Chronic social stress induces cardiomyocyte contractile dysfunction and intracellular Ca2+ derangement in rats

Chronic psychosocial stress triggers cardiovascular diseases although underlying mechanisms are still elusive. This study examined the effect of social stress on cardiomyocyte contractile function and pathological changes in myocardium using the visible burrow system (VBS) model. Chronic social stress was induced using a mixed-sex VBS housing in adult Sprague-Dawley (SD) rats. Contractile and intracellular Ca(2+) properties were evaluated in isolated cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening/relengthening (± dL/dt), Fura-2 fluorescence intensity, and intracellular Ca(2+) decay. Myocardial histology was evaluated using Masson trichrome staining. Social stress led to depressed PS, ± dL/dt, shortened TPS and prolonged TR(90) compared with the unstressed controls. Baseline and electrically-stimulated rise in Ca(2+) were reduced whereas intracellular Ca(2+) decay was delayed in stressed rats. Histological analyses exhibited overt interstitial fibrosis and cardiomyocyte hypertrophy in stressed rats. The GSH/GSSG ratio (indicative of oxidative stress status) was reduced whereas oxidative protein carbonyl formation was elevated in stressed rats. Western blot analysis showed unchanged expression of superoxide dismutase 1 (SOD1), β(1)-adrenoceptor (β(1)-AR) levels, reduced sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) levels, and elevated phosphorylation of the stress signaling protein kinase JNK but not ERK in myocardium from stressed rats. Short-term in vitro treatment of cardiomyocytes with the stress inducer phenylephrine mimicked cell damage and intracellular Ca(2+) mishandling, the effects of which were mitigated by antioxidant, JNK inhibition, carvedilol and SERCA2a adenovirus. These findings indicate that chronic social stress is detrimental to cardiac structure and function possibly via mechanisms associated with oxidative injury and intracellular Ca(2+) mishandling.     

α,β‐Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress

Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β‐unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca²⁺ properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time‐to‐PS (TPS), time‐to‐90% relengthening (TR₉₀), fura‐2 fluorescence intensity (FFI) and intracellular Ca²⁺ decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca²⁺ properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR₉₀ and intracellular Ca²⁺ decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein‐induced cardiomyocyte contractile and intracellular Ca²⁺ anomalies, as well as apoptosis (as evidenced by Bcl‐2, Bax, FasL, Caspase‐3 and ?8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β‐unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution‐induced heart disease via a TRPV1‐ and oxidative stress‐dependent mechanism. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 638–647, 2015.     

胰腺癌免疫治疗及其最新进展

胰腺癌是一种预后极差的恶性肿瘤,胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)是其中最常见的类型,患者被诊断时多为晚期。晚期患者在所有患者中所占比例可超过80%,这类人群的治疗主要是全身化疗,但化疗效果有限。大多数针对PDAC新疗法的研究与开发则开始关注新辅助治疗以及对各种间质成分的靶向,并且旨在缓解免疫抑制的药物疗法也备受关注,但不管是PD-1/PD-L1抗体还是CTLA-4抗体,抑或是两类药物的联合,在改善胰腺癌患者的生存方面均未能获得显著的成效。由此,我们猜测,通过对其他潜在免疫疗法的探索与研究,或许可以给胰腺癌的治疗带来新的希望。本综述旨在总结胰腺癌免疫治疗及其最新进展,通过对其进一步的理解来认识此疾病带来的治疗难点,从而有望改善其治疗策略。     

Systemic lupus erythematosus patients with high disease activity are associated with accelerated incidence of osteonecrosis: a systematic review and meta-analysis

Osteonecrosis (ON) is one of the serious complications for systemic lupus erythematosus (SLE); we aimed to study the risk relationship between disease activity and incidence of ON in SLE patients. The PubMed, Embase, and Cochrane library databases were searched for papers published up to May 2016 with English-language restriction; studies that compared disease activity between SLE patients with and without ON would be included, and eight studies involving a total of 1119 SLE patients were included. The incidence of ON in SLE was significantly associated with high patient’s disease activity, including the degree (pool odds ratio 2.54, 95% confidence interval [CI] [1.33, 4.86], p = 0.005) and the scores (mean difference 2.33, 95% CI [0.86, 3.80], p = 0.002). Besides, immunosuppressive drug use was also a significant risk factor for ON (p = 0.00001), while antimalarial treatment played a protective role (p = 0.01). No evidence of publication bias was detected. In conclusion, disease activity is a significant and independent risk factor for ON, and higher disease activity score is associated with accelerated incidence of ON in SLE patients.     

