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.     

醒脑液对PAP双转基因痴呆小鼠行为学及胆碱能系统的早期干预作用说

目的:观察醒脑液早期干预对阿尔茨海默病模型APPswe/PS△E9双转基因小鼠行为学及脑中胆碱能系统相关酶的影响。方法:将75只PAP双转基因小鼠随机随机分为空白对照组(模型组)、阳性对照组、用药高剂量组、用药中剂量组和用药低剂量组,每组各15只。15只遗传背景相同的转基因阴性的小鼠作为正常动物组。所试药物稀释至相同体积灌胃给药,正常动物组及空白对照组给以等体积蒸馏水灌胃,连续灌胃4个月。采用Morris水迷宫测定小鼠空间学习记忆能力,避暗箱测定其条件学习记忆能力。使用比色法检测小鼠脑中乙酰胆碱(Ach)、乙酰胆碱转移酶(ChAT)及乙酰胆碱酯酶(AchE)的活性。结果:与正常组比较,模型组小鼠的学习记忆能力均有所下降,脑组织中Ach、ChAT、AchE的含量均下降。与模型组比较,阳性对照组、用药高剂量组及用药中剂量组小鼠血浆中Ach含量均有所提高,而AchE含量则出现下降。结论:醒脑液能改善阿尔茨海默病模型小鼠的学习记忆能力,其作用机制可能与调控胆碱能系统有关。     

Primary Hospital Infection Monitoring Analysis of ICU Targeted

目的 了解重症监护病房患者医院感染发生率、危险因素.探讨有效预防与控制感染的方法.方法 对264例入住ICU患者进行医院感染目标性监测.结果 264例患者中,发生医院感染64例,医院感染发生率为38.64％,患者日感染率为43.20‰,根据病情的平均严重程度经ASA法调整后的医院感染发生率为8.00％.检出病原菌82株,主要为革兰阴性杆菌,其次为革兰阳性球菌及真菌.结论 ICU患者多为危重病例,医院感染发病率高,与使用呼吸机、留置导尿管等有关,留置时间越长越易引起感染,在进行各项操作时应严格执行无菌操作技术,加强手卫生规范,减少侵入性操作时间,合理使用抗菌药物,减少医院感染的发生.     

MRI contrast agents: Basic chemistry and safety

Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals used widely in MRI examinations. Gadolinium‐based MRI contrast agents (GBCAs) are by far the most commonly used. To date, nine GBCAs have been commercialized for clinical use, primarily indicated in the central nervous system, vasculature, and whole body. GBCAs primarily lower the T₁ in vivo to create higher signal in T₁‐weighted MRI scans where GBCAs are concentrated. GBCAs are unique among pharmaceuticals, being water proton relaxation catalysts whose effectiveness is characterized by a rate constant known as relaxivity. The relaxivity of each GBCAs depends on a variety of factors that are discussed in terms of both the existing agents and future molecular imaging agents under study by current researchers. Current GBCAs can be divided into four different structural types (macrocyclic, linear, ionic, and nonionic) based on the chemistry of the chelating ligands whose primary purpose is to protect the body from dissociation of the relatively toxic Gd³⁺ ion from the ligand. This article discusses how the chemical structure influences inherent and in vivo stability toward dissociation, and how it affects important formulation properties. Although GBCAs have a lower rate of serious adverse events than iodinated contrast agents, they still present some risk. J. Magn. Reson. Imaging 2012;36:1060–1071. © 2012 Wiley Periodicals, Inc.     

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.     

Associations between physical activity and sedentary time on components of metabolic syndrome among adults with HIV

Recent data show that people living with HIV/AIDS (PLWHA) are at a greater risk of cardiovascular disease (CVD), which could possibly be explained by an increased prevalence of metabolic syndrome (MetSyn) due to the known toxicities associated with antiretroviral therapy (ART). The purpose of this study is to examine the relationships between physical activity (PA) and components of MetSyn in a sample of PLWHA taking ART. A total of 31 males and 32 females living with HIV and currently taking ART were enrolled in a home-based PA intervention aimed to reduce risk factors for CVD. Clinical assessments included measures of resting blood pressure (BP), waist circumference, height, weight, PA levels via accelerometer, and a fasted blood draw. Components of MetSyn were divided into three clusters (1 = 0–1; 2 = 2; 3 = 3 or more). A one-way analysis of variance was used to determine differences between clusters. Multiple linear regressions were used to identify significant associations between moderate intensity PA (MPA) and sedentary time among components of MetSyn. MPA was significantly lower across MetSyn clusters (p < 0.001), whereas sedentary time was significantly higher (p = 0.01). A multiple linear regression showed MPA to be a significant predictor of waist circumference after controlling for age, race, gender, and sedentary time. Routine PA can be beneficial in helping PLWHA reduce waist circumference ultimately leading to metabolic improvements. This in turn would help PLWHA self-manage known components of MetSyn, thus reducing their risk of CVD and mortality.     

