Lower back pain is among the top ten reasons patients visit the emergency department (ED). Tizanidine, a centrally acting alpha-2 adrenergic receptor agonist, is commonly prescribed for managing spasticity in patients with cerebral or spinal injuries. It is also used as an effective treatment for nonspecific lower back pain. One of the most critical and life-threatening causes of lower back pain is abdominal aortic dissection, particularly in patients with hypertension. Nifedipine, a 1,4-dihydropyridine calcium channel blocker (CCB), is a widely used oral antihypertensive and antianginal agent. It lowers systemic vascular resistance and dilates coronary arteries by inhibiting calcium ion (Ca²⁺) entry into the smooth muscle cells of small arteries (arterioles), thereby reducing systemic blood pressure and improving myocardial oxygen delivery. We report a compelling case of a male patient presenting to the ED with high blood pressure and lower back pain. Shortly after the administration of tizanidine and nifedipine, his blood pressure dropped significantly within an hour. Initially suspected to be a ruptured abdominal aortic dissection, the cause was later identified as a drug-drug interaction. The synergistic effects of tizanidine and nifedipine resulted in a rapid and critical drop in blood pressure. The Drug Interaction Probability Scale (DIPS) score of 4 suggests the hypotensive episode was possibly caused by a drug interaction. This case also highlights the importance of point of care ultrasound (POCUS) and repeated examinations in excluding life-threatening conditions like aortic rupture.

Lately, research on the function of microglia in diabetic retinopathy (DR) is becoming increasingly focused. Microglia are immune cells that dwell in the central nervous system and are crucial to the pathophysiology of DR. According to studies, a hyperglycemic environment can activate microglia, bringing them out of a resting state to an active state. This allows them to release a variety of inflammatory factors and chemokines, which can then cause retinal inflammatory reactions. When it comes to angiogenesis in DR, activated microglia release a variety of angiogenic substances, such as vascular endothelial growth factor (VEGF), to create aberrant new blood vessels. Moreover, microglia contribute to the retina's oxidative stress process by generating and releasing reactive oxygen and nitrogen-free radicals, which exacerbates retinal damage. Researchers have proposed a variety of strategies for the activation of microglia and the inflammatory response it triggers. By inhibiting the excessive activation of microglia and reducing the release of inflammatory factors, the inflammatory response and damage to the retina can be alleviated. Drugs that interfere with retinal microglia can also be used to regulate vascular damage and inhibit the formation of new blood vessels. In addition, antioxidants are used to remove reactive oxygen and free radicals, reduce oxidative stress levels, and protect retinal cells. These therapeutic strategies aim to achieve the purpose of treating DR by regulating the function of microglia. Thus, we highlight the possibility that therapy aimed at microglia could offer fresh ideas for treating DR.

Saikosaponin A (SSA) is the primary component of Bupleuri radix, which has a variety of pharmacological properties. However, the potential mechanism of SSA's anti-myocardial ischemia (MI) effect has not yet been clarified. We investigated the exact effects and potential mechanisms of SSA on isoproterenol (ISO)-induced MI. A range of network pharmacology approaches have been applied to explore central targets and their underlying mechanisms. Molecular docking was used to identify the binding ability of the potential active components to the hub targets. A rat model of MI was established by subcutaneous injection of ISO (85 mg/kg/day). The pathological myocardial morphology, myocardial enzymes, reactive oxygen species (ROS) production, myocardial mitochondrial structure, apoptosis level, and expression of key proteins in the apoptotic pathway were analyzed. Our animal studies revealed that SSA attenuated ISO-induced pathological cardiac injury and significantly reduced creatine kinase (CK), lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) levels, ROS production, and damage to mitochondrial structures in the heart. In addition, SSA downregulated P53, Caspase-3, and BAX protein activities, upregulated BCL 2 protein activity, and attenuated cardiomyocyte apoptosis. Saikosaponin A alleviates ISO-induced MI by regulating the expression of proteins involved in the P53/BAX/Caspase-3 signaling pathway. Our data showed show that SSA can improve ISO-induced MI. In addition, the role of SSA may be related to its antioxidant stress, anti-apoptosis, and regulation of P53/BAX/Caspase-3 signaling pathway.

N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels present at most excitatory synapses in the brain that play essential roles in cognitive functions including learning and memory consolidation. However, NMDAR dysregulation is implicated in many nervous system disorders. Diseases that involve pathological hyperactivity of NMDARs can be treated clinically through inhibition by channel blocking drugs. NMDAR channel block can occur via two known mechanisms. First, in traditional block, charged drug molecules can enter the channel directly from the extracellular solution after NMDAR activation and channel opening. Second, uncharged molecules of channel blocking drug can enter the hydrophobic plasma membrane, and upon NMDAR activation the membrane-associated drug can transit into the channel through a fenestration within the NMDAR. This membrane-associated mechanism of action is called membrane to channel inhibition (MCI) and is not well understood despite the clinical importance of NMDAR channel blocking drugs. Intriguingly, a hydrophobic route of access for drugs is not unique to NMDARs. Our review will address inhibition of NMDARs and other ion channels by membrane-associated drugs and consider how the path of access may affect a drug's therapeutic potential.

Many therapeutic applications use the transdermal method to avoid the severe restrictions associated with oral medication delivery. Given the limitations of traditional drug delivery via skin, transdermal microneedle (MN) arrays have been reported to be versatile and very efficient devices due to their outstanding characteristics such as painless penetration, affordability, excellent medicinal efficacy, and relative safety. MNs have recently received increased attention for their ability to cure vascular illnesses such as hypertension and thrombosis, as well as promote wound healing via the angiogenesis impact. The integrant of method manufacturing and biodegradable material allows for the modification of MN form and drug release pattern, hence increasing the flexibility of such drug delivery. In this review, we focused on recent improvements in MN-mediated transdermal administration of protein and peptide medicines for improved functional angiogenesis and vascular therapy. We also provide an overview of the present applications of MNs-mediated transdermal protein and peptide administration, particularly in the realm of vascular system disease therapy. Finally, the current state of clinical translation and a forecast for future progress are provided.

