The aim of this study was to observe the impact of dexmedetomidine on postoperative myocardial injury in patients undergoing off-pump coronary artery bypass (OPCAB) grafting. One hundred and sixty-two patients who were undergoing OPCAB surgery were randomly divided into control and dexmedetomidine groups (groups C and Dex, respectively). Following the first vascular anastomosis grafting, the patients in group Dex received a continuous intravenous infusion of 0.2–0.5 μg/kg/h dexmedetomidine, until they were transferred to the Cardiac Surgery intensive care unit (ICU) for 12 h. Patients in group C received physiological saline intraoperatively and an intravenous infusion of 2–4 mg/kg/h isopropylphenol for postoperative sedation. Invasive arterial pressure and heart rate were continuously monitored for 5 min subsequent to entry into the operating theatre (T0), immediately following surgery (T1), 12 h post-surgery (T2), 24 h post-surgery(T3), 48 h post-surgery(T4) and 72 h post-surgery (T5). Blood samples were taken to determine the plasma levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) at each time point. At 72 h post-surgery, a dynamic electrocardiogram was monitored. The blood pressure, heart rate, levels of cTnI, CK-MB, norepinephrine and cortisol, and postoperative arrhythmic events in the patients in group Dex all decreased compared with those in group C. The duration of mechanical ventilation and ICU residence time were also shorter than those in the control group (P<0.05). Dexmedetomidine reduced post-surgical myocardial injury in patients who had undergone OPCAB surgery.

Myocardial ischemia-reperfusion (MI/R) injury is characterized by iron deposition and reactive oxygen species production, which can induce ferroptosis. Ferroptosis has also been proposed to promote cardiomyocyte death. The current study sought to define the mechanism governing cardiomyocyte death in MI/R injury. An animal model of MI/R was established by ligation and perfusion of the left anterior descending coronary artery, and a cellular model of IR was constructed in cardiomyocytes. ChIP assay was then conducted to determine the interaction among USP22, SIRT1, p53, and SLC7A11. Loss-and gain-of-function assays were also conducted to determine the in vivo and in vitro roles of USP22, SIRT1, and SLC7A11. The infarct size and pathological changes of myocardial tissue were observed using TCC and hematoxylin-eosin staining, and the levels of cardiac function-and myocardial injury-related factors of rats were determined. Cardiomyocyte viability and apoptosis were evaluated in vitro, followed by detection of ferroptosis-related indicators (glutathione (GSH), reactive oxygen species, lipid peroxidation, and iron accumulation). USP22, SIRT1, and SLC7A11 expressions were found to be down-regulated, whereas p53 was highly expressed during MI/R injury. USP22, SIRT1, or SLC7A11 overexpression reduced the infarct size and ameliorated pathological conditions, cardiac function, as evidenced by reduced maximum pressure, ejection fraction, maximum pressure rate, and myocardial injury characterized by lower creatine phosphokinase and lactate dehydrogenase levels in vivo. Moreover, USP22, SIRT1, or SLC7A11 elevation contributed to enhanced cardiomyocyte viability and attenuated ferroptosis-induced cell death in vitro, accompanied by increased GSH levels, as well as decreased reactive oxygen species production, lipid peroxidation, and iron accumulation. Together, these results demonstrate that USP22 overexpression could inhibit ferroptosis-induced cardiomyocyte death to protect against MI/R injury via the SIRT1/p53/SLC7A11 association.

BackgroundAngiotensin II (Ang II)–induced cardiac remodeling with the underlying mechanisms involving inflammation and fibrosis has been well documented. Cytosolic adaptor caspase recruitment domain 9 (CARD9) has been implicated in the innate immune response. We aimed to examine the role of CARD9 in inflammation and cardiac fibrosis induced by Ang II.MethodsTwo-month-old CARD9-deficient (CARD9−/−) and wild-type (WT) male mice were infused with Ang II (1,500 ng/kg/min) or saline for 7 days. Heart sections were stained with hematoxylin and eosin and Masson trichrome and examined by immunohistochemistry; and activity and protein levels were measured in macrophages obtained from mice.ResultsWT mice with Ang II infusion showed a marked increase in CARD9+ macrophages in the heart, but CARD9−/− mice showed significantly suppressed macrophage infiltration and expression of proinflammatory cytokines, including interleukin-1β (IL-1β) and connective tissue growth factor (CTGF). Importantly, Ang II–induced cardiac fibrosis (extracellular matrix and collagen I deposition) was diminished in CARD9−/− hearts, as was the expression of transforming growth factor-β (TGF-β) and level of myofibroblasts positive for α-smooth muscle actin (α-SMA). Furthermore, Ang II activation of nuclear factor-κB (NF-κB), JNK and p38 mitogen-activated protein kinases (MAPKs) in WT macrophages was reduced in CARD9−/− macrophages.ConclusionCARD9 plays an important role in regulating cardiac inflammation and fibrosis in response to elevated Ang II.

