武汉地区成人代谢综合征患病率及相关因素

对参加健康体检的武汉市区成年居民2057人的资料进行了分析，以了解武汉地区部分20岁以上人群代谢综合征的患病率及与部分相关因素的关系，结果表明代谢综合征的总患病率为10．74％．其中男性患病率为13．47％，女性患病率为4．99％。代谢综合征的患病率随血甘油三酯、血尿酸、胰岛素抵抗指数和年龄的增加而增加。     

Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model

RNA-based cancer therapies are hindered by the lack of delivery vehicles that avoid cancer-induced organ dysfunction, which exacerbates carrier toxicity. We address this issue by reporting modular degradable dendrimers that achieve the required combination of high potency to tumors and low hepatotoxicity to provide a pronounced survival benefit in an aggressive genetic cancer model. More than 1,500 dendrimers were synthesized using sequential, orthogonal reactions where ester degradability was systematically integrated with chemically diversified cores, peripheries, and generations. A lead dendrimer, 5A2-SC8, provided a broad therapeutic window: identified as potent [EC₅₀ < 0.02 mg/kg siRNA against FVII (siFVII)] in dose–response experiments, and well tolerated in separate toxicity studies in chronically ill mice bearing MYC-driven tumors (>75 mg/kg dendrimer repeated dosing). Delivery of let-7g microRNA (miRNA) mimic inhibited tumor growth and dramatically extended survival. Efficacy stemmed from a combination of a small RNA with the dendrimer’s own negligible toxicity, therefore illuminating an underappreciated complication in treating cancer with RNA-based drugs.Since the discovery of RNAi and the recognition of its therapeutic potential, there has been a continuous search for optimal delivery carriers (1–10). Tremendous progress has been made with regard to delivery efficacy of small RNAs to healthy livers, but the clinically required combination of high delivery potency to tumors and low hepatotoxicity is not currently met by existing delivery vehicles. This challenge represents an unappreciated complication in treating cancer with RNA-based drugs. Primary liver cancer, a chronic consequence of liver cirrhosis, is a leading cause of cancer death and a major global health problem (11). Unfortunately, all five phase III human clinical trials of small-molecule drugs for hepatocellular carcinoma (HCC) treatment failed within the past four years in part because debilitating, late-stage liver dysfunction amplifies drug toxicity (11, 12). MicroRNAs (miRNAs) present a promising alternative cancer treatment strategy because they can function as tumor suppressors by concurrently targeting multiple pathways involved in cell differentiation, proliferation, and survival (13–19). In this study, we used a highly aggressive, inducible MYC-driven transgenic liver cancer model where the chance for successful therapy is very limited, in equal part due to the rapidly growing cancer and the compromised function of the overtaken liver. Tumors grow endogenously from within the liver in this genetically engineered model, which is biologically faithful and lethal, in contrast to standard xenograft or orthotopic models derived from cell line implantation (20). The development of dendrimer carriers that can mediate a therapeutic benefit in this difficult-to-treat model was set as the paramount goal of the study. Notably, we find that high potency and low toxicity are of critical importance in the context of aggressive liver cancer models, where the carrier’s own toxicity can negate the benefit of on-target small-RNA therapies.To achieve this balance of low toxicity and high potency, we reasoned that one must more precisely examine the influence of chemical structure by expanding the structural diversity and molecular size of delivery carriers. Dendrimers represented an ideal system for this goal because they possess the same high degree of molecular uniformity as small molecules and the broad theoretical space for chemical tuning as polydisperse polymers (21–23). These intrinsic characteristics enable dendrimers to have unique properties for various biomedical applications (24–26). In gene delivery, most studies have used the limited number of commercial dendrimers for further chemical modification (27–29). However, orthogonal click chemistry has recently made a transformative impact on the synthesis of dendritic materials through protecting group-free methodologies to overcome historical limitations in fidelity and provide a larger toolbox for dendrimer design (30–34). The expansion of dendrimer applications therefore depends on the ability to easily tune the size, chemistry, topology, and, ultimately, dendrimer physical properties through chemical synthesis.We hypothesized that, through introduction of ester bonds and molecular diversity at each expansion step, modular degradable dendrimers would possess a critical balance of low toxicity and high delivery potency (Fig. 1). We further speculated that chemical modulation of cores, peripheries, and generations may be accelerated by utilization of efficient click reactions to enable a large increase in both the total number (>1,500) and chemical diversity of dendrimers. Biocompatible, degradable esters were included as a key design component because all RNAi therapies are transient and require sustained and repeated treatment. This ultimately enabled discovery of well-tolerated small-RNA carriers that could produce a therapeutic benefit in a challenging liver cancer model.Open in a separate windowFig. 1.RNA-based liver cancer therapies are hindered by the lack of potent and nontoxic delivery vehicles that avoid late-stage liver dysfunction that exacerbates toxicity. We envisioned that a modular design would allow discovery of dendrimers that balance low hepatotoxicity and high in vivo small-RNA delivery potency to tumor cells by fine-tuning of the identity and position of functional groups within dendrimer architectures.Efficacious delivery requires overcoming a series of extracellular and intracellular barriers (1). The physicochemical properties of small RNAs (high molecular weight, anionic charge, and hydrophilic nature) prevent passive diffusion across cell membranes. Studies of lipid and polymer carriers have implicated at least two common elements: chemical groups to bind small RNAs and nanoparticle (NP)-stabilizing hydrophobicity, which combine to encapsulate RNA molecules inside stable NPs and release small RNAs into the cytosol after endocytosis (35). Particular tertiary amines with optimal pK_a, alkyl chains, and defined topology/structure have been identified in effective carriers (2–10, 35–37).Despite these advances, demonstration of effective survival benefit in aggressive genetic models of human cancer has not been achieved with synthetic carriers due to the lack of delivery vehicles that avoid cancer-induced organ dysfunction. To address this, we designed a dendrimer library organized through binding, stabilization, and chemical functionality within the cores and peripheries. In vitro and in vivo evaluation identified dendrimers with optimal topological structures and high delivery efficacy (EC₅₀ of FVII knockdown < 0.02 mg/kg). Structure–activity knowledge was used to rationally design additional carriers with predicted in vivo activity. Evaluation of lead dendrimer candidates identified 5A2-SC8 as exhibiting low toxicity after repeated 75 mg/kg dendrimer i.v. dosing in chronically ill, tumor-bearing mice. Finally, we demonstrate that 5A2-SC8 can deliver a let-7g tumor suppressor miRNA with high in vivo potency to suppress tumor growth and result in a dramatic survival benefit of transgenic mice bearing aggressive, MYC-driven liver cancer. These findings suggest that modular degradable dendrimers may greatly expand the scope of chemical discovery research for therapeutic dendrimer delivery applications, ultimately providing new avenues for development of RNA cancer treatments by expansion of the therapeutic window.     

