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Background: Obesity and overweight, as determined by the body mass index (BMI), are harmful to metabolic health. However, the BMI can not reflect body composition or fat distribution. The fat-free mass index (FFMI) and the fat mass index (FMI) can provide more information on body composition. The aim of the observational research was to determine whether the FMI and the FFMI are significantly associated with the risk of developing diabetes and prediabetes., Methods: The investigators included data for 10,085 National Health and Nutrition Examination Survey (2011-2018) participants aged over 20 years who underwent dual-energy X-ray absorptiometry (DXA). The FFMI and the FMI were determined based on total fat mass and lean mass measured by DXA. Diabetes and prediabetes status were determined by medical history and laboratory examination. Logistic regression analyses were performed to explore the correlations between the FMI/FFMI and the risk of developing diabetes/prediabetes. Restricted cubic spline analysis was used to explore underlying nonlinear associations., Results: In the present study, 1,135 patients were diagnosed with diabetes, 3,258 had prediabetes, and 5,692 were classified as control participants. The FFMI (odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.04-1.16) and the FMI (OR = 1.08, 95% CI = 1.04-1.12) were independently related to an increased risk of developing diabetes. Moreover, the FFMI (OR 1.08, 95% CI 1.02-1.16) and the FMI (OR 1.07, 95% CI 1.02-1.13) also independently correlated with a rising risk of developing prediabetes. The restricted cubic spline (RCS) outcomes suggested that the associations are approximately linear., Conclusions: Both the FMI and the FFMI significantly correlated with the danger of developing diabetes and prediabetes, and the correlations are approximately linear., Competing Interests: Declarations The protocol for the NHANES study received approval from the Ethics Review Board of the National Center for Health Statistics. Each participant provided written informed consent prior to their involvement in the survey. As this study constitutes a secondary analysis of the publicly available NHANES database, it does not necessitate additional ethical review by the hospital’s ethics committee. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: A cost-effective Escherichia coli expression system has gained popularity for producing virus-like particle (VLP) vaccines. However, the challenge lies in balancing the endotoxin residue and removal costs, as residual endotoxins can cause inflammatory reactions in the body., Results: In this study, porcine parvovirus virus-like particles (PPV-VLPs) were successfully assembled from Decreased Endotoxic BL21 (BL21-DeE), and the effect of structural changes in the lipid A of BL21 on endotoxin activity, immunogenicity, and safety was investigated. The lipopolysaccharide purified from BL21-DeE produced lower IL-6 and TNF-α than that from wild-type BL21 (BL21-W) in both RAW264.7 cells and BALB/c mice. Additionally, mice immunized with PPV-VLP derived form BL21-DeE (BL21-DeE-VLP) showed significantly lower production of inflammatory factors and a smaller increase in body temperature within 3 h than those immunized with VLP from BL21-W (BL21-W-VLP) and endotoxin-removed VLP (ReE-VLP). Moreover, mice in the BL21-DeE-VLP immunized group had similar levels of serum antibodies as those in the BL21-W-VLP group but significantly higher levels than those in the ReE-VLP group. Furthermore, the liver, lungs, and kidneys showed no pathological damage compared with the BL21-W-VLP group., Conclusion: Overall, this study proposes a method for producing VLP with high immunogenicity and minimal endotoxin activity without chemical or physical endotoxin removal methods. This method could address the issue of endotoxin residues in the VLP and provide production benefits., (© 2024. The Author(s).)

Background: To investigate the prevalence and evolution of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) at commercial fattening pig farms, a total of 1397 clinical samples were collected from a single fattening cycle at seven pig farms in five provinces of China from 2020 to 2021., Results: The RT‒PCR results revealed that PRRSV was present on all seven farms, and the percentage of PRRSV-positive individuals was 17.54-53.33%. A total of 344 partial NSP2 gene sequences and 334 complete ORF5 gene sequences were obtained from the positive samples. The statistical results showed that PRRSV-2 was present on all seven commercial fattening farms, and PRRSV-1 was present on only one commercial fattening farm. A total of six PRRSV-2 subtypes were detected, and five of the seven farms had two or more PRRSV-2 subtypes. L1.8 (L1C) PRRSV was the dominant epidemic strain on five of the seven pig farms. Sequence analysis of L1.8 (L1C) PRRSV from different commercial fattening pig farms revealed that its consistency across farms varied substantially. The amino acid alignment results demonstrated that there were 131 aa discontinuous deletions in NSP2 between different L1.8 (L1C) PRRSV strains and that the GP5 mutation in L1.8 (L1C) PRRSV was mainly concentrated in the peptide signal region and T-cell epitopes. Selection pressure analysis of GP5 revealed that the use of the PRRSV MLV vaccine had no significant episodic diversifying effect on L1.8 (L1C) PRRSV., Conclusion: PRRSV infection is common at commercial fattening pig farms in China, and the percentage of positive individuals is high. There are multiple PRRSV subtypes of infection at commercial fattening pig farms in China. L1.8 (L1C) is the main circulating PRRSV strain on commercial fattening pig farms. L1.8 (L1C) PRRSV detected at different commercial fattening pig farms exhibited substantial differences in consistency but similar molecular characteristics. The pressure on the GP5 of L1.8 (L1C) PRRSV may not be directly related to the use of the vaccines., (© 2024. The Author(s).)

