连翘化学成分研究

目的 研究连翘Forsythia suspense果实的化学成分.方法 采用硅胶色谱技术及重结晶等方法进行分离纯化,通过现代波谱技术鉴定化合物的结构.结果 从连翘80％乙醇提取后水沉部位分离得到1 1个化合物,分别鉴定为乙酰齐墩果酸(1)、异降香萜烯醇乙酸酯(2)、β-香树脂醇乙酸酯(3)、长管大青素A(4)、甲基-β-D-吡喃葡萄糖(5)、商陆种酸(6)、积雪草酸(7)、连翘苷(8)、齐墩果酸(9)、β-谷甾醇(10)、β-胡萝卜苷(11).结论 化合物1、4～7均是首次从该属植物中分离得到.     

苦参碱和川芎嗪抑制白血病细胞侵袭转移作用的实验研究

目的探讨苦参碱及川芎嗪对低氧(3%O2)培养条件下人B淋巴细胞白血病细胞株Raji细胞、人慢性髓系白血病细胞株K562细胞侵袭转移的抑制作用及机制。方法体外常规培养细胞,低氧环境下继续培养24 h后,分别加入终浓度为0、0.15、0.2、0.25 g/L苦参碱或0、0.1、0.15、0.2 g/L川芎嗪处理,以常氧培养不加药物的细胞为对照组,分别检测细胞黏附、迁移和侵袭能力,并以RT-PCR方法检测HIF-1α、VEGF mRNA的表达。结果低氧环境下Raji细胞和K562细胞的黏附、迁移和侵袭能力,以及HIF-1α、VEGF mRNA的表达均较常氧对照组显著增强(P<0.01)。0.15、0.2、0.25 g/L苦参碱均有效抑制低氧环境下Raji细胞的黏附、迁移和侵袭能力,并下调HIF-1α、VEGF mRNA的表达(P<0.05)。0.2、0.25 g/L苦参碱均有效抑制低氧环境下K562细胞的黏附、迁移和侵袭能力并下调HIF-1α、VEGF mRNA的表达(P<0.05)。0.1、0.15、0.2 g/L川芎嗪均有效抑制Raji细胞、K562细胞的黏附、迁移和侵袭能力,并下调HIF-1α、VEGF mRNA的表达(P<0.05),均呈剂量依赖性。结论苦参碱和川芎嗪能有效抑制低氧环境下Raji细胞和K562细胞黏附、迁移和侵袭能力,其作用机制可能通过下调细胞内HIF-1αmRNA的表达,从而减少VEGF mRNA的生成来实现。     

1例中间型β-地中海贫血的临床诊断和基因检测

目的通过回顾性分析1例中间型β-地中海贫血（地贫）的诊断及基因检测流程,总结中间型地贫的诊断策略。方法分析1例β-地贫合并α-地贫基因型患儿的临床表现,通过地贫基因多重PCR检测及DNA序列测定明确诊断,结合相关文献复习,探讨影响β-地贫表现型的基因因素。结果该地贫患儿基因型为B珠蛋白基因41／42突变的杂合予合并仅仅仅anti3.7基因杂合子。结论中间型地贫的诊断,需要临床表现与基因病变相一致,多重PCR结合DNA序列测定等方法可确诊罕见型基因突变。     

磁共振成像(T2*)检测重型β-地中海贫血患儿心脏、肝脏铁负荷及左心室射血分数的研究

目的观察我院重型β-地中海贫血(β-TM)患儿血清铁蛋白(SF)和体内铁沉积状况及对心脏功能的影响。方法检测我院28例重型β-TM患儿SF水平,并由我院放射科运用磁共振成像T2*(MRI T2*)技术检测心脏及肝脏铁沉积状况及左室射血分数(LVEF)。结果本组28例患儿中男16例,女12例,中位年龄11.2岁(7岁1个月~16岁11个月)。28例患儿中SF轻度升高者4例(14.3%),中度升高者8例(28.6%),高度升高者16例(57.1%)。肝脏MRI T2*检测结果 :肝铁轻度沉积2例(7.1%),中度沉积8例(28.6%),重度沉积18例(54.8%);心脏MRI T2*检测结果 :心铁正常16例(57.1%),轻度铁沉积4例(14.3%),中度铁沉积4例(14.3%),重度铁沉积4例(14.3%);LVEF降低者19例(67.9%),4例心脏重度铁沉积患儿中有3例(75%)LVEF明显降低(≤55%)。本组患儿SF水平与肝脏T2*值(r=-0.467,P=0.036)、心脏T2*值(r=-0.486,P=0.01)呈明显负相关;SF与输血量呈正相关(r=0.634,P=0.043;r=0.067,P=0.124)而与去铁治疗呈负相关(r=-0.526,P=0.043),SF和心脏T2*值与LVEF均无相关性(r=-0.154,P=0.306;r=0.067,P=0.124)。结论重型β-TM患儿SF增高及肝脏重度铁沉积发生率高,虽然心脏重度铁沉积患儿发生率不高,但心脏重度铁沉积患儿多有LVEF明显降低。     

