PT109改善链脲佐菌素诱导的散发性阿尔茨海默病小鼠认知功能障碍的作用及机制

目的观察PT109能否改善侧脑室注射链脲佐菌素（icv-STZ）诱导的散发性AD小鼠模型的认知功能障碍并对其机制进行初步探讨。方法32只7周龄雄性C57BL/6小鼠分为正常组（7只）、模型组（7只）、PT109低剂量组（9只）、PT109高剂量组（9只）。将STZ于第1和3天注射入小鼠侧脑室建立散发性阿尔茨海默病小鼠模型；（3mg/kg，每个注射位点5μL）造模后，分别腹腔注射PT109（30、100 mg·kg-1·d-1），2周后通过Morris水迷宫和避暗实验评价小鼠学习记忆能力；随后通过免疫荧光、免疫组化、免疫印迹、高尔基染色等方法检测小胶质细胞、神经元、树突棘、磷酸化Tau蛋白等AD相关指标。结果行为学实验结果显示：PT109可改善icv-STZ小鼠的学习记忆障碍；免疫荧光及组化结果显示：与模型组相比，PT109减少海马区域Iba1阳性细胞数量（低剂量：P <0.001， 高剂量：P <0.001），高剂量PT109增加海马和皮层区域MAP2和Tuj1阳性细胞总数量（P <0.05， P <0.01），差异具有统计学意义。高尔基染色结果显示：与模型组相比，PT109增加树突棘密度（低剂量：P <0.001， 高剂量：P <0.001），差异具有统计学意义。免疫印迹实验结果表明：与模型组相比，PT109降低NLRP3（高剂量：P <0.05）、磷酸化Tau蛋白的表达水平（低剂量：P <0.05， 高剂量：P <0.01），高剂量PT109提高PSD95（P <0.05）、磷酸化GSK3β（P <0.05）的表达水平，差异具有统计学差异。结论PT109可改善icv-STZ诱导的小鼠学习记忆障碍，可能与调节GSK3β/Tau相关通路有关

激发态~(17)Ne双质子2p发射的实验

<正>在中国科学院近代物理研究所放射性束流装置RIBLL上完成了17Ne+197Au的实验,采用硅条探测器与CsI(Tl)+PIN探测器阵列进行运动学完全测量,研究了17Ne双质子发射的机制。实验选

Aripiprazole versus other atypical antipsychotics for schizophrenia

BACKGROUND: In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study. MAIN RESULTS: We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended to favour olanzapine (n = 1360, 3 RCTs, MD total Positive and Negative Syndrome Scale (PANSS) 4.68 95% CI 2.21 to 7.16). There was no significant difference in extrapyramidal symptoms (n = 529, 2 RCTs, RR 0.99 95% CI 0.62 to 1.59) but fewer in the aripiprazole group had increased cholesterol levels (n = 223, 1 RCT, RR 0.32 95% CI 0.19 to 0.54) or weight gain of 7% or more of total body weight (n = 1095, 3 RCTs, RR 0.39 95% CI 0.28 to 0.54).When compared with risperidone, aripiprazole showed no advantage in terms of global state (n = 384, 2 RCTs, RR no important improvement 1.14 95% CI 0.81 to 1.60) or mental state (n = 372, 2 RCTs, MD total PANSS 1.50 95% CI -2.96 to 5.96).One study compared aripiprazole with ziprasidone (n = 247) and both the groups reported similar change in the global state (n = 247, 1 RCT, MD average change in Clinical Global Impression-Severity (CGI-S) score -0.03 95% CI -0.28 to 0.22) and mental state (n = 247, 1 RCT, MD change PANSS -3.00 95% CI -7.29 to 1.29).When compared with any one of several new generation antipsychotic drugs the aripiprazole group showed improvement in global state in energy (n = 523, 1 RCT, RR 0.69 95% CI 0.56 to 0.84), mood (n = 523, 1 RCT, RR 0.77 95% CI 0.65 to 0.92), negative symptoms (n = 523, 1 RCT, RR 0.82 95% CI 0.68 to 0.99), somnolence (n = 523, 1 RCT, RR 0.80 95% CI 0.69 to 0.93) and weight gain (n = 523, 1 RCT, RR 0.84 95% CI 0.76 to 0.94). Significantly more people given aripiprazole reported symptoms of nausea (n = 2881, 3 RCTs, RR 3.13 95% CI 2.12 to 4.61) but weight gain (7% or more of total body weight) was less common in people allocated aripiprazole (n = 330, 1 RCT, RR 0.35 95% CI 0.19 to 0.64). Aripiprazole may have value in aggression but data are limited. This will be the focus of another review. AUTHORS' CONCLUSIONS: Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials