patient data every 3 months and essentially five times during the 1 year follow-up period. Effectiveness was assessed by the blood pressure (BP) control rate and average duration of treatment at the end of the study. Safety was monitored by the incidence of adverse events (AEs) and serious adverse events (SAEs). Results: Overall, 985 patients were enrolled (mean ± standard deviation [SD] age: 60.3 ± 11.5 years); of these, 894 were included in the full analysis set, 758 of whom completed the study. At baseline, BP was controlled (<140/90 mmHg) in 64.3% of patients on Val/Aml SPC for at least 4 weeks before enrollment. Office BP control rates significantly improved from baseline in 74.1% of patients at 1 year (p < .0001). Overall, 575 (87.0%) patients remained on Val/Aml SPC at 1 year (average exposure: 311.5 days). AEs were reported in 23.3% of patients. The majority of AEs were mild to moderate, and 0.6% of patients discontinued Val/Aml SPC because of SAEs. Conclusion: This study provides evidence that Val/Aml SPC effectively reduced BP over the long term among Chinese hypertensive patients, with a good adherence and tolerability profile, and that most hypertensive patients may benefit from this combination.

MDM2 and its functional polymorphism SNP309 contribute to the development of esophageal carcinoma.

BACKGROUND: Overexpression of the murine double minute 2 (MDM2) has been explored in many tumors with high proliferation and anti-apoptosis ability. However, the role of MDM2 and its functional single nucleotide polymorphism (SNP) rs2279744 (also known as SNP309) in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: We performed a genotype study of blood samples in 360 ESCC patients and 360 healthy control individuals to determine the risk of various rs2279744 in ESCC. To further evaluate the role of rs2279744 in regulating MDM2 expression, we performed an allele-specific reporter assay and investigated whether the SNP-containing sequences functioned as an active enhancer. To examine the functional role of MDM2 on esophageal cancer cell lines, we carried out an MTS assay and flow cytometry analysis. RESULTS: From the genotyping study, we found that GG genotype of SNP309 significantly increased the risk of ESCC in an additive model [odds ratio (OR) = 2.55, 95% confidence interval (CI) = 1.66-3.89, p = 1.50 × 10-5 ) and in a recessive model (OR = 2.44, 95% CI = 1.69-3.51, p = 1.60 × 10-8 ). Furthermore, the G allele was significantly associated with a higher risk of ESCC (OR = 1.56, 95% CI = 1.26-1.92, p = 2.81 × 10-5 ). In multivariate logistic regression analysis, the GG genotype had increased the occurrence of ESCC by 2.39-fold (95% CI = 1.48-3.8). Compared to the T allele, the variant G allele had significantly higher luciferase activity on the promoter of MDM2 in both cell lines. By transfecting the gene to ESCC lines, we showed that overexpression of MDM2 significantly promote cell proliferation and anti-apoptosis. CONCLUSIONS: The MDM2 promoter SNP309 is a risk factor for esophageal cancer. MDM2 promotes the proliferation and anti-apoptosis of ESCC.

Bakuchiol protects against pathological cardiac hypertrophy by blocking NF-κB signaling pathway.

Bakuchiol (Bak), a monoterpene phenol isolated from the seeds of Psoralea corylifolia, has been widely used to treat a large variety of diseases in both Indian and Chinese folkloric medicine. However, the effects of Bak on cardiac hypertrophy remain unclear. Therefore, the present study was designed to determine whether Bak could alleviate cardiac hypertrophy. Mice were subjected to aortic banding (AB) to induce cardiac hypertrophy model. Bak of 1 ml/100 g body weight was given by oral gavage once a day from 1 to 8 weeks after surgery. Our data demonstrated for the first time that Bak could attenuate pressure overload-induced cardiac hypertrophy and could attenuate fibrosis and the inflammatory response induced by AB. The results further revealed that the effect of Bak on cardiac hypertrophy was mediated by blocking the activation of the NF-κB signaling pathway. In vitro studies performed in neonatal rat cardiomyocytes further proved that the protective effect of Bak on cardiac hypertrophy is largely dependent on the NF-κB pathway. Based on our results, Bak shows profound potential for its application in the treatment of pathological cardiac hypertrophy, and we believe that Bak may be a promising therapeutic candidate to treat cardiac hypertrophy and heart failure.