Overdoses of widely used cardiovascular drugs calcium channel blockers and angiotensin receptor blockers cause severe hemodynamic instability. Timely management with hyperinsulinemia-euglycemia therapy, vasopressors, and calcium gluconate is critical. Enhanced clinical vigilance, prompt intervention, and long-term care, including psychological evaluation, are essential to address underlying factors and prevent recurrence of overdoses.

Hypertension, or high blood pressure, is a major risk factor for cardiovascular diseases (CVDs) worldwide. Variations in body mass index (BMI) may influence the efficacy of calcium channel blockers (CCBs) by affecting drug metabolism, vascular resistance, and inflammatory responses associated with adipose tissue.

This study aims to evaluate the association between BMI and the short-term efficacy of CCBs in managing hypertension among patients with CVDs over a six-month follow-up period.

This prospective observational study was conducted at the Department of General Internal Medicine, Royal Alexandra Hospital, Glasgow, UK, from June 2023 to June 2024, enrolling 220 patients diagnosed with hypertension and at least one underlying cardiovascular condition, such as coronary artery disease, heart failure, or atrial fibrillation. Patients were categorized into BMI groups based on the World Health Organization (WHO) classification, and all were prescribed CCBs either as monotherapy or in combination with other antihypertensive medications. Blood pressure was measured using an automated sphygmomanometer with follow-up ambulatory monitoring, while lipid levels were assessed via fasting blood samples.

The study involved 220 participants, categorized into four BMI groups: underweight (n = 40), normal weight (n = 60), overweight (n = 60), and obese (n = 60). Underweight patients had a baseline systolic/diastolic blood pressure of 150/95 mmHg, which decreased to 135/85 mmHg, showing a reduction of 15/10 mmHg. Normal weight patients experienced a drop from 145/90 mmHg to 130/80 mmHg, overweight patients from 155/95 mmHg to 140/85 mmHg, and obese patients from 160/100 mmHg to 145/90 mmHg, all with the same reduction of 15 mmHg in systolic and 10 mmHg in diastolic pressure. Low-density lipoprotein (LDL) levels decreased in all groups, with a reduction of 5 mg/dL in the underweight (130 to 125 mg/dL) and normal weight (125 to 120 mg/dL) groups, while the overweight (140 to 130 mg/dL) and obese (150 to 140 mg/dL) groups showed a greater reduction of 10 mg/dL. High-density lipoprotein (HDL) levels improved in all categories, increasing by 5 mg/dL in each group. LDL reduction was more pronounced in overweight and obese groups, likely due to metabolic changes associated with higher body fat. Adverse effects, including peripheral edema and dizziness, were more common in higher BMI groups, with a noticeable decline in medication adherence in obese patients. These results suggest that BMI may influence treatment efficacy, particularly in lipid regulation and the occurrence of adverse effects.

BMI does not significantly affect the blood pressure-lowering efficacy of CCBs in patients with hypertension and CVDs. However, a greater reduction in LDL levels was observed in overweight and obese groups, suggesting that BMI may influence lipid metabolism differently than blood pressure regulation.

Yixin Tongmai Granules (YTG) is a popular Chinese herbal granules for the treatment of coronary artery disease (CAD), but its molecular pharmacological mechanism is still unclear. This article explores the mechanism of CAD treatment from the perspective of network pharmacology. We analyzed the chemical composition of YTG using UHPLC-MS/MS and identified 131 ingredients. The relative drug content of 33 ingredients exceeded 0.5%. These ingredients were further screened using the SwissADME platform with ADME criteria. Using the HIT database and SwissTargetPrediction platform, high probability targets for these ingredients were generated. Using Venn Diagram, 96 effective targets associated with CAD were identified, involving 14 core ingredients. This study imported these effective targets into the STRING platform and obtained the core targets through network topology analysis: TP53, STAT3, transcription factor Jun, MAPK3, MAPK1, AKT1, SRC, MYC, BCL2, transcription factor p65, TNF, and ESR2. Then enrichment analysis with Metascape platform indicated that, in the system network of YTG in anti-CAD, the principal pathways are "Lipid and Atherosclerosis", "Pathways in cancer", and "AGE-RAGE signaling pathway in diabetic complications." Next, the affinities between the core ingredients and their associated core targets were examined individually through molecular docking. Finally, based on deep mining of PubMed literature, this study investigated the relationship between each core target and CAD, the relationship between each core target and its associated core ingredients, and inferred the main pharmacological ingredients of YTG, namely Tanshinone IIA, Cryptotanshinone, Caffeic acid, Denshensu, Ononin, and Formononetin.

Chiral capillary electrophoresis (CCE) represents an effective technique for enantioselective separations. However, additional techniques may be necessary to determine the enantiomers migration order (EMO) and elucidate the chiral recognition mechanism. This study details the development and optimization of a CCE method for the enantioseparation of amlodipine (AML). Furthermore, it contributes computationally to determining the EMO and the mechanisms responsible for chiral discrimination. The study proposed the optimization of several key parameters in CCE, including the type, concentration and pH of the background electrolyte, as well as the concentration of the chiral selector. In line with previous research, only one anionic cyclodextrin, carboxymethyl-β-cyclodextrin (CM-β-CD), was evaluated as the chiral selector. Following optimization, the most favorable results were achieved using 50 mM phosphate background electrolyte pH 4.0 with 2.5 mg mL-1 CM-β-CD. These conditions enabled baseline separation of AML enantiomers, reduced analysis time, and minimized consumption of the chiral selector. Calculations were conducted using a sequential methodology, beginning with the PM3 semiempirical followed by density functional theory (DFT) calculations. The theoretical analysis indicated that differences in ΔE and ΔG values are reliable indicators for predicting the EMO. Specifically, the (-)-(S)-AML/CM-β-CD complex exhibited superior energetic characteristics compared to the (+)-(R)-AML/CM-β-CD complex, likely due to differences in their intermolecular interactions, including hydrogen bonds and electrostatic interactions, consequently, this finding can be related to elongation migration time within the electrophoretic system. These results underscore the synergistic benefits of computational and experimental approaches in elucidating chiral discrimination mechanisms and identifying EMO in CCE.

