Melatonin impedes Tet1‐dependent mGluR5 promoter demethylation to relieve pain

Melatonin (N‐acetyl‐5‐methoxytryptamine)/MT2 receptor‐dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten‐eleven translocation methylcytosine dioxygenase 1 (Tet1)‐dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2‐dependent analgesia involves spinal Tet1‐dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1‐encoding vectors to naïve rats produced profound and long‐lasting nociceptive hypersensitivity. In addition, enhanced Tet1 expression, Tet1‐metabotropic glutamate receptor subtype 5 (mGluR5) promoter coupling, demethylation at the mGluR5 promoter, and mGluR5 expression in dorsal horn neurons were observed. Rats subjected to spinal nerve ligation and intraplantar complete Freund's adjuvant injection displayed tactile allodynia and behavioral hyperalgesia associated with similar changes in the dorsal horn. Notably, intrathecal melatonin injection reversed the protein expression, protein‐promoter coupling, promoter demethylation, and pain hypersensitivity induced by Tet1 gene transfer, spinal nerve ligation, and intraplantar complete Freund's adjuvant injection. All the effects caused by melatonin were blocked by pretreatment with a MT2 receptor‐selective antagonist. In conclusion, melatonin relieves pain by impeding Tet1‐dependent demethylation of mGluR5 in dorsal horn neurons through the MT2 receptor. Our findings link melatonin/MT2 signaling to Tet1‐dependent epigenetic demethylation of nociceptive genes for the first time and suggest melatonin as a promising therapy for the treatment of pain.     

麦考酚酯联合糖皮质激素治疗肾小球肾炎临床疗效观察

目的：探讨麦考酚酯联合糖皮质激素治疗肾小球肾炎的临床疗效。方法：选取2009年8月-2010年8月间于我院治疗的肾小球肾炎患者70例，随机平均分为实验组（35例）与对照组（35例）。对照组予以常规加单独激素治疗；实验组在对照组治疗基础上以麦考酚酯联合糖皮质激素联合用药代替单纯激素治疗。一年后对治疗前后的相关临床指标进行比较。结果：两组治疗前后对比，治疗效果实验组明显优于对照组，两组问比较差异具有统计学意义（P〈0．05）。结论：麦考酚酯联合糖皮质激素治疗肾小球肾炎效果安全有效。     

基于医院局域网的知识仓库平台的建立

目的在医院基础网络环境下建立基于Web的医院知识仓库模型,将成熟的商品文献数据库与医院知识仓库等多种不同数据信息集成、传输、存储与管理,为医院临床医疗科研提供信息服务。方法使用SQL Server 2000数据库服务,并结合Datatrans软件系统、CNKI的多媒体知识仓库建库管理系统(KD3.5)和多媒体知识网站管理系统(KW3.5)等工具软件支持,客户端采用IE V6.0或以上浏览器版本,通过Web访问数据库资源。结果利用医院信息系统的基础网络通信资源,有效拓展了医院信息服务功能。结论医院知识仓库平台的建立,促进了图书信息由被动服务向主动服务的转型,在单位时间内,服务对象所获取的信息量成倍增加。     

基于巨噬细胞极化研究“赤芍-附片”治疗慢加急性肝衰竭的作用机制

目的 研究赤芍-附片对慢加急性肝衰竭（ACLF）大鼠的治疗作用及其对M1/M2型巨噬细胞极化的影响。方法 将SD雄性大鼠随机分为正常组、模型组、乳果糖组（乳果糖 1.8 g·kg^-1）、中药组（赤芍-附片 5.85 g·kg^-1），每组6只。采用牛血清白蛋白皮下及尾静脉注射联合腹腔注射D-半乳糖+脂多糖急性攻击建立ACLF模型，并予以相应药物灌胃1周，空白组和模型组予以蒸馏水灌胃。利用苏木素-伊红（HE）染色观察肝组织病理变化，实时荧光定量聚合酶链式反应（Real-time PCR）、蛋白免疫印迹法（Western blot）、免疫组化等方法比较各组大鼠肝组织CD86、诱导型一氧化氮合酶（iNOS）、CD206、精氨酸酶1（Arg1） mRNA和蛋白表达水平。结果 与正常组比较，模型组大鼠肝组织假小叶形成，肝细胞形态变化、坏死，伴大量炎性细胞浸润，CD86、iNOS mRNA及蛋白表达均显著上调（P<0.01）；与模型组比较，各给药组肝组织坏死及炎性浸润均改善，CD86、iNOS mRNA及蛋白表达下调（P<0.01），而CD206、Arg1 mRNA及蛋白表达上调（P<0.05，P<0.01），与乳果糖组比较，中药组上调CD206、Arg1作用更优（P<0.01）。结论 ACLF大鼠存在M1/M2型巨噬细胞极化失衡，失衡向M1方向偏移，赤芍-附片通过促进肝脏巨噬细胞向M2方向极化，抑制M1型巨噬细胞活化，减轻肝衰竭炎症反应。     

基于网络药理学及实验验证探究芪苈强心胶囊治疗射血分数保留型心衰的作用机制

目的 基于网络药理学及实验验证探讨芪苈强心胶囊治疗射血分数保留型心衰（heart failure with preserved ejection fraction,HFpEF）的作用机制。方法 将44个明确鉴定的芪苈强心胶囊体内代谢物检识有效成分，利用Swisstargetprediction、pharmmapper平台预测化合物靶点，OMIM、DisGenet、GenCard数据库中检索HFpEF疾病靶点；取交集靶点，利用String数据库和Cytoscape 3.7.2软件进行蛋白质-蛋白质相互作用（protein-protein interaction,PPI）和拓扑分析；Metescape平台对共同靶点进行基因本体（gene ontology,GO）功能富集分析及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析。构建醋酸脱氧皮质酮（deoxycorticosterone acetate,DOCA）盐敏感型HFpEF大鼠模型，给予沙库巴曲缬沙坦或芪苈强心胶囊进行干预，给药8周后，利用小动物超声成像系统...     

