Successful emergency surgical intervention in acute non-STsegment elevation myocardial infarction with rupture:A case report

BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular free wall rupture(FWR)occurs in approximately 2%of AMI patients and is notably rare in patients with non-STEMI.Types of cardiac rupture include left ventricular FWR,ventricular septal rupture,and papillary muscle rupture.The FWR usually leads to acute cardiac tamponade or electromechanical dissociation,where standard resuscitation efforts may not be effective.Ventricular septal rupture and papillary muscle rupture often result in refractory heart failure,with mortality rates over 50%,even with surgical or percutaneous repair options.CASE SUMMARY We present a rare case of an acute non-STEMI patient who suffered sudden FWR causing cardiac tamponade and loss of consciousness immediate before undergoing coronary angiography.Prompt resuscitation and emergency open-heart repair along with coronary artery bypass grafting resulted in successful patient recovery.CONCLUSION This case emphasizes the risks of AMI complications,shares a successful treatment scenario,and discusses measures to prevent such complications.

Hemogram-derived ratios as prognostic markers for major adverse cardiovascular events in patients with non-ST-segment elevation myocardial infarction

BACKGROUND Non-ST segment elevation myocardial infarction(NSTEMI)poses significant challenges in clinical management due to its diverse outcomes.Understanding the prognostic role of hematological parameters and derived ratios in NSTEMI patients could aid in risk stratification and improve patient care.AIM To evaluate the predictive value of hemogram-derived ratios for major adverse cardiovascular events(MACE)in NSTEMI patients,potentially improving clinical outcomes.METHODS A prospective,observational cohort study was conducted in 2021 at the Internal Medicine Clinic of the University Hospital in Tuzla,Bosnia and Herzegovina.The study included 170 patients with NSTEMI,who were divided into a group with MACE and a control group without MACE.Furthermore,the MACE group was subdivided into lethal and non-lethal groups for prognostic analysis.Alongside hematological parameters,an additional 13 hematological-derived ratios(HDRs)were monitored,and their prognostic role was investigated.RESULTS Hematological parameters did not significantly differ between non-ST segment elevation myocardial infarction(NSTEMI)patients with MACE and a control group at T1 and T2.However,significant disparities emerged in HDRs among NSTEMI patients with lethal and non-lethal outcomes post-MACE.Notably,neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)were elevated in lethal outcomes.Furthermore,C-reactive protein-to-lymphocyte ratio(CRP/Ly)at T1(>4.737)demonstrated predictive value[odds ratio(OR):3.690,P=0.024].Both NLR at T1(>4.076)and T2(>4.667)emerged as significant predictors,with NLR at T2 exhibiting the highest diagnostic performance,as indicated by an area under the curve of 0.811(95%CI:0.727-0.859)and OR of 4.915(95%CI:1.917-12.602,P=0.001),emphasizing its important role as a prognostic marker.CONCLUSION This study highlights the significant prognostic value of hemogram-derived indexes in predicting MACE among NSTEMI patients.During follow-up,NLR,PLR,and CRP/Ly offer important insights into the inflammatory processes underlying cardiovascular events.

Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals

Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.

Bivalirudin for anticoagulation in elderly acute coronary syndrome:Effects on myocardial microcirculation and adverse events

The management of acute coronary syndrome(ACS)in older patients remains challenging because standard anticoagulants often fail to yield optimal outcomes.Bivalirudin,a direct inhibitor of thrombin,serves as an alternative to traditional therapies.This drug is particularly effective in enhancing myocardial microcircu-lation and reducing adverse events after clinical interventions.The present article explores the findings of a recent study that highlighted the clinical benefits of bivalirudin by investigating its effects on myocardial microcirculation and adverse cardiac events after percutaneous coronary intervention in older patients with ACS.Compared with unfractionated heparin,bivalirudin markedly reduced the emergency response time and improved cardiac function indicators.It further mitigated the risks of cardiovascular events and recurrent myocardial infarctions.These findings suggest that bivalirudin can enhance myocardial perfusion and reduce bleeding complications,thus serving as a safe,effective anticoagulation agent for older patients with ACS.Nonetheless,further large-scale,high-quality trials are needed to establish optimal usage guidelines and assess long-term outcomes.Integrating bivalirudin into ACS treatment protocols for older patients may help optimize patient care,balancing efficacy and safety.Continual research and consensus building are necessary for the widespread clinical application of bivalirudin and the improvement of ACS outcomes in older patients.

