The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention of apoptosis of Hep3B cells by interleukin-6

Interleukin-6 (IL-6) is a pleitrophic cytokine that not only regulates growth and differentiation of many cell types, but also induces production of acute phase proteins (AAP) in hepatocytes. Our previous works have demonstrated that both PI 3-K/Akt and STAT3 pathways were concomitantly activated and cooperatively mediated the anti-apoptotic effect of IL-6. This investigation reports that IL-6 protected cells against apoptosis induced by a variety of agents including, TGF-beta, UV and retinoic acid (RA) in Hep3B cells, suggesting that IL-6 is a fundamental determinant of hepatic cell survival. Mcl-1, but not other Bcl-2 family members, was rapidly up-regulated by IL-6, with a peak (approximately 3-4-fold) appearing at 4 h. Transient transfection of cells with a mcl-1 antisense vector, resulting in a 50-60% reduction of the anti-apoptotic effect of IL-6, indicating that Mcl-1 is a downstream effector of IL-6. Which signaling pathway transduced by IL-6 responsible for the Mcl-1 up-regulation was further investigated. In Hep3B cells, the JAK/STAT3, ERK, and PI 3-K/Akt pathways were activated by IL-6 stimulation. Blocking JAK/STAT3 activation with a dominant-negative mutant STAT3F or a JAK inhibitor AG490 could not influence IL-6-mediated Mcl-1 up-regulation. Similarly, PD98059 treatment, a MEK specific inhibitor, also failed to inhibit Mcl-1 expression. However, the IL-6-induced Mcl-1 up-regulation was effectively attenuated in the presence of PI 3-K inhibitors, LY294002 and wortmannin. Expression of dominant-negative Akt, but not Etk, could abrogate the IL-6-induced increase of Mcl-1. In conclusion, our results suggest that the anti-apoptotic effect of IL-6 is mediated, at least in part, by Mcl-1 expression and that is mainly through the PI 3-K/ Akt-dependent pathway.     

七氟烷预先吸入对单肺通气患者肺功能及氧化应激的影响

目的：探讨七氟烷预先吸入对食管癌患者单肺通气（one lung ventilation,OLV）期间肺功能及氧化应激的影响。方法：60例拟行食管癌切除术患者,随机分为七氟烷预先吸入组（SP组）、丙泊酚静脉组（P组）及七氟烷全程吸入组（S组）。3组患者全麻诱导均为静脉注射咪达唑仑0.04 mg/kg,芬太尼3~4 μg/kg,靶控输注丙泊酚血浆靶浓度3 μg/ml,静脉注射罗库溴铵0.6~0.8 mg/kg,插入双腔管后SP组以七氟烷预先吸入维持麻醉至OLV前,OLV后与P组相同,采用丙泊酚、瑞芬太尼维持麻醉,七氟烷全程吸入组全程七氟烷吸入维持麻醉。麻醉诱导后（T1）、OLV开始前（T2）、OLV 30 min（T3）、OLV 60 min（T4）、OLV结束前（T5）及术毕（T6） 共6个时间点,采集桡动脉血和右心房血进行血气分析,计算Qs/Qt值,于T1、T3~T6时取右心房血样,测定血清超氧化物歧化酶（superoxide dismutase,SOD）活性和丙二醛（malondialdehyde,MDA）的浓度,同时记录血流动力学指标以及相关的临床数据。结果：与T1时比较,T3～T5（OLV期间）,3组Qs/Qt有明显增高（P<0.01）,PaO2明显降低（P<0.01）,T3～T6时血清SOD活性降低（P<0.05）,MDA浓度升高（P<0.05）;组间比较：与P组、S组相比,SP组在T4时Qs/Qt降低（P<0.05）,T5时血清SOD活性升高、MDA浓度降低（P<0.05）;S组与P组相比,S组在T3时Qs/Qt降低（P<0.05）,T5时Qs /Qt增加（P<0.05）,T3～T6时血清SOD活性稍降低,MDA浓度稍升高,但无统计学差异（P >0.05）;PaO2在3组各对应时点比较差异无统计学意义（P >0.05）。结论：OLV前用七氟烷预先吸入可降低食管癌患者OLV的肺内分流率,减轻OLV的氧化应激反应,对氧分压无明显改善。     

Patterns of biopsy-proven renal diseases in geriatric patients: A single medical center experience

