Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction

OBJECTIVES

We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.

BACKGROUND

The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.

METHODS

Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.

RESULTS

This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).

CONCLUSIONS

Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.     

Operando unraveling photothermal-promoted dynamic active-sites generation in NiFe2O4 for markedly enhanced oxygen evolution

The ability to develop highly active and low-cost electrocatalysts represents an important endeavor toward accelerating sluggish water-oxidation kinetics. Herein, we report the implementation and unraveling of the photothermal effect of spinel nanoparticles (NPs) on promoting dynamic active-sites generation to markedly enhance their oxygen evolution reaction (OER) activity via an integrated operando Raman and density functional theory (DFT) study. Specifically, NiFe₂O₄ (NFO) NPs are first synthesized by capitalizing on amphiphilic star-like diblock copolymers as nanoreactors. Upon the near-infrared light irradiation, the photothermal heating of the NFO-based electrode progressively raises the temperature, accompanied by a marked decrease of overpotential. Accordingly, only an overpotential of 309 mV is required to yield a high current density of 100 mA cm⁻², greatly lower than recently reported earth-abundant electrocatalysts. More importantly, the photothermal effect of NFO NPs facilitates surface reconstruction into high-active oxyhydroxides at lower potential (1.36 V) under OER conditions, as revealed by operando Raman spectroelectrochemistry. The DFT calculation corroborates that these reconstructed (Ni,Fe)oxyhydroxides are electrocatalytically active sites as the kinetics barrier is largely reduced over pure NFO without surface reconstruction. Given the diversity of materials (metal oxides, sulfides, phosphides, etc.) possessing the photo-to-thermal conversion, this effect may thus provide a unique and robust platform to boost highly active surface species in nanomaterials for a fundamental understanding of enhanced performance that may underpin future advances in electrocatalysis, photocatalysis, solar-energy conversion, and renewable-energy production.

Motivated by the need for accelerating sluggish reaction kinetics at the anode (1, 2), the focus of water electrolysis has been centered heavily on oxygen evolution reaction (OER) toward sustainable hydrogen fuel production. To date, there has been much effort in developing low-cost yet high-performance earth-abundant transition-metal alternatives to commonly used noble metals for OER. Intriguingly, many Ni-, Co-, Fe-, and Mn-based oxides experience a dynamic surface-reconstruction process to form more active oxyhydroxides, which are recognized as true catalytically active species for OER in alkaline media (3, 4). Among various transition metal-based OER catalysts, bimetal spinel-structured oxides in the form of AB₂O₄ (A and B are different metal ions) have garnered much attention due to their rich compositions, electron configurations, and valence states (5). Interestingly, inverse spinel NiFe₂O₄ (NFO), in principle, exhibits enhanced catalytic activity toward OER because of the presence of multivalent elements (i.e., Ni³⁺/Ni²⁺ and Fe³⁺/Fe²⁺) (6). It is important to note that studies on facilitating the surface reconstruction of NFO to achieve high-performance OER are relatively few, and a fundamental understanding as to what makes the derived OER catalysts perform well remains elusive.Recently, introducing thermal energy to promote electrocatalytic conversion has attracted significant interest (7–10). The thermal energy could accelerate the motion of reactant molecules, promote their effective collisions during the reaction, and thus make it easier to overcome the activation barrier (11, 12). Moreover, the use of thermal energy could also promote the surface reconstruction of catalysts into highly active species and accelerate the electrocatalytic kinetics, thereby leading to improved efficiency (13). Electrocatalysts with photothermal effect (referred to as photothermal electrocatalysts) enable in situ heating due to photo-to-thermal conversion under illumination with visible or near-infrared (NIR) light, thereby dispensing with the need for extra devices required to provide thermal energy. More importantly, in sharp contrast to common approaches where the entire solution is heated (14), the photothermal effect is localized on electrocatalysts themselves (15), thus effectively enabling heat modulation to a defined region (i.e., the working electrode). Despite recent impressive advances in transition metal oxides (e.g., Fe₃O₄ and Co₃O₄) as photothermal agents for cancer therapy (15), their implementations for photothermal-assisted OER, in particular spinel oxides, are comparatively few and limited in scope. Moreover, it has been reported that Ni- and Co-based OER catalysts are prone to surface reconstruction into highly active oxyhydroxides (16, 17). Surprisingly, the photothermal effect on promoting surface reconstruction in spinel oxide catalysts has yet to be explored.Herein, we report an integrated operando Raman and density functional theory (DFT) plus Hubbard U (DFT + U) study to exercise and unveil the photo-to-thermal conversion of inverse spinel oxide nanoparticles (NPs) in promoting the generation of dynamic active sites via surface reconstruction into oxyhydroxides and thus greatly enhancing their OER activity. First, a series of amphiphilic star-like poly(acrylic acid)-block-poly(styrene-co-acrylonitrile) (denoted PAA-b-PSAN) diblock copolymers with a well-defined molecular weight (MW) and low polydispersity index (PDI) are exploited as nanoreactors to synthesize a set of PSAN-ligated NFO NPs with different sizes and PSAN chain lengths. The effects of the NFO NP sizes and the outer PSAN chain lengths on catalytic activity of NFO NPs are then scrutinized. Interestingly, NFO NPs of the largest size (∼12 nm) ligated with the shortest PSAN chains (M_n = 7K) display the best OER reactivity on a glassy carbon (GC) electrode in alkaline media as a result of the high fraction of the exposed electrochemically active surface area and the fastest electrocatalytic kinetics. Subsequently, the photothermal effect of PSAN-ligated NFO NPs is exploited to promote their surface reconstruction and thus boost OER. More importantly, an operando Raman spectroelectrochemistry study is performed to unveil the mechanism of photothermal-assisted enhancement in OER reaction, revealing the emergence of electrocatalytically active γ-NiOOH at a lower potential (1.36 V) during the surface-reconstruction process with a photothermal effect. Finally, the first-principle calculations substantiate that the reconstructed surface, i.e., (Ni,Fe)oxyhydroxides, plays a pivotal role as the active site for electrocatalytic reaction. As such, photothermal electrocatalysts (e.g., metal oxides, sulfides, phosphides, etc.) may render significantly low overpotential and fast OER kinetics, representing an array of important materials that couple the localized heating with electrochemistry for effective renewable-energy production.     

