IGFBP6在结直肠癌组织中的表达及其意义

摘要：目的：探讨胰岛素样生长因子结合蛋白6（IGFBP6）在结直肠癌（CRC）组织中的表达水平及其在CRC中的临床意义。 方法：实时荧光定量PCR(qRT-PCR)检测CRC患者癌组织及其相应癌旁组织中IGFBP6 mRNA的表达水平;免疫组织化学法（IHC）检测CRC患者癌组织及癌旁组织石蜡切片中IGFBP6蛋白的表达;分析其与CRC患者临床病理参数及预后关系。 结果：CRC患者癌组织中IGFBP6 mRNA表达水平（0.26±0.39）低于癌旁组织（1.22±0.75）,差异有统计学意义（t=8.288,P＜0.01）;CRC患者癌组织中IGFBP6蛋白阳性率（38.1%）低于癌旁组织(61.9%),且与TNM分期相关（P均＜0.01）。生存曲线分析显示,IGFBP6低表达的CRC患者生存时间明显缩短。 结论：低表达的IGFBP6可作为CRC诊断及预后判断潜在的生物学标志物。     

胃肠道间质瘤胰岛素样生长因子1受体表达水平与伊马替尼耐药的相关性

目的：探讨胃肠道间质瘤（gastrointestinal stromal tumor，GIST）中胰岛素样生长因子1受体（insulin-like growth factor 1 receptor，IGF1R）的表达与伊马替尼（imatinib mesylate，IM）耐药的关系。方法：回顾性分析2008年1月至2014年1月复旦大学附属中山医院普通外科收治的134例GIST患者的临床资料，其中IM耐药26例，非耐药108例。将所有患者术后病理标本制成组织芯片。采用免疫组化法检测组织芯片中IGF1R蛋白表达水平，并分析不同临床病理特征组间IGF1R表达差异。采用Kaplan-Meier绘制生存曲线，对IM耐药患者进行分析。结果：GIST组织IGF1R高表达组与低表达组间性别、年龄、肿瘤大小、原发部位、核分裂相、突变基因、美国国立卫生研究院（NIH）危险度分级差异均无统计学意义。IM耐药患者GIST组织IGF1R的表达率（73.08%）高于非耐药患者（41.67%），差异有统计学意义（χ²=8.286，P=0.004）。IM耐药患者的生存分析显示，IGF1R高表达病例总生存时间（overall survival，OS）显著低于IGF1R低表达患者（35.3 vs 71.3个月），差异有统计意义（P=0.04）。结论：IGF1R可能参与GIST患者IM耐药，IM耐药患者IGF1R高表达可作为不良预后指标。     

中低位直肠癌患者的肛门直肠功能及其影响因素

  目的  研究中低位直肠癌患者的肛门直肠功能及其影响因素  目的  2012年9月至2013年11月连续纳入在北京协和医院就诊的中低位直肠癌患者, 填写中低位直肠癌患者排便功能的研究报告表, 并进行三维高分辨肛门直肠压力测定检查。根据肿瘤远侧缘距肛缘的距离将患者分为中位组和低位组  结果  共纳入66例中低位直肠癌患者, 其中男45例, 女21例; 平均年龄(58.86±10.99)岁; 低位组22例, 中位组44例。95.5%患者有便血, 50.0%排便次数增多, 30.3%~40.9%有粪便性状异常、排便急迫感、排便不尽感、里急后重等症状; 便血、排便次数、排便不尽感与肿瘤浸润深度呈正相关(r=0.308, P=0.012;r=0.290, P=0.018;r=0.305, P=0.013)。所有患者的直肠肛门抑制反射均无受损, 持续便意感阈值和最大耐受量均较正常值明显降低; 持续便意感阈值、最大耐受量与肿瘤浸润深度呈负相关(r=-0.333, P=0.007;r=-0.323, P=0.009)。与中位组相比, 低位组患者排便费力发生率高(27.2%比6.8%, P=0.031), 肛门平均静息压低[87.20(49.80)mmHg比108.25(41.80)mmHg, P=0.017]  结论  在中低位直肠癌患者, 除便血外, 排便症状多样化, 且不具有特异性; 中低位直肠癌患者的直肠感觉功能受损明显, 肿瘤浸润深度和肿瘤远侧缘距肛缘的距离不同程度地影响患者肛门直肠感觉和动力功能。     