Background: The impact of insulin resistance on the prognosis of heart failure with preserved ejection fraction (HFpEF) remains unknown. This study aimed to investigate the association between the triglyceride-glucose (TyG) index, an easily calculated marker of insulin resistance, and the long-term prognosis of HFpEF., Methods: A total of 823 patients with HFpEF were enrolled in the study. The TyG index was determined using the formula ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The primary endpoint was all-cause death. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization. Restricted cubic spline, multivariate Cox proportional hazard models, and competing risk models were used for analyses., Results: During a median follow-up period of 3.16 years, 147 (17.8%) all-cause deaths, 139 (16.8%) CV deaths, and 222 (27.0%) HF rehospitalizations occurred. Restricted cubic spline analysis revealed a J-shaped association between the TyG index and the mortality and rehospitalization rates. In the multivariate Cox proportional hazard models, compared with those in the lowest TyG index tertile, patients in the highest tertile exhibited the greatest susceptibility to all-cause death (HR 1.53, 95% CI 1.19-1.98) and CV death (HR 1.52, 95% CI 1.19-1.96). In the competing risk model, a significant association between the TyG index and HF rehospitalization was observed (HR 1.31, 95% CI, 1.07-1.61)., Conclusion: A high TyG index is associated with an increased risk of mortality and rehospitalization in patients with HFpEF. The TyG index may serve as a promising prognostic marker for patients with HFpEF., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Limited research has been conducted on the potential relationship between the dietary inflammation index (DII) and mortality, particularly in individuals with Helicobacter pylori (H. pylori) infection. This study aimed to investigate the association between the DII and H. pylori infection, as well as their respective impacts on all-cause mortality in a cohort of individuals with or without H. pylori infection., Methods: Data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 4370 participants included. Both univariable and multivariable-adjusted logistic regression analyses were employed to explore the relationship between H. pylori infection and pertinent covariates. Cox regression analysis, as well as restricted regression cubic spline analysis, were utilized to assess the association between DII and all-cause mortality among individuals with or without H. pylori infection., Results: The findings demonstrated a positive correlation between DII scores and H. pylori infection, even after adjusting for potential confounding factors. Moreover, higher DII scores were significantly associated with an elevated risk of mortality exclusively in individuals with H. pylori infection, while no such association was observed in the uninfected population. Additional analysis using restricted cubic spline modeling revealed a positive linear relationship between DII scores as a continuous variable and the adjusted risk of all-cause mortality specifically in H. pylori-infected patients., Conclusion: The results of this study indicated that DII was positively correlated with an increased risk of H. pylori infection and was associated with a heightened risk of all-cause mortality solely in individuals with H. pylori infection. Consequently, DII might serve as a useful tool for risk stratification in the H. pylori-infected population among U.S. adults. Further research is warranted to elucidate the underlying mechanisms and potential clinical implications of these findings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The relationship between stress hyperglycemia and long-term prognosis in acute decompensated heart failure (ADHF) patients is unknown. This study investigated the associations of stress hyperglycemia with mortality and rehospitalization rates among ADHF patients with diabetes., Methods: We consecutively enrolled 1904 ADHF patients. Among them, 780 were with diabetes. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated by the following formula: SHR = admission blood glucose/[(28.7 × HbA1c%) - 46.7]. All diabetic ADHF subjects were divided into quintiles according to the SHR. The primary endpoint was all-cause death at the 3-year follow-up. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization at the 3-year follow-up. A Cox proportional hazards model and restricted cubic spline analysis were used to elucidate the relationship between the SHR and the endpoints in diabetic ADHF patients. Further analyses were performed to examine the relationships between SHR and the outcomes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF)., Results: A total of 169 all-cause deaths were recorded during a median follow-up of 3.24 years. Restricted cubic spline analysis suggested a U-shaped association between the SHR and the mortality and rehospitalization rates. Kaplan-Meier survival analysis showed the lowest mortality in the 2nd quintile (P = 0.0028). Patients categorized in the highest range (5th quintile) of SHR, compared to those in the 2nd quintile, exhibited the greatest susceptibility to all-cause death (with a hazard ratio [HR] of 2.76 and a 95% confidence interval [CI] of 1.63-4.68), CV death (HR 2.81 [95% CI 1.66-4.75]) and the highest rate of HF rehospitalization (HR 1.54 [95% CI 1.03-2.32]). Similarly, patients in the lowest range (1st quintile) of SHR also exhibited significantly increased risks of all-cause death (HR 2.33, 95% CI 1.35-4.02) and CV death (HR 2.32, 95% CI 1.35-4.00). Further analyses indicated that the U-shape association between the SHR and mortality remained significant in both HFpEF and HFrEF patients., Conclusion: Both elevated and reduced SHRs indicate an unfavorable long-term prognosis in patients with ADHF and diabetes., (© 2023. The Author(s).)

