Novel integrative genomic tool for interrogating lithium response in bipolar disorder

We developed a novel integrative genomic tool called GRANITE (Genetic Regulatory Analysis of Networks Investigational Tool Environment) that can effectively analyze large complex data sets to generate interactive networks. GRANITE is an open-source tool and invaluable resource for a variety of genomic fields. Although our analysis is confined to static expression data, GRANITE has the capability of evaluating time-course data and generating interactive networks that may shed light on acute versus chronic treatment, as well as evaluating dose response and providing insight into mechanisms that underlie therapeutic versus sub-therapeutic doses or toxic doses. As a proof-of-concept study, we investigated lithium (Li) response in bipolar disorder (BD). BD is a severe mood disorder marked by cycles of mania and depression. Li is one of the most commonly prescribed and decidedly effective treatments for many patients (responders), although its mode of action is not yet fully understood, nor is it effective in every patient (non-responders). In an in vitro study, we compared vehicle versus chronic Li treatment in patient-derived lymphoblastoid cells (LCLs) (derived from either responders or non-responders) using both microRNA (miRNA) and messenger RNA gene expression profiling. We present both Li responder and non-responder network visualizations created by our GRANITE analysis in BD. We identified by network visualization that the Let-7 family is consistently downregulated by Li in both groups where this miRNA family has been implicated in neurodegeneration, cell survival and synaptic development. We discuss the potential of this analysis for investigating treatment response and even providing clinicians with a tool for predicting treatment response in their patients, as well as for providing the industry with a tool for identifying network nodes as targets for novel drug discovery.     

中药熏蒸结合离子导入治疗护理气滞血瘀型腰椎间盘突出症效果观察

目的探讨中药熏蒸结合离子导入对腰椎间盘突出症患者的护理效果。方法将120例气滞血瘀型腰椎间盘突出症患者随机分为四组,每组30例。对照组给予常规治疗和护理,导入组在此基础上给予中药离子导入治疗,熏蒸组给予中药熏蒸治疗,结合组给予中药熏蒸结合离子导入治疗,干预时间为15d。分别于患者入院第1天和第15天时评价患者JOA评分和腰腿疼痛情况。结果四组患者干预前后JOA及疼痛评分(VAS)组内比较,差异有统计学意义(P0.05,P0.01);干预后组间比较,JOA及VAS评分差异有统计学意义(均P0.05)。结论中药熏蒸结合离子导入法有利于改善气滞血瘀型腰椎间盘突出症患者腰腿部疼痛状况,促进临床康复。     

四川省部分地区肠道蠕虫感染现状调查

目的了解近10年来我省部份地区的肠道蠕虫感染现状。方法采用改良加藤厚涂片法检查肠道蠕虫卵，试管滤纸培养法鉴别钩虫虫种，对12岁以下儿童用透明胶纸肛拭法检查蛲虫卵。结果查出肠道蠕虫7种（线虫4种、吸种2种及带绦虫1种）。总感染率为41．34％。蛔虫、钩虫、鞭虫、蛲虫、带绦虫感染率分别为32．60％、17。30％、13．68％、17．55％、0．86％。部份地区感染率以四川盆地南部边缘的合江县为高，总感染率为77．91％，蛔虫47．90％、钩虫43．51％、鞭虫41．65％、蛲虫44．58％；以川西高原的德格县和位于盆地北部边缘的青川县较低。结论10年来部份地区蛔虫、钩虫、鞭虫及带绦虫感染率均有下降趋势，儿童蛲虫感染率有所回升。调查显示，我省肠道蠕虫感染仍十分严重，应积极普及健康教育，采用综合性防治措施，控制肠道蠕虫感染。     

Evaluation of tumor markers biochip C12 system in the diagnosis of gastric cancer and the strategies for improvement: analysis of 100 cases

BACKGROUND/AIMS: A C12 biochip system using 12 tumor markers has been developed in China for serum diagnosis of common cancers. This work is to evaluate this C12 system in the diagnosis of gastric cancer. METHODOLOGY: Sera from 100 gastric carcinoma patients were screened for 12 tumor markers including carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9, carbohydrate antigen 242, cancer antigen 15-3, cancer antigen 125, prostate specific antigen, free-PSA, neuron-specific enolase, human chorionic gonagotropin-beta, human growth hormone, and ferritin, using the C12 biochip system. The most relevant tumor marker and the contribution of the tumor markers to the improvement of diagnosis were determined. RESULTS: The overall diagnostic rate of C12 biochip system was 37%, and 7.8%, 29.4%, 35.5% and 50%, respectively, for stages I, II, III and IV patients. The differences in diagnostic rates between stage I (7.8%) and stage IV (50%) reached statistical significance (chi-square test, Chi2=7.20, p<0.01). Among all the 12 markers, carbohydrate antigen 19-9 had the highest positive rate up to 23%, against which any form of combinations of 5 most relevant tumor markers (2, 3, 4 or 5 markers combined) could not significantly improve the diagnostic rate. CONCLUSIONS: The C12 biochip system has some value in the diagnosis of advanced stage gastric cancer, but less sensitive in early gastric cancer.     

Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: chemoprevention strategies with antioxidants

Modulation of the cytotoxicity and mutagenicity of 4-hydroxyestradiol (4-OHE(2)), an oxidative metabolite of estrogen, by antioxidants was assessed in human MCF7 cells and TK-6 lymphoblast cells. The cytotoxicity of the catecholic estrogens was potentiated by depletion of intracellular glutathione and was independent of oxygen concentration. Agents such as the nitroxide Tempol can facilitate the oxidation of the semiquinone to the Q and enhanced 4-OHE(2) cytotoxicity. Conversely, reducing agents such as ascorbate, cysteine, and 1,4-dihydroxytetramethylpiperidine (THP) protected against cytotoxicity and decreased mutation induction, presumably by reducing the semiquinone to the hydroquinone. Our results support the proposition that oxidation of the semiquinone to the corresponding Q is crucial in eliciting the deleterious effects of catecholic estrogens. Furthermore, because the deleterious effects of 4-OHE(2) were abrogated by dietary and synthetic antioxidants, our results would support the chemopreventive use of diets rich in reducing substances (vitamins and added synthetic antioxidants) as a means of decreasing the risks associated with estrogen exposure and developing of breast cancer.