Spontaneous multivessel coronary artery spasm: a case report.

A 60-year-old male presented to the emergency department of our hospital with persistent dull pain in the lower and middle sternum with generalized sweating after a heated argument with another person, and his symptoms did not resolve after 3 hours of onset.

Dual hypoxia-responsive supramolecular complex for cancer target therapy.

The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

No causal genetic relationships between atrial fibrillation and vascular dementia: A bidirectional Mendelian randomization study.

Background: Numerous observational studies have suggested that atrial fibrillation (AF) was associated with an increased risk of vascular dementia (VaD). However, the causal genetic relationships between AF and VaD remains unclear. To evaluate the effect of AF on VaD, we performed the Mendelian randomization (MR) analysis to investigate the causal genetic relationships between AF and VaD. Methods: The bidirectional MR analysis was conducted to explore the causal relationships between exposure and disease. We applied a series of quality assessments to select significantly and independently single nucleotide polymorphisms (SNPs) from publicly available large-scale genome-wide association studies (GWAS) databases. Three methods [Inverse variance weighted method (IVW), MR-Egger method, and weighted median (WM)method] were used to derive MR estimates. In order to ensure reliable MR results, sensitivity analyses were performed to evaluate the horizontal pleiotropy and heterogeneity. Results: Our MR analyses revealed no significant genetic relationships between AF and the risk of VaD (IVW: OR = 1.10, 95%CI = 0.95-1.28, P = 0.20). In the reverse direction analysis, there was no evidence to support a significant genetic relationship of VaD with AF risk (IVW: OR = 1.00, 95% CI = 0.99-1.01, P = 0.52). Consistent results were obtained using different MR methods. Sensitivity analyses suggested no significant horizontal pleiotropy and heterogeneity in the study. Conclusion: This MR analysis did not provide evidence to support the causal genetic relationships between AF on VaD risk and the causal effect of VaD on AF risk.

Atrial fibrillation episode status and incidence of coronary slow flow: A propensity score-matched analysis.

Background: Previous studies have shown that patients with a history of atrial fibrillation (AF) have a higher risk of developing coronary slow flow (CSF). However, whether AF episode status affects the incidence of CSF has not been confirmed. This study investigated the correlation between AF episode status and the incidence of CSF. Methods: We enrolled patients with AF who underwent coronary angiography for symptoms of myocardial ischemia between January 1, 2017, and April 30, 2022, at our institution and classified them according to whether they had an episode of AF in the perioperative period. The outcomes were defined the occurrence of CSF overall and in each of the three coronary arteries. The analysis was repeated after adjusting the baseline information by the propensity score matching method in a 1:1 ratio. Results: 214 patients who met the inclusion and exclusion criteria were included in the study (AF episode group: 100 patients, AF non-episode group: 114 patients). Before matching, age, left atrial size, ejection fraction, heart rate, CSF incidence, and mean corrected thrombolysis in myocardial infarction frame counts were higher in patients with intraoperative AF episodes than in patients without episodes. To prevent the dependent variable (CSF incidence) from being confounded by confounding factors, we matched the two groups for age, left atrial size, and ejection fraction. In the logistic regression analysis, the incidence of CSF was significantly higher in the intraoperative AF episode group (P = 0.010, OR = 2.327, 95% CI: 1.226-4.416) than in the non-episode group. Conclusion: In patients with AF, AF episode status is significantly correlated with an increased overall incidence of CSF.

Influence of Stent Length on Periprocedural Outcomes After Primary Percutaneous Coronary Intervention in Patients with ST Segment Elevation Myocardial Infarction.

