唐氏综合征发生率及其受产前筛查干预的研究

目的 探讨住院分娩活产婴儿中唐氏综合征的发生率,以及产前筛查对降低唐氏综合征发生率的作用.方法 计算唐氏综合征的发生率,分析产前筛查率与唐氏综合征发生率的相关性,评估产前筛查对降低唐氏综合征发生率的作用.结果 2000年至2002年门诊的24.3%孕早、中期孕妇参与产前筛查,筛查出并经产前诊断证实1例唐氏综合征胎儿,同期分娩活产婴儿7063名中有唐氏综合征患儿7例,合计发生率为1/883;2003年至2004年产前筛查率上升至81.6%,在5273名活产婴儿中有唐氏综合征3例,发生率降至1/1758.结论 本组唐氏综合征的近似发生率可能高于1/785,产前筛查是能够在孕早、中期筛查出高风险患者的有效方法,提高产前筛查率可降低唐氏综合征发生率.     

Nightmare frequency and psychopathological problems in a large sample of Chinese adolescents

Purpose

Nightmares are common, especially in pediatric populations and psychiatric patients. Nightmares are associated with daytime distress and negative health outcomes. The data on the prevalence and psychopathological profiles of nightmares in Chinese adolescents are limited. This study examined age and gender differences in nightmare frequency and associated psychopathological problems in a large sample of Chinese adolescents.

Methods

A total of 11,831 adolescent students (mean age = 14.9, 12–18 years) participated in the baseline survey of Shandong Adolescent Behavior and Health Cohort. Participants completed a self-administered questionnaire to report their nightmare frequency, trait anger, hopelessness, and multiple domains of behavioral/emotional problems. Univariate and multivariate analyses were performed to examine psychopathological problems in relation to nightmare frequency.

Results

Of the sample, 45.2% reported having nightmares at least once in the past month and 7.9% at least once/week. Girls reported more frequent nightmares than boys. Nightmare frequency significantly declined with age for both boys and girls. Mean scores on trait anger, hopelessness, attention, internalizing problems, and externalizing problems significantly increased with nightmare frequency. Frequent nightmares (at least once/week) were significantly associated with 2–4-fold increased likelihood of behavioral/emotional problems after adjusting for adolescent and family covariates.

Conclusion

Nightmares are prevalent in Chinese adolescents. Frequent nightmares are associated with multiple domains of psychopathological problems. Assessment and intervention of frequent nightmares should be incorporated into routine clinical practice and mental health services in adolescents.

     

纳米粒子作为基因载体在不同动物模型上的基因转染效果

目的验证包载反义单核细胞趋化蛋白-1(A-MCP-1)质粒的聚乳酸聚乙醇酸共聚物(PLGA)纳米粒子在不同动物模型上的基因转染效果。方法采用乳化溶剂挥发法制备A-MCP-1纳米粒子并进行体外物化表征。用血管平滑肌细胞进行体外基因转染,PCR法检测其转染效果。兔移植静脉内膜增生模型和大鼠腹主动脉瘤模型体内局部给予A-MCP-1纳米粒子,应用病理形态学分析、斑点杂交、原位杂交、Western blot等方法观察其在体内的基因转染效果和对内源性MCP-1基因表达的抑制作用。结果基因纳米粒子平均粒径为201·4nm,基因含量为4·14%,基因的包封效率为86%,体外可维持稳定释放两周以上。兔移植静脉内膜增生基因纳米粒子组的动脉组织中检测到明显的A-MCP-1表达,并抑制了正义MCP-1表达,内膜/中膜比为0·56±0·06,与对照组比较差异具有显著性(P<0·05),与阳离子脂质体1,2-二油酰-3-三甲铵基丙烷(DOTAP)诱导的A-MCP-1质粒组比较,差异无显著性。大鼠腹主动脉瘤模型体内转染2周后,基因纳米粒子组腹主动脉直径为(1·79±0·12)mm,明显小于空白纳米粒子悬浮液组(2·58±0·21)mm和生理盐水组(2·63±0·29)mm(P<0·01)。MCP-1基因的mRNA和蛋白表达水平分别为12·5±1·5,17·6±2·1,明显低于空白纳米粒子悬浮液组35·7±4·5,42·3±5·7(P<0·01),生理盐水组32·4±3·9,39·8±4·8(P<0·01)。结论A-MCP-1基因纳米粒子用于兔移植静脉内膜增生模型以及大鼠腹主动脉瘤模型成功实现基因转染的研究结果,显示了其应用于临床的巨大潜力。     

