MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin Homolog in Renal Ischemia-Reperfusion Injury

Ischemia-reperfusion injury contributes to tissue damage and organ failure in clinical settings, but the underlying mechanism remains elusive and effective therapies are still lacking. Here, we identified microRNA 687 (miR-687) as a key regulator and therapeutic target in renal ischemia-reperfusion injury. We show that miR-687 is markedly upregulated in the kidney during renal ischemia-reperfusion in mice and in cultured kidney cells during hypoxia. MiR-687 induction under these conditions was mediated by hypoxia-inducible factor-1 (HIF-1). Upon induction in vitro, miR-687 repressed the expression of phosphatase and tensin homolog (PTEN) and facilitated cell cycle progression and apoptosis. Blockade of miR-687 preserved PTEN expression and attenuated cell cycle activation and renal apoptosis, resulting in protection against kidney injury in mice. Collectively, these results unveil a novel HIF-1/miR-687/PTEN signaling pathway in ischemia-reperfusion injury that may be targeted for therapy.     

不停跳冠状动脉旁路移植术中应用MostCare/PRAM监测系统进行血流动力学监测的临床研究

目的探究Most Care/PRAM系统监测下不停跳冠状动脉旁路移植术(OPCABG)患者术中血流动力学变化情况和预后分析。方法纳入2016年10月至2017年1月安贞医院89例OPCABG患者,其中男53例、女36例,年龄(60.50±8.40)岁。记录术中血流动力学变化情况。按是否发生心肌梗死、低心排血量等严重循环不良事件,分为平稳组和严重循环不良事件组,进行相关分析。结果手术全程监测完整血流动力学数据患者65例,开胸前和关胸后被动抬高试验的每搏量(SV)升高均值分别为23.00%±3.20%和29.40%±3.70%。麻醉、开胸、应用肝素时、搭桥中、应用鱼精蛋白时、关胸和术毕7个时间段,SV明显下降,外周血管阻力指数(SVRI)持续显著增加,最大压力梯度(d P/d T)和心脏循环效率(CCE)在麻醉后明显下降,搭桥时下降到最低,其后逐渐升高;每搏量变异率(SVV)和脉压变异率(PPV)在麻醉后下降,开胸后一直升高。89例患者发生严重循环不良事件共9例,其中4例死亡。严重循环不良事件组术中基础SVRI、SVV和PPV均显著高于平稳组(P<0.05),CCE、d P/d T和SV差异无统计学意义(P>0.05)。术中基础SVRI、CCE、d P/d T、SVV、PPV和SV均值与预后指标均无明显相关性。结论OPCABG术中易出现血流动力学的改变,因此,OPCABG术中宜应用Most Care/PRAM仪进行血流动力学监测,并及时纠正血流动力学异常。     

Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation

BACKGROUND: Interactions between tumor cells and their host environment can play a major role in regulating survival programs required for tumor progression. Osteopontin (OPN) is a glycophosphoprotein overexpressed by tumors, and is a key molecule for tumor progression and metastasis. OPN also inhibits expression of autocrine and paracrine inducible nitric oxide synthase (iNOS). Given the cytotoxic effects of macrophage NO expression, we hypothesized that tumor-derived OPN inhibits expression of local macrophage iNOS to potentiate tumor survival. METHODS: We used a coculture system of murine CT26 colorectal cancer cells with RAW264.7 murine macrophage cells. CT26 expresses OPN at high levels. RNA interference was utilized to produce long-term specific silencing of OPN in CT26. RESULTS: Inhibition of constitutive OPN synthesis in CT26 upregulates local NO production with inhibition of CT26 proliferation and promotion of CT26 apoptosis. Macrophage iNOS expression is accompanied by increased binding activity of nuclear factor-kappaB DNA. When the CT26 culture media were examined for a panel of proinflammatory cytokines, elevated concentrations of granulocyte colony-stimulating factor (G-CSF) were found. Subsequently, in CT26 cells treated with antisense-G-CSF, NO levels in CT26-RAW cocultures were significantly decreased. CONCLUSION: In our system of CT26-RAW264.7 coculture, we conclude that inhibition of OPN synthesis in CT26 results in G-CSF-mediated induction of macrophage iNOS expression with resultant inhibition of CT26 proliferation via increased apoptosis. Our results suggest that tumor-derived OPN may enhance tumor survival by down regulating expression of NO in the local microenvironment. This is one mechanism by which OPN may potentiate cancer survival and progression.     

Human in-vivo 31P MR Spectroscopy of Benign and Malignant Breast Tumors

Objective

To assess the potential clinical utility of in-vivo 31P magnetic resonance spectroscopy (MRS) in patients with various malignant and benign breast lesions.

Materials and Methods

Seventeen patients with untreated primary malignant breast lesions (group I), eight patients with untreated benign breast lesions (group II) and seven normal breasts (group III) were included in this study. In-vivo 31P MRS was performed using a 1.5 Tesla MR scanner. Because of the characteristics of the coil, the volume of the tumor had to exceed 12 cc (3×2×2 cm), with a superoinferior diameter at least 3 cm. Mean and standard deviations of each metabolite were calculated and metabolite ratios, such as PME/PCr, PDE/PCr, T-ATP/PCr and PCr/T-ATP were calculated and statistically analyzed.

Results

Significant differences in PME were noted between groups I and III (p=0.0213), and between groups II and III (p=0.0213). The metabolite ratios which showed significant differences were PME/PCr (between groups II and III) (p=0.0201), PDE/PCr (between groups I and III, and between groups II and III) (p=0.0172), T-ATP/PCr (between groups II and III) (p=0.0287), and PCr/T-ATP (between groups II and III) (p=0.0287). There were no significant parameters between groups I and II.