Objective: This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes., Research Design and Methods: A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan-Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients., Results: The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients., Conclusions: The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis., (© 2023. The Author(s).)

Background: Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009-2021., Methods: The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution., Results: A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution., Conclusions: Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials., (© 2023. The Author(s).)

Background: Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients., Methods: Data from National Health and Nutrition Examination Survey (NHANES) 1999-2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: < 8.5, 8.5-9.0, and > 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves., Results: TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p < 0.001). The risk of ASCVD increased by 74% with every 1 unit increase of TyG index (95%CI: 1.15-2.63, p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p < 0.05)., Conclusion: TyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality., (© 2023. The Author(s).)

Background: The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome., Methods: We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS)., Results: During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups., Conclusions: In ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS., (© 2022. The Author(s).)

Background: Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet., Methods: The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery. Patients who are ≥ 65 years and diagnosed with severe pure AR as defined by the Echocardiographic Core Laboratory will be consecutively enrolled for further multidetector computed tomography (MDCT) scanning and multiplanar analyses. Based on a new anatomical classification and dual anchoring theory, patients will be classified into 4 types according to the level of the anchoring area. Types 1, 2 and 3 (at least 2 anchoring areas) will undergo the TAVR procedure with a domestic Chinese self-expanding valve (VitaFlow Valve, MicroPort, Shanghai, China), whereas type 4 (0 or 1 anchoring area) patients will be considered unsuitable for TAVR and will receive medical treatment. Our goal is to recruit 100 patients to account for 10% missing data or loss of patients to follow-up. Procedural, 30-day, 6-month and 12-month outcomes will be assessed according to Valve Academic Research Consortium-3 criteria., Discussion: The AURORA study will establish a new AR anatomical classification based on dual anchoring theory through MDCT multiplanar measurement and assess the safety and efficacy of TAVR guided by this new classification and strategy in AR patients., Trial Registration: This Study was registered at Chinses Clinical Trial Registry. The registration number: ChiCTR2200055415; The date of registration: 9, January 2022; The URL of the registration: http://www.chictr.org.cn/showproj.aspx?proj=141209 ., (© 2022. The Author(s).)

