Geometry-based pressure drop prediction in mildly diseased human coronary arteries

Pressure drop (△p) estimations in human coronary arteries have several important applications, including determination of appropriate boundary conditions for CFD and estimation of fractional flow reserve (FFR). In this study a △p prediction was made based on geometrical features derived from patient-specific imaging data.     

WWOX蛋白在胰腺癌组织中的表达及其临床意义

目的探讨WWOX蛋白在胰腺癌组织中的表达及其临床意义。方法应用免疫组织化学孓P法检测人胰腺癌组织芯片150芯（包括70例胰腺癌组织和5例胰腺炎）中WWOX蛋白的表达,采用HPIAS-1000图文报告管理系统对WWOX蛋白的表达进行定量分析,并用SPSS11．5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验。结果胰腺癌组织中WWOX蛋白呈低表达,胰腺炎组织中WWOX蛋白呈高表达。结论提示WWOX基因表达下调可能在胰腺癌的发生、发展中起了重要作用。     

炎症与动脉粥样硬化及冠状动脉疾病的关系

炎症在冠状动脉疾病和其他动脉粥样硬化性疾病中起着重要作用.在动脉粥样硬化早期病变处存在大量的免疫细胞,它们所分泌的一系列细胞因子加速病变的进程,激活炎症反应导致急性冠脉综合症的发生.动脉粥样硬化,是冠状动脉疾病的主要病因,是一种炎性疾病,炎症因子参与到免疫反应过程中,使得动脉壁处的病变得以发生、蔓延和活化.     

纤粘连蛋白在实验性牙周炎鼠牙龈组织中的表达

目的:观察分析大鼠实验性牙周炎牙龈组织中纤粘连蛋白(fibronectin,FN)的表达及意义。方法:26只8周龄雄性Wistar大鼠,随机分为局部丝线结扎高糖软食4周和8周两组,每组实验动物10只,空白对照组3只。运用免疫组化方法,观察分析FN在健康牙龈组织中、牙周炎牙龈组织中的表达及意义。结果:健康牙龈组织中,FN相对均匀弥漫表达于整个牙龈结缔组织基质内;牙周炎牙龈组织中,FN表达具有部位特异性,即上皮下结缔组织最上部基质内FN表达明显下调;结合上皮根端基底细胞基底面下FN表达明显上调,表达强度和范围随结合上皮根向增生程度的增加而增强。结论:炎性刺激下调炎症中心区牙龈结缔组织基质内FN表达;炎症刺激上调结合上皮根端基底细胞基底面下FN表达,其表达强度和范围随结合上皮根向增生程度的增加而增强扩大,暗示FN参与牙龈结合上皮根向增生迁移活动。     

Heterogeneous cholinergic reactions of ringed seal coronary arteries

Coronary blood flow of some seal species is unusual in that it is highly variable in both non-diving and diving conditions and shows intermittent fluctuations, especially during dives when it frequently ceases for brief periods. We sought regulatory mechanisms governing these reactions by studying isometric tension recordings of isolated left circumflex (LC) and left anterior descending (LAD) coronary arteries of ringed seals, Phoca hispida, during reactions to a variety of agents for stimulating or blocking autonomic responses of the vascular smooth muscle. Micromolar acetylcholine (ACh) produced constriction of the small diameter segments of the LAD, but relaxation of the LC and larger segments of LAD. Both constrictions and dilations were prevented by atropine. Small vessel constriction by ACh was prevented by micromolar indomethacin and by a thromboxane receptor antagonist. Large vessel ACh dilations were prevented or reduced by rubbing off the endothelium and by the -arginine analog, -NG-nitro-arginine, an inhibitor of nitric oxide synthesis. We conclude that cholinergic, muscarinic, dilation of ringed seal large coronary arteries is mediated by endothelial-derived relaxing factor (EDRF), whereas ACh constriction of small arteries is mediated by a prostaglandin.     