Fully automated diagnostic system with artificial intelligence using endocytoscopy to identify the presence of histologic inflammation associated with ulcerative colitis (with video)

1. Download high-res image (358KB)
2. Download full-size image

     

糖尿病患者血清糖化低密度脂蛋白水平研究

目的研究糖尿病患者血清糖化低密度脂蛋白水平,为糖尿病并发冠心病的预防提供理论依据。方法选取我院收治的110例糖尿病患者作为观察组,选取同时期进行健康体检的健康者110例作为对照组,检测两组患者血清中的血糖、三酰甘油、载脂蛋白、胆固醇、糖化低密度脂蛋白、糖化血红蛋白等。结果观察组患者的GLDL水平明显高于对照组(P<0.05);但两组apo B100、LDL-C水平对比无统计学差异(P>0.05);apo A-Ⅰ与HDL-C的水平明显低于对照组(P<0.05);Clu、TG以及Chol水平明显高于对照组(P<0.05)。观察组的G-LDL水平与Glu呈正相关(r=0.631,P<0.05),与LDL-C、Hb A1c水平无相关关系(r=0.328、0.329,P>0.05)。结论糖尿病患者的血清糖化低密度脂蛋白水平显著提升,且与血糖值呈正相关关系。对评估糖尿病的治疗疗效有重要的临床价值。     

MRI平扫及MRCP显示十二指肠乳头腺癌合并胆道梗阻的研究

目的：分析与探讨MRI平扫及MRCP显示十二指肠乳头腺癌合并胆道梗阻的应用价值。方法选取100例2013年2月—2014年8月在该院接受诊断的十二指肠乳头腺癌合并胆道梗阻患者,以随机方式将其平均分为两组,即：对照组与观察组,对对照组患者实施常规诊断,对观察组患者实施MRI平扫及MRCP检查。两组患者诊断结果和病例相对照。结果对照患者病例,观察组患者病变诊断准确率为90.0%,对照组患者病变诊断准确率为50.0%,观察组明显优于对照组,差异有统计学意义(P<0.05)。结论研究表明,MRI平扫及MRCP能够有效显示十二指肠乳头腺癌合并胆道梗阻,该诊断方式对选择临床治疗方式具有重要价值,值得临床应用与推广。     