The elderly population is expanding rapidly, and that has become a major healthcare burden in terms of chronic kidney disease. The distribution patterns of kidney diseases in these elderly patients remain largely unclear. Here, we compared biopsy-based renal disease patterns between elderly and nonelderly patients. We performed a single-center, retrospective study (1992–2008) on biopsy-proven renal diseases to compare results between geriatric patients (age ≥ 65 years; n = 254) and nongeriatric patients (18 ≤ age < 65 years; n = 2592). Renal pathology was interpreted by pathologists based on light microscopy, immunofluorescence, and electron microscopy. The ages of the geriatric and nongeriatric groups were 71.8 ± 4.5 (65.1–87.3) and 39.7 ± 17.6 (18–64.9) years, respectively, and 74% and 41% of them, respectively, were men. In the geriatric group, the most frequent diagnosis was membranous nephropathy (46.1%), followed by minimal change disease/focal segmental glomerulosclerosis (16.9%), diabetic nephropathy (8.3%), hypertensive nephrosclerosis (7.5%), and IgA nephropathy (5.9%). The geriatric group had more membranous nephropathy and less lupus nephritis and IgA nephropathy than the nongeriatric group. Furthermore, the 5-year survival rate of the geriatric group was significantly low. Our results demonstrated the different distributions of renal biopsy patterns in geriatric patients diagnosed with acute or chronic progressive kidney injury and proteinuria through renal biopsy.     

Effects of Achieving SVR on Clinical Characteristics and Surgical Outcomes in Patients Who Developed Early-Stage HCV-Related Hepatocellular Carcinoma and Received Curative Resection: Preoperative versus Postoperative SVR

The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR.     

Comparison of accuracy between digital and conventional implant impressions: two and three dimensional evaluations

PURPOSEThe present study compared the accuracy between digital and conventional implant impressions.MATERIALS AND METHODSThe experimental models were divided into six groups depending on the implant location and the scanning span. Digital impressions were captured using the intraoral optical scanner TRIOS (3Shape, Copenhagen, Denmark). Conventional impressions were taken with the monophase impression material based on addition-cured silicones, Honigum-Mono (DMG, Hamburg, Germany). A high-precision laboratory scanner D900 (3Shape, Copenhagen, Denmark) was used to obtain digital data of resin models and stone casts. Surface tessellation language (STL) datasets from scanner were imported into the analysis software Geomagic Qualify 14 (3D Systems, Rock Hill, SC, USA), and scan body deviations were determined through two-dimensional and three-dimensional analyses. Each scan body was measured five times. The Sidak t test was used to analyze the experimental data.RESULTSImplant position and scanning distance affected the impression accuracy. For a unilateral arch implant and the mandible models with two implants, no significant difference was observed in the accuracy between the digital and conventional implant impressions on scan bodies; however, the corresponding differences for trans-arch implants and mandible with six implants were extremely significant (P<.001).CONCLUSIONFor short-span scanning, the accuracy of digital and conventional implant impressions did not differ significantly. For long-span scanning, the precision of digital impressions was significantly inferior to that of the traditional impressions.     

雷公藤多苷对类风湿关节炎大鼠Ras/Raf1原癌基因表达的影响

目的：探究雷公藤多苷对类风湿关节炎大鼠关节血清及组织Ras/Raf1表达的影响。方法：将60只SD大鼠随机分为对照组、模型组和干预组,每组20只。模型组与干预组建立大鼠风湿关节炎模型,干预组用雷公藤多苷干预,对照组和模型组给予等量生理盐水。以足趾肿胀度为模型标准和疗效判定指标,实验终点通过酶联免疫吸附试验法（ELISA）检测大鼠血清Ras、Raf1以及炎症介质肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平,实验终点通过Western Blotting检测大鼠滑膜组织Ras和Raf1蛋白表达量并对大鼠踝关节进行HE染色分析。结果：ELISA结果表明,与对照组比较,模型组血清Ras、Raf1、TNF-α、IL-6显著升高（均P<0.01）,与模型组比较,干预组血清Ras、Raf1、TNF-α、IL-6显著降低（均P<0.01）;Western Blotting结果表明：与对照组大鼠比较,模型组大鼠滑膜组织Ras、Raf1显著升高（均P<0.01）,与模型组比较,干预组大鼠滑膜组织Ras、Raf1显著降低（均P<0.05）。HE染色表明：与对照组比较,模型组病理总评分升高（P<0.01）,与模型组比较,干预组病理总评分下降（P<0.05）。结论：雷公藤多苷可抑制大鼠血清炎症介质释放并降低外周血和关节组织中Ras、Raf1蛋白的表达,起到骨保护作用。     

The effects of desipramine, zimelidine, electroconvulsive treatment and lithium on rat brain biogenic amines: a comparison with peripheral changes

