IL-27通过信号通路p38MAPK和P13K途径调节中性粒细胞Mac-1、fMLP-R及IL-1β表达

本研究探讨IL-27调节人外周血中性粒细胞中黏附分子Mac-1、趋化因子受体fMLP—R和促炎因子IL-1β表达的信号通路。采用Ficoll密度梯度离心及低渗裂解残存红细胞方法分离高纯度的外周血中性粒细胞。用RT-PCR方法检测中性粒细胞IL-27受体（WSX-1／TCCR和gp130）mRNA表达。分别应用IL-27及信号通路p38MAPK、P13K和ERK抑制剂SB203580、LY294002、U0126处理中性粒细胞,用实时定量RT-PCR检测作用前后fMLP-R和IL-1βmRNA水平变化;应用放射免疫法检测作用前后培养上清液中IL-1β的水平变化;流式细胞术检测作用前后Mac-1表达水平变化。结果表明：人外周血中性粒细胞协同表达IL-27受体的两个亚单位WSX-1／TCCR和gp130,IL-27下调中性粒细胞表面黏附分子Mac-1表达（P〈0．05）,SB203580阻断了IL-27对Mac-1的下调作用（P〈0．05）,而LY294002及U0126无阻断作用（P〉0．05）。相反,IL-27上调中性粒细胞中fMLP-R和IL-1BmRNA的表达并能增加IL-1β释放（P〈0．05）,LY294002阻断了IL-27对fMLP-R和IL-1β的上调作用（P〈0．05）。而SB203580及U0126无阻断作用（P〉0．05）。结论：IL-27与IL-27R相互作用,可能通过p38MAPK和PI3K信号途径调节人外周血中性粒细胞中Mac-1、fMLP-R及IL-1β表达。     

血清超敏C反应蛋白白细胞介素测定与糖尿病大血管病变的相关性

目的探讨超敏C反应蛋白（hs-CRP）、白细胞介素6（IL-6）和白细胞介素18（IL-18）与2型糖尿病并发大血管病变的相关性。方法采用酶联免疫吸附试验法测定50例2型糖尿病（DM）患者和30名健康对照组血清hs-CRP、IL-6和IL-18的水平，并进行相关性分析。结果2型DM组hs—CRP、IL-6和IL-18水平显著高于健康对照组，差异有统计学意义（P〈0．01），并发大血管病变患者hs-CRP、IL-6和IL-18较非大血管病变者差异有统计学意义（P〈0．05），相关分析显示：血清IL-6、IL-18与hs-CRP呈显著正相关（r=0．261，P〈0．05；r=0．320，P〈0．05），hs-CRP与空腹血糖（r=0．296，P〈0．05）呈正相关。结论hs—CRP、IL-6和IL-18在2型DM并发大血管病患者中升高，可能在2型DM的发病及进展过程中起重要的作用。     

白细胞介素-6在2型糖尿病患者腹部皮下和网膜脂肪组织中的表达及其与胰岛素抵抗的关系

目的探讨白细胞介素石（IL-6）基因在2型糖尿病（T2DM）患者腹部皮下和网膜脂肪组织中的表达情况，及其与胰岛素抵抗的关系。方法用半定量RT-PCR方法检测22例正常人（对照组）和20例T2DM（糖尿病组）患者的大网膜与皮下脂肪组织IL-6mRNA的表达水平，并测量体重、血压、腰围、臀围、血糖、空腹胰岛素、血脂和胰岛素敏感指数（IAI）。结果①糖尿病组网膜和皮下脂肪的IL-6mRNA表达量均高于对照组（P〈0．05）；对照组网膜组织的IL-6mRNA表达量高于皮下脂肪组织（P〈0．05）．而糖尿病组网膜和皮下脂肪组织差异无显著性（P〉0．05）。②将两组数据合并，网膜和皮下脂肪的IL-6mRNA表达量与腰臀比、胰岛素抵抗指数（HOMA-IR）呈正相关（P〈0．05），与血浆IAI呈负相关（P〈0．05），与其他因素均无相关性（均P〉0．05）。③多元逐步回归分析发现，皮下脂肪IL-6mRNA表达量与HOMA—IR、腰臀比相关（P〈0．05），网膜IL-6mRNA表达量与HOMA—IR相关（P〈0．05）。结论，12DM患者网膜和皮下脂肪组织IL-6mRNA表达水平升高，可以作为胰岛素抵抗的一个重要参数。     

