Myocardial Damage Research Articles

High Uric Acid Orchestrates Ferroptosis to Promote Cardiomyopathy Via ROS-GPX4 Signaling.

Aims: High uric acid (HUA), as a pro-oxidant, plays a significant role in the pathophysiology of cardiovascular disease. Studies have indicated that elevated uric acid levels can adversely affect cardiovascular health. Nevertheless, the impact of hyperuricemia on cardiomyopathy remains uncertain. Further research is needed to elucidate the relationship between HUA and cardiomyopathy, shedding light on its potential implications for heart health. Results: We demonstrated that uricase knockout (Uox-KO) mice accelerated the development of cardiomyopathy, causing significantly impaired cardiac function and myocardial fibrosis. Meanwhile, the mitochondrial morphology was destroyed, the lipid peroxidation products increased in number and the antioxidant function was weakened. In addition, we evaluated the effects of ferrostatin-1 (Fer-1), the ferroptosis inhibitor. Myocardial damage can be reversed by the Fer-1 treatment caused by HUA combined with doxorubicin (DOX) treatment. Benzbromarone, a uric acid-lowering drug, decreases myocardial fibrosis, and ferroptosis by alleviating hyperuricemia in Uox-KO mice by DOX administration. In vitro, we observed that the activity of cardiomyocytes treated with HUA combined with DOX decreased significantly, and lipid reactive oxygen species (ROS) increased significantly. Afterward, we demonstrated that HUA can promote oxidative stress in DOX, characterized by increased mitochondrial ROS, and downregulate protein levels of glutathione peroxidase 4 (GPX4). N-acetyl-l-cysteine, an antioxidant, inhibits the process by which HUA promotes DOX-induced ferroptosis by increasing the GPX4 expression. Innovation: We verified that HUA can exacerbate myocardial damage. This has clinical implications for the treatment of cardiac damage in patients with hyperuricemia. Conclusions: Our data suggested that HUA promotes the cardiomyopathy. HUA promotes DOX-induced ferroptosis by increasing oxidative stress and downregulating GPX4. Antioxid. Redox Signal. 00, 00-00.

Evaluation of Right Ventricular Myocardial Properties Using Systolic Myocardial T1 Mapping.

Introduction Myocardial properties can be quantitatively evaluated using myocardial native T1 values (nT1) obtained using cardiac magnetic resonance imaging (CMR). In terms of myocardial wall thickness, the left ventricular nT1 is easy to measure, but the right ventricular nT1 is difficult. Patients with congenital heart disease often develop right ventricular overload. If right ventricular nT1 can be measured consistently, inflammation and fibrosis of the right ventricular myocardium can be quantitatively evaluated. We aimed to determine whether T1 mapping during systole can be used to evaluate right ventricular myocardial properties. Methods T1 mapping was performed at diastole and systole. Systolic T1 mapping was calculated from diastolic T1 mapping and cine images. The myocardial properties of both ventricles were evaluated in 13 healthy volunteers (21-26 years old) and 12 patients with right ventricular overload (12-41 years old) who underwent CMR examination at our hospital. Results From the analysis of left ventricular nT1, we found that nT1 did not change significantly during the cardiac cycle. However, right ventricular nT1 changed between diastole and systole because the right ventricle is affected by blood. Although there was no difference in right ventricular diastolic nT1 between the patients and volunteers (1,346.8 vs. 1,347.6 ms, p = 0.852), the right ventricular systolic nT1 was significantly higher in patients than in volunteers (1,312.7 vs. 1,233.8 ms, p = 0.002). This indicates that right ventricular myocardial damage occurs in patients with right ventricular overload. Conclusion Systolic right ventricular myocardial T1 mapping allows assessment of right ventricular myocardial properties. The right ventricular myocardial systolic nT1 is useful for evaluating myocardial damage due to right ventricular stress and myocardial injury. Measuring right ventricular nT1 may allow consideration of early therapeutic intervention.

Antioxidative and cardioprotective effects of minocycline in ischemia/reperfusion injury in experimental model of hypertension.