Downregulation of microRNA­34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats.

The present study aimed to identify the microRNA (miRNA) responsible for the development of primary hypertension, and examine the downstream signaling pathway, which mediates the effect of the miRNA. Reverse transcription­quantitative polymerase chain reaction analysis was performed to identify which miRNA may be involved in the pathogenesis of hypertension. In silico analysis and a luciferase assay were used to validate the target of the selected miRNA, and miRNA mimics and small interfering (si)RNA of the target were transfected into smooth muscle cells to examine its effect on the biological activity of the cells. miR­34b was found to be upregulated in spontaneously hypertensive rats (SHRs), compared with Wistar Kyoto (WKY) rats. Therefore, the present study used online miRNA target prediction tools to predict the candidate target genes of miR­34b in the database, and consequently identified cyclin G1 (CCNG1) and cyclin­dependent kinase 6 (CDK6) as its possible target genes. CDK6 subsequently identified to be the direct target gene of miR­34b using a luciferase reporter assay in vascular smooth muscle cells (VSMCs). The present study also established the possible negative regulatory association between miR­34b and CDK6 via investigating the mRNA and protein expression levels of CDK6 and CCNG1 in VSMCs collected from the SHRs and WKY rats, respectively. To investigate the signaling pathways between miR­34b and CDK6, the mRNA and protein expression levels of CDK6, and the proliferation rates were compared in VSMCs transfected with CDK6 siRNA or miR­34b mimics, the results of which indicated that the miR­34b mimics exerted the same effects on the expression of CDK6 and cell proliferation as CDK6 siRNA. The negative regulatory association between miR­34b and its target, CDK6, was confirmed, which may offer potential as a novel therapeutic target in the treatment of hypertension.

Clinical effect of ticagrelor administered in acute coronary syndrome patients following percutaneous coronary intervention.

The aim of the present study was to retrospectively analyze the clinical effect and safety of ticagrelor administration in acute coronary syndrome (ACS) patients following percutaneous coronary intervention (PCI). In total, 203 patients were enrolled, who were confirmed with ACS between March 2013 and May 2013, and had successfully undergone PCI. The patients were randomly divided into two groups, including the clopidogrel (group A, n=108) and ticagrelor groups (group B, n=95). Patients in group A were treated with a 600 mg loading dose of clopidogrel followed by 75 mg/day clopidogrel plus 100 mg/day aspirin. Patients in group B received a 180 mg loading dose of ticagrelor followed by 90 mg ticagrelor twice daily plus 100 mg/day aspirin. Light transmission aggregometry was performed to measure the platelet aggregation rate prior to and following 4 weeks of anti-platelet drug treatment. In addition, the rate of cardiovascular events and the adverse drug reactions were recorded within a 1-year treatment period. Compared with the clopidogrel group, the rate of recurrent angina in the ticagrelor group was significantly lower (P=0.05). However, the rate of dyspnea in the ticagrelor group was significantly higher when compared with that in the clopidogrel group (P=0.03). After 4 weeks of treatment, the reduction in the platelet aggregation rate was significantly different between the two groups (P<0.05). Therefore, ticagrelor, which is a novel antiplatelet aggregation drug, may reduce the rate of the adverse cardiovascular events in ACS patients following PCI, but a higher incidence of side-effects, such as dyspnea, may be observed.

Establishment of Relational Model of Congenital Heart Disease Markers and GO Functional Analysis of the Association between Its Serum Markers and Susceptibility Genes.

