组织相容性复合物DQ基因与胰岛素依赖型糖尿病易感相关性剂量效应规律的研究

为研究中国北方汉族人中组织相容性复合物ＤＱ（ＨＬＡ－ＤＱ）基因与胰岛素依赖型糖尿病（ＩＤＤＭ）遗传易感性相关的剂量效应规律，采用聚合酶链反应和序列特异性寡核苷酸探针杂交技术，对５４例胰岛素依赖型糖尿病患儿和４０例正常成年供血员ＨＬＡ－ＤＱ基因进行了研究。结果：携带４个易感性基因的个体只见于患者，携带３个易感性基因的个体在患者中为３３．３％，正常对照中为１０％；携带２个或１个易感性或保护性基因的个体在正常对照中频率较患者为高，但差异无显著意义；携带３个保护性基因的个体只见于正常对照。提示：ＩＤＤＭ易感性基因具有部分隐性遗传的特点且具有累加效应。个体中１个或２个易感性基因的存在不能对ＩＤＤＭ构成显著的易感性，３个或３个以上易感性基因的存在方可对ＩＤＤＭ构成显著易感性。ＤＱ保护性基因具有部分显性遗传的特点并且也具有累加效应。携带１个或２个保护性基因的个体患ＩＤＤＭ的机会将大大减少，而携带３个保护性基因的个体则可以不发生ＩＤＤＭ。     

Postprandial glycaemia after regular and lispro insulin in children and adolescents with diabetes

We compared the postprandial blood glucose (BG)-levels following preprandial regular insulin or lispro insulin before and after eating in adolescents with diabetes. Lispro is a rapidly absorbed insulin analogue. Lispro insulin injected immediately before breakfast reduced the postprandial BG-rise significantly compared to the 20 min preprandially administered regular insulin (P<0.01). Postprandial lispro injection resulted in similar BG values as the standard treatment with regular insulin 20 min preprandially. Conclusion Lispro insulin injected immediately before the meal leads to lower postprandial BG levels and seems to be an option for teenagers who use multiple preprandial insulin injections. Postprandial lispro administration could be a benefit in certain situations since it resulted in similar BG values to preprandial regular insulin. Received: 13 March 1997 / Accepted: 26 May 1997     

先天性感音性聋患者大脑皮层静息态功能磁共振研究

目的：应用血氧水平依赖功能磁共振成像（blood oxygenation level dependent functional magnetic resonance imag ing ,BOLD－ fM RI）技术观察先天性感音神经性聋患者静息态双侧大脑半球皮层功能活动。方法对23例行人工耳蜗植入术的双侧先天性感音性聋患者（实验组）和10例听力正常者（对照组）行静息态BOLD—fMRI检查,采用fMRI低频震荡振幅（ALFF）方法比较实验组和对照组双侧大脑皮层功能活动情况,并进行定量分析。结果实验组大脑皮层左侧颞下回、左侧梭状回、右侧扣带回及左侧中央后回静息态激活强度明显大于对照组相应皮层的激活强度（P＜0．01）。结论先天性感音性聋患者感觉系统相关皮层可能发生了功能重塑,其大脑皮层存在知觉补偿现象。     

非胰岛素依赖型糖尿病患者骨密度变化的探讨

目的 研究非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者的骨密度变化,以了解ＮＩＤＤＭ患者是否易合并骨质疏松及其特点。方法 采用双能Ｘ线骨密度仪（简称为ＤＸＡ）,４８例ＮＩＤＤＭ患者及３５例３０￣３５岁正常人腰椎正侧位、髋部及全身骨密度。病例选择是根据１９８５年世界卫生组织（ＷＨＯ）糖尿病专家委员会提出的诊断和分型标准,结果均经统计学处理分析。结果 ４８例ＮＩＤＤＭ患者的骨密度都有不同程度下降,按ＳＨＯ推     

Hormone-based therapies in the regulation of fuel metabolism and body weight

Background: The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes. Objective: To examine hormone-based therapies targeting these interrelated pathways as potential treatments for obesity and diabetes. Methods: Preclinical and clinical data on therapies based on hormones secreted from the pancreas (glucagon, insulin, amylin and pancreatic polypeptide), gut (glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, cholecystokinin and peptide YY) and adipose tissue (leptin and adiponectin) as potential treatments for diabetes and obesity are reviewed. Results/conclusions: In diabetes, hormone-based treatments have translated into new clinical platforms including insulin analogs, the GLP-1-like peptide receptor agonist exenatide and amylinomimetic pramlintide, which due to their complex interplay and the progressive nature of diabetes, can be utilized in different settings. Various peptide hormones and agonists/antagonists are currently under investigation as new approaches to treatment of obesity and diabetes.     

