Comparison of Outcomes of Edge-to-Edge Mitral Valve Repair Versus Surgical Mitral Valve Repair for Functional Mitral Regurgitation.

AIMS: Patients affected by functional mitral regurgitation represent an increasingly high-risk population. Edge-to-edge mitral valve repair (TEER) has emerged as a promising treatment option for these patients. However, there is limited research on the comparative outcomes of TEER versus surgical mitral valve repair (SMVr). This study seeks to compare the demographics, complications, and outcomes of TEER and SMVr based on a real-world analysis of the National Inpatient Sample (NIS) database. METHODS AND RESULTS: In the NIS database, from the years 2016 to 2018, a total of 6233 and 2524 patients who underwent SMVr and TEER were selected, respectively. The mean ages of the patients were 65.68 years (SMVr) and 78.40 years (TEER) (p < 0.01). The mortality rate of patients who received SMVr was similar to that of patients who were treated with TEER (1.7% vs. 1.9%, p = 0.603). Patients who underwent SMVr more likely suffered from perioperative complications including cardiogenic shock (2.3% vs. 0.4%, p < 0.001), cardiac arrest (1.7% vs. 1.1%, p = 0.025), and cerebrovascular infarction (0.9% vs. 0.4%, p = 0.013). The average length of hospital stay was longer (8.59 vs. 4.13 days, p < 0.001) for SMVr compared to TEER; however, the average cost of treatment was higher ($218 728.25 vs. $215 071.74, p = 0.031) for TEER compared to SMVr. Multiple logistic regression analysis showed that SMVr was associated with worse adjusted cardiogenic shock (OR, 7.347 [95% CI, 3.574-15.105]; p < 0.01) and acute kidney injury (OR, 2.793 [95% CI, 2.356-3.311]; p < 0.01). CONCLUSION: Patients who underwent TEER demonstrated a notable decrease in postoperative complications and a shorter hospitalization period when compared to those who underwent SMVr.

Glucocorticoid therapy for sepsis in the AI era: a survey on current and future approaches.

Sepsis, a life-threatening medical condition, manifests as new or worsening organ failures due to a dysregulated host response to infection. Many patients with sepsis have manifested a hyperinflammatory phenotype leading to the identification of inflammatory modulation by corticosteroids as a key treatment modality. However, the optimal use of corticosteroids in sepsis treatment remains a contentious subject, necessitating a deeper understanding of their physiological and pharmacological effects. Our study conducts a comprehensive review of randomized controlled trials (RCTs) focusing on traditional corticosteroid treatment in sepsis, alongside an analysis of evolving clinical guidelines. Additionally, we explore the emerging role of artificial intelligence (AI) in medicine, particularly in diagnosing, prognosticating, and treating sepsis. AI's advanced data processing capabilities reveal new avenues for enhancing corticosteroid therapeutic strategies in sepsis. The integration of AI in sepsis treatment has the potential to address existing gaps in knowledge, especially in the application of corticosteroids. Our findings suggest that combining corticosteroid therapy with AI-driven insights could lead to more personalized and effective sepsis treatments. This approach holds promise for improving clinical outcomes and presents a significant advancement in the management of this complex and often fatal condition.

Discovery of palmatine derivatives as potent neuroprotective agents.

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment.

Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling.

Patients with Type 2 Diabetes Mellitus are increasingly susceptible to atherosclerotic plaque vulnerability, leading to severe cardiovascular events. In this study, we demonstrate that elevated serum levels of palmitic acid, a type of saturated fatty acid, are significantly linked to this enhanced vulnerability in patients with Type 2 Diabetes Mellitus. Through a combination of human cohort studies and animal models, our research identifies a key mechanistic pathway: palmitic acid induces macrophage Delta-like ligand 4 signaling, which in turn triggers senescence in vascular smooth muscle cells. This process is critical for plaque instability due to reduced collagen synthesis and deposition. Importantly, our findings reveal that macrophage-specific knockout of Delta-like ligand 4 in atherosclerotic mice leads to reduced plaque burden and improved stability, highlighting the potential of targeting this pathway. These insights offer a promising direction for developing therapeutic strategies to mitigate cardiovascular risks in patients with Type 2 Diabetes Mellitus.

