Combined profile of the tandem repeats CAG, TA and CA of the androgen and estrogen receptor genes in breast cancer

Purpose Case–control studies have reported inconsistent results concerning the association between polymorphisms in the androgen and estrogen receptor (ER) genes and breast cancer. While several studies investigated the association between the androgen receptor (AR) gene, CAG repeat and breast cancer, for the CA and TA repeats in the ER genes there are considerably fewer studies (one for CA and none for TA).Methods We have investigated the potential link between three tandem repeats (CAG, TA, and CA) in the AR, ERs α and β genes, respectively, and breast cancer. DNA was isolated from 153 invasive breast tumors and 318 controls, and the three tandem repeats were sized by polyacrylamide electrophoresis. Number of repeats in each allele and the total repeats of both alleles were taken as variables for classification into dichotomous groups using the median of each variable in the control group as cut-off point. Relationship between polymorphic tandem repeats and breast cancer was assessed by multivariate logistic regression models.Results Three variables combined, longer CAGsum (≥28), shorter TA (<23) and CA (<23) repeats could constitute a possible genetic profile associated with breast cancer.Conclusions Our results confirm previous reports regarding an association between longer CAG repeats and breast cancer. In addition to that, we found that the combination of long CAG, short TA and CA repeats are strongly associated with breast cancer.This paper was initially submitted with an additional co-author who withdrew the co-authorship during the review process. All listed authors have now signed that they agree with the content of the current paper.     

Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling

Enpp1 is a membrane-bound glycoprotein that regulates bone mineralization by hydrolyzing extracellular nucleotide triphosphates to produce pyrophosphate. Enpp1 dysfunction causes human diseases characterized by ectopic calcification. Enpp1 also inhibits insulin signaling, and an Enpp1 polymorphism is associated with insulin resistance. However, the precise mechanism by which Enpp1 functions in these cellular processes remains elusive. Here, we report the crystal structures of the extracellular region of mouse Enpp1 in complex with four different nucleotide monophosphates, at resolutions of 2.7–3.2 Å. The nucleotides are accommodated in a pocket formed by an insertion loop in the catalytic domain, explaining the preference of Enpp1 for an ATP substrate. Structural mapping of disease-associated mutations indicated the functional importance of the interdomain interactions. A structural comparison of Enpp1 with Enpp2, a lysophospholipase D, revealed marked differences in the domain arrangements and active-site architectures. Notably, the Enpp1 mutant lacking the insertion loop lost the nucleotide-hydrolyzing activity but instead gained the lysophospholipid-hydrolyzing activity of Enpp2. Our findings provide structural insights into how the Enpp family proteins evolved to exert their diverse cellular functions.     

Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells

AIM：To evaluate the influence of MUC1 mucin variable number of tandem repeats （VNTR） variability on H pylori adhesion to gastric cells.
METHODS： Enzyme linked immunosorbent assay （ELISA）-based adhesion assays were performed to measure the adhesion of different H pylori strains （HP26695 and HPTx30a） to gastric carcinoma cell lines （GP202 and MKN45） and GP202 clones expressing recombinant MUC1 with different VNTR lengths.
RESULTS： Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher （P 〈 0.05） adhesion to all the cell lines and clones tested, when compared to the non-pathogenic strain HPTx30a. Bacteria showed a significantly higher （P 〈 0.05） adhesion to the GP202 cell line, when compared to the MKN45 cell line. Furthermore, both strains showed a significantly higher （P 〈 0.05） adhesion to GP202 clones with larger MUC1 VNTR domains.
CONCLUSION： This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells. The extent of bacterial adhesion depends on the size of theMUC1 VNTR domain. The adhesion is further dependent on bacterial pathogenicity and the gastric cell line. MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.     

