干细胞治疗糖尿病的研究现状及未来

目的:综述干细胞治疗糖尿病的研究现状及未来发展。资料来源:应用计算机检索Pubmed2000-01/2006-11有关干细胞治疗糖尿病方面文献,检索词“diabetes mellitus and stem cell not review”,限定文章语言种类为English。资料选择:对检索到的干细胞治疗糖尿病相关文献进行整理,选取针对性强文章。同一领域文献则选择近期发表或权威杂志文章。资料提炼:共检索到359篇相关文献,有关胚胎干细胞、胰腺干细胞、造血干细胞、神经干细胞、骨髓基质干细胞在糖尿病方面研究文章50篇,其中29篇符合要求。资料综合:干细胞极强的自我更新能力和多向分化潜能为糖尿病的细胞治疗开辟了新途径,按其发育阶段不同可以将干细胞分为胚胎干细胞和胰腺干细胞、造血干细胞、神经干细胞、骨髓基质干细胞等成体干细胞。干细胞移植是治疗糖尿病的一条新途径。干细胞生成胰岛素分泌细胞前需要经过诱导分化、细胞选择和细胞成熟3个阶段。干细胞治疗糖尿病研究已取得一定进展,部分实验已纠正糖尿病动物的高血糖状态。结论:干细胞定向分化为胰岛β细胞研究为糖尿病患者点燃了新希望,其勿庸置疑的成为治疗糖尿病的最佳种子细胞。     

“双重束缚”解析

目的:介绍了Bateson提出双重束缚概念的过程,阐述双重束缚概念的特征,并且论述了这一概念对心理治疗起到的积极作用以及概念本身存在的问题。资料来源:应用计算机在ProQuest数据库、EBSCOhost数据库中搜索1980-01/2006-05相关文章,检索的关键词为“doublebind”,“paradox”;在西南大学图书馆手工查找有关“双重束缚”资料。资料选择:对查找的资料进行筛选,纳入阐述双重束缚提出的历史、概念以及应用的文献。排除:①非实证研究和综述。②管理、文化和道德中双重束缚的研究。③重复性的研究。资料提炼:共收集49篇文章,选择与本文相关的28篇进行综述。另外还参考《理解人性》,《家庭治疗基础》两本书籍。资料综合:“双重束缚”是Bateson结合“再学习”和“Russellian矛盾”两个概念提出的。对“双重束缚”的各种定义均体现了这一概念的如下特征:矛盾性、命令性、不平等性、不可逃避性和长期性。“双重束缚”在心理治疗中有广泛的应用,但是各种对“双重束缚”的研究都存在着不足。结论:“双重束缚”的提出有其特定的历史背景,它对精神分裂、精神错乱的形成有一定的解释力。     

Proven germline mosaicism in a father of two children with CHARGE syndrome

CHARGE syndrome is an autosomal dominant malformation syndrome caused by mutations in the CHD7 gene. The majority of cases are sporadic and only few familial cases have been reported. In these families, mosaicism in one parent, as well as parent- to-child transmission of a CHD7 mutation, has been described. In some further cases, germline mosaicism has been suggested. Here, we report the first case in which germline mosaicism could be demonstrated in a father of two affected children with CHARGE syndrome. The truncating mutation c.7302dupA in exon 34 of the CHD7 gene was found in both affected children but was not detected in parental lymphocytes. However, in DNA extracted from the father's spermatozoa, the c.7302dupA mutation could be identified. Furthermore, mutation analysis of DNA isolated from 59 single spermatozoa revealed that the c.7302dupA mutation occurs in 16 spermatozoa, confirming germline mosaicism in the father of the affected children. This result has a high impact for genetic counselling of the family and for their recurrence risk in further pregnancies.     

脊髓损伤后真皮多能干细胞移植时机的选择

目的:观察脊髓损伤后不同时间移植真皮多能干细胞对大鼠运动功能修复的影响。方法:实验于2006-06/2007-03在第三军医大学生理学教研室完成。①实验材料:实验动物2～4月龄SPF级SD大鼠,体质量(210±40)g,雌雄不限,由第三军医大学实验动物中心提供。真皮多能干细胞为第三军医大学防原医学系从SD大鼠真皮中提取和分离。②实验方法:将42只SD大鼠在L4水平制成脊髓全横断损伤模型。将动物随机分为对照组(n=6)、真皮多能干细胞移植组(n=36)。真皮多能干细胞移植组又分为6个时间点:损伤后1,4,7,10,14,21d移植组,每组6只。各移植组于伤处移植大鼠真皮多能干细胞,而对照组于损伤后7d注射等量磷酸盐缓冲液。③实验评估:分别于移植后1d、1周、4周、8周、12周对各组大鼠进行动物行为学和脊髓诱发电位检测。结果:42只实验大鼠均进入结果分析,无脱落。①动物行为学评分:4周以后各组动物行为学评分比较差异有显著性意义(P<0.05),移植组明显高于对照组(P<0.05),各移植组间比较,以损伤后7,10d移植组动物行为学评分改善最显著。②各组大鼠脊髓诱发电位检查:体感诱发电位和运动诱发电位潜伏期和波幅值于移植后8,12周后明显高于对照组(P<0.05),各移植组间比较,以损伤后7,10d移植组体感诱发电位和运动诱发电位潜伏期和波幅值改善最显著。结论:脊髓损伤后7～14d进行真皮多能干细胞移植可明显改善大鼠后肢的运动功能。     

Liver X receptors orchestrate osteoblast/osteoclast crosstalk and counteract pathologic bone loss

