Synergistic interaction of β-galactosyl-pyrrolidinyl diazeniumdiolate with cisplatin against three tumor cells

Cisplatin is a platinum-based compound that is largely employed as an effective antitumor drug against a wide spectrum of solid neoplasms for many years. Despite of its initial therapeutic success, cisplatin often results in high incidence of chemoresistance and high-dose cytotoxicity. Consequently, considerable efforts in hopes of reducing the dose-dependent side effects of cisplatin while retaining, or even enhancing, its antitumor properties have been undertaken throughout the past three decades. Nitric oxide (NO) is a small lipophilic free radical gas possessing versatile biological functions, including antitumor activities. However, NO, of itself, is difficult to be used, because of its extreme instability and short half-life. Previously, we have reported a stable NO donor, β-galactosyl-pyrrolidinyl diazeniumdiolate (β-Gal-NONOate), which exerts tumor killing effects through site-specific intracellular release of exogenous NO. In this study, we further investigated the combined inhibitory effect of β-Gal-NONOate and cisplatin against C6/LacZ, 9L/LacZ, and HeLa/LacZ tumor cells. It was shown that, in combination with β-Gal-NONOate, the antitumor effects of cisplatin against these common tumor cell lines were increased in a dose-dependent manner. Furthermore, the combination of these chemicals resulted in a synergistic suppression on tumor growth, which was achieved under a much lower cisplatin dosage. Collectively, our findings indicate that β-Gal-NONOate can synergistically improve the antitumor effect of cisplatin, and may therefore reduce its side effects caused by high dose cisplatin monochemotherapies. Accordingly, β-Gal-NONOate is an important therapeutic assistant reagent with great potential of clinical applicability, and thus worth of continuous research in the coming future.     

Silica-coated graphene compared to Si-CdSe/ZnS quantum dots: Toxicity,emission stability,and role of silica in the uptake process for imaging purposes

Quantum dots (QDs) present a special type of nanocrystals (NCs) due to their unique optical and chemical properties. While cadmium-based QDs (Cd-QDs) have the most favorable physicochemical properties, their toxicity, instability in the aqueous phase, and loss of brightness at high temperature are some of the obstacles that prevent the wide use of Cd-QDs. Carbon-based QDs as graphene quantum dots (GQDs) represent a very promising biocompatible replacement. In the present work, we mainly focus on comparing the efficiency and uptake of GQDs and Cd-QDs for fluorescent imaging purposes and studying the effect of growing silica shell on the emission and the uptake of QDs inside living human and bacterial cells. Graphene and CdSe/ZnS QDs were prepared and encapsulated in silica to increase their emission and uptake by living cells. Moreover, we studied their photostability and cytotoxicity. The Prepared G-Si QDs showed good emission inside the cytoplasmic portion of the liver hepatocellular carcinoma cell line (HepG2) and Bacillus subtilis (B. subtilis), but they revealed lower photoluminescence (PL) intensity compared to Si-CdSe/ZnS NCs although G-Si QDs are advantageous in other aspects, i.e. possess lower toxicity and higher stability with temperature variations.     

Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography

BackgroundInflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.MethodsCORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.ResultsThirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55–68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were ?74.9, ?74.2, and ?71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75–1.22, p ?= ?0.71), 1.31 (95% CI: 0.96–1.78, p ?= ?0.09), and 0.98 (95% CI: 0.78–1.22, p ?= ?0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44–1.07), 0.85 (0.56–1.29), and 0.57 (0.41–0.80), respectively.ConclusionsIn patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.     

“一站式”腔内治疗冠心病合并主动脉粥样硬化性疾病的探讨

目的:探讨冠状动脉介入治疗(PCI)联合主动脉腔内修复术(EVAR)"一站式"治疗冠心病和主动脉粥样硬化性疾病的临床策略及其安全性。方法:回顾性分析2016年1月—2016年6月中国医学科学院阜外医院行腔内治疗的7例合并冠心病的主动脉粥样硬化性疾病患者资料,其中男6例,女1例,平均年龄76.2(64~86)岁,术前主动脉CT和冠脉CT确诊主动脉病变和冠脉病变并存,术中造影确认主动脉和冠脉病变均符合介入治疗指征后,实施"一站式"手术治疗。结果:手术成功率100%,无围术期死亡。术后并发症包括切口附近皮下瘀斑2例,其中合并血肿1例,后者因血色素下降予以输注浓缩红细胞2 U治疗。1例主动脉弓降部溃疡患者以烟囱技术重建左锁骨下动脉,其左侧肱动脉穿刺点出现假性动脉瘤,予以外科修复。所有患者均获得门诊或电话随访,随访时间7(6~10)个月,所有患者临床症状消失或明显减轻,生活质量改善,无再次手术或死亡。结论:PCI联合EVAR"一站式"治疗冠心病和主动脉粥样硬化性疾病早中期疗效满意,切口或穿刺部位出血性并发症应予警惕。术后药物治疗方案严格按照冠心病的治疗原则进行。     

Detection of coronary artery stenosis with sub-milliSievert radiation dose by prospectively ECG-triggered high-pitch spiral CT angiography and iterative reconstruction

Objectives

To evaluate the diagnostic accuracy of sub-milliSievert (mSv) coronary CT angiography (cCTA) using prospectively ECG-triggered high-pitch spiral CT acquisition combined with iterative image reconstruction.

