Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis.

A genome-wide screen was conducted using a large white sample to identify QTLs for FNCS geometry. We found significant linkage of FNCS parameters to 20q12 and Xq25, plus significant epistatic interactions and sex-specific QTLs influencing FNCS geometry variation. INTRODUCTION: Bone geometry, a highly heritable trait, is a critical component of bone strength that significantly determines osteoporotic fracture risk. Specifically, femoral neck cross-sectional (FNCS) geometry is significantly associated with hip fracture risk as well as genetic factors. However, genetic research in this respect is still in its infancy. MATERIALS AND METHODS: To identify the underlying genomic regions influencing FNCS variables, we performed a remarkably large-scale whole genome linkage scan involving 3998 individuals from 434 pedigrees for four FNCS geometry parameters, namely buckling ratio (BR), cross-sectional area (CSA), cortical thickness (CT), and section modulus (Z). The major statistical approach adopted is the variance component method implemented in SOLAR. RESULTS: Significant linkage evidence (threshold LOD = 3.72 after correction for tests of multiple phenotypes) was found in the regions of 20q12 and Xq25 for CT (LOD = 4.28 and 3.90, respectively). We also identified eight suggestive linkage signals (threshold LOD = 2.31 after correction for multiple tests) for the respective geometry traits. The above findings were supported by principal component linkage analysis. Of them, 20q12 was of particular interest because it was linked to multiple FNCS geometry traits and significantly interacted with five other genomic loci to influence CSA variation. The effects of 20q12 on FNCS geometry were present in both male and female subgroups. Subgroup analysis also revealed the presence of sex-specific quantitative trait loci (QTLs) for FNCS traits in the regions such as 2p14, 3q26, 7q21 and 15q21. CONCLUSIONS: Our findings laid a foundation for further replication and fine-mapping studies as well as for positional and functional candidate gene studies, aiming at eventually finding the causal genetic variants and hidden mechanisms concerning FNCS geometry variation and the associated hip fractures.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

血清前列腺特异性抗原增高的病理基础

对血请前列腺特异性抗原（ＰＳＡ）高于４μｇ／Ｌ，且有病理检查资料的６７例前列腺疾病患者，进行了分析。其中前列腺癌２４例，非癌前列腺病变４３例。结果显示前列腺癌组血清ＰＳＡ明显高于非癌组（Ｐ＜０．０１）。以血清ＰＳＡ１０μｇ／Ｌ为低限值，诊断癌的灵敏性为８３．３％。特异性为７４．４％，认为血请ＰＳＡ４～１０μｇ／Ｌ应视为癌的危险范围。上皮血屏障的破坏和上皮细胞增生是血清ＰＳＡ升高的基础     

人胎盘提取组织凝血活酶及其质量评价

利用人胎盘抽提得组织凝血活酶，并对其质量进行了评价，同时初步应用于临床。结果显示：用含表面活性剂的抽提剂粉碎抽提的效果较好，所得组织凝血活酶重复性、灵敏度、稳定性均令人满意；与上海荣盛生物制品厂生产的ＰＴ试剂盒比较相关性好：Ｙ＝２．７５＋０．９０５ｘ，ｒ＝０．９２５３，经相关系数ｔ检验，ｔ＝２６．５４６９，Ｐ＜０．００１，呈直线正相关。临床初步应用显示：肝病及抗凝治疗等病人ＰＴ时间明显延长，９３例正常人ｘ＝１１．３秒，ｓ＝０．９６秒，正常范围９．４２－１３．１８秒。     

Comparison of clinical outcomes of frozen-thawed blastocysts transfer in natural and hormonally controlled cycles

