Associations between bone mineral density and abdominal aortic calcification: Results of a nationwide survey.

BACKGROUND AND AIMS: Vascular calcification has been linked to bone mineral density (BMD). This study aimed to investigate the association between BMD and abdominal aortic calcification (AAC). METHODS AND RESULTS: Data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were utilized. Participants lacking BMD and AAC score data were excluded. BMD at the femoral neck was measured using dual-energy X-ray absorptiometry. AAC scores were assessed using the Kauppila scoring system, with AAC defined as a score greater than zero, and severe AAC defined as a score greater than six. Weighted multivariable regression analysis and subgroup analysis were conducted to examine the independent relationship between BMD and AAC score, AAC, and severe AAC. A total of 2965 participants were included. After adjusting for multiple covariates, BMD showed a negative association with higher AAC scores (ß = -0.17, 95% CI -0.29, -0.05, p = 0.0066). The odds of having AAC and severe AAC decreased by 9% and 16%, respectively, for every one-unit increase in BMD (AAC: odds ratio [OR] = 0.91, 95% CI 0.82, 1.00, p = 0.0431; severe AAC: OR = 0.84, 95% CI 0.71, 0.99, p = 0.0334). CONCLUSION: Low BMD is associated with higher AAC scores and an increased risk of AAC and severe AAC. Considering the detrimental impact of low BMD on cardiovascular health, individuals with AAC should be evaluated for osteopenia and osteoporosis in clinical settings.

Effects of percutaneous closure of atrial septal defects via the right internal jugular vein.

Background: Percutaneous atrial septal defect (ASD) closure is the preferred treatment for patients with suitable ASD anatomy. The safety and effectiveness of transcatheter closure have been established. However, reports on transesophageal echocardiography (TEE)-guided percutaneous closure of ASD via the right internal jugular vein (RIJV) are limited. The study aims to discuss the safety and effectiveness of percutaneous trans-jugular vein closure of ASD. Methods: We conducted a retrospective analysis of patients (n=103) with secondary ASD who underwent surgical treatment in the Department of Cardiovascular Surgery, the Second Hospital of Jilin University between July 2015 to July 2022. The article is a cross-sectional study. Clinical data, including age, gender, weight, defect diameter, tricuspid regurgitation, left atrial (LA) size, and the operation results, were collected and evaluated. Nonparametric rank sum tests were used to assess tricuspid regurgitation before and after surgery, while paired sample t-tests were used to compare LA size before and after surgery. Results: TEE-guided percutaneous closure of ASD via the RIJV was successfully performed in 97 out of 103 (94.2%) cases. The average procedure time was 34.48±13.06 min, and the mean age at the time of the procedure and ASD size were 36±18 years and 15.45±5.82 mm, respectively. On analyzing medical records and echocardiographic images, postoperative complications were found to occur in four (3.9%) patients. Among these, three patients had residual shunt as indicated by echocardiography during the operation, which subsequently disappeared at the three-month follow-up. One patient developed atrial fibrillation after surgery but returned to normal sinus rhythm with medication. Percutaneous closure of ASD via the RIJV was unsuccessful in 6 patients (5.8%), with 5 of them undergoing transthoracic ASD closure and achieving satisfactory results. One patient refused further surgical treatment. No pericardial effusion, thrombosis, atrioventricular block, or other complications were observed during the 3-month to 1-year follow-up period. Conclusions: ASD closure via the RIJV is a safe and effective therapeutic approach. The initial results are satisfactory, but further studies with large sample sizes and long-term follow-up are warranted to assess the long-term outcomes.

Biomaterials-mediated targeted therapeutics of myocardial ischemia-reperfusion injury.

Reperfusion therapy is widely used to treat acute myocardial infarction. However, its efficacy is limited by myocardial ischemia-reperfusion injury (MIRI), which occurs paradoxically due to the reperfusion therapy and contributes to the high mortality rate of acute myocardial infarction. Systemic administration of drugs, such as antioxidant and anti-inflammatory agents, to reduce MIRI is often ineffective due to the inadequate release at the pathological sites. Functional biomaterials are being developed to optimize the use of drugs by improving their targetability and bioavailability and reducing side effects, such as gastrointestinal irritation, thrombocytopenia, and liver damage. This review provides an overview of controlled drug delivery biomaterials for treating MIRI by triggering antioxidation, calcium ion overload inhibition, and/or inflammation regulation mechanisms and discusses the challenges and potential applications of these treatments clinically.

Hydrogen sulfide: A new therapeutic target in vascular diseases.

