Thioredoxin-Interacting Protein Deficiency Protects against Diabetic Nephropathy

Expression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. We previously reported that TxNIP-deficient mesangial cells showed protection from HG-induced reactive oxygen species, mitogen-activated protein kinase phosphorylation, and collagen expression. Here, we investigated the potential role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP^−/−, and TxNIP^+/− mice were rendered equally diabetic with low-dose streptozotocin. In contrast to effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum cystatin C, or serum creatinine levels in TxNIP^−/− mice. Whereas morphometric studies of kidneys revealed a thickened glomerular basement membrane and effaced podocytes in the diabetic WT mice, these changes were absent in the diabetic TxNIP^−/− mice. Immunohistochemical analysis revealed significant increases in the levels of glomerular TGF-β1, collagen IV, and fibrosis only in WT diabetic mice. Additionally, only WT diabetic mice showed significant increases in oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and inflammation (IL-1β mRNA, F4/80 immunohistochemistry). Expression levels of Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A significant loss of podocytes, assessed by Wilms’ tumor 1 and nephrin staining and urinary nephrin concentration, was found in diabetic WT but not TxNIP^−/− mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown with siRNA abolished the increased mitochondrial O₂⁻ generation and apoptosis. These data indicate that TxNIP has a critical role in the progression of DN and may be a promising therapeutic target.     

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

TNF ligand superfamily member 12, also known as TNF-related weak inducer of apoptosis (TWEAK), acts through its receptor, fibroblast growth factor-inducible 14 (Fn14), to mediate several key pathologic processes involved in tissue injury relating to lupus nephritis. To explore the potential for renal protection in lupus nephritis by targeting this pathway, we introduced the Fn14 null allele into the MRL-lpr/lpr lupus mouse strain. At 26–38 weeks of age, female Fn14-knockout MRL-lpr/lpr mice had significantly lower levels of proteinuria compared with female wild-type MRL-lpr/lpr mice. Furthermore, Fn14-knockout mice had significantly improved renal histopathology accompanied by attenuated glomerular and tubulointerstitial inflammation. There was a significant reduction in glomerular Ig deposition in Fn14-knockout mice, despite no detectable differences in either serum levels of antibodies or splenic immune cell subsets. Notably, we found that the Fn14-knockout mice displayed substantial preservation of podocytes in glomeruli and that TWEAK signaling directly damaged barrier function and increased filtration through podocyte and glomerular endothelial cell monolayers. Our results show that deficiency of the Fn14 receptor significantly improves renal disease in a spontaneous lupus nephritis model through prevention of the direct injurious effects of TWEAK on the filtration barrier and/or modulation of cytokine production by resident kidney cells. Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN.     

地佐辛联合舒芬太尼用于全麻术后患者静脉自控镇痛的临床效果及安全性:Meta分析

目的 系统评价地佐辛联合舒芬太尼与单独舒芬太尼用于术后患者自控静脉镇痛(patient controlled intravenous analgesia,PCIA)的临床效果及副作用.方法 计算机检索Cochrane Library、PubMed、Embase、CBM、Ovid、ScienceDirect、ProQuest、Springer、CNKI、万方和维普等数据库从建库至2014年6月文献,在按纳入和排除标准进行资料提取和文献质量评价后,采用RevMan 5.1版软件进行Meta分析.结果 共纳入6个随机对照实验,共计患者477例.Meta分析结果显示:地佐辛联合舒芬太尼与单独舒芬太尼分别用于PCIA后,患者术后4、8、12、24 h视觉模拟评分(visual analogue scales,VAS)比较,差异无统计学意义(P＞0.05),术后48 h VAS[加权均数差(weighted mean difference,WMD)=-0.36,95％置信区间(confidence interval,CI)(-0.69,-0.04)]差异有统计学意义(P＜0.05);副作用总发生率差异有统计学意义[比值比(odds ratio,OR)=0.36,95％CI(0.26,0.50)](P＜0.05);术后24、48 h白细胞介素(interleukin,IL)-6及IL-10水平差异有统计学意义(P＜0.05).结论 地佐辛联合舒芬太尼镇痛效果明显且副作用少,能在一定程度上改善免疫功能.     

去细胞化肝脏生物支架的应用进展

肝脏替代治疗是目前终末期肝病最有效的治疗措施,而去细胞化肝脏生物支架拓宽了肝脏替代治疗的研究领域.目前普遍的支架制备过程是在一定的物理条件下,经灌注设备将化学试剂(去垢剂、消化酶等)注入肝脏自身的脉管结构中,达到去除细胞成分,保留支架内ECM和超微脉管结构的目的.再将种子细胞注入到去细胞化肝脏生物支架,获得再细胞化肝脏,模拟机体内肝脏生物环境进行体外或体内培养,观察种子细胞附着情况,检测肝脏代谢功能,评估肝脏替代效果.目前,种子细胞的选取、再细胞化流程、再细胞化肝脏移植等问题仍处于探索阶段.笔者围绕去细胞化肝脏生物支架的制备与评价、检测和应用作一综述,为进一步应用于实验研究和临床实践提供参考.     

