A new protective gel to facilitate ulcer healing in artificial ulcers following oesophageal endoscopic submucosal dissection: a multicentre, randomized trial.

There are significant risks of adverse events following oesophageal endoscopic submucosal dissection (ESD), such as stricture, delayed bleeding and perforation. Therefore, it is necessary to protect artificial ulcers and promote the healing process. The current study was performed to investigate the protective role of a novel gel against oesophageal ESD-associated wounds. This was a multicentre, randomized, single-blind, controlled trial that recruited participants who underwent oesophageal ESD in four hospitals in China. Participants were randomly assigned to the control or experimental group in a 1:1 ratio and the gel was used after ESD in the latter. Masking of the study group allocations was only attempted for participants. The participants were instructed to report any adverse events on post-ESD days 1, 14, and 30. Moreover, repeat endoscopy was performed at the 2-week follow-up to confirm wound healing. Among the 92 recruited patients, 81 completed the study. In the experimental group, the healing rates were significantly higher than those in the control group (83.89 ± 9.51% vs. 73.28 ± 17.81%, P = 0.0013). Participants reported no severe adverse events during the follow-up period. In conclusion, this novel gel could safely, effectively, and conveniently accelerate wound healing following oesophageal ESD. Therefore, we recommend applying this gel in daily clinical practice.

COVID-19 instigates adipose browning and atrophy through VEGF in small mammals.

Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3-7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature-adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.

Pharmacological OGG1 inhibition decreases murine allergic airway inflammation.

Background and aim: Allergic asthma is a complex inflammatory disease involving type 2 innate lymphoid cells, type 2 T helper cells, macrophages, and eosinophils. The disease is characterized by wheezing, dyspnea, coughing, chest tightness and variable airflow limitation for which there is no cure and is symptomatically treated with inhaled corticosteroids and ß2-agonists. Molecular mechanisms underlying its complex pathogenesis are not fully understood. However, 8-oxoguanine DNA glycosylase-1 (OGG1), a DNA repair protein may play a central role, as OGG1 deficiency decreases both innate and allergic inflammation. Methods: Using a murine ovalbumin (OVA) model of allergic airway inflammation we assessed the utility of an inhibitor of OGG1 (TH5487) in this disease context. Cytokines and chemokines, promoting immune cell recruitment were measured using a 23-multiplex assay and Western blotting. Additionally, immune cell recruitment to bronchi was measured using flow cytometry. Histological analyses and immunofluorescent staining were used to confirm immune cell influx and goblet cell hyperplasia of the airways. A PCR array was used to assess asthma-related genes in murine lung tissue following TH5487 treatment. Finally, airway hyperresponsiveness was determined using in vivo lung function measurement. Results: In this study, administration of TH5487 to mice with OVA-induced allergic airway inflammation significantly decreased goblet cell hyperplasia and mucus production. TH5487 treatment also decreased levels of activated NF-κB and expression of proinflammatory cytokines and chemokines resulting in significantly lower recruitment of eosinophils and other immune cells to the lungs. Gene expression profiling of asthma and allergy-related proteins after TH5487 treatment revealed differences in several important regulators, including down regulation of Tnfrsf4, Arg1, Ccl12 and Ccl11, and upregulation of the negative regulator of type 2 inflammation, Bcl6. Furthermore, the gene Clca1 was upregulated following TH5487 treatment, which should be explored further due to its ambiguous role in allergic asthma. In addition, the OVA-induced airway hyperresponsiveness was significantly reduced by TH5487 treatment. Conclusion: Taken together, the data presented in this study suggest OGG1 as a clinically relevant pharmacological target for the treatment of allergic inflammation.

Monensin inhibits mast cell mediated airway contractions in human and guinea pig asthma models.