2006年人禽流感H_5N_1毒株PA基因特性、变异和进化

目的通过对人禽流感H5N1毒株PA基因序列的变异分析,揭示毒株PA基因特征、变异与进化。方法检测广东地区人禽流感H5N1毒株PA基因核苷酸序列,同时检索全球人禽流感H5N1毒株PA基因序列,采用MEGA4.0软件对检索的人禽流感H5N1毒株PA基因核苷酸序列进行比对和分析;并结合流行病学资料对变异毒株进行进化速度分析。结果PA蛋白呈酸性,等电点pH5.4。1997-2006年52株毒株PA基因核苷酸序列同源性分成两组,1997年毒株为第一组(G1),2003-2006年香港、越南、泰国、印尼、中国大陆毒株、土耳其、伊拉克、阿塞拜疆、埃及毒株为第二组(G2)。PA基因114个氨基酸位点置换,占15.9(114/716),其中2003-2006年毒株PA基因有17个氨基酸位点不同于1997年毒株。PA基因Ks值为30.9×10-6～46.1×10-6Nt/d,Ka值为4.50×10-6～8.13×10-6Nt/d;而PA基因的同义突变速度是错义突变速度的5.7～6.9倍,显示PA基因受到机体免疫压力较小;检验发现PA基因进化存在负选择性压力。PA基因中潜在的7个糖基化位点基本稳定,毒株IDNS-569H-06的PA基因半胱氨酸发生置换(S224C)。结论PA基因进化分成两系列,PA基因进化特点是自发突变较快,而受到机体免疫机制压力较小;A基因与其它多聚酶基因(PB2和PB1)比较,核苷酸序列同源性和进化在时间特征和地区特征方面具有一致性;来自中国大陆的毒株进化值得关注。人禽流感H5N1毒株PA基因在自然界变异频繁,可能影响HN毒株致病性和在人-人传播能力。     

nm23H1 expression and its role in the evolution of non-gastrointestinal malignancies

The role of nm23H1 genetic instability is not limited to gastrointestinal malignancies. A similar close relationship exists between nm23H1 genetic instability and other non gastrointestinal systemic malignancies. For instance, in oral malignant melanomas with lymphoid metastasis, the nm23H1 expression is significantly lower in contrast to tumors with no lymphoid metas- tasis. Similarly, increased metastasis is seen in non small cell lung cancers following down regulation of nm23H1 in conjunction with KAI-1 down regulation. There is an inverse relationship between tumor stage and metastasis and nm23H1 expression in individuals with prostate carcinomas and a similar relationship ex- ists between microsatellite instability of the nm23H1 gene and ovarian carcinogenesis. For instance, nearly 70.5% of stage Ⅰ-Ⅱ ovarian tumors express nm23H1 in sharp contrast to only 25% of stage Ⅲ-Ⅳ ovarian tumors. As is clearly evident, nm23H1 has a major role in gastrointestinal and non-gastrointestinal carcinogenesis. The coming few years will hopefully see the development of new strategies by virtue of which we can alter nm23H1 expression and thus decrease the risk of metastasis in malignant tumors.     

Inhibition of the RhoA/Rho-associated,coiled-coil-containing protein kinase-1 pathway is involved in the therapeutic effects of simvastatin on pulmonary arterial hypertension

Background: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. Methods: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i.p.) on the first day of the study. The MCT + simvastatin group received simvastatin (2 mg/kg) daily for 4 weeks, after which pulmonary arterial pressure was measured by right heart catheterization. The protein and mRNA levels of Rho and ROCK1 were measured by immunohistochemistry, Western blot, and PCR. For in vitro experiments, human pulmonary endothelial cells were divided into seven groups: control, simvastatin, monocrotaline pyrrole (MCTP), MCTP + simvastatin, MCTP + simvastatin + mevalonate, MCTP + simvastatin + farnesyl pyrophosphate (FPP), and MCTP + simvastatin + FPP + geranylgeranyl pyrophosphate (GGPP). After 72 h exposed to the drugs, the protein and mRNA levels of RhoA and ROCK1 were measured by Western blot and PCR. Results: The MCT group showed increased mean pulmonary arterial pressure, marked vascular remodeling, and increased protein and mRNA levels of RhoA and ROCK1 compared to the other groups (P < 0.05). In vitro, the MCTP group showed a marked proliferation of vascular endothelial cells, as well as increased protein and mRNA levels of RhoA and ROCK1 compared to the MCTP + simvastatin group. The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Conclusions: Simvastatin improved vascular remodeling and inhibited the development of PAH. The effects of simvastatin were mediated by inhibition of RhoA/ROCK1. Simvastatin decreased RhoA/ROCK1 overexpression by inhibition of mevalonate, FPP, and GGPP synthesis.     

