The epidemiology of preterm labour

Although the definition of preterm birth is birth before 37 completed weeks, the major transition in terms of needing special care occurs between 34 and 37 weeks. The Homo sapiens neonate is born much more immature than other anthropoid species, perhaps because earlier birth has evolved to avoid the large head of the human fetus becoming impacted in the small pelvis of the mother, who has become adapted to a bipedal gait. The main burden of preterm birth exists in developing countries. There are no accurate recent worldwide data, but estimates of preterm birth rates range from 5% in developed countries to 25% in developing countries. The preterm delivery rate has been relatively stable at 5–10% in developed countries for many years. The North Thames database of 517,381 pregnancies demonstrates significant ethnic variation in preterm birth rates, with higher rates in black women. This is associated with an accelerated rate of maturity in the black fetus and neonate, with correspondingly lower gestation-specific neonatal mortality rates below 38 weeks, and higher at 38 weeks of gestation and beyond. Ethnic differences can explain only a very small proportion of global preterm births. The greatest aetiological factor worldwide is infection, mainly due to malaria and HIV. In developed countries, iatrogenic delivery is responsible for almost half of the births between 28 and 35 weeks; hypertension and pre-eclampsia are the major pathologies. Other factors include multiple pregnancy, intrauterine growth restriction, maternal stress and heavy physical work.     

Personality Vulnerability, Psychiatric Diagnoses, and Symptoms: Cluster Analyses of the Sociotropy-Autonomy Subscales

To determine whether psychiatric outpatients represented distinct personality types with respect to sociotropy and autonomy, the Sociotropy and Autonomy Scale (SAS; Beck, Epstein, Harrison, & Emery, 1983) was administered to 2,067 psychiatric outpatients with predominantly DSM-III-R mood or anxiety disorders. Both agglomerative-hierarchical and nonhierarchical cluster analyses performed on the six subscales of the SAS revealed four personality types—Independence, Dependence, Individualistic Achievement and Low Scoring Controls. Loglinear analyses failed to reveal significant differences between clusters in specific Axis I diagnoses, though a significantly higher proportion of the sociotropic Dependent type had a Dependent or Avoidant personality disorder. The autonomous Independent and sociotropic Dependent clusters also had higher levels of self-reported and clinically rated depression and anxiety than did the Individualistic Achievement and Low Scoring groups. The implications of these results for understanding the relationship between personality and psychopathology are discussed.     

Neuroprotection by a bile acid in an acute stroke model in the rat.

Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, is a strong modulator of apoptosis in both hepatic and nonhepatic cells, and appears to function by inhibiting mitochondrial membrane perturbation. Excitotoxicity, metabolic compromise, and oxidative stress are major determinants of cell death after brain ischemia-reperfusion injury. However, some neurons undergo delayed cell death that is characteristic of apoptosis. Therefore, the authors examined whether TUDCA could reduce the injury associated with acute stroke in a well-characterized model of transient focal cerebral ischemia. Their model of middle cerebral artery occlusion resulted in marked cell death with prominent terminal deoxynucleotidyl transferase-mediated 2;-deoxyuridine 5;-triphosphate-biotin nick end labeling (TUNEL) within the ischemic penumbra, mitochondrial swelling, and caspase activation. Tauroursodeoxycholic acid administered 1 hour after ischemia resulted in significantly increased bile acid levels in the brain, improved neurologic function, and an approximately 50% reduction in infarct size 2 and 7 days after reperfusion. In addition, TUDCA significantly reduced the number of TUNEL-positive brain cells, mitochondrial swelling, and partially inhibited caspase-3 processing and substrate cleavage. These findings suggest that the mechanism for in vivo neuroprotection by TUDCA is, in part, mediated by inhibition of mitochondrial perturbation and subsequent caspase activation leading to apoptotic cell death. Thus, TUDCA, a clinically safe molecule, may be useful in the treatment of stroke and possibly other apoptosis-associated acute and chronic injuries to the brain.     

