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.     

Peripheral blood CD45RO+T cells is a predictor of the effectiveness of neoadjuvant chemoradiotherapy in locally advanced rectal cancer

To investigate the relationship between the changes in circulating CD45RO⁺T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO⁺T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO⁺ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO⁺ratio.Circulating CD45RO⁺ratio of 1.07 was determined as the optimal cut-off point and CD45RO⁺ratio-high was associated with lower tumor regression grade grading (P = .031), T stage (P = .001), and tumor node metastasis (TNM) stage (P = .012). The 3-year DFS and OS rate in the CD45RO⁺ratio-high group was significantly higher than that in the CD45RO⁺ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO⁺ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153–0.752; P = .008) and OS (OR, 0.244; 95% CI,0.082–0.726; P = .011).Circulating CD45RO⁺ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.     

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.     

The value of speckle-tracking echocardiography in identifying right heart dysfunction in patients with chronic thromboembolic pulmonary hypertension

Right ventricular (RV) function is a significantly important factor in the determination of the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH) patients. Speckle-tracking echocardiography (STE) is an angle-independent new technique for quantifying myocardial deformation that is capable of providing data on multiple parameters including longitudinal and transverse information of the myocardium. In the present study, we aimed to study the advantages of STE-derived parameters in identifying RV dysfunction in CTEPH patients. Sixty CTEPH patients (mean age: 55 years?±?13 years; 25 males) and 30 normal controls (mean age: 54 years?±?14 years; 14 males) were enrolled in this study. RV free wall (RVFW) systolic peak longitudinal strain (LS) including the basal, mid-, and apical-segments and the basal longitudinal and transverse displacement (basal-DL and basal-DT) were measured by STE. Global LS (GLS) of the RV was calculated by averaging the LS value of the 3 segments of RVFW. Clinical data of CTEPH patients were collected. CTEPH patients were divided into 2 subgroups according to the World Health Organization function classification. Clinical right heart failure (RHF) was defined as the presence of symptoms of heart failure and signs of systemic circulation congestion during hospitalization. The apical segment LS of the RVFW was lower than that in the basal and mid-segments in the control group (P?<?0.001), but no significant difference was found among the 3 segments of LS in the CTEPH group (P?=?0.263). When we used the cutoff value recommended by the American Society of Echocardiography guidelines to identify abnormal RV function, 30 CTEPH patients (50%) by tricuspid annular plane systolic excursion (TAPSE), 42 patients (70%) by fractional area change (FAC), 20 patients (33.33%) by RV index of myocardial performance (RVIMP), and 46 patients (77%) patients by GLS were determined to have abnormal RV function, respectively. Among multiple RV function indicators, TAPSE, FAC, GLS, basal-DL, and N-terminal pronatriuretic B-type natriuretic peptide showed significant differences between CTEPH patients with mild (WHO II) and severe symptoms (WHO III/IV) (all P?<?0.001), while RVIMP and basal-DT showed no significant difference (P?=?0.188 and P?=?0.394, respectively). Pearson correlation analysis showed that GLS has no correlation with sPAP as evaluated by echocardiography in CTEPH patients (r = ??0.079, P?=?0.574), and a weak to moderate correlation with RA area (r?=?0.488, P?=?0.000), the RV diameter (r?=?0.429, P?=?0.001), and the RVFW thickness (r?=?0.344, P?=?0.009). On receiver operating characteristic analysis, GLS has the largest area under the curve to identify RHF when the cutoff value was ??13.45%, the sensitivity was 78.2%, and the specificity was 84.6%, separately. Our study demonstrated that the depression of regional LS of RVFW is more pronounced in the basal and middle segments in CTEPH patients. Also, the longitudinal movement is much more important than the transverse movement when evaluating RV systolic function. As compared with conventional parameters, RVFW GLS showed more sensitivity to identify abnormal RV function and had the largest AUC for identifying RHF. Additionally, GLS showed no correlation with sPAP and a weak correlation with right heart morphological parameters in our CTEPH cohort.     

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.