双侧股神经阻滞用于双膝关节置换术患者的麻醉效果和对血清炎性因子水平的影响

目的:研究双侧股神经阻滞术用于双膝关节置换术患者麻醉效果和对患者血清炎性因子水平的影响。方法:选择2015年10月～2018年10月在我院进行双膝关节置换术的110例患者,按照其入院顺序经随机数字表法分为两组,每组55例。对照组采用全身麻醉,研究组采用双侧股神经阻滞联合全身麻醉。比较两组的麻醉情况,治疗前后血清炎性因子白介素6(IL-6)、C反应蛋白(CRP)、舒张压(DBP)、收缩压(SBP)、心率(HR)水平的变化。结果:两组麻醉时间比较差异无统计学意义(P0.05);研究组拔管、恢复室停留和苏醒时间均显著短于对照组(P0.05)。两组术后24 h、48 h血清炎性因子IL-6、CRP水平均高于术前,但研究组以上指标均显著低于对照组(P0.05);两组术中DBP、SBP、HR水平均较术前显著降低(P0.05),但研究组DBP、SBP、HR水平均显著高于对照组(P0.05),两组术后DBP、SBP、HR水平比较差异均无统计学意义(P0.05)。结论:与单纯采用全身麻醉相比,双侧股神经阻滞可有效改善双膝关节置换术患者的麻醉效果,并降低其血清炎症因子和稳定其血流动力学。     

血小板衍生生长因子对面部凹陷自体脂肪移植成活率的影响

目的:探讨血小板衍生生长因子(PDGF)对面部凹陷自体脂肪移植成活率的影响。方法:选取我院自2016年3月-2017年11月收治的62例面部凹陷患者,根据治疗方案的不同分为观察组和对照组,对照组30例患者仅采用自体脂肪颗粒移植治疗,观察组32例患者在对照组基础上加用血小板衍生生长因子治疗,比较两组患者治疗的优良率和并发症的发生情况。结果:治疗后,观察组患者的优良率为93.75%,明显高于对照组(73.33%,P0.05)。观察组患者治疗后3个月、6个月时身体脂肪吸收率明显高于术后1个月时(P0.05),且与对照组同时点比较,观察组患者治疗后3个月、6个月时的身体脂肪吸收率显著升高(P0.05)。观察组患者对治疗满意度为87.55%,显著高于对照组(70.0%,P0.05)。结论:血小板衍生生长因子应用于治疗面部凹陷能够有效提高自体脂肪移植的成活率。     

小柴胡汤加减联合奥美拉唑对慢性胃炎具有治疗增效作用

本研究选取本院收治的慢性胃炎患者114例并根据治疗方法不同分为对照组和观察组。对照组患者采用奥美拉唑治疗,观察组患者采用奥美拉唑联合小柴胡汤加减治疗,分析小柴胡汤加减联合奥美拉唑对慢性胃炎血清表皮生长因子(EGF)、胃黏膜氧化酶-2 (COX-2)蛋白表达情况的影响及护理对策。研究结果表明,治疗前两组患者胃镜检查充血水肿、糜烂、黏膜白相、颗粒增生发生率比较无统计学差异(p>0.05);治疗后,观察组患者各项指标发生率低于对照组(p<0.05);治疗前,两组患者血清EGF、Bcl-2、CRP和胃黏膜COX-2、P-p65表达水平比较无统计学差异(p>0.05),治疗后发现观察组患者血清EGF水平高于对照组,血清Bcl-2、CRP和胃黏膜COX-2、P-p65表达水平低于对照组(p<0.05);治疗前,两组患者在躯体功能、躯体职能、躯体疼痛、情感职能、心理健康评分等生活质量评分上比较无统计学差异(p<0.05),治疗后,观察组患者各项评分高于对照组(p>0.05)。本研究初步结论说明,小柴胡汤加减联合奥美拉唑治疗慢性胃炎疗效显著,可改善患者血清EGF、Bcl-2和胃黏膜COX-2表达水平,提高患者生活质量。     

Simvastatin preparations promote PDGF‐BB secretion to repair LPS‐induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway

Endothelial barrier dysfunction is a critical pathophysiological process of sepsis. Impaired endothelial cell migration is one of the main reasons for endothelial dysfunction. Statins may have a protective effect on endothelial barrier function. However, the effect and mechanism of statins on lipopolysaccharide (LPS)‐induced endothelial barrier dysfunction remain unclear. Simvastatin (SV) was loaded in nanostructured lipid carriers to produce SV nanoparticles (SV‐NPs). Normal SV and SV‐NPs were used to treat human umbilical vein vascular endothelial cells (HUVECs) injured by LPS. Barrier function was evaluated by monitoring cell monolayer permeability and transendothelial electrical resistance, and cell migration ability was measured by a wound healing assay. LY294002 and imatinib were used to inhibit the activity of PI3K/Akt and platelet‐derived growth factor receptor (PDGFR) β. IQ‐GTPase‐activating protein 1 (IQGAP1) siRNA was used to knockdown endogenous IQGAP1, which was used to verify the role of the PDGFRβ/PI3K/Akt/IQGAP1 pathway in SV/SV‐NPs‐mediated barrier protection in HUVECs injured by LPS. The results show that SV/SV‐NPs promoted the migration and decreased the permeability of HUVECs treated with LPS, and the efficacy of the SV‐NPs exceeded that of SV significantly. LY294002, imatinib and IQGAP1 siRNA all suppressed the barrier protection of SV/SV‐NPs. SV/SV‐NPs promoted the secretion of platelet‐derived growth factor‐BB (PDGF‐BB) and activated the PDGFRβ/PI3K/Akt/IQGAP1 pathway. SV preparations restored endothelial barrier function by restoring endothelial cell migration, which is involved in the regulation of the PDGFRβ/PI3K/Akt/IQGAP1 pathway and PDGF‐BB secretion. As an appropriate formulation for restoring endothelial dysfunction, SV‐NPs may be more effective than SV.     

Vascular progenitor cell senescence in patients with Marfan syndrome

Vascular progenitor cells (VPCs) present in the adventitia of the vessel wall play a critical role in the regulation of vascular repair following injury. This study aimed to assess the function of VPCs isolated from patients with Marfan syndrome (MFS). VPCs were isolated from control and MFS donors and characterized. Compared with control‐VPCs, MFS‐VPCs exhibited cellular senescence as demonstrated by increased cell size, higher SA‐β‐gal activity and elevated levels of p53 and p21. RNA sequencing showed that several cellular process‐related pathways including cell cycle and cellular senescence were significantly enriched in MFP‐VPCs. Notably, the expression level of TGF‐β1 was much higher in MFS‐VPCs than control‐VPCs. Treatment of control‐VPCs with TGF‐β1 significantly enhanced mitochondrial reactive oxidative species (ROS) and induced cellular senescence whereas inhibition of ROS reversed these effects. MFS‐VPCs displayed increased mitochondrial fusion and decreased mitochondrial fission. Treatment of control‐VPCs with TGF‐β1 increased mitochondrial fusion and reduced mitochondrial fission. Nonetheless, treatment of mitofusin2 (Mfn2)‐siRNA inhibited TGF‐β1‐induced mitochondrial fusion and cellular senescence. Furthermore, TGF‐β1‐induced mitochondrial fusion was mediated by the AMPK signalling pathway. Our study shows that TGF‐β1 induces VPC senescence in patients with MFS by mediating mitochondrial dynamics via the AMPK signalling pathway.     

MiR‐802 causes nephropathy by suppressing NF‐κB‐repressing factor in obese mice and human