骨保护素、核因子κB受体活化因子配体与绝经后骨质疏松症中医证型变化的关系

目的:探讨骨保护素、核因子κB受体活化因子配体在绝经后骨质疏松症不同中医证型间变化的内在关系,为绝经后骨质疏松症的辨证分型提供理论和实验依据。方法:于2005-09/2006-09选择广州中医药大学附属骨伤科医院和广州军区总医院入院及门诊治疗的绝经后骨质疏松症患者108例。根据中医辨证分型的原则分为肾阳虚组、肝肾阴虚组、脾肾阳虚组、气滞血瘀组,组间在年龄分布、绝经年限及体质量指数有可比性(P>0.05)。采用双能X射线骨密度仪测量第2～4腰椎椎体侧位的骨密度。采用ELISA法测定患者雌激素、骨保护素、核因子κB受体活化因子配体的水平,应用方差分析方法分析绝经后骨质疏松症患者骨保护素、核因子κB受体活化因子配体、骨密度和雌激素在不同证型间的关系。结果:气滞血瘀组骨保护素和核因子κB受体活化因子配体水平高于肾阳虚组、脾肾阳虚组、肝肾阴虚组,差异均有显著性意义[分别为(504.71±353.14),(332.03±323.88),(448.22±304.16),(418.78±382.66)ng/L;(1348.22±489.87),(1245.62±510.53),(1258.31±575.71),(1233.14±594.32)ng/L,F=1196.31,287.54;137.42,216.56;280.39,342.72;P<0.01],雌激素水平及骨密度值明显低于肾阳虚组,差异有显著性意义[分别为(0.48±0.04),(0.68±0.08)g/cm2;(18.77±9.03),(22.14±8.16)ng/L,F=9.39,17.93,P<0.05]。脾肾阳虚组和肝肾阴虚组雌激素水平低于肾阳虚组,差异有显著性意义[分别为(19.44±8.67),(19.41±8.72),(22.14±8.16)ng/L,F=11.23,11.25,P<0.05],而血清骨保护素、核因子κB受体活化因子配体、骨密度组间比较差异无显著性意义(P>0.05)。结论:骨保护素/核因子κB受体活化因子配体/核因子κB受体活化因子平衡关系的破坏与绝经后骨质疏松症的发生发展有关,“肾阳虚损,瘀血阻滞”病机转变可能是绝经后骨质疏松症病理演变的一个重要环节。血清骨保护素、核因子κB受体活化因子配体水平有可能作为区别绝经后骨质疏松症气滞血瘀型与其他三型的客观检测指标。     

重组人粒细胞集落刺激因子动员对淋巴细胞功能相关抗原1/细胞间黏附分子1信号途径诱导CD4+T淋巴细胞活化及增殖的影响

目的:观察在异基因外周血造血干/祖细胞移植中重组人粒细胞集落刺激因子动员对淋巴功能相关抗原1/细胞间黏附分子1信号途径诱导的外周血CD4~ T淋巴细胞的影响,验证重组人粒细胞集落刺激因子动员对淋巴细胞功能相关抗原1/细胞间黏附分子1信号通路的抑制作用。方法:选择2006-06/2007-06在解放军总医院血液科异基因外周血造血干细胞移植前进行重组人粒细胞集落刺激因子动员的10例健康供者,对治疗方案均知情同意,且得到医院伦理道德委员会批准。给予重组人粒细胞集落刺激因子10μg/(kg·d)进行动员,在动员前1天和动员后第5天取供者外周静脉血,用miniMACS磁珠分选系统分离纯化CD4~ T淋巴细胞.分别用CD3单克隆抗体OKT3 细胞间黏附分子1、佛波酯 离子霉素刺激活化CD4~ T淋巴细胞.用双色荧光标记检测动员前后CD4~ T淋巴细胞激活后活化标记CD69,CD25的表达;用四甲基偶氮唑盐法检测动员前后OKT3 细胞间粘黏附分子1、佛波酯 离子霉素刺激CD4~ T淋巴细胞增殖能力变化。结果:①纯化后CD4~ T淋巴细胞纯度均在90%以上。②动员后OKT3 细胞间黏附分子1组、佛波酯 离子霉素组CD4~ T淋巴细胞活化标记CD69和CD25的表达均明显低于动员前(P<0 01)。③动员后OKT3 细胞间黏附分子1组、佛波酯 离子霉素组CD4~ T淋巴细胞增殖率均明显低于动员前(P<0.05)结论:重组人粒细胞集落刺激因子动员可能抑制了淋巴功能相关抗原1/细胞间黏附分子1协同刺激信号,从而使CD4~ T淋巴细胞活化、增殖能力下降。     

Increased Risk of Breast Cancer at a Young Age in Women with Fibrous Dysplasia

Fibrous dysplasia (FD) is a rare bone disorder caused by mutations of the GNAS gene, which are also identified in malignancies. We explored the potential relationship between breast cancer and fibrous dysplasia in two fibrous dysplasia cohorts from the Netherlands and the United States. Data on fibrous dysplasia and breast cancer diagnosis were retrieved from hospital records of 134 (Netherlands) and 121 (US) female patients. Results were validated with breast cancer data of 645 female fibrous dysplasia patients from the Dutch Pathology Registry (PALGA). Standardized morbidity ratios for breast cancer were estimated with data from Dutch and US general population registries. GNAS mutation was analyzed in 9 available breast cancer specimens. A combined total of 15 patients (6 polyostotic, 9 McCune‐Albright Syndrome) had breast cancer (87% thoracic localizations). In the Netherlands, a breast cancer incidence rate of 7.5% at median age of 46 years was validated in PALGA (6.5% at age 51 years). Breast cancer risk was 3.4‐fold increased (95% confidence interval [CI] 1.6–5.9) compared with the Dutch general population; OR 13.2‐fold (95% CI 6.2–22.8) in thoracic disease. In the US cohort, breast cancer incidence rate was 4.5% at a median age of 36 years. Breast cancer risk was 3.9‐fold increased (95% CI 1.2–8.2) compared with the general population; 5.7‐fold (95% CI 1.4–13.0) in thoracic disease. GNAS mutation was positive in 4 breast cancer specimens (44%). Risk of breast cancer is increased at a younger age, particularly in polyostotic FD, suggesting that screening for breast cancer should be considered in this particular group at a younger age than currently advocated by national guidelines. © 2017 American Society for Bone and Mineral Research.     