Conclusion

In-vivo 31P MRS is not helpful for establishing a differential diagnosis between benign and malignant breast lesions, at least with relatively large lesions greater than 3 cm in one or more dimensions.     

针刺在防治术后认知功能障碍中的机制研究进展

术后认知功能障碍(postoperative cognitive dysfunction,POCD)可导致患者术后发展为痴呆的可能性大大增加,影响患者预后,并增加医疗护理成本和家庭负担。基础研究表明,针刺可通过多重作用机制起到一定的脑保护效应,降低POCD的发生率。文章回顾了近年针刺在POCD领域内的研究进展,综述了可能存在的几种相关机制,包括抑制神经炎症、抑制氧化应激水平、减少神经元损伤、增强突触可塑性以及调节微生物菌群脑-肠轴等。将针刺应用于POCD确实取得了一定的成果,但其作用机制仍未完全明确。随着针刺研究的不断深入,需要尽快明确其作用机制,以便于更好地指导POCD的临床治疗。     

Biological Advantages of Porous Hydroxyapatite Scaffold Made by Solid Freeform Fabrication for Bone Tissue Regeneration

Presently, commercially available porous bone substitutes are manufactured by the sacrificial template method, direct foaming method, and polymer replication method (PRM). However, current manufacturing methods provide only the simplest form of the bone scaffold and cannot easily control pore size. Recent developments in medical imaging technology, computer‐aided design, and solid freeform fabrication (SFF), have made it possible to accurately produce porous synthetic bone scaffolds to fit the defected bone shape. Porous scaffolds were fabricated by SFF and PRM for a comparison of physical and mechanical properties of scaffold. The suggested three‐dimensional model has interconnected cubic pores of 500 μm and its calculated porosity is 25%. Whereas hydroxyapatite scaffolds fabricated by SFF had connective macropores, those by PRM formed a closed pore external surface with internally interconnected pores. SFF was supposed to be a proper method for fabricating an interconnected macroporous network. Biocompatibility was confirmed by testing the cytotoxicity, hemolysis, irritation, sensitization, and implantation. In summary, the aim was to verify the safety and efficacy of the scaffolds by biomechanical and biological tests with the hope that this research could promote the feasibility of using the scaffolds as a bone substitute.     

听觉诱发电位指数、脑电双频指数及心血管反应评估"过浅麻醉"的价值

目的通过研究丙泊酚诱导过程中,听觉诱发电位指数(AAI)、脑电双频指数(BIS)及心血管反应与插管体动的关系,探讨上述监测手段是否能够反映“过浅麻醉”。方法35例ASAⅠ~Ⅱ级妇科择期手术患者,以丙泊酚进行诱导,患者入睡后,用压力袖带隔离一侧前臂,静注维库溴铵0·1mg/kg。当丙泊酚靶控输注(TCI)达到设定血浆靶浓度(3·5μg/ml)后行气管内插管。记录隔离侧手臂运动(体动)情况,并以是否发生体动反应为准将患者分为体动组与非体动组。记录患者诱导前、插管前的SBP、DBP、HR、BIS、AAI及插管后2min内上述指标的最大值。结果体动组AAI插管后明显高于插管前(P<0·01),而非体动组插管前、后的差异无显著意义;两组患者BIS插管前、后组内及组间的差异均无显著意义;插管引起的DBP、SBP增高体动组明显大于非体动组(P<0·01),但HR变化两组相似。结论BIS仅是衡量睡眠深度的指标,AAI及BP反映“过浅麻醉”,反映机体对伤害性刺激的反应较BIS敏感。     

Leucine‐rich glioma inactivated 3 promotes HaCaT keratinocyte migration

Our finding that human skin expresses leucine‐rich glioma inactivated 3 (LGI3) raises the question of the function of this cytokine in keratinocytes. We have shown that LGI3 stimulates human HaCaT keratinocyte migration without affecting viability or proliferation. Western blot analysis showed that LGI3 induced focal adhesion kinase activation, Akt phosphorylation, and glycogen synthase kinase 3β (GSK3β) phosphorylation in these cells. Using the scratch wound assay and a modified Boyden chamber, we found that LY294002, a selective phosphatidylinositol 3‐kinase inhibitor, and LiCl, a selective GSK3β inhibitor, abolished LGI3‐induced cell migration. We tested β‐catenin levels after LGI3 treatment because the Akt‐GSK3β pathway regulates β‐catenin accumulation, and β‐catenin promotes cell migration. LGI3 treatment increased β‐catenin protein and nuclear localization, whereas LY294002 prevented LGI3‐induced focal adhesion kinase and Akt activation as well as β‐catenin accumulation. Overall, these data suggest that LGI3 stimulates HaCaT cell migration following β‐catenin accumulation through the Akt pathway.     

不同养老模式下老年人心理健康状况的比较

目的 比较不同养老模式下老年人的心理健康状况,并分析相关影响因素.方法 采用吴振云编制的老年心理健康问卷,对四川地区550名年龄60岁以上的居家、机构、社区养老者进行问卷调查.结果 除了认知维度外,社区养老组的总分和其余分量表分均高于居家养老组和机构养老组,差异有统计学意义(P＜0.001).不同婚姻状况、文化程度的老年人在总体心理健康、情绪、适应和人际维度等方面比较,差异有统计学意义(P＜0.05).结论 社区养老对于老年人来说,是一种可取的养老模式.