Obesity is associated with significant microvascular complications including renal injuries and may induce end‐stage renal disease. Emerging studies have demonstrated microRNAs (miRNAs) are potential mediators in the pathophysiological process of nephropathy. The present study aimed to investigate the role of miR‐802 in obesity‐related nephropathy and potential molecular mechanisms. Through utilizing obese mouse model and human subjects, we explored the therapeutic benefits and clinical application of miR‐802 in protecting against nephropathy. Renal miR‐802 level was positively correlated with functional parameters, including blood urea nitrogen and creatinine in obese mice. Specific silencing of renal miR‐802 improved high fat diet (HFD)‐induced renal dysfunction, structural disorders and fibrosis. The up‐regulated inflammatory response and infiltrated macrophages were also significantly decreased in miR‐802 inhibitor‐treated obese mice. Mechanistically, miR‐802 directly bond to 3?‐UTR of NF‐κB‐repressing factor (NRF) and suppressed its expression. In clinical study, the circulating miR‐802 level was significantly increased in obese subjects, and positively correlated with plasma creatinine level but negatively correlated with creatinine clearance. Taken together, our findings provided evidence that miR‐802/NRF signalling was an important pathway in mediating obesity‐related nephropathy. It is a possible useful clinical approach of treating miR‐802 inhibitor to combat nephropathy.     

DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild‐type NSCLC cells to AZD9291

DYRK1A is considered a potential cancer therapeutic target, but the role of DYRK1A in NSCLC oncogenesis and treatment requires further investigation. In our study, high DYRK1A expression was observed in tumour samples from patients with lung cancer compared with normal lung tissues, and the high levels of DYRK1A were related to a reduced survival time in patients with lung cancer. Meanwhile, the DYRK1A inhibitor harmine could suppress the proliferation of NSCLC cells compared to that of the control. As DYRK1A suppression might be effective in treating NSCLC, we next explored the possible specific molecular mechanisms that were involved. We showed that DYRK1A suppression by siRNA could suppress the levels of EGFR and Met in NSCLC cells. Furthermore, DYRK1A siRNA could inhibit the expression and nuclear translocation of STAT3. Meanwhile, harmine could also regulate the STAT3/EGFR/Met signalling pathway in human NSCLC cells. AZD9291 is effective to treat NSCLC patients with EGFR‐sensitivity mutation and T790 M resistance mutation, but the clinical efficacy in patients with wild‐type EGFR remains modest. We showed that DYRK1A repression could enhance the anti‐cancer effect of AZD9291 by inducing apoptosis and suppressing cell proliferation in EGFR wild‐type NSCLC cells. In addition, harmine could enhance the anti‐NSCLC activity of AZD9291 by modulating STAT3 pathway. Finally, harmine could enhance the anti‐cancer activity of AZD9291 in primary NSCLC cells. Collectively, targeting DYRK1A might be an attractive target for AZD9291 sensitization in EGFR wild‐type NSCLC patients.     

Combined brain‐derived neurotrophic factor with extinction training alleviate impaired fear extinction in an animal model of post‐traumatic stress disorder

Impaired fear memory extinction (Ext) is one of the hallmark symptoms of post‐traumatic stress disorder (PTSD). However, since the precise mechanism of impaired Ext remains unknown, effective interventions have not yet been established. Recently, hippocampal‐prefrontal brain‐derived neurotrophic factor (BDNF) activity was shown to be crucial for Ext in naïve rats. We therefore examined whether decreased hippocampal‐prefrontal BDNF activity is also involved in the Ext of rats subjected to a single prolonged stress (SPS) as a model of PTSD. BDNF levels were measured by enzyme‐linked immunosorbent assay (ELISA), and phosphorylation of TrkB was measured by immunohistochemistry in the hippocampus and medial prefrontal cortex (mPFC) of SPS rats. We also examined whether BDNF infusion into the ventral mPFC or hippocampus alleviated the impaired Ext of SPS rats in the contextual fear conditioning paradigm. SPS significantly decreased the levels of BDNF in both the hippocampus and mPFC and TrkB phosphorylation in the ventral mPFC. Infusion of BDNF 24 hours after conditioning in the infralimbic cortex (ILC), but not the prelimbic cortex (PLC) nor hippocampus, alleviated the impairment of Ext. Since amelioration of impaired Ext by BDNF infusion did not occur without extinction training, it seems the two interventions must occur consecutively to alleviate impaired Ext. Additionally, BDNF infusion markedly increased TrkB phosphorylation in the ILC of SPS rats. These findings suggest that decreased BDNF signal transduction might be involved in the impaired Ext of SPS rats, and that activation of the BDNF‐TrkB signal might be a novel therapeutic strategy for the impaired Ext by stress.