How should we regulate risk in biomedical research? An ethical analysis of recent policy proposals and initiatives

The existing regulatory framework for research is increasingly attacked for its “one-size-fits-all” approach. Many stakeholders contend that existing regulations formulate the same regulatory requirements for research involving very different levels of risk, and thereby unnecessarily stifle medical progress. To address this criticism, regulators are currently developing more risk-adapted approaches to regulating research. A key feature of these approaches is that they aim to calibrate subject protections, including ethical review and safety monitoring, to the risks that studies pose to participants.     

Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels

The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150–499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings.     

PCR法检测人类脲原体U.Parvum和U.Urealyticum

目的 建立2个快速、同步检测脲原体U. Parvum和U. Urealyticum的PCR反应体系.方法 根据脲原体尿素酶B基因序列,设计2对分别针对U. Parvum和U. Urealyticum的特异性引物,建立2个PCR反应体系.通过脲原体标准株和临床阳性标本的PCR产物测序以及进行特异性和敏感性实验,对2个PCR体系进行评价.应用2个PCR反应体系对48例临床标本进行脲原体检测以及与培养法检测脲原体进行方法学比较.结果 2个PCR体系能够检测U. Parvum、U. Urealyticum标准株和临床标本中脲原体,扩增产物长度与目的片段大小一致.标准株和2个临床阳性标本扩增产物测序结果与GenBank中公布的序列完全一致.2个PCR体系与其他14株细菌(包括5株有尿素酶细菌)无交叉反应,检测限度均为10拷贝/ul的重组质粒DNA.对48例临床标本同时进行PCR和培养法脲原体检测,PCR的阳性检出率为54.2%,培养法为39.6%(P＜0.05).与培养法比较,PCR的灵敏度为94.7%,而与PCR法相比,培养法的灵敏度为69.2%.结论 2个PCR反应体系能够快速、同步进行临床标本中脲原体的分种鉴别,具有高度特异性和灵敏度.     

齐墩果酸通过MAPK/ERK信号传导通路对U87 MG细胞增殖及凋亡的体外实验研究

目的 探讨齐墩果酸(0A)对神经胶质母细胞瘤U87MG细胞增殖及细胞凋亡的影响.方法 以U87MG细胞为研究对象,使用25、50、80、100、150和200μg/ml的OA处理24、48和72h后,采用MTT实验检测OA对体外培养U87MG细胞增殖抑制作用,计算其抑制率;采用划痕法检测OA对U87MG细胞迁移能力的影响;用流式细胞仪分析OA对U87MG细胞周期与凋亡的影响;通过Western blot检测OA对MAPK/ERK信号传导通路活性的影响.结果 50μg/ml以上浓度的OA处理48h后,U87MG细胞的形态发生不同程度的变化,大量细胞脱落.150μg/ml和200μg/ml的OA处理U87MG细胞72h后,生长抑制率可达100％,与对照组相比差异有统计学意义(P＜0.01).25μg/ml的OA处理48 h后,迁移至划痕区的细胞数量相比于对照组明显减少.经50μg/mlOA作用48h后,处于Go/G1期的细胞从64.23％上升至75.03％,说明发生Go/G1期阻滞.同一浓度下,细胞凋亡率达到18.77％.U87MG细胞中MEK和ERK蛋白的磷酸化水平受到明显的抑制.结论 OA可显著抑制U87 MG细胞的生长增殖,呈一定的量效关系;OA可明显抑制U87MG细胞的迁移,并能抑制MAPK/ERK信号传导通路的激活.OA通过抑制MAPK/ERK信号传导通路的激活,可以抑制神经胶质母细胞瘤细胞的增殖生长.     

促酰化蛋白通过PLC信号途径调控脂滴相关蛋白TIP47的表达

目的 研究在3T3－L1脂肪细胞诱导分化过程中促酰化蛋白（ASP）对脂滴相关蛋白TIP47表达的影响,及阻断细胞PLC信号途径后此影响的变化。方法 (1)对诱导分化过程中的3T3－L1脂肪细胞分别给予ASP、U73122及U73122和ASP处理,并设立相应空白对照;(2)RT-PCR检测细胞中TIP47 mRNA的表达,Western blot检测细胞中TIP47蛋白的表达。结果 (1) ASP对3T3－L1脂肪细胞中TIP47 mRNA和蛋白表达有显著的上调作用;(2)PLC信号途径阻断剂U73122对其有显著的下调作用;(3) U73122和ASP处理后脂肪细胞中TIP47 mRNA和蛋白表达水平较仅ASP处理的脂肪细胞有显著降低,而较仅U73122处理的脂肪细胞有明显增高。 结论 PLC信号途径参与ASP调节TIP47表达的信号转导,从分子水平深化了对ASP成脂作用的认识,为肥胖症的认识及防治开拓新的思路。     

