FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity

BackgroundObesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice.Materials and MethodsMale wild-type (WT) and FNDC5^−/− mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5^−/− mice.ResultsFNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5^−/− mice.ConclusionsFNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing inflammation and insulin resistance in obesity and diabetes.     

Interferon gamma regulates HLA-D expression on solid tumors in vivo

In vivo administration of recombinant human interferon-γ, rIFN-γ, to nude mice bearing human tumor xenografts resulted in a strong induction of HLA-DR expression on the tumor cells in 2 of 3 lines tested. The induction was dose-dependent and declined rapidly after cessation of therapy. IFN-γ also switched on DQ and DP products when the xenograft cells were treated in vitro. The in vivo alteration of tumor surface properties by rIFN-γ may have therapeutic implications.     

远端流出道不良致严重下肢缺血39例的旁路移植术分析

目的探讨严重下肢缺血动脉的旁路移植手术方法 ,以挽救肢体避免截肢或降低截肢平面。方法 39例共 4 5条下肢仅有小腿单支流出道动脉的患者接受了动脉旁路移植手术。主要方式为股动脉 动脉人工血管 小腿动脉自体血管旁路移植术 2 1条 (4 6 7% )和动脉 小腿动脉旁路移植 10条 (2 2 2 % )。结果 39例患者中 ,1例术后第 5天因呼吸功能衰竭死亡 ,围手术期死亡率为 2 6 % ;围手术期移植血管闭塞 1例 (2 6 % ) ,手术成功率 97 4 %。出院时血管通畅率 10 0 % ,足部创面的愈合率 30 %。结论采用下肢远端动脉旁路移植治疗由仅有小腿单支流出道动脉供血的严重下肢缺血 ,可以挽救肢体或降低截肢平面 ,还可以为足部创面的愈合提供较好的营养环境。     

自体外周血干细胞移植治疗血栓闭塞性脉管炎的临床应用

目的探讨自体外周血干细胞移植治疗血栓闭塞性脉管炎(TAO)的疗效及安全性。方法对我院2007年4月至2011年12月期间收治的50例TAO患者(62条患肢)行自体外周血干细胞移植术,采用主观指标包括患肢疼痛、冷感以及客观指标包括间歇性跛行距离、踝肱指数(ABI)、足部溃疡变化、皮温进行疗效评价。结果 4例患者(4条患肢)移植后3周因小腿中段以下出现坏死导致低位截肢;46例保肢患者(58条患肢),移植后1个月,小腿疼痛及冷感觉均消失,足部疼痛和冷感评分均优于移植前(P<0.05)。移植后3个月,10例(10条患肢)溃疡全部愈合;46例保肢患者,间歇性跛行距离由(80.38±45.53)m增加到(330.56±142.31)m,下肢皮温由(26.50±0.46)℃增加到(31.49±0.45)℃,ABI由0.41±0.02增加到0.71±0.05,移植后以上三项指标均明显优于移植前(P<0.05)。移植后6个月,46例保肢患者58条患肢动脉造影,均有不同程度的新生侧支血管形成。所有患者经实验室或CT检测,均未发现恶性肿瘤、视网膜增生、动脉瘤等并发症。40例患者移植后随访9～36个月(平均22.5个月)症状改善后无加重;6例患者6个月后因下肢疼痛加重,疼痛评分为4分,并伴有足趾溃疡,再次行外周血干细胞移植,再次移植后18个月,患者仅有下肢乏力,疼痛改善,疼痛评分为1分,足趾溃疡愈合,无间歇性跛行。结论自体外周血干细胞移植治疗TAO是一种简单、安全、有效的方法,尤其是下肢远端动脉流出道差无法进行搭桥的患者,可使一部分患者免除截肢或降低截肢平面,改善生活质量。     

