Search

BackgroundHypertension is the most common cause of pathological left ventricular hypertrophy, a condition causally associated with debilitating heart failure and cardiovascular events in hypertensive patients. It is well recognized that the disease burden of hypertension-linked heart failure remains unabated with existing treatments. New therapies controlling hypertensive left ventricular hypertrophy are thus required to decelerate or prevent the development of heart failure. Our previous study has demonstrated that cinnamic acid, a naturally occurring monocarboxylic acid, mitigates transverse aortic constriction-induced pressure overload-mediated cardiac hypertrophy. However, whether cinnamic acid is effective at controlling hypertensive left ventricular hypertrophy remains unknown. Angiotensin II (ang II) plays a pivotal role in driving the pathogenesis of hypertensive left ventricular hypertrophy. The current work thus investigates the therapeutic potential and pharmacological mechanisms of cinnamic acid in the context of ang II-mediated hypertensive left ventricular hypertrophy.MethodsAng II-infused mice and cardiomyocytes were analyzed by histological, immunohistochemical, cellular and molecular biological methods to delineate the impact of cinnamic acid on hypertensive left ventricular hypertrophy.ResultsThe results showed that cinnamic acid lowered blood pressure and attenuated left ventricular hypertrophic and fibrotic alterations in the ang II-infused mice. Cinnamic acid counteracted hypertrophic responses, impairment of the mitochondrial function and overproduction of mitochondrial reactive oxygen species (ROS) in the cardiomyocytes exposed to ang II. At the molecular level, cinnamic acid mitigated ang II-induced activation of signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2) in cardiomyocytes. Additionally, cinnamic acid blunted STAT3 and ERK1/2 activation as well as the hypertrophic responses in cardiomyocytes exposed to interleukin 6 (IL-6) as well.ConclusionIn summary, this is the first study demonstrating that cinnamic acid is effective at mitigating hypertensive left ventricular hypertrophy. Cinnamic acid antagonizes the vasopressor activity of ang II at the systemic level and the ligand-dependent pro-hypertrophic signaling of ang II in cardiomyocytes. Furthermore, our present study presents new evidence supporting that cinnamic acid lessens the activation of STAT3 and ERK1/2, which may in part contribute to its anti-hypertrophic actions in cardiomyocytes.

Abstract Activated microglia play an important role in driving photoreceptor degeneration-associated neuroinflammation in the retina. Controlling pro-inflammatory activation of microglia holds promise for mitigating the progression of photoreceptor degeneration. Our previous study has demonstrated that pre-light damage treatment of hyperoside, a naturally occurring flavonol glycoside with antioxidant and anti-inflammatory activities, prevents photooxidative stress-induced photoreceptor degeneration and neuroinflammatory responses in the retina. However, the direct impact of hyperoside on microglia-mediated neuroinflammation during photoreceptor degeneration remains unknown. Upon verifying the anti-inflammatory effects of hyperoside in LPS-stimulated BV-2 cells, our results here further demonstrated that post-light damage hyperoside treatment mitigated the loss of photoreceptors and attenuated the functional decline of the retina. Meanwhile, post-light damage hyperoside treatment lowered neuroinflammatory responses and dampened microglial activation in the illuminated retinas. With respect to microglial activation, hyperoside mitigated the pro-inflammatory responses in DNA-stimulated BV-2 cells and lowered DNA-stimulated production of 2′3′-cGAMP in BV-2 cells. Moreover, hyperoside was shown to directly interact with cGAS and suppress the enzymatic activity of cGAS in a cell-free system. In conclusion, the current study suggests for the first time that the DNA sensor cGAS is a direct target of hyperoside. Hyperoside is effective at mitigating DNA-stimulated cGAS-mediated pro-inflammatory activation of microglia, which likely contributes to the therapeutic effects of hyperoside at curtailing neuroinflammation and alleviating neuroinflammation-instigated photoreceptor degeneration.

Abstract Background Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM. Methods In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018. Results Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (β = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio

Abstract Background Photoreceptor degeneration underpinned by oxidative stress-mediated mitochondrial dysfunction and cell death leads to progressive and irreversible vision impairment. Drug treatments that protect against photoreceptor degeneration are currently available in the clinical settings. It has been shown that hyperoside, a flavonol glycoside, protects against neuronal loss in part by suppressing oxidative stress and maintaining the functional integrity of mitochondria. However, whether hyperoside protects against photoreceptor degeneration remains unknown. Methods To address the pharmacological potentials of hyperoside against oxidative stress-mediated photoreceptor degeneration on molecular, cellular, structural and functional levels, multiple in vitro and in vivo methodologies were employed in the current study, including live-cell imaging, optical coherence tomography, electroretinography, histological/immunohistochemical examinations, transmission electron microscopy, RNA-sequencing and real-time qPCR. Results The in vitro results demonstrate that hyperoside suppresses oxidative stress-mediated photoreceptor cell death in part by mitigating mitochondrial dysfunction. The in vivo results reveal that hyperoside protects against photooxidative stress-induced photoreceptor morphological, functional and ultrastructural degeneration. Meanwhile, hyperoside treatment offsets the deleterious impact of photooxidative stress on multiple molecular pathways implicated in the pathogenesis of photoreceptor degeneration. Lastly, hyperoside attenuates photoreceptor degeneration-associated microglial inflammatory activation and reactive Müller cell gliosis. Conclusions All things considered, the present study demonstrates for the first time that hyperoside attenuates oxidative stress-induced photoreceptor mitochondrial dysfunction and cell death. The photoreceptor-intrinsic protective effects of hyperoside are corroborated by hyperoside-conferred protection against photooxidative stress-mediated photoreceptor degeneration and perturbation in retinal homeostasis, warranting further evaluation of hyperoside as a photoreceptor protective agent for the treatment of related photoreceptor degenerative diseases.

Background: Rapid progression of coronary non-target lesions is essential for the determination of future cardiovascular events. Clinical factors that predict rapid progression of non-target lesions are unclear. The purpose of this study was to identify the clinical predictors of rapid progression and revascularization of coronary non-target lesions. Methods: Consecutive patients with coronary heart disease who had undergone two serial coronary angiograms were enrolled. All coronary non-target lesions were identified and evaluated at both procedures. Multivariable Cox regression analysis was used to investigate the clinical risk factors associated with rapid progression or revascularization of coronary non-target lesions. Results: A total of 1255 patients and 1670 lesions were enrolled. In this cohort of patients, 239 (19%) had rapid progression and 186 (14.8%) underwent revascularization. At the lesion level, 251 (15.0%) had rapid progression and 194 (11.6%) underwent revascularization. The incidence of lesion revascularization and myocardial infarction was significantly higher in patients with rapid progression. In multivariable analyses, hypertension (hazard ratio [HR], 0.76; 95% confidence interval [95% CI], 0.58–1.00; p = 0.049), ST-segment elevation myocardial infarction (STEMI) (HR, 1.46; 95% CI, 1.03–2.07; p = 0.035), glycosylated hemoglobin (HR, 1.16; 95% CI, 1.01–1.33; p = 0.039) and lesion classification (B2/C versus A/B1) (HR, 1.73; 95% CI, 1.27–2.35; p = 0.001) were significant factors associated with rapid progression. The level of triglycerides (HR, 1.10; 95% CI, 1.00–1.20; p = 0.040) and lesion classification (B2/C versus A/B1) (HR, 1.53; 95% CI, 1.09–2.14; p = 0.014) were predictors of lesion revascularization. Conclusions: Hypertension, STEMI, glycosylated hemoglobin and lesion classification may be used as predictors of rapid progression of coronary non-target lesions. The level of triglyceride and lesion classification may predict the revascularization of non-target lesions. In order to prevent future cardiovascular events, increased attention should be paid to patients with these factors.

Abstract Obstructive sleep apnea (OSA) is much common and associated with worse clinical outcomes in patients with hypertrophic cardiomyopathy (HCM), however, the diagnosis of OSA in HCM is still insufficient. We aim to investigate the clinical predictors of OSA in a large series of patients with HCM. A total of 589 patients with HCM who underwent sleep evaluations were retrospectively enrolled. Data from clinical characteristics and polysomnography studies were recorded. OSA was present in 346 patients (58.7%). Patients who had OSA were older, more likely to be male and had more clinical comorbidities such as hypertension, atrial fibrillation and cardiac remodeling. Multivariate logistic analyses showed that male, age, body mass index, hypertension and left ventricular outflow tract obstruction were significant factors associated with OSA. The area under the ROC curve (AUC) was 0.78 (95% CI 0.74–0.82; P

