BACKGROUND & AIMS: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.

背景与目标：

BACKGROUND & AIMS: :Left ventricular (LV) dysfunction and/or heart failure (HF) are frequent complications of hypertension and myocardial infarction (MI), placing affected patients at increased risk of significant morbidity and premature death. Given that the renin-angiotensin-aldosterone system (RAAS) is activated and of pathophysiological importance in such patients, a strong therapeutic rationale exists to target the main effector mechanism (that is, angiotensin II [Ang II]) in order to lessen the associated morbidity and mortality burden. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce mortality and LV dysfunction and to slow disease progression in patients with HF, including high-risk, post-MI patients. However, ACE inhibitors (ACE-Is) may not provide optimal long-term RAAS blockade (a finding that is associated with a worse prognosis) and many patients are unable to tolerate such therapy (because of troublesome dry cough, for example). In contrast, Ang II receptor blockers (ARBs) may block the RAAS more completely than ACE-Is and appear to be better tolerated. Several large-scale trials gave evaluated the efficacy of ARBs in patients with LV dysfunction and/or HF (including high-risk, post-MI patients), and have confirmed their utility as an efficacious and well-tolerated alternative to ACE-Is in this setting.

背景与目标： : 左心室 (LV) 功能障碍和/或心力衰竭 (HF) 是高血压和心肌梗塞 (MI) 的常见并发症，使受影响的患者具有显着发病率和过早死亡的风险。鉴于肾素-血管紧张素-醛固酮系统 (RAAS) 在此类患者中被激活并且具有病理生理重要性，因此存在针对主要效应机制 (即血管紧张素II [Ang II]) 的强有力的治疗依据，以减轻相关的发病率和死亡率负担。血管紧张素转换酶 (ACE) 抑制剂已被证明可降低HF患者 (包括高危MI后患者) 的死亡率和LV功能障碍，并可减缓疾病进展。然而，ACE抑制剂 (ACE-Is) 可能无法提供最佳的长期RAAS阻断 (这一发现与更差的预后相关)，并且许多患者无法耐受这种治疗 (例如，由于麻烦的干咳)。相比之下，Ang II受体阻滞剂 (arb) 可能比ACE-Is更完全地阻断RAAS，并且似乎具有更好的耐受性。几项大规模试验评估了ARBs在LV功能障碍和/或HF患者 (包括高危MI后患者) 中的疗效，并已证实其作为ACE-Is的有效且耐受性良好的替代方法在这种情况下。

BACKGROUND & AIMS: OBJECTIVE:To investigate clinically relevant intra-individual and mean changes in health-related quality of life (HRQoL) with the Short Form-36 Health Survey (SF-36) need to acknowledge that SF-36 is trademarked ie: SF-36(R) following cardiac intervention for Australian and Danish patients. DESIGN:Prospective observational study in tertiary cardiac centres in Townsville, Queensland, Australia and Copenhagen, Denmark. Two hundred coronary artery bypass graft surgery (CABG) patients of two Townsville hospitals, and 47 CABG or percutaneous coronary intervention (PCI) patients of a Copenhagen hospital. The main outcome measures are eight SF-36 health subscales at baseline and six months post-intervention. RESULTS:Australian and Danish patients experienced similar HRQoL pre-intervention. By six months post-intervention, patients experienced a significant mean improvement in all subscales of the SF-36 survey (p < or = 0.05), although up to 27% of patients had a clinically significant decline in HRQoL from baseline. CONCLUSIONS:These results demonstrate that it is necessary to investigate intra-individual changes in HRQoL as well as group mean changes as they produce different conclusions. In addition, establishing clinically significant intra-individual change standards may assist researchers and clinicians in determining whether an individual may benefit from therapy or intervention.