Glycemic Control and Diabetes Duration in Relation to Subsequent Myocardial Infarction among Patients with Coronary Heart Disease and Type 2 Diabetes

Objective This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction(MI)in patients with both coronary heart disease(CHD)and type 2 diabetes(T2D).Methods We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen,China.Patients were categorized into 6 groups based on baseline fasting plasma glucose(FPG)levels and diabetes duration(from the date of diabetes diagnosis to the baseline date)to examine their combined effects on subsequent MI.Cox proportional hazards regression models were used,with further stratification by age,sex,and comorbidities to assess potential interactions.Results Over a median follow-up of 2.4 years,2,110 patients experienced MI.Compared to those with optimal glycemic control(FPG<6.1 mmol/L)and shorter diabetes duration(<10 years),the fullyadjusted hazard ratio(HR)(95%Confidence Interval[95%CI])for those with a diabetes duration of≥10 years and FPG>8.0 mmol/L was 1.93(95%CI:1.59,2.36).The combined effects of FPG and diabetes duration on MI were largely similar across different age,sex,and comorbidity groups,although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation.Conclusion Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D.Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.

Functional metabolomics analysis of the protective mechanism of total flavonoids of Scutellaria baicalensis on acute myocardial ischemia rats

Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats were divided into the Control,Model,AMI positive control(Propranolol hydrochloride,30 mg/kg),low dose TFSB(50 mg/kg),and high dose TFSB(100 mg/kg)groups.Rats received the corresponding treatment by intragastric administration once daily for 10 consecutive days.Electrocardiogram,myocardial enzyme,triphenyltetrazolium chloride staining,hematoxylin-eosin,and enzyme-linked immunosorbent assay were performed to evaluate the protective effect of TFSB on AMI rats.Then,the UHPLC-Q-Orbitrap MS method based on serum metabolomics was utilised to search for metabolic biomarkers and metabolic pathways.Subsequently,Western blot and RT-PCR techniques were employed to identify the respective genes and proteins.Results:Pharmacodynamics revealed that TFSB could ameliorate AMI in rats.The results of the metabolomics analysis indicated that the alterations in metabolic profile observed in rats with AMI were partially improved by treatment with TFSB.Moreover,the mRNA expression levels of 5-lipoxygenase(5-LOX)and 15-lipoxygenase(15-LOX)and the protein expression levels of 5-LOX,15-LOX,interleukin-1β(IL-1β),and NF-κB p65 were reduced following treatment with TFSB.Conclusion:The potential treatment of TFSB in AMI may be ascribed to its ability to regulate arachidonic acid metabolism.

Effect of bivalirudin on myocardial microcirculation and adverse events after interventional therapy in older patients with acute coronary syndrome

BACKGROUND Bivalirudin,a direct thrombin inhibitor,is used in anticoagulation therapies as a substitute for heparin,especially during cardiovascular procedures such as percutaneous coronary intervention.AIM To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome(ACS).METHODS In total,165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study.From June 2020 to June 2022,elderly patients with ACS with complete data were selected and treated with interventional therapy.The study cohort was randomly divided into a study group(n=80,administered bivalirudin)and a control group(n=85,administered unfractionated heparin).Over a 6-mo follow-up period,differences in emergency processing times,including coronary intervention,cardiac function indicators,occurrence of cardiovascular events,and recurrence rates,were analyzed.RESULTS Significant differences were observed between the study cohorts,with the observation group showing shorter emergency process times across all stages:Emergency classification;diagnostic testing;implementation of coronary intervention;and conclusion of emergency treatment(P<0.05).Furthermore,the left ventricular ejection fraction in the observation group was significantly higher(P<0.05),and the creatine kinase-MB and New York Heart Association scores were CONCLUSION In elderly patients receiving interventional therapy for ACS,bivalirudin administration led to increased activated clotting time achievement rates,enhanced myocardial reperfusion,and reduced incidence of bleeding complications and adverse cardiac events.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes

BACKGROUND Coronary heart disease and type 2 diabetes mellitus(T2DM)frequently coexist,creating a complex and challenging clinical scenario,particularly when complicated with acute myocardial infarction(AMI).AIM To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion.METHODS In total,98 patients were categorized into control(n=47)and observation(n=51)groups.The control group received noxital,while the observation group was treated with dapagliflozin combined with noxital for 6 months.Changes in myocardial microperfusion,blood glucose level,cardiac function,N-terminal prohormone of brain natriuretic peptide(NT-proBNP)level,growth differentiation factor-15(GDF-15)level,and other related factors were compared between the two groups.Additionally,the incidence of major adverse cardiovascular events(MACE)and adverse reactions were calculated.RESULTS After treatment,in the observation and control groups,the corrected thrombolysis in myocardial infarction frame counts were 37.12±5.02 and 48.23±4.66,respectively.The NT-proBNP levels were 1502.65±255.87 and 2015.23±286.31 pg/mL,the N-terminal pro-atrial natriuretic peptide(NT-proANP)levels were 1415.69±213.05 and 1875.52±241.02 ng/mL,the GDF-15 levels were 0.87±0.43 and 1.21±0.56 g/L,and the high-sensitivity C-reactive protein(hs-CRP)levels were 6.54±1.56 and 8.77±1.94 mg/L,respectively,with statistically significant differences(P<0.05).The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group(P<0.05).The incidence of adverse reactions was 13.73%(7/51)in the observation group and 10.64%(5/47)in the control group,with no statistically significant difference(P>0.05).CONCLUSION Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM.The underlying mechanism may be related to the reduction in the expression levels of NT-proANP,GDF-15,and hs-CRP.

Activation of the Macrophage-Associated Inflammasome Exacerbates Myocardial Fibrosis Through the 15-HETE-Mediated Pathway in Acute Myocardial Infarction

This investigation elucidates the spatiotemporal dynamics of NOD-like receptor family pyrin domain con-taining 3(NLRP3)inflammasome activation following myocardial infarction(MI),a process that has not been fully characterized.We revealed early activation of the NLRP3 inflammasome in mice with MI and characterized its dynamic temporal expression.Notably,the knockout and inhibition of Nlrp3 expression were found to significantly mitigate infarct size and enhance cardiac function.Furthermore,our analysis of the spatial characteristics of inflammasome activation revealed predominant activation in macro-phages and subsequent activation in fibroblasts on the third day post-MI.To elucidate the nexus between macrophage-associated NLRP3 inflammasome activation and myocardial fibrosis,we employed targeted metabolomics analyses of inflammatory oxylipins,small interfering RNA(siRNA)interference experi-ments,and various molecular assays.These findings revealed that macrophage-associated inflammasome activation facilitates the conversion of fibroblasts into myofibroblasts via the 15-hydroxy-5,8,11,13-eicosatetraenoic acid(15-HETE)-mediated small mother against decapentaplegic(Smad)pathway.Additionally,both mass spectrometry imaging(MSI)and targeted metabolomics analyses confirmed the significant increase in 15-HETE levels in mice with MI and in patients with MI and acute coronary syndrome(ACS).Our comprehensive dataset suggests that NLRP3 inflammasome activation in MI is char-acterized by distinct temporal and spatial patterns.These insights mark a significant advancement toward precise MI prevention and treatment strategies,particularly early myocardial fibrosis intervention.