Abstract Background The pathophysiology of isolated coronary artery ectasia (CAE) with the coronary slow flow (CSF) phenomenon is still unclear. The purpose of this study was to investigate the risk factors for isolated CAE complicated with CSF. Methods A total of 126 patients with isolated CAE were selected retrospectively. The patients were grouped into the no CSF (NCSF) group (n = 55) and the CSF group (n = 71) according to the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). Data on demographics, laboratory measurements, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), CTFC and diameters of three coronary arteries were collected. Results The proportions of males (84.5% vs. 61.8%, p = 0.004) and patients with a smoking history (63.4% vs. 43.6%, p = 0.021) were higher in the CSF group than in the NCSF group. The neutrophil-to-lymphocyte ratio (NLR) (2.08(1.68–3.21) vs. 1.89 ± 0.58, p = 0.001), mean diameter of coronary arteries (mean D) (5.50 ± 0.85 vs. 5.18 ± 0.91, p

Cuscuta chinensis Lam. (CCL) is a medicinal herb widely used in traditional Chinese medicine for the treatment of ophthalmic diseases, including age-dependent vision-threatening retinal degenerative disorders that involve irreversible loss of the first-order retinal neurons, photoreceptors. However, evidence is lacking if CCL is pharmacologically active at protecting against loss of photoreceptors and photoreceptor degeneration-associated retinal structural and functional impairment. The current study thus evaluates the potential photoreceptor protective effects of CCL to better support its clinical applications in the prevention and treatment of photoreceptor degenerative diseases. Non-invasive full-retinal optical coherence tomography, electroretinography, histological examination, immunohistochemistry and real-time qPCR analysis were performed to assess the retinal protective effects of CCL in light-exposed BALB/c mice characterized by photooxidative stress-mediated photoreceptor loss and associated retinal morphological and functional impairment. The results showed that CCL treatment protected against light-induced degeneration of the photoreceptor structure and deterioration of the retinal function. Furthermore, CCL treatment increased the retinal expression of rhodopsin, S-opsin and M-opsin, supporting the protective effects of CCL in both rod and cone photoreceptors. CCL treatment suppressed photoreceptor cell death in the light-exposed retinas. The morphological integrity of the second-order retinal neurons was also preserved as a result of CCL treatment. In addition, CCL treatment attenuated light-induced reactive müller gliosis, microglial activation and inflammation in the retina. In conclusion, the current work demonstrates for the first time that CCL protects against photooxidative stress-mediated degeneration of photoreceptors and associated disturbance of structural, functional and immune homeostasis of the retina. The findings here thus provide novel experimental evidence supporting the clinical application of CCL in the prevention and treatment photoreceptor degenerative diseases.

Abstract Background To investigate the relationship between fragmented QRS (fQRS) quantified by a new method and myocardial fibrosis (MF) and the diagnostic value of quantitative fQRS (Q-fQRS) to detect MF in hypertrophic obstructive cardiomyopathy (HOCM) patients based on histological validation. Methods We performed a retrospective study that included 69 patients with HOCM who underwent ventricular septal surgery. Nine individuals who died from accidents were studied as a control reference for the histological parameters. Septal myocardium samples were subjected to Masson’s trichrome staining to quantify the collagen volume fraction (CVF). An fQRS pattern was defined as the presence of additional R waves or RSR’, evidenced by notched R or S wave on electrocardiography (ECG). The Q-fQRS was quantified as the total amount of deflections in the QRS complex in all 12 routine ECG leads together. Cardiac magnetic resonance imaging was conducted, and late gadolinium enhancement (LGE) was measured at 2, 4, 6 and 8 standard deviations (SDs). Results Of the 69 patients, fQRS was documented in 38 (55.1%) patients, the mean number of leads with fQRS was 3.7 ± 1.6, and the mean Q-fQRS was 17 ± 7.2. Compared with HOCM patients without fQRS, HOCM patients with fQRS had a higher CVF and more LGE at 6 SD (P

Abstract Background Coronary artery fistula (CAF) is an abnormal connection between a coronary artery and either a cardiac chamber or the great vessels. Although most patients are asymptomatic, potential complications such as heart failure, angina pectoris or acute myocardial infarction can be fatal. Case presentation We present here a 62-year-old man diagnosed with giant coronary artery fistula complicated with gross coronary artery aneurysm and acute myocardial infarction. He underwent intravenous thrombolysis treatment at a local hospital, coronary angiography at a regional hospital and complex surgery at a national centre for cardiovascular disease. The patient had no major adverse cardiac events during the 3-year follow-up. Conclusion Early diagnosis of CAF patients and an appropriate treatment plan are the key factors for avoiding serious complications. Because of the rare incidence of this disease, it is necessary to discover and discuss management strategies, including medical management, percutaneous interventions or surgical treatment, for a successful outcome.