Role of advanced glycation end products in diabetic vascular injury: molecular mechanisms and therapeutic perspectives.

BACKGROUND: In diabetic metabolic disorders, advanced glycation end products (AGEs) contribute significantly to the development of cardiovascular diseases (CVD). AIMS: This comprehensive review aims to elucidate the molecular mechanisms underlying AGE-mediated vascular injury. CONCLUSIONS: We discuss the formation and accumulation of AGEs, their interactions with cellular receptors, and the subsequent activation of signaling pathways leading to oxidative stress, inflammation, endothelial dysfunction, smooth muscle cell proliferation, extracellular matrix remodeling, and impaired angiogenesis. Moreover, we explore potential therapeutic strategies targeting AGEs and related pathways for CVD prevention and treatment in diabetic metabolic disorders. Finally, we address current challenges and future directions in the field, emphasizing the importance of understanding the molecular links between AGEs and vascular injury to improve patient outcomes.

MRI advances in the imaging diagnosis of tuberculous meningitis: opportunities and innovations.

Tuberculous meningitis (TBM) is not only one of the most fatal forms of tuberculosis, but also a major public health concern worldwide, presenting grave clinical challenges due to its nonspecific symptoms and the urgent need for timely intervention. The severity and the rapid progression of TBM underscore the necessity of early and accurate diagnosis to prevent irreversible neurological deficits and reduce mortality rates. Traditional diagnostic methods, reliant primarily on clinical findings and cerebrospinal fluid analysis, often falter in delivering timely and conclusive results. Moreover, such methods struggle to distinguish TBM from other forms of neuroinfections, making it critical to seek advanced diagnostic solutions. Against this backdrop, magnetic resonance imaging (MRI) has emerged as an indispensable modality in diagnostics, owing to its unique advantages. This review provides an overview of the advancements in MRI technology, specifically emphasizing its crucial applications in the early detection and identification of complex pathological changes in TBM. The integration of artificial intelligence (AI) has further enhanced the transformative impact of MRI on TBM diagnostic imaging. When these cutting-edge technologies synergize with deep learning algorithms, they substantially improve diagnostic precision and efficiency. Currently, the field of TBM imaging diagnosis is undergoing a phase of technological amalgamation. The melding of MRI and AI technologies unquestionably signals new opportunities in this specialized area.

The diagnosis of tuberculous meningitis: advancements in new technologies and machine learning algorithms.

Tuberculous meningitis (TBM) poses a diagnostic challenge, particularly impacting vulnerable populations such as infants and those with untreated HIV. Given the diagnostic intricacies of TBM, there's a pressing need for rapid and reliable diagnostic tools. This review scrutinizes the efficacy of up-and-coming technologies like machine learning in transforming TBM diagnostics and management. Advanced diagnostic technologies like targeted gene sequencing, real-time polymerase chain reaction (RT-PCR), miRNA assays, and metagenomic next-generation sequencing (mNGS) offer promising avenues for early TBM detection. The capabilities of these technologies are further augmented when paired with mass spectrometry, metabolomics, and proteomics, enriching the pool of disease-specific biomarkers. Machine learning algorithms, adept at sifting through voluminous datasets like medical imaging, genomic profiles, and patient histories, are increasingly revealing nuanced disease pathways, thereby elevating diagnostic accuracy and guiding treatment strategies. While these burgeoning technologies offer hope for more precise TBM diagnosis, hurdles remain in terms of their clinical implementation. Future endeavors should zero in on the validation of these tools through prospective studies, critically evaluating their limitations, and outlining protocols for seamless incorporation into established healthcare frameworks. Through this review, we aim to present an exhaustive snapshot of emerging diagnostic modalities in TBM, the current standing of machine learning in meningitis diagnostics, and the challenges and future prospects of converging these domains.