Purpose: A longer stent is associated with adverse events after percutaneous coronary intervention (PCI). However, little information is available on the relationship between stent length and periprocedural prognosis in patients with ST segment elevation myocardial infarction (STEMI). We aimed to assess the target vessel stent length influence on angiographic outcomes and in-hospital major adverse cardiovascular event (MACE) during primary PCI in patients with STEMI. Patients and Methods: This single-center retrospective observational study included 246 patients with STEMI admitted to the Zhejiang Provincial People's Hospital between January 2019 and December 2021, who underwent primary PCI and successful stent implantation. The exclusion criteria included left main lesion, multiple diseased vessel-stenting, bleeding disorders, contrast allergy, and incomplete data. Patients were divided into two groups based on the median stents length: group A (≤29 mm, n=125) and group B (>29mm, n=121). Periprocedural outcomes were slow flow/no-reflow (SF-NR) and in-hospital MACE, which included acute heart failure, malignant arrhythmia, cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, and urgent revascularization. Multivariate logistic analyses were used to explore the correlation between stent length and SF-NR. Results: A total of 246 patients (82.9% males) with a mean age of 59.9±12.6 years were included in the analysis. The incidence of SF-NR was significantly higher in group B than in group A (36.4% vs 23.2%, p=0.024). However, the in-hospital MACE incidence rate was similar between the two groups (7.2% vs 7.4%, p=0.943). Multivariate logistic regression analysis showed that stent length and diameter, and peak troponin I level were independent risk factors for SF-NR. Conclusion: Excessive stent length is an independent risk factor for SF-NR, without any significant influence on the risk of MACE during hospitalization.

Transient receptor potential vanilloid subtype 1: A potential therapeutic target for fibrotic diseases.

The transient receptor potential vanilloid subtype 1 (TRPV1), belonging to the TRPV channel family, is a non-selective, calcium-dependent, cation channel implicated in several pathophysiological processes. Collagen, an extracellular matrix component, can accumulate under pathological conditions and may lead to the destruction of tissue structure, organ dysfunction, and organ failure. Increasing evidence indicates that TRPV1 plays a role in the development and occurrence of fibrotic diseases, including myocardial, renal, pancreatic, and corneal fibrosis. However, the mechanism by which TRPV1 regulates fibrosis remains unclear. This review highlights the comprehensive role played by TRPV1 in regulating pro-fibrotic processes, the potential of TRPV1 as a therapeutic target in fibrotic diseases, as well as the different signaling pathways associated with TRPV1 and fibrosis.

[Screening and Verification of Antioxidant Small Molecular Compounds for Expansion of Human Hematopoietic Stem Cells Ex Vitro].

OBJECTIVE: To screen the antioxidant small molecular compounds with optimal efficiency of expansing the human hematopoietic stem cells (hHSC) In vitro based on antioxidant small molecular compound database of LKT laboratory, and to verify the effects of these compounds on the biological functions of hHSC. METHODS: The umbilial cord blood CD34+ cells were enriched by using the MACS beads; the absolute number and percentage of CD34+ cells and CD34+ CD49f+ cells were detected by high throughput flow cytometry after culture of hHSC with compounds in vitro for 1 week, the SR1 (1 µmol/L) was used as positive control, the candidate compounds were screened out; then 4 compounds were selected for follow-up experiments by comprehensive evaluation of concentration, safety and expansion efficacy, the optimal used concentrations of selected compounds were determined through the concentration gradient analysis, and CFC short-term colony-forming cell test was performed by using the determined concentration so as to verify the effect of compounds on the self-renewal, multilineage differentiation. RESULTS: Out of 85 antioxidant small molecular compounds, 4 compounds (C2968, D3331, B1753 and B3358) with obvious expansion efficacy for CD34+ cells and CD34+ CD49f+ cells were screened out by high throughput flow cytometry; their optimal concentrations of 4 compounds were 0.5 µmol/L for C2968, 1.5 µmol/L for D3331 and 1.5 µmol/L for B1753 and 15 µmol/L for B3358. The CFC assay showed the colony formation number in compound-treated group significantly increased as compared with control group, moreover the self-renewal and multilineage differentiation were maintained. CONCLUSION: The antioxidant small molecular compounds C2968 (0.5 µmol/L), D3331 (1.5 µmol/L), B1753 (1.5 µmol/L) and B3358 (1.5 µmol/L) possess good expansion efficacy for hHSC, they can maintain hHSC self-renewal, at the same time ensure the multilineage differentiation potentiality of hHSC.

Transforming growth factor ß: A potential biomarker and therapeutic target of ventricular remodeling.