CXCL12/CXCR4/CXCR7轴在胎盘滋养细胞中作用机制的探讨

CXCL12介导的信号通路参与调节免疫细胞的活化和募集、造血干细胞的动员和归巢、新生血管形成、胚胎发育、肿瘤侵袭转移等过程.最近,CXCL12/CXCR4/CXCR7生物轴在胎盘植入和发育中的重要作用越来越受到关注.研究发现,CXCL12介导的信号通路参与调节胎盘滋养细胞的分化、增殖和侵袭,同时又可以趋化滋养细胞定向移动到蜕膜间质及血管周围,促进胎盘的植入、子宫-胎盘血管重塑和免疫耐受,进而维持妊娠的正常进行.深入理解CXCL12/CXCR4/CXCR7轴在胎盘滋养细胞中的作用机制,将有助于进一步认识胎盘植入的内在机制,为滋养细胞功能紊乱相关疾病的治疗提供新的思路.     

APRIL及其受体在结直肠癌变过程中表达水平的改变

目的探讨APRIL及其受体表达水平在结直肠癌变过程中的作用.方法采用实时荧光定量PCR(RFQ-PCR) 技术检测大肠癌发生各阶段组织中APRIL及其受体mRNA水平,并以靶基因和内参β2-M mRNA含量的比值作为评价靶基因表达水平的指标.结果 APRIL在中、重度异型增生肠组织及原位癌、浸润癌组织中表达水平显著高于正常肠黏膜(P＜0.05),APRIL在癌组织中表达水平显著高于中、重度异型增生肠组织(P<0.05),而其受体BCMA和TACI在结直肠癌发生各阶段的表达水平无统计学意义(P>0.05).结论 APRIL在结直肠癌的病变演进过程中呈现累积和渐进趋势,可能在结直肠癌发生、发展过程中起了重要作用,有可能成为结直肠癌早期诊断和抗癌治疗的靶分子.     

慢性重型肝炎伴门静脉高压性胃病及急性胃黏膜病变的研究

目的观察慢性重型肝炎患者合并胃黏膜病变的特点。方法521例研究对象共分为3组:A组191例,为肝硬化基础上的慢性重型肝炎住院患者;B组175例,为慢性肝炎基础上的慢性重型肝炎住院患者;C组155例,为对照组,既往无慢性肝病史的急性黄疸性肝炎住院患者。所有研究对象于入院后3 d内行胃镜检查,观察门静脉高压性胃病(PHG)及急性胃黏膜病变(AGML)的检出情况。结果A组患者有131例(68.6%)检出PHG,81例(42.4%)检出AGML,B组患者PHG和AGML检出例数分别为119例(68.0%)和79例(45.1%),C组PHG和AGML的检出例数分别为11例(7.0%)和21例(13.5%);A组与B组患者其PHG及AGML检出例数之间的差异均无统计学意义(P>0.05),但无论A组或是B组其PHG及AGML检出例数与C组相比,差异均有统计学意义(P<0.05)。结论慢性肝炎或肝硬化基础上的慢性重型肝炎患者易合并PHG及AGML,上述2种胃黏膜病变的胃镜检出率远高于急性黄疸性肝炎患者。PHG及AGML可能与慢性肝病基础有关。     

恶性周围神经外胚层瘤(附6例临床病理观察及文献复习)

本文对6例恶性外周原始神经外胚层瘤的临床病理特点进行了观察,同时对近年来的文献进行复习,其目的在于总结此瘤的临床病理特点,探讨此瘤的病理诊断。     

中医挂线疗法治疗肛裂120例临床观察

目的观察中医挂线疗法治疗肛裂的临床疗效。方法采用多中心前瞻性随机对照临床试验研究方法,将240例肛裂患者随机分为治疗组和对照组各120例,治疗组运用肛裂挂线疗法,对照组运用肛裂切除术。观察两组患者手术时间、术中出血量、切口愈合时间、疼痛程度、肛管静息压及安全性指标。结果治疗组患者手术时间、术中出血量明显小于对照组(P0.01);两组患者伤口愈合时间、术后疼痛视觉模拟量表评分、肛管静息压力差异均无统计学意义(P0.05),治疗组术后出血量明显小于对照组(P0.01);3个月随访其复发率两组差异无统计学意义(P0.05)。结论挂线疗法治疗肛裂临床疗效确切,具有操作简便、出血少的特点。     

鸟苷酰环化酶C质粒标准品的构建

目的:制备人鸟苷酰环化酶C(GC-C)质粒标准品,为实时荧光定量PCR检测GC-C含量,探讨大肠癌患者外周血单个核细胞(PBMC)GC-C mRNA表达水平及临床意义奠定基础。方法:在鸟苷酰环化酶C(GC-C)基因高保守区设计特异性的引物和探针,RT-PCR扩增目的片段并连接于pGEM-T载体,以得到GC-C质粒标准品。结果:经过蓝白斑筛选,PCR或EcoR I酶切初步鉴定,阳性克隆测序分析确定GC-C质粒标准品正确性。结论:正确构建GC-C质粒标准品为RFQ-PCR标准曲线的绘制及GC-C的定量检测奠定了基础。