NOD1在肥胖糖尿病患者脂肪细胞中的表达及对胰岛素抵抗的作用

【目的】探讨肥胖糖尿病（DM）患者脂肪细胞免疫受体核苷酸结合寡聚化结构域蛋白1（nucleotide-binding oligomerization domain-containing protein,NOD1）的表达与胰岛素抵抗的关系。【方法】取10例肥胖 DM患者（DM组）及10例非DM肥胖患者（NDM组）腹部皮下脂肪细胞,采用Real-time PCR方法检测两组脂肪细胞受体 NOD1的表达,加入 NOD1受体激动剂 iE-DAP,用酶联免疫吸附法（ELISA）检测两组细胞炎性细胞因子白细胞介素（IL）-6、IL-8及单核细胞趋化因子1（MCP-1）水平,2-脱氧-3 H-D-葡萄糖摄入法观察基础状态和 iE-DAP刺激状态的葡萄糖摄取率。【结果】DM组脂肪细胞 NOD1 mRNA的表达显著高于 NDM组（P＜0．05）;iE-DAP刺激下DM组 IL-6、IL-8及 MCP-1的分泌水平均显著高于 NDM组（P ＜0．05）,DM组胰岛素刺激状态下脂肪细胞葡萄糖摄取率显著低于 NDM组（P＜0．05）。【结论】NOD1介导的炎症反应可能参与肥胖糖尿病胰岛素抵抗的发生。     

哮喘患者诱导痰CC16mRNA表达的变化及意义

目的探讨诱导痰CC16mRNA测定在哮喘临床中的应用价值。方法选择23例缓解期和45例急性发作期哮喘患者，以逆转录聚合酶链反应检测诱导痰CC16mRNA的表达，并与诱导痰细胞分类、IL-8水平及中华医学会呼吸病学分会制订的哮喘分期和严重程度分级标准进行对照研究。结果哮喘急性发作组诱导痰CC16mRNA水平显著低于缓解组（P〈0．01），中至重度发作组诱导痰CC16mRNA水平低于轻度发作组（P〈0．01）。中重度哮喘患者治疗后，诱导痰CC16mRNA、中性粒细胞计数、IL-8水平与治疗前比较差异均有统计学意义（P均〈0．01）。哮喘患者诱导痰CC16mRNA与患者第1秒用力呼气容积占用力肺活量百分比成正相关（r=0．723，P〈0．01），而诱导痰CC16mRNA与中性粒细胞计数与IL-8水平均呈负相关（r分别为-0．653、-0．698，P均〈0．05）。结论诱导痰CC16mRNA可能成为监测哮喘气道炎症、评价药物疗效的指标。     

CRP、IL-6、IL-10在儿童血液病化疗后感染中的变化

【目的】通过观察C-反应蛋白（CRP）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）在儿童血液病化疗后感染中的变化,探讨CRP、IL-6和IL-10对临床治疗的指导价值。【方法】对40例符合本研究标准的血液病患儿,分别在化疗前的基础值（T0）,化疗后3d（T1）,发热后d1（T2）、d7（即使用抗生素d7,T3）采集血标本,分析儿童血液病化疗后合并感染前后CRP、IL-6,IL-10的变化及其与感染的发生发展之间的关系。【结果】T0与T1相比CRP、IL-6、IL-10差异无统计学意义（P〉0．05）;T1与T2相比CRP、IL-6差异有统计学意义（P〈0．05）,IL-10差异无统计学意义（P〉0．05）;T2与T3相比CRP、IL-6、IL-10差异有统计学意义（P〈O．05）。【结论】CRP、IL-6水平在儿童血液病化疗后感染中均有显著上升,感染控制时其水平趋于正常水平,且与中性粒细胞减少与否无关,动态联合监测CRP与IL-6作为早期发现感染、指导治疗、判断疗效的指标是值得在临床工作中推广。IL-10在儿童血液病化疗后中性粒细胞减少并感染中增高不明显,提示IL-10水平与中性粒细胞数目相关。     

48例糖尿病并发感染时单核细胞趋化蛋白与蛋白表达

目的采用两种技术检测糖尿病并发感染患者单核细胞趋化蛋白（MCP-1）mRNA与蛋白表达的变化。方法随机选择初诊糖尿病并发感染患者,应用酶联免疫吸附试验（ELISA）、竞争法逆转录聚合酶链反应（RT-PCR）及实时荧光定量PCR（FQ-PCR）检测患者感染治愈前、后MCP-1蛋白及mRNA定量水平;同时还分析了与其他参数的关系。结果糖尿病并发感染治疗前后趋化因子MCP-1 mRNA与蛋白表达均明显升高,MCP-1mRNA（FQ-PCR）与蛋白表达水平呈正相关性,mRNA（竞争性密度比法）与其他结果未见明显相关性。结论利用FQ-PCR技术检测糖尿病并发感染患者MCP-1mRNA与蛋白水平具有较高的一致性,对研究其病理机制和I临床观察有重要意义。     