The effects of 4 common treatments for affective disorders on total body norepinephrine (NE) and dopamine (DA) turnover and metabolism were evaluated in rats. The treatments were chronic desipramine (DMI), zimelidine (ZMI), electroconvulsion (ECT) and lithium (Li). The central effects of ECT and Li were also assessed in the brain. The results obtained were compared with the effects of these 4 treatments on total NE (Sum NE) and DA (Sum DA) turnover in depressed patients. We have also evaluated central and/or peripheral effects of these treatments on phenylethylamine, p-tyramine and serotonin metabolism. The urinary changes in Sum NE and DA observed after DMI, ZMI and Li in the rat were similar to those found in depressed patients; Sum NE was significantly reduced. In contrast to its effects on depressed patients, chronic ECT significantly increased Sum NE. Similar to depressed patients, ECT reduced the fraction of NE escaping re-uptake in the rat. Sum DA was not affected by DMI, ZMI or ECT, but was significantly reduced by chronic Li treatment. All 4 treatments significantly reduced serotonin metabolism as indicated by reduced 5-hydroxyindoleacetic acid excretion rates. DMI, ZMI and Li treatments significantly reduced phenylethylamine urinary but not p-tyramine urinary outputs. The opposite effect was observed after ECT. Consistent with their effects on Sum NE, Li reduced while ECT increased hypothalamic NE turnover as deduced from the changes in 3-methoxy-4-hydroxyphenylglycol's rate of formation. As for Sum DA, Li had no effect on 3,4-dihydroxyphenylacetic acid or homovanillic acid's rates of formation in the caudate nucleus. Chronic ECT produced a small, but significant increase in homovanillic acid's rate of formation in the caudate nucleus.     

Antioxidative and in vitro hepatoprotective activity of Bupleurum kaoi leaf infusion

The roots of Bupleurus spp. have been used in traditional Chinese herbal medicine for curing liver diseases. Although bioactive saikosaponins have been detected in the leaves as well as in the roots, the aerial parts of the plants are discarded as waste. In the present study, a leaf infusion of B. kaoi Liu, Chao et Chuang, an indigenous Bupleurus species in Taiwan, was prepared and the antioxidant properties and in vitro hepatoprotective activity were demonstrated. The results show that the leaf infusion exerted DPPH free radical scavenging activity, inhibitory capacity on superoxide anion formation and superoxide anion scavenging activity. The hepatotoxicity of acetaminophen (APAP) and carbon tetrachloride (CCl4) on the rat liver cells were also decreased by the leaf infusion.     

不同提取方法制备石菖蒲挥发性成分的GC-MS比较研究

目的:比较不同提取方法制备的石菖蒲挥发油中的挥发性化学成分。方法:采用传统的水蒸气蒸馏提取挥发油,超临界流体萃取挥发油和顶空进样直接采集挥发性成分3种方法,对石菖蒲中的挥发性成分进行GC-MS分析。结果:顶空进样技术鉴定出44种挥发性化学成分;水蒸气蒸馏法可鉴定出23种挥发性化学成分;超临界流体萃取可鉴定出25种化合物,经GC-MS分析,水蒸气蒸馏法与粉末顶空进样有14种化合物相同,超临界流体萃取与粉末顶空进样有8种化合物相同,相对含量均有一定的差异。结论:顶空进样技术分析石菖蒲中挥发性成分更简单、快速、无溶剂残留并节省药材。     

人参15个组织器官中皂苷量与6种人参皂苷生物合成基因表达的相关性研究

以四年生红果期吉林人参的15个组织器官为材料,利用HPLC和香草醛-硫酸比色法分别测定15个组织器官中6种单体皂苷(人参皂苷Rg₁,Re,Rb₁,Rc,Rb₂,Rd)和总皂苷含量;同时,利用实时荧光定量PCR测定15个组织器官中法尼基焦磷酸合成酶(farnesyl pyrophosphate synthase,FPS)、鲨烯合成酶(squalene synthase,SQS)、鲨烯环氧酶(squalene epoxidase,SQE)、氧化鲨烯环化酶(oxidized squalene cyclase,OSC)、β-香树脂合成酶(β-amyrin synthase,β-AS)和细胞色素P450超家族(cytochrome P450 family,P450)基因的相对表达量。研究试图通过相关性分析,获得吉林人参15个组织器官中人参皂苷含量与生物合成途径相关酶基因表达量之间相关关系。结果表明,6种单体皂苷含量之间具有线性正相关的协同增减趋势,而单体皂苷含量与总皂苷含量之间具有相关性极显著(P<0.01)的正相关关系;总皂苷含量与人参中SQS,OSC,β-AS,SQE,P450,FPS基因之间的相关性极显著(P<0.01),单体皂苷含量与6种酶基因之间相关性各不相同。说明这6种参与人参皂苷生物合成酶基因调控人参总皂苷与单体皂苷的生物合成,它们在人参不同组织器官中的表达呈现协同增减趋势,并以集群协调表达的方式来调控人参皂苷生物合成。