Sharper Confidence Intervals for Hochberg- and Hommel-Related Multiple Tests Based On an Extended Simes Inequality

This article concerns recent developments related to the now classical multiple-testing procedures (MTPs) of Holm, Hochberg, and Hommel based on marginal p-values. For a long time, the derivation of simultaneous confidence intervals (SCIs) corresponding to these MTPs was considered to be a difficult problem, but solutions were published in 2008 for Holm's MTP, and in 2012 for Hochberg's and Hommel's MTPs. These SCIs turned out to be as simple and easily implemented as the MTPs themselves, and to be remarkably similar. However, they also turned out to have the property/limitation, shared with other powerful stepwise MTPs, that no confidence assertions sharper than rejection assertions are possible unless all null hypotheses are rejected. A possibility is then to construct related families of MTPs that do not have this limitation but are somewhat less powerful, so users may choose among various such trade-off MTPs. It is shown in this article how an extended Simes inequality can be used to construct Hochberg- and Hommel-related MTPs of this kind that: (i) are more powerful than corresponding trade-off MTPs proposed previously, and (ii) lead to SCIs that are sharper than the ones proposed previously. Corresponding Holm-related MTPs and SCIs are considered for completeness and comparisons.     

大黄水提物的促智作用研究

目的：观察大黄水提物对小鼠促智作用的影响。方法：跳台法。结果：大黄水提物能增强自然衰老小鼠的学习和记忆能力，并对由东莨菪碱、亚硝酸钠和40％乙醇分别引起的小鼠记忆获得、巩固及再现障碍病理模型有较明显的改善作用。结论：大黄水提物中含有促智作用的药效物质，它可能是临床常用以大黄为主药的汤剂治疗中风失语、老年记忆障碍、脑外伤后遗症等疾病并获良效的物质基础。     

电针结合经颅磁刺激对脑缺血大鼠神经干细胞增殖和电跳台的影响

目的研究电针结合经颅磁刺激（rTMS）对急性脑缺血大鼠神经干细胞激活、增殖以及学习、记忆能力的影响。方法将120只雄性Wistar大鼠随机分成正常组、模型组、电针组、rTMS组和电针加rTMS组。复制急性大脑中动脉缺血模型，选取1日作为开始治疗的时间点，分别施以电针、rTMS和电针加rTMS方法处理，大鼠在各相应时间点处死前12h内每4小时腹腔注射溴脱氧尿嘧啶核苷（BrdU）1次，分别于治疗第7、14、28日进行BrdU免疫组化检测，观察鼠脑梗死面积以及鼠脑BrdU阳性细胞数，并在治疗前后对大鼠行电跳台评测。结果电针组、rTMS组和电针加rTMS组梗死侧海马齿状回颗粒细胞层（SGZ）、室管膜下层（SVZ）周围BrdU在第7、14日表达较模型组增强（P〈0．05），尤其以电针加rTMS组明显，第28日各组差异无统计学意义，电针组、rTMS组和电针加rTMS组第7、14、28日电跳台实验评分均较模型组改善（P〈0．05），尤以电针加rTMS组明显。结论电针结合rTMS治疗能促进大鼠神经干细胞的增殖，改善大鼠学习记忆能力。     

反复缺血再灌注制备小鼠血管性痴呆模型的评价

目的对应用反复缺血再灌注法制备的小鼠血管性痴呆(VD)模型进行评价,为VD的基础研究提供较为理想的动物模型。方法50只小鼠随机分为模型组(n=30)和假手术对照组,模型组采用双侧颈总动脉丝线结扎方法、经连续3次反复缺血再灌注,制备VD模型;对照组仅分离双侧颈总动脉,但不阻断血流。测试2组小鼠的学习记忆成绩;光学显微镜下观察海马CA1区神经细胞形态学变化,并采用免疫组化技术观测该区胆碱乙酰转移酶(ChAT)表达的变化。结果跳台试验中模型组小鼠术后第29d的反应时间(125.4±32.5)s较对照组(24.9±2.9)s明显延长(P<0.01),错误次数增多(P<0.01);术后第30d的潜伏时间(80±29)s较对照组(200±37)s明显缩短(P<0.01),错误次数增多(P<0.01)。水迷宫试验中模型组小鼠术后第29d、30d游完全程时间[(143±17)s,(162±11)s]较对照组[(68±8)s,(52±5)s]明显延长(P<0.01),错误次数增多(P<0.01)。海马CA1区ChAT免疫组化观察中模型组阳性神经元面密度值为0.086±0.009,较假手术组(0.123±0.015)明显降低(P<0.01)。结论反复缺血再灌注法制备的小鼠模型是研究血管性痴呆较为理想的动物模型。     