RNAi沉默Stat1基因对胶质瘤细胞FAT10表达的影响

目的 观察U251人胶质瘤细胞中Stat1基因沉默对FAT10蛋白表达的影响.方法 采用电穿孔法将Stat1 siRNA转染人胶质瘤细胞系U251细胞,采用Western印迹检测各组细胞中Stat1和FAT10蛋白的表达变化,用染色体核型分析Stat1干扰对FAT10过表达而导致的非整倍体现象的阻断作用.结果 Westem印迹结果显示,Stat1 siRNA干扰可以有效抑制U251细胞中Stat1的表达,并且通过抑制Stat1可以有效抑制TNF-α诱导的FAT10高表达,进而通过有效抑制TNF-α诱导的FAT10高表达而阻断TNF-α诱导的非整倍体现象.结论 Stat1的表达下调可以抑制TNF-α诱导的FAT10高表达及非整倍体现象.     

不同类型糖尿病患者的血清干扰素γ诱导蛋白10的改变及其意义

目的探讨不同类型糖尿病患者的血清干扰素7诱导蛋白10（IP—10）水平及其意义。方法检测1型糖尿病（T1DM，n=78）、2型糖尿病（T2DM，n=49）和正常对照组（NC，n=33）的IP—10水平。T1DM组根据病情进展分为经典T1DM和成人隐匿性自身免疫糖尿病（LADA）组；又根据胰岛自身抗体IAA阳性与否分为自身免疫性T1DM和特发性T1DM组。T2DM组根据大动脉内中膜厚度IMT分为无动脉粥样硬化AS组和有AS组。Cl／SA检测各组IP-10水平。结果（1）IP-10水平在T1DM、T2DM与NC组之间无统计学差异。（2）胰岛自身抗体阳性的自身免疫性T1DM组IP-10水平高于NC组，差异有统计学意义，而T2DM与NC组无统计学差异；病程不同的T1DM IP-10水平无统计学差异。（3）伴或不伴动脉粥样硬化病变的T2DM亚组IP—10水平无统计学差异。结论自身免疫性1型糖尿病患者IP-10水平升高，可能与其介导Th1型细胞免疫反应有关。     

From the Cover: Dietary changes of large herbivores in the Turkana Basin,Kenya from 4 to 1 Ma

