六种螯合剂对镉的解毒、排泄作用的比较

本文报道螯合剂7603、8102、8307和811对镉中毒动物的解毒和促排作用,并同临床应用的有效药物DTPA、EDTA进行了比较。小鼠氯化镉中毒后,给予不同剂量的螯合剂解毒,观察7天内存活率。结果表明DTPA、EDTA和8102对氯化镉中毒的小鼠有明显解毒作用,尤以DTPA、EDTA解毒作用为佳。大鼠镉中毒后肌注螯合剂,收集48小时尿液,用PE—3030原子吸收分光光度计测定尿镉总量,发现六种螯合剂对大鼠镉中毒均有显著促排作用,其中以DTPA、EDTA、8102效果更好,三药对尿镉促排效果的次序为:DTPA>EDTA>8102。     

In-hospital mortality rate in the national heart, lung, and blood institute percutaneous transluminal coronary angioplasty registry

Twenty-nine patients died among the first 3,079 patients enrolled in the NHLBI PTCA Registry. The overall morality rate was 0.9%; the mortality rate was 0.8% in patients with 1-vessel CAD, 1.0% in those with multivessel CAD (excluding left main CAD), and 3.8% in those with left main CAD (p < 0.01). The in-hospital morality rate was significantly higher among women (p < 0.01), in patients older than 60 years, in patients with previous CABG (p < 0.01), the presence of left main CAD, (p < 0.01), in patients who required dilatation of a vein graft stenosis (p < 0.05), and in patients who had had angina for longer than 6 months (p < 0.01).     

Low lymphocyte monocyte ratio after neoadjuvant therapy predicts poor survival after pancreatectomy in patients with borderline resectable pancreatic cancer

BackgroundThe impact of systemic immune inflammatory markers to predict survival in patients receiving neoadjuvant therapy for borderline resectable pancreatic cancer has not been sufficiently investigated. This study aims to evaluate whether systemic immune inflammatory markers after neoadjuvant therapy followed by pancreatectomy become preoperative prognostic factors to predict survival in patients with borderline resectable pancreatic cancer.MethodsWe retrospectively reviewed 67 borderline resectable pancreatic cancer patients receiving neoadjuvant therapy and 58 borderline resectable pancreatic cancer patients undergoing upfront surgery between 2010 and 2016. The association between survival and systemic immune inflammatory markers was evaluated by univariate and multivariate analysis. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and prognostic nutrition index were assessed as systemic immune inflammatory markers.ResultsIn univariate analysis, the postneoadjuvant neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and prognostic nutrition index are significantly associated with survival as systemic immune inflammatory markers. The optimal cutoff value of the postneoadjuvant neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and prognostic nutrition index were 2.5, 3.0, and 45, respectively. Patients with a lymphocyte-to-monocyte ratio <3.0 had significantly poor survival compared with those who had a lymphocyte-to-monocyte ratio ≥3.0 (14.9 months vs 31.7 months, P = .006). The multivariate analysis identified the following as predictors of poor prognosis: postneoadjuvant lymphocyte-to-monocyte ratio <3.0 (HR 2.59; 95% CI 1.02–6.58; P = .045), T4 (HR 1.82; 95% CI 1.11–3.01; P = .029), lymph node status (HR 2.62; 95% CI 1.24–5.51; P = .012), and no completion of adjuvant therapy (HR 7.09; 95% CI 3.08–16.4; P < .001).ConclusionA low lymphocyte-to-monocyte ratio after neoadjuvant therapy is useful prognostic information for patients with borderline resectable pancreatic cancer. This result might indicate a potential role of lymphocyte-to-monocyte ratios in stratification of treatment strategy in borderline resectable pancreatic cancer patients.     

NIM811对Na2S2O4引起小鼠HT22细胞缺氧/复氧损伤的保护作用的研究

目的探讨环孢菌素衍生物NIM811对连二亚硫酸钠(Na₂S₂O₄)引起的小鼠海马神经元细胞(HT22)的缺氧/复氧损伤的保护作用及其机制。方法以小鼠HT22培养细胞制备缺氧/复氧细胞模型,实验分组为正常对照组、Na₂S₂O₄组、Na₂S₂O₄+NIM811组、NIM811组。CCK-8检测细胞生存率、流式细胞术检测细胞凋亡、JC-1试剂检测线粒体膜电位、用钙离子指示剂Rhod-2 AM观察线粒体内钙离子水平、DCFH-DA法检测细胞活性氧(ROS)水平。结果与Na₂S₂O₄组比较,给予NIM811处理后:(1)细胞活性增高38%(P<0.01);(2)细胞凋亡减少27%(P<0.01);(3)线粒体膜电位上升(P<0.01);(4)线粒体内钙离子水平下降(P<0.01);(5)活性氧(ROS)水平降低(P<0.01)。结论NIM811对Na₂S₂O₄引起小鼠海马神经元细胞缺氧/复氧损伤有保护作用,其机制可能为NIM811维持线粒体动态平衡和抑制细胞凋亡有关,NIM811对未来临床治疗缺血性脑卒中具有潜力。     