Hypertension is a major contributor to cardiovascular disease and its associated morbidity and mortality. The low efficacy observed with some anti-hypertensive therapies has been attributed partly to inter-individual genetic variability. This paper reviews the major findings regarding these genetic variabilities that modulate responses to anti-hypertensive therapies such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, calcium channel blockers (CCBs) and β-adrenoceptor blockers. The importance of studying these genetic polymorphisms stems from the goal to optimise anti-hypertensive therapy for each individual patient, aiming for the highest efficacy and lowest risk of adverse effects. It is important to recognise that environmental and epigenetic factors can contribute to the observed variations in drug responses. Owing to the multigenic and multifactorial nature of drug responses, further research is crucial for translating these findings into clinical practice and the establishment of reliable recommendations.

There is a lack of studies investigating the safety of combination regimens specifically for cardiovascular and cerebrovascular diseases. This study aimed to evaluate the safety of combination drugs for cardiovascular and cerebrovascular diseases using real-world data.

We analyzed adverse drug reaction data received by the Hubei Adverse Drug Reaction Center from the first quarter of 2014 to the fourth quarter of 2022. The safety of combined drugs for cardiovascular and cerebrovascular diseases in different people was assessed using the association rule method and Ω shrinkage measurement.

A total of 53,038 reports were included in this study, revealing 9 signals of adverse reactions caused by combination drugs. The strongest signal found in this study was jaundice caused by the combination of amlodipine and atorvastatin (Ω 0.025:3.08, lift: 1116.69, conviction: 1.75). Additionally, the combination of aspirin with other drugs was associated with hemorrhaging in various organs. Female patients showed a cold signal when taking vitamin C and vitamin B6 together compared to male patients (Ω 0.025:0.89, lift: 7.15, conviction: 1.12). Patients under 60 years old had a palpitations signal when combining eritrea bei sha Tanzania and felodipine (Ω 0.025:0.41, lift: 14.65, conviction: 3.8), and an erythema signal when combining nifedipine (Ω 0.025:0.23, lift: 8.17, conviction: 1.077).

Among the 9 signals identified in this study, 4 were off-label adverse drug reactions that require further clinical research for exploration and confirmation, in order to provide more scientifically informed drug labeling. Five adverse events associated with aspirin-induced bleeding were identified. Notably, different adverse drug reactions were observed in different populations, suggesting the need for future studies to expedite the development of personalized medicine.

Hypertension is a multifactorial and complex disease influenced by genetic and environmental factors, and it has become one of the most serious public health challenges. This study aimed to investigate the changes in hypertension based on urinary proteome. The stroke-prone spontaneously hypertensive rats (SHRSPs) model was used to examined urinary proteome changes during the development of hypertension. Urine proteome profiling was conducted at months 1, 4, 8, 10, 12, and 14 using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Given that the progression of hypertension may vary among individuals, each rat was compared before and after hypertension developed to screen for differential proteins. Differential proteins in each rat can be enriched into some important biological processes and pathways associated with hypertension, such as the regulation of systemic arterial blood pressure by renin-angiotensin, renin-angiotensin signaling, response to glucocorticoid and glucocorticoid receptor signaling, calcium transport I, aldosterone adipocyte signaling pathway, apelin adipocyte signaling pathway, and oxidative stress response. The biological processes and pathways enriched at the same time point in the progression of hypertension differed significantly among different rat individuals. This study demonstrated that the changes in hypertension can be reflected in urine proteins. Urinary proteomics has potential in researching the mechanisms underlying hypertension, discovering new drug targets, and developing personalized strategies for antihypertensive treatment.

Hypertension remains a critical global health issue, despite significant advancements in treatment, management and preventive approaches. Current antihypertensive drugs have limitations, such as low adherence, renin-angiotensin-aldosterone system reactivation, and drug resistance,. Ongoing preclinical and clinical studies for siRNA therapies show promising results, demonstrating significant blood pressure reductions and their potential as effective, durable treatments. This narrative review explores the potential of siRNA therapies in transforming hypertension management covering the literature until May 2024 and offering a precision medicine approach. We searched various databases, including PubMed, http://www.clinicaltrial.gov, and www.Espacenet.com, using 'hypertension' and 'siRNA' as the main keywords to retrieve relevant studies. The impact of these therapies could be profound, offering improved efficacy, reduced side effects, and enhanced patient adherence. As research continues to validate their safety and effectiveness, siRNA therapies may become integral components of hypertension management.

Literature reveals two kinds of menstruation-related anginas-cardiac syndrome X (CSX) and catamenial angina. CSX generally occurs in perimenopausal or postmenopausal women; catamenial angina affects females from puberty to menopause with existing/preexisting or predisposed to coronary artery disease. CSX involves recurring anginal-type retrosternal chest pains during exercise or rest with no significant findings on angiogram. Catamenial angina is menstruation-associated recurrent nonexertional left-sided chest pain alongside diaphoresis, hot flushes, and persistent lethargy. Pathophysiology of both anginas revolve around decreased levels of estrogen. Estrogen is known to act via genomic and nongenomic pathways on cardiomyocytes, endothelial cells, and smooth muscle cells to exert its cardioprotective effect. These cardioprotective effects could be lost during the postovulation phase and at the end of menstruation as well as during perimenopause or menopause owing to the decreased levels of estrogen. Evaluation should begin with a history and physical examination and focus on noninvasive tests such as exercise tolerance test, electrocardiogram, and echocardiogram. Reducing symptoms that cause discomfort and improving quality of life should be the main goal in management. Nitrates along with β blockers and analgesics for pain are the main pharmacologic modalities. Exercise training, smoking cessation, weight loss, and dietary changes are nonpharmacological modalities. Proper awareness and effective communication with patients or caregivers can lead to early diagnosis and treatment initiation.