地塞米松-PLGA纳米粒兔眼玻璃体内注射的药物代谢动力学

目的地塞米松(dexamethasone,DM)是眼科临床常用药物,但目前缺乏高效、低毒的给药途径。借助生物降解性多聚体材料聚乳酸-羟乙酸(PLGA)构建DM-PLGA纳米粒,兔眼玻璃体内注射可望在眼后节较长时间维持稳定的有效药物浓度。方法乳化/溶剂蒸发法制备载药量分别为20%和50%的DM-PLGA纳米粒,兔眼玻璃体内注射给药后于第1、7、14和21d分别进行临床观察和组织药物浓度的高效液相色谱分析。结果给药后21d内,角膜和房水中药物浓度均低于检测水平下限(10μg·L-1);血浆药物浓度最高为024mg·L-1;载药量20%和50%的2组中视网膜脉络膜药物浓度分别为011-0.42mg·L-1和0.38-0.88mg·L-1,玻璃体药物浓度分别为0.82-26.52mg·L-1和1.78-85.72mg·L-1。临床观察眼底未见异常。结论载药量50%组的DM-PLGA纳米粒在兔眼玻璃体内可维持药物浓度达3周,提示具有眼内注射应用的潜力。     

胶原膜用于血管内基因投递的实验研究

目的评价胶原膜上通过抗体结合腺病毒或质粒DNA作为基因投递载体的可行性及效果。方法采用交联剂N-琥珀酰亚胺基3-（2-吡啶二硫基）丙酸酯（SPDP）将抗腺病毒或抗DNA抗体共价键结合在胶原膜上,通过这些抗体将腺病毒载体（Ad-GFP）和质粒DNA（pEGFP-C1）结合在膜上。采用同位素标记的质粒DNA（pDNA）在体外测定基因的释放,用细胞转染试验评价这种新型基因递送体系的功能。结果通过SPDP交联剂成功地将抗体共价键连接在胶原膜上,并结合了表达绿色荧光蛋白（GFP）的腺病毒和质粒DNA。细胞实验发现胶原膜上有大量表达GFP的阳性细胞,而膜以外的区域则没有GFP阳性细胞,表明具有局部递送特征。偶联Ad-GFP的胶原膜最大转染效率达到92.8%,而且在10^7-10^10病毒粒子/mL范围内,转染效率呈正剂量相关性。偶联pEGFP-C1的胶原膜诱导的细胞转染效率约为21.8%,结合32P标记的pDNA的胶原膜体外基因释放持续13天以上。用胶原涂层的不锈钢血管支架进行了同样的试验,在细胞培养中支架表面有大量GFP阳性细胞,其他区域没有GFP阳性细胞。结论胶原膜携带抗体偶联基因是一种新型的基因投递体系,可实现高效和局部定位的基因转染。     

BSA-PLGA微球的制备条件优化及不同添加剂对包封率的影响

目的探讨不同优化条件及添加剂对BSA-PLGA微球包封率的影响。方法采用水/油/水(W1/O/W2)的双乳化技术制备了BSA-PLGA微球,对影响其包封率的工艺进行了研究并考察了蔗糖、聚乙二醇和甘油对包封率的影响。结果采用优化条件制备的微球包封率为89.1%;BSA溶液中加入添加剂后,包封率可以提高到97.5%。结论采用水/油/水(W1/O/W2)的双乳化制备的BSA-PLGA微球可用于运载生物大分子药物,同时,提高内水相的粘度能够提高蛋白的包封率。     