背景与目标：

BACKGROUND & AIMS: :Immunocompromise after a major injury is presumed to be a predisposing factor for sepsis. Mice subjected to sublethal cecal ligation and puncture (CLP) and challenged 5 days later with Pseudomonas aeruginosa had more bacterial growth in lung tissue, lower serum interferon gamma (IFN-gamma) and interleukin (IL) 12,and higher serum IL-10 when compared with sham CLP mice challenged with Pseudomonas. To test the functional significance of these alterations in cytokine production in the immune response to bacteria, we administered IFN-gamma and anti-IL-10 to post-CLP mice before the Pseudomonas challenge. Administration of IFN-gamma and anti-IL-10 did not improve bacterial clearance or mortality in post-CLP mice. In further studies, we administered IFN-gamma to IL-10 knockout mice before a challenge with P. aeruginosa. Our results showed no significant differences in bacterial clearance or mortality in IL-10 knockout mice with or without IFN-gamma treatment compared with wild-type controls. Finally, because most mortality occurred within 2 to 3 days of the Pseudomonas challenge in the aforementioned studies and was likely associated with a marked proinflammatory response, we investigated the effect of IFN-gamma and anti-IL-10 on clearance of Pseudomonas in C3H/HeJ mice, which do not mount an exaggerated proinflammatory response to endotoxin or Gram-negative bacteria. Neither clearance of the Pseudomonas bacteria nor mortality was improved in C3H/HeJ mice receiving anti-IL-10 and IFN-gamma. These results suggest that the suppressed IFN-gamma and IL-12 responses, in combination with an exaggerated IL-10 response to P. aeruginosa challenge after injury, do not correlate with bacterial clearance or survival.

背景与目标： : 重大损伤后的免疫损害被认为是败血症的诱发因素。与假单胞菌相比，接受亚致死性盲肠结扎和穿刺 (CLP) 并在5天后用铜绿假单胞菌攻击的小鼠肺组织中细菌生长更多，血清干扰素 γ (IFN-γ) 和白介素 (IL) 12降低，血清IL-10更高。为了测试这些细胞因子产生变化在对细菌的免疫反应中的功能意义，我们在假单胞菌攻击之前对CLP后小鼠施用IFN-γ 和anti-IL-10。施用IFN-γ 和anti-IL-10不会改善CLP后小鼠的细菌清除率或死亡率。在进一步的研究中，我们在用铜绿假单胞菌攻击之前对IL-10基因敲除小鼠施用IFN-γ。我们的结果表明，与野生型对照相比，有或没有IFN-γ 处理的IL-10基因敲除小鼠的细菌清除率或死亡率没有显着差异。最后，由于大多数死亡率发生在上述研究中假单胞菌攻击的2至3天内，并且可能与明显的促炎反应有关，因此我们研究了IFN-γ 和anti-IL-10对C3H/HeJ小鼠中假单胞菌清除的影响，它们不会对内毒素或革兰氏阴性细菌产生夸张的促炎反应。在接受anti-IL-10和IFN-γ 的C3H/HeJ小鼠中，假单胞菌的清除率和死亡率均未改善。这些结果表明，受抑制的IFN-γ 和IL-12反应，再加上损伤后对铜绿假单胞菌攻击的过度IL-10反应，与细菌清除或存活无关。

BACKGROUND & AIMS: :Given the paucity of data on the distribution of serotonin (5-HT) receptors of type 6 (5-HT(6)) in the human brain, the aim of this study was to investigate their distribution in postmortem human prefrontal cortex, striatum and hippocampus by either immunohistochemical or immunofluorescence techniques. The brain samples were obtained from 6 subjects who had died for causes not involving primarily or secondarily the CNS. The 5-HT(6) receptor distribution was explored by the [(125)I]SB-258585 binding to brain membranes followed by immunohistochemical and immunofluorescence evaluations. A specific [(125)I]SB-258585 binding was detected in all the regions under investigation, whilst the content in the hippocampus and cortex being about 10-30 times lower than in the striatum. Immunohistochemistry and double-label immunofluorescence microscopy experiments, carried out in the prefrontal cortex and hippocampus only, since data in the striatum were already published, showed the presence of 5-HT(6) receptors in both pyramidal and glial cells of prefrontal cortex, while positive cells were mainly pyramidal neurons in the hippocampus. The heterogeneous distribution of 5-HT(6) receptors provides a preliminary explanation of how they might regulate different functions in different brain areas, such as, perhaps, brain trophism in the cortex and neuronal firing in the hippocampus. This study, taking into account all the limitations due to the postmortem model used, represents the starting point to explore the 5-HT(6) receptor functionality and its sub-cellular distribution.

