干细胞诱导分化与糖尿病治疗

学术背景：对于丧失胰岛细胞功能的糖尿病患者来说，最根本的治疗方法是行胰腺移植或胰岛移植，但此法存在胰岛来源短缺及需要终生服用免疫抑制剂等问题。目的：充分认识干细胞在定向分化胰岛素分泌细胞及其在糖尿病细胞替代疗法中的作用。检索策略：由论文的研究人员应用计算机检索Pubmed、ISI Web of Knowledge、Blackwell Synergy数据库2000—01／2006—12的相关文献，检索词“stem cell，insulin producing cells，diabetes”，并限定文章语言种类为English。同时计算机检索中国期刊全文数据库2000—01/2006—12的相关文献，检索词“干细胞，胰岛素分泌细胞，糖尿病”，并限定文章语言种类为中文。此外手工检索相关干细胞中文书籍。共检索到111篇文献，对资料进行初审，纳入标准：人/鼠胚胎干细胞、成体干细胞定向分化胰岛素分泌细胞的研究，整理不同的诱导方法包括基因修饰、序贯的诱导因子等。排除标准：明显不随机的文献、Meta分析、重复性文献。文献评价：文献的来源主要是通过对人，鼠胚胎干细胞、成体干细胞定向分化胰岛素分泌细胞的研究进行汇总分析。所选用的30篇文献中，1篇为综述，其余均为临床或基础实验研究。资料综合：①干细胞以其极强的自我更新能力及多向分化潜能成为获得大量胰岛β细胞的最佳种子细胞来源。②目前已证实人／鼠胚胎干细胞可以在基因调控或条件诱导分化培养等情况下被诱导分化为胰岛素分泌细胞。③扩增及诱导胰腺干细胞分化是获得β细胞替代物的更直接的途径。但若将胰腺干细胞应用于临床，还需要做很多工作，如寻找最佳的扩增及诱导方案、最佳移植部位等。④胰腺外组织的前体细胞也因其可作为成体干细胞来源而受到关注，如肝干细胞、骨髓间充质干细胞。（函更新的研究着手于骨髓来源的干细胞、胎儿脐带血、脐带间充质干细胞及胎盘多潜能细胞等定向分化，以寻求更多的种子细胞来源应用于细胞替代疗法。结论：尽管目前应用干细胞治疗糖尿病研究处于动物实验阶段，但各种干细胞定向分化为胰岛β细胞的可能性为糖尿病患者点燃新的希望。深入了解胰腺个体发生机制及干细胞定向分化为胰岛β细胞分子调控机制，将加快糖尿病细胞治疗的研究进展。     

Neonatal prebiotic (BGOS) supplementation increases the levels of synaptophysin,GluN2A‐subunits and BDNF proteins in the adult rat hippocampus

Compelling data suggest that perturbations in microbial colonization of the gut in early‐life, influences neurodevelopment and adult brain function. If this is the case, then ensuring the growth of beneficial bacteria at an early age will lead to optimal brain development and maturation. We have tested whether feeding neonatal rats daily (from post‐natal days 3‐21) with a galacto‐oligosaccharide prebiotic (Bimuno®, BGOS) or a control solution, alters the levels of hippocampal N‐Methyl‐D‐Aspartate receptor (NMDAR) subunits (GluN1, GluN2A, GluN2B), synaptic proteins (synaptophysin, MAP2, and GAP43) and brain‐derived‐neurotrophic factor (BDNF), at post‐natal days 22 and 56. The administration of BGOS significantly elevated GluN2A subunits, synaptophysin and BDNF in the hippocampus of 22 day old rats. The effect was also observed on day 56 (26 days after the feeding ceased). The levels of all other proteins (GluN1, GluN2B, MAP2, GAP43) remained unaltered. Increased GluN2A, synaptophysin, BDNF, but not MAP2, may suggest that neonatal BGOS feeding alters neurotransmission rather than synaptic architecture. Although the functional consequences of our findings require further investigation, the current study confirms that the manipulation of gut bacteria in early‐life, has central effects that persist until at least young adulthood. Synapse 70:121–124, 2016. © 2016 Wiley Periodicals, Inc.     