U型螺钉系统固定在寰枢椎不稳中的应用

目的 探讨运用U型螺钉系统（CUF）内固定治疗寰枢椎不稳的临床效果。方法 2004年1月至2005年12月,运用自行设计的CUF行C1.2椎弓根固定治疗C1不稳8例。其中枢椎齿状突骨折7例,Jefferson骨折1例,伴颈髓损伤6例。结果 术中未发生神经血管损伤,术后复查寰枢关节脱位全部纠正。CT轴位扫描,32枚椎弓根钉中有2枚钉部分进入椎管,1枚钉部分进入横突孔。3个月至2年平均6个月随访,7例达到骨性融合,无断钉断棒。结论 后路椎弓根钉系统固定是目前治疗C1.2不稳的较好装置。它具有固定牢固、能提拉复位且放置方便等特点。手术成功的关键在于准确置入椎弓根钉。借助U型螺钉提拉复位的同时,配合体位复位是必要的。     

稳定整合靶向EGFL7基因的shRNA载体的胶质瘤细胞系的建立

目的构建针对EGFL7基因的特异性RNA干扰载体,建立稳定转染该干扰载体的人胶质瘤细胞系。方法根据EGFL7基因的编码序列设计并合成针对EGFL7基因的特异性shRNA,将其克隆入pSilencer3.1-H1neo载体中,重组载体经脂质体LipofectamineTM2000介导转染胶质瘤细胞株U251;转染细胞经G418筛选,采用Westernblot方法在蛋白水平检测筛选出的G418抗性的克隆细胞。结果酶切鉴定和测序证实,成功构建了靶向EGFL7基因的shRNA真核表达载体pSilencer-shEGFL7,并获得了稳定表达靶向EGFL7基因的shRNA的胶质瘤细胞株。结论 EGFL7基因特异性RNA干扰载体能够显著抑制EGFL7基因在U251细胞中的表达,这为进一步研究EGFL7在胶质瘤细胞系U251中的生物学功能和作用机制奠定了基础。     

“U”形耳廓软骨在鼻翼缺损修复中的应用

目的:观察应用"U"形耳廓软骨支架修复鼻翼软骨缺损的临床疗效,总结其优越性。方法:本组35例鼻翼缺损患者,采取单侧或双侧耳甲腔、耳屏间切迹和耳屏区域的"U"形耳廓软骨,将其游离移植修复鼻翼支架缺损,并对其疗效进行评估。结果:应用耳甲腔、耳屏间切迹和耳屏区域的"U"形耳廓软骨修复鼻翼缺损,效果良好、可靠,不易遗留供区缺损、畸形。结论:采取的耳甲腔、耳屏间切迹、耳屏区域的"U"形耳廓软骨的局部解剖形态与鼻翼软骨较为相似,应用其修复鼻翼缺损,手术效果可靠,疗效满意,值得推广。     

24-Hour QT variability in heart failure

Background

Previous studies have shown that increased temporal variability of repolarization, as reflected by QT interval variability measured for 10 minutes, predicted spontaneous ventricular arrhythmias in implantable cardioverter defribrillator patients, but it is unclear how these measures perform in 24-hour recordings.

Methods

Twenty-four-hour digital Holter recordings from 372 subjects with chronic heart failure enrolled in Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca, (GISSI) Heart Failure study were analyzed using a template-matching, semiautomatic algorithm to measure QT and heart rate time series in sequential 5-minute epochs for 24 hours. QT variability was expressed as normalized QT variance (QTVN) or as the log ratio of the QTVN over normalized heart rate variance (QT variability index, or QTVI).

Results

A pronounced diurnal variation was seen in both QTVI and QTVN. Both were lowest in the midnight to 6 am time frame and increased throughout the day, peaking at noon to 6 pm, then decreasing 6 pm to midnight. For QTVI, all 4 time points were significantly different (P < .0001). QT variability index correlated with heart rate (r = 0.38, P < .0001) and was significantly higher for those in higher New York Heart Association (NYHA) classes (r = 0.22, P = .0003). Normalized QT variance did not correlate with heart rate or NYHA but correlated negatively with serum potassium (r = −0.22, P = .0002) and manifested the greatest increase during midmorning hours.

Conclusions

Repolarization lability as reflected in QT variability has a pronounced diurnal variation and increases significantly after 6 am, the time of greatest arrhythmic risk. QT variability for 24 hours might improve risk prediction in chronic heart failure patients and should be tested in appropriate trials.     

剖宫产第三产程产后出血的防治

目的探讨剖宫产第三产程产后出血的防治措施。方法回顾性观察我院剖宫产产妇486例,随机分为3组,A组：缩宫素组（158例）;B组：手法组（162例）;C组：缩宫素加手法组（166例）。准确测量产后2h及24h出血量,记录第三产程时间。结果剖宫产各组中,C组的产后出血量及产后出血发生率与A组、B组相比,差异有显著性。结论胎儿娩出后及时使用缩宫素等促宫缩药,并采取主动手法辅助娩出胎盘,可明显减少剖宫产产后出血,其防治产后出血的效果显著优于上述其它处理方法。