Cardiovascular diseases remains leading cause of death and disabilities. Coronary artery occlusion and consequent ischemia leads to acute myocardial infarction, but restoration of blood flow, paradoxically, provokes further myocardial damage known as reperfusion injury. Minocycline is possessing anti-inflammatory and anti-apoptotic activity, immune-modulating and antioxidative properties besides its primary antibacterial effect. Recently it gained significant interest in preventing cardiac damage especially due to myocardial ischemia/reperfusion injury (MI/RI). The aim of this study was to assess the protective ability of pre-treatment and post-treatment of isolated hearts from healthy and spontaneously hypertensive rats with minocycline, on functional recovery and redox status after MI/RI using Langendorff technique. Using sensor in the left ventricle, the cardiodynamic parameters were recorded and in the samples of the coronary venous effluent oxidative stress biomarkers were analyzed. Minocycline was injected directly into the coronary vessels, in pre-treatment 5min before global ischemia, and in post-treatment during the first 5min of reperfusion. Changes in redox balance induced by minocycline were more prominent in post-treatment fashion of application. Cardioprotective effects of minocycline due to MI/RI are even more significant in hypertensive hearts. Minocycline showed significant cardioprotective effects, which was more pronounced in hypertensive compared to healthy hearts. Reduction of pro-oxidative biomarkers was more prominent in hypertensive hearts compared to the normotensive, especially if it is applied in the form of post-treatment. Minocycline could be important tool in reduction of heart damage induced by MI/RI due to its antioxidative potential, if these results are confirmed by clinical study.

Enhanced detection of damaged myocardium and risk stratification in hypertrophic cardiomyopathy using integrated [68Ga]Ga-FAPI-04 PET/CMR imaging.

This study aims to explore the correlation between PET and CMR in integrated [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging and its value in the diagnosis and risk assessment of hypertrophic cardiomyopathy (HCM). This study included 20 HCM patients and 11 age- and gender-matched controls. PET analysis evaluated left ventricular (LV) [68Ga]Ga-FAPI-04 uptake, including SUVmax, TBR, cardiac fibroblast activity (CFA) and volume (CFV), and total SUV of the 16 segments. CMR tissue characterization parameters included cardiac function, myocardial thickness, late gadolinium enhancement (LGE), relaxation time, extracellular volume (ECV), and peak strain parameters. The 5-year sudden cardiac death (SCD) risk score and the 2-year and 5-year atrial fibrillation (AF) risk scores were calculated for each patient. The study analyzed differences between HCM patients and controls, the correlation between [68Ga]Ga-FAPI-04 PET and concurrent CMR imaging results, and the predictive value of PET/CMR. The FAPI uptake, myocardial mass, myocardial thickness, and T1/T2 mapping values were significantly higher in HCM patients compared to controls. Twenty HCM patients and their 320 myocardial segments were discussed. Increased [68Ga]Ga-FAPI-04 uptake in the left ventricular wall was observed in 95% (19/20) of the patients, covering 48.8% (156/320) of the segments. On concurrent CMR, 80% (16/20) of the patients showed LGE, including 95 (29.7%) segments. The FAPI(+)LGE(+) segments exhibited the highest myocardial PET uptake, greatest thickness, longest T1/T2 native values, largest ECV value and the greatest loss of myocardial strain capacity (P < 0.05). There was a significant correlation between FAPI uptake and CMR parameters (P < 0.05). Higher [68Ga]Ga-FAPI-04 uptake showed a positive correlation with SCD and AF risk scores (P < 0.05). The number of LGE(+) segments, mapping parameters, and ECV values in CMR also had prognostic significance. Combining PET with CMR aided in further risk stratification of HCM. [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging has potential value in the detection of damaged myocardial lesions and risk assessment of HCM patients. [68Ga]Ga-FAPI-04 PET can detect more affected myocardium compared to CMR, and segments with abnormalities in both PET and CMR show more severe myocardial damage.