Asthma is a common respiratory disease associated with airway hyperresponsiveness (AHR), airway inflammation and mast cell (MC) accumulation in the lung. Monensin, an ionophoric antibiotic, has been shown to induce apoptosis of human MCs. The aim of this study was to define the effect of monensin on MC responses, e.g., antigen induced bronchoconstriction, and on asthmatic features in models of allergic asthma. Tracheal segments from house dust mite (HDM) extract sensitized guinea pigs were isolated and exposed to monensin, followed by histological staining to quantify MCs. Both guinea pig tracheal and human bronchi were used for pharmacological studies in tissue bath systems to investigate the monensin effect on tissue viability and antigen induced bronchoconstriction. Further, an HDM-induced guinea pig asthma model was utilized to investigate the effect of monensin on AHR and airway inflammation. Monensin decreased MC number, caused MC death, and blocked the HDM or anti-IgE induced bronchoconstriction in guinea pig and human airways. In the guinea pig asthma model, HDM-induced AHR, airway inflammation and MC hyperplasia could be inhibited by repeated administration of monensin. This study indicates that monensin is an effective tool to reduce MC number and MCs are crucial for the development of asthma-like features.

Prophylactic Clipping to Prevent Delayed Bleeding and Perforation After Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: To help prevent delayed adverse events after endoscopic surgery, endoscopists often place clips at the site. This meta-analysis aimed to assess the efficacy and safety of prophylactic clipping in the prevention of delayed bleeding and perforation after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). METHODS: Multiple databases were searched from the inception dates to April 2021. And we included all relevant studies. Pooled odds ratio comparing the prophylactic clipped group versus nonprophylactic clipped group were calculated using the random effects model. RESULTS: Twenty-seven articles fulfilled the inclusion criteria, with a total size of 8693 participants. There was statistically significant difference in prophylactic clipping versus no prophylactic clipping for delayed bleeding and perforation found in all studies (odds ratio: 0.35, 95% confidence interval: 0.25-0.49, P <0.01; odds ratio: 0.42, 95% confidence interval: 0.21-0.83, P <0.05; respectively). Besides, statistically significant difference was also found in subgroup analyses based on patients with lesions larger than 20 mm. Prophylactic clipping was more protective for duodenal delayed adverse events than colorectum. The use of clip closure was more protective to ESD-related delayed adverse events than EMR. CONCLUSIONS: Prophylactic clipping after ESD and EMR was beneficial in preventing delayed bleeding and perforation.

The safety and efficacy of peroral endoscopic cardial constriction in gastroesophageal reflux disease.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is one of the most common digestive disorders, which seriously affects the quality of life and brings a heavy burden to the medical care. Peroral endoscopic cardial constriction (PECC) can narrow the cardia through mucosal ligation to alleviate acid reflux symptoms. This study aims to assess the clinical efficacy of PECC. METHODS: This was a retrospective case series including patients diagnosed with GERD and undergoing PECC from September 2019 to July 2021. GERD-Q questionnaire and GERD-QOL questionnaire were applied to evaluate the symptom severity and the impact of life because of GERD. RESULTS: A total of 16 patients were included in our study. The mean GERD-Q score was 10.94 ± 2.11 before PECC, while 5.38 ± 3.90 after PECC. The mean GERD-QOL score was 43.60 ± 16.94 before PECC, while 73.65 ± 22.08 after PECC. 62.5% of patients were satisfied with the symptom control and no serious complications were reported in our study. CONCLUSIONS: PECC is an efficient and safe minimally invasive endoscopic intervention for GERD. It can significantly improve GERD-related symptoms and quality of life.

The LDL/HDL ratio predicts long-term risk of coronary revascularization in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: a cohort study.

Clinical indicators do not adequately predict the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio is expected to be a reliable predictor of the long-term prognosis of these patients. This study aimed to explore the correlation between the LDL/HDL ratio and long-term prognosis in STEMI patients undergoing PCI. Patients with confirmed STEMI who underwent PCI in 7 hospitals in China from January 2009 to December 2011 were enrolled. Information about clinical endpoints, including all-cause death and major adverse cardiovascular events, was collected. Overall, 915 patients were included for analysis, the average follow-up time was 112.2 months. According to the LDL/HDL ratio, the patients were divided into 3 groups using the three-quantile method: low (LDL/HDL≤1.963), medium (1.963

Cardiovascular disease burden attributable to dietary risk factors from 1990 to 2019: A systematic analysis of the Global Burden of Disease study.