Harnessing gradient gelatin nanocomposite hydrogels: a progressive approach to tackling antibacterial biofilms.

Infectious wounds pose significant challenges due to their susceptibility to bacterial infections, hindering tissue repair. This study introduces gradient gelatin nanocomposite hydrogels for wound healing and antibacterial biofilm management. These hydrogels, synthesized via UV light polymerization, incorporate copper-doped polydopamine nanoparticles (PDA-Cu) and GelMA (gelatin methacrylate). The hydrogels have a unique structure with a porous upper layer and a denser lower layer, ensuring superior swelling (over than 600%) and effective contact with bacterial biofilms. In vitro experiments demonstrate their remarkable antibacterial properties, inhibiting S. aureus and E. coli biofilms by over 45% and 53%, respectively. This antibacterial action is attributed to the regulation of reactive oxygen species (ROS) production, an alternative mechanism to bacterial cell wall disruption. Moreover, the hydrogels exhibit high biocompatibility with mammalian cells, making them suitable for medical applications. In vivo evaluation in a rat wound infection model shows that the gradient hydrogel treatment effectively controls bacterial biofilm infections and accelerates wound healing. The treated wounds have smaller infected areas and reduced bacterial colony counts. Histological analysis reveals reduced inflammation and enhanced granulation tissue formation in treated wounds, highlighting the therapeutic potential of these gradient nanocomposite hydrogels. In summary, gradient gelatin nanocomposite hydrogels offer promising multifunctional capabilities for wound healing and biofilm-related infections, paving the way for innovative medical dressings with enhanced antibacterial properties and biocompatibility.

AGEs induce high expression of Dll4 via endoplasmic reticulum stress PERK signaling-mediated internal ribosomal entry site mechanism in macrophages.

Background and aim: Advanced glycation end products (AGEs)- exposed macrophages was characterized by Delta-like ligand 4 (Dll4) high expressed and has been shown to participate in diabetes-related atherosclerosis. This study was aimed to investigate the translational regulatory mechanism of Dll4 high expression in macrophages exposed to AGEs. Methods: Human Dll4 5' untranslated region (5'UTR) sequence was cloned and inserted into a bicistronic reporter plasmid. Human THP-1 macrophages transfected with the bicistronic reporter plasmids were exposed to AGEs. Dual-luciferase assay was used to detect internal ribosome entry site (IRES) activity contained in Dll4 5'UTR. Small interference RNA transfection was used to knock-down specific gene expression. Localization of protein was analyzed. Results: AGEs exposure significantly induced IRES activity in Dll4 5' UTR in human macrophages. Internal potential promoter and ribosome read-through mechanisms were excluded. Inhibition of endoplasmic reticulum stress and specific silencing of protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) signaling pathway activation reduced IRES activity in Dll4 5' UTR in human macrophages. Dll4 5' UTR IRES activity was also inhibited by targeted silencing of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Moreover, specific inhibition of PERK/eIF2α signaling pathway led to deactivation of hnRNPA1, resulting to reduction of AGEs- induced Dll4 5' UTR IRES activity in human macrophages. Conclusions: AGEs induced Dll4 5' UTR IRES activity in human macrophages which was dependent on endoplasmic reticulum stress PERK/eIF2α signaling pathway. hnRNPA1 acted the role as an ITAF was also indispensable for AGEs-induced Dll4 5'UTR IRES activity in human macrophages.

Hydrothermal carbonization of food waste for sustainable biofuel production: Advancements, challenges, and future prospects.