The Serial Mediation of the Association between Breakfast Skipping and Suicidality by Weight Status and Depressive Symptoms: Findings from the National Youth Risk Behavior Surveys of the United States

Background: The evidence is limited for the dose–response association between breakfast skipping and suicidality. The underlying pathway from breakfast skipping to suicidality has also rarely been explored in previous studies. Methods: The data of Youth Risk Behavior Surveys (YRBSs) of the United States from 2011 to 2019 were used with a sample size of 74,074. The male: female ratio was nearly 1:1. Binary logistic regression models with complex sampling design were adopted to show the effect of breakfast skipping on weight status, depressive symptoms, and suicidality. Serial mediation was used to explore the association between breakfast skipping and suicidality by overweight/obesity and depressive symptoms. Findings: The weighted prevalence rates (95% confidence interval) of suicidal ideation, suicide plan, suicide attempt, and medically serious suicide attempt for skipping breakfast totally (0 times/week) were 25.6% (24.4–26.8%), 21.7% (20.5–22.9%), 14.2% (13.0–15.3%), and 5.3% (4.6–5.9%). Breakfast skipping was significantly associated with increased risk of suicidal ideation, suicide plan, suicide attempt, and medically serious suicide attempt. There was statistical significance for the linear dose–response association between breakfast skipping and overweight/obesity, depressive symptoms, and suicidality regardless of sex and age. A serial mediation with effect sizes between 39.68% and 51.30% for the association between breakfast skipping and suicidality by overweight/obesity and depressive symptoms was found in this study. Conclusions: This study emphasizes the hazards of breakfast skipping, which could increase the risk of suicidality among adolescents. Overweight/obesity and depressive symptoms as the mediating factors for the association between breakfast skipping and suicidality should also be with more attention.     

Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by oridonin nanosuspension

The mechanism for anti-tumor activity of oridonin (ORI) nanosuspension, prepared by the high pressure homogenization method, was studied using MCF-7 human breast carcinoma cells in vitro. MTT assay, observation of morphologic changes, flow cytometric analysis, and western blot analysis indicated that ORI nanosuspension could significantly intensify the in vitro anti-tumor activity to MCF-7 cells, as compared with ORI solution. Furthermore, ORI nanosuspension induced G?/M stage proliferation arrest and apoptosis in MCF-7 cells depending on its concentration. In addition, western blot analysis indicated that the pro-caspase-3 protein was not cleaved into the activated form and the expression of anti-apoptotic Bcl-2 protein decreased, on the contrary, the expression of pro-apoptotic Bax protein increased in a dose-dependent manner in ORI nanosuspension-treated cells. These observations indicated that the anti-tumor activity of ORI nanosuspension was intensified by cell-cycle arrest and apoptosis induction.     

Degradable PLGA Scaffolds with Basic Fibroblast Growth Factor: Experimental Studies in Myocardial Revascularization

