郑州地区2型糖尿病肾功能衰竭患者芳香酯酶与基因Q192R多态性的关系

目的 探讨郑州地区汉族人群2型糖尿病慢性肾功能衰竭(DN-CRF)与血清芳香酯酶(ArE／PON1)活性及其192位基因多态性的关系。方法 通过检测2型糖尿病组(DM，121例)、DN-CRF组(123例)、健康对照组(127例)等观察对象的血清ArE／PONl活性及其192位基因多态性、血脂和脂蛋白等，进行分析研究。结果 郑州地区汉族人群中存在有ArE／PON1 192位等位基因Q与R，DN-CRF组Q、R基因频率为0．45和0．55，与DM、对照组比较，差异无统计学意义；两病例组患者血清酶活性均低于对照组，DN-CFR组降低幅度最大；DN-CFR组内RR基因型患者高密度脂蛋白胆固醇(HDL-C)、高密度脂蛋白2胆固醇(HDL2-C)水平低于QQ基因型，总胆固醇(TC)、甘油三酯(TG)和氧化型低密度脂蛋白(oxLDL)高于QQ基因型。结论 DN-CRF组ArE／PONl192位基因多态性与DM、健康对照组间虽差异无统计学意义，但不能排除DM合并DN-CRF与ArE／PON1的192位基因多态性有关；DN-CRF患者血清ArE／PON1活性降低，可能是DM合并DN的危险因素。     

凝血因子Ⅶ基因Arg353Gln多态性、活性和冠状动脉病变的关系

目的:探讨不同严重程度的冠状动脉病变与凝血因子Ⅶ(FⅦ)活性及其Arg353Gln多态性的关系。方法:运用聚合酶链反应(PCR)、变性梯度胶电泳(DGGE)方法筛查123例冠心病患者和120例正常对照者FⅦ基因Arg353Gln多态性,以一期法检测研究对象FⅦ活性,分析冠状动脉病变、FⅦ基因Arg353Gln多态性和FⅦ活性之间的关系。结果:发现F基因8号外显子Arg353Gln多态性(等位基因M1/M2)与FⅦ活性显著相关(P<0.05),等位基因M2与低FⅦ活性有关。冠脉多支病变患者FⅦ活性显著高于正常对照者(P<0.05)。结论:FⅦ基因Arg353Gln多态性可能是影响FⅦ活性的重要遗传标志,FⅦ活性增高可能是引起冠状动脉严重病变的原因之一。     

XRCC1、XPD单核苷酸多态性与肺癌铂类化疗的临床预后研究

目的DNA修复基因XRCC1和XPD是参与铂-DNA加合物修复中的关键因子。探讨肿瘤石蜡组织中XR-（321、XPD单核苷酸多态性与接受铂类药物化疗非小细胞肺癌（NSCLC）患者临床预后之间的关系。方法采用TaqMan探针Real-time PCR方法评价53例石蜡包埋NSCLC组织中DNA修复基因XRCC1第399位密码子、XPD第751位密码子的多态性，并比较不同基因型与NSCLC肿瘤组织临床病理及铂类化疗预后之间的关系。结果XRCC1 Arg399Gin、XPD Lys751Gln基因多态性与NSCLC患者临床及肿瘤病理特征均未见相关性。携带XRC1 Arg／Arg或Arg／Gln基因型NSCLC患者经铂类化疗后的平均总生存时间为24．0月，而携带Gln／Gln基因型患者仅为8．0月，两者有统计学差异（P=0．02）。XPD Lys751Gln与NSCLC患者无进展生存期和总生存时闯均未见显著性差异（P〉0．05）。XPD和XROC1的多态性联合分析显示变异型等位基因的个数增加与总生存时间（P=0．015）相关。Cox比例风险模型显示XRCC1 Arg399Gln可以独立预测NSCLC患者的总生存时间（P=0．011）。结论XRCC1 Arg399Gln、XPD Lys751Gln基因多态性与NSCLC肿瘤临床病理特征无关。XRCC1 Arg399GIn基因多态性与NSCLC患者的总生存时间有关，在一定程度上可以作为判断NSCLC患者铂类药物化疗的预后指标。XRCC1和XPD SNP在铂类药物化疗预后方面可能存在一定的联合作用。     

