普芦卡必利治疗慢性便秘的中国多中心随机、双盲、安慰剂对照临床研究

目的 评价普芦卡必利(2 mg,每日1次)对中国慢性便秘患者的疗效及安全性.方法 采用多中心、随机、双盲、安慰剂对照方法进行Ⅲ期临床研究,慢性便秘患者连续12周每日口服1次普芦卡必利(2 mg)或安慰剂.主要疗效指标为12周治疗期间平均每周完全自发排便(SCBM)≥3次的受试者比例.关键次要疗效指标为治疗前4周内平均每周完全自发排便(SCBM)≥3次的受试者比例.其他次要疗效指标包括每周平均SCBM次数、首次服药后出现第1次SCBM所需的时间、平均每周使用比沙可啶成灌肠剂的天数,并通过比较治疗前后PAC-SYM评分及PAC-QOL评分的变化评价患者的症状及生活质量改善情况.观察不良反应、实验室检查及心血管事件等安全性指标.结果 共筛选受试者446例,其中313例患者接受治疗,295例患者完成研究.治疗12周时,普芦卡必利组平均每周SCBM≥3次者的比例为39.4％,明显高于安慰剂组(12.7％,x2=29.50,P＜0.01).治疗4周时,普芦卡必利组平均每周SCBM≥3次者的比例为40.0％,明显高于安慰剂组(13.3％,x2=28.58,P＜0.01).患者总体症状及生活质量改善方面,普芦卡必利组优于安慰剂组.治疗期间常见的不良反应为腹泻、恶心、腹痛及头痛,基本为轻至中度,持续数天后即缓解.结论 普芦卡必利能显著且持续改善肠道功能,有效改善慢性便秘患者的相关症状,用以治疗中国慢性便秘患者安全、有效.     

多系统萎缩老年患者早期临床特点分析

目的 探讨多系统萎缩(MSA)的早期的临床表现及发病特点,为早期诊断提供依据.方法 回顾性分析我院102例诊断“很可能”的MSA老年患者首发症状、临床特点及辅助检查等,结合文献进行复习. 结果 102例诊断为“很可能”的MSA老年患者,其中诊断为MSA-P亚型57例(55.9％),MSA-C亚型45例(44.1％).首发症状以自主神经功能障碍27例,在MSA-P亚型与MSA-C亚型中分别为15例(26.3％)和12例(26.6％),主要表现为排尿、排便障碍14例,直立性低血压11例,性功能障碍8例.首发症状以帕金森样症状49例,主要表现为步态异常24例,静止性震颤3例,肌强直16例,动作迟缓15例.首发症状以小脑症状33例,主要表现为步态、肢体共济失调27例,构音障碍6例,眼球震颤2例.首发锥体束征2例.早期发生误诊36例(35.3％). 结论 MSA早期表现多样,容易被误诊.注意临床表现和辅助检查,提高临床早期诊断的准确性.     

2型糖尿病合并非酒精性脂肪性肝病与胰岛素抵抗及血脂代谢紊乱的关系

目的 分析2型糖尿病合并非酒精性脂肪性肝病( NAFLD)与胰岛素抵抗及血脂代谢紊乱之间的关系,并探讨诱发这些疾病的相关危险因素.方法 选取2型糖尿病患者200例,其中合并NAFLD者99例,未合并NAFLD者101例.测量身高、体重、腰围、臀围;检测肝酶、糖脂代谢指标,计算体重指数(BMI)、腰臀比以及改良的胰岛素C肽指数(HOMA-C肽),2组进行比较.结果 NAFLD组体重、BMI、腰围、臀围、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶、甘油三酯(TG)、总胆固醇、低密度脂蛋白胆固醇均明显增高(均P＜0.01),而年龄、病程、高密度脂蛋白胆固醇低于非NAFLD组(均P＜0.05).NAFLD组高脂血症尤以高TG血症发生率明显增加(P＜0.01).NAFLD组空腹和餐后1h血糖[(2.07±0.36对1.83±0.43) mmol/L,(14.04±3.96对12.59±3.90)mmol/L]、空腹及餐后1hC肽[(2.79±1.15对2.08±1.29) ng/ml,(1.33±0.45对1.12±0.54)ng/ml]、HbA1c[(2.09±0.33对1.96±0.28)％]、HOMA-C肽指数均明显增高(P＜0.05或P＜0.01).logistic 回归分析显示TG、BMI、ALT是2型糖尿病合并NAFLD的主要危险因素(P＜0.05或P＜0.01).结论 高TG血症、肥胖以及ALT升高增加2型糖尿病合并NAFLD的患病风险.     