N- 乙酰转移酶NAT10 在软组织肿瘤中的表达及意义

目的：观察N-乙酰转移酶NAT10蛋白在软组织肉瘤中的表达及与类型、分级的关系。方法：通过原核表达NAT10蛋白免疫制备特异性多克隆抗体,并经免疫印迹鉴定;以组织芯片一免疫组化检测166例软组织肉瘤和28例良性肿瘤及瘤样病变中NAT10蛋白的表达。结果：制备多克隆抗体经Western印迹鉴定与NAT10具有特异结合性。免疫组化显示166例软组织肉瘤中NAT10蛋白阳性95例,阳性率为57％（95／166）,28例良性肿瘤及瘤样病变中4例阳性14％（4／28）。两者间有显著性差异（P〈0．05）。NAT10表达的主要分布为：滑膜肉瘤76％（13／17）、恶性纤维组织细胞瘤75％（15／20）、原始神经外胚叶瘤（PNET）70％（16／23）、横纹肌肉瘤70％（7／10）、恶性外周神经鞘膜瘤50％（11,／22）、隆突性皮肤纤维肉瘤50％（7／14）、平滑肌肉瘤43％（6／14）、脂肪肉瘤42％（8／19）、黏液性纤维肉瘤38％（6／16）。统计比较显示：滑膜肉瘤与黏液性纤维肉瘤和脂肪肉瘤,以及恶性纤维组织细胞瘤与黏液性纤维肉瘤之间NAT10表达具有显著性差异（P〈0．05）;而其它各组间无明显差异（P〉0．05）。同时,NAT10蛋白强阳性表达（≥＋＋）多存在于滑膜肉瘤（53％,9／17）、横纹肌肉瘤（40％,4／10）及恶性纤维组织细胞瘤（40％,8／20）。在FNCLGC分级中,19例I级肉瘤中NAT10阳性表达率为42％（8／19）,44例Ⅱ级肉瘤为43％（19／44）,70例Ⅲ级肉瘤为73％（51／70）。Ⅲ级NAT10阳性率显著高于Ⅱ级组和Ⅰ级组（均为P〈0．05）。结论：研究表明N-乙酰转移酶NAT10表达于多种人软组织肉瘤,尤其在高度恶性肉瘤,因此有可能为软组织肉瘤的分级及预后因子。     

Association of the mutation for the human carboxypeptidase E gene exon 4 with the severity of coronary artery atherosclerosis

Objective: To test the hypothesis that the identification of mutation in the carboxypeptidase E (CPE) gene which leads to marked hyperproinsulinaemia is consistent with a possible role for mutations in CPE in the development of coronary atherosclerosis. Methods: The study subjects consisted of 1084 consecutive patients (812 males and 272 females) who will undergo coronary angiography. The severity of coronary atherosclerosis was defined by the Gensini’s score system. The proinsulin level was measured using highly sensitive two-site sandwich ELISA methods. Screening for mutations of the 4th exon and exon-intron junctional region of the CPE gene was performed by polymerase chain reaction followed by bidirectional sequencing. Results: Sequencing of the CPE gene exon 4 in 1084 consecutive patients revealed 2 genetic variants, the G–to-A substitution at nucleotide 2855 in exon 4 (synonymous mutation) and A-to-G substitution at nucleotide 2925 in intron 4. Although the proinsulin level was not influenced by the presence of the two point mutation, the Gensini score was significantly influenced by the presence of the A2925G mutant (P = 0.023). Furthermore, we found a higher prevalence of subjects with the A2925G heterozygous mutant among higher Gensini score subjects than it among lower Gensini score subjects, and this difference reached statistical significance (P = 0.006, OR 1.465, 95%CI 1.116–1.924). In addition, the frequency distribution of the G2855A mutant was differed in the higher Gensini score subjects than it in the lower Gensini score subjects belonging to high-risk category as smokers, and the statistical significance was reached (P = 0.043, OR 2.075, 95%CI 1.024–4.207). Conclusions: In the present study, the severity of the coronary atherosclerosis estimated by Gensini score was significantly influenced by the presence of the A2925G mutant and G2855A mutant of the CPE gene, and the exactly mechanism underlying the association needs further study.     

