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。     

An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

Aim:

SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.

Methods:

Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.

Results:

Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.

Conclusion:

NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.     

Acetone vapour-assisted growth of 2D single-crystalline organic lead halide perovskite microplates and their temperature-enhanced photoluminescence

We adopt an acetone vapour-assisted method to grow high quality single-crystalline microplates of two-dimensional (2D) perovskite, 2-phenylethylammonium lead bromide [(C₆H₅C₂H₄NH₃)₂PbBr₄]. The microplates, converted from the spin-coated films, are well-defined rectangles. Temperature dependent photoluminescence (PL) spectroscopy shows that the band gap PL is enhanced markedly with increasing temperature up to 218 K, accompanied by the quenching of the PL related to the trap states, which perhaps results from the exciton–phonon couplings. The optical phonon energy around 50 meV and the exciton binding energy around 120 meV are derived by fitting the band gap PL linewidths and intensities at different temperatures, respectively.

We report an acetone vapour-assisted method to grow single-crystalline 2D perovskite microplates and find their temperature-enhanced photoluminescence.