中国人群胰腺癌与胃癌HER2/neu基因表达

  目的  探讨胰腺癌与胃癌组织中HER2/neu基因表达状态及其在治疗与评估临床结局中的作用。  方法  应用免疫组织化学和多色荧光原位杂交技术, 检测北京协和医院手术切除的81例胰腺导管癌及癌旁胰腺组织和100例胃癌及癌旁胃组织标本中HER2/neu蛋白表达及基因状态的变化, 分析HER2/neu蛋白表达与基因状态间的关系及其与胰腺癌和胃癌临床病理改变间的关系。  结果  免疫组织化学显示, 81例胰腺癌组织中9例(11.1%)HER2/neu蛋白表达阳性(2+及3+), 100例胃癌组织中13例(13%)HER2/neu蛋白表达阳性(2+及3+); 荧光原位杂交结果显示, 81例胰腺癌组织中15例(18.5%)HER2/neu基因扩增, 100例胃癌组织中11例(11%)HER2/neu基因扩增。胰腺癌HER2/neu基因扩增与淋巴结转移有显著相关性(P=0.001)。胃癌组织中6例HER2/neu蛋白3+病例均显示HER2/neu基因扩增, 且胃癌组织HER2/neu蛋白表达与其基因扩增有显著相关性(P < 0.0001)。无论是癌旁胰腺组织还是癌旁胃组织均未检测到HER2/neu蛋白表达及基因扩增。  结论  胰腺癌组织HER2/neu蛋白表达与基因扩增不一致, 而胃癌组织HER2/neu蛋白表达与基因扩增有显著相关性。HER2/neu基因异常可能在胰腺癌及胃癌的发生发展中起着重要作用, 对胰腺癌及胃癌患者进行HER2/neu基因状态检测可能对其靶向治疗具有一定的指导意义。     

miRNA-21在结直肠癌中的表达研究

目的 检测MicroRNA-21（miRNA-21）在正常人和结直肠癌患者血清,以及结直肠癌患者癌组织和癌旁组织中的表达,探讨其与结直肠癌临床病理参数的关系.方法 采用实时荧光定量PCR（RT-qPCR）技术检测正常人和结直肠癌患者血清,以及结直肠癌患者癌组织和癌旁组织中的表达,分析miRNA-21的表达与结直肠癌临床病理参数的关系.结果 miRNA-21在结直肠癌患者血清中表达水平显著高于正常人血清（P＜0.05）;结直肠癌组织中miRNA-21表达水平明显高于癌旁组织;中晚期（Ⅲ期和Ⅳ期）结直肠癌组织中miRNA-21表达水平明显高于早期（Ⅰ期和Ⅱ期）结直肠癌（P＜0.05）;低分化肿瘤组织中miRNA-21表达水平明显高于中高分化者;有淋巴结转移的结直肠癌组织中miRNA-21表达水平明显高于无淋巴结转移者.结论 miRNA-21在结直肠癌患者血清及肿瘤组织中呈高表达,可能与结直肠癌的发生发展有关.     