A large stable isotope dataset from East and Central Africa from ca. 30 regional collection sites that range from forest to grassland shows that most extant East and Central African large herbivore taxa have diets dominated by C₄ grazing or C₃ browsing. Comparison with the fossil record shows that faunal assemblages from ca. 4.1–2.35 Ma in the Turkana Basin had a greater diversity of C₃–C₄ mixed feeding taxa than is presently found in modern East and Central African environments. In contrast, the period from 2.35 to 1.0 Ma had more C₄-grazing taxa, especially nonruminant C₄-grazing taxa, than are found in modern environments in East and Central Africa. Many nonbovid C₄ grazers became extinct in Africa, notably the suid Notochoerus, the hipparion equid Eurygnathohippus, the giraffid Sivatherium, and the elephantid Elephas. Other important nonruminant C₄-grazing taxa switched to browsing, including suids in the lineage Kolpochoerus-Hylochoerus and the elephant Loxodonta. Many modern herbivore taxa in Africa have diets that differ significantly from their fossil relatives. Elephants and tragelaphin bovids are two groups often used for paleoecological insight, yet their fossil diets were very different from their modern closest relatives; therefore, their taxonomic presence in a fossil assemblage does not indicate they had a similar ecological function in the past as they do at present. Overall, we find ecological assemblages of C₃-browsing, C₃–C₄-mixed feeding, and C₄-grazing taxa in the Turkana Basin fossil record that are different from any modern ecosystem in East or Central Africa.The expansion of C₄ biomass beginning in the late Miocene marks a major vegetation change in the history of Earth. Today C₄ plants comprise ca. 50% of net primary productivity (NPP) in the tropics (1) yet contributed less than 1% of NPP only 10 million years ago. C₄ plants are primarily grasses and sedges, although C₄ photosynthesis is known to be used in ∼20 plant families (2, 3). C₄ photosynthesis is an adaptation to low (ca. <500 ppm by volume) concentrations of CO₂ in Earth’s atmosphere along with high growing-season temperatures (4). Although genetic evidence indicates an Oligocene origin of C₄ photosynthesis in the grasses (5, 6), macrofossil evidence for C₄ photosynthesis in grasses is extremely sparse (7, 8).The expansion of C₄ biomass has been documented through stable isotopes in paleosols (9–12), grass phytoliths (13), herbivore tooth enamel (14–16), and biomarkers in deep-sea sediments (17, 18). At 10 Ma in Africa, Asia, and North America, the δ¹³C values for equid tooth enamel indicate a diet dominated by C₃ vegetation; by ca. 7 Ma, equids in Africa have a diet dominated (>75%) by C₄ vegetation (14, 15). In East Africa today there is a distinct difference in diets of major herbivores, with most mammals either being predominantly browsing (>ca. 75% C₃) or grazing (>ca. 75% C₄), and there are relatively few mixed feeders (Fig. 1).Open in a separate windowFig. 1.δ¹³C₁₇₅₀ values for tooth enamel (or equivalent) for >1,900 mammals from East and Central Africa (principal localities in SI Appendix, Table S1; data from Dataset S1).A recent study of the early transition of C₃ to C₄ dietary change in the Turkana Basin from 10 Ma to ca. 4 Ma (15) showed that equids were the earliest mammals to fully exploit the C₄ dietary resource, attaining a predominantly C₄-grazing diet by 7 Ma. Other mammal groups (hippopotamids, elephantids, and bovids) changed to a C₄ diet later than did the equids. In this paper we document dietary changes in the major Artiodactyla-Perissodactyla-Proboscidea (APP) taxa in the Turkana Basin between ca. 4 Ma and 1 Ma and compare those to dietary preferences of extant APP taxa in East and Central Africa. The Turkana Basin has an excellent stratigraphy (19–22) with excellent preservation of fossils from 4 to 1 Ma; this study focuses on fossils recovered from the Koobi Fora, Kanapoi, and Nachukui Formations of northern Kenya.We compare dietary changes within the major APP taxa through the past 4 Ma in the formations listed above using >900 individual fossils that represent the major taxa collected within the principal stratigraphic intervals of these formations. Fossil mammalian diets are compared with those of >1,900 extant mammal individuals sampled from >30 different regions and habitats in eastern and central Africa. We compare the ecosystem structure (C₃ browsers, C₃/C₄ mixed diets, and C₄ grazers) through the Pliocene and Pleistocene and document changes in ungulate diets over time.     

大骨节病患者血清NO、NOS、sFas/APO-1检测分析

目的探讨一氧化氮(NO)、一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、可溶性Fas(sFas)诱导大骨节病发生发展的作用与特点,为大骨节病防治研究提供新的思路。方法选择陕西省永寿县、榆林市榆阳区大骨节病区与咸阳市渭城区非大骨节病区120例调查对象,分为成人、儿童大骨节病组;成人、儿童病区对照组;成人、儿童非病区对照组,每组20例,平均年龄、性别无差别。用酶还原法检测了血清NO,化学比色法检测了血清NOS、iNOS,ELISA法检测了血清sFas水平。结果①大骨节病成人组血清NO、iNOS显著高于病区和非病区成人对照组(P< 0.05);血清NOS、sFas/APO鄄1水平高于非病区成人对照组(P< 0.005)。②大骨节病儿童组血清NO高于非病区儿童对照组(P< 0.05);血清NOS、iNOS均高于病区和非病区儿童对照组(P< 0.005)。结论儿童大骨节病发生发展中NO诱导途径起一定的作用,而Fas途径作用不明显。当疾病发展到成人大骨节病时,二者均起一定作用。     

