New antifungal pyranoisoflavone from Ficus tikoua Bur

建立苗药地瓜藤的UHPLC指纹图谱,研究其与抗氧化活性的谱效关系,筛选抗氧化活性成分群。

采用UHPLC建立地瓜藤指纹图谱,运用《中药指纹图谱相似度评价系统》(2012版)进行相似度评价并指认共有峰,运用SPSS 16.0、SIMCA 14.1软件进行聚类分析(hierarchical cluster analysis,HCA) 和主成分分析(principal component analysis,PCA);采用1,1-二苯基-2-三硝基苯肼自由基清除法、2,2’-联氮-二(3-乙基苯并噻唑啉-6-磺酸)二铵盐自由基清除法和总抗氧化能力测定法评价16批地瓜藤抗氧化活性;运用灰色关联度分析(grey relational analysis,GRA)、双变量相关分析、偏最小二乘回归(partial least squares regression,PLSR)3种分析方法研究谱效关系。

建立了16批地瓜藤的UHPLC指纹图谱并标定13个共有峰,相似度为0.613~0.996,同时指认出峰9为芦丁、峰10为异槲皮素、峰12为水仙苷,HCA结果显示样品共聚为两类,与PCA结果一致;16批地瓜藤均有不同程度抗氧化活性。GRA结果显示13个共有峰与抗氧化活性之间的关联度>0.8,均具有高关联性,双变量相关性分析及PLSR分析结果表明峰5、峰9(芦丁)、峰10(异槲皮素)、峰11、峰12(水仙苷)的相关系数及回归系数与抗氧化活性呈正相关,且贡献度较大(变量重要性投影>1),为抗氧化活性的主要有效成分。

16批地瓜藤均具有较好的抗氧化活性,其发挥抗氧化作用是内部抗氧化成分群协同作用的结果,而共有峰5,9,10,11,12所对应的成分与其抗氧化活性密切相关,揭示了地瓜藤抗氧化活性的药效物质基础。

     

电针对健康家兔体表胃电图和17肽胃泌素的影响

本文观察到，电针足三里及刺激中脑导水管周围灰质（ＰＡＧ），对健康家兔胃电（ＥＧＧ）均呈抑制性效应，并使血清胃泌素（Ｇ１７）含量减少。损毁ＰＡＧ后，电针足三里的效应消失；静脉注射α受体阻断剂酚妥拉明（Ｒｅｇｉｔｉｎｅ）和β受体阻断剂心得安（Ｐｒｏｐｒａｎｏｌｏｌ）阻断交感肾上腺素能神经的功能后，对电针和电刺激的效应没有影响；静脉注射阿托品（Ａｔｒｏｐｉｎｅ）也不能遏止电针和电刺激的效应；切断双侧颈部迷走神经后，电针足三里及电刺激ＰＡＧ的效应均减弱，甚或消失。说明电针足三里抑制ＥＧＧ和降低血清Ｇ１７含量的效应是通过激发ＰＡＧ的活动而实现的，迷走神经非胆碱能纤维是其主要传出途径。     

Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease

BackgroundThe “gray zone” of myocardial fibrosis (GZF) on cardiovascular magnetic resonance may be a substrate for ventricular arrhythmias (VAs).ObjectivesThe purpose of this study was to determine whether GZF predicts sudden cardiac death (SCD) and VAs (ventricular fibrillation or sustained ventricular tachycardia) in patients with coronary artery disease (CAD) and a wide range of left ventricular ejection fractions (LVEFs).MethodsIn this retrospective study of CAD patients, the presence of myocardial fibrosis on visual assessment (MF_VA) and GZF mass in patients with MF_VA were assessed in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs.ResultsAmong 979 patients (mean age [± SD]: 65.8 ± 12.3 years), 29 (2.96%) experienced SCD and 80 (8.17%) met the arrhythmic endpoint over median 5.82 years (interquartile range: 4.1 to 7.3 years). In the whole cohort, MF_VA was strongly associated with SCD (hazard ratio: 10.1; 95% confidence interval [CI]: 1.42 to 1,278.9) and the arrhythmic endpoint (hazard ratio: 28.0; 95% CI: 4.07 to 3,525.4). In competing risks analyses, associations between LVEF <35% and SCD (subdistribution hazard ratio [sHR]: 2.99; 95% CI: 1.42 to 6.31) and the arrhythmic endpoint (sHR: 4.71; 95% CI: 2.97 to 7.47) were weaker. In competing risk analyses of the MF_VA subcohort (n = 832), GZF using the 3SD method (GZF_3SD) >5.0 g was strongly associated with SCD (sHR: 10.8; 95% CI: 3.74 to 30.9) and the arrhythmic endpoint (sHR: 7.40; 95% CI: 4.29 to 12.8). Associations between LVEF <35% and SCD (sHR: 2.62; 95% CI: 1.24 to 5.52) and the arrhythmic endpoint (sHR: 4.14; 95% CI: 2.61 to 6.57) were weaker.ConclusionsIn CAD patients, MF_VA plus quantified GZF_3SD mass was more strongly associated with SCD and VAs than LVEF. In selecting patients for implantable cardioverter-defibrillators, assessment of MF_VA followed by quantification of GZF_3SD mass may be preferable to LVEF.     

Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system driven by peripheral immune cell infiltration and glial activation. The pathological hallmark of MS is demyelination, and mounting evidence suggests neuronal damage in gray matter is a major contributor to disease irreversibility. While T cells are found in both gray and white matter of MS tissue, they are typically confined to the white matter of the most commonly used mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Here, we used a modified EAE mouse model (Type-B EAE) that displays severe neuronal damage to investigate the interplay between peripheral immune cells and glial cells in the event of neuronal damage. We show that CD4⁺ T cells migrate to the spinal cord gray matter, preferentially to ventral horns. Compared to CD4⁺ T cells in white matter, gray matter-infiltrated CD4⁺ T cells were mostly immobilized and interacted with neurons, which are behaviors associated with detrimental effects to normal neuronal function. T cell-specific deletion of CXCR2 significantly decreased CD4⁺ T cell infiltration into gray matter in Type-B EAE mice. Further, astrocyte-targeted deletion of TAK1 inhibited production of CXCR2 ligands such as CXCL1 in gray matter, successfully prevented T cell migration into spinal cord gray matter, and averted neuronal damage and motor dysfunction in Type-B EAE mice. This study identifies astrocyte chemokine production as a requisite for the invasion of CD4⁺T cell into the gray matter to induce neuronal damage.

Multiple sclerosis (MS) is a prevalent, chronic neurologic autoimmune disease that results in accumulating disability. Disease onset usually occurs at 20–50 y of age and is characterized by symptoms of numbness, pain, fatigue, and/or visual impairment (1–3). Within 15–25 y of onset, 50% of MS patients require assistance with walking (4, 5) and 50% of MS patients report neurocognitive impairment (6). Accumulation of debilitating symptoms is attributed to an episodically inflamed central nervous system (CNS) as a result from recurrent attacks by immune cells (7).Demyelinated lesions are the classical hallmark of MS (8, 9); thus, the disease is historically considered a disease that primarily affects white matter of the CNS. In the past 20 y, mounting evidence suggested that inflammatory lesions in the CNS are not restricted to white matter but are also observed in CNS gray matter (9–11). In addition to myelin loss, gray matter lesions present with neuronal damage characterized by axonal transection, synaptic loss, and even neuronal loss (12–16). Neuronal damage is proposed to underlie the permanent and irreversible neurological dysfunctions in persons with MS (17, 18).The infiltration of antigen-specific lymphocytes such as T cells is implicated in CNS gray matter damage observed in MS (19) and an established mouse model, experimental autoimmune encephalomyelitis (EAE) (7–9). In the classical EAE model, T cells are mainly restricted to white matter of the spinal cord (20, 21) and are rarely found in spinal cord gray matter, with few exceptions (22). How T cells arise in CNS gray matter during MS pathogenesis is poorly understood. To mediate neuronal damage, T cells must be trafficked from lymphoid organs of peripheral tissues, such as lymph nodes and spleen, before transmigrating into the CNS. Such migration can occur via a vascular route through the blood–brain barrier, blood-cerebrospinal fluid, or meningeal lymphatic system (23, 24). Lymphocyte infiltration into the CNS is a tightly regulated process that is controlled by multiple factors that are cell-intrinsic or cell-extrinsic, including blood–brain barrier status, adhesion molecule expression, and presence of migratory cues (24, 25). During neuroinflammation, invading immune cells and local reactive glial cells create signaling gradients by secreting chemoattracting small peptide mediators to attract pathogenic cells to sites of inflammation. CNS-resident astrocytes have been identified as a key producer of important chemokines to induce the migration of T cells (26, 27).Here, while exploring the drivers of severe neuronal damage in spinal cord gray matter of mice induced to have a neurodegenerative form of EAE (termed Type-B EAE), we made the serendipitous observation that Type-B EAE is characterized by massive infiltration of CD4⁺ T cells into gray matter of the spinal cord. Accumulation of CD4⁺ T cells in spinal cord gray matter was prevented by genetic ablation of T cell CXCR2. Additionally, genetic ablation of astrocyte TAK1, an upstream molecule of CXCR2 ligand CXCL1, successfully prevented T cell migration to spinal cord gray matter, neuronal damage, and motor dysfunction.     