Diabetes mellitus (DM) affects 537 million people as of 2021, and is projected to rise to 783 million by 2045. This positions DM as the ninth leading cause of death globally. Among DM patients, cardiovascular disease (CVD) is the primary cause of morbidity and mortality. Notably, the prevalence rates of CVD is alarmingly high among diabetic individuals, particularly in North America and the Caribbean (46.0%), and Southeast Asia (42.5%). The predominant form of CVD among diabetic patients is coronary artery disease (CAD), accounting for 29.4% of cases. The pathophysiology of DM is complex, involving insulin resistance, β-cell dysfunction, and associated cardiovascular complications including diabetic cardiomyopathy (DCM) and cardiovascular autonomic neuropathy (CAN). These conditions exacerbate CVD risks underscoring the importance of managing key risk factors including hypertension, dyslipidemia, obesity, and genetic predisposition. Understanding the genetic networks and molecular processes that link diabetes and cardiovascular disease can lead to new diagnostics and therapeutic interventions. Imeglimin, a novel mitochondrial bioenergetic enhancer, represents a promising medication for diabetes with the potential to address both insulin resistance and secretion difficulties. Effective diabetes management through oral hypoglycemic agents (OHAs) can protect the cardiovascular system. Additionally, certain antihypertensive medications can significantly reduce the risk of diabetes-related CVD. Additionally, lifestyle changes, including diet and exercise are vital in managing diabesity and reducing CVD risks. These interventions, along with emerging therapeutic agents and ongoing clinical trials, offer hope for improved patient outcomes and long-term DM remission. This study highlights the urgent need for management strategies to address the overlapping epidemics of DM and CVD. By elucidating the underlying mechanisms and risk factors, this study aims to guide future perspectives and enhance understanding of the pathogenesis of CVD complications in patients with DM, thereby guiding more effective treatment strategies.

Purpose: High blood pressure (HBP) is the leading cause of mortality and years of disability, and its prevalence is increasing. Therefore, diagnosis and effective treatment of HBP is one of the main goals to prevent and reduce its complications, and pharmacological treatment is the cornerstone of hypertension management.Materials and Methods: The gradual introduction of different drug families has led to the development of new molecules that have improved efficacy and reduced adverse effects. Results: Current drugs include a large number that target key mechanisms of blood pressure regulation as well as those that contribute to hypertension-induced organ damage. Recently, new antihypertensive drugs have been introduced that not only aim to lower blood pressure but also provide additional protection against organ damage and metabolic disorders. Some of them were introduced for specific indications other than hypertension and other are based in a pharmacogenomic approach. Other routes of administration, such subcutaneous injection, are also being explored to improve protection and compliance.Conclusions: The main characteristics of each class of antihypertensive drug are summarised.

Standard-of-care (SoC) medications for the treatment of obstructive hypertrophic cardiomyopathy (oHCM) are recommended as first-line therapy despite the lack of evidence from controlled clinical trials and well known off-target side effects.

We describe the impact of SoC therapy downtitration and withdrawal in patients already receiving aficamten in FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in Hypertrophic Cardiomyopathy; NCT04848506).

Patients receiving SoC therapy (beta-blocker, nondihydropyridine calcium-channel blocker, and/or disopyramide) were eligible for protocol-guided SoC downtitration and withdrawal at the discretion of the investigator and after achieving a stable dose of aficamten for ≥4 weeks. Successful SoC withdrawal was defined as at least a 50% dose-reduction in ≥1 medication. Adverse events (AEs) were prospectively evaluated 1 to 2 weeks after any SoC withdrawal.

Of 145 patients with oHCM who were followed for at least 24 weeks (mean age 60.5 ± 13.2 years; 44.8% female; 42% NYHA functional class III), 136 (93.8%) were receiving ≥1 SoC therapy; of those, 64 (47%) had an attempt at withdrawal, with 59 (92.2%) successful. Thirty-eight (64.4%) patients completely discontinued ≥1 medication, and 27 (45.8%) achieved aficamten monotherapy with 2 later restarting a SoC medication. There were no significant differences in baseline characteristics on day 1 in FOREST-HCM in those with a SoC-withdrawal vs no-withdrawal attempt. In patients who underwent successful SoC therapy withdrawal, NYHA functional class improved by ≥1 class in 79.2% from baseline, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score improved to 83.0 ± 15.8 points, and resting and Valsalva left ventricular outflow tract gradient improved to 14.3 ± 10.9 and 32.9 ± 21.4 mm Hg, respectively. N-terminal pro-B-type natriuretic peptide levels improved to a median of 220.0 pg/mL (Q1-Q3: 102.0-554.0.0 pg/mL) and high-sensitivity troponin I improved to a median of 6.0 ng/L (Q1-Q3:3.5-10.7 ng/L). Downtitration and withdrawal of SoC therapy did not impact these results (all P values for change were >0.05), and these changes were similar in patients who did not undergo SoC therapy withdrawal. There were no serious AEs attributed to SoC withdrawal and treatment emergent AEs were similar between groups.

In FOREST-HCM, one-half of the patients with oHCM attempted downtitration and withdrawal of SoC medications while receiving aficamten treatment, with infrequent instances of resumption of SoC. Stopping and dose reduction of SoC medications were well tolerated with no adverse consequences in clinical measures of efficacy (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in Hypertrophic Cardiomyopathy [FOREST-HCM]; NCT04848506).

Cardiac screening of newly discovered drugs remains a longstanding challenge for the pharmaceutical industry. While therapeutic efficacy and cardiotoxicity are evaluated through preclinical biochemical and animal testing, 90 % of lead compounds fail to meet safety and efficacy benchmarks during human clinical trials. A preclinical model more representative of the human cardiac response is needed; heart tissue engineered from human pluripotent stem cell derived cardiomyocytes offers such a platform. In this study, three functionally distinct and independently validated engineered cardiac tissue assays are exposed to increasing concentrations of known compounds representing 5 classes of mechanistic action, creating a robust electrophysiology and contractility dataset. Combining results from six individual models, the resulting ensemble algorithm can classify the mechanistic action of unknown compounds with 86.2 % predictive accuracy. This outperforms single-assay models and offers a strategy to enhance future clinical trial success aligned with the recent FDA Modernization Act 2.0.

To describe the epidemiological distribution of hemorrhoids in a physical examination population in China, which could provide evidence for precision prevention and early intervention of hemorrhoids.

Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design, which collected information by a questionnaire and physical examination results from each subject. The epidemiological distribution of hemorrhoids was described using Logistic models. The gender-, age-, and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China (2010).

A total of 2 940 295 adult subjects were included in the study, of whom the average age was (41.7±14.0) years, and 52.6% were females. The standardized detection rate of hemorrhoids was higher for females (43.7%) than that for males (17.7%; P < 0.001) in this study. In the females, the age distribution of hemorrhoids was inverted U-shaped, with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years (63.5%). In the males, the standardized detection rate of hemorrhoids increased along with age, with the highest percentage of 17.2% in the age group of 50-59 years, and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly (P < 0.001 for trend test). The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females (P < 0.001). The standardized detection rate of hemorrhoids showed a positive correlation with body mass index (P < 0.001 for trend test in males).