Sequence type 1 group B Streptococcus,an emerging cause of invasive disease in adults,evolves by small genetic changes

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans.The recent increase in large-scale DNA sequencing feasibility has allowed for significant advances in understanding the population genetics of bacteria that cause disease in humans (1, 2). A major outcome of the rapid expansion of available bacterial genomes has been the appreciation of the marked intraspecies genetic variability present in a wide variety of human bacterial pathogens (3, 4). This genetic variation can have profound impact on host–pathogen interaction by affecting transmissibility, infection severity, and antimicrobial resistance (2, 5, 6). The observed genetic intraspecies variability can arise via many distinct mechanisms including large-scale events such as recombination and bacteriophage-mediated horizontal gene transfer as well as small-scale genetic changes such as short insertions, deletions, and/or single nucleotide changes (2, 3, 5).Group B Streptococcus (GBS) is a common colonizer of humans that emerged in the 1970s as the leading cause of invasive bacterial disease in neonates and infants less than 3 mo of age (7). GBS is divided into 10 serotypes based on the carbohydrate composition of its sialic acid containing capsule, but gene content at the genomic level does not necessarily correlate with capsular serotype (8, 9). A seven-gene multilocus sequence typing (MLST) allows for the classification of the majority of GBS strains isolated from humans into five major clonal complexes (CCs) with a recent study by Da Cunha et al. showing that the major GBS CCs are primarily derived from a limited number of tetracycline-resistant clones, suggesting a key role of tetracycline resistance in GBS strain emergence (10, 11). CC-17 GBS strains have been particularly well studied given their role as the major cause of severe, invasive infant disease (10, 12). In contrast, serotype V strains cause a larger percentage of invasive disease in nonpregnant adults compared with neonates (13–15). Importantly, rates of invasive GBS disease have been increasing during the past 25 y in nonpregnant adults, with a significant part of the rise resulting from serotype V GBS strains (15–17).Despite the clear and increasing impact of serotype V strains, data are limited regarding molecular epidemiology of serotype V GBS causing invasive disease in nonpregnant adults (14, 15, 18). Only a few studies of serotype V strains have investigated the noncapsular genetic makeup of the strains, and those that have done so have included colonizing and invasive GBS strains isolated from infants or have not described the clinical origin of the tested strains (18, 19). Thus, we sought to analyze a large cohort of clinically well-defined, geographically distinct, and temporally disparate GBS isolates by using a whole-genome approach to elucidate the population structure of serotype V GBS causing invasive disease in nonpregnant adults. Data using non–genome-wide level approaches found that many serotype V strains were closely related, suggesting that a particular clone, rather than a genetically diverse array of strains arising from large-scale recombination, might be responsible for the majority of serotype V disease (18). Thus, we specifically sought to test the hypothesis that genetic diversity among invasive serotype V GBS strains is driven by small genetic changes at loci that are critical to GBS host–pathogen interaction.     

Expression of progesterone receptor membrane component 1 and its partner serpine 1 mRNA binding protein in uterine and placental tissues of the mouse and human

Although activation of the nuclear progesterone (P(4)) receptor (PGR) is required for uterine function, some of the actions of P(4) are mediated through a PGR-independent mechanism. The receptors that account for the PGR-independent actions have not been identified with certainty. The purpose of this study was to assess the expression, localization and hormonal regulation of two novel P(4) receptor candidates, P(4) receptor membrane component (PGRMC) 1 and PGRMC2, as well as the PGRMC1 partner Serpine 1 mRNA binding protein (SERBP1). Unlike Pgrmc1 and Serbp1, which remained unchanged throughout the estrous cycle, Pgrmc2 was highly up-regulated during proestrus and metestrus. Immunohistochemical analyses suggest that PGRMC1 and SERBP1 promote differentiation, since the expression of these proteins increased in endometrial cells undergoing steroid-depended terminal differentiation. Progesterone rather than estrogen appears to be primarily responsible for up-regulating the expression of PGRMCs. PGRMC1 and SERBP1 also showed overlapping patterns of expression in the human placenta and associated membranes with the most abundant expression in smooth muscle of the placental vasculature, villous capillaries and the syncytiotrophoblast. Based on these findings, it is proposed that PGRMC1:SERBP1 protein complex functions in events important to early pregnancy including cellular differentiation, modulation of apoptosis and steroidogenesis. These studies provide a platform from which to build a clearer understanding of P(4) actions in the female reproductive tract and placental tissues that are mediated by non-classical mechanisms.     