三维应变参数评价肝硬化左心室心肌力学功能

目的应用三维应变参数评价早期肝硬化患者左心室心肌力学功能状态,探讨超声诊断肝硬化性心肌病的有效指标。方法健康对照组为28名健康志愿者,肝硬化组为25例早期肝硬化患者。应用三维斑点追踪技术(3D-STI)分析两组左心室整体三维峰值应变(G3DS)、整体纵向峰值应变(GLS)、心肌不同步指数(ASDI),常规超声测量左室射血分数(LVEF),左室舒张末期容积(LVEDV),二尖瓣口血流E/A比值。结果 B组左心室整体G3DS、GLS较A组减低(P0.05)、ASDI较A组增加(P0.05),LVEDV、LVEF较A组差异无统计学意义,B组二尖瓣口血流E/A比值较A组减低,差异有统计学意义(P0.05)。结论超声三维应变参数可有效评价早期肝硬化引起的左心室心肌收缩功能障碍。     

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays. Three contacts gave positive results in first generation anti-HCV EIA and negative results in second generation assay. This latter result was confirmed by further tests (neutralization test, synthetic peptides, and supplemental assay). Percent positivity for anti-HBc was about the same in non-sexual household contacts and sexual partners (13 of 109 [12%] and 7 of 54 [13%], respectively). Percent prevalence of anti-HBc was higher in contacts of index patients with chronic hepatitis B than in those of index patients who had recovered from that disease (6 of 20 [30%] and 14 of 133 [10%], respectively; P < .05). The HBV infection rate of contacts participating in controlled self-treatment was not higher than that of controls (3 of 57 [5%] and 10 of 98 [10%], respectively). Of 44 sexual partners, 5 (11%) were found to be positive for anti-HIV. Prevalence of anti-HAV matched with the age-related distribution in the German population. These findings suggest that intrafamilial transmission of HCV to family members of hemophilia patients is uncommon. In contacts of hemophilia patients, the risk of acquiring HBV infection seems to be as high in household contacts as in sexual contacts. Participation in controlled self-treatment does not appear to be an additional risk for HCV and HBV infection. There is no doubt that sexual transmission of HCV is less common than that of HBV and HIV.     

Repeat associated small RNAs vary among parents and following hybridization in maize

Small RNAs (sRNAs) are hypothesized to contribute to hybrid vigor because they maintain genome integrity, contribute to genetic diversity, and control gene expression. We used Illumina sequencing to assess how sRNA populations vary between two maize inbred lines (B73 and Mo17) and their hybrid. We sampled sRNAs from the seedling shoot apex and the developing ear, two rapidly growing tissues that program the greater growth of maize hybrids. We found that parental differences in siRNAs primarily originate from repeat regions. Although the maize genome contains greater number and complexity of repeats compared with Arabidopsis or rice, we confirmed that, like these simpler plant genomes, 24-nt siRNAs whose abundance differs between maize parents also show a trend of down-regulation following hybridization. Surprisingly, hybrid vigor is fully maintained when 24-nt siRNAs are globally reduced by mutation of the RNA-dependent RNA polymerase 2 encoded by modifier of paramutation1 (mop1). We also discovered that 21-22-nt siRNAs derived from a number of distinct retrotransposon families differentially accumulate between B73 and Mo17 as well as their hybrid. Thus, maize possesses a unique source of genetic variation for regulating transposons and genes at a genomic scale, which may contribute to its high degree of observed heterosis.     

Inhibited apoptosis and drug resistance in acute myeloid leukaemia

Despite extensive investigation into mechanisms of drug resistance in acute myeloid leukaemia (AML), the aetiology of therapeutic resistance is unclear. We found that five leukaemia cell lines (K562, HL-60, CEM, CEM induced to overexpress bcl-2, and REH) displayed parallel sensitivity to four antileukaemia drugs with different mechanisms of action, with K562 generally being the least sensitive and REH being the most sensitive. The amount of spontaneous apoptosis in the cell lines after serum-free culture paralleled their drug sensitivity: K562 cells displayed the least apoptosis at 24 h (2.50 ± 0.24%) and REH the most (24.47 ± 8.22%). The extent of spontaneous apoptosis of leukaemic blasts from 39 patients with newly diagnosed de novo AML also correlated with the success of the intensive, infusional cytarabine-based induction therapy. There was a median of 19.5% (range 3.6–64%) apoptotic AML cells after 24 h of serum-free culture in patients who entered a complete remission compared with 4.2% (1.8–7.0%) apoptotic AML cells in patients who did not achieve a complete remission ( P  = 0.0007). Thus, inhibited apoptosis was associated with both in vitro and in vivo pan-resistance to antileukaemic chemotherapy. The cause of inhibited apoptosis in AML is probably a function of interactions among multiple signals that influence apoptosis. Assessment of spontaneous apoptosis may serve as an important prognostic factor for AML.     