微创经皮肾镜碎石术对肾内型肾盂结石的治疗评价

目的评价微创经皮肾镜碎石术对肾内型肾盂结石的治疗效果。方法回顾性分析肇庆市第二人民医院2013年1月1日至2013年12月31日由同一术者完成的微创经皮肾镜碎石术187例,其中肾内型肾盂肾结石58例,非肾内型肾盂肾结石129例,比较二者之间的一期结石清除率、二期结石清除率、一期手术时间、手术中取石通道个数、二期体外冲击波碎石例数、输血率、胸膜损伤发生率。结果肾内型肾盂结石病例一期结石清除率低于非肾内型肾盂结石病例,而一期手术时间、双通道取石率均高于后者(P<0.05)。二期结石清除率、术后体外冲击波碎石例数、输血率、胸膜损伤发生率均无统计学差异(P>0.05)。结论微创经皮肾镜碎石术对肾内型肾盂合并结石的治疗安全有效。     

局麻微创经皮肾镜对全身炎症反应及肾功能损害的影响

目的通过对局麻微创经皮肾镜治疗肾结石及输尿管上段结石导致的全身炎症反应、肾功能损害等临床资料进行分析,评估局麻微创经皮肾镜的安全性、有效性、可行性、经济效益及其临床推广应用价值。方法东莞市大朗医院泌尿外科在2012年8月至2014年8月将经皮肾镜患者随机分成观察组及对照组(各40例),观察组行局麻,对照组行腰硬联合麻醉。对比两组术前晨、手术结束时及术后一周血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、β2-微球蛋白(β2-MG)、C-反应蛋白(CRP)、肌酐(Cr)及尿素氮(BUN)的表达水平;同时对比两种麻醉状态对患者心率(HR)、血氧饱和度(SPO2)及平均动脉压(MAP)的影响;并比较两组间手术时间、术中出血量、住院时间、住院费用及残石率的差异。结果两组患者术前晨血BUN、Cr、β2-MG、IL-6、TNF-α及CRP组间比较差异无统计学意义(P>0.05),两组各项参考指标在手术结束时明显高于术前。对照组术后一周血清IL-6、TNF-α、CRP含量高于观察组,两组术后一周血清BUN、Cr、β2-MG低于术前,差异有统计学意义(P<0.05)。观察组及对照组MAP、HR、SPO2在手术开始前、手术中与麻醉前比较差异有统计学意义(P<0.05)。两组间手术时间、术中出血量及残石率比较无统计学差别(P>0.05),观察组住院时间及住院费用明显低于对照组,差异有统计学意义(P<0.05)。结论局麻微创经皮肾镜治疗肾结石及输尿管上段结石引起的全身炎症反应较轻,总费用及住院时间明显低于腰硬联合麻醉组,两组患者肾功能损伤差别无统计学意义。     

妊高症患者血液中核因子κB介导的PTX3和CRP的表达及意义

目的：研究核因子（NF）κB介导的 PTX3和 CRP通路,是否可作为治疗妊高症的潜在靶点并分析其临床意义。方法选取2012年3月至2014年12月收治的妊高症患者（NH BPEP 标准）60例作为观察组,其中妊高症20例[血压（131.2±17.4）／（79.7±10.0）mmHg],轻度先兆子痫20例[血压（141.2±15.6）／（89.5±11.2）mmHg],重度先兆子痫20例[血压（150.3±17.6）／（97.6±14.8）mmHg];选取同期入院血压正常的晚期妊娠妇女20例作为对照组,采用全自动生化分析仪检测两组对象外周单个核细胞PTX3和 CRP水平,采用免疫印迹杂交检测 NF-κB的水平;加入 NF-κB抑制剂（PTDC）,观察 PTX3和 CRP表达水平的变化;同时观察其与患者血压波动的关系。结果观察组 PTX3和 CRP随血压升高而升高,均明显高于对照组,组内、组间差异均有统计学意义（ P ＜0.05）;加入 PTDC后,PTX3和 CRP水平均降低,与对照组比较,差异无统计学意义（P ＞0.05）。重度先兆子痫患者NF-κB表达最高[（25.8±4.9）％],应用 PTDC 后降低[（13.9±4.9）％],与对照组[（13.5±3.6）％]比较,差异无统计学意义（P ＞0.05）。结论血浆PTX3和CRP是核因子κB的下游因子,在妊高症患者中表达升高,该通路可作为药物治疗妊高症的潜在靶点。     

利多卡因外擦导管预防桡动脉痉挛的临床分析

目的 研究在经桡动脉冠状动脉介入诊疗中应用利多卡因外擦动脉鞘管和造影(导引)导管对预防桡动脉痉挛(RAS)的有效性.方法 选取2013年11月至2014年8月经桡动脉途径行冠状动脉造影(CAG)和CAG+经皮冠状动脉介入治疗(PCI)的患者429例,采用随机对照单盲实验,随机分为两组,分别于动脉鞘和造影(导引)导管插入前应用2％利多卡因溶液(215例,观察组)或0.9％氯化钠溶液 (214例,对照组)外擦其表面.记录并比较两组桡动脉痉挛的发生率.结果 实际入选病例为观察组213例,对照组213例.手术用时观察组明显低于对照组(P＜0.05);行单纯CAG,观察组的RAS发生率低于对照组(5.3％ vs 12.8％,P＜0.05);行CAG+PCI,观察组的RAS发生率低于对照组(4.8％ vs 19.2％,P＜0.05);总RAS发生率,观察组的RAS发生率低于对照组(5.2％ vs 14.6％,P＜0.05),差异均有统计学意义.结论 经桡动脉途径行冠脉介入诊疗过程中,利多卡因溶液外擦介入导管表面可以有效防止桡动脉痉挛的发生.