Activation of sirtuin 1/3 improves vascular hyporeactivity in severe hemorrhagic shock by alleviation of mitochondrial damage

Vascular hyporeactivity is one of the major causes responsible for refractory hypotension and associated mortality in severe hemorrhagic shock. Mitochondrial permeability transition (mPT) pore opening in arteriolar smooth muscle cells (ASMCs) is involved in the pathogenesis of vascular hyporeactivity. However, the molecular mechanism underlying mitochondrial injury in ASMCs during hemorrhagic shock is not well understood. Here we produced an in vivo model of severe hemorrhagic shock in adult Wistar rats. We found that sirtuin (SIRT)1/3 protein levels and deacetylase activities were decreased in ASMCs following severe shock. Immunofluorescence staining confirmed reduced levels of SIRT1 in the nucleus and SIRT3 in the mitochondria, respectively. Acetylation of cyclophilin D (CyPD), a component of mPT pore, was increased. SIRT1 activators suppressed mPT pore opening and ameliorated mitochondrial injury in ASMCs after severe shock. Furthermore, administration of SIRT1 activators improved vasoreactivity in rats under severe shock. Our data suggest that epigenetic mechanisms, namely histone post-translational modifications, are involved in regulation of mPT by SIRT1/SIRT3- mediated deacetylation of CyPD. SIRT1/3 is a promising therapeutic target for the treatment of severe hemorrhagic shock.     

预测子痫前期的生物学标志物研究进展

子痫前期(PE)是围生期母婴发病和死亡的主要原因之一。该病目前尚缺乏有效的治疗手段,终止妊娠是其唯一有效的治疗方法。预测和诊断PE的生物学标志物具有非常重要的临床意义。过去10年对PE发病机制的研究发现,生物学标志物在PE预测、诊断和治疗中发挥了重要作用。笔者总结了目前最新及最有可能用于临床预测和诊断PE的生物学标志物进行综述如下。     

TBL联合CBL在军人积极心理学教学中的应用

目的　探讨以团队为基础的教学（team-based learning，TBL）联合以案例为基础的教学（case-based learning，CBL）在军人积极心理学教学中的应用效果。方法　选取陆军军医大学校2017级临床医学专业100名本科生作为教学对象，随机分为TBL联合CBL教学组（n=50）和传统教学组（n=50）。通过基础理论知识及案例分析考核、问卷调查和心理测评等方式评估两种教学方法的教学效果。运用SPSS 19.0 对结果进行t检验。结果　TBL联合CBL教学组在理论知识得分（54.87±4.98）高于传统教学组（48.65±3.51）；案例分析考核得分（36.84±2.73）也高于传统教学组（32.37±2.34）；在心理测评结果中，TBL联合CBL教学组在SCL-90后测得分（143.31±43.62）低于传统教学组（149.89±46.96）；ERC、GWB后测得分（48.76±5.37）、（107.87±15.56）均高于传统教学组（43.58±5.79）、（102.32±12.13）。此外，TBL联合CBL教学组学生对该教学满意率达95.83%（46/50）。结论　TBL联合CBL教学在军人积极心理学教学中能取得良好的教学效果，提高学员的知识应用水平和心理调适能力，具有较好的可行性和适用性。     

唇裂Ⅱ期鼻畸形修复术后患者佩戴硅胶鼻模初始时间的探讨

目的探索唇裂Ⅱ期鼻畸形修复术后患者佩戴硅胶鼻模适宜的初始时间。方法选取我科唇部整形门诊2016年3月-2018年1月收治的鼻修复手术的47例唇裂Ⅱ期鼻畸形患者,根据患者门诊号的奇偶数分为观察组(25例)和对照组(22例),观察组于术后拆线日起佩戴硅胶鼻模,对照组于术后即刻佩戴硅胶鼻模。比较两组术后即刻、术后6个月患者和手术医生对鼻部外型满意度;比较两组术后拆线日切口愈合恢复情况及患者自我清洁能力和舒适度。结果术后即刻、术后6个月患者和手术医生对鼻部外型满意度比较两组差异无统计学意义(P>0.05)。伤口愈合率、患者自我清洁能力和舒适度观察组明显优于对照组,差异有统计学意义(P<0.05)。结论术后拆线日开始佩戴硅胶鼻模,既不影响术后鼻部外型的巩固与维持,又有利于患者的自我护理和观察,改善术后早期舒适度的体验,有利于伤口愈合,增加手术成功率。     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

