Post-procedural elevated cardiac troponin I and the association with 5-year mortality in patients undergoing elective PCI.

Background: The clinically meaningful cardiac troponin I (cTnI) threshold associated with the long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Objective: To assess the association between different thresholds for post-procedural cTnI and 5-year mortality. Methods: The study included 4059 consecutive patients with normal baseline cTnI values who underwent elective PCI. The post-procedural cTnI level was measured at 8-48 h after PCI. The main study endpoints were 5-year all-cause mortality and cardiovascular mortality. Results: A cTnI ≥5 times the upper reference limit (URL) as defined by the fourth universal definition of myocardial infarction (4th UDMI), ≥35 times as defined by the Academic Research Consortium-2 criteria, and ≥70 times as defined by the Society for Cardiovascular Angiography and Interventions (SCAI [2014]) was identified in 33%, 6.6%, and 3.3% of patients, respectively. During 5 years of follow-up, the all-cause mortality rate was 3.4% (n = 132) and the cardiovascular mortality rate was 2.0% (n = 77). Both all-cause mortality and cardiovascular mortality increased with higher peak cTnI, and were independently predicted by a cTnI ≥70 times the URL (adjusted hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.20-5.02 and adjusted HR 3.17, 95% CI 1.31-7.67, respectively; reference, cTnI <1 × URL]. The SCAI (2014) threshold was significantly associated with 5-year cardiovascular mortality (adjusted HR 2.66, 95% CI 1.20-5.89; reference, cTnI, <70 × URL) and all-cause mortality (adjusted HR 2.23, 95% CI 1.16-4.30; reference, cTnI <70 × URL). Conclusion: In patients with normal pre-procedural cTnI who underwent elective PCI, a post-procedural cTnI ≥70 times the URL independently predicted 5-year all-cause and cardiovascular mortality. Therefore, only the SCAI (2014) post-procedural cTnI threshold was independently associated with long-term mortality.

Association between obstructive sleep apnea and visceral adiposity index and lipid accumulation product: NHANES 2015-2018.

BACKGROUND: Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. METHODS: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. RESULTS: Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51-68.26) and 1.27 (0.75-2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged < 60 years. Through smooth curve fitting, specific saturation effects of LAP, VAI, and BMD were identified, with inflection points at 65.684 and 0.428, respectively. CONCLUSION: This study demonstrates that elevated levels of LAP and VAI increase the risk of OSA, suggesting their potential as predictive markers for OSA and advocating for dietary and exercise interventions to mitigate OSA risk in individuals with high LAP and VAI levels.

Inflammation modifies the platelet reactivity among thrombocytopenia patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53-0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41-0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63-1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.

What is the context? Recent studies reported a paradoxical phenomenon that percutaneous coronary intervention (PCI) patients with thrombocytopenia (TP) were prone to experience thrombotic events. The potential mechanisms underlying the increased thrombotic risk and how to manage antiplatelet therapy in PCI patients with TP remain unclear.Growing attention has been paid to immunothrombosis. Inflammation is closely associated with high-on treatment platelet reactivity (HTPR) and thrombotic risk.HTPR is an independent risk factor of thrombosis and can provide information for guiding antiplatelet therapy.What is new? This prospective cohort study enrolled 10 724 patients undergoing PCI in Fuwai Hospital (National Center for Cardiovascular Diseases, Beijing, China), with HTPR risk being the study endpoint of interest.We first reported that inflammation significantly modified the platelet reactivity of PCI patients with TP.When hsCRP level <2 mg/L, PCI patients with TP had a decreased risk of HTPR. However, when hsCRP ≥2 mg/L, TP patients had similar HTPR risk as those without TP.HsCRP levels could modify the relationship between TP and HTPR risks both in patients with acute coronary syndrome and chronic coronary syndrome.What is the impact? These results provide insights into potential mechanisms of the increased thrombotic risk in PCI patients with TP. Specifically, inflammation might be involved in the thrombotic risk of PCI patients with TP by modifying the platelet reactivity.As for future management, personalized antiplatelet therapy should be administrated to TP patients with inflammation status.

Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.

The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 mislocalization and broadly remodeled signaling. Notably, although HAPSTR1 potently suppresses p53, we find that Hapstr1 is essential for life even in mice lacking p53. Altogether, we identify novel components and functional insights into the conserved HAPSTR1-HUWE1 pathway and demonstrate its requirement for mammalian life.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

Isoalantolactone exerts anti-melanoma effects via inhibiting PI3K/AKT/mTOR and STAT3 signaling in cell and mouse models.

BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.

Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study.

Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.