Objectives:To assess the clinical outcomes of frozen-thawed blastocysts transfer in natural and hormonally controlled cycles.Methods:A retrospective analysis of natural and hormonally controlled cycle for 246 frozen-thawed blastocyst transfer cycles,the clinical pregnancy rate,implantation rate,early abortion rate were compared.Results:Of the 192 hormonally controlled cycles,the cancel rate,clinical pregnancy rate per ET,implantation rate and abortion rate were 7.3%(14/192),53.9%(96/178),38.8%(131/338)and 11.5%(11/96)respectively,whereas in 54 natural cycles,these rates were 16.7%(9/54),68.9%(31/45),52.9%(45/85)and 16.1%(5/31)respectively.There was no significant difference between the two groups with regard to the clinical pregnancy and abortion rate per ET,but the cancel rate and implantation rate were higher in natural cycles.However,the pregnancy and implantation rates of patients without PCOS in hormonal control cycles(57.2%,40.9%)were similar with those in natural cycles(P>0.05).Conclusion:These findings suggested that both hormonally controlled and natural cycles had similar pregnancy outcomes in frozen-thawed blastocysts transfer.     

营养补充品中刺激剂的分析测定

介绍营养补充品中刺激剂的毛细管气相色谱和气相色谱质谱联用检测方法.试样采用碱提,液-液分配提取,以HP-5毛细管柱为分离柱,用氮磷检测器测定.实验结果表明:该方法操作简便,分析速度快,结果可靠.添加平均回收率为75.4%～143.1%,相对标准偏差为0.27%～5.5%,检出限为5～40μg/L.     

高血压病肠系膜动脉平滑肌细胞端粒酶活性表达的研究

目的 :探讨高血压病动脉平滑肌组织端粒酶活性与高血压的发病关系。方法 :采用PCR -ELISA法检测 30例高血压病患者和 2 0例血压正常者肠系膜动脉平滑肌细胞 (SMC)端粒酶活性。结果 :高血压患者端粒酶阳性表达 2 8例 (93.3% )。血压正常者端粒酶阳性表达 3例 (15 % )。差异非常显著 (P <0 .0 5 )。结论 :高血压病动脉平滑肌细胞端粒酶活性的表达升高 ,可能与高血压发病有关。     

Complex segregation analyses of bone mineral density in Chinese

China has the largest population in the world; approximately 7% of the total population suffers from primary osteoporosis. Osteoporosis is mainly characterized by low bone mineral density (BMD). In the present study, familial correlation and segregation analyses for spine and hip BMDs have been undertaken for the first time in a Chinese sample composed of 401 nuclear families with a total of 1,260 individuals. The results indicate a major gene of additive inheritance for hip BMD, whereas there is no evidence of a major gene influencing spine BMD. Significant familial residual effects are found for both traits, and heritability estimates (±SE) for spine and hip BMDs are 0.807(0.099) and 0.897(0.101), respectively. Sex and age differences in genotype‐specific average BMD are also observed. This study provides the first evidence quantifying the high degree of genetic determination of BMD variation in the Chinese.     

探索经络本质的新途径

作者首先对近20年来我国在经络本质方面的研究工作进行了回顾与评价。指出若长期在宏观(组织解剖学)层面上难以找到经络的物质存在，应努力在多层面、多学科交叉领域系统开展研究；特别是在微观层面，只有充分借助细胞分子生物学、基因组学、生物物理学、生物化学的理论和实验成果，构筑研究平台，方能有所创新和突破。作者强调经络本质的研究重点应放在对调控人体经络生理网络的信息载体上，并且根椐细胞信号转导的理论和相关实验数据指出，当针刺穴位时，细胞所产生的Ca^2 振荡(在胞内)和Ca^2 波(在胞问)的幅频信号中可能蕴含有经络通路和生理功能调节信息；Ca^2 通过与其结合的蛋白(如钙调素CaM等)参与了人体从生殖、代谢、肌缩运动。直至认知、记忆的几乎所有生命过程。因此，作者认为Ca^2 以及配合针刺实现在细胞问Ca^2 波接力传递的三磷酸肌醇(IP3)，可能就是人们长期探寻的调控人体经络网络的信息载体，它们联同在经线上的细胞缝隙连接蛋白，构成了经络的物质基础。作者最后指出了进一步研究的途径和实验方法。