血管性痴呆小鼠海马组织学改变及乙酰胆碱酯酶活性变化特征

目的:探讨血管性痴呆(VD)小鼠海马组织病理学改变及乙酰胆碱酯酶病理(AchE)活性的变化特征.方法:将50只小鼠随机分为假手术组和模型组。模型组采用双侧颈总动脉反复缺血再灌注法制备VD模型,术后第29天和第30天测试学习记忆成绩,术后第30天检测海马CA1区组织学变化及AchE含量。结果:VD模型组小鼠学习记忆成绩较假手术组明显下降;海马CA1区锥体细胞数目减少,细胞核体积变小;且模型组小鼠海马AchE活性明显低于假手术组(P<0.01)。结论:小鼠海马组织内的AchE活性下降参与了VD的形成,进一步导致VD小鼠的学习和记忆障碍。     

30日龄脆性X基因敲除小鼠的被动回避行为观察

目的观察30日龄的脆性x基因（Fmrl）敲除小鼠（KO鼠）的被动回避行为。方法选取Fmrl基因敲除型（KO）纯合子（-／-）及其野生型（wT）纯合子（＋／＋）FVB近交系小鼠3013龄各15只,采用PCR鉴定实验动物KO鼠和wT鼠的基因型,进行2d的被动回避行为的避暗和跳台实验,比较2组小鼠电击次数和潜伏期时问。结果避暗实验中,第1天KO鼠的电击次数为（8．28＋0．50）次,与wT鼠（7．10±0．46）次相比显著增多（P〈0．05）;潜伏期时间虽增加但差异无统计学意义。第2天KO鼠的电击次数及潜伏期时间与wT鼠相比,差异均无统计学意义。KO和wT鼠第1天与第2天的潜伏期和电击次数相比,差异均有统计学意义（均P〈0．05）。跳台实验中,第1天KO鼠的潜伏期为（94．96±10．56）s,比wT鼠（135．73±12．17）s明显缩短（P〈0．05）;而电击次数为（1．81±0.31）次,比wT鼠（O．67±0．13）次明显增多（P〈O．05）。第2天KO鼠的电击次数及潜伏期时间与wT鼠相比,差异也无统计学意义。第1天wT鼠的电击次数与第2天相比,差异无统计学意义,潜伏期则低于第2天（P〈O．05）;而第1天KO鼠的潜伏期和电击次数与第2天相比,差异有统计学意义（均P〈O．05）。结论30日龄Fmrl基因敲除小鼠存在认知功能障碍。     

The relationship between ankle dorsiflexion range of motion,frontal plane projection angle,and patellofemoral pain syndrome

BackgroundAnkle range of motion abnormalities have been often linked with alteration in knee kinematics leading to the development of patellofemoral pain syndrome (PFPS). Literature exploring the relationship between ankle dorsiflexion range of motion (DF ROM) and knee kinematics during functional tasks is scanty. This study aims to assess the relation between ankle DF ROM and frontal plane projection angle (FPPA), one of the knee kinematic variables, in individuals with and without PFPS during a step-down test.MethodsThis is a case-control study in which seventy PFPS patients and other 70 asymptomatic control subjects had their ankle DF ROM measured using an inclinometer with the knee flexed and extended. Their FPPA angles were measured using Kinovea software while doing the step-down test.ResultsWhen the two groups were compared, ankle DF ROM measured with the knee flexed was higher in the control group (33.15 ± 4.96) than in the PFPS group (30.20 ± 6.93) (p = 0.03). In both the PFPS group and the control group, the correlation between FPPA and ankle DF ROM with the knee flexed was statistically insignificant (p = 0.075 and 0.323 respectively).ConclusionDecreased ankle DF ROM can be one of the contributing factors to the development of PFPS in the context of greater dynamic knee valgus.     

