Prevalence and Risk Factors of Silent Cerebral Microbleeds in Patients with Coronary Artery Disease

ObjectivesCerebral microbleeds (CMBs), which can be detected by gradient-echo T2*-weighted magnetic resonance imaging (MRI), represent small chronic brain hemorrhages caused by structural abnormalities in cerebral small vessels. CMBs are known to be a potential predictor of future stroke, and are associated with age, various cardiovascular risk factors, cognitive impairment, and the use of antithrombotic drugs. Patients with coronary artery disease (CAD) are at potentially high risk of CMBs due to the presence of coexistent conditions. However, little is known about CMBs in patients with CAD. We aimed to identify the factors associated with the presence of CMBs among patients with CAD.MethodsWe evaluated 356 consecutive patients [mean age, 72 ± 10 years; men = 276 (78%)] with angiographically proven CAD who underwent T2*-weighted brain MRI. The brain MRI was assessed by researchers blinded to the patients’ clinical details.ResultsCMBs were found in 128 (36%) patients. Among 356 patients, 119 (33%) had previously undergone percutaneous coronary intervention (PCI), and 26 (7%) coronary artery bypass grafting (CABG). There was no significant relationship between CMBs and sex, hypertension, dyslipidemia, diabetes mellitus, anticoagulation therapy, antiplatelet therapy, or prior PCI. CMBs were significantly associated with advanced age, previous CABG, eGFR, non-HDL cholesterol, carotid artery disease, long-term antiplatelet therapy, and long-term dual antiplatelet therapy (DAPT) using univariate logistic regression analysis. The multivariate logistic regression analysis showed that long-term antiplatelet therapy (odds ratio, 1.73; 95% CI, 1.06 – 2.84; P = 0.03) or long-term DAPT (odds ratio, 2.92; 95% CI, 1.39 – 6.17; P = 0.004) was significantly associated with CMBs after adjustment for confounding variables.ConclusionsCMBs were frequently observed in patients with CAD and were significantly associated with long-term antiplatelet therapy, especially long-term DAPT.     

EphB6受体在恶性肿瘤中的研究进展

受体酪氨酸激酶(RTKs)是一种主要的膜受体,调控细胞增殖、分化和迁移。解除RTK信号通路的管制会导致许多疾病,如癌症和发育障碍。促红细胞生成素肝细胞受体(Erythropoietin-producing hepatocellular,Eph)家族是酪氨酸激酶受体家族中最大的一个亚族,其与配体Ephrin的相互作用在生长发育和肿瘤发生过程中发挥着重要作用。研究表明,一种缺乏酪氨酸激酶活性的特殊Eph受体EphB6在乳腺癌、结直肠癌等许多恶性肿瘤中表达下降,而大量证据表明EphB6表达的缺失依赖于其启动子DNA的高甲基化,进而促进肿瘤的进展与转移。EphB6是近期研究的热点因子,本文就其目前在恶性肿瘤中研究进展做一综述。     

Independent 6D quality assurance of stereotactic radiotherapy repositioning on linacs

PurposeA high level of accuracy while positioning the patient is mandatory for frameless stereotactic radiotherapy (SRT), as large doses in multiple fractions can be delivered near organs at risk. The objective of this study is to propose an end-to-end quality assurance method to verify that submillimetre alignment can be achieved with stereotactic conventional linacs.MethodsWe used a TrueBeam® linear accelerator equipped with a 6DOF robotic couch. The “ISO Cube” phantom was used with a homemade stand designed to generate known translational and rotational offsets. A reference CT scan was performed with straight alignment of the phantom. The procedure introduced 1.6° angular offset for the couch pitch and roll, at various gantry angles. The couch base was also moved between 0° and 270°. We compared the results with the daily machine performance check tests (MPC, Varian).ResultsThe mean isocentre size, MV and kV imager offsets were found to agree to within 0.1 mm, 0.1 mm and 0.3 mm respectively, and were in close agreement between the methods. For a total four months data collection period, the mean deviation between requested and measured 6DOF couch shifts was 0.6 mm and 0.2°. Errors on field size were smaller than 1 mm for 97.7% of the 324 data points.ConclusionResults demonstrate that the linac equipped with a 6DOF robotic positioner and CBCT imaging satisfies requirements for SRT. Our methodology, based on a modified Winston-Lutz quality control, allowed us to quantitatively assess end-to-end accuracy of a linac in order to safely deliver SRT.     