Our goal was to investigate the efficacy of degradable poly(D,L-lactic-coglycolic acid) (PLGA) scaffolds loaded with basic fibroblast growth factor (bFGF) in inducing cardiac neovascularization, increasing perfusion, and improving cardiac function.For ease of scaffold implantation into the ventricular wall, we developed a channel-producing device. Mini-swine, established as the animal model, were grouped as follows: channels-alone (control) group, channels and blank scaffolds (CBS) group, and channels and bFGF-incorporating scaffolds (CFS) group. Two scaffolds were implanted in each animal in the CBS and CFS groups. Six weeks postoperatively, endothelial cells were immunohistologically stained for von Willebrand factor, and proliferating cells for Ki-67 antigen. The density of new vessels was counted by image-analysis software. Left ventricular function and myocardial perfusion were documented by echocardiography and nuclear scanning, respectively, before implantation and 6 weeks postoperatively.The combined application of PLGA and bFGF ensured sustained release of growth factor in the target region. In the CFS group, Ki-67-positively stained cells, vascular density, and perfusion-defect percentage all showed significant improvement (P < 0.001), compared with the control and CBS groups, which did not. Moreover, the left ventricular fractional shortening percentage in the CFS group (28.98% ± 1.24%) showed a significant increase, compared with the control group (26.57% ± 1.92%, P = 0.009) and the CBS group (27.11% ± 0.71%, P = 0.033), neither of which showed a difference (P = 0.508).The bFGF-incorporating PLGA scaffold can promote neovascular formation, enhance blood-flow perfusion, and improve myocardial function, although the original scaffold lumina were eventually occluded by inflammatory cells and scar tissue.Key words: Angiogenesis inducing agents/administration & dosage, disease models, animal, drug delivery systems/methods, fibroblast growth factors/administration & dosage, glycolates, implants, experimental, lactic acid, myocardial infarction, myocardial ischemia, neovascularization, physiologic, polyglycolic acid, swine, tissue engineering/methodsBecause the number of patients who have diffuse coronary atherosclerosis not amenable to coronary artery bypass grafting or percutaneous coronary angioplasty continues to increase,^1,2 alternative therapies for improving myocardial perfusion have been explored. One promising treatment is “angiogenic biologic bypass,”³ which is the application of exogenous angiogenic growth factors to promote collateral vascular development in ischemic regions.Of these growth factors, basic fibroblast growth factor (bFGF) is known to be a pluripotent mitogenic polypeptide for fibroblasts, smooth muscle cells, and vascular endothelial cells, all of which are involved in neovascular formation.^4–6 In addition, bFGF is capable of inhibiting apoptosis and protecting acute ischemic myocardium⁷ by regulating the expression of protein kinase C⁸ and BCL-2.⁹ Nonetheless, the short biological half-life of free bFGF in vivo¹⁰ and its rapid washout from large vascular structures in myocardial interstitium¹¹ limit its ability to induce collateral vessel development continuously. In this setting, many studies^12–14 have explored the development of slow-release carrier systems for bFGF. However, the above-mentioned bFGF-loaded carriers were all in solution and were injected into the beating heart, which possibly led to rapid loss of drugs into the cardiac chamber when the needle penetrated the endocardium a little too deeply or when cardiac squeezing caused continuous leakage from epicardial puncture sites.¹⁵On the basis of these considerations, we fabricated a novel bFGF-incorporating tubular scaffold from poly(D,L-lactic-coglycolic acid) (PLGA). The objective of this study was to investigate whether this scaffold could keep the lumen patent and, via continuous bFGF bioactivity, promote new vascular formation around the stenotic artery, thereby improving myocardial perfusion and cardiac function over the level attainable through angioplasty alone.     

内皮型一氧化氮合酶基因G894T变异与超重和高血压的关系

目的 探讨内皮型一氧化氮合酶(eNOS)基因第7外显子G894T变异与超重在高血压患病中的意义。方法 在人群中筛检出未经药物系统治疗的116例高血压患者及136名血压正常者为研究对象;运用PCR-限制性片段长度多态性检测G894T变异;用相加模型分析G894T变异与超重之间的交互作用;用人群归因危险度百分比(PAR％)反映人群中的病因分值。结果 G894T变异与超重对高血压患病具有正交互作用;归因交互效应为1．99;归因交互效应百分比为30．76％;纯因子间归因交互效应百分比为36．38％。用多元logistic回归分析调整年龄、性别、吸烟指数及饮酒指数后,G894T变异与超重对高血压患病仍具有正交互作用。调整上述混杂因素后,归因交互效应为2．85;归因交互效应百分比为39．97％;纯因子间归因交互效应百分比为46．49％。在给定条件下计算的PAR％约为15％。结论 eNOS基因第7外显子G894T变异与超重之间的交互作用在该研究人群高血压患病中具有重要意义;在仅仅对具有G894T。变异与超重同时存在的部分人群中控制超重可明显降低一般人群高血压的患病率。