The detection rate of hemorrhoids varied to gender, age, obesity, and hypertension status, which could help to identify the risk factors and the high-risk sub-groups, and hence to strengthen health education and early detection accordingly, which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population. This study was conducted in a physical examination population, and the conclusions of this study should be extrapolated with caution.

Background/Objectives: Firefighters are exposed to a high level of stress as they often perform physically challenging work in hazardous environments while responsible for rescuing and keeping those around them safe. To add to this stress, they are also required to work in heavy, unbreathable personal protective equipment which promotes dehydration. These occupational demands paired with dehydration may lead to increased core temperatures, cardiac strain, and overall risk for sudden cardiac events. Thus, it is important to include hydration assessments and determine fluid needs when firefighters are on shift to ensure their personal safety as well as the safety of those around them by optimizing physical performance by maintaining adequate hydration. Therefore, the purpose of this review is to identify markers of hydration, classifications of hydration status, current hydration recommendations, and hydration interventions that may contribute to the overall clarity of hydration protocols that may optimize performance and health of firefighters. In addition, the impact of common medications, exercise training, and health conditions on hydration status related to firefighters will be discussed. Methods: A comprehensive literature search was conducted to discuss the purpose statements. Results: Hydration recommendations for firefighters include (1) assessing hydration status with multiple measurements including body mass, urine specific gravity and thirst sensation, and (2) following general hydration recommendations on rest days and exercise hydration protocols during firefighting activities which may be altered according to hydration status measurements. Conclusion: Randomized controlled trials in firefighters are needed to determine the impact of maintaining adequate hydration on health markers.

Kratom, also known as Mitragyna speciosa, is a plant that originates in Southeast Asia and possesses unique pharmacological characteristics. It is commonly consumed in the form of tea made by boiling the leaves or using the leaves to create the powder. According to its pain-relieving effects, the prevalence of kratom use around the world has increased, which has various implications for healthcare providers. Mitragynine is a well-known active compound in kratom.

This review aims to provide a comprehensive perspective on the cardiovascular effects of mitragynine and its potential cardiotoxicity through the literature.

Authors searched PubMed, Scopus, and Google Scholar databases using appropriate search strategies for each database. After the screening, all relevant studies were included.

Although kratom may have the potential for therapeutic benefits, it has been associated with multi-organ damage and cardiac toxicity in some cases. According to the available data, tachycardia and hypertension are the most common adverse effects. Other possible cardiovascular effects include atherosclerosis, ventricular arrhythmia, cardiomyopathy, dose-dependent prolonged QTc interval, myocarditis, cardiomegaly, and cardiopulmonary arrest.

While prior research has indicated the possible negative effects of mitragynine overdose on the cardiovascular system, there are no definitive conclusions, and additional investigations are needed.

Aim: Calcium channel antagonists are of considerable interest in treating elevated blood pressure and its pathologies.Materials & methods: Schiff base derivatives of amlodipine were produced to check its urease inhibition potentials as well antibacterial and antioxidant activities. Structural illustration along with chemical characterization were achieved by spectral techniques (1H NMR, FTIR, 13C NMR) and docking studies also performed.Results & conclusion: 3g displayed remarkable anti-hypertensive activity compared with parent drug. 3b, 3f and 3g showed urease inhibition potentials. These compounds can aid as lead for further investigations since they exhibited comparable or superior interactions.

Cardiovascular diseases (CVDs) continue to be a major global health concern, representing a leading cause of morbidity and mortality. This review provides a comprehensive examination of CVDs, encompassing their pathophysiology, diagnostic biomarkers, advanced imaging techniques, pharmacological treatments, surgical interventions, and the emerging role of herbal remedies. The review covers various cardiovascular conditions such as coronary artery disease, atherosclerosis, peripheral artery disease, deep vein thrombosis, pulmonary embolism, cardiomyopathy, rheumatic heart disease, hypertension, ischemic heart disease, heart failure, cerebrovascular diseases, and congenital heart defects. The review presents a wide range of cardiac biomarkers such as troponins, C-reactive protein, CKMB, BNP, NT-proBNP, galectin, adiponectin, IL-6, TNF-α, miRNAs, and oxylipins. Advanced molecular imaging techniques, including chest X-ray, ECG, ultrasound, CT, SPECT, PET, and MRI, have significantly enhanced our ability to visualize myocardial perfusion, plaque characterization, and cardiac function. Various synthetic drugs including statins, ACE inhibitors, ARBs, β-blockers, calcium channel blockers, antihypertensives, anticoagulants, and antiarrhythmics are fundamental in managing CVDs. Nonetheless, their side effects such as hepatic dysfunction, renal impairment, and bleeding risks necessitate careful monitoring and personalized treatment strategies. In addition to conventional therapies, herbal remedies have garnered attention for their potential cardiovascular benefits. Plant extracts and their bioactive compounds, such as flavonoids, phenolic acids, saponins, and alkaloids, offer promising cardioprotective effects and enhanced cardiovascular health. This review underscores the value of combining traditional and modern therapeutic approaches to improve cardiovascular outcomes. This review serves as a vital resource for researchers by integrating a broad spectrum of information on CVDs, diagnostic tools, imaging techniques, pharmacological treatments and their side effects, and the potential of herbal remedies.

There are no nationwide surveys on antihypertensive drugs in China. In order to assess the current status of antihypertensive drug therapy in patients with hypertension and analyzed factors that may affect combination therapy, using convenience sampling, we recruited 305,624 patients with hypertension from the Chinese Cardiovascular Association Database-Hypertension Center between January 2019 and December 2021. Chi-squared test was performed to analyze the administered antihypertensive drug types and their combinations in different hospital settings. Logistic regression was used to assess the factors influencing combination therapy. We found around 33.1% of the participants had stage 2 and above hypertension, of which 67.9% were treated with combination therapy. In community or general hospitals, the most common monotherapy was calcium channel blockers (CCB), angiotensin-converting enzyme inhibitor/angiotensin II receptor inhibitor (ACEI/ARB) and diuretic were the main single-pill combinations (SPCs), and ACEI/ARB and CCB were the main free combination. From 2019 to 2021, the rates of combination therapy increased (58.8%-64.1%) with SPCs from 25.9% to 31.0% and free combination from 31.9% to 32.6%. Patients aged < 60 years, with stage 2 and above hypertension, with an education level of high school and above, visiting general hospitals, living in the eastern region of China, with hypertension risk factors and comorbidities, and without anxiety or depression were more likely to receive combination therapy (all P < .05). The combination therapy use rate increased yearly and the rate of SPCs rose obviously. Individual, hospital, and regional differences in patients with hypertension influenced combination therapy.