In-silico binding affinity of a phage display library screened novel peptide against various FABPs.

In accordance to the American Heart Association (AHA), cardiovascular diseases (CVDs) are the leading cause of death around the globe, causing more than 19.1million deaths in 2020. Heart-type fatty acid binding protein (H-FABP) is required for the metabolism of fatty acids (FA) inside cardiomyocytes is reported as a biomarker for myocardial damage. As early as one hour after an Acute myocardial infarction (AMI), H-FABP can be used to detect myocardial ischemia. Thus, H-FABP based detection can reduce the burden on the emergency department. A peptide-based detection system can provide point-of-care diagnostics for CVDs. There is a lot of research being done on peptide-based detection, and it has a lot of potential to help with unmet medical diagnostic needs. A twelve (12) amino acid peptide has been discovered using Phage Display Library Screening. The affinity of peptide with H-FABP and other FABPs has been done using molecular docking and ADMET profile has been done. Molecular docking of small peptides against the target protein can play a crucial role in recognizing peptide binding sites and poses. The docking study was done using the HDOCK server and the visualization of the docked complex was done using Pymol and UCSF chimera. The molecular simulation study of three protein-peptide complexes were done which also validated the binding affinity of peptide with the proteins. The RMSD, RMSF and radius of gyration are also analyzed. The results indicate that H-FABP shows higher level of binding interaction with the peptide having bond length ranging from 2.3 to 3.4 Å. The screened peptide is suitable for H-FABP binding and can be used for prognosis purposes in the heart ischemic conditions.

Role of Cathelicidins in Atherosclerosis and Associated Cardiovascular Diseases

Cathelicidins (human LL-37 and rat CRAMP) are multifunctional peptides involved in various cardiovascular conditions. This review integrates the recent findings about the functional involvement of LL-37/CRAMP across atherosclerosis, acute coronary syndrome, myocardial infarction, heart failure, diabetic cardiomyopathy, and platelet aggregation/thrombosis. In atherosclerosis, LL-37 interacts with scavenger receptors to modulate lipid metabolism and binds with mitochondrial DNA and lipoproteins. In acute coronary syndrome, LL-37 influences T cell responses and mitigates calcification within atherosclerotic plaques. During myocardial infarction and ischaemia/reperfusion injury, LL-37/CRAMP exhibits dual roles: protecting against myocardial damage through the AKT and ERK1/2 signalling pathways, while exacerbating inflammation via TLR4 and NLRP3 inflammasome activation. In heart failure, LL-37/CRAMP attenuates hypertrophy and fibrosis via NF-κB inhibition and the activation of the IGFR1/PI3K/AKT and TLR9/AMPK pathways. Moreover, in diabetic cardiomyopathy, these peptides alleviate oxidative stress and fibrosis by inhibiting TGFβ/Smad and AMPK/mTOR signalling and provide anti-inflammatory effects by reducing NF-κB nuclear translocation and NLRP3 inflammasome formation. LL-37/CRAMP also modulates platelet aggregation and thrombosis through the FPR2 and GPVI receptors, impacting apoptosis, autophagy, and other critical cellular processes. This comprehensive overview underscores LL-37/CRAMP as a promising therapeutic target in cardiovascular diseases, necessitating further elucidation of its intricate signalling networks and biological effects for clinical translation.

Endosomal Toll-Like Receptors intermediate negative impacts of viral diseases, autoimmune diseases, and inflammatory immune responses on the cardiovascular system.