Our previous study has reported that the plasma microRNA-505 (miR-505) is elevated in hypertensive patients. However, the pathophysiological significance of miR-505 in hypertension remains to be elucidated. Hypertension is not only a vascular disorder, but also an inflammatory condition. The current study therefore aims to further investigate the pathophysiological implications of miR-505 in hypertension-associated vascular and inflammatory changes. In vivo experiments reveal that the plasma level of miR-505 is elevated in spontaneously hypertensive rats and angiotensin II-infused mice. In addition, miR-505 agomir treatment results in elevated blood pressure, endothelial dysfunction, increased vascular expression of inflammatory genes and renal inflammatory injuries as well as pre-activation of PBMCs in mice. In vitro experiments further demonstrate that miR-505 agomir increases the expression of IL1B and TNFA, whereas miR-505 antagomir attenuates TNF-α-induced upregulation of IL1B and TNFA in endothelial cells, HUVECs. In addition, miR-505 modulates the levels of endothelial activation markers VCAM1 and E-selectin in HUVECs as well as the adhesion of THP-1 monocytes to HUVECs. Lastly, the plasma level of miR-505 is positively correlated with systolic blood pressure and the level of C-reactive protein in human subjects. Our work links for the first time miR-505 to endothelial dysfunction and inflammation under hypertensive conditions, supporting the translational value of miR-505 in prognosticating hypertension-associated endothelial impairment and inflammatory injuries in target organs such as the vessels and kidneys.

Background: To investigate the risk factors for myocardial infarction, recurrent in-stent restenosis (ISR) and target vessel revascularization (TVR) in patients with coronary ISR within 4 years after revascularization. Methods: A total of 1884 patients who were hospitalized at Fuwai Hospital for ISR and successfully treated with coronary intervention between January 2017 and December 2018 were included to determine whether there were myocardial infarction, recurrent ISR, TVR and other major adverse cardiovascular events (MACEs) within 4 years after intervention. The patients were divided into the MACE group (215 patients) and the non-MACE group (1669 patients). The clinical data of patients in the two groups were compared, and the risk factors for postoperative MACEs in the ISR patients were obtained by multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to determine the optimal prediction threshold for postoperative MACEs in ISR patients. The difference in survival curves between the two groups was compared using Kaplan‒Meier survival analysis. Results: The albumin (43.42 ± 4.77 vs. 44.17 ± 4.46, p = 0.021), direct bilirubin (2.5 (2, 3.5) vs. 2.8 (2.07, 3.73), p = 0.036) and free triiodothyronine (FT3) (2.85 ± 0.43 vs. 2.92 ± 0.42, p = 0.019) levels in the MACE group were significantly lower than those in the non-MACE group, and there was a significant negative correlation between albumin and FT3 and MACEs. The results of univariate and multivariate logistic regression analyses revealed that FT3 was an independent predictor of postoperative MACEs in ISR patients (Odds Ratio (OR) = 0.626, 95% CI: 0.429–0.913, p = 0.015). The ROC curve analysis determined that an FT3 value of 2.785 pmol/L was the optimal prediction threshold. According to the threshold, ISR patients were divided into the FT3