The illicit use of the psychostimulant methamphetamine (METH) is a major concern, with overdose deaths increasing substantially since the mid-2010s. One challenge to treating METH use disorder (MUD), as with other psychostimulant use disorders, is that there are no available pharmacotherapies that can reduce cravings and help individuals achieve abstinence. The purpose of the current review is to discuss the molecular targets that have been tested in assays measuring the physiological, the cognitive, and the reinforcing effects of METH in both animals and humans. Several drugs show promise as potential pharmacotherapies for MUD when tested in animals, but fail to produce long-term changes in METH use in dependent individuals (eg, modafinil, antipsychotic medications, baclofen). However, these drugs, plus medications like atomoxetine and varenicline, may be better served as treatments to ameliorate the psychotomimetic effects of METH or to reverse METH-induced cognitive deficits. Preclinical studies show that vesicular monoamine transporter 2 inhibitors, metabotropic glutamate receptor ligands, and trace amine-associated receptor agonists are efficacious in attenuating the reinforcing effects of METH; however, clinical studies are needed to determine if these drugs effectively treat MUD. In addition to screening these compounds in individuals with MUD, potential future directions include increased emphasis on sex differences in preclinical studies and utilization of pharmacogenetic approaches to determine if genetic variances are predictive of treatment outcomes. These future directions can help lead to better interventions for treating MUD.

Background: Impaired gastric motility in the form of constipation may often occur in elderly patients with chronic heart failure. Candidates for trans-catheter aortic replacement (TAVR) are of old age and have multiple comorbidities, probably including constipation. However, the clinical implication of a history of constipation in patients receiving TAVR remains unknown. Methods: Patients who underwent TAVR at our large academic center between 2015 and 2022 were eligible. The prognostic impact of the prescribed laxative type and number, which was assumed as the severity of constipation, on the incidence of death or heart failure readmission two years after index discharge was investigated. Results: A total of 344 patients were included. Median age was 85 years, and 99 patients were men. Patients with any laxatives (N = 166) had higher systolic blood pressure, higher plasma B-type natriuretic peptide levels, and a lower prescription rate of renin-angiotensin system inhibitors at the time of index discharge after TAVR (p < 0.05 for all). The number of laxative types was independently associated with the composite primary outcome with an adjusted hazard ratio of 1.83 (95% confidence interval 1.27-2.63, p = 0.001) with a cutoff of one type of laxative used, which significantly stratified the 2-year cumulative incidence of the primary outcome (18% versus 7%, p = 0.001). Conclusions: The presence of constipation was associated with worse clinical outcomes following TAVR. The prognostic impact of an aggressive intervention for constipation remains a future concern in this cohort.

As the percentage of geriatric patients continues to increase in both the United States and globally, the prevalence of both cardiovascular disease and dementia continues to climb. Both dementia and cardiovascular disease are devastating diseases that impose a significant burden economically, socially, and medically on both a local and systemic level. The most common fatal manifestation of cardiovascular disease is acute myocardial infarction, responsible for death in more than 80% of patients with cardiovascular disease. Prominent risk factors for acute myocardial infarction including hypertension and atherosclerosis have been independently associated with an increased risk for cognitive decline and all-cause dementia and Alzheimer disease, separate from vascular dementia. Acute myocardial infarction itself has also been independently associated with an increased incidence of all-cause dementia and Alzheimer disease. It is based on the connection between acute myocardial infarction, its major risk factors, and the incidence of dementia that it is of importance to define and explore the potential role that therapies for these conditions, as well as acute myocardial infarction itself, may play in mitigating the risk of dementia onset and severity. In this review, we assess current therapeutics that exist for atherosclerosis, hypertension and acute myocardial infarction that have been demonstrated to reduce later risk of dementia, and explore the mechanism that underlies the association between the incidence of acute myocardial infarction and the risk of dementia.

Telomeres are part of chromatin structures containing repeated DNA sequences, which function as protective caps at the ends of chromosomes and prevent DNA degradation and recombination, thus ensuring the integrity of the genome. While telomere length (TL) can be genetically inherited, TL shortening has been associated with ageing and multiple xenobiotics and bioactive substances. TL has been characterised as a reliable biomarker for the predisposition to developing chronic pathologies and their progression. This narrative review aims to provide arguments in favour of including TL measurements in a complex prognostic and diagnostic panel of chronic pathologies and the importance of assessing the effect of different pharmacologically active molecules on the biology of telomeres. Medicines used in the management of cardiovascular diseases, diabetes, schizophrenia, hormone replacement therapy at menopause, danazol, melatonin, and probiotics have been studied for their positive protective effects against TL shortening. All these classes of drugs are analysed in the present review, with a particular focus on the molecular mechanisms involved.

Worldwide, hypertension is the leading risk factor for cardiovascular disease and death. An estimated 122 million people, per the American Heart Association in 2023, have been diagnosed with this common condition. It is generally agreed that the primary goal in the treatment of hypertension is to reduce overall blood pressure to below 140/90 mmHg, with a more optimal goal of 130/80 mmHg. Common medications for treating hypertension include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics. CCBs are one of the most widely studied agents and are generally recommended as first-line therapy alone and in combination therapies. This is largely based on the vast knowledge of CCB mechanisms and their minimal side effect profile. CCBs can be separated into two classes: dihydropyridine and non-dihydropyridine. Non-dihydropyridine CCBs act on voltage-dependent L-type calcium channels of cardiac and smooth muscle to decrease muscle contractility. Dihydropyridine CCBs act by vasodilating the peripheral vasculature. For many patients with only mild increases in systolic and diastolic blood pressure (e.g., stage 1 hypertension), the medical literature indicates that CCB monotherapy can be sufficient to control hypertension. In this regard, CCB monotherapy in those with stage 1 hypertension reduced renal and cardiovascular complications compared to other drug classes. Combination therapy with CCBs and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors has been shown to be an effective dual therapy based on recent meta-analyses. This article is a review of calcium channel blockers and their use in treating hypertension with some updated and recent information on studies that have re-examined their use. As for new information, we tried to include some information from recent studies on hypertensive treatment involving calcium channel blockers.