Hydrogen sulfide (H2S) is one of most important gas transmitters. H2S modulates many physiological and pathological processes such as inflammation, oxidative stress and cell apoptosis that play a critical role in vascular function. Recently, solid evidence show that H2S is closely associated to various vascular diseases. However, specific function of H2S remains unclear. Therefore, in this review we systemically summarized the role of H2S in vascular diseases, including hypertension, atherosclerosis, inflammation and angiogenesis. In addition, this review also outlined a novel therapeutic perspective comprising crosstalk between H2S and smooth muscle cell function. Therefore, this review may provide new insight inH2S application clinically.

Filamentous Bacteriophage-A Powerful Carrier for Glioma Therapy.

Glioma is a life-threatening malignant tumor. Resistance to traditional treatments and tumor recurrence present major challenges in treating and managing this disease, consequently, new therapeutic strategies must be developed. Crossing the blood-brain barrier (BBB) is another challenge for most drug vectors and therapy medications. Filamentous bacteriophage can enter the brain across the BBB. Compared to traditional drug vectors, phage-based drugs offer thermodynamic stability, biocompatibility, homogeneity, high carrying capacity, self-assembly, scalability, and low toxicity. Tumor-targeting peptides from phage library and phages displaying targeting peptides are ideal drug delivery agents. This review summarized recent studies on phage-based glioma therapy and shed light on the developing therapeutics phage in the personalized treatment of glioma.

Uncovering the Underlying Mechanisms of Ketamine as a Novel Antidepressant.

Major depressive disorder (MDD) is a devastating psychiatric disorder which exacts enormous personal and social-economic burdens. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been discovered to exert rapid and sustained antidepressant-like actions on MDD patients and animal models. However, the dissociation and psychotomimetic propensities of ketamine have limited its use for psychiatric indications. Here, we review recently proposed mechanistic hypotheses regarding how ketamine exerts antidepressant-like actions. Ketamine may potentiate α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR)-mediated transmission in pyramidal neurons by disinhibition and/or blockade of spontaneous NMDAR-mediated neurotransmission. Ketamine may also activate neuroplasticity- and synaptogenesis-relevant signaling pathways, which may converge on key components like brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) and mechanistic target of rapamycin (mTOR). These processes may subsequently rebalance the excitatory/inhibitory transmission and restore neural network integrity that is compromised in depression. Understanding the mechanisms underpinning ketamine's antidepressant-like actions at cellular and neural circuit level will drive the development of safe and effective pharmacological interventions for the treatment of MDD.

GABAergic System Dysfunction in Autism Spectrum Disorders.

Autism spectrum disorder (ASD) refers to a series of neurodevelopmental diseases characterized by two hallmark symptoms, social communication deficits and repetitive behaviors. Gamma-aminobutyric acid (GABA) is one of the most important inhibitory neurotransmitters in the central nervous system (CNS). GABAergic inhibitory neurotransmission is critical for the regulation of brain rhythm and spontaneous neuronal activities during neurodevelopment. Genetic evidence has identified some variations of genes associated with the GABA system, indicating an abnormal excitatory/inhibitory (E/I) neurotransmission ratio implicated in the pathogenesis of ASD. However, the specific molecular mechanism by which GABA and GABAergic synaptic transmission affect ASD remains unclear. Transgenic technology enables translating genetic variations into rodent models to further investigate the structural and functional synaptic dysregulation related to ASD. In this review, we summarized evidence from human neuroimaging, postmortem, and genetic and pharmacological studies, and put emphasis on the GABAergic synaptic dysregulation and consequent E/I imbalance. We attempt to illuminate the pathophysiological role of structural and functional synaptic dysregulation in ASD and provide insights for future investigation.

An Addition of U0126 Protecting Heart Grafts From Prolonged Cold Ischemia-Reperfusion Injury in Heart Transplantation: A New Preservation Strategy.

