Prediabetes (pre-DM) is recognized as an intermediate state of glucose metabolism with a high potential to progress to diabetes mellitus (DM). However, its prognostic value in patients with premature acute myocardial infarction (PAMI) under the age of 35 remains unclear. This study aimed to investigate the relationship between pre-DM and long-term cardiovascular outcomes in this unique population. This retrospective cohort study included 796 PAMI patients under 35 years of age who were categorized into three groups based to glycated hemoglobin levels or previous history: normal glucose regulation (NGR), pre-DM, and DM. The primary endpoint was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause death, non-fatal myocardial infarction, non-fatal stroke, or revascularization. Multivariable Cox regression, Kaplan–Meier and Subgroup analyses were performed. Pre-DM was observed in 22.1
BACKGROUND:Angiography-derived index of microcirculatory resistance (IMR) has emerged as a feasible alternative to wire-based IMR, due to the elimination of specialized wire and simplifying of the procedure. However, the differences in diagnostic accuracy between hyperemic and resting angiography with this technology remain underexplored. METHODS:This prospective, multicenter study was conducted to evaluate the feasibility and diagnostic accuracy of x-ray angiography-derived IMR (xaIMR) in patients with chronic coronary syndrome using wire-based functional indices as the reference. Angiography-derived functional indices were calculated using a computational fluid dynamics model. The xaIMR indices were derived from hyperemic and resting angiography, respectively. RESULTS:A total of 139 vessels were included in the analysis of the present study. Both hyperemic xaIMR (r=0.82; P<0.001) and resting xaIMR (R-xaIMR) (r=0.25; P=0.003) exhibited positive linear correlations with wire-based IMR. Notably, hyperemic xaIMR was associated with a higher diagnostic yield (area under the receiver operating characteristic curve) than resting xaIMR (area under the receiver operating characteristics curve, 0.95 versus 0.72; P<0.001). Significant differences in diagnostic yield between these modalities were observed in vessels with compromised coronary flow reserve (<2.0). In contrast, such differences were not observed in vessels with normal coronary flow reserve (≥2.0). CONCLUSIONS:xaIMR, especially derived from hyperemic angiography, is a reliable, noninvasive alternative to wire-based IMR for assessing coronary microcirculatory resistance in chronic coronary syndrome. However, resting angiography-derived xaIMR may have limited diagnostic accuracy in patients with reduced coronary flow reserve. Further studies are warranted to validate these findings in broader populations.
The microenvironment characterized by inflammation and oxidative stress plays a crucial role in the pathogenesis of myocardial ischemia-reperfusion (I/R) injury. The death receptor 5 fusion protein (sDR5-Fc) specifically targets and blocks the key protein-tumor necrosis factor related apoptosis inducing ligand (TRAIL), which is involved in cell apoptosis. This study focuses on the development of reactive oxygen species (ROS) intelligent responsive sDR5-Fc nanoparticles, aimed at improving the pathological microenvironment associated with oxidative stress and inflammatory damage, inhibiting myocardial cell apoptosis while worsening, and enhancing the bioavailability and selectivity of sDR5-Fc. The successful synthesis of 6S-PLGE-PO-PEG was verified through infrared nuclear magnetic resonance and other analytical experiments. The ROS intelligent responsive sDR5-Fc nanoparticles (DPP) were successfully constructed in vitro, exhibiting a particle size of approximately 200 nm, as well as a certain stability and H2O2 responsive release ability. DPP demonstrated good biocompatibility. The cell viability and apoptosis assays indicated that DPP significantly reduced myocardial cell damage caused by hypoxia reoxygenation and decreased cell apoptosis. In myocardial I/R rat model, the administration of DPP nanoparticle displayed superior therapeutic effects compared to the sDR5-Fc group, evidenced by the reduction in myocardial infarction area, improvement in fibrosis, decreased myocardial cell apoptosis, increased cell proliferation, enhanced angiogenesis, and inhibition of myocardial hypertrophy. The synergistic effect of ROS responsive sDR5-Fc nanoparticles in mitigating I/R injury is expected to provide a new interdisciplinary treatment approach.