COPD患者血浆IL-17、sICAM-1的研究

目的探讨慢性阻塞性肺疾病（COPD）患者血浆白细胞介素-17（IL-17）、可溶性细胞间粘附分子-1（sICAM-1）浓度的变化及相关性。方法30例急性加重期和稳定期COPD患者、25例健康体检者,分别查血常规、测定肺功能,用ELISA法检测血浆IL-17、sICAM-1浓度。结果同一患者COPD急性加重期血浆IL-17浓度、sICAM-1浓度均明显高于稳定期（P〈0.01,P〈0.01）;患者COPD急性加重期血浆IL-17浓度、sICAM-1浓度明显高于健康对照组（P〈0.01,P〈0.01）,患者COPD稳定期血浆IL-17浓度、sICAM-1浓度明显高于健康对照组（P〈0.01,P〈0.01）且在急性加重期IL-17、sICAM-1与Neu／Leu％呈正相关（r=0.824,P〈0.01;r=0.827,P〈0.01）。结论COPD急性加重期及稳定期IL-17、sICAM-1水平显著升高,提示IL-17、sICAM-1参与了COPD的发病,可能是引起肺内炎症细胞浸润及肺实质破坏的主要原因之一。     

Relation between the insulin lowering rate and changes in bone mineral density: Analysis among subtypes of type 1 diabetes mellitus

Aims/IntroductionThe bone mineral density in patients with type 1 diabetes mellitus is reduced due to impaired insulin secretion. However, it is unclear whether the rate of bone mineral density reduction is affected by the type 1 diabetes mellitus subtype. This study aimed to clarify the difference in bone mineral density across type 1 diabetes mellitus subtypes: slowly progressive (SP), acute‐onset (AO), and fulminant (F).MethodsThis was a retrospective, single‐center, cross‐sectional study conducted on 98 adult type 1 diabetes mellitus patients. The main outcome included the bone mineral density Z‐score (BMD‐Z) measured at the lumbar spine and femoral neck.ResultsThe lumbar spine BMD‐Z was lower in the acute‐onset than in the slowly progressive subtype (P = 0.03). No differences were observed when compared with the fulminant subtype. The femoral neck BMD‐Z tended to be higher in the slowly progressive than in the acute‐onset and fulminant subtypes. Multiple regression analyses showed that the lumbar spine BMD‐Z was associated with subtypes (AO vs SP) (P = 0.01), but not subtypes (F vs SP), adjusted for sex, duration, retinopathy, and C‐peptide immunoreactivity (CPR). When the patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the acute‐onset or fulminant than in the slowly progressive subtype. In contrast, the lumbar spine and femoral neck BMD‐Z differed between the acute‐onset and slowly progressive only in the second tertiles (both P < 0.01), with a similar tendency between the fulminant and slowly progressive subtypes.ConclusionsAmong the type 1 diabetes mellitus subtypes, bone mineral density undergoes time‐dependent changes, which reveals that the bone mineral density decline follows the impaired insulin secretion. These results provide novel insights into the association between the low insulin exposure duration and bone mineral density.     