Cardiovascular disease (CVD) is the leading cause of morbidity globally, with chronic inflammation as a key modifiable risk factor. Toll-like receptors (TLRs), pivotal components of the innate immune system, including TLR-3, -7, -8, and -9 within endosomes, trigger intracellular cascades, leading to inflammatory cytokine production by various cell types, contributing to systemic inflammation and atherosclerosis. Recent research highlights the role of endosomal TLRs in recognizing self-derived nucleic acids during sterile inflammation, implicated in autoimmune conditions like myocarditis. This review explores the impact of endosomal TLRs on viral infections, autoimmunity, and inflammatory responses, shedding light on their intricate involvement in cardiovascular health and disease by examining literature on TLR-mediated mechanisms and their roles in CVD pathophysiology. Removal of endosomal TLRs mitigates myocardial damage and immune reactions, applicable in myocardial injury. Targeting TLRs with agonists enhances innate immunity against fatal viruses, lowering viral loads and mortality. Prophylactic TLR agonist administration upregulates TLRs, protecting against fatal viruses and improving survival. TLRs play a complex role in CVDs like atherosclerosis and myocarditis, with therapeutic potential in modulating TLR reactions for cardiovascular health.

First time ACS in patients with on-target lipid levels: Inflammation at admission and re-event rate at follow-up.

Dyslipidaemia, inflammation and elevated Lp(a) levels are associated with the progression of atherosclerosis. This study investigates whether patients with a first-time presentation of chest pain and on-target LDL-C levels and intermediate FRS/ESC-Score risks, display a high inflammatory burden linked to myocardial injury and whether inflammation at admission affects the re-event rate up to 6 years follow-up. Blind assessments of novel inflammatory markers such as Glycoprotein A and B via nuclear magnetic resonance (NMR), cytokines, hsCRP, Neutrophil-to-Lymphocyte ratio (NLR) and Lipoprotein(a) levels were examined. Out of 198 chest pain patients screened, 97 met the inclusion criteria at admission. cTnI(+) patients (>61 ng/L) with elevated Lipoprotein(a), showed significantly increased levels of Glycoprotein A and B, hsCRP, IL-6, a high NLR and a reduced left ventricular ejection fraction (%) compared to cTnI(-) individuals. Those patients, with a higher inflammatory burden at hospital admission (hsCRP, IL-6, Glycoprotein A and B, and Lipoprotein(a)) had a higher re-event rate at follow-up. Inflammation and Lipoprotein(a) levels were particularly prominent in patients presenting with reduced left ventricular ejection fraction. Notably, Glycoproteins A/B emerge as novel markers of inflammation in these patients. Our study highlights the significantly higher impact of inflammatory burden in patients with chest pain and high level of myocardial damage than in those with lower myocardial affectation, even when they all had lipid levels well controlled. Inflammation at the time of admission influenced the re-event rate over a follow-up period of up to 6 years.

Clinical utility of ambulatory ECG monitoring and 2D-ventricular strain for evaluation of post-COVID-19 ventricular arrhythmia

BackgroundA relatively common complication of COVID -19 infection is arrhythmia. There is limited information about myocardial deformation and heart rate variability (HRV) in symptomatic post COVID patients presented by ventricular arrhythmia.Aim of the studyOur goal was to assess 2D-ventricular strain and heart rate variability indices (evaluated by ambulatory ECG monitoring) in post-COVID-19 patients suffering from ventricular arrhythmia.MethodsThe current observational case–control study performed on 60 patients one month after they had recovered from the COVID-19 infection. Thirty healthy volunteers served as the control group. Each participant had a full medical history review, blood tests, a 12-lead surface electrocardiogram (ECG), 24-h ambulatory ECG monitoring, and an echo-Doppler examination to evaluate the left ventricular (LV) dimensions, tissue Doppler velocities, and 2D-speckle tracking echocardiography (2D-STE) for both the LV and right ventricular (RV) strain.ResultsSymptomatic post-COVID patients with monomorphic premature ventricular contractions (PVCs) showed a substantial impairment of LV/RV systolic and diastolic functions, LV/RV myocardial performance (MPI) with reduced indices of HRV. Patients with higher versus lower ventricular burden had poorer functional status, higher levels of inflammatory biomarkers and reduced parameters of HRV (New York Heart Association (NYHA) class: 2.1 ± 0.9 vs. 1.5 ± 0.6, p < 0.001, C-reactive protein (CRP): 13.3 ± 4.1 vs. 8.3 ± 5.9 mg/L, p < 0.0001, low frequency/high frequency (LF/HF): 3.6 ± 2.4 vs. 2.2 ± 1.2, p < 0.002, the root mean square of the difference between successive normal intervals (rMSSD): 21.8 ± 4.7 vs. 29.3 ± 14.9 ms, p < 0.039 and the standard deviation of the RR interval (SDNN): 69.8 ± 19.1 vs.108.8 ± 37.4 ms, p < 0.0001). The ventricular burden positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.33, p < 0.001), CRP (r = 0.60, p < 0.0001), while it negatively correlated with LV-global longitudinal strain (GLS) (r = -0.38, p < 0.0001), and RV-GLS (r = -0.37, p < 0.0001).ConclusionsPatients with post-COVID symptoms presented by ventricular arrhythmia had poor functional status. Patients with post-COVID symptoms and ventricular arrhythmia had subclinical myocardial damage, evidenced by speckle tracking echocardiography while having apparently preserved LV systolic function. The burden of ventricular arrhythmia in post-COVID patients significantly correlated with increased inflammatory biomarkers and reduced biventricular strain.

