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Aims To provide the first systematic analysis of the burden and underlying causes of heart failure (HF) in 195 countries and territories from 1990 to 2017. Methods and results We collected detailed information on prevalence, years lived with disability (YLDs), and underlying causes of HF from the Global Burden of Disease study 2017. Numbers and age-standardized rates of HF prevalence and YLDs were compared by age, sex, socio-demographic index (SDI), and location. The proportions of HF age-standardized prevalence rates due to 23 underlying causes were also presented. Globally, the age-standardized prevalence and YLD rates of HF in 2017 were 831.0 and 128.2 per 100 000 people, a decrease of −7.2% and −0.9% from 1990, respectively. Nevertheless, the absolute numbers of HF prevalent cases and YLDs have increased by 91.9% and 106.0% from 1990, respectively. There is significant geographic and socio-demographic variation in the levels and trends of HF burden from 1990 to 2017. Among all causes of HF, ischaemic heart disease accounted for the highest proportion (26.5%) of age-standardized prevalence rate of HF in 2017, followed by hypertensive heart disease (26.2%), chronic obstructive pulmonary disease (23.4%). Conclusion HF remains a serious public health problem worldwide, with increasing age-standardized prevalence and YLD rates in countries with relatively low SDI. More geo-specific strategies aimed at preventing underlying causes and improving medical care for HF are warranted to reduce the future burden of this condition.

Aims The aim of this study was to estimate the burden and risk factors for ischaemic heart disease (IHD) in 195 countries and territories from 1990 to 2017. Methods and results Data from the Global Burden of Disease Study 2017 were used. Prevalence, incidence, deaths, years lived with disability (YLDs), and years of life lost (YLLs) were metrics used to measure IHD burden. Population attributable fraction was used to estimate the proportion of IHD deaths attributable to potentially modifiable risk factors. Globally, in 2017, 126.5 million [95% uncertainty interval (UI) 118.6 to 134.7] people lived with IHD and 10.6 million (95% UI 9.6 to 11.8) new IHD cases occurred, resulting in 8.9 million (95% UI 8.8 to 9.1) deaths, 5.3 million (95% UI 3.7 to 7.2) YLDs, and 165.0 million (95% UI 162.2 to 168.6) YLLs. Between 1990 and 2017, despite the decrease in age-standardized rates, the global numbers of these burden metrics of IHD have significantly increased. The burden of IHD in 2017 and its temporal trends from 1990 to 2017 varied widely by geographic location. Among all potentially modifiable risk factors, age-standardized IHD deaths worldwide were primarily attributable to dietary risks, high systolic blood pressure, high LDL cholesterol, high fasting plasma glucose, tobacco use, and high body mass index in 2017. Conclusion Our results suggested that IHD remains a major public health challenge worldwide. More effective and targeted strategies aimed at implementing cost-effective interventions and addressing modifiable risk factors are urgently needed, particularly in geographies with high or increasing burden.

BackgroundEffective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19.MethodIn this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events.ResultsA total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians −6.0 days; 95% CI −6.0 to −4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose.ConclusionsAlthough randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating 102 the COVID-19 pandemic.