Cytopenia induction by 5-fluorouracil identifies thrombopoietic mutants in sensitized ENU mutagenesis screens

The ability of random mutagenesis techniques to annotate the mammalian genome can be hampered due to genetic redundancy and compensatory pathways that mask heterozygous mutations under homeostatic conditions. The objective of this study was to devise a pharmacologically sensitized screen using the chemotherapeutic drug, 5-fluorouracil (5FU), to induce cytopenia. 5FU dose was optimized in the 129/SvImJ, C57BL/6J, BALB/cJ, and C3H/HeJ strains of laboratory mice. N-ethyl-N-nitrosourea (ENU) mutagenesis was performed on 129/SvImJ males and phenotypic variants were identified by backcrossing on to the C57BL/6J background. G1 animals were challenged with 100 μg/g 5FU and phenodeviants with altered platelet recovery were monitored. Of 546 G1 animals tested, 15 phenodeviants were identified that displayed increased baseline platelet number, a platelet overshoot, or delayed platelet recovery, thereby demonstrating the utility of this approach for uncovering mutations in megakaryocyte and platelet development. Four G1 mice were selected for further analysis. The phenotypes were heritable in all four strains and genetic mapping identified a chromosome location in two of the three G2 lines tested. In conclusion, our group has developed a sensitized random mutagenesis screen utilizing 5FU and has shown that the strain combination of 129/SvImJ × C57BL/6J is robust for identification of founder lines with defects in megakaryocyte and platelet development.     

Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group

This placebo controlled, double-blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B. Patients were randomized to receive 100 mg lamivudine orally once daily for 52 weeks (n = 60) or placebo for 26 weeks (n = 65). Patients who were HBV DNA positive at week 24 were withdrawn at week 26. The primary efficacy endpoint was loss of serum HBV DNA plus normalization of alanine transaminase (ALT) at week 24. A significantly higher proportion of patients receiving lamivudine (63%) had a complete response at week 24 compared with patients receiving placebo (6%) (P <.001). Secondary efficacy parameters included histological response from baseline to week 52 in the lamivudine-treated patients. At week 52, 60% of lamivudine-treated patients with liver biopsy specimens available showed histological improvement (>/=2-point reduction in Knodell necro-inflammatory score), 29% showed no change, and 12% worsened. In a ranked assessment of pretreatment and post-treatment biopsy pairs 11% improved, 86% showed no change, and 2% worsened in fibrosis. At week 52, 27% of patients receiving lamivudine had YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. The incidence of adverse events and laboratory abnormalities was similar in both groups. In conclusion, lamivudine treatment results in a significant virological and biochemical improvement compared with placebo, induces an improvement or no change in histology in most patients, and is well tolerated. The response to lamivudine therapy in HBeAg-negative patients is similar to the response reported in previous studies of patients with HBeAg-positive chronic hepatitis B.     

双水平气道正压通气治疗高龄心力衰竭的临床观察

目的：探讨双水平气道正压通气（BiPAP）对高龄慢性心力衰竭急性加重期患者辅助治疗的有效性及安全性。方法分析2011年7月至2012年12月期间在武汉市亚心七医院心内科住院的40例慢性心力衰竭急性加重期的高龄患者[男22例,女18例,年龄（79.0±5.5）岁]的临床资料,对比分析使用BiPAP治疗前、后临床参数的变化（包括呼吸频率、血压、心率、血氧饱和度、血气分析、氨基端脑钠肽前体水平、心功能NYHA分级）,统计气管插管率、呼吸机相关并发症发生率。结果与治疗前相比,BiPAP治疗后动脉血气分析氧分压、血氧饱和度均升高（P＜0.001）;收缩压、舒张压、心率、呼吸频率、心功能分级、氨基端脑钠肽前体水平均下降（P＜0.01）;治疗有效38例,气管插管2例;死亡2例。无呼吸机相关性肺炎、恶性心律失常、新发心肌梗死病例。结论 BiPAP辅助治疗能够改善高龄心力衰竭急性加重期患者的多项临床参数,迅速、安全地改善患者的心肺功能。