[Biological Effect of Microplastics with Different Functional Groups on the Bacterial Communities and Metabolic Functions of Zebrafish (Danio rerio) Embryos].

To investigate the influences of functional groups on the biological effects caused by microplastics, the accumulation of three polystyrene microplastics (PS, PS-NH2, and PS-COOH) in zebrafish (Danio rerio) embryos were analyzed, and then the responses of metabolic functions and microbial communities in zebrafish larvae were revealed using the combination of the microbiome and metabolome methods. The results showed that all microplastics could accumulate in zebrafish with concentrations ranging from 143 to 175 µg·g-1, and there were no significant differences in the accumulation potentials among different PS treatments. Exposure to plain PS significantly affected the metabolic capacity of aminoglycosides in zebrafish larvae, whereas the metabolic processes of amino acids were affected by PS-NH2. In the PS-COOH treatment, the metabolic pathways of the tricarboxylic acid cycle, amino acids, and glycolysis in zebrafish were markedly altered. The metabolic functions of zebrafish larvae were changed by all PS microplastics, resulting in toxic effects on zebrafish, and the functional group modification of microplastics may have further enhanced these toxicities. Compared to that in the control, exposure to PS-NH2 significantly reduced the diversity of microbial communities in zebrafish larvae and increased the proportion of Proteobacteria in the composition, leading to an imbalance of the bacterial community in zebrafish and thus disrupting the metabolic functions in the fish. Therefore, the functional modifications of microplastics may significantly alter the related stresses on aquatic organisms, leading to unpredictable ecological risks.

pH/Ion Dual-Responsive Emulsion Via a Cationic Surfactant and Positively Charged Magnesium Hydroxide Nanosheets.

Emulsions, formed by dispersing a liquid into another immiscible one by virtue of emulsifiers, have been widely applied in commercial applications like foods, pharmaceuticals, cosmetics, and personal care, which always confront environmental and/or toxic questions due to emulsifiers' high dosage. Recently, a study on Pickering emulsions points out a solution to stable emulsions based on the costabilizing effect of colloidal particles, which focused on surface-active particles cooperating with oppositely charged ionic surfactants. Costabilized emulsions adopting a charge-similar ionic surfactant and particles were less studied. In this article, a hexane-in-water emulsion was prepared in use of a cationic surfactant cetyltrimethylammonium bromide (CTAB) with positively charged magnesium hydroxide (MH) nanosheets at low concentrations (10-5 M and 10-2 wt %, respectively). The emulsion is stable due to the synergy by CTAB and MH nanosheets, which functions in virtue of the electric repulsion by similarly charged particles, the mechanical shielding by MH nanosheets, and restrained water drainage in lamellae between droplets due to the gelation of MH nanosheets. Moreover, the emulsion is doubly switchable within emulsification/demulsification via convenient pH or ion manipulation, a mechanism based on the breakdown and rebuilding of the costabilizing synergy. Such dual-responsive emulsions show high potential for the delicate control of drug delivery, release, and biphasic biocatalysis applications.

A Cysteine-Maleimide-Based Design for Hemostatic, Antibacterial, and Biodegradable Wound Dressing.

The field of clinical surgery frequently encounters challenges related to atypical wound tissue healing, resulting in the development of persistent chronic wounds or aesthetically displeasing scar tissue. The use of wound dressings crafted from mussel adhesive proteins and hyaluronic acid has demonstrated the potential in mitigating these undesirable outcomes. However, the synergistic effects of these two biomaterials remain underexplored. In this study, we have engineered a versatile, degradable, and biocompatible dressing that comprises recombinant 3,4-dihydroxyphenylalanine (DOPA)-modified mussel adhesive proteins and maleimide-functionalized hyaluronic acid. We have successfully fabricated this biocompatible dressing and conducted comprehensive experimental assessments to confirm its hemostatic, antibacterial, and biocompatible characteristics. Importantly, this dressing exclusively incorporates biologically derived materials characterized by low toxicity and minimal immunogenicity, thus holding immense promise for clinical applications in the field of wound healing.

Baseline high-sensitivity C-reactive protein and glycosylated hemoglobinA1c predict adverse outcomes in patients with chronic coronary syndromes undergoing percutaneous coronary intervention.

Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066-2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716-2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032-1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091-1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079-3.601, P = 0.027 and HR 1.560, 95 % CI 1.191-2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001). Conclusions: Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.

Identification of pigeon mitochondrial antiviral signaling protein (MAVS) and its role in antiviral innate immunity.