结合二维灰度直方图与PCNN的医学图像多类分割

针对医学图像中对组织器官多类分割的要求,提出一种结合二维灰度直方图的脉冲耦合神经网络（pulse coupled neural networks,PCNN）图像多类分割算法.首先根据PCNN模型的局部连接作用和阈值衰减特性对图像进行多类分割,然后利用基于类内最小离散度的二维直方图算法计算出PCNN网络迭代时的最佳门限值,从而实现医学图像的多类分割.通过对仿真的正常颅脑和非正常的颅脑核磁共振图像进行测试,结果显示本PCNN图像多类分割算法能够有效地分割出核磁共振颅脑图像中不同脑组织.因此,本文算法具有应用于医学图像的多类分割的可行性,并提高计算机辅助分割医学图像的准确性.     

空气细颗粒物暴露水平与健康成人大脑灰质体积和认知功能的关联研究

目的:应用磁共振成像(MRI)技术探究空气细颗粒物PM2.5暴露水平对健康成年人大脑灰质体积(GMV)和认知功能的影响。方法:选取487例健康成人,采集一般人口学信息及详细居住信息,并根据居住信息获取各受试近6个月和8岁～15岁期间的PM2.5暴露水平,对所有研究对象完成高分辨率结构MRI扫描,使用中文版精神分裂症认知功能成套测验-共识版(MCCB)进行认知测查,使用相关和回归分析探索空气PM2.5暴露水平与GMV和认知功能的关联。结果:近6个月PM2.5暴露水平与大脑右侧额下回三角部(brodmann分区[BA] 45)和右侧颞中回(BA 22)GMV存在负性关联(FWE校正,P<0.05,团块>10体素);与MCCB认知评估的信息处理速度-连线测试(r=-0.17,P<0.01)和推理和问题解决-迷宫测验评分(r=-0.22,P<0.01)负相关。8～15岁时的累积空气PM2.5暴露量与左侧梭状回(BA 18)和右侧舌回(BA 17)GMV负相关(FWE校正,P<0.05,团块>10体素),且与信息处理速度-连线测试、推理和问题解决-迷宫测验评分...     