环状RNA在慢性阻塞性肺疾病诊断及预后判断中的研究价值

目的探讨血清环状核糖核酸(circRNA)在慢性阻塞性肺病(COPD)诊断及预后判断中的研究价值。 方法选择连云港市第二人民医院2014年1月至2016年12月收治的80例COPD患者以及同期在该院进行健康体检人群30例为研究对象进行回顾性随机对照研究，其中男性58例，女性52例；年龄61~82岁，平均(70±6)岁。通过Arraystar circRNA芯片筛选获得两组受试者血清样本中差异表达的circRNA，再利用qRT-PCR验证了获得的目标circRNA分子，并结合生物信息学软件对其进行注释和功能预测。 结果本研究对circRNA-001988、circRNA-0000344和circRNA-0000284在COPD组和正常组血清中的表达的差异进行了探究：发现与正常组相比，circRNA-001988和circRNA-0000344在COPD组血清样本中的表达分别下调了(6.54±2.75)倍和(5.94±2.89)倍；circRNA-0000284则在COPD组的血清样本中上调表达了(8.54±3.25)倍。差异均有统计学意义(P<0.05)。 结论血清circRNA可作为COPD诊断和预后判断的生物标志物，具有较好的临床预测价值。     

Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics

Complex three-dimensional (3-D) heart structure is an important determinant of cardiac electrical and mechanical function. In this study, we set to develop a versatile tissue-engineered system that can promote important aspects of cardiac functional maturation and reproduce variations in myofiber directions present in native ventricular epicardium. We cultured neonatal rat cardiomyocytes within a 3-D hydrogel environment using microfabricated elastomeric molds with hexagonal posts. By varying individual post orientations along the directions derived from diffusion tensor magnetic resonance imaging (DTMRI) maps of human ventricle, we created large (2.5 × 2.5 cm²) 3-D cardiac tissue patches with cardiomyocyte alignment that replicated human epicardial fiber orientations. After 3 weeks of culture, the advanced structural and functional maturation of the engineered 3-D cardiac tissues compared to age-matched 2-D monolayers was evident from: 1) the presence of dense, aligned and electromechanically-coupled cardiomyocytes, quiescent fibroblasts, and interspersed capillary-like structures, 2) action potential propagation with near-adult conduction velocity and directional dependence on local cardiomyocyte orientation, and 3) robust formation of T-tubules aligned with Z-disks, co-localization of L-type Ca²⁺ channels and ryanodine receptors, and accelerated Ca²⁺ transient kinetics. This biomimetic tissue-engineered platform can enable systematic in vitro studies of cardiac structure–function relationships and promote the development of advanced tissue engineering strategies for cardiac repair and regeneration.     

Atractylodin attenuates lipopolysaccharide-induced acute lung injury by inhibiting NLRP3 inflammasome and TLR4 pathways

Acute lung injury (ALI) arises from uncontrolled pulmonary inflammation with high mortality rates. Atractylodin (Atr) is a polyethylene alkynes and has been reported to possess anti-inflammation effect. Thus, we aimed to investigate the protective effect of Atr on lipopolysaccharide (LPS)-induced inflammatory responses ALI. The results indicated that Atr treatment not only significantly attenuated LPS-stimulated histopathological changes but also lessened the myeloperoxidase (MPO) activity, the wet-to-dry weight ratio of the lungs, protein leakage and infiltration of inflammatory cells. Moreover, Atr inhibited the tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and monocyte chemoattractant protein (MCP)-1 secretion in BALF. Further study demonstrated that such inhibitory effects of Atr were due to suppression of nucleotide-binding domain-(NOD-) like receptor protein 3 (NLRP3) inflammasome and toll like receptor 4 (TLR4) activation, likely contributing to its anti-inflammatory effects. Collectively, these findings suggest that Atr may be an effective candidate for alleviating LPS-induced inflammatory responses.