Transforming growth factor ß (TGF-ß) is a multifunctional cytokine that is synthesized by many types of cells and regulates the cell cycle. Increasing evidence has led to TGF-ß receiving increased and deserved attention in recent years because it may play a potentially novel and critical role in the development and progression of myocardial fibrosis and the subsequent progress of ventricular remodeling (VR). Numerous studies have highlighted a crucial role of TGF-ß in VR and suggest potential therapeutic targets of the TGF-ß signaling pathways for VR. Changes in TGF-ß activity may elicit anti-VR activity and may serve as a novel therapeutic target for VR therapy. This review we discusses the smad-dependent signaling pathway, such as TGF-ß/Smads, TGF-ß/Sirtuins, TGF-ß/BMP, TGF-ß/miRNAs, TGF-ß/MAPK, and Smad-independent signaling pathway of TGF-ß, such as TGF-ß/PI3K/Akt, TGF-ß/Rho/ROCK,TGF-ß/Wnt/ß-catenin in the cardiac fibrosis and subsequent progression of VR. Furthermore, agonists and antagonists of TGF-ß as potential therapeutic targets in VR are also described.

Linking atrial fibrillation with non-alcoholic fatty liver disease: potential common therapeutic targets.

Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are common chronic non-infectious diseases with rising incidences. NAFLD is an independent risk factor for the onset of AF, after adjusting potentially related factors. The pathogenesis of these diseases share several mechanisms including reduced adiponectin level, insulin resistance, and renin angiotensin aldosterone system (RAAS) activation, in addition to activation of common disease pathways that promote inflammation, oxidative stress, and fibrosis. Furthermore, statins and RAAS blockers exert therapeutic effects concurrently on NAFLD and AF. The common pathogenesis of NAFLD and AF may serve as a potential therapeutic target in the future.

Human menstrual blood-derived mesenchymal stem cells as a cellular vehicle for malignant glioma gene therapy.

Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics. Secretable trimeric TRAIL (stTRAIL) contains the receptor-binding domain of TRAIL, a death ligand that induces apoptosis in tumor cells. To overexpress stTRAIL, MenSCs were infected with efficient adenoviral serotype 35 vectors that had no influence on its broad multipotency and low immunophenotype. The modified MenSCs served as an excellent local drug delivery system for tumor site-specific targeted delivery and demonstrated therapeutic efficacy in an animal xenografts tumor model of U-87 MG cells. The MenSC-stTRAIL cells induced antitumor effects in vitro by significantly increasing apoptosis (P < 0.05). It also significantly reduced tumor burden in vivo (P < 0.05). The results showed that the proliferation of tumor cells was significantly reduced (P < 0.05). The MenSC, as a cellular delivery vehicle has a wide potential therapeutic role, which includes the treatment of tumors.

The regulation of immune cells by Lactobacilli: a potential therapeutic target for anti-atherosclerosis therapy.

Atherosclerosis is an inflammatory disease regulated by several immune cells including lymphocytes, macrophages and dendritic cells. Gut probiotic bacteria like Lactobacilli have been shown immunomodificatory effects in the progression of atherogenesis. Some Lactobacillus stains can upregulate the activity of regulatory T-lymphocytes, suppress T-lymphocyte helper (Th) cells Th1, Th17, alter the Th1/Th2 ratio, influence the subsets ratio of M1/M2 macrophages, inhibit foam cell formation by suppressing macrophage phagocytosis of oxidized low-density lipoprotein, block the activation of the immune system with dendritic cells, which are expected to suppress the atherosclerosis-related inflammation. However, various strains can have various effects on inflammation. Some other Lactobacillus strains were found have potential pro-atherogenic effect through promote Th1 cell activity, increase pro-inflammatory cytokines levels as well as decrease anti-inflammatory cytokines levels. Thus, identifying the appropriate strains is essential to the therapeutic potential of Lactobacilli as an anti-atherosclerotic therapy.

Iodine-125 Brachytherapy Prophylaxis after Radiofrequency Ablation Cannot Benefit Patients in High Risk of Locoregional Hepatocellular Carcinoma Recurrence.