Pigeons can be infected with various RNA viruses, and their innate immune system responds to viral infection to establish an antiviral response. Mitochondrial antiviral signaling protein (MAVS), an important adaptor protein in signal transduction, plays a pivotal role in amplifying the innate immune response. In this study, we successfully cloned pigeon MAVS (piMAVS) and performed a bioinformatics analysis. The results showed that the caspase recruitment domain (CARD) and transmembrane (TM) domain are highly conserved in poultry and mammals but poorly conserved in other species. Furthermore, we observed that MAVS expression is upregulated both in pigeons and pigeon embryonic fibroblasts (PEFs) upon RNA virus infection. Overexpression of MAVS resulted in increased levels of ß-interferon (IFN-ß), IFN-stimulated genes (ISGs), and interleukin (ILs) mRNA and inhibited Newcastle disease virus (NDV) replication. We also found that piMAVS and human MAVS (huMAVS) induced stronger expression of IFN-ß and ISGs when compared to chicken MAVS (chMAVS), and this phenomenon was also reflected in the degree of inhibition of NDV replication. Our findings demonstrate that piMAVS plays an important role in repressing viral replication by regulating the activation of the IFN signal pathway in pigeons. This study not only sheds light on the function of piMAVS in innate immunity but also contributes to a more comprehensive understanding of the innate immunity system in poultry. Our data also provide unique insights into the differences in innate immunity between poultry and mammal.

NMAAP1 regulated macrophage polarizion into M1 type through glycolysis stimulated with BCG.

Bacillus Calmette Guerin (BCG) perfusion is widely used as cancer adjuvant therapy, in which macrophages play an important role. Novel macrophage activated associated protein 1 (NMAAP1), upregulated after BCG's activation, was proved to promote macrophage polarization to the M1 type. We found that BCG could stimulate mice BMDM to the M1 type and kill tumor cells. After the deletion of NMAAP1, the tumor volume of mice became larger, and the number of M1 type macrophages in the tumor decreased significantly. When macrophages were induced into the M1 type, aerobic glycolysis, the Warburg effect manifested in the increased uptake of glucose and the conversion of pyruvate to lactic acid. NMAAP1 could bind with IP3R and regulate macrophage polarization to the M1 type. However, the specific mechanism of how NMAAP1 regulates macrophage polarization towards the M1 type and plays an antitumor role must be clarified. NMAAP1 could promote the release of lactic acid and pyruvate, enhance the glycolysis of macrophages, and affect the expression of HIF-1α. After inhibition of glycolysis by 2-DG and lactic acid generation by FX11, the effects of NMAAP1 promoting macrophage polarization to the antitumor M1 type were weakened. Furthermore, NMAAP1 upregulated the expression of HIF-1α, which is associated with glycolysis. Moreover, the Ca2+/NF-κB pathway regulated HIF-1α expression by NMAAP1 in the macrophages. NMAAP1 promotes the polarization of macrophages towards the M1 type by affecting the Warburg effect stimulated by BCG.

Association between multiple inflammatory biomarkers and remnant cholesterol levels in patients with percutaneous coronary intervention: A large-scale real-world study.

BACKGROUND AND AIM: Remnant cholesterol (RC) has garnered increasing attention recently due to its association with adverse cardiovascular events. However, the relationship between RC levels and inflammation remains unclear. The goal of this study was to investigate and compare the predictive value of multiple inflammatory biomarkers for high RC in patients with percutaneous coronary intervention (PCI). METHODS AND RESULTS: Initially, a total of 10,724 consecutive individuals hospitalized for PCI at Fu Wai Hospital in 2013 were enrolled. Finally, 9983 patients receiving dual antiplatelet therapy and drug-eluting stent were selected for analysis. The inflammatory biomarkers included high-sensitivity C-reactive protein (hs-CRP), hs-CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-hs-CRP ratio (LCR), and systemic immune-inflammation index (SII). Patients were divided into higher RC and lower RC groups based on the median RC level. Multivariate logistic regression showed that hs-CRP (OR per SD: 1.254), CAR (OR per SD: 1.245), PLR (OR per SD: 1.139), and SII (OR per SD: 1.077) were associated with high RC (≥median), while LCR (OR per SD: 0.792) was associated with low RC (

Study on diagnosing thyroid nodules of ACR TI-RADS 4-5 with multimodal ultrasound radiomics technology.