The effect of interleukin 6 deficiency on myocardial signal transduction pathways activation induced by bacterial lipopolysaccharide in young and old mice

PurposeExaggerated release of proinflammatory mediators during sepsis contributes to inadequate vasodilatation and depressed myocardial contractility, which lead to development of shock and circulatory collapse. The aim of the study was to evaluate the effect of IL-6 and aging on activation of intracellular signaling pathways in the myocardium induced by bacterial lipopolysaccharide (LPS) administration.Material/methodsLPS was injected intraperitoneally to male 3- and 24-month old mice with systemic IL-6 gene knock-out (IL-6KO) and the reference strain (WT). LPS was given intraperitoneally in single low (0.1 mg/kg) or high (10 mg/kg) dose, or in two doses (0.1 + 10 mg/kg) with 24-h delay. The expression and phosphorylation of STAT3, ERK1/2, Akt1/2/3 proteins in the left ventricular myocardium was evaluated after 24 h using Western blotting.ResultsLow LPS dose induced higher STAT3 phosphorylation only in old IL-6KO mice, not affecting ERK1/2 and Akt1/2/3 phosphorylation in any group. High LPS dose upregulated STAT3 phosphorylation similarly in all groups, reduced ERK1/2 expression in young WT mice and upregulated Akt1/2/3 expression and phosphorylation in young IL-6KO mice. Pretreatment with low LPS dose attenuated phosphorylation of STAT3 in both old groups and phosphorylation of Akt1/2/3 in young IL-6KO group. Two-dose approach also significantly potentiated ERK1/2 phosphorylation in both old groups.ConclusionsObtained results show that IL-6 deficiency alters the activity of intracellular signaling pathways: JAK/STAT in old and Akt in young LPS-treated mice. This may indicate that lack of IL-6 attenuates Akt-related cytoprotective effect of pretreatment with low LPS dose in young but not in aged animals.     

PFKFB3参与脂多糖诱导肺成纤维细胞及肺组织有氧糖酵解的观察性研究

目的:观察脂多糖(lipopolysaccharide,LPS)诱导肺成纤维细胞及肺组织有氧糖酵解关键酶6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3(6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3,PFKFB3)表达及其与有氧糖酵解的关系,探讨在LPS诱导肺纤维化过程中肺成纤维细胞和肺组织有氧糖酵解的潜在机制。方法:将人胚肺成纤维细胞MRC-5细胞系采用随机数字表法分为PBS对照组(PBS组)和LPS组(每组3孔),Western blot检测LPS刺激细胞6h后PFKFB3表达情况,同时免疫荧光显示PFKFB3在细胞内的定位情况;于LPS刺激后48 h采用海马细胞能量代谢仪检测细胞耗氧率(oxygen consumption rate,OCR)和产酸率(extracellular acidification rate,ECAR),并采用比色法检测有氧糖酵解产物乳酸产生情况,同时Western blot检测LPS刺激48 h后Ⅰ型胶原蛋白合成情况。将24只C57BL/6小鼠按随机数字表法分为生理盐水对照组(C组)、LPS组(L组),每组12只,L组、C组连续5d分别腹腔注射5 mg/kg LPS、等容量生理盐水;每组各6只于造模后第7天无痛处死小鼠,取血浆和肺组织,Western blot和免疫荧光检测各组肺组织中PFKFB3表达情况,比色法检测各组小鼠血浆中乳酸的含量;剩余小鼠于造模后第28天取肺组织,一侧肺通过Western blot检测肺组织Ⅰ型胶原蛋白合成情况,另一侧肺做石蜡切片进行病理学检测。结果:与PBS组比较,LPS刺激细胞6h后PFKFB3表达明显升高(P<0.05);LPS刺激细胞48 h后,与PBS组比较,LPS组细胞耗氧率降低、产酸率增加,代谢产物乳酸含量明显升高(P<0.05),同时细胞Ⅰ型胶原蛋白合成显著增加(P<0.05)。与C组比较,L组小鼠腹腔注射LPS 7 d后肺组织中PFKFB3表达明显升高(P<0.05),血浆乳酸含量明显升高(P<0.05);LPS注射28 d后,L组小鼠Ⅰ型胶原蛋白表达明显升高(P<0.05),肺组织出现明显纤维化。结论:在LPS诱导的肺纤维化过程中,LPS可诱导肺成纤维细胞和肺组织中PFKFB3蛋白表达,该过程与其有氧糖酵解过程相关,PFKFB3的表达上调可能是LPS诱导肺成纤维细胞和肺组织有氧糖酵解和肺纤维化的关键环节。     