Tobacco smoking causes pulmonary inflammation, resulting in emphysema, an independent risk factor for lung cancer. Induction of insulin-like growth factor 2 (IGF2) in response to lung injury by tobacco carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and polycyclic aromatic hydrocarbon benzo[a]pyrene in combination (NB), is critical for the proliferation of alveolar type 2 cells (AT2s) for lung repair. However, persistent IGF2 overexpression during NB-induced severe injury results in hyperproliferation of AT2s without coordinated AT2-to-AT1 differentiation, disrupting alveolar repair, which leads to the concurrent development of emphysema and lung cancer. The current study aims to verify the role of IGF2 signaling in the associated development of emphysema and cancer and develop effective pharmaceuticals for the diseases using animal models that recapitulate the characteristics of these chronic diseases.

The pathogenesis of pulmonary emphysema and cancer was analyzed by lung function testing, histological evaluation, in situ zymography, dihydroethidium staining, and immunofluorescence and immunohistochemistry analyses utilizing mouse models of emphysema and cancer established by moderate exposure to NB for up to seven months.

Moderate NB exposure induced IGF2 expression in AT2s during the development of pulmonary emphysema and lung cancer in mice. Using AT2-specific insulin receptor knockout mice, we verified the causative role of sustained IGF2 signaling activation in AT2s in emphysema development. IGF2-targeting strategies, including voltage-dependent calcium channel blocker (CCB) and a neutralizing antibody, significantly suppressed the NB-induced development of emphysema and lung cancer. A publicly available database revealed an inverse correlation between the use of calcium channel blockers and a COPD diagnosis.

Our work confirms sustained IGF2 signaling activation in AT2s couples impaired lung repair to the concurrent development of emphysema and cancer in mice. Additionally, CCB and IGF2-specific neutralizing antibodies are effective pharmaceuticals for the two diseases.

In different areas of the heart, action potential waveforms differ due to differences in the expressions of sodium, calcium, and potassium channels. One of the characteristics of myocardial infarction (MI) is an imbalance in oxygen supply and demand, leading to ion imbalance. After MI, the regulation and expression levels of K+, Ca2+, and Na+ ion channels in cardiomyocytes are altered, which affects the regularity of cardiac rhythm and leads to myocardial injury. Myocardial fibroblasts are the main effector cells in the process of MI repair. The ion channels of myocardial fibroblasts play an important role in the process of MI. At the same time, a large number of ion channels are expressed in immune cells, which play an important role by regulating the in- and outflow of ions to complete intracellular signal transduction. Ion channels are widely distributed in a variety of cells and are attractive targets for drug development. This article reviews the changes in different ion channels after MI and the therapeutic drugs for these channels. We analyze the complex molecular mechanisms behind myocardial ion channel regulation and the challenges in ion channel drug therapy.

Calcium channel blockers (CCBs) are common antihypertensive agents among patients receiving hemodialysis (HD). Despite this, the association of CCBs with intradialytic hypotension (IDH), an important adverse outcome that is associated with cardiovascular morbidity and mortality, remains largely unexplored.

Using kinetic modeling sessions data from the Hemodialysis (HEMO) Study, random effects regression models were fit to assess the association of CCB use versus nonuse with IDH (defined as systolic blood pressure [SBP] < 90 mm Hg if pre-HD SBP < 160 mm Hg or < 100 mm Hg if pre-HD SBP ≥160 mm Hg). Models were adjusted for age, biological sex (distinguishing between males and females), race, randomized Kt/V and flux assignments, heart failure, ischemic heart disease, peripheral vascular disease, diabetes mellitus, blood urea nitrogen, ultrafiltration rate, access type, pre-HD SBP, and other antihypertensives.

Data were available for 1838 patients and 64,538 sessions. At baseline, 49% of patients were prescribed CCBs. The overall frequency of IDH was 14% with a mean decline from pre- to nadir-SBP of 33 ± 15 mm Hg. CCB use was associated with lower adjusted risk of IDH, compared with no use (incidence rate ratio [IRR]: 0.84; 95% confidence interval [CI]: 0.78-0.89). The association was most pronounced for those in the pre-HD SBP lowest quartile (IRR: 0.77; 95% CI: 0.70-0.85); compared with the highest quartile (IRR: 0.86; 95% CI: 0.77-0.97; P-interaction < 0.001).

Among patients receiving HD, CCB use was associated with a lower risk of developing IDH, independent of pre-HD SBP and other antihypertensives use. Mechanistic studies are needed to better understand the effects of CCB and other antihypertensives on peridialytic blood pressure (BP) parameters among patients receiving HD.

Heart failure (HF) is a major global health problem afflicting millions worldwide. Despite the significant advances in therapies and prevention, HF still carries very high morbidity and mortality, requiring enormous healthcare-related expenditure, and the search for new weapons goes on. Following initial treatment strategies targeting inotropism and congestion, attention has focused on offsetting the neurohormonal overactivation and three main therapies, including angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor antagonists, β-adrenoceptor antagonists, and mineralocorticoid receptor antagonists, have been the foundation of standard treatment for patients with HF. Recently, a paradigm shift, including angiotensin receptor-neprilysin inhibitor, sodium glucose co-transporter 2 inhibitor, and ivabradine, has been added. Moreover, soluble guanylate cyclase stimulator, elamipretide, and omecamtiv mecarbil have come out as a next-generation therapeutic agent for patients with HF. Although these pharmacologic therapies have been significantly successful in relieving symptoms, there is still no complete cure for HF. We may be currently entering a new era of treatment for HF with animal experiments and human clinical trials assessing the value of antibody-based immunotherapy and gene therapy as a novel therapeutic strategy. Such tempting therapies still have some challenges to be addressed but may become a weighty option for treatment of HF. This review article will compile the paradigm shifts in HF treatment over the past dozen years or so and illustrate current landscape of antibody-based immunotherapy and gene therapy as a new therapeutic algorithm for patients with HF.