β2-肾上腺素能受体基因多态性与慢性心力衰竭后室性心律失常的关系

目的探究β2-肾上腺素能受体基因多态性与慢性心力衰竭后室性心律失常的关系。方法聚合酶链式反应法(PCR)对115例慢性心力衰竭后室性心律失常患者(观察组)及90例健康体检正常人员(对照组)进行β2-肾上腺素能受体基因多态性检测,比较两组β2-肾上腺素能受体基因多态性位点16Arg/Gly、27Gln/Glu、178Arg A/C基因型、等位基因频率,并分析不同性别、心功能分级、原发性疾病类型与β2-肾上腺素受体基因型的关系。结果观察组27Gln/Glu基因型中G/C型、等位基因G频率均显著高于对照组,差异有统计学意义(P<0.05),多态性位点16Arg/Gly、178Arg A/C基因型、等位基因频率方面两组比较均无显著差异(P>0.05);不同性别、原发性疾病类型患者β2-肾上腺素能受体27Gln/Glu基因型、等位基因频率比较差异均无统计学意义(P>0.05);多位点27Gln/Glu基因型G/C心功能分级显著高于CC型(P<0.05)。结论β2-肾上腺素能受体基因多态性位点27Gln/Glu与慢性心力衰竭后室性心律失常发生有关,特别是G/C型,为其发生易感基因,且与心功能分级相关。     

瘦素受体基因Gln223Arg多态性与2型糖尿病合并慢性肾功衰竭关系

目的探讨瘦素受体基因Gln223Arg多态性与2型糖尿病合并慢性肾功衰竭关系。方法采用聚合酶链反应及限制性片段长度多态性方法(PCR-RFLP)分别测定126例2型糖尿病、108例2型糖尿病合并慢性肾功衰竭和185例对照组样本的瘦素受体基因Gln223Arg的基因型,同时检测各组不同基因型样本的血清瘦素水平。结果 2型糖尿病合并慢性肾功衰竭组与正常对照组瘦素受体基因Gln223Arg基因型频率及等位基因频率比较差异有显著性(P0.01)。糖尿病组与正常对照组瘦素受体基因Gln223Arg基因型及等位基因分布频率差异显著性(P0.05)。2型糖尿病合并慢性肾功衰竭组中GG基因型与AA+AG基因型血清瘦素水平比较差异有显著性(P0.05)。相同基因型样本的血清瘦素水平组间比较,任意两组比较均有差异(P0.05)。结论瘦素受体基因Gln223Arg多态性与2型糖尿病合并慢性肾功衰竭相关。     

DNA修复基因XRCC1单核苷酸多态性与晚期非小细胞肺癌铂类药物化疗后生存期的关系

目的 研究DNA修复基因XRCC1单核苷酸多态性与晚期非小细胞肺癌（NSCLC）患者对顺铂或卡铂为主的方案化疗后生存期的关系。方法 经病理学确诊的晚期NSCLC患者135例，采用顺铂或卡铂为主的方案进行化疗。化疗前采集患者外周血，以聚合酶链反应-限制性长度片段分析（PCR—RFLP）方法进行XRCC1 Arg194Trp和XRCC1 Arg399Gln基因多态性的分型。比较不同基因型患者化疗后的中位生存时间（MST）和1、2年生存率。结果 中位随访12个月，135例患者的MST和1、2年生存率分别为12个月和48．1％、13．1％。携带XRCC1 399Arg／Arg的NSCLC患者化疗后MST和1、2年生存率分别为14．0个月和56．3％、20．8％；携带XRCC1 399Arg／Gin或Gin／Gln基因型的NSCLC患者化疗后MST和1、2年生存率分别为10．0个月和39．0％、7．6％，差异均有显著性（P〈0．05）。携带XRCC1 194Arg／Arg的NSCLC患者的MST和1、2年生存率分别为11．0个月和43、6％、13．2％；携带XRCC1 194Arg／Gln或Gln／Gln基因型的NSCLC患者MST和1、2年生存率分别为13．0个月和49．6％、11．3％，两组之间差异无显著性（P〉0．05）。结论 XRCC1 Arg399Gln基因多态性与晚期NSCLC患者铂类药物化疗后的生存期有关。XRCC1 Arg3 99Gln基因多态性可以在一定程度上判断晚期NSCLC患者铂类药物化疗后的预后。     