2012年全球上市新药

对2012年全球上市新药的基本信息，包括通用名、商品名、结构式、CAS号、研发公司、上市国家和主要适应证进行汇总，为新药研发工作者提供参考。     

从脾阴虚论治2型糖尿病心得

2型糖尿病是代谢性疾病中的常见病和多发病,基于临床实践及2型糖尿病一般病程较长,加之现代人民生活水平的提高及生活方式的改变,饮食厚味以及七情之变等化热化火,使营阴受损,伤及脾阴,故致脾阴虚者较多见。笔者通过理论学习和临床实践,2型糖尿病从脾阴虚辨治,用甘淡滋补脾阴法,每每能收到良好疗效。故有必要做一探讨,以期对指导临床治疗有所裨益。     

Methuselah‐like genes affect development,stress resistance,lifespan and reproduction in Tribolium castaneum

Methuselah (Mth) is associated with lifespan, stress resistance and reproduction in Drosophila melanogaster, but Mth is not present in nondrosophiline insects. A number of methuselah‐likes (mthls) have been identified in nondrosophiline insects, but it is unknown whether the functions of mth are shared by mthls or are divergent from them. Five mthls have been identified in Tribolium castaneum. Although they have different developmental expression patterns, they all enhance resistance to starvation. Only mthl1 and mthl2 enhance resistance to high temperature, whereas mthl4 and mthl5 negatively regulate oxidative stress in T. castaneum. Unlike in the fly with mth mutation, knockdown of mthls, except mthl3, shortens the lifespan of T. castaneum. Moreover, mthl1 and mthl2 are critical for Tribolium development. mthl1 plays important roles in larval and pupal development and adult eclosion, while mthl2 is required for eclosion. Moreover, mthl1 and mthl2 silencing reduces the fertility of T. castaneum, and mthl1 and mthl4 are also essential for embryo development. In conclusion, mthls have a significant effect on insect development, lifespan, stress resistance and reproduction. These results provide experimental evidence for functional divergence among mthls/mth and clues for the signal transduction of Mthls.     

Role of Oxalobacter formigenes in preventing calcium oxalate kidney stones

Objective To screen Oxalobacter formigenes (OxF) from fresh feces of healthy adults, and study its effect on the the prevention of calcium oxalate kidney stones. Methods OxF was screened and cultured from fresh feces of healthy adults. The rat model of calcium oxalate stone was established by esophageal gavage of 0.8% of ethylene glycol. Rats were divided into a control group and four groups of rats with ethylene glycol-induced calcium oxalate kidney stones according to random number table. Three groups were treated with 106 CFU, 107 CFU, 108 CFU viable OxF every day, respectively, for 4 weeks. The blood and 24-hour urine samples were collected to detect the serum creatinine, urea nitrogen, serum and urine calcium, phosphorus, magnesium and urine oxalate every week. At the end of the 4th week, the rats were sacrificed and the kidney tissues were stained with HE and Yasue. The deposition and content of calcium oxalate crystals were observed under a light microscope. Results The bacteria strain isolated from fresh feces of healthy adults was 100% as same as the known ATCC35274 bacteria strain, which means the strain screened is OxF. Among the 5 groups, there were no significant differences in body weight, Scr, BUN, serum calcium, blood magnesium, blood phosphorus, urinary magnesium and urinary phosphorus. The 24-hour urinary calcium excretion in the model group was significantly lower than that of the control group (P＜0.05). After intervention with OxF solution, the 24-hour urinary calcium excretion in the 108 CFU OxF group was significantly higher than that in the model group (P＜0.05), while there was no significant difference between the other intervention groups and the model. The oxalic acid excretion of 106 CFU OxF group and 107 CFU OxF group was lower than that of the model, but the difference did not reach statistical significance (P＞0.05). The 24 h oxalic acid excretion in the 108 CFU OxF group was significantly lower than that of the model at the end of first week (P＜0.05), and continued to decrease for the next 3 weeks. After 4 weeks of intervention, no crystal formation was observed in the control group under the deflection microscope, but a large amount of calcium oxalate crystals were formed in the renal cortex and renal medulla. The crystals were piled up and connected to each other. Yasue staining coincided with the calcium oxalate crystal in the same part of the kidneys. Compared with the model, there was no significant change in the score of calcium oxalate crystal in the kidneys of 106 CFU OxF group and 107 CFU OxF group, while the score of calcium oxalate crystal in the kidneys of 108 CFU OxF group was significantly lower (P＜0.05). Conclusions OxF are successively screened from healthy adults. Daily administration of 108 CFU OxF can safely and effectively reduce the urinary oxalic acid excretion, prevent the formation of calcium oxalate crystals and inhibit the formation of stones in kidneys of rats.