Value of Myocardial Strain in Monitoring Fluorouracil-Based Chemotherapy-Related Cardiac Dysfunction in Gastrointestinal Cancer Patients

Objective To investigate the predictive value of myocardial strain for cardiotoxicity associated with fluorouracil-based chemotherapies in gastrointestinal cancer patients.Methods Patients with diagnosis of gastrointestinal cancers,who were hospitalized for chemotherapy involving antimetabolic drugs,were eligible in this prospective study.Echocardiography was performed before and after each chemotherapy cycle during hospitalization until the completion of chemotherapy.Cancer therapy-related cardiac dysfunction(CTRCD)was identified if there was a decrease in left ventricular ejection fraction(LVEF)by at least 5%to an absolute value of<53%from the baseline,accompanied by symptoms or signs of heart failure;or a decrease in LVEF of at least 10%to an absolute value of<53%from the baseline,without symptoms or signs of heart failure.Subclinical cardiac impairment is defined as a decrease in the left ventricular global longitudinal strain(GLS)of at least 15%from baseline.Clinical data and myocardial strain variables were collected.Changes of echocardiographic indexes after chemotherapy at each cycle were observed and compared to those of pre-chemotherapy.Cox regression analysis was used to determine the associated indexes to CTRCD,and receiver operating characteristic(ROC)curves were plotted for evaluation of their predicting efficacy.Results Fifty-one patients completed 4 cycles of chemotherapy and were enrolled in the study analysis.LVEF,GLS,GLS epicardium(GLS-epi),and GLS endocardium(GLS-endo)were decreased after the 4 cycles of chemotherapy.Throughout the chemotherapy period,6 patients(11.8%)progressed to CTRCD.The Cox regression analysis revealed that the change in left atrial ejection fraction(LAEF)and LAS during the reservoir(LASr)phase after the first cycle of chemotherapy(C1v-LAEF and C1v-LASr,respectively)were significantly associated with the development of CTRCD[C1v-LAEF(HR=1.040;95%CI:1.000-1.082;P=0.047);C1v-LASr(HR=1.024;95%CI:1.000-1.048;P=0.048)].The sensitivity and specificity were 50.0%and 93.3%,respectively,for C1v-LAEF predicting CTRCD when C1v-LAEF>19.68%was used as the cut-off value,and were 66.7%and 75.6%,respectively,for C1v-LASr predicting CTRCD when C1v-LASr>14.73%was used as the cut-off value.The areas under the ROC curve(AUC)for C1v-LAEF and C1v-LASr predicting CTRCD were 0.694 and 0.707,respectively.Conclusion GLS changes among patients with subclinical impairment of cardiac function who were treated with fluorouracil-based chemotherapies,and C1v-LAEF and C1v-LASr of the left atrium are early predictors of cardiac function deterioration.

Network pharmacology and subsequent experimental validation reveal the synergistic myocardial protection mechanism of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.

Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and subsequent experimental validation.Methods:Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of s.miltiorrhiza and C.tinctorius as herb pair.Molecular docking was used to verify the binding of the components of these herbs and their potential targets.An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects,which were evaluated using the combination index.Western blot was performed to detect the protein expression of these targets.Results:Network pharmacology analysis revealed 5 pathways and 8 core targets of s.miltiorrhiza and C.tinctorius in myocardial protection.Five of the core targets were enriched in the hypoxia-inducible factor-1(HIF-1)signaling pathway.S.miltiorrhiza-C.tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway.As an upstream gene of the HIF-1 pathway,STAT3 can be activated by the active ingredients cryptotanshinone(Ctan),salvianolic acid B(Sal.B),and myricetin(Myric).Cell experiments revealed that Myric,Sal.B,and Ctan also exhibited synergistic myocardial protective activity.Molecular docking verified the strong binding of Myric,Sal.B,and Ctan to STAT3.Western blot further showed that the active ingredients synergistically upregulated the protein expressionof STAT3.Conclusion:The pharmacodynamic transmission analysis revealed that the active ingredients of S.miltiorrhiza and C.tinctorius can synergistically resist ischemia through various targets and pathways.This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm

Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells.They are clinically classifiable into four main diseases:chronic myeloid leukemia,essential thrombocythemia,polycythemia vera,and primary myelofibrosis.These pathologies are closely related to cardio-and cerebrovascular diseases due to the increased risk of arterial thrombosis,the most common underlying cause of acute myocardial infarction.Recent evidence shows that the classical Virchow triad(hypercoagulability,blood stasis,endothelial injury)might offer an explanation for such association.Indeed,patients with MPN might have a higher number and more reactive circulating platelets and leukocytes,a tendency toward blood stasis because of a high number of circulating red blood cells,endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell.These abnormal cancer cells,especially when associated with the JAK2V617F mutation,tend to proliferate and secrete several inflammatory cytokines.This sustains a pro-inflammatory state throughout the body.The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation.Clinically,MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.

MiR-106a targets ATG7 to inhibit autophagy and angiogenesis after myocardial infarction

Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the prevention of heart failure after MI,and miR-106a is considered to be an important regulatory factor in MI.But the specific mechanism remains unknown.In this study,using cultured venous endothelial cells and a rat model of MI,we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and angiogenesis.Methods:We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial cells.Then we identified ATG7,which was the down-stream target gene of miR-106a.The expression of miR-106a and ATG7 was investi-gated in the rat model of MI.Results:We found that miR-106a inhibits the proliferation,cell cycle,autophagy and angiogenesis,but promoted the apoptosis of vein endothelial cells.Moreover,ATG7 was identified as the target of miR-106a,and ATG7 rescued the inhibition of autophagy and angiogenesis by miR-106a.The expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas.Conclusion:Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting ATG7.This mechanism may be a potential therapeutic treatment for MI.

Bleeding characteristics and mortality outcomes following ST-elevation myocardial infarction thrombolysis:a 5-year analysis in an Asian population

BACKGROUND:Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents.This study aimed to determine the incidence,characteristics and mortality outcomes of bleeding following ST-elevation myocardial infarction(STEMI)thrombolysis in an Asian population.METHODS:This single-centre retrospective study included all STEMI patients who received thrombolytic therapy from 2016 to 2020 in a Malaysian tertiary hospital.Total population sampling was used in this study.The primary outcome was bleeding events post-thrombolysis,categorised using the Thrombolysis in Myocardial Infarction(TIMI)bleeding criteria.Inferential statistics were used to determine the associations between relevant variables.RESULTS:Data from 941 patients were analysed.A total of 156(16.6%)STEMI patients bled post-thrombolysis.Major,minor,and minimal TIMI occurred in 7(0.7%),17(1.8%),and 132(14.0%)patients,respectively.Age 65 years(P=0.031)and Malaysian Chinese(P=0.008)were associated with a higher incidence of bleeding post-thrombolysis.Conversely,foreigners(P=0.032)and current smoker(P=0.007)were associated with a lower incidence of bleeding.Both TIMI major(P<0.001)and TIMI minor(P<0.001)were associated with a higher incidence of all-cause in-hospital mortality among STEMI patients.TIMI minor bleeding was significantly higher in the streptokinase recipients.The bleeding sites were comparable between streptokinase and tenecteplase recipients,except for a significantly higher incidence of gastrointestinal bleeding in the streptokinase recipients(P=0.027).CONCLUSION:In our Asian population,the incidence of total bleeding events following STEMI thrombolysis is comparable to that previously reported.The development of TIMI major and minor bleeding complications is associated with higher mortality.

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

Buxu Tongyu Granule Alleviates Myocardial Ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion

Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Polar residual network model for assisting evaluation on rat myocardial infarction segment in myocardial contrast echocardiography

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P>0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P<0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P<0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.

