The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide Affects Stress Response and Fate of Lipopolysaccharide-Primed RAW 264.7 Macrophage Cells

The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is commonly used to study free radicals. Due to its free radical trapping properties, DMPO is thought to reduce free radial-mediated oxidative damage and other related cellular responses. The purpose of this study was to assess the effect of DMPO on lipopolysaccharide (LPS)-induced inflammation, endoplasmic reticulum (ER) stress, and apoptosis in RAW 264.7 cells. The results showed that DMPO at 50 mM inhibited inducible nitric oxide synthase expression when added shortly after LPS treatment (≤3 h). Interestingly, DMPO increased anti-inflammatory heme oxygenase-1 (HO-1) expression and reversed LPS-induced decrease in HO-1 expression. LPS could increase cellular ER stress as indicated by C/EBP homologous protein (CHOP) induction; DMPO reduced LPS effect on CHOP expression. Unexpectedly, DMPO had a synergistic effect with LPS on increased caspase-3 activity. Overall, DMPO harbors multiple modulating effects but may induce apoptosis in LPS-stressed cells when given at 50 mM, an effective dose for its anti-inflammatory activity in vitro. Our data provide clues for further understanding of the nitrone spin trap with therapeutic potential.     

Psychological dysregulation during adolescence mediates the association of parent-child attachment in childhood and substance use disorder in adulthood

Objective: This prospective study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10–12) and development of substance use disorder (SUD) in adulthood (age 22). Method: The Youth Attachment to Parents Scale (YAPS) was developed in 10–12-year-old boys and girls (N?=?694) at baseline residing in western Pennsylvania. Psychological dysregulation was measured by the neurobehavior disinhibition trait. Substance use was assessed at ages 10–12, 12–14, 16 and 19. SUD was diagnosed at age 22 using the Structured Clinical Interview for DSM Disorders. The mediation of parent-child attachment and SUD by neurobehavior disinhibition was tested separately for mothers and fathers while controlling for baseline substance use. Results: Psychological dysregulation mediates the association between attachment to mothers and SUD, and partially mediates the association between attachment to fathers and SUD. Significant mediation effects remains after controlling for baseline substance use. Conclusion: Optimal prevention of SUD should include ameliorating both psychological dysregulation predisposing to SUD and quality of the parent-child relationship.     

心血管内科医护人员焦虑状况调查分析

目的探讨心血管内科医护人员的焦虑状况。方法采用焦虑自评量表(self-rating anxiety scale,SAS)对98名心血管内科医护人员进行问卷调查,并与国内常模比较。了解心血管内科医护人员焦虑状况。结果非焦虑者35名,占35.7%,焦虑者63名,占64.3%;心血管内科医护人员焦虑水平明显高于国内常模(P<0.05);心血管内科护士焦虑水平明显高于医生(P<0.05)。结论心血管医务人员心理健康状况与医疗职业特点密切相关,医护人员焦虑水平明显高于国内常模,护士焦虑水平明显高于医生,应切实提高其心理应对能力。     

Melatonin receptor‐mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1

Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 signaling. This study investigated the protective effect of melatonin treatment on MI/R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT1, Bcl‐2 expression and downregulating Bax, caspase‐3 and cleaved caspase‐3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91^phox expression, malondialdehyde level, and increased myocardium superoxide dismutase (SOD) level, which indicate that the MI/R‐induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX527 or luzindole, indicating that SIRT1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI/R injury by reducing oxidative stress damage via activation of SIRT1 signaling in a receptor‐dependent manner.     

A simulator for percutaneous hepatic microwave thermal ablation under ultrasound guidance

The purpose of this study was to provide a simulation therapy environment for microwave thermal ablation (MWA) under the guidance of ultrasound, and to present an inexpensive and portable simulator built on real patient-based pre-operative computed tomography (CT) data. We established an experimental simulation system for teaching MWA and present the results of a preliminary evaluation of the simulator’s realism and utility for training. The system comprises physical elements of an electromagnetic tracking device and an abdominal phantom, and software elements providing three-dimensional (3D) image processing tools, real-time navigation functions and objective evaluation function module. Details of the novel aspects of this system are presented, including a portable electromagnetic tracking device, adoption of real patient-based pre-operative CT data of liver, operation simulation of MWA, and recording and playback of the operation simulation. Patients with liver cancer were selected for evaluation of the clinical application value of the experimental simulation system. A total of 50 consultant interventional radiologists and 20 specialist registrars in radiology rated the simulator’s hardware reality and overall ergonomics. Results show that the simulator system we describe can be used as a training tool for MWA. It enables training with real patient cases prior to surgery, and it can provide a realistic simulation of the actual procedure.     