Background: Non-diabetic coronary artery disease (CAD) patients are thought to encounter metabolic dysfunction and while these changes may be imperceptible to the patient they probably influence outcomes. At present, there is no system to support patients sensing these subtle changes, nor is there an established model for prognoses. The Atherogenic Index of Plasma (AIP) index has already proven useful for atherosclerosis although further research is needed, especially for those without hyperglycemia., Methods: This is a prospective study of 5538 non-diabetic CAD patients who had received percutaneous coronary intervention (PCI). Participants were assigned to one of three groups according to their AIP index. High AIP index cases were then compared to low index patients according to major adverse cardiac events (MACE). Restricted cubic spline (RCS) analysis was also conducted to investigate interrelations between AIP index levels and hazard ratios (HR) for MACEs., Results: Patients with a high AIP index encountered metabolic dysfunction compared to those with a low AIP index i.e., higher Body Mass Index (BMI), Total Cholesterol (TC), Triglycerides (TG), and uric acid as well as lower HDL-C. Each of the aforementioned interrelations were significant with p values of less than 0.001. There was also a significant increase in the number of MACEs in the high AIP index group compared to the low AIP index group (HR: 1.37, 95% CI 1.04-1.81; p = 0.025). A J-shaped RCS curve highlighted a change in the HR after the 0.18 juncture (HR per SD: 1.20, 95% CI 0.96-1.50). Further subgroup analysis supported the main findings, all with HRs greater than one., Conclusion: The AIP index could be used in prognostics for non-diabetic CAD patients 2 years after PCI. The relationship between hazard ratio and the AIP index appears to be J-shaped. Although, further multi-center studies designed for non-diabetic patients with potential metabolic dysfunction should be conducted to determine the value of the AIP index., (© 2022. The Author(s).)

Background: Evidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented., Methods: This study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern., Results: There were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5-6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (p trend  < 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles [Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011]., Conclusions: Adherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives., (© 2021. The Author(s).)

Innate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.

Membrane-associated RING-CH (MARCH) ubiquitin ligases belong to a RING finger domain E3 ligases family. Recent studies have demonstrated that MARCH proteins play critical roles during various viral infections. MARCH proteins can directly antagonize different steps of the viral life cycle and promote individual viral infection. This mini-review will focus on the latest advances of MARCH family proteins' emerging roles during viral infections.

Pseudorabies virus (PRV) is an important pathogen that threatens the global swine industry. Currently, there is no effective drug that can clinically prevent or treat PRV infections. Isobavachalcone (IBC), a natural chalcone compound derived from Psoralea corylifolia, displays multiple biological activities, such as antibacterial, antifungal, and anticancer activities. Recently, it was found that IBC exhibited antiviral activity against an RNA virus, porcine reproductive and respiratory syndrome virus (PRRSV), in vitro. In the current study, we further demonstrated for the first time that IBC has a strong inhibitory effect on PRV. Through a viral luciferase expression assay, we showed that the inhibition step occurs mainly in the late stage of viral replication. Finally, via a cell-to-cell fusion assay, we demonstrated that IBC inhibits PRV by blocking virus-mediated cell fusion. Thus, IBC may be a candidate for further therapeutic evaluation against PRV infection in vivo.

Pre-clinical animal studies have shown that triiodothyronine (T3) replacement therapy improves cardiac contractile function after myocardial infarction (MI). We hypothesized that T3 treatment could prevent adverse post-infarction cardiomyocyte remodeling by maintaining transverse-tubule (TT) structures, thus improving calcium dynamics and contractility. METHODS: Myocardial infarction (MI) or sham surgeries were performed on female Sprague-Dawley rats (aged 12 wks), followed by treatment with T3 (5μg/kg/d) or vehicle in drinking water for 16 wks (n = 10-11/group). After in vivo echocardiographic and hemodynamic analyses, left ventricular myocytes were isolated by collagenase digestion and simultaneous calcium and contractile transients in single cardiomyocytes were recorded using IonOptix imaging. Live cardiomyocytes were stained with AlexaFluor-488 conjugated wheat germ agglutinin (WGA-488) or di-8-ANEPPS, and multiple z-stack images per cell were captured by confocal microscopy for analysis of TT organization. RTqPCR and immunoblot approaches determined expression of TT proteins. RESULTS: Echocardiography and in vivo hemodynamic measurements showed significant improvements in systolic and diastolic function in T3- vs vehicle-treated MI rats. Isolated cardiomyocyte analysis showed significant dysfunction in measurements of myocyte relengthening in MI hearts, and improvements with T3 treatment: max relengthening velocity (Vmax, um/s), 2.984 ± 1.410 vs 1.593 ± 0.325, p < 0.05 and time to Vmax (sec), 0.233 ± 0.037 vs 0.314 ± 0.019, p < 0.001; MI + T3 vs MI + Veh, respectively. Time to peak contraction was shortened by T3 treatment (0.161 ± 0.021 vs 0.197 ± 0.011 s., p < 0.01; MI + T3 vs MI + Veh, respectively). Analysis of TT periodicity of WGA- or ANEPPS-stained cardiomyocytes indicated significant TT disorganization in MI myocytes and improvement with T3 treatment (transverse-oriented tubules (TE%): 9.07 ± 0.39 sham, 6.94 ± 0.67 MI + Veh and 8.99 ± 0.38 MI + T3; sham vs MI + Veh, p < 0.001; MI + Veh vs MI + T3, p < 0.01). Quantitative RT-PCR showed that reduced expression of BIN1 (Bridging integrator-1), Jph2 (junctophilin-2), RyR2 (ryanodine receptor) and Ca v 1.2 (L-type calcium channel) in the failing myocardium were increased by T3 and immunoblot analysis further supporting a potential T3 effect on the TT-associated proteins, BIN1 and Jph2. In conclusion, low dose T3 treatment initiated immediately after myocardial infarction attenuated adverse TT remodeling, improved calcium dynamics and contractility, thus supporting the potential therapeutic utility of T3 treatment in heart failure.