背景与目标： : 鉴于人脑中6型5-羟色胺 (5-HT(6)) 受体分布的数据很少，本研究的目的是通过免疫组织化学或免疫荧光技术研究其在死后人类前额叶皮层，纹状体和海马中的分布。大脑样本来自6名因不主要或次要涉及CNS的原因而死亡的受试者。5-羟色胺 (6) 受体分布通过 [(125)I]SB-258585与脑膜结合，然后进行免疫组织化学和免疫荧光评估来探索。在所研究的所有区域中检测到特定的 [(125)I]SB-258585结合，而海马和皮层的含量比纹状体低约10-30倍。免疫组织化学和双标记免疫荧光显微镜实验，仅在前额叶皮层和海马中进行，因为纹状体中的数据已经发表，显示在前额叶皮层的锥体和神经胶质细胞中都存在5-HT(6) 受体，而阳性细胞主要是海马中的锥体神经元。5-HT(6) 受体的异质分布提供了它们如何调节不同大脑区域的不同功能的初步解释，例如，也许，皮质中的脑营养和海马中的神经元放电。这项研究考虑到使用的死后模型所造成的所有局限性，代表了探索5-HT(6) 受体功能及其亚细胞分布的起点。

BACKGROUND & AIMS: INTRODUCTION:Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS:BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS:Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION:Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.

背景与目标：

BACKGROUND & AIMS: :Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).

背景与目标： : 美国 (20世纪70年代1985年) 和瑞士 (1988-1993) 的精神科医生和心理治疗师合法使用MDMA作为处方药，以提高心理治疗的有效性。早期报告表明，它在治疗创伤相关疾病中很有用。最近，第一个完成的MDMA辅助心理治疗PTSD的初步研究取得了令人鼓舞的结果。旨在测试MDMA辅助心理治疗在治疗耐药的PTSD患者中的安全性和有效性; 我们的随机，双盲，活性安慰剂对照试验招募了12名患者接受低剂量 (25 mg，加12.5 mg补充剂量) 或全剂量MDMA (125 mg，加62.5 mg补充剂量)。MDMA在三个实验课程中进行，并散布在每周的非基于药物的心理治疗课程中。使用的结果指标是临床医生管理的PTSD量表 (CAPS) 和创伤后诊断量表 (PDS)。在基线，第二次和第三次MDMA疗程 (治疗结束) 后三周以及2个月和1年随访时对患者进行评估。我们发现MDMA辅助心理治疗可以在临床环境中安全施用。未发生与药物相关的严重不良事件。尽管有临床和统计学上显着的自我报告 (PDS) 改善 (p = 0.066)，但我们没有看到CAPS评分的统计学显着降低 (p = 0.014)。在1年的随访中，CAPS评分进一步提高。此外，三个MDMA会话比两个更有效 (p = 0.016)。