DWI评估宫颈鳞状细胞癌增殖和侵袭性

目的 探讨DWI不同ADC值预测宫颈鳞状细胞癌（CSCC）增殖和侵袭性的价值。方法 对96例CSCC患者术前行盆腔常规MRI和DWI,测量肿瘤最小ADC值、平均ADC值和最小ADC率（最小ADC值/平均ADC值）,比较不同Ki-67表达及临床病理特征患者间的差异。结果 与低侵袭性宫颈癌相比,最小ADC值在Ki-67高表达、肿瘤最长径 ≥ 4 cm、高FIGO分期、低分化、宫颈间质浸润深度 ≥ 1/2、宫旁受累、LVI、淋巴结转移和PNI阳性的高侵袭性宫颈癌患者中显著降低（P均<0.05）。与平均ADC值和最小ADC率相比,最小ADC值预测CSCC不同临床病理特性的ROC曲线下面积和效能较高,且与Ki-67指数呈负相关（r=-0.48,P<0.001）,与其他临床病理特征如肿块大小、FIGO分期、病理分级、间质浸润深度、宫旁受累、LVI、淋巴结转移和PNI呈负相关（r=-0.36、-0.34、-0.27、-0.40、-0.33、-0.60、-0.61、-0.41,P均<0.05）。结论 最小ADC值可有效反映CSCC的增殖和侵袭性。     

PROX1通过上皮间质转化促进非小细胞肺癌进展

目的： 探讨转录因子Prospero同源框1（Prospero-related homeobox 1，PROX1）在非小细胞肺癌（non-small cell lung cancer，NSCLC）进展中的作用和机制。方法： 对含有108对非小细胞肺癌组织的组织芯片进行免疫组化染色，分析PROX1表达和NSCLC患者预后间的关系。采用Western印迹法和实时定量PCR分析PROX1在NSCLC细胞系中的表达情况和上皮间质转化的标志物。采用CCK-8、Transwell试验检测肿瘤细胞的增殖、迁移和侵袭能力。结果： PROX1在非小细胞肺癌组织中的表达上调。PROX1的表达与肿瘤直径、淋巴转移显著相关（P=0.003、0.042）。高表达PROX1的NSCLC患者其5年复发率高于PROX1低表达组（70.9%vs 50.9%，P=0.005），而5年生存率低于PROX1低表达组（49.1%vs 66.0%，P=0.016）。CCK-8和Transwell实验的结果显示，敲减PROX1后肿瘤的增殖、侵袭和转移能力明显减弱（P<0.01、P<0.05）。敲减PROX1后E-钙粘蛋白表达上调而波形蛋白表达下降（P<0.001）。结论： PROX1表达增高可通过促进上皮间质转化而促进NSCLC进展；PROX1是潜在的NSCLC预后预测因子。     

不同病理特征直肠癌的MR灌注成像参数分析

目的 探讨不同病理特征直肠癌MR灌注成像参数的改变。方法 回顾性分析经病理确诊为直肠癌的35例患者影像及病理资料,所有患者均接受MR灌注成像检查,并获得直肠癌和癌周正常直肠壁各MR灌注参数值[对比剂容积转换常数（Ktrans）、速率常数（Kep）、血管外细胞外间隙容积分数（Ve）及初始强化曲线下面积（iAUC）]。分析病理学特征,包括组织分化程度、T分期、N分期、脉管浸润和神经周围浸润情况;对不同病理状态的MR灌注参数值进行统计学分析。结果 直肠癌Ktrans及iAUC均高于癌周正常直肠壁（P均<0.05）,直肠癌Ve低于癌周正常直肠壁（P<0.05）,Kep差异无统计学意义（P=0.345）。不同组织分化程度直肠癌的Ktrans、Ve、Kep和iAUC差异均无统计学意义（P均>0.05）。T3~4期直肠癌Ktrans及Kep较T1~2期显著升高（P均<0.05）;T1~2期与T3~4期直肠癌的iAUC及Ve差异无统计学意义（P均>0.05）。N1~2分期的Kep高于N0分期（P=0.006）,余各灌注参数差异均无统计学意义（P均>0.05）。有无脉管浸润和神经周围浸润的直肠癌MR灌注参数差异均无统计学意义（P均>0.05）。结论 直肠癌的MR灌注成像参数可反映其不同病理特征。     