Impact of Different Emergency Treatment Methods on Prognosis of Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Retrospective Study

Purpose: This study aimed to investigate the impact of different emergency treatment methods on the prognosis of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Methods: A retrospective study was conducted involving 114 patients admitted to the hospital between January 2022 and December 2022. The patients were divided into two groups based on their emergency treatment methods: First Transport and Then Treatment Group (n = 56) and Treatment Before Transport Group (n = 58). Baseline characteristics, biomarker levels, echocardiographic findings, curative effects, and 1-year follow-up outcomes were compared between the two groups. Results: Biomarker levels and echocardiographic parameters differed significantly between the two groups, thus indicates potential variations in disease severity and prognosis. Moreover, the 1-year follow-up outcomes showed higher rates of all-cause mortality (16.07% vs. 3.45%, p = 0.022), recurrent myocardial infarction (19.64% vs. 5.17%, p = 0.019), rehospitalization for cardiovascular causes (25.05% vs. 8.62%, p = 0.019), and PCI for new lesions (23.21% vs. 6.92%, p = 0.014) in the First Transport and Then Treatment Group compared with the Treatment Before Transport Group. Conclusion: The timing of emergency treatment methods in patients with AMI undergoing PCI appeared to significantly impact clinical outcomes, echocardiographic parameters, and 1-year follow-up outcomes. Immediate administration of treatment before transport showed potential benefits in mitigating myocardial damage and improving long-term prognosis compared with the approach of transporting the patient to the healthcare facility before initiating treatment.

The correlation between indicators of time intervals of left ventricular activity and markers of myocardial damage in patients with non-ST-segment elevation acute coronary syndrome

The correlation between indicators of time intervals of left ventricular activity and markers of myocardial damage in patients with non-ST-segment elevation acute coronary syndrome

Prognostic Role of Tissue Iron Deficiency Measured by sTfR Levels in Heart Failure Patients without Systemic Iron Deficiency or Anemia.

Background. Iron deficiency (ID) is a significant, high-prevalence comorbidity in chronic heart failure (HF) that represents an independent predictor of a worse prognosis. However, a clear-cut diagnosis of ID in HF patients is not assured. The soluble transferrin receptor (sTfR) is a marker that reflects tissue-level iron demand and may be an early marker of ID. However, the impact of sTfR levels on clinical outcomes in non-anemic HF patients with a normal systemic iron status has never been evaluated. Methods. This is a post hoc analysis of an observational, prospective cohort study of 1236 patients with chronic HF of which only those with normal hemoglobin levels and a normal systemic iron status were studied. The final cohort consisted of 215 patients. Tissue ID was defined as levels of sTfR > 75th percentile (1.65 mg/L). Our aim was to describe the association between sTfR and clinical outcomes (all-cause death and HF hospitalization) and to explore its association with a wide array of serum biomarkers. Results. The sTfR level (HR 1.48, 95% CI 1.13-1.96, p = 0.005) and tissue ID (HR 2.14, 95% CI 1.22-3.75, p = 0.008) was associated with all-cause death. However, we found no association between sTfR levels and the risk of HF hospitalization. Furthermore, high sTfR levels were associated with a worse biomarker profile indicating myocardial damage (troponin and NT-proBNP), systemic inflammation (CRP and albumin), and impaired erythropoiesis (erythropoietin). Conclusions. In this cohort, the presence of tissue ID defined by sTfR levels is an independent factor for all-cause death in patients with normal systemic iron parameters.