研究探讨心血管超声诊断在肺动脉栓塞诊断中的临床应用

目的：探讨研究心血管超声诊断在肺动脉栓塞诊断中的应用价值,为肺动脉栓塞的临床诊断提供切实依据。方法随机选取2009年6月-2014年12月来该院经CT、心电图、肺灌注扫描及通气显影等方法确诊的肺动脉栓塞的患者60例,同时对其行无创心血管超声检查,并对所做超声检查的结果进行分析。结果有3例患者检测到肺动脉栓塞的直接征象,其中有2例左肺动脉栓塞的患者,表现为部分阻塞,另有1例在患者为右心房栓塞,栓子在右心房侧壁上附着;有45例患者存在肺栓塞的间接征象,具有室间隔向左侧移位、右心房及右心室出现扩大、右室/左室的比值增大等表现;另外有36例患者存在三尖瓣返流的情况。通过心血管超声检查诊断为肺动脉栓塞的患者共48例,对肺栓塞的诊断率为80.0%,另外12例患者未能通过心血管超声检查及时作出肺栓塞的诊断,其漏诊率为20.0%。结论对患者行心血管超声检查,能够对肺动脉栓塞的患者或疑似患者的诊断提供一定的依据,并且具有无创、方便、快捷及成本低等优点,值得在临床上推广应用。     

老年2型糖尿病血尿酸水平与骨密度的相关性研究

目的:探讨老年2型糖尿病患者(T2DM)血尿酸水平(SUA)与骨密度值(BMD)的关系.方法:测定200例(男性110例,女性90例)老年2型糖尿病患者SUA及相关临床资料,应用双能X线测定BMD,根据性别分为男性组及女性组,根据SUA水平分为高尿酸血症组及正常血尿酸组,分析各组BMD差异及SUA与BMD的相关性.结果:老年2型糖尿病患者中,男性各部位BMD均高于女性.SUA与腰椎BMD存在正相关关系(r =0.236,P＜0.05),SUA是影响腰椎BMD的独立危险因素(标准偏回归系数β'=0.294,P＜0.01),而体重指数和血脂水平主要影响股骨的BMD.结论:在老年T2DM患者中,维持一定的SUA水平有利于预防骨量丢失.     

Breast density in dedicated breast computed tomography: Proposal of a classification system and interreader reliability

The aim of this study was to develop a new breast density classification system for dedicated breast computed tomography (BCT) based on lesion detectability analogous to the ACR BI-RADS breast density scale for mammography, and to evaluate its interrater reliability.In this retrospective study, 1454 BCT examinations without contrast media were screened for suitability. Excluding datasets without additional ultrasound and exams without any detected lesions resulted in 114 BCT examinations. Based on lesion detectability, an atlas-based BCT density (BCTD) classification system of breast parenchyma was defined using 4 categories. Interrater reliability was examined in 40 BCT datasets between 3 experienced radiologists.Among the included lesions were 63 cysts (55%), 18 fibroadenomas (16%), 7 lesions of fatty necrosis (6%), and 6 breast cancers (5%) with a median diameter of 11 mm. X-ray absorption was identical between lesions and breast tissue; therefore, the lack of fatty septae was identified as the most important criteria for the presence of lesions in glandular tissue. Applying a lesion diameter of 10 mm as desired cut-off for the recommendation of an additional ultrasound, an atlas of 4 BCTD categories was defined resulting in a distribution of 17.5% for density A, 39.5% (B), 31.6% (C), and 11.4% (D) with an intraclass correlation coefficient (ICC) among 3 readers of 0.85 to 0.87.We propose a dedicated atlas-based BCTD classification system, which is calibrated to lesion detectability. The new classification system exhibits a high interrater reliability and may be used for the decision whether additional ultrasound is recommended.