良性前列腺增生患者TURP术后腺体再次增生的高危因素分析

目的:探讨TURP术后腺体再次增生的高危因素。方法:对行TURP的990例BPH患者临床资料作回顾性分析,32例(3.23%)术后腺体再次增生。结果:BPH患者的发病年龄小,OR=3.568,95%CI(2.620⁹.731)、前列腺前后径大,OR=7.708,95%CI(1.7159.731)、前列腺前后径大,OR=7.708,95%CI(1.715³4.638)、残余尿量,OR=3.850,95%CI(1.50234.638)、残余尿量,OR=3.850,95%CI(1.502⁹.868)是TURP术后腺体再次增生、症状复发的危险因素。结论:泌尿外科临床对BPH患者行TURP时,对发病年龄<60岁、前列腺前后径>4 cm、残余尿量<50 ml的患者应引起高度重视,以防复发。     

维药唇香草总黄酮微波提取工艺研究

目的：优选唇香草总黄酮的最佳提取工艺。方法以唇香草总黄酮的提取率为指标,采用正交设计法优选唇香草总黄酮微波提取工艺。结果唇香草总黄酮微波最佳提取工艺为,提取功率800 W,提取时间45 min,提取温度80℃,测得唇香草中总黄酮的含量为5．53％。结论微波提取唇香草总黄酮工艺经济、合理,工艺条件可行。     

唇香草挥发油对自发性高血压大鼠降压作用的研究

目的：探讨唇香草挥发油对自发性高血压大鼠（SHR）的降压作用。方法采用随机数字表法将60只 SHR 大鼠随机分为6组,模型对照组（生理盐水）、卡托普利组（20 mg/kg）、氢氯噻嗪组（20 mg/kg）、唇香草挥发油高（40 mg/kg）、中（20 mg/kg）、低（10 mg/kg）剂量组,另外10只 Wista 大鼠作为空白对照,分别进行药物干预4周,于给药前后2h 测定各组大鼠尾动脉血压。结果给药3 w 后唇香草挥发油高、中剂量组及卡托普利、氢氯噻嗪组 SHR 大鼠收缩压、舒张压均显著低于阳性对照组（P ＜0．05）。结论唇香草挥发油对 SHR 大鼠具有显著的降压作用。     

雄激素对机体严重创伤后免疫反应、肝脏及心血管功能的影响

动物研究证实,创伤预后存在明显的性别差异,雄性动物创伤后并发症发生率及死亡率均明显高于雌性。但是,临床关于创伤预后性别差异的研究则一直存在争议。实验室研究证实,雄性动物创伤后机体免疫反应及各脏器功能明显受到抑制,而睾丸切除或服用雄激素受体抑制剂后上述抑制作用得到明显改善。关于性激素水平对创伤后机体免疫反应的研究发现,雌激素具有免疫增强作用;而相反,雄激素则会诱导免疫抑制。本文主要阐述雄激素水平变化对机体创伤后免疫反应、肝脏及心血管系统功能的影响作用,进一步分析创伤预后性别差异的潜在机制,从而在动物研究的结果中寻求新的干预措施来改善创伤患者的预后。     