GDF15 attenuates sepsis-induced myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the SOCS1/GPX4 signaling pathway

Sepsis is a systemic inflammatory response syndrome triggered by infection, presenting with symptoms such as fever, increased heart rate, and low blood pressure. In severe cases, it can lead to multiple organ dysfunction, posing a life-threatening risk. Sepsis-induced cardiomyopathy (SIC) is a critical factor in the poor prognosis of septic patients, leading to myocardial dysfunction characterized by cell death, inflammation, and diminished cardiac function. Ferroptosis, an iron-dependent form of programmed cell death, is a key mechanism causing cardiomyocyte damage in SIC. Growth differentiation factor 15 (GDF15), a member of the TGF-β superfamily, is associated with various cardiovascular diseases and can inhibit oxidative stress, reduce reactive oxygen species (ROS), and suppress ferroptosis. Elevated serum GDF15 levels in sepsis are correlated with organ injuries, suggesting its potential as a therapeutic target. However, its role and mechanisms in SIC remain unclear. Glutathione peroxidase 4 (GPX4), the only enzyme capable of reducing lipid peroxides within cells, protects cells by reducing lipid peroxidation levels and inhibiting ferroptosis. Investigating the regulatory factors of GPX4 may provide a theoretical basis for SIC treatment. In this study, a mouse SIC model revealed that elevated GDF15 exerts a protective effect. Antagonizing GDF15 exacerbates myocardial damage. Through transcriptomic analysis and other methods, we confirmed that GDF15 inhibits the expression of SOCS1 by activating the ALK5-SMAD2/3 pathway, thereby activates the JAK2/STAT3 pathway, promotes the transcription of GPX4, inhibits ferroptosis in cardiomyocytes, and plays a myocardial protective role in SIC.

In-Hospital Mortality in Patients With Acute Myocardial Infarction: A Literature Overview.

Acute myocardial infarction (AMI) continues to be a predominant cause of global morbidity and mortality, with in-hospital mortality (IHM) serving as a pivotal metric for patient outcomes. This review explores the influence of several clinical variables on IHM in individuals with AMI. Factors such as age, gender, body mass index (BMI), smoking habits, existing comorbidities, prior coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), and biomarkers, including high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase MB (CK-MB), significantly affect the prognosis of the patient. Advanced age and comorbid conditions such as diabetes and hypertension exacerbate myocardial damage and systemic impacts, thus increasing IHM. Gender and BMI are also critical, and women and patients with obesity face different risks. Smoking increases both the risk of AMI and IHM, underscoring the importance of cessation interventions. ST-elevation myocardial infarctionis associated with elevated IHM and requires immediate reperfusion therapy, while non-ST-elevation myocardial infarctionrequires customized management for risk assessment. Previous CABG and PCI add complexity to AMI treatment and elevate IHM due to pre-existing coronary pathology and the intricacies of the procedures involved. The application of biomarker-centered techniques facilitates the swift identification of individuals at elevated risk, improves therapeutic planning, and reduces IHM for patients with AMI. Understanding and incorporating these clinical determinants are essential to optimize the management of AMI, minimize IHM, and improve patient outcomes. This all-encompassing strategy requires ongoing research, quality improvement efforts, and personalized care approaches.

Mycoplasma pneumoniae infection outbreak in Guangzhou, China after COVID-19 pandemic

BackgroundsMycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic.MethodsThroat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020–2022 and after COVID-19 pandemic (2023).ResultsM. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236).ConclusionOutbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.