HIV-1-specific cytotoxic T lymphocyte (CTL) responses against immunodominant optimal epitopes slow the progression of AIDS in China

To assess the immunodominance patterns of HIV-1-specific cytotoxic T lymphocyte (CTL) responses and the contribution of these responses against the peptides scanning optimal epitopes in chronic infection, we test the HIV-1-specific CTL responses against a panel of 413 overlapping peptides spanning HIV-1 Asian B sequence, including 147 peptides corresponding to optimal clade B epitopes in 49 chronically HIV-1 infected individuals by interferon-gamma Elispot assay. A large variation in the recognition of peptides restricted by the same HLA class I allele is presented. Some epitopes are targeted frequently by individuals while other epitopes restricted by the same allele are rarely recognized in our research. HLA-B35 and HLA-A03 rather than other HLA alleles contribute greatly to total virus-specific CTL responses. Furthermore, there is a significant inverse correlation between the total contribution of HIV-1-specific CTL responses restricted by different HLA alleles to virus-specific immune responses and viral load in the individuals during advanced infection (P=0.002, r=-0.549). The peptides targeted by individuals have significantly lower entropy compared with those not targeted but restricted by the same HLA class I alleles (P<0.05) in 49 individuals infected by HIV-1, especially the advanced infection subgroup (P=0.044). These data demonstrate that the consistent immunodominance patterns of HIV-1-specific CTL responses of Chinese HIV-1 infected individuals and an inverse correlation between the relative contribution of responses restricted by HLA alleles and viral load, which indicates the important protective effect of optimal epitopes against slow disease progression even in advanced infection.     

万古霉素首剂给予负荷剂量对临床结局影响的系统评价

摘 要 目的:系统评价万古霉素首剂给予负荷剂量对患者临床结局的影响。方法：系统检索英文数据库PubMed,Embase,Cochrane Library,中文数据库CNKI,WanFang,CBM,纳入所有关于万古霉素首剂给予负荷剂量的研究。结局指标为感染治疗的有效率、目标浓度的达标率和肾毒性的发生率。结果：纳入1篇随机对照试验,2篇队列研究,共199名患者,其中1篇研究报道负荷剂量可以提高感染治疗的有效率[RR=1.27,95%CI(0.97,1.67),P＞0.05],2篇研究报道负荷剂量可以提高目标浓度的达标率[RR=1.54,95%CI (0.72,3.30),P＞0.05],1篇研究报道负荷剂量组与对照组的肾毒性发生率[RR=3.87,95%CI(0.46,32.57),P＞0.05]。结论：万古霉素首剂给予负荷剂量可以提高感染治疗的有效率和目标浓度的达标率,但未显示出临床优势。     

基孔肯雅热临床特点及治疗与预后

目的 探讨基孔肯雅热临床特点及治疗与转归.方法 选取2010年9月至2010年11月东莞市诊治的133例基孔肯雅热患者为研究对象,所有患者行3年随访,分析其临床特征及治疗与预后.结果 基孔肯雅热病常见临床症状为发热、皮疹及关节疼痛,发生率分别为100.00％、91.72％和90.98％;关节疼痛中膝关节、脚踝及肘部关节受累较多,发生率分别为69.92％、64.66％和48.87％;关节疼痛女性明显多于男性,15岁以上患者易发生关节疼痛;关节疼痛症状在1年内基本消失,部分患者在2年甚至3年内消失,个别患者在3年后仍未消失.结论 基孔肯雅热病主要以发热、皮疹及关节痛为主要临床表现,关节疼痛受年龄等因素影响,治疗后1年患者内关节疼痛基本可消失,对症、支持治疗对基孔肯雅热有显著治疗效果.