冠状动脉粥样硬化大鼠实验动物模型的改进与评价

目的通过对文献报道的动脉粥样硬化大鼠造模方法的改进,建立一种适合进行心血管疾病研究的冠状动脉粥样硬化Wistar大鼠模型。方法将40只大鼠随机分为对照组与模型组,对照组15只,模型组25只。模型组高脂饲料喂养配合前3个月,每月按15万U/kg每月腹腔注射维生素D3一次,对照组喂养普通饲料,造模时长150 d。实验结束后通过对血管内皮、脂代谢、炎症浸润几个方面对模型大鼠进行考察。结果证实模型组大鼠较对照组血清LDL-C、CHO、TG水平明显升高,HDL-C/LDL-C、NO/ET-1值明显降低;AI值显著增高;血清NO、ET-1、ox-LDL、AngⅡ、sICAM-1表达明显增高;HE染色显示：模型组大鼠冠状动脉出现血栓、内皮破坏、粥样斑块形成,血管壁钙化情况;心肌纤维组织增生,炎细胞浸润,心肌轻度变性;主动脉出现动脉粥样硬化斑块形成,而对照组无病变产生。结论本方法能够提供一种稳定的、复制性好的用于冠状动脉粥样硬化实验研究的大鼠模型。     

冠状动脉粥样硬化患者肠道菌群与嘌呤碱基分解代谢的相关性

目的 研究冠状动脉粥样硬化患者肠道菌群结构与嘌呤碱基分解代谢的相关性。方法 选取2016年12月至2019年4月我院收治的92例冠状动脉粥样硬化患者为研究对象,测定患者嘌呤碱基代谢物含量并按照不同嘌呤碱基代谢物水平分为I组（22例,代谢物水平≤430 μmol/L）、II组（24例,代谢物水平431~480 μmol/L）、III组（22例,代谢物水平481~530 μmol/L）、IV组（24例,代谢物水平＞530 μmol/L）。选取同期到我院体检的30例健康者为对照组。采用实时荧光定量PCR法检测两组对象肠道菌群数量,采用OTU聚类分析肠道菌群多样性。肠道菌群结构与嘌呤碱基分解代谢的相关性分析采用Pearson分析。结果 I~IV组患者嘌呤碱基代谢物水平、肠道菌群总量依次升高,差异有统计学意义（均P＜0.05）,同时各组冠状动脉脉粥样硬化患者嘌呤碱基代谢物水平、肠道菌群总量均高于对照组,差异有统计学意义（均P＜0.05）。IV组患者肠道大肠埃希菌数量高于I组、II组、III组及对照组（均P＜0.05）。IV组患者肠道幽门螺杆菌、产气杆菌数量高于I组、II组及对照组,而肠道乳杆菌、双歧杆菌数量低于I组、II组及对照组（均P＜0.05）。III组患者肠道幽门螺杆菌、产气杆菌数量高于I组,而乳杆菌、双歧杆菌数量低于I组（均P＜0.05）。III组患者肠道幽门螺杆菌、乳杆菌、双歧杆菌数量均低于对照组（均P＜0.05）。II组患者肠道产气芽胞杆菌数量高于对照组,而乳杆菌、双歧杆菌数量低于对照组（均P＜0.05）。IV组、III组患者肠道菌群OTU指数均高于对照组、I组和II组,差异均有统计学意义（均P＜0.05）,说明IV组、III组患者肠道菌群丰富度指数较高,菌群种类较多。Pearson分析显示嘌呤碱基水平与大肠埃希菌、幽门螺杆菌、产气芽胞杆菌、乳杆菌和双歧杆菌呈现正相关性（P＜0.05）。结论 冠状动脉粥样硬化患者嘌呤碱基水平可能影响肠道菌群结构。     

Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries

We detected urotensin-II-like immunoreactivity in the endothelium of normal human blood vessels from heart, kidney, placenta, adrenal, thyroid and umbilical cord. Immunoreactivity was also detected in endocardial endothelial and kidney epithelial cells. In atherosclerotic coronary artery, immunoreactivity localized to regions of macrophage infiltration. Urotensin-II constricted human atherosclerotic epicardial coronary arteries with pD2=10.58 +/- 0.46 (mean +/- S.E.M.) and Emax=11.4 +/- 4.2% KCl and small coronary arteries with pD2=9.25 +/- 0.38 and Emax=77 +/- 16% KCl. Small coronary arteries clearly exhibited a greater maximum response to urotensin-II than epicardial vessels. This enhanced responsiveness may be of importance in heart failure, where circulating concentrations of U-II are increased, or in atherosclerosis where focally up-regulated urotensin-II production may act down stream to produce significant vasospasm, compromising blood flow to the myocardium. We conclude that urotensin-II is a locally released vasoactive mediator that may be an important regulator of blood flow particularly to the myocardium and may have a specific role in human atherosclerosis.     

A novel tissue array technique for high-throughput tissue microarray analysis — microarray groups

Tissue microarrays are ordered arrays of hundreds to thousands of tissue cores in a single paraffin block. We invented a novel method to make a high-throughput microarray group. Conventional smaller tissue microarrays were made first and then sectioned. Separate paraffin films were arrayed orderly onto a regular-sized glass slide to form a larger microarray group. Sections were not floated in a water bath but, rather, were cut singly using conventional microtome, arrayed orderly onto the glass slide with forceps instead of using a tape-based tissue transfer system, and then unfolded with warm water (46° C) using a micropipette. This not only lowers the difficulty in sectioning but the overall tissue disks can be included in the same section. A microarray group of 2,534 small disks (theoretically, 2,560 disks can be made; 26 fell off during the procedure), the most up to now, was successfully made and may be used in immunohistochemistry, mRNA in situ hybridization, and flourescent in situ hybridization.     

Plasma oxysterols and angiographically determined coronary atherosclerosis: a case control study

Several in vitro and in vivo experiments have implicated oxysterols in the aetiology and progression of atherosclerosis. Oxysterols may be formed endogenously by oxidation of cholesterol and thus may form a marker of LDL oxidation. They may also be obtained exogenously through dietary intake. We investigated the association of oxysterols with the degree of coronary stenosis in patients undergoing coronary angiography. Cases with severe coronary atherosclerosis 80 stenosis in one of the major coronary vessels, n =80 were compared with controls with no or minor stenosis 50 stenosis in all three major coronary vessels, n =79 . Cases and controls were prestratified on age, gender and smoking habits. Evaluated were plasma levels of unesterified 7 hydroxycholesterol, 7 hydroxycholesterol, 25 hydroxycholesterol, 7 ketocholesterol, cholestane triol and 5,6 epoxycholestanol. 7 Hydroxycholesterol made up 67 of the total amount of plasma oxysterol concentration and was the only one significantly higher in cases 1.53 mu g per 100 ml vs 1.27 mu g per 100 ml, p 0.05 . Further, cases had somewhat higher LDL cholesterol levels and significantly lower HDL cholesterol levels than controls. After multivariate adjustment to account for this difference in lipid levels and for the prestratification factors the mean difference between cases and controls for 7 hydroxycholesterol 0.14 mu g per 100 ml was no longer significant. Also the other oxysterols showed no significant association with the degree of coronary stenosis. Multiple logistic regression analyses showed an adjusted odds ratio of 1.07 95 CI, 0.45-2.59 in the highest tertile of total plasma oxysterol level. We conclude, that this study does not support the hypothesis that plasma oxysterols form an additional risk factor for coronary atherosclerosis.     