With the improvement of living standards, food waste (FW) has become one of the most important organic solid wastes worldwide. Owing to the high moisture content of FW, hydrothermal carbonization (HTC) technology that can directly utilize the moisture in FW as the reaction medium, is widely used. Under mild reaction conditions and short treatment cycle, this technology can effectively and stably convert high-moisture FW into environmentally friendly hydrochar fuel. In view of the importance of this topic, this study comprehensively reviews the research progress of HTC of FW for biofuel synthesis, and critically summarizes the process parameters, carbonization mechanism, and clean applications. Physicochemical properties and micromorphological evolution of hydrochar, hydrothermal chemical reactions of each model component, and potential risks of hydrochar as a fuel are highlighted. Furthermore, carbonization mechanism of the HTC treatment process of FW and the granulation mechanism of hydrochar are systematically reviewed. Finally, potential risks and knowledge gaps in the synthesis of hydrochar from FW are presented and new coupling technologies are pointed out, highlighting the challenges and prospects of this study.

Automatic pavement texture recognition using lightweight few-shot learning.

Texture is a crucial characteristic of roads, closely related to their performance. The recognition of pavement texture is of great significance for road maintenance professionals to detect potential safety hazards and carry out necessary countermeasures. Although deep learning models have been applied for recognition, the scarcity of data has always been a limitation. To address this issue, this paper proposes a few-shot learning model based on the Siamese network for pavement texture recognition with a limited dataset. The model achieved 89.8% accuracy in a four-way five-shot task classifying the pavement textures of dense asphalt concrete, micro surface, open-graded friction course and stone matrix asphalt. To align with engineering practice, global average pooling (GAP) and one-dimensional convolution are implemented, creating lightweight models that save storage and training time. Comparative experiments show that the lightweight model with GAP implemented on dense layers and one-dimensional convolution on convolutional layers reduced storage volume by 94% and training time by 99%, despite a 2.9% decrease in classification accuracy. Moreover, the model with only GAP implemented on dense layers achieved the highest accuracy at 93.5%, while reducing storage volume and training time by 83% and 6%, respectively. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.

Long-range hydrophobic force enhanced interfacial photocatalysis for the submerged surface anti-biofouling.

Developing anti-biofouling and anti-biofilm techniques is of great importance for protecting water-contact surfaces. In this study, we developed a novel double-layer system consisting of a bottom immobilized TiO2 nanoflower arrays (TNFs) unit and an upper superhydrophobic (SHB) coating along with the assistance of nanobubbles (NBs), which can significantly elevate the interfacial oxygen level by establishing the long-range hydrophobic force between NBs and SHB and effectively maximize the photocatalytic reaction brought by the bottom TNFs. The developed NBs-SHB/TNFs system demonstrated the highest bulk chemical oxygen demand (COD) reduction efficiency at approximately 80% and achieved significant E. coli and Chlorella sp. inhibition efficiencies of 5.38 and 1.99 logs. Meanwhile, the system showed a sevenfold higher resistance to biofilm formation when testing in a wastewater matrix using a wildly collected biofilm seeding solution. These findings provide insights for implementing nanobubble-integrated techniques for submerged surface protection.

Hydroxychloroquine Attenuates hERG Channel by Promoting the Membrane Channel Degradation: Computational Simulation and Experimental Evidence for QT-Interval Prolongation with Hydroxychloroquine Treatment.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to millions of confirmed cases and deaths worldwide and has no approved therapy. Currently, more than 700 drugs are tested in the COVID-19 clinical trials, and full evaluation of their cardiotoxicity risks is in high demand. METHODS: We mainly focused on hydroxychloroquine (HCQ), one of the most concerned drugs for COVID-19 therapy, and investigated the effects and underlying mechanisms of HCQ on hERG channel via molecular docking simulations. We further applied the HEK293 cell line stably expressing hERG-wild-type channel (hERG-HEK) and HEK293 cells transiently expressing hERG-p.Y652A or hERG-p.F656A mutants to validate our predictions. Western blot analysis was used to determine the hERG channel, and the whole-cell patch clamp was utilized to record hERG current (IhERG). RESULTS: HCQ reduced the mature hERG protein in a time- and concentration-dependent manner. Correspondingly, chronic and acute treatment of HCQ decreased the hERG current. Treatment with brefeldin A (BFA) and HCQ combination reduced hERG protein to a greater extent than BFA alone. Moreover, disruption of the typical hERG binding site (hERG-p.Y652A or hERG-p.F656A) rescued HCQ-mediated hERG protein and IhERG reduction. CONCLUSION: HCQ can reduce the mature hERG channel expression and IhERG via enhancing channel degradation. The QT prolongation effect of HCQ is mediated by typical hERG binding sites involving residues Tyr652 and Phe656.