Abstract Aims Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r) and Na-Cl co-transporter (NCC). In human and mouse AAA lesions, IL18 colocalizes to its receptors at regions rich in adipocytes, suggesting a role of adipocytes in promoting IL18 actions in AAA development. Methods and results We localized both IL18r and NCC in human and mouse AAA lesions. Murine AAA development required both receptors. In mouse AAA lesions, IL18 binding to these receptors increased at regions enriched in adipocytes or adjacent to perivascular adipose tissue. 3T3-L1 adipocytes enhanced IL18 binding to macrophages, aortic smooth muscle cells (SMCs), and endothelial cells by inducing the expression of both IL18 receptors on these cells. Adipocytes also enhanced IL18r and IL18 expression from T cells and macrophages, AAA-pertinent protease expression from macrophages, and SMC apoptosis. Perivascular implantation of adipose tissue from either diet-induced obese mice or lean mice but not that from leptin-deficient ob/ob mice exacerbated AAA development in recipient mice. Further experiments established an essential role of adipocyte leptin and fatty acid-binding protein 4 (FABP4) in promoting IL18 binding to macrophages and possibly other inflammatory and vascular cells by inducing their expression of IL18, IL18r, and NCC. Conclusion Interleukin-18 uses both IL18r and NCC to promote AAA formation. Lesion adipocyte and perivascular adipose tissue contribute to AAA pathogenesis by releasing leptin and FABP4 that induce IL18, IL18r, and NCC expression and promote IL18 actions.

Objective Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other. Approach and Results Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II (Ang-II) into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell (SMC) loss, cell proliferation, and angiogenesis in AAA lesions. ALI also increased plasma IgE, reduced plasma IL5, and increased bronchioalveolar total inflammatory cell and eosinophil accumulation. Intraperitoneal administration of an anti-IgE antibody suppressed AAA lesion formation and reduced lesion inflammation, plasma IgE, and bronchioalveolar inflammation. Pre-establishment of ALI also increased AAA lesion size and lesion accumulation of macrophage, mast cell, and media SMC loss, increased plasma IgE, reduced plasma IL5, IL13, and TGF-β, and increased bronchioalveolar inflammation. Consequent production of ALI also doubled lesion size of pre-established AAA and increased lesion mast cell and T cell accumulation, media SMC loss, lesion cell proliferation and apoptosis, plasma IgE, and bronchioalveolar inflammation. In peri-aortic CaCl2 injury-induced AAA in mice, production of ALI also increased AAA formation, lesion inflammation, plasma IgE, and bronchioalveolar inflammatory cell accumulation. Conclusion This study suggests a pathologic link between airway allergic disease and AAA. Production of one disease aggravates the progression of the other.

Immune escape of renal cell carcinoma (RCC) impacts patient survival. However, the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in RCC immune escape remains unclear. Quantitative real‐time PCR and western blotting results revealed that the expression of lncRNA SNHG1 and STAT3 were upregulated in RCC tissues and cells and that the expression of miR‐129‐3p was downregulated. Enzyme‐linked immunosorbent assay results revealed the increased levels of immune‐related factors (interferon‐γ, tumour necrosis factor α, and interleukin‐2) in RCC tissues. SNHG1 knockdown or miR‐129‐3p overexpression inhibited the proliferation and invasion of A498 and 786‐O cells, while the proliferation and cytotoxicity of CD8+ T cells increased, which promoted the secretion of immune‐related factors. STAT3 overexpression decreased the protective effect of miR‐129‐3p overexpression on RCC cell immune escape. In addition, miR‐129‐3p knockdown and STAT3 overexpression decreased the protective effect of lncRNA SNHG1 knockdown on RCC cell immune escape. In addition, PD‐L1 expression was downregulated after lncRNA SNHG1 knockdown but upregulated after miR‐129‐3p knockdown and STAT3 overexpression. Dual‐luciferase assays showed that lncRNA SNHG1 targets miR‐129‐3p, and miR‐129‐3p targets STAT3. RNA pull‐down and RNA immunoprecipitation assays verified the regulatory relationship between SNHG1 and STAT3. In vivo, shSNHG1 prolonged the overall survival of RCC tumour model mice and inhibited RCC tumour growth and immune escape but increased CD8+ T cell infiltration in mice. Our findings provide an experimental basis for elucidating the molecular mechanisms of immune escape by RCC and reveal a novel target to treat this disease.

No abstract

Laparoscopic cholecystectomy is a broadly used technique for gallbladder treatment. However, situs inversus, a rare anomaly, is reportedly difficult to treat by conventional laparoscopic cholecystectomy. A 36-year-old woman with chronic cholecystitis and multiple gallstones was found to have dextrocardia on a chest X-ray. Magnetic resonance imaging demonstrated situs inversus, cholecystitis, and cholelithiasis. We successfully performed laparoscopic cholecystectomy using our modified technique, which mainly involved a left-handed operation and adjustment of the port positions. This case will be very instructive for right-handed surgeons in the management of cholelithiasis by laparoscopic cholecystectomy in patients with situs inversus.