The miR-17～92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma

Medulloblastomas (MBs) are the most common brain tumors in children. Some are thought to originate from cerebellar granule neuron progenitors (GNPs) that fail to undergo normal cell cycle exit and differentiation. Because microRNAs regulate numerous aspects of cellular physiology and development, we reasoned that alterations in miRNA expression might contribute to MB. We tested this hypothesis using 2 spontaneous mouse MB models with specific initiating mutations, Ink4c−/−; Ptch1+/− and Ink4c−/−; p53−/−. We found that 26 miRNAs showed increased expression and 24 miRNAs showed decreased expression in proliferating mouse GNPs and MBs relative to mature mouse cerebellum, regardless of genotype. Among the 26 overexpressed miRNAs, 9 were encoded by the miR-17∼92 cluster family, a group of microRNAs implicated as oncogenes in several tumor types. Analysis of human MBs demonstrated that 3 miR-17∼92 cluster miRNAs (miR-92, miR-19a, and miR-20) were also overexpressed in human MBs with a constitutively activated Sonic Hedgehog (SHH) signaling pathway, but not in other forms of the disease. To test whether the miR-17∼92 cluster could promote MB formation, we enforced expression of these miRNAs in GNPs isolated from cerebella of postnatal (P) day P6 Ink4c−/−; Ptch1+/− mice. These, but not similarly engineered cells from Ink4c−/−; p53−/− mice, formed MBs in orthotopic transplants with complete penetrance. Interestingly, orthotopic mouse tumors ectopically expressing miR-17∼92 lost expression of the wild-type Ptch1 allele. Our findings suggest a functional collaboration between the miR-17∼92 cluster and the SHH signaling pathway in the development of MBs in mouse and man.     

双虎清肝颗粒对四氯化碳诱发大鼠肝损伤模型肝组织基因表达谱的影响

目的探讨双虎清肝颗粒对四氯化碳诱发大鼠肝损伤模型肝组织基因表达谱的影响。方法清洁级Sprague—Dawley大鼠60只,随机均分为6组。除正常对照组外,均皮下注射40％四氯化碳8周,各治疗组再给予不同剂量双虎清肝颗粒干预8周;水飞蓟索对照组给予水飞蓟素干预8周,观察干预前后6组大鼠肝脏组织基因表达谱的变化。结果A组大鼠各基因表达无明显变化。四氯化碳干预后B、C1、C2、C3、D组与A组相比,表达下调的基因有：CY相关基因、脂代谢相关基因、蛋白质糖基化相关基因;表达上调的基因有：与细胞周期和细胞凋亡相关的基因、与脂转运相关基因、参与细胞黏附、细胞连接和胶原形成的基因。双虎清肝颗粒干预后C1、C2、C3、D组与B组比较,CY相关基因、蛋白质糖基化相关基因、脂代谢相关基因的表达均上调;双虎清肝颗粒干预前后C1、C2、C3组间比较,干预前上调者干预后下调明显,干预前下调者干预后上调明显,且随着双虎清肝颗粒剂量的增加,基因表达的幅度也增加。双虎清肝颗粒干预后C1、C2、C3组与D组比较,其基因表达的改变和双虎清肝颗粒导致的基因表达改变不同（有下调、有无变化、也有上调）。结论双虎清肝颗粒能够从基因水平减轻四氯化碳所诱发的肝脏损伤,并且量效关系明显。     

Functional dentate gyrus neurogenesis in a rapid kindling seizure model

Neurogenesis in the adult mammalian hippocampus resulting in long-term persistence of new neurons with features of capacity for functional activation is recognized. Many stimuli are capable of increasing the rate of neurogenesis, including seizure activity. Whether these insults result in an increased number of new functionally active neurons over and above the baseline rate of neurogenesis is not known. The rapid electrical amygdala kindling (REAK) model of seizures isolates the effects of seizures alone in the absence of neuronal death and the resulting seizures induce expression of c-Fos in the vast majority of dentate gyrus (DG) granule cells. C57BL/6 mice were exposed to REAK then injected with bromodeoxyuridine (BrDU) to label dividing cells, then re-exposed to REAK after a delay period to allow detection of functional activation in new neurons by measurement c-Fos expression in response to seizures. Adult subgranular zone cells migrated into the DG granule cell layer (GCL), assumed a neuronal phenotype and demonstrated seizure-dependent responsiveness. Larger absolute numbers of new neurons demonstrating seizure-dependent activation were found in the GCL of previously kindled mice. Seizures are capable of increasing the number of new neurons with the capacity for functional activation laid down in the postseizure period and incorporated into seizure-activated circuitry.     

粉刺净颗粒剂中盐酸小檗碱的双波长薄层扫描测定

采用双波长薄层扫描法,测定粉刺净颗粒剂中盐酸小檗碱的含量.展开剂为正丁醇-醋酸-水(7∶1∶2),回归方程为M=1.423×104A+2.566×103,r=0.9915,线性范围1～5μg/ml.     