BACKGROUND: Ischemia-reperfusion injury (IRI) is the major cause of primary graft dysfunction in organ transplantation. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) signaling pathway plays a crucial role in cell physiological and pathological processes including IRI. This study aims to investigate whether inhibition of ERK signaling with U0126 can prevent prolonged cold IRI in heart transplantation. METHODS: Rat cardiac cell line H9c2 cells were treated with U0126 before exposure to hypothermic hypoxia/reoxygenation (H/R) conditions. The effect of U0126 on H9c2 cells in response to H/R stress was determined by measuring cell death, reactive oxygen species production, mitochondrial membrane potential, and ERK signaling activation. Mouse syngeneic heterotopic heart transplantation was conducted, where a donor heart was preserved in the University of Wisconsin (UW) solution supplemented with U0126 for 24 hours at 4°C before transplantation. Heart graft function, histopathologic changes, apoptosis, and fibrosis were measured to assess IRI. RESULTS: Phosphorylated ERK was increased in both in vitro H/R-injured H9c2 cells and in vivo heart grafts with IRI. Pretreatment with U0126 inhibited ERK phosphorylation and prevented H9c2 cells from cell death, reactive oxygen species generation, and mitochondrial membrane potential loss in response to H/R. Preservation of donor hearts with U0126-supplemented solution improved graft function and reduced IRI by reductions in cell apoptosis/death, neutrophil infiltration, and fibrosis of the graft. CONCLUSIONS: Addition of U0126 to UW solution reduces ERK signal activation and attenuates prolonged cold IRI in a heart transplantation model. ERK inhibition with U0126 may be a useful strategy to minimize IRI in organ transplantation.

Circular RNA Foxo3 in cardiac ischemia-reperfusion injury in heart transplantation: A new regulator and target.

Ischemia-reperfusion (I/R) injury occurring in heart transplantation (HT) remains as a leading cause of transplant heart graft failure. Circular RNAs (circRNAs) play important roles in gene regulation and diseases. However, the impact of circRNAs on I/R injury during HT remains unknown. This study aims to investigate the role of circular RNA Foxo3 (circFoxo3) in I/R injury in HT. Using an in vivo mouse HT model and an in vitro cardiomyocyte culture model, we demonstrated that circFoxo3 is significantly upregulated in I/R-injured hearts and hypoxia/reoxygenation (H/R)-damaged cardiomyocytes. Knockdown of circFoxo3 using siRNA not only reduces cell apoptosis and death, mitochondrial damage, and expression of apoptosis/death-related genes in vitro, but also protects heart grafts from prolonged cold I/R injury in HT. We also show that circFoxo3 interacts with Foxo3 proteins and inhibits the phosphorylation of Foxo3 and that it indirectly affects the expression of miR-433 and miR-136. In conclusion, circRNA is involved in I/R injury in HT and knockdown of circFoxo3 with siRNA can reduce I/R injury and improve heart graft function through interaction with Foxo3. This study highlights that circRNA is a new type of molecular regulator and a potential target for preventing I/R injury in HT.

A New Aortic Arch Inclusion Technique with Frozen Elephant Trunk for Aortic Arch Aneurysm Treatment.

Various surgical techniques have been proposed for treating aortic arch aneurysm (AAA); however, the optimal treatment has not been well defined. This study introduces a new aortic arch inclusion technique with frozen elephant trunk (FET) for AAA treatment.A retrospective analysis was performed among 22 patients for AAA surgical treatment between March 2010 and March 2019. Patients were classified into Z1, Z2, and Z3 groups based on the origins of aneurysms. A stent graft with a 10 cm stented graft and 5-9 cm proximal vascular prosthesis was released into the descending thoracic aorta as FET through an incision in the aortic arch. The proximal vascular prosthesis was retracted into the aortic arch, trimmed to expose the orifices of the brachiocephalic vessels, and sutured inside the aortic arch using the inclusion technique. The proximal sealing location of the vascular graft was tailored to cover the origins of aneurysms.There was no 30-day mortality. No patient had postoperative stroke or paraplegia. Complete aneurysm thrombosis was achieved in all patients. One patient died of severe respiratory tract stenosis 3 months postoperatively. All other 21 patients were alive during 53.3 ± 36.5-month follow-up. Computed tomography angiography was obtained in 15 patients during follow-up. Endoleak was observed in one patient, and the other 14 patients were free from aneurysm-related or graft-related complications during follow-up.The aortic arch inclusion technique with FET provides an alternative technique in treating AAA with satisfactory mid-term follow-up results. A larger patient population with long-term follow-up results is warranted.

The role of miR-711 in cardiac cells in response to oxidative stress and its biogenesis: a study on H9C2 cells.