BACKGROUND & AIMS: :Although mean efficacy of multivalent pneumococcus vaccines has been intensively studied, variance in vaccine efficacy (VE) has been overlooked. Different net individual protection across settings can be driven by environmental conditions, local serotype and clonal composition, as well as by socio-demographic and genetic host factors. Understanding efficacy variation has implications for population-level effectiveness and other eco-evolutionary feedbacks. Here I show that realized VE can vary across epidemiological settings, by applying a multi-site-one-model approach to data post-vaccination. I analyse serotype prevalence dynamics following PCV7, in asymptomatic carriage in children attending day care in Portugal, Norway, France, Greece, Hungary and Hong-Kong. Model fitting to each dataset provides site-specific estimates for vaccine efficacy against acquisition, and pneumococcal transmission parameters. According to this model, variable serotype replacement across sites can be explained through variable PCV7 efficacy, ranging from 40% in Norway to 10% in Hong-Kong. While the details of how this effect is achieved remain to be determined, here I report three factors negatively associated with the VE readout, including initial prevalence of serotype 19F, daily mean temperature, and the Gini index. The study warrants more attention on local modulators of vaccine performance and calls for predictive frameworks within and across populations.

背景与目标： : 尽管已经深入研究了多价肺炎球菌疫苗的平均效力，但疫苗效力 (VE) 的差异却被忽略了。环境条件，当地血清型和克隆组成以及社会人口统计学和遗传宿主因素可以驱动不同环境的净个体保护。了解功效变化会对人口水平的有效性和其他生态进化反馈产生影响。在这里，我表明，通过将多站点一模型的方法应用于疫苗接种后的数据，实现的VE可以在流行病学设置中有所不同。我分析了PCV7之后在葡萄牙，挪威，法国，希腊，匈牙利和香港的日托儿童中无症状携带的血清型患病率动态。对每个数据集的模型拟合提供了针对采集的疫苗功效和肺炎球菌传播参数的特定站点估计。根据该模型，可以通过从挪威的40% 到香港的10% 的可变PCV7功效来解释跨位点的可变血清型替代。尽管如何实现这种效果的细节仍有待确定，但在这里我报告了与VE读数负相关的三个因素，包括血清型19F的初始患病率，每日平均温度和基尼指数。该研究需要更多地关注疫苗性能的局部调节剂，并呼吁在人群内部和人群之间建立预测框架。

BACKGROUND & AIMS: :In a neoadjuvant setting, three parameters for Ki-67 could be obtained: pre-treatment Ki-67, post-treatment Ki-67 and Ki-67 change between pre- and post-treatments. It is uncertain which of the three parameters has the greatest prognostic significance, and whether this parameter has significance in each subtype of breast cancer. A total of 385 patients who received neoadjuvant anthracycline followed by taxane chemotherapy and subsequent surgery for breast cancer were analyzed retrospectively. By immunohistochemistry (IHC), patients were divided into four subtypes (Luminal A, Luminal B, Triple negative, and HER2). Ki-67 was examined by IHC in pre-treatment core needle samples and post-treatment surgical excision specimens. The relapse-free survival (RFS) rate was compared among each subtype. The median follow-up period was 56 months. The rate of pathological complete response was higher for HER2 (34.8 %) and Triple negative (24.3 %) subtypes than for Luminal B (8.3 %) and Luminal A (3.8 %) subtypes (p < 0.0001). A reduction in Ki-67 was observed in 58.5, 83.4, 70.2, and 74.2 % of patients in the Luminal A, Luminal B, Triple negative, and HER2 subtypes, respectively. Ki-67 change between pre- and post-treatments was an independent prognostic factor, but pre-treatment Ki-67 and post-treatment Ki-67 were not independent prognostic factors in a multivariate analysis. The RFS was significantly different between patients whose Ki-67 was reduced and those not reduced for Luminal B (81.4 vs. 50.0 %, p = 0.006), Triple negative (74.8 vs. 43.5 %, p = 0.006) and HER2 (82.7 vs. 59.0 %, p = 0.009). However, for Luminal A, the difference in RFS was not associated with changes of Ki-67 (78.8 vs. 75.3 %, p = 0.193). Ki-67 change between pre- and post-neoadjuvant chemotherapy is an independent prognostic factor in patients of Luminal B, Triple negative, and HER2 subtypes. Pre-treatment Ki-67 and post-treatment Ki-67 were not independent prognostic factors in a multivariate analysis.