Impact of early myocardial injury on patients with severe pneumonia.

Pneumonia often causes myocardial damage. This study sought to understand how early myocardial injury affects severe pneumonia patients' prognoses. This multi-center prospective cohort study from March 2020 to October 2023 comprised severe pneumonia patients. Binary logistic regression analysis examined how myocardial damage affects cardiac complications and acute renal injury (AKI). We used Spearman correlation analysis to examine the relationship between troponin I levels and the vasoactive inotropic score (VIS) in shock patients with myocardial injury. We used the Kaplan-Meier survival curve to evaluate the impact of myocardial injury on 30-day and 1-year survival rates. Mediation investigations examined how AKI and cardiac complications mediate myocardial injury and death. This study included 363 severe pneumonia patients, of whom 204 (56.2%) developed myocardial damage, 132 (36.4%) had cardiac problems, and 146 (40.2%) had AKI. Myocardial damage independently elevated the incidence of cardiac complications (OR = 2.548, 95% CI = 1.404-4.303, P = 0.002) and AKI (OR = 1.946, 95% CI = 1.177-3.219, P = 0.009). There was a positive link between troponin I and VIS in myocardial injury and shock patients (r = 0.43, P < 0.001). COX regression found myocardial injury to be a death risk (HR = 1.472, 95% CI = 1.043-2.077, P = 0.028). Adjusted Kaplan-Meier survival analysis showed significantly decreased short-term and long-term survival rates with myocardial injury (log-rank test P < 0.05). The mediation study showed that cardiac complications and AKI mediated myocardial injury and death by 19.30% and 17.18%, respectively. Early myocardial injury in severe pneumonia patients raises the likelihood of cardiac problems, AKI, and refractory shock, reducing short- and long-term survival.

Preliminary analysis of PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for local advanced non-small cell lung cancer (NSCLC).

200 Background: The benefits of neoadjuvant immunotherapy and chemotherapy for resectable NSCLC suggest that this combined treatment may provide more surgical opportunities and survival benefits for potentially resectable locally advanced NSCLC. Methods: We retrospectively collected data from 28 patients with stage III EGFR/ALK/ROS wild-type NSCLC. Eligible patients received 2-8 cycles of neoadjuvant chemoimmunotherapy (squamous carcinoma: PD-1 inhibitor combined with albumin-bound paclitaxel and cisplatin/carboplatin; adenocarcinoma: PD-1 inhibitor combined with pemetrexed and carboplatin), followed by re-evaluation for surgery. Afterwards, patients underwent surgery after downstaging, with some receiving adjuvant immunotherapy maintenance for one year. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: All 28 patients were male, with 7 (25%) in stage IIIA, 10 (35.7%) in IIIB, 4 (14.3%) in IIIC, 2 (7.14%) in IVA, and 2 (7.14%) in IVB. There were 22 cases of squamous cell carcinoma, 4 of adenocarcinoma, 1 of large cell lung cancer, and 1 of lymphoepithelioma-like carcinoma. 23 patients (82.1%) completed neoadjuvant treatment and underwent resection, achieving 100% R0 resection rate (23/23); 5 patients did not undergo surgery, 3 of whom received combined radiochemotherapy due to disease progression, 1 delayed surgery due to immunotherapy associated myocardial damage, and 1 died from massive hemoptysis and hemorrhagic shock. The objective response rate (ORR) was 60.7%, 95%CI [40.6-78.5%] and the disease control rate (DCR) was 85.7%, 95%CI [67.3-96.0%]. Among the 23 patients who underwent surgery, the pCR was 60.9%, 95%CI [38.5-80.3%], MPR was 4.3%, 95%CI [0.1-21.9%], clinical downstaging rate was 50%, 95%CI [30.6-69.4%] and pathological downstaging rate was 86.9%, 95%CI [66.4-97.2%]. 17 patients (77.3%) underwent lobectomy, and 5 (22.7%) underwent bilobectomy with a median blood loss of 100 ml, IQR [55.0-100]. There were no surgery-related deaths. Postoperatively, one patient developed chylothorax, one had a lung infection, and the two improved after conservative treatment. 11 patients (47.8%) received post-surgery immunotherapy maintenance, and 2 of them (8.7%) developed immune-related pneumonia. As of April 7, 2024, the median follow-up time was 21.5 months (95%CI: 17-34 Mo), At 12 months。 PFS rate was 82.1% (95%CI: 69.1-97.6%); OS rate was 96.3% (95%CI: 89.4-100%). Conclusions: Neoadjuvant immunotherapy combined with surgery for unresectable locally advanced NSCLC may benefit patients and significantly extend survival.