This study evaluated if iodine-125 brachytherapy prophylaxis after radiofrequency ablation (RFA) prolongs time to recurrence (TTR) and overall survival (OS) of patients in high risk of locoregional hepatocellular carcinoma (HCC) recurrence. 116 patients with total tumor necrosis after RFA were divided into iodine-125 brachytherapy prophylaxis treatment group and control group. The primary endpoint was TTR, and secondary endpoints were OS and treatment-related adverse events. There were no significant differences among the baseline characteristics of two subgroups patients. The mean iodine-125 particles were 29.8 (26.59 ± 12.51 mCi) per patient. The mean follow-up was 25 months, and mean TTR of treatment and control groups were 21.7 and 15.9 months (P = 0.733); mean OS of two subgroups were 41.7 and 40.9 months (P = 0.316). There were no significant differences of 1-, 2-, 3-, 4-and 5-years TTR and OS and patients' immunity pre- and 1 month post-treatment. Extrahepatic metastasis was found to have a statistically significant influence on TTR, and AFP, extrahepatic metastasis were found to have a statistically significant influence on OS by multivariate analysis. There was no major complications and procedure related death. Iodine-125 brachytherapy prophylaxis after RFA can't improve TTR and OS of HCC patients who were in high risk of locoregional tumor recurrence.

Antineoplastic effects of CPPTL via the ROS/JNK pathway in acute myeloid leukemia.

Drug resistance and human leukocyte antigen (HLA) matching limit conventional treatment of acute myeloid leukemia (AML). Although several small molecule drugs are clinically used, single drug administration is not sufficient to cure AML, which has a high molecular diversity. Metabolic homeostasis plays a key role in determining cellular fate. Appropriate levels of reactive oxygen species (ROS) maintain the redox system balance, and excessive amounts of ROS cause oxidative damage, thus providing a strategy to eliminate cancer cells. CPPTL is a novel analogue of parthenolide that exhibited significant cytotoxicity to AML cells in vitro and induced apoptosis in a dose-dependent manner. Additionally, CPPTL's prodrug DMA-CPPTL decreased the burden of AML engraftment and prolonged survival in a mouse model administered human primary AML cells in vivo. CPPTL induced apoptosis of AML cells by stimulating ROS production, and accumulation of ROS then activated the JNK pathway, thereby promoting mitochondrial damage. These results demonstrated that CPPTL effectively eradicated AML cells in vitro and in vivo and suggested that CPPTL may be a novel candidate for auxiliary AML therapy.

Trimetazidine in conditions other than coronary disease, old drug, new tricks?

Trimetazidine (TMZ) has traditionally been used as an anti-ischemic drug for coronary artery disease by selectively inhibiting the mitochondrial long-chain 3-ketoacyl-CoA thiolase. Recently, new applications for this therapy have been investigated. This article reviews alternative uses for TMZ in non-coronary artery diseases, such as non-ischemic cardiomyopathy, sepsis, myocardial dysfunction induced by anti-cancer drugs, diabetic cardiomyopathy and contrast-induced nephropathy.

Association between serum 25-hydroxyvitamin D and carotid atherosclerotic plaque in Chinese type 2 diabetic patients.

In this study, we investigated the distribution of vitamin D and its association with carotid atherosclerotic plaque (CP) in Chinese type 2 diabetic (T2D) patients. We performed a cross-sectional study in 210 T2D and 94 age- and gender-matched nondiabetic patients during winter months, by determining serum 25-hydroxyvitamin D (25(OH)D) levels in both diabetic and nondiabetic controls. We carried out measurements of B-mode ultrasonography of carotid arteries in each T2D patient. The 25(OH)D concentration was 26.25 nmol/L among the T2D patients. About 93.3% T2D patients suffered from hypovitaminosis D. First, we found a clear inverse correlation between the 25(OH)D concentration and CP (P <0.001). Second, an association between 25(OH)D and macrovascular disease was significant (P = 0.005). In multivariate logistic regression analysis, decreasing 25(OH)D concentration was markedly associated with CP in T2D patients. Third, after adjusting for the confounding factors, we also observed a positive correlation between low levels of 25(OH)D in T2D patients with CP, when the following parameters were measured: old age (odds ratio [OR] = 2.533, P = 0.013); smoking (OR = 3.872, P = 0.001); and high level of low-density lipoprotein (LDL) cholesterol (OR = 2.776, P = 0.009). Thus, we concluded that high prevalence of hypovitaminosis D exists in Chinese T2D patients. Further, we found a significant association between low concentration of serum 25(OH)D and the existence of high body mass index, and high circulating LDL to be substantially positive predictors of patients with CP in T2D.