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

鼻咽癌组织中Survivin蛋白和HIF-1α表达水平及临床意义

目的 探讨鼻咽癌组织中Survivin蛋白和缺氧诱导因子-1α(HIF-1 α)表达水平及临床意义.方法 选取2010年12月-2015年12月经病理切片确诊为鼻咽癌的患者72例;同时选取24例慢性鼻咽炎组织标本进行对照.应用免疫组织化学检测Survivin蛋白和HIF-1α的表达情况,并分析其表达水平的临床意义.结果 鼻咽癌组织中Survivin蛋白和HIF-1α阳性表达率均高于慢性鼻咽炎组织(P＜ 0.001).Ⅲ+Ⅳ期鼻咽癌组织Survivin蛋白和HIF-1α的阳性表达率、中等及以上阳性表达率均高于Ⅰ+Ⅱ期鼻咽癌组织(P ＜0.001);有淋巴结转移的患者Survivin蛋白和HIF-1α的阳性表达率均高于无淋巴结转移的患者(P＜0.05和P＜0.001).结论 Survivin和HIF-1α表达在鼻咽癌组织中具有较高的表达,两者在鼻咽癌的分期,进展过程中起到了重要的作用.     

聚乙二醇1000维生素E琥珀酸酯在纳米制剂中的应用进展

目的综述聚乙二醇1000维生素E琥珀酸酯(D-α-tocopherol polyethylene glycol 1000 succi-nate,TPGS)在各种纳米制剂中的最新进展。方法查阅国内外相关文献共48篇,对这些文献进行分析、概括和总结。结果 TPGS能够提高药物包封率和细胞吸收,改善药物释放,提高药物生物利用度,并能协同起抗癌疗效。广泛应用于聚合物纳米粒、聚合物胶束、纳米脂质体、纳米药物等纳米给药系统中。结论 TPGS在纳米制剂中有着良好应用前景。     

Treatments and compositions targeting α-synuclein: a patent review (2010-2016)

Introduction: Abnormal deposition of α-synuclein (ASN) is a hallmark and possible central mechanism of Parkinson’s disease and other synucleinopathies. Their therapy is currently hampered by the lack of early, screening-compatible diagnostic methods and efficient treatments.

Areas covered: Patent applications related to synucleinopathies obtained from Patentscope and Espacenet databases are described against the background of current knowledge regarding the regulatory mechanisms of ASN behavior including alternative splicing, post-translational modifications, molecular interactions, aggregation, degradation, and changes in localization.

Expert opinion: As the central pathological feature and possibly one of root causes in a number of neurodegenerative diseases, deregulation of ASN is a potentially optimal diagnostic and therapeutic target. Changes in total ASN may have diagnostic value, especially if non-invasive /peripheral tissue tests can be developed. Targeting the whole ASN pool for therapeutic purposes may be problematic, however. ASN mutations, truncation, and post-translational modifications have great potential value; therapeutic approaches selective towards aggregated or aggregation-prone ASN forms may lead to more successful and safe treatments. Numerous ASN interactions with signaling pathways, protein degradation and stress mechanisms widen its potential therapeutic significance dramatically. However, significant improvement in the basic knowledge on ASN is necessary to fully exploit these opportunities.     

PAK1、HIF-1α在结肠癌组织中侵袭、转移中的表达研究

目的 探讨PAK1(p-21活化激酶1)、缺氧诱导因子1α (HIF-1α)在结肠癌组织中侵袭、转移中的表达.方法 分别采用免疫组化法和荧光原位杂交检测41例结肠癌组织和癌旁正常组织中的HIF-1α、PAK1表达,并分析HIF-1α、PAK1与临床病理的关系.结果 本组研究中,结肠癌组织HIF-1α mRNA、PAK1 mRNA阳性表达率和HIF-1α蛋白、PAK1蛋白阳性表达率均显著高于癌旁正常组织(P＜0.05).从蛋白水平上讲,HIF-1α、PAK1在淋巴结转移、TNM分期为Ⅲ～Ⅵ期和Dukes分期为C、D期中阳性表达率显著高于无淋巴结转移、TNM分期为Ⅰ～Ⅱ期、Dukes分期为A、B期患者,差异具有统计学意义(P＜0.05).Spearman等级相关性分析显示,在蛋白水平,HIF-1α、PAK1在结直肠癌表达中呈正相关关系.结论 HIF-1α、PAK1可能参与结肠转侵袭和转移中.     

不同产地槐米炮制前后主成分的含量变化对α－葡萄糖苷酶活性抑制的影响

目的：比较研究10批不同产地槐米炒制前后对槐米中芦丁,槲皮素的含量变化及其对α－糖苷酶活性抑制作用的影响。方法对10批不同产地的槐米药材分别进行炒制,采用高效液相色谱法分别测定各槐米药材提取液中芦丁和槲皮素含量;以对硝基苯酚－β－1,4－葡萄糖苷（ pNPG）为底物,阿卡波糖为阳性对照,测定各槐米药材提取液对α－葡萄糖苷酶活性抑制率,比较了芦丁和槲皮素含量变化对α－葡萄糖苷酶的抑制活性的影响。结果经过炒制后,10批槐米炒制品中的芦丁含量均有所降低,而槲皮素含量则明显升高;槐米炒制品对α－糖苷酶活性抑制作用均优于生品。结论不同产地槐米炮制后,由于槲皮素含量的普遍升高,导致了槐米炒制品对α－葡萄糖苷酶活性抑制作用升高,表明槲皮素在对α－糖苷酶抑制活性起着重要作用。在治疗糖尿病疾病时选用炒制槐米更为合理。