MRI影像组学预测结直肠癌患者KRAS基因突变

目的 构建MR T2WI影像组学模型,评价其预测结直肠癌患者Kirsten大鼠肉瘤（KRAS）病毒癌基因亚型的价值。方法 将99例经病理证实的结直肠癌患者分为训练组（n=68）及验证组（n=31）,根据KRAS基因检测结果进一步将其分为突变亚组及野生亚组,训练组2亚组分别含36、32例,验证组2亚组分别含16、15例,比较亚组间实验室检查结果及肿瘤大小的差异;提取并筛选训练组MR T2WI影像组学特征,构建影像组学模型、临床模型及影像组学-临床联合模型。绘制受试者工作特征（ROC）曲线,计算曲线下面积（AUC）,评价各模型预测结直肠癌患者KRAS基因亚型的效能;以DeLong检验比较各模型间效能差异。通过校正曲线分析3种模型的校正性能,以Hosmer-Lemeshow检验评价校准曲线的校准度;以决策曲线分析（DCA）评价3种模型临床应用价值。结果 训练组和验证组内亚组间实验室检查结果及肿瘤大小差异均无统计学意义（P均>0.05）。共提取3个组学特征用于构建预测模型。影像组学模型与临床模型、影像组学-临床联合模型预测2组KRAS基因亚型的AUC差异均无统计学意义（P均>0.05）;影像组学-临床联合模型预测训练组KRAS基因亚型的AUC显著高于临床模型（P<0.05）,但在验证组差异均无统计学意义（P>0.05）。校准曲线及Hosmer-Lemeshow检验显示3种模型预测值和观察值的一致性良好（P均>0.05）。影像组学模型和影像组学-临床联合模型在2组中的DCA曲线净收益值均高于临床模型。结论 MR T2WI影像组学纹理特征预测结直肠癌患者KRAS基因突变亚型具有一定潜力。     

长链非编码RNA SERTAD1-1在结直肠癌中的表达及意义

目的 探讨长链非编码RNA-癌基因SEI1-1（lnc-SERTAD1-1）对结直肠癌增殖、迁移及预后的影响。方法 选取125例结直肠癌患者的标本,检测癌组织和癌旁正常组织中lnc-SERTAD1-1的表达水平,分析lnc-SERTAD1-1与临床病理特征的相关性,分析lnc-SERTAD1-1对结直肠癌预后的影响。检测正常人结肠组织细胞CCD-18Co与人结直肠癌细胞HCT15中lnc-SERTAD1-1的表达。慢病毒转染构建含有目的基因lnc-SERTAD1-1过表达的HCT15（HO）及含有空白载体质粒的HCT15（HOC）,检测其lnc-SERTAD1-1以及SERTAD1蛋白的表达,并检测lnc-SERTAD1-1对结直肠癌细胞增殖和迁移能力的影响。结果 与癌旁正常组织比较,lnc-SERTAD1-1在结直肠癌组织（0.002 198±0.000 499 vs. 0.002 998±0.000 392,P < 0.001）和癌细胞（0.000 123±0.000 010 vs. 0.000 182±0.000 012,P = 0.004）中呈低表达水平 ;其表达高低与结直肠癌患者的肿瘤部位、肿瘤大小及肿瘤的大体分型相关（P均< 0.05）。在125例结直肠癌患者中,lnc-SERTAD1-1高表达（≥0.000 970）是其术后总生存及无病生存的独立保护因素（总生存HR = 0.228,95% CI：0.107 ~ 0.485,P < 0.001;无病生存HR = 0.228,95% CI：0.103 ~ 0.506,P < 0.001）。体外实验显示lnc-SERTAD1-1表达上调能抑制结直肠癌细胞的增殖和迁移（P均< 0.05）。结论 lnc-SERTAD1-1通过抑制结直肠癌细胞的增殖和迁移发挥抑癌基因的作用,是结直肠癌重要的预后影响因素。     

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.     

手转胎头术失败的原因与分娩结局临床分析

目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4％(55/72)]明显高于成功组[31.7％(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3％(42/72)]高于成功组[38.1％ (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9％ (28/72)]高于成功组[23.8％(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大＜6 cm、胎头位于坐骨棘上及宫口开大8～10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1％(44/72)]高于成功组[38.9％(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2％(52/72)]明显高于成功组[34.1 ％(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.