Nonalcoholic steatohepatitis (NASH) is a highly prevalent metabolic disorder. Currently, there are no effective pharmacotherapeutic options for preventing and treating NASH. Portulaca oleracea L. (POL) is an edible herb that has been used for preventing and treating some metabolic disorders in China, but the bioactive constituents in POL and the related mechanisms for treating NASH are still unclear. Here, a comprehensive research strategy was used to identify the core genes and the key constituents in POL for treating NASH, via integrating bioinformatics analysis and experimental pharmacology both in vitro and in vivo. The phenotypes and mechanisms of POL were carefully investigated by performing a set of in vivo and in vitro experiments. Bioinformatics analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target and myricetin (Myr) was the key constituent in POL for treating NASH. In NASH mice model induced by methionine choline deficiency diet, POL significantly alleviated hepatic steatosis and liver injury. In free fatty acids-induced hepatocytes, POL and Myr significantly down-regulated the expression of PTGS2, decreased the number of lipid droplets, and regulated the mRNA expression of lipid synthesis and homeostasis genes, including FASN, CPT1a, SERBP1c, ACC1, and SCD1. In lipopolysaccharide-induced macrophages, POL and Myr significantly reduced the expression of PTGS2 and blocked the secretion of inflammatory mediators TNF-α, IL-6, and IL-1β. Further investigations demonstrate that Myr acts as both suppressor and inhibitor of PTGS2. Collectively, POL and its major component Myr can ameliorate NASH via down-regulating and inhibiting PTGS2, suggesting that POL and Myr can be developed as novel medicines for treating NASH.

Tripartite motif‐containing 14 (TRIM14) is a mitochondrial adaptor that promotes innate immune signaling and plays important roles in antiviral defense. Expression of TRIM14 is induced by interferon (IFN)‐I. However, the mechanism by which IFN‐I induces TRIM14 production is not yet determined. In this study, we have examined the function of TRIM14 promoter and found that a GC box and an IFN‐stimulated response element (ISRE) are necessary for the basal level transcription of TRIM14. We further observed that IFN‐I activates the TRIM14 promoter through the ISRE. In particular, interferon regulatory factor (IRF)‐1 and IRF‐2 bind to the TRIM14 promoter and activate transcription of TRIM14. Moreover, knockdown of IRF‐1 reduces the stimulation of TRIM14 transcription by IFN‐α, suggesting that IRF‐1 is involved in the activation of TRIM14 by IFN‐I. IRF‐2 has little effect on IFN‐α‐induced TRIM14 transcription but is essential for the basal transcription of TRIM14.

Background Collagen cross‐linking is covalent bonds among collagen fibers from catalysis of lysyl oxidase (LOX) and advanced glycation end products (AGEs). We aimed to evaluate the formation of enzymatic and nonenzymatic collagen cross‐linking and its clinical significance in patients with hypertrophic obstructive cardiomyopathy. Methods and Results Forty‐four patients with hypertrophic obstructive cardiomyopathy who underwent surgical myectomy were consecutively enrolled. Cardiovascular magnetic resonance parameters of left atrial/left ventricular function were measured, including peak filling rate (PFR) and early peak emptying rate (PER‐E). Total collagen was the sum of soluble and insoluble collagen, which were assessed by collagen assay. The myocardial LOX and AGEs expression were measured by molecular and biochemical methods. Compared with patients without atrial fibrillation, insoluble collagen (P=0.018), insoluble collagen fraction (P=0.017), and AGEs (P=0.039) were higher in patients with atrial fibrillation, whereas LOX expression was similar (P=0.494). The insoluble collagen fraction was correlated with PFR index (PFR normalized by left ventricular filling volume) (r=−0.44, P=0.005), left atrial diameters (r=0.36, P=0.021) and PER‐E index (PER‐E normalized by left ventricular filling volume) (r=−0.49, P=0.001).Myocardial LOX was positively correlated with total collagen (r=0.37, P=0.025) and insoluble collagen fraction (r=0.53, P

Objectives This study sought to investigate the relationship between occlusion length and long-term outcomes of patients with recanalised chronic total occlusion (CTO) lesion.Design A retrospective cohort study.Setting Fuwai Hospital, National Center for Cardiovascular Disease, Beijing, ChinaParticipants Consecutive patients with successfully recanalised CTO were included from January 2010 to December 2013.Primary and secondary outcome measures The primary endpoint of the present study was a composite event of all-cause death and myocardial infarction (MI). The secondary endpoints included target lesion revascularisation (TLR) and target vessel revascularisation (TVR).Results A total of 1987 patients were included and 1801 (90.6%) subjects completed 5-year follow-up in this study. Based on occlusion length, the patients were divided equally into two groups: short (length

