Objective To evaluate the effects of all intravenous anesthesia and total inhalation anesthesia on left ventricular systolic and diastolic function in elderly patients undergoing intestinal surgery. Methods Forty elderly patients without any history or signs of cardiovascular disease, 23 males and 17 females, aged 65-80 years, ASA physical status Ⅱ or Ⅲ, were randomly allocated into two groups. Maintenance of anesthesia was achieved by propofol-remifentanil respectively (group P) or sevoflurane inhalation (group S). Transesophageal echocardiography was performed as a baseline after intubation. Left ventricular ejection fraction (LVEF), fractional shortening (FS), peak E, E/A, peak E deceleration time (EDT) were measured after anesthesia induction (T0), 10 min after incision (T1), end of surgery (T2), respectively. Results Compared with T0, LVEF, FS, Peak E, E/A of both groups were similar at T1. There were no statistical differences in LVEF and FS between the two groups at T2. However, the value of peak E and E/A of group S at T2 were significantly increased than the baseline T0 and higher than that of group P (P ＜ 0.05). Meanwhile, EDT at T2 in group S was shorter than that at T0 and significant shorter than in group P (P ＜ 0.05). There were two PONV cases in each of the two groups. Conclusion Sevoflurane had a favourable effect on diastolic function in the elderly patients. Furthermore, sevoflurane showed advantage in maintaining hemodynamic stability during the operative period.

Objective:This study aimed to explore and analyze correlated factors of the characteristics of moderate and severe pain in head and neck cancer (HNC) patients after tissue flap repairment, to provide the basis for the following pain management.Methods:The convenience sampling method was used to enroll 239 patients who underwent tissue flap repairment at the Department of Oral and Maxillofacial Surgery, Peking University Hospital of Stomatology between December 2017 and December 2018 in this study. To classify the types of pain, Verbal Rating Scale (VRS) scores were used to collect the pain symptoms of patients with 6 time periods of wound, throat, infusion, other and non-intervention for 6 days, and analyze the characteristics and correlated factors of moderate and severe pain.Results:Eighty-seven of the 239 patients complained of moderate or severe pain. The distribution of patients age and education level had statistical differences in the presence or absence of moderate to severe pain ( P<0.05) . The cases of sore throat and frequency occurred most frequently among all types of pain. Conclusions:Although patient-controlled analgesia is given to patients after flap repairment, more than one-third of patients still complained of moderate and severe pain. Different types of pain have different characteristics, and throat pain occurred more frequently. Moderate pain was more common in male patients, while severe pain has a much higher proportion in female patients.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.