PURPOSE: The purpose of present study was to construct the best screening model of congenital heart disease serum markers and to provide reference for further prevention and treatment of the disease. METHODS: Documents from 2006 to 2014 were collected and meta-analysis was used for screening susceptibility genes and serum markers closely related to the diagnosis of congenital heart disease. Data of serum markers were extracted from 80 congenital heart disease patients and 80 healthy controls, respectively, and then logistic regression analysis and support vector machine were utilized to establish prediction models of serum markers and Gene Ontology (GO) functional annotation. RESULTS: Results showed that NKX2.5, GATA4, and FOG2 were susceptibility genes of congenital heart disease. CRP, BNP, and cTnI were risk factors of congenital heart disease (p < 0.05); cTnI, hs-CRP, BNP, and Lp(a) were significantly close to congenital heart disease (p < 0.01). ROC curve indicated that the accuracy rate of Lp(a) and cTnI, Lp(a) and BNP, and BNP and cTnI joint prediction was 93.4%, 87.1%, and 97.2%, respectively. But the detection accuracy rate of the markers' relational model established by support vector machine was only 85%. GO analysis suggested that NKX2.5, GATA4, and FOG2 were functionally related to Lp(a) and BNP. CONCLUSIONS: The combined markers model of BNP and cTnI had the highest accuracy rate, providing a theoretical basis for the diagnosis of congenital heart disease.

Prognostic value of total bilirubin in patients with angina pectoris undergoing percutaneous coronary intervention.

BACKGROUND: Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis. OBJECTIVE: To evaluate the prognostic value of serum total bilirubin (STB) in patients with angina pectoris undergoing percutaneous coronary intervention (PCI). METHODS: In total of 1419 patients (931 men, mean age 60.9±10.5 years) with angina pectoris who had undergone successfully percutaneous coronary intervention (PCI) were included in this study. Patients were divided into 2 groups according to the median baseline STB (0.49 mg/dL in this cohort), which was measured before the PCI. Patients with a STB ≥0.49 mg/dL were classified into the high STB group and those with a STB <0.49 mg/dL were classified into the low STB group. RESULTS: The incidence of in-hospital mortality and myocardial infraction was similar in the two groups. After a mean follow-up of 29.0±7.6 months, the incidence of death/myocardial infarction/stroke was significantly higher in low STB group compared with high STB group. Multivariate Cox regression analysis showed that low STB was an independent predictor of death/myocardial infarction/stroke (hazard ratio (HR) = 1.59, 95% confidence interval (CI) = 1.04-2.41, P = 0.031). The cumulative survival rate free from death/myocardial infarction/stroke was lower in low STB group than in high STB group (P = 0.002). CONCLUSION: Low STB levels before PCI is an independent predictor of long-term adverse clinical outcomes in patients with angina pectoris.

ADRB2 polymorphisms predict the risk of myocardial infarction and coronary artery disease.

Recently, the rs1042713 G > A and rs1042714 C > G polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene were shown to be related to atherosclerosis diseases. Therefore, we performed a systemic meta-analysis to determine whether the two functional polymorphisms are related to the risk of myocardial infarction (MI) and coronary artery disease (CAD). We identified published studies that are relevant to our topic of interest. Seven case-control studies, with a total of 6,843 subjects, were incorporated into the current meta-analysis. Our analysis showed a higher frequency of rs1042713 G > A variant in patients with MI or CAD compared to healthy controls. A similar result was also obtained with the rs1042714 C > G variant under both the allele and dominant models. Ethnicity-stratified subgroup analysis suggested that the rs1042714 C > G variant correlated with an increased risk of the two diseases in both Asians and Caucasians, while rs1042713 G > A only contributes to the risk of two diseases in Asians. In the disease type-stratified subgroups, the frequencies of both the rs1042713 G > A and rs1042714 C > G variants were higher in the cases than in the controls in both the MI and CAD subgroups. Collectively, our data contribute towards understanding the correlation between the rs1042713 G > A and rs1042714 C > G polymorphisms in ADRB2 and the susceptibility to MI and CAD.