Pretreatment with the ciclosporin derivative NIM811 reduces delayed neuronal death in the hippocampus after transient forebrain ischaemia

Objectives There have been several previous studies showing that ciclosporin, a ligand for cyclophilin D (CypD), reduces mitochondrial permeability transition (mPT) and ameliorates delayed neuronal death. NIM811 is a non‐immunosuppressive ciclosporin derivative that also inhibits mPT, but has significantly less cytotoxicity than ciclosporin. Actually, in animal experiments, several investigators have reported that NIM811 ameliorates central nervous system disorders, such as traumatic brain injury, transient focal cerebral ischaemia and spinal cord injury. Therefore, we evaluated whether the ciclosporin derivative, NIM811 reduces mPT and ameliorates delayed neuronal death in the hippocampal CA1 sectors in mice when subjected to transient forebrain ischaemia. Methods Male C57BL/6 mice were treated with 50 mg/kg ciclosporin, 10, 50 or 100 mg/kg NIM811 or phosphate‐buffered saline. At 30 min post‐injection, all mice were subjected to 20 min bilateral common carotid artery occlusion (BCCAO). To estimate delayed neuronal death, the sections were prepared for HE staining and terminal deoxynucleotidyl transferase‐mediated dUTP end‐labelling (TUNEL) staining at 72 h after 20 min BCCAO. Furthermore, using 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimidazolocarbocyanine iodide (JC‐1) staining technique, we evaluated whether NIM811 (1, 10, 100 or 1000 μm ) inhibited mPT in the neurons exposed to 100 μm glutamate. Results Both delayed neuronal injury and apoptosis in the hippocampal CA1 sectors were significantly ameliorated at 72 h after transient forebrain ischaemia in the mice treated with 100 mg/kg NIM811 or 50 mg/kg ciclosporin. The treatments with 100 μm and 1000 μm NIM811 significantly inhibited the reduction of mitochondrial membrane potential in the neurons exposed to 100 μm glutamate. Conclusions These findings strongly suggest that NIM811 inhibits mPT and ameliorates delayed neuronal death in mice subjected to transient forebrain ischaemia.     

DTPA-Ca和811对大白鼠体内钪-46促排作用的研究

本文报道了DTPA和811对大白鼠体内钪-46的促排效果。结果表明,注射811、DTPA组大鼠使钪-46的排除途径排除量和生物半排期发生明显变化。使钪-46随粪便排除为主改变为随尿排除为主,与对照组比较,811、DTPA使钪-46的生物半排除期快排除相均缩短2.40天(对照组为4.3天),中排除相分别缩短2.77天和4.90天(对照组为9.40天),而慢排除相分别延长7.60天和8.60天(对照组为18天)。以上证明,811和DTPA早期肌肉注射对大白鼠作体内钪-46有较好的促排用,且DTPA-Ca优于811。     

Ex vivo study of the efficacy of H-files and rotary Ni-Ti instruments to remove gutta-percha and four types of sealer

AIM: To compare the efficacy of ProFile rotary Nickel-Titanium (Ni-Ti) instruments and Hedstroem-files (H-files) combined with Gates-Glidden (GG) drills during removal of gutta-percha root fillings used in combination with one of the four representative sealers. METHODOLOGY: Forty-eight single-rooted human teeth, with fully formed apices and straight root canals were used. The root canals were accessed and instrumented using a stepback technique with H-files. They were randomly assigned to four groups and subsequently filled with a combination of lateral and vertical condensation of gutta-percha and one of the following sealers: Roth 811, AH26, Endion and Roekoseal. The root fillings were removed 1 year later, using either H-files in combination with GG drills or the ProFile Ni-Ti system. Teeth were then grooved longitudinally and split. The amount of gutta-percha and sealer remaining on the root canal walls was traced and scored visually with the aid of a stereomicroscope. The scores were analysed and statistically compared with the Kruskal-Wallis test between the ProFile and H-file groups, as well as among the four sealer subgroups. Two samples from each group were studied under the scanning electron microscope to enhance inspection of canal walls and remaining material. RESULTS: Sealer remnants were observed with both techniques mainly in the middle and apical third of the root canal. The ProFile system and the H-files were associated with similar amounts of remaining filling material (P > 0.05). In the cervical third of the root canal all sealer remnants were removed with both techniques. In the middle and apical third AH26 was associated with a statistically significant greater quantity of remnants on the root canal walls with both removal techniques (P < 0.05). Endion, Roth 811 and Roekoseal were associated with approximately the same amount of filling material in the middle third of the root canal (P > 0.05), whereas in the apical third Endion was associated with significantly more remnants of filling material than the other two sealers with either ProFile or H-files (P < 0.05). CONCLUSIONS: None of the methods used for the removal of root fillings was totally effective, especially in the apical third of the root canal.