实验性心房颤动血栓形成时内皮型一氧化氮合酶和纤溶酶原激活剂抑制物-1的变化

目的研究心房颤动(房颤)犬心房心内膜一氧化氮(NO)浓度、内皮型一氧化氮合酶(eNOS)和纤溶酶原激活剂抑制物-1(PAl-1)蛋白表达的变化,探讨房颤左房血栓形成的可能机制。方法应用埋藏式高频心脏起搏器快速起搏心房(400次／min)6周,建立房颤犬动物模型。采用ISO-NOP3005N0敏感电极测定心内膜NO含量,Western blot和免疫组化检测eNOS、PAl-1蛋白表达,酶联免疫吸附双抗体夹心法检测血浆PAl-1含量。结果房颤组左房心内膜NO含量明显低于窦性心律组,eNOS蛋白表达下调,PAl-1蛋白表达上调,右房无明显变化。房颤组血浆PAl-1含量亦明显高于窦性心律组。结论房颤引起的左房心内膜NO含量降低、eNOS蛋白表达下调、PAl-1蛋白表达上调可能是左房血栓形成的重要原因。     

免疫受损大鼠感染铜绿假单胞菌时细胞间黏附分子1及基质金属蛋白酶2、9的变化

目的 了解免疫受损大鼠铜绿假单胞菌肺部感染前后肺组织中细胞间黏附分子（ICAM）-1、基质金属蛋白酶（MMP）-2和MMP-9的改变及其与肺部炎症反应和肺损伤的关系。方法 建立免疫受损大鼠铜绿假单胞菌肺部感染的模型，观察其肺部炎症反应，测定湿／干比和支气管肺泡灌洗液中总蛋白（TP）了解肺损伤情况，对其肺组织分别行ICAM-1、MMP-2和MMP-9免疫组织化学研究。结果 1．铜绿假单胞菌肺部感染后，两组大鼠肺泡上皮细胞中ICAM-1染色强度较未感染时增加，接种后6h、9h、24h明显高于接种前（P〈0．05）；2．两组大鼠在铜绿假单胞菌肺部感染肝，肺组织中MMP-2染色增强，于接种后6h或9h达高峰，并持续至24h。两组大鼠感染前后MMP-2在各组织结构中的积分差异无统计学意义。MMP-9在感染前后的改变与MMP-2相仿；3．两组大鼠组织中ICAM-1积分与中性粒细胞半定量计数具有相关性（对照组rs=0．64l，P=0．001，免疫受损组rs=0．668，P〈0．001）；4．两组大鼠肺组织中MMP-2、MMP-9染色积分与PMN平定量计数呈正相关（P〈0．01）；5．免疫受损组大鼠支气管上皮细胞中MMP-9染色强度积分与TP具相关性（rs=0．434，P〈0．05），肺泡上皮细胞、小血管内皮细胞及内皮下组织中MMP-2染色强度与TP皆具相关性（rs分别为0．457、0．492、0．429，P00．05）。结论 免疫受损大鼠肺部铜绿假单胞菌感染后，肺组织中ICAM-1、MMP-2、MMP-9免疫组织化学显示染色增强，于感染后6～9h达高峰，与免疫受损大鼠肺组织中明显的中性粒细胞浸润及严重的肺损伤有关。     

深圳市宝安区医务人员甲型H1N1流感疫苗接种率及影响因素研究

目的了解深圳市宝安区医务人员甲型H1N1流感疫苗接种率及其影响因素。方法在宝安区区级医院、街道医院以及所辖社区健康服务中心中随机抽取770名医务人员作为调查对象,进行不记名问卷调查。采用卡方检验和Logistic回归分析分别对疫苗接种率的影响因素进行单因素和多因素分析。结果宝安区医务人员甲型H1N1流感疫苗接种率为55.03%,未接种的主要原因是担心出现疫苗不良反应,占39.10%。影响疫苗接种率的因素分别为高文化程度(大专:OR=0.462,95%CI 0.269~0.794;大学及以上:OR=0.250,95%CI 0.140~0.446)、医疗岗位为护士(OR=0.392,95%CI 0.228~0.675)、工作年限≤5年(OR=0.303,95%CI 0.197~0.465)、知道甲流疫苗接种时间(OR=1.413,95%CI 1.022~1.953)和近3年接种过季节性流感疫苗(OR=3.822,95%CI 2.634~5.544)等。结论宝安区医务人员甲流疫苗接种率较高,但仍需加强甲流疫苗有效性和安全性宣传,重点为大专以上文化程度、护士、工作年限小于5年、不知道甲流接种时间和近3年无季节性流感疫...