Diastolic dysfunction occurs when the left ventricle loses its ability to relax normally, impairing ventricular filling during diastole. This most commonly occurs as a pathological sequela of left ventricular hypertrophy and remodeling due to chronic hypertension and/or age-related sclerotic changes of the aortic valve. This can subsequently deteriorate to diastolic heart failure or heart failure with preserved ejection fraction. There is a substantive interplay between atrial fibrillation and diastolic dysfunction, as atrial fibrillation can cause, exacerbate, or be a direct result of diastolic dysfunction and vice versa. In this review, we first independently define diastolic heart failure and atrial fibrillation while discussing the diagnostic guidelines, which encompass various modalities such as medical history, electrocardiography, echocardiography, and laboratory tests. We subsequently examine their interplay and pathophysiological links drawing on recent evidence in the literature. Finally, we discuss management approaches, including pharmacological interventions targeting rate and rhythm control, diuretics, and addressing comorbidities.

Patients with hypertension have a higher risk of having constipation and vice versa. The causal association between these 2 variables is not proven. We performed a retrospective Mendelian randomization analysis to determine the causal association between constipation and hypertension. Two-sample 2-way Mendelian randomization analysis was used. Genetic variants for constipation were derived from genome-wide association study data of European origin (15,902 cases and 395,721 controls). Corresponding genetic associations for hypertension were derived from European ancestry GWAS data (54,358 cases and 408,652 controls). Genetic susceptibility to hypertension was associated with an increased risk of constipation (OR: 3.459, 95% CI: 1.820-6.573, P < .001). In an inverse Mendelian randomization analysis, no causal effect of constipation on hypertension was found (OR: 0.999, 95% CI: 0.987-1.011, P = .834). In sensitivity analyses, these associations persisted and no multiple effects were found. This study suggests that there is a causal relationship between hypertension and constipation and that hypertension may increase the risk of developing constipation.

To understand the incidence of postoperative constipation and the risk factors of constipation in patients with lumbar interbody fusion, we constructed and verified the constipation risk prediction model, so as to provide reference for the prevention and treatment of postoperative constipation.

The data of patients undergoing lumbar interbody fusion in our hospital were retrospectively analyzed from December 2021 to December 2022. According to postoperative constipation, the patients were divided into constipation group and non-constipation group. Univariate logistic regression analysis and multivariate logistic regression analysis were used to determine independent risk factors for postoperative constipation. Based on independent risk factors, a nomogram was developed to predict the risk of constipation after lumbar interbody fusion. The prediction performance was assessed using receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA). Finally, bootstrapping method for internal validation was further evaluated the nomogram.

A total of 282 patients participated in the study. 176 patients (62.41%) after lumbar interbody occurred constipation, and 106 patients were asymptomatic. Multivariate regression analysis showed independent risk factors, including the use of calcium channel blockers, polypharmacy, postoperative bed time, and constipation history. Multivariate regression analysis was used to establish the model. The C-index of the nomogram was 0.827 (95% CI 0.779-0.875), and the C-index of interval bootstrapping validation was 0.813 (95% CI 0.765-0.861), and the area under the AUC was 0.800. The nomogram showed good discrimination ability.

The use of calcium channel blockers, polypharmacy, postoperative bed time, and history of constipation are independent risk factors for postoperative constipation in patients undergoing lumbar interbody fusion. The constructed risk prediction model has good discriminative ability.

Despite the noteworthy advancements and the introduction of new technologies in diagnostic tools for cardiovascular disorders, the electrocardiogram (ECG) remains a reliable, easily accessible, and affordable tool to use. In addition to its crucial role in cardiac emergencies, ECG can be considered a very useful ancillary tool for the diagnosis of many non-cardiac diseases as well. In this narrative review, we aimed to explore the potential contributions of ECG for the diagnosis of non-cardiac diseases such as stroke, migraine, pancreatitis, Kounis syndrome, hypothermia, esophageal disorders, pulmonary embolism, pulmonary diseases, electrolyte disturbances, anemia, coronavirus disease 2019, different intoxications and pregnancy.

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. β-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include β-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a β-blocker. β-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A β-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a β-blocker may be supported by a pacemaker if the β-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.

Cancer and cardiovascular disease are the two most common causes of death worldwide. As the fields of cardiovascular medicine and oncology continue to expand, the area of overlap is becoming more prominent demanding dedicated attention and individualized patient care. We have come to realize that both fields are inextricably intertwined in several aspects, so much so that the mere presence of one, with its resultant downstream implications, has an impact on the other. Nonetheless, cardiovascular disease and cancer are generally approached independently. The focus that is granted to the predominant pathological entity (either cardiovascular disease or cancer), does not allow for optimal medical care for the other. As a result, ample opportunities for improvement in overall health care are being overlooked. Herein, we hope to shed light on the interconnected relationship between cardiovascular disease and cancer and uncover some of the unintentionally neglected intricacies of common cardiovascular therapeutics from an oncologic standpoint.

Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis.

A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable.

Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear.

Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness among the working-age population. Microglia, resident immune cells in the retina, are recognized as crucial drivers in the DR process. Microglia activation is a tightly regulated immunometabolic process. In the early stages of DR, the M1 phenotype commonly shifts from oxidative phosphorylation to aerobic glycolysis for energy production. Emerging evidence suggests that microglia in DR not only engage specific metabolic pathways but also rearrange their oxidation-reduction (redox) system. This redox adaptation supports metabolic reprogramming and offers potential therapeutic strategies using antioxidants. Here, we provide an overview of recent insights into the involvement of reactive oxygen species and the distinct roles played by key cellular antioxidant pathways, including the NADPH oxidase 2 system, which promotes glycolysis via enhanced glucose transporter 4 translocation to the cell membrane through the AKT/mTOR pathway, as well as the involvement of the thioredoxin and nuclear factor E2-related factor 2 antioxidant systems, which maintain microglia in an anti-inflammatory state. Therefore, we highlight the potential for targeting the modulation of microglial redox metabolism to offer new concepts for DR treatment.