背景与目标： : 在新佐剂环境中，可以获得三个Ki-67参数: 治疗前Ki-67，治疗后Ki-67以及治疗前和治疗后之间的Ki-67变化。不确定这三个参数中哪个具有最大的预后意义，以及该参数在每种乳腺癌亚型中是否具有意义。回顾性分析了总共385例接受新辅助蒽环类药物后进行紫杉烷化疗和随后进行乳腺癌手术的患者。通过免疫组织化学 (IHC) 将患者分为四种亚型 (Luminal A，Luminal B，三重阴性和HER2)。用IHC检查治疗前的芯针样品和治疗后的手术切除标本中的Ki-67。比较每种亚型之间的无复发生存率 (RFS)。中位随访期为56个月。HER2 (34.8%) 和三阴性 (24.3%) 亚型的病理完全缓解率高于管腔B (8.3%) 和管腔A (3.8%) 亚型 (p <0.0001)。在腔A，腔B，三阴性和HER2亚型中分别观察到58.5，83.4，70.2和74.2% 患者的Ki-67降低。在多变量分析中，治疗前后的Ki-67变化是独立的预后因素，但治疗前Ki-67和治疗后Ki-67不是独立的预后因素。Luminal B (81.4 vs. 50.0%，p = 0.006)，三阴性 (74.8 vs. 43.5%，p = 0.006) 和HER2 (82.7 vs. 59.0%，p = 0.009) 的Ki-67降低和未降低的患者之间的RFS显着不同。然而，对于Luminal A，RFS的差异与Ki-67的变化无关 (78.8 vs. 75.3%，p = 0.193)。新辅助化疗前后的Ki-67变化是Luminal B，三阴性和HER2亚型患者的独立预后因素。在多变量分析中，治疗前Ki-67和治疗后Ki-67不是独立的预后因素。

BACKGROUND & AIMS: Presented is the first reported case of an anaphylactoid reaction following Norplant contraceptive implant insertion. The 19-year-old UK woman denied any history of allergic reaction to local anesthesia. After subcutaneous infiltration with 50 mg of 1% lidocaine (without adrenalin), 6 Norplant capsules were inserted through use of the standard insertion technique. Shortly after completion of the procedure, the patient collapsed and had 2 short convulsions. Her blood pressure dropped to 80/40 mm Hg and her radial pulse was 60 beats/minute and thready. Recovery was rapid following administration of intramuscular adrenalin and intravenous hydrocortisone. The woman later recalled a similar episode during a visit to her dentist. An estimated 3 in every 100,000 patients receiving lignocaine hydrochloride have an episode of anaphylaxis in the hospital. In type I hypersensitivity reactions, there is often a history of previous exposure to the allergen, as occurred in this patient. Those undertaking Norplant insertion and removal should be aware of the potential for serious allergic reactions and have access to resuscitative equipment.

背景与目标： 提出了第一例报道的Norplant避孕植入物插入后发生类过敏反应的病例。这位19岁的英国妇女否认对局部麻醉有任何过敏反应史。在皮下浸润50 mg 1% 利多卡因 (不含肾上腺素) 后，通过使用标准插入技术插入6个Norplant胶囊。手术完成后不久，患者晕倒并出现2次短暂抽搐。她的血压下降到80/40毫米汞柱，她的桡动脉脉搏是60次/分钟和微弱的。肌肉注射肾上腺素和静脉注射氢化可的松后恢复迅速。这位女士后来在去看牙医时回忆起类似的情节。每100,000名接受盐酸利诺卡因的患者中估计有3名在医院发生过敏反应。在I型超敏反应中，通常有先前暴露于过敏原的病史，如在该患者中发生的。那些进行Norplant插入和移除的人应该意识到严重过敏反应的可能性，并可以使用复苏设备。

BACKGROUND & AIMS: :Old and frail patients with advance breast malignancy require mastectomy which often results in large defects requiring soft tissue cover. We present three cases of large fasciocutaneous perforator based V-Y advancement flaps for reconstruction of large post-mastectomy wounds in older patients with large tumours. This technique reduces the morbidity of patients who have severe co-existing morbidity factor in addition to the advance breast disease.