Background: Subclinical hypothyroidism is a common condition in patients with heart failure and is defined as elevated serum thyroid hormone (TSH) with normal circulating free thyroxine (FT4). Evidence on the effect of thyroid hormone treatment is lacking. We designed a randomized controlled trial to compare the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism., Methods/design: Eligible participants were identified from the cardiology units of five study centers based on the following criteria: 18 years or older, systolic heart failure with NewYork Heart Association (NYHA) class II-III, left ventricular ejection fraction ≤ 40%, and subclinical hypothyroidism (TSH > 4.78μIU/ml, < 10 μIU/ml + FT4 level within reference range). Eligible patients will be randomly assigned in a 1:1 manner to receive thyroxine replacement therapy plus standard chronic heart failure (CHF) treatment or only standard CHF therapy. Levothyroxine will be administered at an initial dose of 12.5 μg once daily and will be titrated until TSH is within the normal range. The primary endpoints include the difference in distance of the six-minute walk test between 24 weeks and baseline. The secondary endpoints include differences in plasma NT-proBNP levels and serum lipid profiles, changes in the NYHA classification, cardiovascular death, re-hospitalization, differences in echocardiographic and cardiac magnetic resonance imaging measures, and Minnesota Living With Heart Failure Questionnaire (MLHFQ) results between 24 weeks and baseline., Discussion: ThyroHeart-CHF is designed as a prospective, multi-center, randomized, controlled clinical trial to study the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism. The study findings will have significant implications for discovering the new therapeutic targets and methods of heart failure., Trail Registration: ClinicalTrials.gov, NCT03096613 . Registered on 30 March 2017.

Background: Nonalcoholic fatty liver disease (NAFLD) refers to fatty infiltration of liver in the absence of excessive alcohol abuse. However, the problem that whether NAFLD is correlated with subclinical atherosclerosis assessed by carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) remains a source of controversy. This can be attributed to the differences in diagnosis methods, population ethnicity, sampling size and bias. This study aimed to further investigate the association of NAFLD with subclinical atherosclerosis., Methods: A cross-sectional study was carried out in the current study on population aged over 40 years derived from Kailuan community-based prospective study among Chinese adults from June 2010 to June 2011. NAFLD was evaluated through ultrasonography and histories of alcohol consumption. Clinical parameters and medical histories of patients were collected in the manner of interview performed by trained investigators using the standardized questionnaires. The biochemical parameters were analyzed at the central laboratory. CIMT and ba-PWV of each patient were measured. Multivariate logistic regression was used to analyze the associations of NAFLD with subclinical atherosclerosis assessed by CIMT or ba-PWV., Results: A total of 4112 participants aged over 40 years were enrolled from Kailuan cohort, including 2229 men and 1883 women. The overall prevalence of NAFLD was 38.2% in the total population. Statistically significant differences were found in CIMT (P < 0.0001) and ba-PWV (P = 0.0007) according to the presence of NAFLD. It is notably that the multivariate logistic regression revealed NAFLD was independently associated with elevated CIMT after adjusting the conventional cardiovascular and metabolic risk factors (OR = 1.663, 95% CI = 1.391-1.989, P < 0.0001). In addition, NAFLD was also found to be positively associated with elevated ba-PWV after adjusting age, gender, BMI, current smoking and regular exercising (OR = 1.319, 95% CI = 1.072-1.624, P = 0.0089)., Conclusions: Our findings suggest that NAFLD is remarkably correlated with subclinical atherosclerosis, which should be strongly advised to engage in the preventive strategies for cardiovascular diseases (CVDs).