基于尿动力学客观指标的神经原性膀胱概率预测模型构建

目的:建立概率预测的Logistic回归模型,分析影响神经原性膀胱尿动力学的主要危险因素和保护因素,并评价模型的灵敏度、特异度和准确性。方法:收集2004-03/2006-03在中山大学附属第一医院尿流动力学室行尿动力学检查的患者80例,对其尿动力学图的客观指标进行回顾性分析。①80例中尿流动力学图正常者29例为对照组,尿流动力学图显示神经原性膀胱者51例为病例组。②将两组资料采用统一的变量指标(包括性别、年龄以及尿流动力学仪器自动采集计算的34个数据)输入SPSS12.0版本数据库,进行主成分分析,将贡献率高的主成分进行单因素分析,取其中有统计学意义的主成分作多因素Logistic回归分析,建立Logistic回归方程,计算各因素的OR值,并计算模型的灵敏度、特异度和准确度。结果:①尿动力学34个客观指标进行主成分分析后得出8个主成分(C1～8),取贡献率高的5个主成分进行单因素分析,结果有2个主成分可以进入多因素Logistic回归分析。获得Logistic回归概率预测模型,此概率预测模型灵敏度为82.4%,特异度75.9%,准确度为80.0%。②主成分C1的OR值=4.606,C1中的首次尿意膀胱压力和逼尿肌压力、正常尿意膀胱压力和逼尿肌压力、强烈尿意膀胱压力和逼尿肌压力、尿急尿意膀胱压力和逼尿肌压力、充盈期最大逼尿肌压力的系数分别是0.823,0.834,0.781,0.913,0.924,0.932,0.883,0.916,0.857,高于C1中其他变量的系数,故可把主成分C1看作是一个“压力型”指标。③C3的OR值=0.183,C3中系数较高的变量是最大流率、平均流率、压力流率中最大流率和平均流率,分别是0.694,0.777,0.768,0.771,因此把C3看作为“流率”变量指标。结论:①成功构建了人神经原性膀胱尿流动力学图的概率预测模型,其中“压力”因子主成分是危险因素,“流率”因子主成分是保护因素。②概率预测模型的灵敏度、特异度和准确性显示其有较好的代表性。     

Can the reading for serologic reactivity following 37 degrees C incubation be omitted?

The need to detect antibodies that agglutinate and/or hemolyze red cells (RBCs) directly at 37 degrees C, but do not react in subsequently performed indirect antiglobulin tests (IATs), is of concern relative to the streamlining and automation of antibody detection methods. To determine incidence and significance of such reactions, data from 87,480 tests, which used low-ionic-strength saline, 10-minute incubation at 37 degrees C, and anti-IgG, were analyzed for unexpected antibodies. There were 3590 positive tests, of which 475 showed reactions at 37 degrees C but not in subsequently performed IATs (37 + IAT-). Of these, 196 reactions were due to autoantibodies or other factors usually considered insignificant with respect to the survival of transfused incompatible RBCs, 176 were due to alloantibodies of questionable clinical significance (M, Lea, P1, etc.), and 103 were associated with alloantibodies of potential clinical significance (63 E, 27 K, 5 Jka, 4 D, 3 cE, and 1 C). This latter reaction was seen in 72 patients, with two 37 + IAT-antibodies occurring in each of 3 patients. Of the 75 potentially significant 37 + IAT-antibodies, 57 were seen in patients recently exposed to homologous RBCs, 13 in patients with a history of transfusion and/or pregnancy, and 5 in patients with no known exposure to homologous RBCs. IAT reactivity was observed in subsequent samples with 27 of these antibodies. The predictive value of a 37 + IAT-test was 21.7 percent for a potentially significant antibody. The incidence was 0.12 percent of all tests for unexpected antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous umbilical blood sampling and umbilical vein transfusions. Rapid serologic differentiation of fetal blood from maternal blood