Nonalcoholic fatty liver disease (NAFLD) become a main public health concern, and is characterized by lipid accumulation in the hepatocytes. We found that overexpression of lncRNA MEG3 significantly reduced the expression of FOXO1, ACC1, and FAS, and subsequently decreased the lipid accumulation in HepG2 cells. Moreover, inhibition of lncRNA MEG3 could increase the lipid accumulation and the mRNA and protein levels of FOXO1, ACC1, and FAS. Further study showed that lncRNA MEG3 regulates the lipogenesis process by inhibiting the entry of FOXO1 into the nucleus translocation. Our study demonstrated that lncRNA MEG3 regulates de novo lipogenesis by decreasing the expression and nucleus translocation of FOXO1 in HepG2 cells, suggesting that lncRNA MEG3 could be a promising therapeutic target in lipid metabolic disorders.
Based on data from a large sample in the United States, this study did not find an association between the triglyceride-glucose index and femoral neck bone mineral density or the occurrence of low bone density in community-dwelling males and females without diabetes. ObjectiveTo determine the potential association between the triglyceride-glucose (TyG) index and bone mineral density (BMD) in community-dwelling adults without diabetes using a nationally representative database from the United States (US).MethodsData were extracted from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, 2013-2014, and 2017-2018. Men and postmenopausal women aged >= 50 years with complete data on femoral neck BMD, triglycerides, and fasting plasma glucose levels were eligible for inclusion. Participants with diabetes, history of malignancy, thyroid disease, underweight status, end-stage kidney disease, rheumatoid arthritis, estrogen/selective estrogen receptor modulators, bisphosphonate or bone resorption inhibitors, or missing dataset weight values were excluded. Univariate and multivariable logistic regression analyses were performed to determine the associations between low BMD, TyG index, and other study variables.ResultsA total of 1,844 participants (1,161 men and 683 women) were included, representing 31,517,106 community-dwelling individuals in the US. The mean age of the study population was 60.7 years old, and 26.7% of the men and 60.4% of the women had low bone density. In both males and females, the mean TyG index was 8.6. After adjusting for demographic, lifestyle, and clinical factors, no significant association was observed between TyG and femoral neck BMD among men (adjusted odds ratio [aOR] = -0.0002, 95% confidence interval [CI]: -0.02 to 0.02) and women (aBeta = 0.005, 95% CI: -0.02 to 0.04). Similarly, no significant association was observed between TyG index and the odds for low bone density among men (aOR = 1.09, 95% CI: 0.73-1.63) and women (aOR = 0.99, 95% CI: 0.49-2.01).ConclusionsBased on data from a large sample in the US, this study did not find an association between the TyG index and femoral neck BMD or the occurrence of low bone density in community-dwelling males and females without diabetes.
Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.
Background Patients with DeBakey type II aortic dissection or ascending aortic aneurysms involving the right innominate artery require hemiarch replacement and placement of a right innominate artery graft. Traditional aortic hemiarch replacement surgery must be performed under right axillary artery cannulation perfusion and moderate or deep hypothermia circulatory arrest. However, the axillary artery perfusion is always associated with left subclavian artery “steal blood”, and it cannot guarantee blood supply to the left cerebral hemisphere in patients with an incomplete circle of Willis, and hypothermia and hypoperfusion cause damage to the brain and spinal cord; therefore, postoperative complications of the nervous system are common. Herein, we present a hemiarch replacement procedure with the use of the single branch-first combined with the mid-arch clamping technique. This procedure can not only reduce the axillary artery incision but also eliminate the need for mid-deep hypothermia and circulatory arrest. Case presentation A 41-year-old male patient underwent surgery with this technique. Computed tomography angiography performed upon admission showed calcified plaques scattered throughout the aorta and showed DeBakey type II aortic dissection involving the right innominate artery, accompanied by cardiac tamponade. The patient underwent aortic root repair, ascending aorta replacement, and hemiarch replacement as well as the placement of a right innominate artery graft. Aortic root anastomosis was performed with the embedded anastomosis technique. There were no postoperative complications. The patient was discharged 11 days after the operation. During more than 3 months of follow-up, there were no cases of aortic valve regurgitation or anastomotic fistula. Conclusions The single branch-first combined with the mid-arch clamping technique for the right innominate artery can reduce the axillary artery incision and avoid damage to the body under mid-deep hypothermia and circulatory arrest. The embedded anastomosis technique is easy to perform, results in a limited amount of bleeding and requires almost no extra needling. We believe that these techniques can serve as good alternative strategies for patients with DeBakey type II aortic dissection or ascending aortic aneurysms involving the right innominate artery.