模拟寒区冷暴露环境大鼠胃黏膜内皮素-1与缺氧诱导因子-1α的改变及冬胃颗粒对其影响

[目的]观察模拟寒区冷暴露环境下大鼠胃黏膜内皮素-1（ET-1）与缺氧诱导因子-1α（HIF-1α）改变及冬胃颗粒保护作用。[方法]健康雄性Wistar大鼠40只，随机分为4组：正常组、模型组、冬胃颗粒组、0．9％氯化钠溶液组，每组10只；正常组室温喂养，正常饮食，其他各组均以寒冷暴露法模拟寒区低温[（-10±2）℃]，处理5d，冬胃颗粒组在其过程中给予冬胃颗粒保护。5d后取各组大鼠胃黏膜以免疫组化方法检测其ET-1与HIF-1α表达。[结果]正常组未见异常；模型组及0．9％氯化钠溶液组大鼠冷暴露后出现寒战、蜷缩少动、尾部紫暗等症状，肉眼可见胃黏膜充血水肿与糜烂，光镜下可见有明显损伤；冬胃颗粒组仅表现有轻微的畏寒喜暖、少动等症状，肉眼与镜下仅可见胃黏膜轻微损伤。冬胃颗粒组胃黏膜ET-1与HIF-1α表达明显低于0．9％氯化钠溶液组与模型组，差异有统计学意义（P〈0．05）。[结论]冬胃颗粒可减轻冷暴露大鼠症状，减轻胃黏膜损伤，并使其胃黏膜ET-1与HIF-1α表达减弱。     

美安颗粒治疗黄褐斑的效果观察

目的 评价美安颗粒治疗黄褐斑的效果和安全性,并观察其复发率.方法 将确诊并符合一定入选标准的黄褐斑患者158例分为3组进行治疗:A组54例,口服美安颗粒1次1袋,1日1次；B组51例,口服美安颗粒1次1袋,1日2次；C组(对照组)53例,口服安体欣3粒,1日2次.疗程均为2个月,评价黄褐斑疗效和安全性.随访1个月,评价黄褐斑的复发率.结果 A、B、C组治疗黄褐斑的有效率分别为58％、52％、60％,3组有效率差异无统计学意义(P＞0.05).停药1个月后,3组的复发率分别为3.3％、15.3％、10.0％.3组的不良反应发生率分别为14.8％、15.6％、7.5％.结论 美安颗粒治疗黄褐斑疗效明显,临床用药安全.     

连贯抗病毒颗粒的HPLC指纹图谱研究及含量测定

摘 要 目的：采用指纹图谱结合多成分含量测定，提升院内制剂连贯抗病毒颗粒质量标准。方法：采用HPLC-UV法，色谱柱为YMC-Pack Pro C18 （250 mm × 4.6 mm，5 μm）色谱柱，流动相为乙腈-0.2%甲酸水溶液，梯度洗脱，流速为1.0 mL·min-1，检测波长为280 nm，柱温35℃，进样量为10 μL；建立10批次连贯抗病毒颗粒指纹图谱；同时测定了连翘酯苷A、连翘苷和咖啡酸的含量。结果：指纹图谱中，共标定了13个共有峰，指认了其中4个色谱峰，并测定连翘酯苷A、连翘苷及咖啡酸的含量分别为13.22 ~ 18.05、2.432 ~ 3.540、0.271 1 ~ 0.342 8 mg·g-1。结论：本文通过指纹图谱定性、含量定量方式，多维度提升院内制剂连贯抗病毒颗粒的质量控制水平。     

清热解毒扶正颗粒联合西药治疗老年肺炎及对血清降钙素原影响随机平行对照研究

[目的]观察清热解毒扶正颗粒联合西药治疗老年肺炎疗效。[方法]使用随机平行对照方法,将80例住院患者按随机数字表方法分为两组,对照组32例西药常规治疗;治疗组48例清热解毒扶正免煎颗粒(云南省中医医院制剂室生产,制剂批号:20031013。翼首草30g,芙蓉叶15g,鱼腥草30g,麦冬15g,太子参30g,丹参15g,等。每克颗粒剂含2.04g生药材),20g/次,3次/d。西药治疗同对照组。观测临床症状、体征改善时间、血清降钙素原、WBC变化。均1周为1疗程,连续治疗1疗程(14d),判定疗效。随访30d,观测血清降钙素原。[结果]临床疗效两组无显著性差异(P>0.05);症状、体征改善时间治疗组优于对照组(P<0.05);血清降钙素改善治疗组优于对照组(P<0.05);治疗第5天起,WBC两组均有改善,治疗组优于对照组(P<0.05)。[结论]清热解毒扶正颗粒抗感染作用显著,并可缩短疗程。