BACKGROUND: Oxidative stress results in cell apoptosis/death and plays a detrimental role in disease development and progression. Stressors alter the miRNA expression profile and miRNAs play a role in the cell response to stress. We previously showed that miR-711 is significantly over-expressed in extended cold ischemia reperfusion injured hearts in heart transplant. In this study, we aimed to investigate the role of miR-711 in cardiac cell damage in response to oxidative stress and how miR-711 is regulated. METHODS: Rat cardiac cell line H9c2 cells were cultured and exposed to oxidative conditions (Antimycin A (AA), H2O2, CoCl2, or cold hypoxia/reoxygenation (H/R)) in vitro. H9c2 cells were transfected with miR-711 mimics, miR-711 inhibitors, or small interference RNA, using transfection reagents. The expression of miR-711 was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell apoptosis/death was detected by flow cytometry and an IncuCyte system. Mitochondrial damage was detected by measuring the mitochondria membrane potential by flow cytometry. Gene expression was detected by qRT-PCR at the mRNA level and Western blotting and immunocytochemistry staining at the protein level. RESULTS: We found that miR-711 was significantly up-regulated in cells treated with H2O2, AA, CoCl2, and cold H/R. Over-expression of miR-711 increased cell apoptosis/death induced by AA and H/R whereas cell death was reduced by miR-711 inhibitors. MiR-711 induced cell death through negative regulation of angiopoietin 1 (Ang-1), fibroblast growth factor 14 (FGF14) and calcium voltage-gated channel subunit alpha1C (Cacna1c) genes. Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. CONCLUSION: Oxidative stress increases the expression of miR-711. Over-expression of miR-711 induces cell apoptosis/death. HIF-1α and NFКB regulate miR-711 in H9c2 cells during oxidative stress. miR-711 is a new target for preventing oxidative stress.

Plk2 Regulated by miR-128 Induces Ischemia-Reperfusion Injury in Cardiac Cells.

Ischemia-reperfusion (I/R) injury occurs during cardiac surgery and is the major factor leading to heart dysfunction and heart failure. Our previous study showed that gene and microRNA expression profiles are altered in heart grafts with extended I/R injury. In this study, we, for the first time, demonstrated that I/R injury upregulates the expression of Polo-like kinase 2 (Plk2) but decreases miR-128 expression in heart cells both in vitro and in vivo. Silencing Plk2 using small interfering RNA (siRNA) protects cells from Antimycin A-induced cell apoptosis/death. Silencing Plk2 also decreases phosphorylated p65 expression but increases Angiopoietin 1 expression. In addition, Plk2 is negatively regulated by miR-128. miR-128 exerts a protective effect on cell apoptosis similar to Plk2 siRNA in response to I/R stress. Methylation inhibitor 5-azacytidine (5-AZ) increases the expression of miR-128 and subsequently reduces Plk2 expression and cell apoptosis. In conclusion, this study demonstrated that Plk2 regulated by miR-128 induces cell apoptosis/death in response to I/R stress through activation of the nuclear factor κB (NF-κB) signal pathway. miR-128 and Plk2 are new targets for preventing cardiac I/R injury or oxidative stress-mediated injury.

A New Aortic Arch Inclusion Technique With Frozen Elephant Trunk for Type A Aortic Dissection.

OBJECTIVE: Our aims were to describe a new surgical technique for the treatment of type A aortic dissection (TAAD) and to report the operative outcomes of 154 patients. SUMMARY BACKGROUND DATA: Surgical treatment of TAAD is complicated and carries a high mortality risk. To lower this risk, we developed a simplified procedure in which a stent graft was implanted as frozen elephant trunk (FET), and the proximally trimmed vascular graft was sutured from the inside of the aortic arch using the inclusion technique under moderate hypothermic circulatory arrest and antegrade selective cerebral perfusion. METHODS: We conducted a retrospective analysis of 154 cases of TAAD treated with our novel technique (93 men and 61 women, 52.5 ±â€Š11.4 years). Computed tomography angiography was performed before discharge and at 6 months postoperatively. RESULTS: In-hospital mortality rate was 5.19%, with paraplegia occurring in 2 patients (1.3%) and stroke in 6 (3.9%). The rate of closure of the aortic arch false lumen was 77.8%, with a 69.2% rate of descending thoracic aorta thrombosis at discharge. The survival rate was 91.1% at a mean follow-up of 21 ±â€Š10 months, with rates of aortic arch false lumen closure of 92.4% and descending thoracic aorta thrombosis of 74.3% at 6 months postoperatively. CONCLUSIONS: The aortic arch inclusion technique with FET provides a safe alternative for TAAD treatment, with satisfactory operative results. Short-term follow-up results are encouraging, and long-term outcomes need further evaluation.

A New Aortic Root Reinforcement Technique for Acute Type A Aortic Dissection Surgery.