血管紧张素转换酶、血管紧张素原及载脂蛋白E基因多态性与冠心病的关系

目的：评估血管紧张素转换酶（ACE）基因、血管紧张素原基因（AGT）及载脂蛋白E（ApoE）基因多态性与冠心病的关系。方法：选择133例冠心病患者及122例健康对照者，用基因芯片技术检测ACE、AGT和ApoE基因多态性，并对比其基因型及等位基因频率。结果：冠心病组ACE DD基因型频率与对照组相比有显著差异，28．57％VS．13．12％，P〈0．01，ACE基因多态性与冠心病明显相关。AGT TT基因型频率与对照组相比有显著性差异，75．94%VS．47．54％，P〈0．001，两组T等位基因频率亦有显著性差异，0．87VS．0．71，P〈0.01。AGT基因多态性与冠心病明显相关。分析冠心病组ApoE基因型有六种，E2／E2，E2／E3，E2／E4，E3／E3，E3／E4和E4／E4，基因型及等位基因频率与对照组相比无显著性差异，P〉0．05。结论：ACE和AGT基因多态性可能是中国人冠心病的危险因素。基因芯片技术为研究多种易感基因与冠心病的相关性提供了高效、敏感的方法。     

中国北方汉族人乙二醛酶I基因AlalllGlu多态性与糖尿病并发冠心病的关系研究

目的探讨中国北方地区汉族人乙二醛酶I（GLO—I）基因AlalllGlu多态性与糖尿病并发冠心病的关系。方法应用聚合酶链反应限制性片段长度多态性（PCR—RFLP）技术，检测了161名对照组、99例糖尿病组和71例糖尿病并发冠心病组GLO-I基因AlalllGlu多态性的基因型和等位基因频率分布。分析基因多态性对糖化血红蛋白（HbAlc）、血糖、血脂水平的影响。结果3组研究对象的GLO—I基因AlalllGlu多态性基因型和等位基因频率分布差异无显著意义，不同基因型亚组间HbAlC、血糖、血脂水平无明显差别。Logistic回归分析显示，年龄、HbAlc是糖尿病并发冠心病的危险因素，HDL—C则是糖尿病并发冠心痛的保护因素（β=-2．708，Exp（β）=0．067，95％CI=0．009～0．488，P=0．008）。结论GLO-I基因AlalllGlu多态性与糖尿病并发冠心病无明显关联性，不是中国北方汉族人糖尿病并发冠心病发病的独立危险因素。     

老年原发性高血压患者β2肾上腺素受体基因Argl6Gly多态性研究

目的 探讨老年人（≥60岁）β2肾上腺素受体（β2-AR）基因Argl6Gly多态性与高血压病的关系。方法 随机抽取115名无血缘关系的老年原发性高血压患者（EH）为病例组，150名无血缘关系的健康老年人为对照组，采用PCR扩增技术测定两组对象的β2-AR基因型。结果高血压组的Arg／Arg、Gly／Gly和Arg／Gly基因型频率分别为22．81％、53．51％和23．68％；对照组分别为27．33％、67．33％和5．33％，两组间有显著性差异（P〈0．05）。Arg和Gly的等位基因频率高血压组为49．56％、50．44％；对照组为61．00％和39．00％，两组间亦有显著性差异（p〈0．05），但两组的Arg／Gly多态性分布均符合Hardy-Weinberg定律。结论 本研究对象的β2-AR基因多态性可能与原发性高血压有关。     

XRCC1和XPD基因多态性与喉癌遗传易感性的关系

目的:探讨X线修复交叉互补组1基因(X-ray repair cross complementing group 1,XRCC1)、人类着色性干皮病基因D(xeroderma pigmentosum complementary group D,XPD)多态性与喉癌遗传易感性的关系。方法:采用病例-对照设计方法对72例经病理确诊的喉鳞状细胞癌患者(病理组)和随机抽取的72例非癌症患者为对照组,均进行一般资料问卷调查和抽取外周静脉血进行XRCC1-Arg399Gln、XPD-Lys751Gln多态性检测和聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP)检测。结果:与携带XRCC1-399野生型(Arg/Arg)个体相比,病例组XRCC1第399位密码子杂合型(Arg/Gln)及突变型(Gln/Gln)分布频率高于对照组(P0.05),携带该基因型的个体喉癌的发病风险升高3.37(OR=3.37,95%,CI=1.69-6.70)倍;XPD-Lys751Gln各基因型差异2组间无统计学意义;交互作用分析显示,吸烟与不吸烟患者比较,携带XRCC1-399Arg/Gln+Gln/Gln基因型个体的喉癌发病风险差异未发现有统计学意义(χH2=0.09)。结论:XRCC1-399位点Arg→Gln的氨基酸替换可能导致喉癌的发病风险增加,XRCC1-Arg399Gln多态性可能与喉癌的遗传易感性有关。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.