吡美莫司乳膏联合强脉冲光治疗面部糖皮质激素依赖性皮炎疗效观察

目的：观察外用吡美莫司乳膏联合强脉冲光治疗面部糖皮质激素依赖性皮炎的临床疗效和安全性。方法：给予34例面部糖皮质激素依赖性皮炎患者外用1％吡美莫司乳膏,每日1次,共4周。结束2周后,采用强脉冲光进行4次治疗,每次间隔3周。于治疗前、外用药物4周后及4次强脉冲光治疗结束后3周时各随访1次。结果：34例患者中28例完成临床试验。外用药治疗4周时及联合4次强脉冲光结束后3周时临床显效率分别为39．3％、53．6％,外用药治疗中10．7％的患者局部有一过性刺激反应。患者的红斑丘疹、脱屑性皮疹改变较好;联合强脉冲光治疗后可进一步改善患者色素沉着和毛细血管扩张等症状,从而提高疗效,且无不良反应。结论：外用吡美莫司乳膏联合强脉冲光治疗面部激素依赖性皮炎安全、有效。     

A neutralizing anti-fibroblast growth factor (FGF) 8 monoclonal antibody shows anti-tumor activity against FGF8b-expressing LNCaP xenografts in androgen-dependent and -independent conditions

BACKGROUNDS: Fibroblast growth factor 8-isoform b (FGF8b) has been detected in human clinical sex-organ related cancers including hormone-refractory prostate cancer. There are, however, few relevant experimental models. A murine monoclonal anti-FGF8 antibody, KM1334, has been shown to neutralize FGF8b and inhibit the growth of androgen-dependent mouse mammary SC-3 cells in vitro and in vivo. In the present study, we evaluated the anti-tumor activity of KM1334 against androgen-dependent and -independent progression of FGF8b-expressing human prostate cancer xenografts. METHODS: FGF8b cDNA was transfected into androgen-dependent human prostate cancer cell line LNCaP, and its xenograft tumors were established subcutaneously in SCID mice with or without castration. KM1334 at the dose of 400 microg/head was injected twice weekly. RESULTS: FGF8b-expressing LNCaP cells secreted FGF8b, showed enhanced level of Erk1/2 phosphorylation, and showed more potent growth properties than mock-expressing cells in vitro and in vivo. KM1334 reduced these properties in vitro, inhibited tumorigenecity in vivo (T/C=0.33), and showed anti-tumor activity against established tumors (T/C=0.47) of FGF8b-expressing cells. FGF8b-expressing LNCaP tumors were androgen-dependent. However, they recurred as androgen-independent FGF8b positive tumors after castration. KM1334 also inhibited the growth of established FGF8b-expressing tumors in the androgen-independent states (T/C=0.47). CONCLUSIONS: These results indicate that humanized monoclonal antibodies, conserving the paratope of KM1334, are a promising candidate for therapy of FGF8b-expressing clinical prostate cancers. Follow-up studies using xenograft models with clinical FGF8b-expressing tumors are required to validate these early findings.     

Spatial learning and neurogenesis: Effects of cessation of wheel running and survival of novel neurons by engagement in cognitive tasks

Physical exercise stimulates cell proliferation in the adult dentate gyrus and facilitates acquisition and/or retention of hippocampal‐dependent tasks. It is established that regular physical exercise improves cognitive performance. However, it is unclear for how long these benefits last after its interruption. Independent groups of rats received both free access to either unlocked (EXE Treatment) or locked (No‐EXE Treatment) running wheels for 7 days, and daily injections of bromodeoxyuridine (BrdU) in the last 3 days. After a time delay period of either 1, 3, or 6 weeks without training, the animals were tested in the Morris water maze (MWM) either in a working memory task dependent on hippocampal function (MWM‐HD) or in a visible platform searching task, independent on hippocampal function (MWM‐NH). Data confirmed that exposure of rats to 7 days of spontaneous wheel running increases cell proliferation and neurogenesis. In contrast, neurogenesis was not accompanied by significant improvements of performance in the working memory version of the MWM. Longer time delays between the end of exercise and the beginning of cognitive training in the MWM resulted in lower cell survival; that is, the number of novel surviving mature neurons was decreased when this delay was 6 weeks as compared with when it was 1 week. In addition, data showed that while exposure to the MWM‐HD working memory task substantially increased survival of novel neurons, exposure to the MWM‐NH task did not, thus indicating that survival of novel dentate gyrus neurons depends on the engagement of this brain region in performance of cognitive tasks. © 2015 Wiley Periodicals, Inc.     

Guaranteed cost control for switched LPV systems via parameter and state‐dependent switching with dwell time and its application

This paper is concerned with the problem of guaranteed cost control for switched linear parameter‐varying (LPV) systems. A parameter and state‐dependent switching law with dwell time is designed. The guaranteed cost control problem for switched LPV systems is still solvable even though this problem for each subsystem is unsolvable. First, a sufficient condition ensuring the solvability of the guaranteed cost control problem for switched LPV systems is presented via multiple parameter‐dependent Lyapunov functions. Then, the parameter‐dependent controller is designed, such that the closed‐loop system is asymptotically stable with the guaranteed cost index. Finally, the effectiveness of the proposed control design scheme is illustrated by its application to an aero‐engine. Copyright © 2016 John Wiley & Sons, Ltd.