Background Obstructive sleep apnea (OSA) is common and independently associated with atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). This study aimed to investigate the relationship between apnea‐hypopnea index (AHI), a measure of OSA severity, and prevalence of AF in a large series of patients with HCM. Methods and Results A total of 555 patients with HCM who underwent sleep evaluations were retrospectively included. Data from polysomnography studies, echocardiography, and baseline clinical characteristics were collected. OSA was present in 327 patients (58.9%). Patients with OSA or higher AHI quartiles were older, more often male, had a higher body mass index, and more clinical comorbidities. The prevalence of AF increased in patients with OSA (23.9% versus 13.6%, P=0.003) or across AHI quartiles (9.4%, 17.3%, 26.6%, and 25.2%, respectively; P for trend

Abstract Background Atrial fibrillation (AF) is the most common complication in hypertrophic cardiomyopathy (HCM). The mechanisms of AF is associated with left atrial (LA) structural remodeling in HCM patients. However, the impact of left ventricular (LV) remodeling on the presence of AF in HCM patients has not been evaluated yet. We sought to investigate effect of LV remodeling on the presence of AF assessed by cardiovascular magnetic resonance (CMR) in HCM patients. Methods A total of 394 HCM patients were enrolled into this study, including HOCM patients (n = 293) and NOHCM patients (n = 101). Patients were divided into HCM with AF (50) and HCM without AF (n = 344). Data were collected from hospital records. Results LA diameter and LV remodeling index (LVRI) were significantly higher in HCM patients with AF than that of HCM patients without AF (46.6 ± 7.4 mm versus 39.9 ± 8.0 mm, p

Abstract Photoreceptor degeneration is a central pathology of various retinal degenerative diseases which currently lack effective therapies. Antioxidant and anti-inflammatory activities are noted for Panax notoginsenoside saponins (PNS) and related saponin compound(s). However, the photoreceptor protective potentials of PNS or related saponin compound(s) remain unknown. The current study revealed that PNS protected against photoreceptor loss in bright light-exposed BALB/c mice. Combination of ginsenoside Rb1 and Rd, two major saponin compounds of PNS, recapitulated the retinal protection of PNS and attenuated retinal oxidative stress and inflammatory changes. Rb1 or Rd partially alleviated all-trans-Retinal-induced oxidative stress in ARPE19 cells. Rb1 or Rd suppressed lipopolysaccharides (LPS)-induced proinflammatory gene expression in ARPE19 and RAW264.7 cells. Rb1 or Rd also modulated the expression of proinflammatory microRNA, miR-155 and its direct target, anti-inflammatory SHIP1, in LPS-stimulated RAW264.7 cells. The retinal expression of miR-155 and SHIP1 was altered preceding extensive retinal damage, which was maintained at normal level by Rb1 and Rd combination. This work shows for the first time that altered expression of miR-155 and SHIP1 are involved in photoreceptor degeneration. Most importantly, novel retinal protective activities of combination of Rb1 and Rd justify further evaluation for the treatment of related retinal degenerative disorders.

Objectives. We aim to present a new way to introduce reverse wire in crusade microcatheter-facilitated reverse wire technique to solve markedly angulated bifurcated lesions. Background. Markedly angulated coronary bifurcation lesions are still one of the considerable challenges of treatment with percutaneous coronary intervention especially with severe proximal stenosis. Microcatheter-facilitated reverse wire technique improved the efficacy of crossing a guide wire to such an extremely angulated complex targeted vessel. However, there has been a debate regarding what kind of curve was the best to introduce reverse guide wire in this technique. Methods. We analyzed 7 patients who were admitted to Fuwai Hospital and underwent antegrade wiring which failed. Crusade microcatheter-facilitated reverse wire technique with simple short tip one round curve was used successfully to solve in all 7 bifurcation lesions. We investigated the bifurcation lesion’s characteristics and details of the reverse wire technique procedures. Results. All 7 bifurcations exhibit both a smaller take-off angle and a larger carina angle and severe proximal significant stenosis. After having suitable size of balloon predilation, reverse wire with simple short distal one curve was delivered to distal segment of targeted vessel successfully. We performed all PCI procedures without any complications and no major adverse cardiac event was observed during hospitalization. Conclusions. In solving markedly angulated bifurcated lesions, especially with severe proximal stenosis, crusade microcatheter-facilitated reverse wire technique with simple short tip one curve is an effective and safe way of wiring.