Background Traditional aortic arch replacement surgery must be performed under moderate or deep hypothermia (22–28 °C) and circulatory arrest. Hypothermia and hypoperfusion can cause damage to the nervous system; therefore, postoperative brain and spinal cord complications are common. Improvements in surgical techniques are necessary to solve this problem. Herein, we report a method of total aortic arch replacement that can be performed at a core temperature of 34 °C, similar to other simple cardiac operations. Case presentation Four patients underwent surgery with this technique (3 males and 1 female, aged 48 to 67 years). Computed tomography angiography performed at admission showed a total aortic dissection, resulting in a diagnosis of Stanford type A aortic dissection. The patients underwent emergency aortic sinus remodelling, ascending aortic replacement, modified aortic arch replacement, and elephant trunk stenting. No patients had neurological complications. During a follow-up of more than 1-month, no patients had aortic valve regurgitation or anastomotic leak. Conclusions This technique can increase the operating temperature by approximately 6 to 12 °C and reduce the circulatory arrest time by approximately 18 to 28 min. All of the patients recovered well without any neurological complications, demonstrating the feasibility and safety of this technique. We believe that this technique can serve as a good alternative strategy for managing aortic dissection and aneurysm, especially for young surgeons who are acquiring experience in arch replacement surgery.
Vascular calcification is an important pathogenic process in atherosclerosis (AS); however, its immediate cause is unknown. Our previous study demonstrated that carbonic anhydrase 1 (CA1) stimulates ossification and calcification in ankylosing spondylitis and breast cancer. The current study investigated whether CA1 plays an important role in AS calcification and whether the CA inhibitor methazolamide (MTZ) has a therapeutic effect on AS. We successfully established an AS model by administration of a high-fat diet to apolipoprotein E (ApoE-/-) mice. The treated animals had significantly increased serum levels of high-density lipoprotein cholesterol (HDL-c) and nitric oxide (NO) and decreased serum concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), interleukin (IL-6), interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand 1/keratinocyte-derived chemokine (CXCL1/KC), and C-C motif chemokine ligand 2 (CCL2)/monocyte chemoattractant protein 1 (MCP-1). The treated mice also had reduced AS plaque areas and fat accumulation, with no clear calcium deposition in the intima of the blood vessels. CA1 expression was significantly increased in the aortic lesions, particularly in calcified regions, but the expression was dramatically lower in the mice that received MTZ treatment or MTZ preventive treatment. CA1 was also highly expressed in human AS tissues and in rat vascular smooth muscle cells (VSMCs) with β-glycerophosphate (㒐β-GP)-induced calcification. Acetazolamide (AZ), a CA inhibitor with a chemical structure similar to MTZ, markedly suppressed calcification and reduced CA1, IL-6, IFN-γ, GM-CSF, and TNF-α expression in cultured VSMCs. Anti-CA1 small interfering ribonucleic acid (siRNA) significantly suppressed calcification, cell proliferation, and migration, promoted apoptosis, and reduced IL-6, IFN-γ, GM-CSF, and TNF-α secretion in cultured VSMCs. These results demonstrated that CA1 expression and CA1-mediated calcification are significantly associated with AS progression. MTZ significantly alleviated AS and suppressed CA1 expression and proinflammatory cytokine secretion, indicating the potential use of this drug for AS treatment.