肿瘤坏死因子α和吡格列酮对3T3-L1脂肪细胞葡萄糖转运子4表达的影响

目的:观察肿瘤坏死因子α和噻唑烷二酮类药物吡格列酮对3T3-L1脂肪细胞中葡萄糖转运子4(glucose transporter4,GLUT4)mRNA和蛋白表达的影响,并了解其是否有时间依赖性。方法:实验于2005-09/2006-05在安徽医科大学病原微生物分子生物学教研室进行。对3T3-L1细胞进行培养并诱导分化为成熟的3T3-L1脂肪细胞后随机分为对照组、肿瘤坏死因子α组和吡格列酮组3组。肿瘤坏死因子α组和吡格列酮组分别加含20μg/L肿瘤坏死因子α或10-4mol/L吡格列酮培养基培养,提取干预后1,3,6d细胞总RNA和总蛋白做RT-PCR和Western-blot,测定GLUT4mRNA和蛋白的表达,以未加任何药物干预组做对照。结果:①GLUT4mRNA表达:对照组细胞为0.506±0.049;肿瘤坏死因子α组干预后1,3,6d表达低于对照组(0.465±0.039,0.410±0.010,0.320±0.019,F=17.8,P=0.001),并随干预时间呈递减关系;吡格列酮组干预后1,3,6d表达高于对照组(0.544±0.064,0.616±0.065,0.664±0.070,F=4.87,P=0.043),且与干预时间呈正比。②GLUT4蛋白的相对含量:对照组细胞为0.624±0.093;肿瘤坏死因子α组干预后1,3,6d低于对照组(0.549±0.112,0.460±0.111,0.286±0.117,F=7.39,P=0.011),且随干预时间递减;而吡格列酮组GLUT4干预后1,3,6d高于对照组(0.693±0.098,0.750±0.106,0.866±0.074,F=4.0,P=0.048),随干预时间呈递增关系。结论:①肿瘤坏死因子α可降低3T3-L1脂肪细胞中GLUT4mRNA和蛋白表达量,吡格列酮的作用与肿瘤坏死因子α相反,两者作用均呈时间依赖性。②在3T3-L1脂肪细胞中,吡格列酮可能通过增加GLUT4的表达来提高胰岛素敏感性,并可能部分拮抗肿瘤坏死因子α诱导的胰岛素抵抗。     

细胞-支架复合物体内植入修复肌腱缺损的研究与应用

学术背景:肌腱损伤后传统的手术治疗虽然可以减轻患者的痛苦,但其功能重建结果往往不令人乐观。随着组织工程化肌腱的发展,利用组织工程技术修复肌腱缺损已成为一种新的治疗手段。目的:对种子细胞、支架材料、工程化肌腱的构建以及动物实验的方法和检测等研究进展进行综述。检索策略:由作者应用计算机检索Medline,EBSCO以及google scholar引擎中1990-02/2007-05关于组织工程化肌腱的文献,检索词"tissue engineering,engineered tissue,tissue-engineered tendon,scaffold,implantation in vivo,seed cells",检索词被分别组合进行检索,限定文献语言种类为"English"。同时计算机检索维普数据库1990-02/2007-05关于细胞和支架材料的文献,检索词"组织工程,工程化组织,种子细胞,支架,体内植入,组织工程化肌腱",限定文献语言种类为中文。纳入标准:重点选取与构建组织工程化肌腱以及体内植入修复肌腱缺损相关的基础与临床研究。排除标准:关于配子、胚胎和组织工程化骨、血管等的文章。文献评价:①文献来源有RCT,循证医学系统综述、汇总分析、个例报道、经验交流。②共检索到214篇关于细胞和支架材料以及体内植入的文献,其中与本实验关系密切的文献14篇,间接相关45篇,最终纳入35篇符合标准的文献。资料综合:目前运用于组织工程化肌腱的种子细胞主要有间充质干细胞、胚胎干细胞和成纤维细胞,多用聚乳酸、聚羟基乙酸及二者的共聚物作为支架材料。在复合物的培养方面,提出细胞-支架材料复合物体外构建过程中引入动态的机械力牵拉,可使修复后的肌腱具有更好的生物力学强度。组织工程肌腱植入体内后的检测方法除大体观察和组织学检测外,其力学性能检测也是必要的,且分子生物学检测技术也越来越多的应用于研究中。结论:组织工程化肌腱可以成为一种较好修复临床肌腱损伤的方法,但需要探索最适的种子细胞、支架材料、培养条件以及植入体内后的检测方法。