98例左诀诺孕酮宫内缓释系统临床疗效观察

目的探讨子宫内膜异位症、功能失调性子宫出血(功血)及单纯避孕妇女放置左诀诺孕酮宫内缓释系统(LNG-IUS)后的临床疗效。方法随访我院计生门诊98例子宫内膜异位症、功血及单纯避孕患者,分别于放置LNG-IUS后3、6、12个月观察其月经、副反应及患者满意度情况;同时采用口诉评分(VRS)法对47例子宫内膜异位症患者痛经程度进行评估。结果 34例功血患者放环后3、6、12个月月经量较放环前减少,差异有统计学意义(P0.001);47例子宫内膜异位症患者放环后3、6、12个月VRS评分较放环前减小,差异有统计学意义(P0.001)。治疗12个月,无一例发生妊娠,59例(64.9%,59/91)患者对治疗的综合效果表示非常满意或满意。结论 LNG-IUS是一种治疗子宫内膜异位症、功血及避孕的安全有效方法 。     

白介素-1β基因-511和+3954多态性与男性煤矿职工慢性阻塞性肺疾病的相关性

目的探讨白细胞介素-1β(IL-1β)基因-511和+3954多态性与男性煤矿职工慢性阻塞性肺疾病(COPD)的相关性。方法收集2009年1月-2013年6月河北联合大学附属开滦总医院呼吸科门诊筛查的234例煤矿职工COPD患者(煤矿职工COPD组)及250例同期健康对照人群(健康对照组),用酶联免疫吸附试验(ELISA)检测血清IL-1β水平,应用聚合酶链反应-限制性片段长度多态性(PCR—RFLP)方法检测-511C/T,+3954C/T位点的基因型。结果煤矿职工COPD组的血清IL-1β水平为(3.98±0.42)ng/ml,健康对照组为(2.76±0.18)ng/ml,2组间差异具有统计学意义(P<0.01)。煤矿职工COPD组IL-1β-511的CC、CT和TT基因型频率分别为20.1%、62.8%和17.1%,健康对照组分别为21.6%、60.4%和18.0%,2组相比差异无统计学意义(P>0.05)。煤矿职工COPD组IL-13+3954 CC、CT和TT基因型频率分别为83.8%、16.2%和0,健康对照组分别为86.8%、13.2%和0,2组相比无统计学意义(P>0.05)。2组人群IL—1β-511,+3954等位基因频率比较差异无统计学差异(P均>0.05)。结论煤矿职工COPD组血清IL-1β水平高于健康对照组,IL—1β-511、+3954的基因型频率与等位基因频率与煤矿职工CC)PD的发生无明显相关性。     

推拿对坐骨神经损伤大鼠NT-3、TrkC的影响

目的研究推拿对坐骨神经损伤大鼠感觉功能及NT-3、TrkC表达的影响。方法采用夹持法建立坐骨神经损伤模型,将大鼠随机分为正常组、假手术组、模型组、模型对照组、推拿组,以按摩推拿手法模拟仪进行干预,通过热痛阈实验观察各组大鼠行为学变化;通过免疫组织化学染色观察各组大鼠背根节内NT-3、TrkC表达情况。结果模型组、模型对照组大鼠的PWL值与正常组相比明显延长,推拿组与模型组相比PWL值明显缩短,与正常组相比无显著差异。模型组、模型对照组及推拿组NT-3免疫组化表达与正常组比较均有明显提高,推拿组与模型组比较有显著性差异(P0.05)。结论中医推拿可以改善神经损伤大鼠的行为学表现,通过促进NT-3及其受体TrkC的表达,发挥抑制细胞凋亡,对神经元胞体和突起的生长产生积极的影响,促进损伤神经的修复,改善坐骨神经损伤大鼠的感觉功能。     

小儿术后皮下自控镇痛的效果

目的比较皮下自控镇痛（PCSA）与静脉自控镇痛（PCIA）在小儿术后自控镇痛的安全性和有效性。方法全麻下行扁桃体切除术后患儿50例,随机均分为PCSA组和PCIA组。PC－SA组配方为芬太尼0．5mg,PCIA组配方为芬太尼0．3mg,两组均加甲氧氯普胺5mg,均以生理盐水稀释成100ml,背景剂量2ml／h,锁定时间15min,单次按压负荷量0．5ml,镇痛持续48h。观察患儿术后的镇痛效果,记录镇痛满意率、PCA总按压次数、PCA有效按压次数及并发症。结果PC－SA组与PCIA组满意率分别为88％（22／25例）和92％（23／25例）,差异无统计学意义（P〉O．05）。但PCSA组恶心呕吐发生率（8％）低于PCIA组（20％）（P〈0．05）。两组均未见嗜睡、呼吸抑制病例。结论PCSA可安全有效地用于全麻患儿术后镇痛。