BACKGROUND AND AIMS: Dietary risks have always been a major risk factor for cardiovascular diseases (CVDs), especially in young people. This article aimed to provide an updated and comprehensive view of the spatial, temporal and sexual heterogeneity in diet-attributable CVD burdens from 1990 to 2019. METHODS AND RESULTS: Data on diet-attributable CVD burdens were extracted from the Global Burden of Disease (GBD) Study 2019. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs) and corresponding estimated annual percentage change (EAPC) were determined. Globally, the number of diet-attributable CVD deaths and DALYs in 2019 were 6.9 million and 153.2 million, marking 43.8% and 34.3% increases since 1990, respectively. However, ASRs of death and DALYs have declined over time. The regions with the highest ASRs of diet-related CVD deaths and DALYs were in Central Asia, whereas the lowest ASRs of CVD deaths and DALYs were observed in the high-income Asia Pacific region. Globally, men suffered higher death and DALY burdens than women. Ischemic heart disease and stroke were the leading causes of CVD deaths and DALYs, globally. Regarding the specific diet group, diets low in whole grains, high in sodium, low in fruits, low in nuts and seeds, low in vegetables and low in seafood omega-3 fatty acids contributed to CVD deaths and DALYs the most. Dietary risks accounted for a higher proportion in people aged less than 65 years old. CONCLUSIONS: Diet-attributable CVDs threaten public health, particularly in low SDI countries and younger generations. As diet-related CVDs are nation-specific, the prioritization of public health interventions should be evidence-based.

The LDL/HDL ratio predicts long-term risk of coronary revascularization in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: a cohort study

Clinical indicators do not adequately predict the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio is expected to be a reliable predictor of the long-term prognosis of these patients. This study aimed to explore the correlation between the LDL/HDL ratio and long-term prognosis in STEMI patients undergoing PCI. Patients with confirmed STEMI who underwent PCI in 7 hospitals in China from January 2009 to December 2011 were enrolled. Information about clinical endpoints, including all-cause death and major adverse cardiovascular events, was collected. Overall, 915 patients were included for analysis, the average follow-up time was 112.2 months. According to the LDL/HDL ratio, the patients were divided into 3 groups using the three-quantile method: low (LDL/HDL≤1.963), medium (1.963<LDL/HDL<2.595), and high (LDL/HDL≥2.595) LDL/HDL groups. The rate of coronary revascularization was higher in the high LDL/HDL group (28.52%) than in the low (17.38%, P=0.001) and medium (19.34%, P=0.010) LDL/HDL groups. The hazard ratio of coronary revascularization was significantly higher in the high LDL/HDL group than in the low (P=0.007) and medium (P=0.004) LDL/HDL groups. Increased LDL/HDL ratio was an independent risk factor for long-term coronary revascularization in STEMI patients undergoing PCI (HR=1.231, 95%CI: 1.023-1.482, P=0.028). These findings suggest that an increased LDL/HDL ratio was an independent risk factor for long-term coronary revascularization in STEMI patients undergoing PCI. The risk of coronary revascularization was significantly increased in patients with LDL/HDL≥2.595.

Animal models used in the research of nanoparticles for cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Tremendous progress has been made in the prevention and treatment of CVD; however, there are still lots of limitations and new technology is needed. Nanoparticles have been studied recently for CVD due to their nanoscale size and unique properties, and hold a potential to be a novel therapy for the treatment. To test the safety and effectiveness of drug-loaded nanoparticles for CVD prior to human studies, animal disease models are unavoidably needed. This review summarized the animal models used in the research of nanoparticles for CVD and provided a generic picture of current use of CVD animal models according to the different types of diseases which should be prioritized when considering the application of nanoparticles in treating CVD. This review would be useful resources not only for life science researchers and clinicians but also for those from chemistry and materials sciences background who may not have a systematic knowledge about CVD animal models.

Global burden of cardiovascular diseases attributable to hypertension in young adults from 1990 to 2019.