Alchemilla vulgaris modulates isoproterenol-induced cardiotoxicity: interplay of oxidative stress, inflammation, autophagy, and apoptosis.

Introduction: Isoproterenol (ISO) is regarded as an adrenergic non-selective β agonist. It regulates myocardial contractility and may cause damage to cardiac tissues. Alchemilla vulgaris (AV) is an herbal plant that has garnered considerable attention due to its anti-inflammatory and antioxidant bioactive components. The present investigation assessed the cardioprotective potential of AV towards ISO-induced myocardial damage. Methods: Four groups of mice were utilized: control that received saline, an ISO group (85mg/kg, S.C.), ISO + AV100, and ISO + AV200 groups (mice received 100 or 200mg/kg AV orally along with ISO). Results and discussion: ISO induced notable cardiac damage demonstrated by clear histopathological disruption and alterations in biochemical parameters. Intriguingly, AV treatment mitigates ISO provoked oxidative stress elucidated by a substantial enhancement in superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione (GSH) content, as well as a considerable reduction in malondialdehyde (MDA) concentrations. In addition, notable downregulation of inflammatory biomarkers (IL-1β, TNF-α, and RAGE) and the NF-κB/p65 pathway was observed in ISO-exposed animals following AV treatment. Furthermore, the pro-apoptotic marker Bax was downregulated together with autophagy markers Beclin1 and LC3 with in ISO-exposed animals when treated with AV. Pre-treatment with AV significantly alleviated ISO-induced cardiac damage in a dose related manner, possibly due to their antioxidant and anti-inflammatory properties. Interestingly, when AV was given at higher doses, a remarkable restoration of ISO-induced cardiac injury was revealed.

Mitochondrial Function After Normothermic Regional Perfusion or Direct Procurement Followed by Hypothermic Oxygenated Machine Perfusion in Heart Transplantation After Circulatory Death.

Strategies to minimize ischemic damage during heart transplantation (HTX) by donation after circulatory death (DCD) are warranted because the inevitable ischemic injury linked to DCD HTX deteriorates mitochondrial respiratory capacity and ultimately graft quality. This study aimed to examine the myocardial mitochondrial function during DCD HTX with hypothermic oxygenated machine perfusion (HOPE) and compare the effect of normothermic regional perfusion (NRP) with that of direct procurement and perfusion (DPP). A porcine DCD HTX model was used with hearts subjected to either DPP (n = 6) or NRP (n = 7) followed by HOPE and orthotopic HTX. Mitochondrial respiratory function was analyzed by high-resolution respirometry in left ventricle biopsies at baseline, after 180 min of HOPE, and after 60 min of reperfusion post-HTX. Mitochondrial oxidative phosphorylation (P = 0.0008), respiratory control ratio (P = 0.04), and coupling efficiency (P = 0.04) declined during DCD HTX. Fatty acid oxidation was preserved after 3 h of HOPE with a modest, statistically nonsignificant decline after reperfusion (P = 0.2). Oxidative phosphorylation was inversely correlated with troponin-T levels (r = -0.70, P = 0.0004). No statistically significant difference in mitochondrial respiratory capacity was observed between participants exposed to NRP and DPP. Mitochondrial respiratory capacity declined gradually throughout the course of DCD HTX and correlated with the degree of myocardial damage. Following HOPE, the extent of mitochondrial deterioration was comparable between NRP and DPP.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.