脂肪和肥胖相关基因通过TLR2/p38信号通路促进异位子宫内膜间质细胞纤维化

目的：探讨脂肪和肥胖相关基因（FTO）对异位子宫内膜间质细胞（eESCs）纤维化的影响及其机制。方法：采用实时定量聚合酶链反应（qRT-PCR）检测子宫内膜异位症（EMs）患者病变组织中m6A相关基因的表达；通过慢病毒载体过表达FTO，在eESCs中检测纤维化相关基因的表达；通过m6A2 Target数据库和MeRIP-qPCR预测和验证eESCs中FTO与Toll样受体2（TLR2）的关系；Western blot法检测p38的蛋白表达变化。结果：FTO在EMs中表达下调（P ＜0.05）；FTO过表达促进eESCs纤维化并抑制其增殖（P ＜0.05）；在eESCs中，FTO通过TLR2 的m6A修饰途径上调其蛋白水平（P ＜0.05）；FTO在eESCs中经TLR2/p38 信号通路促进细胞纤维化（P ＜0.05）。结论：FTO在EMs中低表达，上调FTO可能通过TLR2/p38信号通路促进eESCs纤维化。     

C57BL/6小鼠放射性心肺功能不全动物模型建立

目的 建立C57BL/6小鼠放射性心肺功能不全动物模型。方法 24只雄性C57BL/6小鼠随机分为对照组、照射组。照射组接受胸部局部单次20 Gy电子线照射,照后饲养6个月。超声心动检查心功能,血气分析检测血氧分压(PaO₂),Tunel染色法检测细胞凋亡,Masson染色法检测心肺纤维化。结果 照射组LVEF (68.60±10.92)%与对照组(81.75±8.79)%降低(P<0.01);照射组心脏凋亡指数(23.90±6.60)%比对照组(3.25±3.38)%增高(P<0.01);照射组心脏CVF (15.42±5.72)%比对照组(1.45±0.64)%增高(P<0.01)。照射组PaO₂(86.10±7.60) mmHg比对照组PaO₂(107.16±9.01) mmHg下降(P<0.01);照射组肺脏凋亡指数(27.90±8.94)%比对照组(2.50±3.55)%增高(P<0.01);照射组肺脏CVF (17.76±5.77)%比对照组(2.50±3.55)%增高(P<0.01)。结论 辐射使心肺凋亡纤维化重塑,进而导致心肺功能的下降,成功构建C57BL/6小鼠放射性心肺功能不全动物模型。     

MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma

MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis.     

Coronavirus disease 2019-associated immunoglobulin A vasculitis/Henoch–Schönlein purpura: A case report and review

Immunoglobulin A (IgA) vasculitis or Henoch–Schönlein purpura is a predominantly pediatric disease occurring after a triggering viral or bacterial infection. Conversely, drug exposure is the most common inciting event in adult cases of IgA vasculitis. Recently, data has suggested a temporal association between coronavirus disease 2019 (COVID-19) and the development of IgA vasculitis in children and adults. Here, we describe a case of IgA vasculitis with nephritis in a 70-year-old man with COVID-19 and perform a comprehensive review of eight reported cases of suspected COVID-19-associated IgA vasculitis. When compared to classical IgA vasculitis, COVID-19-associated IgA vasculitis exclusively affects males (p < 0.00002) and is more common in adults (p < 0.005). Among cases of COVID-19-associated IgA vasculitis, adult cases were associated with significantly more arthralgia than pediatric cases (p = 0.04). In cases where skin biopsy was obtained, direct immunofluorescence (DIF) was negative for IgA in 50% of cases; thereafter, kidney biopsy DIF was positive for IgA in all cases. With this study, we provide support for an association between IgA vasculitis and severe acute respiratory syndrome coronavirus 2 infection and provide clinical information differentiating its manifestations from classical IgA vasculitis.