BACKGROUND: Hypertension grows into a serious public health problem among young adults, linking to a set of life-threatening cardiovascular diseases (CVDs). Young adults are not well represented in current knowledge about the CVDs burden attributable to hypertension. METHODS: In this analysis of data from the GBD (Global Burden of Disease) study 2019, we focus on young adults and provide the first comprehensive and comparative assessment of the hypertension attributable CVDs burden, in terms of its mortality and years of living with disability (YLD) from 1990 to 2019, stratified by location, sex, and development status. RESULTS: Globally in 2019, the death and YLD numbers caused by hypertension-related CVDs were 640 239 and 2 717 474 in young adults, marking a 43.0 and 86.6% increase from 1990, respectively. The corresponding mortality rate dropped by 10.5%, whereas the YLD rate increased by 16.8% during the same period. V-shaped association between CVDs burden and social development status was observed. The largest burden and the most pronounced increase were borne by middle-income countries, while high-income countries had the lowest death/YLD rate with a quicker annual decline. Men largely outpaced women in hypertension attributable CVDs mortality. Ischemic heart disease and stroke were the leading cause for death and YLD burden, correspondingly. CONCLUSIONS: Hypertension attributable CVDs burden in young adults has greatly increased from 1990 to 2019, with considerably spatiotemporal and sexual heterogeneity. The largest burden was borne by middle-income countries, especially by men. Establishment of geographically and sexually tailored strategies were needed to prevent hypertension-related CVDs in young adults.

U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study.

BACKGROUND: The endogenous lipid molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. The purpose of our study was to identify the distribution characteristics of S1P in systolic heart failure patients and the prognostic value of S1P for long-term prognosis. METHODS: We recruited 210 chronic systolic heart failure patients from June 2014 to December 2015. Meanwhile 54 healthy people in the same area were selected as controls. Plasma S1P was measured by liquid chromatography-tandem mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described the association between S1P and all-cause death. Cox proportional hazard analysis was used to determine the relationship between category of S1P and all-cause death. RESULTS: Compared with the control group, the plasma S1P in chronic heart failure patients demonstrated a higher mean level (1.269 µmol/L vs 1.122 µmol/L, P = 0.006) and a larger standard deviation (0.441 vs 0.316, P = 0.022). Based on multivariable Cox regression with restricted cubic spline analysis, a non-linear and U-shaped association between S1P levels and the risk of all-cause death was observed. After a follow-up period of 31.7 ± 10.3 months, the second quartile (0.967-1.192 µml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (adjusted HR = 2.368, 95%CI 1.006-5.572, P = 0.048) or a decrease (adjusted HR = 0.041, 95%CI 0.002-0.808, P = 0.036) predicted a worse prognosis. The survival curves showed that patients in the lowest quartile and highest quartile were at a higher risk of death. CONCLUSIONS: Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation. TRIAL REGISTRATION: CHiCTR, ChiCTR-ONC-14004463. Registered 20 March 2014.

Life Cycle of the Cardiac Voltage-Gated Sodium Channel NaV1.5.

Cardiac voltage-gated sodium channel NaV1.5, encoded by SCN5A, is crucial for the upstroke of action potential and excitation of cardiomyocytes. NaV1.5 undergoes complex processes before it reaches the target membrane microdomains and performs normal functions. A variety of protein partners are needed to achieve the balance between SCN5A transcription and mRNA decay, endoplasmic reticulum retention and export, Golgi apparatus retention and export, selective anchoring and degradation, activation, and inactivation of sodium currents. Subtle alterations can impair NaV1.5 in terms of expression or function, eventually leading to NaV1.5-associated diseases such as lethal arrhythmias and cardiomyopathy.

Nanoparticles for postinfarct ventricular remodeling.

In recent years, tremendous progress has been made in the treatment of acute myocardial infarction, but pathological ventricular remodeling often causes survivors to suffer from fatal heart failure. Currently, there is no effective therapy to attenuate ventricular remodeling. Recently, nanoparticle-based drug delivery systems are widely applied in biomedicine especially in cancer and liver fibrosis, owing to its excellent physical, chemical and biological properties. Therefore, the use of nanoparticles as delivery vehicles of small molecules, polypeptides, etc. to improve postinfarct ventricular remodeling is expected. In this review, we summarize the updated researches in this fast-growing area and suggest further works needed.