Osteoporosis is characterized by enhanced differentiation of bone‐resorbing osteoclasts, resulting in a rapid loss of functional trabecular bone. Bone‐forming osteoblasts and osteoblast‐derived osteocytes perform a key role in the regulation of osteoclast development by providing both the pro‐osteoclastogenic cytokine receptor activator of NF‐κB ligand (RANKL) and its natural decoy receptor osteoprotegerin (OPG). By regulating the RANKL/OPG ratio, osteoblasts hence determine the rate of both osteoclast differentiation and bone turnover. Here, we describe a novel role for liver X receptors (LXRs) during the crosstalk of bone‐forming osteoblasts and bone‐resorbing osteoclasts. By using a system of osteoblast/osteoclast cocultures, we identify LXRs as regulator of RANKL expression and the RANKL/OPG ratio in osteoblasts. Activation of LXRs drastically reduced the RANKL/OPG ratio and interfered with osteoblast‐mediated osteoclast differentiation in vitro. During an ovariectomy (OVX)‐induced model of postmenopausal osteoporosis, the application of an LXR agonist shifted the RANKL/OPG ratio in vivo, ameliorated the enhanced osteoclast differentiation, and provided complete protection from OVX‐induced bone loss. These results reveal an unexpected involvement of LXRs in the regulation of bone turnover and highlight a potential role for LXRs as novel targets in the treatment of osteoporosis and related diseases. © 2012 American Society for Bone and Mineral Research.     

Neurodevelopmental outcome over time of preterm born children ≤750 g at birth

Background

Extremely low birth weight (ELBW) infants are at risk of cognitive impairment and follow-up is therefore of major importance. The age at which their neurodevelopmental outcome (NDO) can reliably be predicted differs in the literature.

Aims

To describe NDO at 2, 3.5 and 5.5 years in an ELBW cohort. To examine the value of NDO at 2 years corrected age (CA) for prediction of NDO at 3.5 and 5.5 years.

Study design

A retrospective cross-sectional and longitudinal cohort study.

Subjects

101 children with a BW ≤ 750 g, born between 1996 and 2005, who survived NICU admission and were included in a follow-up program.

Outcome measures

NDO, measured with different tests for general development and intelligence, depending on age of assessment and classified as normal (Z-score ≥ − 1), mildly delayed (− 2 ≤ Z-score < − 1) or severely delayed (Z-score < − 2).

Results

At 2, 3.5 and 5.5 years 74.3, 82.2 and 76.2% had a normal NDO. A normal NDO at 2 years CA predicted a normal NDO at 3.5 and 5.5 years in 92% and 84% respectively. Of the children with a mildly or severely delayed NDO at 2 years CA the majority showed an improved NDO at 3.5 (69.2%) and 5.5 years (65.4%) respectively.

Conclusions

The majority of the children with a BW ≤ 750 g had a normal NDO at all ages. A normal NDO at 2 years CA is a good predictor for normal outcome at 3.5 and 5.5 years, whereas a delayed NDO at 2 years CA is subject to change with the majority of the children showing a better NDO at 3.5 and 5.5 years.     

骨骼肌缺血再灌注损伤的机制

目的:对近年来骨骼肌缺血再灌注损伤的发病机制进行综述。资料来源:应用计算机检索MEDLINE、CBM、CNKI数据库及手工检索1998-01/2006-11期间的相关文献。中文检索词包括"骨骼肌,缺血再灌注损伤,发病机制";英文检索词有"Skeletal muscle","ischemia and reperfusion injury","oxygen freeradical","calcium overload"和"neutrophil"。资料选择:共收集到相关文献300篇,阅读全部文章的文题和大部分文章的摘要。选择文献所述内容与骨骼肌缺血再灌注损伤机制相关的文献。排除重复性研究。资料提炼:共得到符合纳入条件的文献55篇,排除145篇。选择其中30篇进行分析,英文24篇,中文6篇。资料综合:骨骼肌缺血再灌注损伤的机制由于有许多因素的介入而变的十分复杂,目前主要以氧自由基学说,钙超载学说和中性粒细胞学说为主,同时也注意到了一氧化氮和细胞凋亡以及微循环的无复流现象在其中的作用。结论:氧自由基学说,钙超载学说,中性粒细胞学说,一氧化氮,细胞凋亡以及微循环的无复流现象在骨骼肌缺血再灌注损伤中起着重要作用。     

Vaginal delivery compared with caesarean section in early preterm breech delivery: a comparison of long term outcome.

OBJECTIVE: To determine the optimum mode of delivery of the early preterm fetus in breech presentation. DESIGN: Retrospective comparison of two cohorts of preterm breech fetus. SETTING: Two tertiary care centres: at one centre the preferred management for preterm breech presentation was vaginal delivery; at the other centre, the preferred method was caesarean section. POPULATION: All singleton infants delivered after breech presentation from 1984 through 1989, at a gestational age of 26 to 31 weeks. Those with lethal congenital abnormalities, placenta praevia, placental abruption, fetal death or fetal distress before the onset of labour were excluded. MAIN OUTCOME MEASURES: Survival without disability or handicap documented at two years corrected age. The influence of a number of relevant variables on this outcome was assessed by logistic regression analysis. RESULTS: There was no difference in survival without disability or handicap between the centres (odds ratio 1.5, 95% CI 0.6-3.9 vaginal delivery compared with caesarean section). Survival without disability or handicap was positively influenced by increasing birthweight and corticosteroids > 24 h before birth, and negatively influenced by footling presentation. CONCLUSION: A policy of caesarean section for early preterm (26-31 weeks) breech delivery is not associated with increased survival without disability or handicap.