Comparison of outcomes between transcatheter tricuspid valve repair and surgical tricuspid valve replacement or repair in patients with tricuspid insufficiency.

BACKGROUND: Tricuspid regurgitation is associated with significant morbidity and mortality, but with limited treatment options. The objective of this study is to compare the demographic characteristics, complications, and outcomes of transcatheter tricuspid valve repair (TTVr) versus surgical tricuspid valve replacement (STVR) or surgical tricuspid valve repair (STVr), using real-world data from the National Inpatient Sample (NIS) database. METHODS AND RESULTS: Our study analyzed data from the National Inpatient Sample (NIS) database from 2016 to 2018 and identified 92, 86, and 84 patients with tricuspid insufficiency who underwent STVr, STVR, and TTVr, respectively. The mean ages of patients who received STVr, STVR, and TTVr were 65.03 years, 66.3 years, and 71.09 years, respectively, with TTVr patients significantly older than those who received STVr (P < 0.05). Patients who received STVr or STVR had higher mortality rates (8.7% and 3.5%, respectively) compared to those who received TTVr (1.2%). Patients who underwent STVr or STVR were also more likely to experience perioperative complications, including third-degree atrioventricular block (8.7% STVr vs. 1.2% TTVr, P = 0.329; 38.4% STVR vs. 1.2% TTVr, P < 0.05), respiratory failure (5.4% STVr vs. 1.2% TTVr, P = 0.369; 15.1% STVR vs. 1.2% TTVr, P < 0.05), respiratory complications (6.5% STVr vs. 1.2% TTVr, P = 0.372; 19.8% STVR vs. 1.2% TTVr, P < 0.05), acute kidney injury (40.2% STVr vs. 27.4% TTVr, P = 0.367; 34.9% STVR vs. 27.4% TTVr, P = 0.617), and fluid and electrolyte disorders (44.6% STVr vs. 22.6% TTVr, P = 0.1332; 50% STVR vs. 22.6% TTVr, P < 0.05). In addition, the average cost of care and the average length of hospital stay were higher for patients who underwent STVr or STVR than for those who received TTVr (USD$37995 ± 356008.523 STVr vs. USD$198397 ± 188943.082 TTVr, P < 0.05; USD$470948 ± 614177.568 STVR vs. USD$198397 ± 188943.082 TTVr, P < 0.05; 15.4 ± 15.19 STVr vs. 9.6 ± 10.21 days TTVr, P = 0.267; 24.7 ± 28.81 STVR vs. 9.6 ± 10.21 days TTVr, P < 0.05). CONCLUSION: TTVr has shown to have favorable outcomes compared to STVr or STVR, but more research and clinical trials are required to help formulate evidence-based guidelines for the role of catheter-based management in tricuspid valve disease.

A Retrospective Study to Evaluate the Role of Dynamic Fracture Mobility in the Conservative Treatment of Osteoporotic Vertebral Compression Fractures.