This study aimed to investigate the link between the inhibitory effect of ginsenoside Rg3 on the ectopic endometrium growth and the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway, a mechanism known to inhibit angiogenesis and induce ectopic endometrial cell apoptosis.A model of endometriosis was established by allotransplantation in rats. The rats were randomly divided into 5 groups: the ginsenoside Rg3 low-dose group (group A,5mg/kgBW/d of ginsenoside Rg3), the ginsenoside Rg3 high-dose group (group B, 10mg/kgBW/d of ginsenoside Rg3), the gestrinone group (group C, 0.5mg/kgBW/d of gestrinone), the control group (groupD, 10ml/kg BW/d of 0.5%CMC-Na) and the ovariectomized group (group E, 10ml/kgBW/d of 0.5%CMC-Na). Rats were executed after 21 days of continuous administration. The ectopic endometrium volume was measured and the inhibitory rate was calculated. The levels of serum estradiol (E2) and progesterone (P) were detected by Electro-Chemiluminescence Immunoassay (ECLI). The protein expressionof VEGF, VEGFR-2, p-Akt, and p-mTOR inthe ectopic endometrium wastested by immunohistochemistry(IHC) and Western Blotting. The mRNA expression levels of VEGF, VEGFR-2, Akt, and mTOR were tested by Real-Time Polymerase Chain Reaction (PCR). The apoptosis rate of the ectopic endometrial cells was detected by Terminal Deoxynucleotidyl Transferase-mediated Digoxigenin-dUTP Nick-End Labeling Assay(TUNEL).Tissue measurements revealed a dose-dependent inhibition effect of ginsenoside Rg3 on the growth of the ectopic endometrium in treated rats compared to controls. Immunohistochemical and Western Blotting assays confirmed that the expression of VEGF, p-Akt, and p-mTOR was down-regulated in ginsenoside Rg3 -treated lesions. Real-time PCR results also showed that the mRNA expression levels of VEGF, Akt, and mTOR in the ectopic endometrium were reduced.The present study demonstrates, for the first time, that ginsenoside Rg3 suppresses angiogenesis in developing endometrial lesions. The ginsenoside Rg3 inhibitory effect on the growth of the ectopic endometrium in EMs rats might occur through the blocking of the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway, thus halting angiogenesis and promoting the apoptosis of ectopic endometrial cells.

BACKGROUND:Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM. METHODS:Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis. RESULTS:LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6-2340.8] vs. 866.6 [707.2-1875.2] pmol/L, P = 0.003; 0.024 [0.010-0.049] vs. 0.010 [0.005-0.021] ng/ml, P

AIMS: Atherosclerosis is the primary cause of cardiovascular diseases and stroke. The current study evaluated the interventional effects of a naturally occurring compound Notoginsenoside R1 (NR1) on atherosclerosis in ApoE-/- mice. METHODS AND RESULTS: The atherosclerotic lesion was significantly alleviated by NR1 treatment and this attenuation was marked by reduction in lipid deposition, fibrosis and oxidative stress. Increased serum levels of GSH and SOD and decreased level of MDH were observed in NR1-treated ApoE-/- mice. NR1 treatment also significantly decreased the levels of CHO, TG, ox-LDL and increased the level of HDL. Additionally, the levels of inflammatory cytokines including IL-2, IL-6, TNF-α and γ-IFN were markedly reduced in NR1-treated ApoE-/- mice. Furthermore, significantly increased aortic expression of miR-26a, miR-21, miR-126a, miR-132, miR-146 and miR-155 and decreased expression of miR-20a and miR-92a were observed in the vehicle-treated ApoE-/- mice. While NR1 treatment led to a significant reduction in the expression of miR-21, miR-26a, miR-126 and increased expression of miR-20a. CONCLUSION: Collectively, our results demonstrated for the first time the anti-atherosclerotic effects of NR1, which could be in part mediated through its multiple targeting effects on inflammation, oxidative stress, lipid metabolism and microRNA expression. These results therefore justify further evaluation of NR1 as a therapeutic agent treating atherosclerosis.

Stimulated by a recent experimental report, charge transfer and photophysical properties of donor-acceptor ambipolar polymer were studied with the quantum chemistry calculation and the developed 3D charge difference density method. The effects of electronic acceptor strength on the structure, energy levels, electron density distribution, ionization potentials, and electron affinities were also obtained to estimate the transporting ability of hole and electron. With the developed 3D charge difference density, one visualizes the charge transfer process, distinguishes the role of molecular units, and finds the relationship between the role of DPP and excitation energy for the three polymers during photo-excitation.