背景与目标： : 患有晚期乳腺恶性肿瘤的年老体弱患者需要进行乳房切除术，这通常会导致大量缺损，需要软组织覆盖。我们介绍了3例基于大型筋膜皮肤穿孔器的v-y推进皮瓣，用于重建患有大肿瘤的老年患者的大型乳房切除术后伤口。除了晚期乳腺疾病外，该技术还可以降低具有严重并存发病率因素的患者的发病率。

BACKGROUND & AIMS: :The existence of a chest wall "steal" of blood away from the myocardium through patent internal mammary artery branches has been hypothesized as a cause of recurrent angina pectoris after coronary artery bypass grafting. Although some authors believe that such a steal is physiologically impossible because coronary flow occurs in diastole and chest wall flow in systole, we recently documented ischemia in the left anterior descending coronary artery distribution before embolization of a large left internal mammary artery first intercostal branch that had been left intact at the time of operation. After embolization of the branch, clinical and objective evidence of ischemia resolved.

背景与目标： : 假设存在胸壁通过未闭的乳内动脉分支从心肌 “窃取” 血液，这是冠状动脉旁路移植术后再发心绞痛的原因。尽管一些作者认为这种偷窃在生理上是不可能的，因为冠状动脉血流发生在舒张期，胸壁血流发生在收缩期，但我们最近记录了左前降支在栓塞大的左乳内动脉第一肋间分支之前的缺血。在手术时保持完整。分支栓塞后，缺血的临床和客观证据得以解决。

BACKGROUND & AIMS: :Recent findings demonstrate that multiple mRNAs are co-regulated by one or more sequence-specific RNA-binding proteins that orchestrate their splicing, export, stability, localization and translation. These and other observations have given rise to a model in which mRNAs that encode functionally related proteins are coordinately regulated during cell growth and differentiation as post-transcriptional RNA operons or regulons, through a ribonucleoprotein-driven mechanism. Here I describe several recently discovered examples of RNA operons in budding yeast, fruitfly and mammalian cells, and their potential importance in processes such as immune response, oxidative metabolism, stress response, circadian rhythms and disease. I close by considering the evolutionary wiring and rewiring of these combinatorial post-transcriptional gene-expression networks.

背景与目标： : 最近的发现表明，多种mrna由一种或多种序列特异性RNA结合蛋白共同调控，这些蛋白协调了它们的剪接，输出，稳定性，定位和翻译。这些和其他观察结果产生了一个模型，在该模型中，编码功能相关蛋白的mrna在细胞生长和分化过程中通过核糖核蛋白驱动的机制作为转录后RNA操纵子或调控子被协同调控。在这里，我描述了最近发现的几个在发芽的酵母，果蝇和哺乳动物细胞中的RNA操纵子的例子，以及它们在免疫反应，氧化代谢，应激反应，昼夜节律和疾病等过程中的潜在重要性。最后，我考虑了这些组合转录后基因表达网络的进化和重新布线。

BACKGROUND & AIMS: :The aim of this study was to investigate the effects of the application of gaseous ozone and Nd:YAG laser on glass-fibre post bond strength. Forty-two madibular premolar roots were cut, endodontically instrumented and irrigated with 2.5% NaOCl. Post spaces were prepared and roots were divided into three groups (n = 14). The antimicrobial pretreatment was conducted as follows: gaseous ozone, Nd:YAG laser and control (no additional disinfection methods). Scanning electron microscope analysis was made for each group (n = 2). A resin cement was used for luting the posts. For push-out test, each root was cut horizontally (two cervical, two middle and two apical). Statistical analyses were performed with one-way anova (α = 0.05). Fracture types were observed. There was no statistically significant difference between the groups (P > 0.05). There were statistically significant differences in cervical and apical segments of laser and control groups (P < 0.05). The disinfection of the post spaces with Nd:YAG laser and ozone had no adverse effects on bond strength of glass-fibre post.