Percutaneous umbilical blood samples (PUBS), obtained under ultrasound guidance, are used for prenatal diagnosis and management of hemolytic disease of the newborn (HDN) and other fetal disorders. Rapid testing at the time of sampling is vital to distinguish fetal from maternal blood. Blood typing was performed by slide technique in the treatment room during 38 procedures on 25 patients. Anti-I was used to test 50 presumed PUBS; venous I-positive maternal blood was tested in parallel. Because anti-I cannot detect fetal blood after umbilical vein transfusion (UVT) of I-positive donor blood, ABO and Rh blood typing reagents were used to test 29 samples when maternal and fetal or donor blood groups differed. Monoclonal reagents were used for optimal detection of weak AB antigens in fetal blood. Avid, chemically modified anti-D was used for Rh typing. Blood typing showed 27 (34%) of 79 samples to be maternal blood. Fetal blood was obtained in 8 of 10 cases investigated for fetal disorder and in 16 cases of potential HDN (anti-D, 5; -CD, 5; -cE, 2; -K, 2; -c; -E). The absence of HDN (antigen-negative fetus) was determined in 4 cases. UVT afforded live birth of 9 of 10 infants with HDN and was not indicated in two cases.     

Sepsis-associated encephalopathy: a magnetic resonance imaging and spectroscopy study

Brain dysfunction is frequently observed in sepsis as a consequence of changes in cerebral structure and metabolism, resulting in worse outcome and reduced life-quality of surviving patients. However, the mechanisms of sepsis-associated encephalopathy development and a better characterization of this syndrome in vivo are lacking. Here, we used magnetic resonance imaging (MRI) techniques to assess brain morphology and metabolism in a murine sepsis model (cecal ligation and puncture, CLP). Sham-operated and CLP mice were subjected to a complete MRI session at baseline, 6 and 24 h after surgery. Accumulation of vasogenic edematic fluid at the base of the brain was observed in T₂-weighted image at 6 and 24 h after CLP. Also, the water apparent diffusion coefficients in both hippocampus and cortex were decreased, suggesting a cytotoxic edema in brains of nonsurvival septic animals. Moreover, the N-acetylaspartate/choline ratio was reduced in brains of septic mice, indicating neuronal damage. In conclusion, noninvasive assessment by MRI allowed the identification of new aspects of brain damage in sepsis, including cytotoxic and vasogenic edema as well as neuronal damage. These findings highlight the potential applications of MRI techniques for the diagnostic and therapeutic studies in sepsis.     

Reducing Diagnostic Errors in Musculoskeletal Trauma by Reviewing Non-Admission Orthopaedic Referrals in the Next-Day Trauma Meeting

INTRODUCTION

Diagnostic errors in orthopaedics are usually caused by missing a fracture or misreading radiographs. The aim of this study was to document the pick-up rate of the wrong diagnoses by reviewing X-rays and casualty notes in the next-day trauma meeting.

PATIENTS AND METHODS

The casualty notes and radiographs of 503 patients were prospectively reviewed in the daily trauma meeting between August 2002 and December 2002 in a district general hospital. The relevant data were collected and analysed by a single assessor.

RESULTS

The false positive rate for making an orthopaedic diagnosis was 12.6% (i.e.) diagnosing a fracture, when none existed). The false negative (missing) rate was 4%, while 2.4% incidental findings were missed, or at least not documented, after reading the X-rays. There were 7.8% wrong diagnoses made. The majority of the patients were seen by the senior house officers.

CONCLUSIONS

The medicolegal significance of false negative diagnosis is obviously greater. In a busy emergency department, where a large number of patients are seen, there is a greater risk. This study shows the importance in a small-to-medium sized accident and emergency unit as well, where there is no senior cover available out-of-hours for final radiological interpretation. A morning trauma meeting which covers reviewing admitted patients as well as non-admission orthopaedic referrals has an effective risk management solution to early detection of missed and wrong diagnoses.