Methods

Forty consecutive patients (52.9?±?8.7 years; 30 men) underwent dual-source cCTA using prospectively ECG-triggered high-pitch spiral acquisition. The tube current-time product was set to 50 % of standard-of-care CT examinations. Images were reconstructed with sinogram-affirmed iterative reconstruction. Image quality was scored and diagnostic performance for detection of ≥50 % stenosis was determined with catheter coronary angiography (CCA) as the reference standard.

Results

CT was successfully performed in all 40 patients. Of the 601 assessable coronary segments, 543 (90.3 %) had diagnostic image quality. Per-patient sensitivity for detection of ≥50 % stenosis was 95.7 % [95 % confidence interval (CI), 76.0-99.8 %] and specificity was 94.1 % (95 % CI, 69.2-99.7 %). Per-vessel sensitivity was 89.5 % (95 % CI, 77.8-95.6 %) with 93.2 % specificity (95 % CI, 86.0-97.0 %). The area under the receiver-operating characteristic curve on per-patient and per-vessel levels was 0.949 and 0.913. Mean effective dose was 0.58?±?0.17 mSv. Mean size-specific dose estimate was 3.14?±?1.15 mGy.

Conclusions

High-pitch prospectively ECG-triggered cCTA combined with iterative image reconstruction provides high diagnostic accuracy with a radiation dose below 1 mSv for detection of coronary artery stenosis.

Key Points

? Cardiac CT with sub-milliSievert radiation dose is feasible in many patients ? High-pitch spiral CT acquisition with iterative reconstruction detects coronary stenosis accurately. ? Iterative reconstruction increases who can benefit from low-radiation cardiac CT.     

The effect of immunosuppressive regimens on the recurrence of primary biliary cirrhosis after liver transplantation

Recurrence of primary biliary cirrhosis (PBC) has been described in liver transplant recipients. Type of immunosuppression has been reported to influence the frequency of recurrence. The aim of this study is to evaluate the occurrence and pattern of recurrent PBC in our liver transplant recipients and determine any association of immunosuppressive agents with its recurrence. Patients who underwent orthotopic liver transplantation (OLT) for PBC were identified from the University of Chicago Liver Transplant Database. Recurrent PBC was diagnosed based on specific pathological criteria. Of 46 patients who underwent OLT for PBC between 1984 and 2000, a total of 7 patients (15%) were diagnosed with recurrent PBC at a median of 78 months (range, 27 to 120 months) after OLT. Forty-three percent of patients were administered cyclosporine, whereas 57% were administered tacrolimus before disease recurrence. Rates of recurrence were not different between patients maintained on cyclosporine therapy (16%) compared with those maintained on tacrolimus therapy (18%; P = 1.0). There also was no difference in frequency of rejection episodes or duration of corticosteroid therapy between those who did and did not have recurrent PBC. In conclusion, recurrent PBC developed in a small number of patients 2 years or longer after OLT. In our population, there was no difference in recurrence rates between those administered cyclosporine or tacrolimus for immunosuppression. (Liver Transpl 2003;9:733-736.)     

Anaesthesia for abdominal vascular surgery

Abdominal vascular surgery is required for aneurysmal and symptomatic occlusive disease of the aorta. Abdominal aortic aneurysms account for more than 8,500 deaths per year in England and Wales. Most deaths occur as a result of rupture of the abdominal aortic aneurysm, which has an overall mortality of 80%. These deaths are potentially preventable because elective repair of the abdominal aorta can be performed with an operative mortality of less than 7%. This article reviews the current indications and anaesthetic practices for open and endovascular abdominal aortic aneurysm repair.     

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created using covered stents of different diameters: A systematic review and meta-analysis

PurposeThe purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8 mm vs. 10 mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsFour databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8 mm covered stents and those with 10 mm covered stents.ResultsFive eligible studies were selected, which included 489 patients (316 men, 173 women). The 8 mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P = 0.003) and (OR, 1.81; P = 0.04) and lower hepatic encephalopathy (OR, 0.69; P = 0.04) compared with 10 mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P = 0.67). However, shunt dysfunction was lower in 10 mm covered stent group (OR, 2.26; P = 0.003).ConclusionsOur results suggest that the use of 8 mm covered stents should be preferred to that of 10 mm covered stents for TIPS placement when portal pressure is frequently monitored.