Background: Tenofovir (TDF) has a detrimental effect on bone mineral density (BMD), while nonalcoholic fatty liver disease (NAFLD) is associated with a lower BMD. Objective: To help understand the mutual effects of NAFLD and TDF on BMD, this study was designed to explore the potential association between NAFLD and BMD in HIV-infected patients receiving long-term TDF-based antiretroviral therapy (ART). Methods: A total of 89 HIV-infected patients who received TDF-based ART for more than three years were enrolled in this cross-sectional study. We measured BMD using an ultrasonic bone density apparatus, and liver ultrasonography was performed to determine the severity of the fatty liver. The association of NAFLD with BMD was examined using multiple logistic regression analyses. Results: Patients with NAFLD showed a worse BMD status than those without NAFLD. The incidence rates of osteopenia (42.86% versus 25.93%) and osteoporosis (17.14% versus 3.70%) were significantly higher in HIV-infected patients with NAFLD than in those without NAFLD. After multivariate adjustment, the odds ratio (OR) for patients with NAFLD exhibiting a worse BMD status compared with those without NAFLD was 4.49 (95% confidence interval [CI] 1.42, 14.15). Conclusion: Based on our results, NAFLD was significantly associated with a worse BMD status, including osteopenia and osteoporosis, in HIV patients after receiving long-term TDF-based ART. Furthermore, we may want to avoid using TDF for ART in HIV-infected patients with NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent liver pathology marked by hepatic steatosis and commonly accompanied by systematic inflammation and metabolic disorder. Despite an accumulating number of studies, no pharmacological strategy is available to treat this condition in the clinic. The current work applied extensive gain- and loss-of-function approaches to identify the key immune factor leukocyte immunoglobulin-like receptor B4 (LILRB4) as a negative regulator of NAFLD. The hepatocyte-specific knockout of LILRB4 (LILRB4-HKO) significantly exacerbated high-fat diet (HFD)-induced insulin resistance, glucose metabolic imbalance, hepatic lipid accumulation, and systematic inflammation in mice, whereas LILRB4 overexpression in hepatocytes showed a completely opposite phenotype relative to that of LILRB4-HKO mice when compared to their corresponding controls. Further investigations on molecular mechanism demonstrated that LILRB4 recruit SHP1 for inhibiting TRAF6 ubiquitination and subsequently inactivating NF-κB and MAPK cascades. From a therapeutic perspective, the overexpression of LILRB4 in a genetic model of NAFLD, ob/ob mice, largely reversed the inherent hepatic steatosis, inflammation, and metabolic disorder. Conclusions: Targeting hepatic LILRB4 to improve its expression or activation might represent a promising strategy for the treatment of NAFLD as well as related liver and metabolic diseases. This article is protected by copyright. All rights reserved.

Background Regulator of G protein signaling 6 ( RGS 6) is an important member of the RGS family and produces pleiotropic regulatory effects on cardiac pathophysiology. However, the role of RGS 6 protein in cardiomyocytes during angiotensin II – and pressure overload–induced cardiac hypertrophy remain unknown. Methods and Results Here, we used a genetic approach to study the regulatory role of RGS 6 in cardiomyocytes during pathological cardiac hypertrophy. RGS 6 expression was significantly increased in failing human hearts and in hypertrophic murine hearts. The extent of aortic banding–induced cardiac hypertrophy, dysfunction, and fibrosis in cardiac‐specific RGS 6 knockout mice was alleviated, whereas the hearts of transgenic mice with cardiac‐specific RGS 6 overexpression exhibited exacerbated responses to pressure overload. Consistent with these findings, RGS 6 also facilitated an angiotensin II –induced hypertrophic response in isolated cardiomyocytes. According to the mechanistic studies, RGS 6 mediated cardiac hypertrophy by directly interacting with apoptosis signal–regulating kinase 1, which further activates the P38‐c‐ JUN N‐terminal kinase 1/2 signaling pathway. Conclusions Based on our findings, RGS 6 aggravates cardiac hypertrophy, and the RGS 6‐apoptosis signal–regulating kinase 1 pathway represents a potential therapeutic target to attenuate pressure overload–driven cardiac remodeling.

Purpose To explore the readability and content integrity of informed consent forms (ICFs) used in China and to compare the quality of Chinese local ICFs with that of international ICFs. Methods The length, readability and content of 155 consent documents from phase II-IV drug clinical trials from the Third Xiangya Hospital Ethics Committee from November 2009 to January 2015 were evaluated. Reading difficulty was tested using a readability formula adapted for the Chinese language. An ICF checklist containing 27 required elements was successfully constructed to evaluate content integrity. The description of alternatives to participation was assessed. The quality of ICFs from different sponsorships were also compared. Results Among the 155 evaluable trials, the ICFs had a median length of 5286 words, corresponding to 7 pages. The median readability score was 4.31 (4.02–4.41), with 63.9% at the 2nd level and 36.1% at the 3rd level. Five of the 27 elements were frequently neglected. The average score for the description of alternatives to participation was 1.06, and 27.7% of the ICFs did not mention any alternatives. Compared with Chinese local ICFs, international ICFs were longer, more readable and contained more of the required elements (P < 0.05). Conclusion The ICFs used in China were difficult to read for most participants. These forms had poor description of alternatives to participation, and failed to provide a high degree of information disclosure, including an explanation of informed consent, follow-up processing of the data/sample, inclusion/exclusion criteria, double blinding, and unpredictable risks. International ICFs had better readability and content integrity than Chinese local ICFs. More efforts should thus be made to improve the quality of consent documents in China.