OBJECTIVE: To investigate whether dynamic fracture mobility could affect the outcome of conservative treatment in patients with acute osteoporotic vertebral compression fracture (OVCF). METHODS: A total of 158 patients who underwent conservative treatment in our hospital for painful OVCFs were included in this study and their data were retrospectively analyzed. According to the degree of pain relief, patients were divided into an excellent efficacy group and a poor efficacy group. Factors that may affect the outcome of conservative treatment were recorded for each patient. Variables with a statistical difference between the 2 groups were entered into multivariate logistic regression analysis to identify the factors influencing the outcome of conservative treatment. Receiver operating characteristic curve analysis was also performed. RESULTS: The result showed that dynamic fracture mobility, overweight, age, and bone mineral density (BMD) (all P < 0.001) were independent factors influencing the outcome of conservative treatment. Receiver operating characteristic curve analysis showed that the cutoff values for age and BMD that predicted treatment effect were 72.5 years and -3.30, respectively. CONCLUSIONS: This study confirmed that dynamic fracture mobility could be used as an independent factor predicting the outcome of conservative treatment in patients with acute OVCFs. It was also shown that overweight, age, and BMD were other independent factors influencing the outcome of conservative treatment. A comprehensive evaluation of these related factors can guide the doctor to take appropriate treatment for a unique acute OCVF.

Advanced glycation end products induce skeletal muscle atrophy and insulin resistance via activating ROS-mediated ER stress PERK/FOXO1 signaling.

Skeletal muscle atrophy is often found in patients with type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance. As the largest tissue in the body, skeletal muscle plays important roles in insulin resistance. Advanced glycation end products (AGEs) are a type of toxic metabolite that are representative of multiple pathophysiological changes associated with T2DM. Mice were exposed to AGEs. Forkhead box O1 (FOXO1) was silenced by using a constructed viral vector carrying siRNA. Skeletal muscle atrophy was evaluated by using hematoxylin-eosin (H&E), oil red O, myosin skeletal heavy chain (MHC), and laminin immunofluorescent stains. Reactive oxygen species (ROS) generation was assessed by using the dihydroethidium (DHE) stain. Western blotting was used to evaluate protein expression and phosphorylation. Insulin resistance was monitored via the insulin tolerance test and the glucose infusion rate (GIR). Mice exposed to AGEs showed insulin resistance, which was evidenced by reduced insulin tolerance and GIR. H&E and MHC immunofluorescent stains suggested reduced cross-sectional muscle fiber area. Laminin immunofluorescent and oil red O stains indicated increased intramuscular fibrosis and lipid deposits, respectively. Exposure to AGEs induced ROS generation, increased phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and FOXO1, facilitated FOXO1 nuclear translocation, and elevated expression of muscle atrophy F-box (MAFbx) in gastrocnemius muscle. foxo1 silencing significantly suppressed skeletal muscle atrophy and insulin resistance without affecting ROS production. AGEs exacerbated skeletal muscle atrophy and insulin resistance by activating the PERK/FOXO1 signaling pathway in skeletal muscle.NEW & NOTEWORTHY In this study, we proposed a molecular mechanism underlying the skeletal muscle atrophy-associated insulin resistance in type 2 diabetes mellitus (T2DM). Our investigation suggests that exposure to AGEs, which are characteristic metabolites of T2DM pathology, induces the activation of reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, leading to the upregulation of the protein kinase RNA-like ER kinase (PERK)/forkhead box O1 (FOXO1)/muscle atrophy F-box pathway and subsequent skeletal muscle atrophy, ultimately resulting in insulin resistance.

Transcatheter Mitral Valve Repair Versus Transcatheter Mitral Valve Replacement in Patients with Mitral insufficiency.

AIMS: Mitral regurgitation (MR) is the most prevalent form of valvular heart disease. Transcatheter mitral valve repair (TMVr) and transcatheter mitral valve replacement (TMVR) have recently emerged as alternatives to open heart surgical repair or replacement. However, studies on the comparative outcomes of TMVr and TMVR are limited. This study aims to compare the demographics, complications and outcomes of TMVr and TMVR based on a real-world investigation of the National Inpatient Sample (NIS) database. METHODS AND RESULTS: From 2016-2018 in the NIS database, a total of 210 and 3370 patients who underwent TMVR and TMVr, respectively, were selected. The mean age of the patients was 75.99 years (TMVr) and 69.6 years (TMVR) (p <0.01). The mortality of patients who received TMVR was higher compared to that of patients who were treated with TMVr (8.1 vs. 1.9%, p <0.01). The patients who underwent TMVR were more likely to suffer perioperative complications including blood transfusions (16.2 vs. 5.0%, p <0.01) and acute kidney injury (22.9 vs. 13.3%, p <0.01). The average cost of treatment was higher (USD $278864 vs. USD $216845, p <0.01), and the average duration of hospitalization was longer (8.73 vs. 4.17 d, p <0.01) for TMVR compared to TMVr. When taking into account perioperative comorbidities and other factors, TMVR was associated with a worse adjusted in-hospital mortality (odds ratio [OR], 3.307 [95% CI, 1.533-7.136]; p <0.01). CONCLUSION: TMVr is associated with lower mortality, peri-procedural morbidity, and resource use compared to TMVR. A patient-centered approach can help guide decision-making about the choice of intervention for the individual patient and more studies evaluating the long-term outcomes and durability of TMVR are needed at present.

Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway.

When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology. Cardiac phenotypic observations revealed that Trim44 knockout affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3ß/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.

Neutrophilic granulocyte percentage is associated with anxiety in Chinese hospitalized heart failure patients.

BACKGROUND: In patients with heart failure, anxiety disorder is common and associated with adverse prognosis. This study intended to find more confounding factors of Chinese heart failure patients. METHODS: We enrolled 284 hospitalized heart failure patients, whose New York Heart Association (NYHA) classed as II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. All the patients were scaled in Hamilton Rating Scale for Anxiety (14-items) (HAM-A14). Ordinal logistic regression analysis was performed to examine the association of correlated factors with anxiety disorder. RESULTS: There were 184 patients had anxiety accounting for 64.8% of all 284 hospitalized heart failure patients. The neutrophilic granulocyte percentage, urea nitrogen, total bilirubin and brain natriuretic peptide were positively associated with HAM-A14 score, meanwhile, the hemoglobin, red blood cells counts, albumin and LVEF were negatively associated with HAM-A14 score (All P < 0.05). After the adjustments of sex, hemoglobin, urea nitrogen, total bilirubin, albumin and brain natriuretic peptide, the neutrophilic granulocyte percentage was significantly associated with anxiety (OR = 43.265, P = 0.012). The neutrophilic granulocyte percentage was 0.616 ± 0.111, 0.640 ± 0.102, 0.681 ± 0.106 and 0.683 ± 0.113 in heart failure patients with no anxiety, possible anxiety, confirmed anxiety and obvious anxiety, respectively. CONCLUSIONS: Neutrophilic granulocyte percentage as well as the traditional risk factors such as sex, urea nitrogen and brain natriuretic peptide is associated with anxiety in hospitalized heart failure patients.

The Exosomal miR-1246 of Laryngeal Squamous Cell Carcinoma Induces Polarization of M2 Type Macrophages and Promotes the Invasiveness of Laryngeal Squamous Cell Carcinoma.

Background: The possible role and detailed mechanisms of Tumor-associated macrophages (TAMs) in laryngeal squamous cell carcinoma (LSCC) have not been revealed. Methods: The expressions of typical markers were evaluated by qRT-PCR. In macrophages cocultured with TU212 cells, CD163, and CD206 protein expressions were detected by western blot analysis; IL-10 and IL-12 expressions were detected by ELISA assay. Exosomes isolated from TU212 cells were characterized by TEM analysis. As for the TU212 cells cocultured with macrophages processed with HOK or TU212 cells derived exosomes, their viability, migration, and invasion were assessed by CCK-8 assay, wounding healing, and Transwell assays, respectively. Results: In this study, macrophages processed with exosomes from human TU212 cells notably advanced LSCC cell viability, migration, and invasion. miR-1246 inhibitor suppressed the M2 polarization of macrophages. Macrophages transfected with miR-1246 inhibitor suppressed LSCC cell viability, migration, and invasion. Conclusion: In summary, our data implied that the exosomal, miR-1246 of LSCC, induced polarization of M2 type macrophages and promoted the progression of LSCC. This trial is registered with 2020-13.