Aldo-Keto reductase 1C3 reduces myocardial cell damage after acute myocardial infarction by activating the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2-antioxidant response element pathway to inhibit ferroptosis

Background Acute myocardial infarction(AMI)is a high-risk cardiovascular condition associated with increased cellular damage and oxidative stress.Aldo-Keto Reductase 1C3(AKR1C3)is a stress-regulating gene.Nevertheless,its specific role and mechanisms regarding AMI remain unclear.Methods We assessed cardiac function through echocardiography;tissue damage was evaluated using Hematoxylin and Eosin(HE)and Masson trichrome staining.AKR1C3 expression levels were measured through Reverse transcription-quantitative polymerase chain reaction and western blot.Assessed cell viability using Cell Counting Kit-8 and lactate dehydrogenase(LDH)assays.The extent of ferroptosis was determined by measuring the levels of Fe2+,boron-dipyrromethane(BODIPY)and malondialdehyde(MDA),the glutathione/glutathione disulfide(GSH/GSSG)ratio,and the expression of Glutathione Peroxidase 4(GPX4)and Solute carrier 7A11(SLC7A11).Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2-Antioxidant response element(Keap1-Nrf2-ARE)pathway activation was analyzed through western blotting.Nrf2 was inhibited with ML385and activated with(R)-Sulforaphane to investigate the Keap1-Nrf2-ARE pathway.Results The rats in the AMI group displayed reduced heart function,more tissue damage,and lower AKR1C3 expression compared to the Sham group.Similarly,hypoxia-treated H9C2 cells showed reduced viability,and decreased AKR1C3 expression.Overexpressing AKR1C3 in H9C2 cells enhanced viability.Knocking down AKR1C3 exhibited the opposite effect.Of the inhibitors tested,Ferrostatin-1 most effectively restored cell viability in hypoxia-treated H9C2 cells.Moreover,H9C2 cells subjected to hypoxia suggested Keap1-Nrf2-ARE pathway inhibition.Overexpressing AKR1C3 reduced ferroptosis and activated the Keap1-Nrf2-ARE pathway in hypoxia-treated cells,knocking down AKR1C3 exhibited the opposite effect.Further experiments using ML385 in hypoxia-treated H9C2 cells with overexpressed AKR1C3 showed decreased viability and increased ferroptosis compared to the control.Using(R)-Sulforaphane in hypoxia-treated H9C2 cells with knocked-down AKR1C3 exhibited the opposite effect.Conclusion This study's findings indicate that AKR1C3 plays a role in regulating ferroptosis in myocardial cells,with the Keap1-Nrf2-ARE pathway likely being a key mechanism behind it.

Bibliometrics of trends in global research on the roles of stem cells in myocardial fibrosis therapy

BACKGROUND Myocardial fibrosis,a condition linked to several cardiovascular diseases,is associated with a poor prognosis.Stem cell therapy has emerged as a potential treatment option and the application of stem cell therapy has been studied extensively.However,a comprehensive bibliometric analysis of these studies has yet to be conducted.AIM To map thematic trends,analyze research hotspots,and project future directions of stem cell-based myocardial fibrosis therapy.METHODS We conducted a bibliometric and visual analysis of studies in the Web of Science Core Collection using VOSviewer and Microsoft Excel.The dataset included 1510 articles published between 2001 and 2024.Countries,organizations,authors,references,keywords,and co-citation networks were examined to identify evolving research trends.RESULTS Our findings revealed a steady increase in the number of publications,with a projected increase to over 200 publications annually by 2030.Initial research focused on stem cell-based therapy,particularly for myocardial infarction and heart failure.More recently,there has been a shift toward cell-free therapy,involving extracellular vesicles,exosomes,and microRNAs.Key research topics include angiogenesis,inflammation,apoptosis,autophagy,and oxidative stress.CONCLUSION This analysis highlights the evolution of stem cell therapies for myocardial fibrosis,with emerging interest in cellfree approaches.These results are expected to guide future scientific exploration and decision-making.