BACKGROUND: Explore the feasibility of using the multimodal ultrasound (US) radiomics technology to diagnose American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) 4-5 thyroid nodules. METHOD: This study prospectively collected the clinical characteristics, conventional, and US elastography images of 100 patients diagnosed with ACR TI-RADS 4-5 nodules from May 2022 to 2023. Independent risk factors for malignant thyroid nodules were extracted and screened using methods such as the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model, and a multimodal US radiomics combined diagnostic model was established. Using a multifactorial LR analysis and a Rad-score rating, the predictive performance was validated and evaluated, and the final threshold range was determined to assess the clinical net benefit of the model. RESULTS: In the training set, the US radiomics combined predictive model area under curve (AUC = 0.928) had higher diagnostic performance compared with clinical characteristics (AUC = 0.779), conventional US (AUC = 0.794), and US elastography model (AUC = 0.852). In the validation set, the multimodal US radiomics combined diagnostic model (AUC = 0.829) also had higher diagnostic performance compared with clinical characteristics (AUC = 0.799), conventional US (AUC = 0.802), and US elastography model (AUC = 0.718). CONCLUSION: Multi-modal US radiomics technology can effectively diagnose thyroid nodules of ACR TI-RADS 4-5, and the combination of radiomics signature and conventional US features can further improve the diagnostic performance.

Prognostic significance of inflammation in patients with coronary artery disease at low residual inflammatory risk.

Patients with coronary artery disease (CAD) at low residual inflammatory risk are often overlooked in research and practice. This study examined the associations between fourteen inflammatory indicators and all-cause mortality in 5,339 CAD patients with baseline high-sensitivity C-reactive protein (hsCRP) <2 mg/L who received percutaneous coronary intervention and statin and aspirin therapy. The median follow-up time was 2.1 years. Neutrophil-derived systemic inflammatory response index (SIRI) yielded the strongest and most robust association with all-cause mortality among all indicators. Lower hsCRP remained to be associated with a lower risk of all-cause mortality. A newly developed comprehensive inflammation score (CIS) showed better predictive performance than other indicators, which was validated by an independent external cohort. In conclusion, neutrophil-derived indicators, particularly SIRI, strongly predicted all-cause mortality independent of hsCRP in CAD patients at low residual inflammatory risk. CIS may help identify individuals with inflammation burdens that cannot be explained by hsCRP alone.

Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention.

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS: For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Remnant cholesterol but not LDL cholesterol is associated with 5-year bleeding following percutaneous coronary intervention.

This study was aimed to investigate the association between remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) concentrations and long-term bleeding. A total of 10,724 consecutive patients who underwent percutaneous coronary intervention in 2013 were prospectively enrolled. During a median follow-up of 5.1 years, 411 bleeding events and 42 intracranial hemorrhages (ICH) were recorded. The findings revealed that lower RC concentrations were independently associated with an increased risk of long-term bleeding events (continuous RC hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.26-0.85; Q4 vs. Q1 HR: 0.66, 95% CI: 0.45-0.98), whereas lower LDL-C concentrations did not show a similar association. Additionally, a non-linear relationship was observed between RC concentrations and the risk of ICH (P for non-linear trend = 0.014), but no such relationship was found for LDL-C concentrations. These results provided insights into the safety of LDL-C-lowering therapy and emphasized the significance of RC concentrations in lipid management.

First Identification and Pathogenicity Evaluation of an EV-G17 Strain Carrying a Torovirus Papain-like Cysteine Protease (PLCP) Gene in China.

Enterovirus G (EV-G) is prevalent in pig populations worldwide, and a total of 20 genotypes (G1 to G20) have been confirmed. Recently, recombinant EV-Gs carrying the papain-like cysteine protease (PLCP) gene of porcine torovirus have been isolated or detected, while their pathogenicity is poorly understood. In this study, an EV-G17-PLCP strain, 'EV-G/YN23/2022', was isolated from the feces of pigs with diarrhea, and the virus replicated robustly in numerous cell lines. The isolate showed the highest complete genome nucleotide (87.5%) and polyprotein amino acid (96.6%) identity in relation to the G17 strain 'IShi-Ya4' (LC549655), and a possible recombination event was detected at the 708 and 3383 positions in the EV-G/YN23/2022 genome. EV-G/YN23/2022 was nonlethal to piglets, but mild diarrhea, transient fever, typical skin lesions, and weight gain deceleration were observed. The virus replicated efficiently in multiple organs, and the pathological lesions were mainly located in the small intestine. All the challenged piglets showed seroconversion for EV-G/YN23/2022 at 6 to 9 days post-inoculation (dpi), and the neutralization antibody peaked at 15 dpi. The mRNA expression levels of IL-6, IL-18, IFN-α, IFN-ß, and ISG-15 in the peripheral blood mononuclear cells (PBMCs) were significantly up-regulated during viral infection. This is the first documentation of the isolation and pathogenicity evaluation of the EV-G17-PLCP strain in China. The results may advance our understanding of the evolution characteristics and pathogenesis of EV-G-PLCP.