三种方法预备后牙细弯根管的比较

目的探讨逐步后退法、逐步深入法、被动逐步后退法（超声波与手用器械联合应用、三种不同方法预备后牙细弯根管对根管壁的清理能力及操作时间的差别。方法应用逐步后退法、逐步深入法、被动逐步后退法（超声波与手用器械联合应用）对45个新鲜拔除的人恒磨牙近中颊侧根管进行预备．并记录操作时间，将牙根纵向劈开，分为根冠1／3、根中1／3及根尖1／3，扫描电镜下评价其根管内壁牙本质碎屑和玷污层的形成情况。结果三种方法对根管清理能力差异无统计学意义（P〉0．05）而无论使用何种预备方法，其对根中1／3及根冠1／3处的清理能力优于根尖1／3部．两者差异有统计学意义（P〈0．05）。3种方法根管预备时间分别为：逐步后退法（12．8±1．26）min．逐步深入法（9．02±0．74）min，被动逐步后退法（超声与手用器械联合应用法）（12．21±1．90）min．三组差异无统计学意义（P〉0．05）。结论三种根管预备方法均不能达到完全的根管清理，尤其是对于根尖1／3部，清洁效果很不理想：总体上看，根中及根冠1／3清洁度显著优于根尖1／3。被动逐步后退法（超声与手用器械联合应用）及逐步后退法操作均较费时、费力，而逐步后退法根管预备时间略短于另两种方法且较省力。     

Maintaining asthma control in persistent asthma: comparison of three strategies in a 6-month double-blind randomised study

In patients controlled with SFC250 Diskus bd, this double-blind, randomised 6-month study compared continuing SFC250 to stepping down to either SFC100 bd or FP250 bd. Six hundred and three patients previously using 1,000 microg BDP (or equivalent) daily +LABA and controlled according to investigator's judgement were recruited. Patients received SFC250 bd during an 8-week open run-in period. Four hundred and seventy six patients (mean age=43 years, mean FEV(1)=2.9+/-1.0) who fulfilled the randomisation criterion ('Well-controlled' asthma according to the GOAL weekly definition for the last 2 weeks of the run-in period) entered a 24-week treatment period. The statistical hypothesis was based on a non-inferiority of SFC100 or FP250 compared to SFC250. The main criterion was the change from baseline in morning PEF over weeks 1-12 in the per-protocol population. The non-inferiority limit was -15 L/min. At inclusion, the three treatment groups were well balanced. Mean morning PEF was 476, 470 and 465 L/min in the SFC250, SFC100 and FP250 groups, respectively. The adjusted mean change in morning PEF over weeks 1-12 was +1.76+/-2.43 L/min for SFC250, -3.07+/-2.32 L/min for SFC100 and -16.51+/-2.46 L/min for FP250. SFC100 was at least as effective as SFC250 (treatment difference -4.83 [-12.39; 2.72], p=0.151) whereas FP250 was not (treatment difference -18.27 [-26.05; -10.49], p<0.001). Similar results were observed over weeks 13-24 in morning PEF (SFC100-SFC250=-4.54+/-3.84, p=0.238; FP250-SFC250=-20.11+/-3.92, p<0.0001). Secondary endpoints showed a similar pattern. Over weeks 1-12, SFC250 was significantly more effective than FP250 on evening PEF, daily symptoms and bronchodilator use. There was no difference between SFC100 and SFC250. The mean annual rate of moderate exacerbations was 0.16 in both SFC 250 and SFC 100 groups, and 0.21 in FP 250 group (ns, Poisson analysis). All treatments were well tolerated. CONCLUSION: In patients achieving asthma control with SFC250, stepping treatment down with SFC100 was at least as effective on lung function and symptoms as continuing SFC250, whereas FP250 was not.     

Intrastriatal injection of hypoxanthine impairs memory formation of step-down inhibitory avoidance task in rats

The aim of this study was to investigate the effects of intrastriatal injection of hypoxanthine, the major compound accumulated in Lesch–Nyhan disease, on performance step-down inhibitory avoidance task in the rat. Male adult Wistar rats were divided in two groups: (1) saline-injected and (2) hypoxanthine-injected group. Treated-group received intrastriatal hypoxanthine solution 30min before training session (memory acquisition) or immediately after training session (memory consolidation) or 30 before test session (memory retrieval) on step-down inhibitory avoidance task. Results show that hypoxanthine administration caused significant memory impairment in all periods tested. These results show that intrastriatal hypoxanthine administration provoked memory process impairment of step-down inhibitory avoidance task, an effect that might be related to the cognitive memory alterations in Lesch–Nyhan patients.