不同剂量氯胺酮对体外循环心脏手术患者CRP、IL-6及IL-8的影响

【目的】探讨不同小剂量氯胺酮对体外循环（Cardiopumonary bypass，CPB）瓣膜替换手术患者超敏C反应蛋白（hypersensitive C-reactive protein，hs—CRP）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）的影响。【方法】30例择期瓣膜替换术病人，随机分成氯胺酮Ⅰ组（n=10）、氯胺酮Ⅱ组（n=10）和对照组（n=10）。氯胺酮Ⅰ、Ⅱ组于麻醉诱导开始时分别按0．25mg／kg和0．5mg／kg静注氯胺酮一次，对照组则采用等量生理盐水注射。三组分别于麻醉诱导前（T1）、术后1h（T2）及术后24h（T3）三个时间点测定动脉血中hs—CRP、IL6和IL-8的水平。【结果】三组hs-CRP的水平在L均较T1有明显升高（P〈0．05）；IL-6和IL-8的水平在T2、T3较T1有明显升高（P〈0．05）。氯胺酮Ⅱ组hs-CRP的水平在T3较对照组明显降低（P〈0．05），且氯胺酮Ⅰ,Ⅱ组间hPCRP的水平差异有显著性（P〈0．05）；氯胺酮Ⅰ、Ⅱ组IL6、IL-8的水平在T2、T3较对照组均明显降低（P〈0．05），但氯胺酮两组间差异无显著性（P〉0．05）。【结论】小剂量氯胺酮能有效抑制CPB诱发的CRP、IL-6和IL-8水平升高，0．5mg／kg剂量氯胺酮比0．25mg／kg剂量似乎更有效。     

2型糖尿病合并冠心病与Leptin及IL-6、CRP的相关性

目的探讨瘦素（Leptin）水平与2型糖尿病（T2DM）合并冠心病（CHD）炎性反应的关系,以及炎性反应蛋白和炎性因子在合并冠心病中的相关性及意义。方法选择临床确诊的住院和门诊T2DM患者151例,分为T2DM组（76例）和T2DM合并CHD组（75例）。采用ELISA法检测血清Leptin和IL-6、hs—CRP水平,进行对比分析。结果①T2DM患者外周血血清Leptin和IL-6、hs—CRP水平与对照组相比较,差异有统计学意义（P〈0．05）;T2DM合并CHD患者组的外周血血清Leptin和IL-6、hs—CRP水平与T2DM相比较,差异有统计学意义（P〈0．05）。②T2DM合并CHD组外周血Leptin水平与IL-6、hs—CRP水平呈显著正相关（r=0．776、P〈0．05,r=0．791、P〈0．05）;hs—CRP与IL-6呈显著正相关（r=0．824、P〈0．05）。结论T2DM患者体内存在Leptin和IL-6、CRP的异常表达,合并CHD患者更为显著,且三者具有显著相关性。Leptin及IL-6、CRP参与了T2DM合并CHD的发生、发展．此为早期干预T2DM患者合并CHD提供了理论依据。     

毒素清对肺炎克雷伯杆菌肺炎老龄大鼠心肌损伤中炎症细胞因子表达的影响

目的从心肌组织肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、巨噬细胞炎症蛋白-2（MIP-2）蛋白表达和MIP-2 mRNA表达变化揭示中药毒素清对老年肺炎心肌损伤的保护作用机制。方法将老龄大鼠随机分为对照组、模型组、毒素清组和左氧氟沙星组，制备肺炎克雷伯杆菌肺炎模型。计数外周血和支气管肺泡灌洗液（BALF）中的白细胞（WBC）计数和中性粒细胞（PMN）计数，采用放射免疫法测定外周血IL-1、TNF—α水平，采用免疫组化方法和原位杂交方法结合图像分析技术测定心肌组织MIP-2、IL-1、TNF-α蛋白表达及MIP-2 mRNA表达。结果与对照组比较，模型组外周血和BALF中WBC、PMN明显升高，血清和心肌组织IL-1、TNF-α水平明显增加，MIP-2的蛋白和mRNA表达明显增强（P〈0．05或P〈0．01）；与模型组比较，左氧氟沙星组和毒素清组外周血和BALF中WBC、PMN明显减少，血清和心肌组织IL-1、TNF-α水平降低，MIP-2的蛋白和mRNA表达明显减弱（P均〈0．01）。结论细胞因子TNF-α、IL-1、MIP-2紊乱参与老年肺炎导致心肌损伤的发生发展。阻抑TNF-α、IL-1、MIP-2介导的损伤可能是毒素清保护老年肺炎时心肌损伤的主要途径。     

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.     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.