To analyze the relationship between the collateral flow of coronary chronic total occlusion (CTO) and myocardial viability detected by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging.
Coronary angiography(CAG) often showed collateral flow supply for the coronary artery of chronic total occluded(CTO) in asynergic myocardial regions. However, little is reported on the relationship between collateral circulation and positron emission tomographic (PET) patterns of viable myocardium
Background Left-ventricular diverticulum (LD) associated with patent ductus arteriosus (PDA) is extremely rare. We have not found any previous reports of the coexistence of these two malformations. Such an association presenting with chest pain mimicking an infarct aneurysm with angina or a takotsubo cardiomyopathy with chest pain is difficult to differentiate clinically. Here, we discuss several diseases characterized by left-ventricular apical protrusion with chest pain to familiarize clinicians with the differential diagnosis of these diseases. Case presentation A 58-year-old woman was referred to our hospital because of complaints of chest pain and dyspnoea, mainly on exertion. An electrocardiograph on admission showed a q-wave in lead I, a Q-wave in lead aVL, and an abnormal T-wave in the limb leads and leads V4 to V6. A transthoracic echocardiograph revealed a PDA and a protrusion arising from the apex of the left ventricle. The diagnosis on admission was PDA and coronary artery disease with infarct aneurysm. To evaluate the source of the chest pain, further evaluations were performed. Coronary angiography showed no abnormal findings. Left ventriculography confirmed the presence of an apical contractile out-pouching. Based on these findings, we revised the diagnosis as LD associated with PDA. The patient underwent transcatheter occlusion of the PDA and was discharged 3 days later. Unexpectedly, transcatheter occlusion resolved the paroxysmal chest pain in this case. Conclusion This is the first case report of LD combined with PDA. PDA should be considered in the list of differential diagnosis of chest pain. Several diseases characterized by left-ventricular apical protrusion with chest pain, such as LD, infarct aneurysm and takotsubo cardiomyopathy, can be misdiagnosed as one another. Therefore, it is important to familiarize clinicians with the differential diagnosis of these diseases.
This study comparatively evaluates the characteristics of glutaraldehyde-treated acellular bovine and donkey pericardium using histological and electronic microscopic observation techniques, shrinkage temperature, and mechanical properties, as well as determining calcium and phosphorus content at 4 and 8 weeks after the subcutaneous implantation of donkey and bovine pericardium in Wistar rats. Donkey pericardium was significantly thinner compared with bovine pericardium (1.622 ± 0.161 mm vs. 4.027 ± 0.401 mm, P < 0.0001) and was associated with significantly greater tensile strength (14.21 ± 3.81 MPa vs. 3.78 ± 1.20 MPa, P = 0.001) and elastic modulus (81.67 ± 20.41 MPa vs. 21.67 ± 11.69 MPa, P < 0.0001) over bovine pericardium. Shrinkage temperature of donkey pericardium was similar to that of bovine pericardium (87.43 ± 0.55°C vs. 87.50 ± 0.36°C, P = 0.810). No differences between groups were observed for maximum load (donkey: 21.64 ± 7.02 KN/m vs. bovine: 15.05 ± 4.50 KN/m, P = 0.082) and tear strength (donkey: 11.54 ± 5.33 MPa vs. bovine: 10.69 ± 3.77 MPa, P = 0.757). Calcium content was significantly lower in donkey pericardium compared with bovine pericardium at 4 weeks (690.15 ± 191.27 µg/g vs. 1381.73 ± 62.52 µg/g, P = 0.001) and 8 weeks (205.24 ± 62.40 µg/g vs. 910.48 ± 398.29 µg/g, P = 0.037). This preliminary study has confirmed that glutaraldehyde-tanned donkey pericardium, demonstrating reduced calcification and increased tensile strength, may provide a suitable bioprosthetic valve substitute.