Nocistatin excites rostral agranular insular cortex-periaqueductal gray projection neurons by enhancing transient receptor potential cation conductance via Gαq/11-PLC-protein kinase C pathway

Rostral agranular insular cortex (RAIC) projects to periaqueductal gray (PAG) and inhibits spinal nociceptive transmission by activating PAG-rostral ventromedial medulla (RVM) descending antinociceptive circuitry. Despite being generated from the same precursor prepronociceptin, nocistatin (NST) and nociceptin/orphanin FQ (N/OFQ) produce supraspinal analgesic and hyperalgesic effects, respectively. Prepronociceptin is highly expressed in the RAIC. In the present study, we hypothesized that NST and N/OFQ modulate spinal pain transmission by regulating the activity of RAIC neurons projecting to ventrolateral PAG (RAIC–PAG). This hypothesis was tested by investigating electrophysiological effects of N/OFQ and NST on RAIC–PAG projection neurons in brain slice. Retrogradely labeled RAIC–PAG projection neurons are layer V pyramidal cells and express mRNA of vesicular glutamate transporter subtype 1, a marker for glutamatergic neurons. N/OFQ hyperpolarized 25% of RAIC–PAG pyramidal neurons by enhancing inwardly rectifying potassium conductance via pertussis toxin-sensitive G_αi/o. In contrast, NST depolarized 33% of RAIC–PAG glutamatergic neurons by causing the opening of canonical transient receptor potential (TRPC) cation channels through G_αq/11-phospholipase C-protein kinase C pathway. There were two separate populations of RAIC–PAG pyramidal neurons, one responding to NST and the other one to N/OFQ. Our results suggest that G_αq/11-coupled NST receptor mediates NST excitation of RAIC–PAG glutamatergic neurons, which is expected to cause the supraspinal analgesia by enhancing the activity of RAIC–PAG–RVM antinociceptive pathway. Opposite effects of NST and N/OFQ on supraspinal pain regulation are likely to result from their opposing effects on RAIC–PAG pyramidal neurons.     

基于灰度共生矩阵和人工神经网络的肺癌CT图像的分类研究

目的研究小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）的分类问题。方法217例肺癌患者．其中男性165例．殳性52例;年龄35～80岁,平均年龄61．5岁。其中SCLC108例,NSCLC109例。提取患者764幅肺癌CT图像的灰度共生矩阵,选取对比度、熵、能量和逆差矩4个特征值,借助临床确诊结果,利用多层前向（BP）、径向基函数（RBF）人工神经网络对特征进行训练测试。结果BP人工神经网络对10％的78例样本进行测试,SCLC42例预测正确．NSCLC33例预测正确．3例预测失败。RBF神经网络对10％的78例测试样本进行测试,SCLC42例预测正确．NSCLC36例预测正确、类似方法对样本总数的70％进行训练,用30％的230例进行测试;BP人工神经网络有209例预测正确。正确率为90．9％：其中SCLC111例预测正确,正确检出率为88．8％;NSCLC98例预测正确,正确检出率为93.3％。RBF人工神经网络有216例预测正确．正确率为93．9％,其中SCLC117例预测正确,正确率为93．6％;NSCLC99例预测正确,止确检出率为94.3％。可见BP、RBF人1二神经网络对SCLC和NSCLC均具有90％以上的正确率,高于人工诊断结果。结论基于灰度共生矩阵的对比度、熵、能量和逆差矩4个特征值能反映SCLC和NSCLC的有效特征参量．通过人工神经网络能达到分类目的,辅助临床治疗。     

团块状灰度变化减轻子宫良性疾病聚焦超声消融术中的远场不良反应

目的：评估团块状灰度变化能否减轻子宫良性疾病聚焦超声消融术中的远场不良反应。方法：开展单中心回顾性临床观察研究,纳入重庆医科大学附属第二医院行聚焦超声消融术的40例子宫良性疾病。比较团块状灰度变化出现前后,在相同能量水平（最小不可耐受能量）下,术中即刻骶尾部或臀部疼痛、放射痛、会阴部痛、肛门胀痛的发生率及不良反应程度。结果：在相同能量水平（最小不可耐受能量）下,团块状灰度变化出现后术中即刻骶尾部或臀部疼痛、放射痛、会阴部痛、肛门胀痛的发生率及不良反应程度明显低于团块状灰度变化出现前（P<0.05）。结论：团块状灰度变化能减轻子宫良性疾病聚焦超声消融术中的远场不良反应。