血管再狭窄的分子生物学研究进展

目的了解血管再狭窄分子生物学研究进展。方法对国内、外有关血管再狭窄分子生物学研究的文献进行综述。结果各种基因转移方法有一定的优点，亦有一定的缺点，但都不够理想。细胞毒素基因胸腺嘧啶核苷酸，抑癌基因突变型视网膜母细胞瘤基因蛋白，周期蛋白依赖激酶抑制因子p21、p27和p53，反义核酸c-myc和c-myb，血管内皮细胞生长因子，反义碱性成纤维生长因子，血小板衍化生长因子，增加一氧化氮的合成、抑制平滑肌细胞的细胞核因子κB，促进Gax和Fas配体表达等基因治疗可明显抑制血管再狭窄。结论构建一种更好的基因转移体系以及多基因、多环节的联合基因治疗血管再狭窄是今后的发展方向。     

SCD14、TNF-α、E-SLT及IL-10在感染发病中的作用及临床意义

目的探讨SCD14、TNF-α、E-SLT及IL-10在感染发病机制中的作用及其意义.方法采用酶联免疫吸附法测定37例腹部外伤合并感染患者及内毒素血症兔模型中可溶性CD14(SCD14)、肿瘤坏死因子α(TNF-α)、E选择素(E-SLT)及白细胞介素10(IL-10)血清浓度变化情况.结果与对照组相比,SCD14与TNF-α在术后第1天开始升高,E-SLT与IL-10在术后合并感染组中于第3天出现增高[(1.61±0.47)μg/ml与(28.63±8.29)pg/ml,(153.6±48.9)ng/ml 与(38.21±10.87)pg/ml,P均＜0.05];在兔内毒素血症中则分别于第30、120min开始增高[(0.50±0.02)μg/ml与(1.00±0.02)pg/ml,(20.9±0.5)ng/ml 与(49.7±0.5)pg/ml,P均＜0.05].结论血清SCD14、TNF-α、E-SLT及IL-10浓度的变化在反映感染发生发展及预后方面具有一定的价值.     

The accuracy of ultrasonic duplex scanning in carotid artery disease

Ultrasonic duplex scanning of the internal carotid artery is highly accurate in the detection of disease as expressed in its sensitivity of 0.97 and specificity of 0.82 for haemodynamic significant lesions. For the detection of obstructions of 20% or over, these parameters are 0.94 and 0.77 respectively. The most striking problem is the poor classification of normal vessels and those with minor lesions. The duplex scanning overestimates the degree of disease in these cases. For the external carotid artery the method differentiates reasonably well between non-haemodynamic and haemodynamic significant lesions.     

A randomized Phase III trial of neoadjuvant recombinant human endostatin,docetaxel and epirubicin as first‐line therapy for patients with breast cancer (CBCRT01)

To further assess the efficacy and safety of recombinant human endostatin (rh‐endostatin), a Phase III, multicenter, prospective, randomized, controlled clinical trial was conducted. Patients to be treated with neoadjuvant docetaxel and epirubicin (DE) or DE plus rh‐endostatin (DEE) were eligible for this trial. The primary endpoint was clinical/pathological response. Secondary endpoints included adverse events and quality of life (QOL). Finally, 803 patients were enrolled and randomly assigned to receive DE (n = 402) or DEE (n = 401) regimen. After three cycles of neoadjuvant therapy, “complete response” achieved in 14.2% of patients in DEE group versus 6.7% in DE group, “partial response” achieved in 76.8% versus 71.1%, while “stable disease” in 6.0% versus 18.9%, “progressive disease” in 3.0% versus 3.2% of patients. The rate of objective response in DEE and DE group was 91.0% and 77.9%, respectively (p < 0.001). In spite of a relatively higher pathological complete response achieved following the combination therapy, no significant difference was found between two arms. Adverse events were mostly of Grades 1–2. No significant difference in adverse event and QOL was found between the two arms. In conclusion, the combination of chemotherapy and rh‐endostatin achieved better outcomes than chemotherapy alone, and thus can be considered as a promising therapeutic strategy for breast cancer.