Acquisition of anal human papillomavirus (HPV) infection in women: the Hawaii HPV Cohort study

BACKGROUND: The majority of anal cancer is associated with human papillomavirus (HPV) infection, yet little is known about women's risk of acquisition of anal HPV infection. METHODS: Risk factors for the acquisition of anal HPV infection were examined in a longitudinal cohort study of 431 women, via repeated measurement of HPV DNA. RESULTS: Seventy percent of women were positive for anal HPV infection at one or more clinic visits from baseline through a follow-up period that averaged 1.3 years. The incidence of a high-risk (HR) infection was 19.5 (95% confidence interval [CI], 16.0-23.6) per 1000 woman-months. The most common incident HR HPV types were HPV-53, -52 and -16. The presence of an HR anal HPV infection at baseline increased the risk of an incident anal infection by 65%. Baseline HR cervical HPV infection also predicted the acquisition of an HR anal HPV infection (odds ratio, 1.81 [95% CI, 1.09-3.02]). Nonviral risk factors for acquisition of HR HPV infection included younger age, lower socioeconomic status, greater lifetime number of sexual partners, past use of hormones, and condom use. CONCLUSIONS: The results of this study suggest that women's risk of anal HPV infection is as common as their risk of cervical HPV infection.     

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.     

FGF19与多囊卵巢综合征相关性研究

多囊卵巢综合征(PCOS)是一种在育龄期妇女中比较常见的内分泌紊乱性疾病。PCOS与生殖系统及代谢紊乱有关,具有肥胖、血脂异常、胰岛素抵抗等心血管疾病( CVD)的高危因素,其远期CVD风险增高。成纤维细胞生长因子19(FGF19)是新近发现的能够调节糖脂代谢、胆汁酸代谢,提高能量代谢,调节胆囊充盈等的内分泌激素。FGF19可能通过调节糖脂代谢逆转高脂肪饮食(HFD)引起的体重增加、肝脏脂肪堆积、胰岛素抵抗和血脂水平的增加等。推测FGF19可通过调节糖脂代谢降低体重、血脂水平及改善葡萄糖利用、胰岛素敏感性等在PCOS发生发展中起着一定的作用,为PCOS提供一种新的治疗靶点,本文就此做一综述。     

PTEN，p53 和 EGFR 在乳腺癌不同分子亚型中的表达及其相关性

目的：研究PTEN,p53,表皮生长因子受体(epidermal growth factor receptor,EGFR)在乳腺癌分子亚型中 的表达情况,并分析在三阴性乳腺癌中的相关性。方法：免疫组织化学MaxVisionTM法检测291例乳腺浸润性导管癌中 PTEN,p53,EGFR,雌激素受体(estrogen receptor,ER),孕激素受体(progesterone receptor,PR),人类表皮生长因子 受体2(human epidermal growth factor receptor 2,HER2)蛋白的表达水平。结果：PTEN,p53和EGFR在乳腺癌中的表达 率为57.0%,57.0%及38.5%,与良性乳腺病差异有统计学意义(P<0.05)。PTEN及EGFR表达与肿瘤大小、组织学分级、 淋巴结转移、TNM分期、ER和HER2状态有关(均P<0.05);P53表达与肿瘤大小、组织学分级、ER状态有关(P<0.05)。 腺腔A型、腺腔B型(HER2−)、腺腔B型(HER2+)、HER2过表达型及三阴性型中,PTEN,p53和EGFR的阳性表达率差 异均有统计学意义(P<0.05)。PTEN,p53及EGFR的表达在三阴性乳腺癌中具有高相关性。结论：在三阴性乳腺癌中 PTEN低表达,p53及EGFR高表达,三者密切相关,可能在该分子亚型发生中具有协同作用。