Statins in conditions other than hypocholesterolemic effects for chronic subdural hematoma therapy, old drug, new tricks?

Chronic subdural hematoma (CSDH) is one of the most common intracranial hematomas worldwide with a high incidence in the general population. However, the optimum treatment for CSDH is Burr-hole drainage with or without rinse Considering the poor outcomes of CSDH in aged patients, and ambiguous prediction of recurrence in many sides of recurrent CSDHs who have been analyzed, new effective therapies are needed for those CSDHs who are predicated to have poor prognosis for surgery and/or have a higher risk of recurrence. Statins, which is the first-line treatment for patients with high cholesterol and coronary heart disease. However, statins are still not solely limited in the treatment of these diseases. It has been demonstrated that statins could improve CSDH due to its effect of regulation of angiogenesis and inflammation. In this review, in order to provide potential new treatment for CSDH we summarize the recent findings of statins in CSDH in order to try to clarify the mechanisms of this effect.

Cholesterol pericarditis associated with rheumatoid arthritis: A rare case report.

BACKGROUND: Cholesterol pericarditis (CP) is a special type of pericarditis. It is characterized by chronic pericardial effusion with high cholesterol concentration and with or without the formation of crystals in pericardial effusion. METHODS: In this case report, we described a 74-year-old male with massive pericardial effusion. He presented with no symptoms. However, he had 8-year history of rheumatoid arthritis medicated with methotrexate, celecoxib, and prednisone, and 5-year history of hypertension medicated with amlodipine besylate. On admission, transthoracic echocardiography revealed a large pericardial effusion. RESULTS: We performed pericardiocentesis for this patient and a lot of cholesterol crystals were found in pericardial effusion under the microscope. A successful operation of thoracoscopic pericardiectomy was proceeded, and the diagnosis was confirmed by surgical pathology. The patient was well recovered and discharged on the tenth day after surgery. It could be predicted that pericardiectomy under video-assisted thoracoscope could be a promising therapy for CP. CONCLUSION: Rheumatoid arthritis may cause CP with no symptoms. Pericardiectomy could be a promising therapy for CP.

Regulatory T cells, especially ICOS+ FOXP3+ regulatory T cells, are increased in the hepatocellular carcinoma microenvironment and predict reduced survival.

Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3+, CD4+, and CD8+ cytotoxic lymphocytes (CTLs) as well as CD56+ NK cells and CD68+ macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3+ (FOXP3+) Tregs were found in intratumoural tissue. Additionally, regarding ICOS+ FOXP3+ Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3+ cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3+ Tregs/CD4+ T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3+ Tregs, especially ICOS+ FOXP3+ Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC.

Treatment strategy for treating atrial-esophageal fistula: esophageal stenting or surgical repair?: A case report and literature review.

INTRODUCTION: Atrial-esophageal fistula (AEF) is a rare severe disease, which may be associated with radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) or intraoperative radiofrequency ablation of atrial fibrillation (IRAAF). CLINICAL FINDINGS: We reported a case of a 67-year-old man with AEF following RFCA of AF, who treated with esophageal stenting and surgical repair. OUTCOMES: He was attacked by out-of-control sepsis and infectious shock after surgery and died. LITERATURE REVIEW: We analyzed 57 relevant articles about AEF from 2003 to 2015 by searching PubMed database. According literatures, the most common symptoms were fever, rigor, sepsis, and neurologic symptoms. Chest computer tomography (CT) and contrast enhanced CT may be the reliable noninvasive diagnosis methods because of high sensitive for AEF. CONCLUSION: Make a definition diagnosis in time with early primary surgical repair may save their lives. Conservative treatment or esophageal stenting alone may not be a better choice for AEF patients.