Reinforcing the dissected and fragile aortic root is critical in acute type A aortic dissection (ATAAD) surgery. This study introduces our new aortic root reinforcement technique and reports our early operative results and midterm follow-up results.A retrospective analysis study was performed on 235 patients (aged 53.2 ±15.5 years) who were admitted to our hospital for ATAAD surgery and underwent the procedure with our new technique between October 2011 and June 2016. Two vascular graft rings were placed inside and outside aortic root, followed by a running horizontal mattress suture, placed just above the coronary artery ostiums and aortic valve commissures, with another horizontal suture at distal end of the aortic root stump, to reinforce the inner vascular graft, aortic wall, and outside vascular graft. Then additional 3-5 vertical mattress sutures were placed for further reinforcement within the reconstructed aortic root. Computed tomography angiography was performed at discharge and annually during follow-up.The patients' 30-day mortality was 5.1% (12/235). There was no uncontrollable intraoperative bleeding from the aortic root, and re-exploration for bleeding occurred in 0.79% (2/235). The survival rate was 90.2% during follow-up of 4.2 ± 2.1 years. There were no requests for aortic root reoperations during follow-up. All patients were free from aortic root disruptions, proximal anastomosis complications, and re-dissections of the reconstructed aortic root.Our new aortic root reinforcement technique provides a safe and effective technique for aortic root in ATAAD surgery, by reinforcing friable aortic root tissues and minimizing aortic root complications.

Supplementing preservation solution with mitochondria-targeted H2 S donor AP39 protects cardiac grafts from prolonged cold ischemia-reperfusion injury in heart transplantation.

Heart transplant has been accepted as the standard treatment for end-stage heart failure. Because of its susceptibility to ischemia-reperfusion injury, the heart can be preserved for only 4 to 6 hours in cold static preservation solutions. Prolonged ischemia time is adversely associated with primary graft function and long-term survival. New strategies to preserve donor hearts are urgently needed. We demonstrate that AP39, a mitochondria-targeting hydrogen sulfide donor, significantly increases cardiomyocyte viability and reduces cell apoptosis/death after cold hypoxia/reoxygenation in vitro. It also decreases gene expression of proinflammatory cytokines and preserves mitochondria function. Using an in vivo murine heart transplant model, we show that preserving donor hearts with AP39-supplemented University of Wisconsin solution (n = 7) significantly protects heart graft function, measured by quantitative ultrasound scan, against prolonged cold ischemia-reperfusion injury (24 hours at 4°C), along with reducing tissue injury and fibrosis. Our study demonstrates that supplementing preservation solution with AP39 protects cardiac grafts from prolonged ischemia, highlighting its therapeutic potential in preventing ischemia-reperfusion injury in heart transplant.

Role of Leptin in Mood Disorder and Neurodegenerative Disease.

The critical regulatory role of leptin in the neuroendocrine system has been widely reported. Significantly, leptin can improve learning and memory, affect hippocampal synaptic plasticity, exert neuroprotective efficacy and reduce the risk of several neuropsychiatric diseases. In terms of depression, leptin could modulate the levels of neurotransmitters, neurotrophic factors and reverse the dysfunction in the hypothalamic-pituitary-adrenal axis (HPA). At the same time, leptin affects neurological diseases during the regulation of metabolic homeostasis. With regards to neurodegenerative diseases, leptin can affect them via neuroprotection, mainly including Alzheimer's disease and Parkinson's disease. This review will summarize the mechanisms of leptin signaling within the neuroendocrine system with respect to these diseases and discuss the therapeutic potential of leptin.

A Vaginal Stillbirth after Aortic Surgery of Type B Aortic Dissection in a Pregnant Woman.

Acute aortic dissection occurring during pregnancy poses great danger to both the mother and fetus. Cesareans are usually performed before or after the aortic repair depending on the conditions of the mother and fetus. Here we report our experience in treating a 32-week pregnant woman with a type B aortic dissection, whose baby had died before admission. A cesarean section was initially arranged after emergency aortic repair. However, the patient started to deliver the fetus vaginally after the aortic surgery and the stillborn baby was delivered vaginally. This case report provides new insight into the method of delivery in a pregnant woman with an aortic dissection.

Aberrant origin of left subclavian artery from the pulmonary artery and right aortic arch in an aortopulmonary window.

Aortopulmonary window (APW) is a rare congenital anomaly that occurs in 0.2-0.6% of congenital heart diseases. APW often coexists with other cardiac malformations. However, APW together with aberrant origin of the left subclavian artery (LSA) from the main pulmonary artery is rarely seen. Here, we report an infant with right aortic arch in APW, who was found to have aberrant origin of the LSA from the main pulmonary artery. We confirmed its origin in the anatomical settings and modified a repair technique according to his individual situation, which brought successful results to the patient.

Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.

Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.