Plasma oxysterols and angiographically determined coronary atherosclerosis: a case control study

Several in vitro and in vivo experiments have implicated oxysterols in the aetiology and progression of atherosclerosis. Oxysterols may be formed endogenously by oxidation of cholesterol and thus may form a marker of LDL oxidation. They may also be obtained exogenously through dietary intake. We investigated the association of oxysterols with the degree of coronary stenosis in patients undergoing coronary angiography. Cases with severe coronary atherosclerosis 80 stenosis in one of the major coronary vessels, n =80 were compared with controls with no or minor stenosis 50 stenosis in all three major coronary vessels, n =79 . Cases and controls were prestratified on age, gender and smoking habits. Evaluated were plasma levels of unesterified 7 hydroxycholesterol, 7 hydroxycholesterol, 25 hydroxycholesterol, 7 ketocholesterol, cholestane triol and 5,6 epoxycholestanol. 7 Hydroxycholesterol made up 67 of the total amount of plasma oxysterol concentration and was the only one significantly higher in cases 1.53 mu g per 100 ml vs 1.27 mu g per 100 ml, p 0.05 . Further, cases had somewhat higher LDL cholesterol levels and significantly lower HDL cholesterol levels than controls. After multivariate adjustment to account for this difference in lipid levels and for the prestratification factors the mean difference between cases and controls for 7 hydroxycholesterol 0.14 mu g per 100 ml was no longer significant. Also the other oxysterols showed no significant association with the degree of coronary stenosis. Multiple logistic regression analyses showed an adjusted odds ratio of 1.07 95 CI, 0.45-2.59 in the highest tertile of total plasma oxysterol level. We conclude, that this study does not support the hypothesis that plasma oxysterols form an additional risk factor for coronary atherosclerosis.     

Expression profiling of liver receptor homologue 1 (LRH-1) in mouse tissues using tissue microarray

Liver receptor homologue 1 (LRH-1) is a nuclear receptor that plays important roles in lipid homeostasis and embryogenesis. To elucidate systemic physiological functions of LRH-1, we used tissue microarray-based immunohistochemistry to examine the tissue distribution and localization of LRH-1 in adult mouse tissues. LRH-1 immunoreactivity was observed in the nucleus of multiple epithelial lineage cells in the digestive system (including absorptive epithelial cells in the small and large intestines, goblet cells, acinar cells of the exocrine glands, chief cells and mucus neck cells in the stomach, granular and prickle layer cells in the tongue and forestomach, and gall bladder epithelium); respiratory system (alveolar type II cells); and urinary system (transitional epithelium). Nuclear LRH-1 immunoreactivity was also localized in cells involved in fatty acid/glucose metabolism, including hepatocytes, brown adipocytes, and cardiomyocytes, and neurons involved in the regulation of food intake, including the arcuate nucleus in the hypothalamus and paraventricular nucleus of thalamus. Additionally, LRH-1 immunoreactivity was observed in testicular Leydig cells and ovarian follicular cells. These data suggest that LRH-1 functions in multiple organ systems to regulate epithelial cell physiology and differentiation, energy metabolism, and reproduction. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

DNA haplotypes of the human apoprotein B gene in coronary atherosclerosis

Summary Haplotypes of the apoprotein B gene, localised to chromosome 2, were identified using restriction fragment length polymorphisms (RFLPs) for the enzymes XbaI and EcoRI. Four haplotypes were identified at this locus, X1R1 (H1), X1R2 (H2), X2R1 (H3) and X2R2 (H4); where the X1 and X2 alleles were characterised by gene-related fragments of 5.0 and 8.6 kb respectively and the R1 and R2 alleles by fragments of 13.0 and 11.0 kb respectively. Although the polymorphic sites are less than 10 kb apart, they were found to be in linkage equilibrium. The value of the disequilibrium parameter (D) was 0.0042, approximately 7.5% of the theoretical maximum (D_max=0.054). No disease association could be demonstrated between either apoB RFLP, or haplotype, and coronary athersclerosis in our population from south-east England. This was in accordance with a study of apoB RFLPs for a population from the West Coast of the United States, but in contrast to a study of an East-Coast population. There are no previous data for the association between apoB haplotypes and coronary atherosclerosis.