背景与目标： : 这项研究的目的是研究气态臭氧和Nd:YAG激光对玻璃纤维后粘结强度的影响。切开42个颌前磨牙根，进行牙髓器械治疗并用2.5% NaOCl冲洗。准备了柱子空间，将根分为三组 (n = 14)。抗菌预处理如下: 气态臭氧，Nd:YAG激光和对照 (无其他消毒方法)。对每组进行扫描电子显微镜分析 (n = 2)。使用树脂水泥来润滑柱子。对于推出测试，将每个根部水平切割 (两个子宫颈，两个中间和两个顶端)。用单因素方差分析 (α = 0.05) 进行统计分析。观察到骨折类型。各组间差异无统计学意义 (P> 0.05)。激光组和对照组的宫颈和根尖节段差异有统计学意义 (P <0.05)。Nd:YAG激光和臭氧对桩间隙的消毒对玻璃纤维桩的粘结强度没有不利影响。

BACKGROUND & AIMS: :Cancer is one of the major causes of mortality in organ transplant patients receiving immunosuppressive regimen based on Cyclosporin A (CsA). Organ transplantation and chronic immunosuppression are typically associated with skin cancers (both squamous cell carcinoma and melanoma) and renal cell carcinoma (RCC). Recent studies have shown that in addition to its immunosuppressive effects, accounted for by the inhibition of calcineurin and the modulation of the transcriptional programme of lymphocytes, CsA also directly stimulates the growth and aggressive behaviour of various cancer cells. Using renal carcinogenesis as an example, we discuss the current evidence for a role of cellular proteostasis, i.e. the regulation of the production, maturation and turnover of proteins in eukaryotic cells, in tumorigenesis arising under conditions of chronic immunosuppression. We present the recent studies showing that CsA induces the unfolded protein response (UPR) in normal and transformed kidney cells. We examine how the UPR might be important, considering in particular the genomic analyses showing the existence of a correlation between the levels of expression of the actors of the UPR, the chaperones of the endoplasmic reticulum (ER) and the aggressiveness of renal carcinoma. The UPR may offer a possible explanation for how immunosuppressive regimens based on CsA promote renal carcinogenesis. We discuss the opportunities offered by this biological knowledge in terms of screening, diagnosis and treatment of post-transplant cancers, and propose possible future translational studies examining the role of tumour proteostasis and the UPR in this context.

背景与目标： : 癌症是接受基于环孢菌素A (CsA) 的免疫抑制方案的器官移植患者死亡的主要原因之一。器官移植和慢性免疫抑制通常与皮肤癌 (鳞状细胞癌和黑色素瘤) 和肾细胞癌 (RCC) 相关。最近的研究表明，除了其免疫抑制作用 (通过抑制钙调神经磷酸酶和调节淋巴细胞的转录程序) 外，CsA还直接刺激各种癌细胞的生长和攻击行为。以肾癌发生为例，我们讨论了细胞蛋白质平衡作用的当前证据，即在慢性免疫抑制条件下发生的肿瘤发生中，真核细胞中蛋白质的产生，成熟和更新的调节。我们介绍了最近的研究，表明CsA在正常和转化的肾细胞中诱导未折叠蛋白反应 (UPR)。我们研究了UPR可能是如何重要的，特别是考虑到基因组分析，这些分析显示UPR参与者的表达水平，内质网 (ER) 的伴侣与肾癌的侵袭性之间存在相关性。UPR可能为基于CsA的免疫抑制方案如何促进肾癌发生提供了可能的解释。我们讨论了这种生物学知识在移植后癌症的筛查，诊断和治疗方面提供的机会，并提出了可能的未来转化研究，以检查肿瘤蛋白质平衡和UPR在这种情况下的作用。