慢性常压缺氧和缺氧伴CO_2潴留大鼠红细胞变形能力与膜收缩蛋白的研究

本文测定了慢性常压缺氧（Ⅱ组）、缺氧伴ＣＯ－２潴留（Ⅲ组）及对照组（Ⅰ组）大鼠红细胞变形能力与红细胞膜收缩蛋白二聚体（ＳＰ－Ｄ）和四聚体（ＳＰ－Ｔ）的相对含量。结果表明，Ⅱ、Ⅲ组红细胞变形指数（ＤＩ）和ＳＰ－Ｄ、ＳＰ－Ｔ相对含量与Ⅰ组均有显著差异，且Ⅱ、Ⅲ组的ＤＩ与ＳＰ－Ｄ／ＳＰ－Ｔ比值呈显著负相关。提示膜收缩蛋白的异常，可能是导致慢性缺氧和伴ＣＯ－２潴留大鼠红细胞变形能力降低的重要因素之一。     

Serum protein profiles to identify head and neck cancer.

PURPOSE: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples. EXPERIMENTAL DESIGN: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA). RESULTS: Several proteins, with masses ranging from 2778 to 20800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls. CONCLUSIONS: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.     

The early detection research network surface-enhanced laser desorption and ionization prostate cancer detection study: A study in biomarker validation in genitourinary oncology

Prostate-specific antigen (PSA) screening has led to a dramatic increase in prostate cancer detection with a concurrent stage migration. Although the test has revolutionized prostate cancer detection by identifying disease that is potentially curable in the majority of men, only 25% of men receiving test results of PSA > 4 ng/ml will have prostate cancer and many men receiving a normal PSA will have disease, including high-grade disease. There is a need for improved biomarkers for detecting prostate cancer. One such method of cancer detection is surface-enhanced laser desorption and ionization (SELDI). The Early Detection Research Network (EDRN) validation study for SELDI for prostate cancer is described. In a three-stage study, the portability and reproducibility of the technique will be determined; the predictive algorithm will be refined in a multi-institutional case-control population; followed by ultimate validation in the context of a prospective trial with complete disease ascertainment. The unique aspect of the EDRN SELDI validation study is the novel use of two groups of cancer cases: those cases with higher-risk disease (Gleason > or = 7) and those cases with lower-risk disease (Gleason < or = 6). This study will allow the first evaluation of a predictive algorithm that includes prognosis in disease screening. The EDRN SELDI prostate cancer biomarker validation study is a rigorous evaluation of a new detection method for prostate cancer. The methodologies used for this evaluation will prove useful for guiding future biomarker studies in this challenging disease.     

Boosted decision tree analysis of surface-enhanced laser desorption/ionization mass spectral serum profiles discriminates prostate cancer from noncancer patients

BACKGROUND: The low specificity of the prostate-specific antigen (PSA) test makes it a poor biomarker for early detection of prostate cancer (PCA). Because single biomarkers most likely will not be found that are expressed by all genetic forms of PCA, we evaluated and developed a proteomic approach for the simultaneous detection and analysis of multiple proteins for the differentiation of PCA from noncancer patients. METHODS: Serum samples from 386 men [197 with PCA, 92 with benign prostatic hyperplasia (BPH), and 96 healthy individuals], randomly divided into training (n = 326) and test (n = 60) sets, were analyzed by surface-enhanced laser desorption/ionization (SELDI) mass spectrometry. The 124 peaks detected by computer analyses were analyzed in the training set by a boosting tree algorithm to develop a classifier for separating PCA from the noncancer groups. The classifier was then challenged with the test set (30 PCA samples, 15 BPH samples, 15 samples from healthy men) to determine the validity and accuracy of the classification system. RESULTS: Two classifiers were developed. The AdaBoost classifier completely separated the PCA from the noncancer samples, achieving 100% sensitivity and specificity. The second classifier, the Boosted Decision Stump Feature Selection classifier, was easier to interpret and used only 21 (compared with 74) peaks and a combination of 21 (vs 500) base classifiers to achieve a sensitivity and specificity of 97% for the test set. CONCLUSIONS: The high sensitivity and specificity achieved in this study provides support of the potential for SELDI, coupled with a bioinformatics learning algorithm, to improve the early detection/diagnosis of PCA.     

30例老年非霍奇金淋巴瘤的临床病理学特征、疗效及预后分析

本研究探讨老年非霍奇金淋巴瘤（non—Hodgkin’s lymphoma,NHL）的临床病理学特征、疗效和预后相关因素.对2003年1月-2012年12月中国人民解放军总医院老年血液科收治的30例老年NHL患者的临床资料进行回顾性分析,包括患者的一般临床特征、病理特点、化疗方案选择及临床反应,并运用Kaplan—Meier曲线进行生存分析,应用cOx回归模型对相关预后因素（包括年龄、IPI评分、B组症状、Ann—Arbor分期和LDH水平）进行多变量分析.结果表明,30例患者中位年龄82．5岁;所有患者均有合并症,其中以心血管系统疾病（包括高血压、冠心病、心律失常等）最常见,少数（8／30）合并第二肿瘤;出现B组症状的占63％（19／30）;病理分型中仅2例为T细胞淋巴瘤,其余为B细胞淋巴瘤,其中弥漫大B细胞淋巴瘤占所有B细胞淋巴瘤的57％（17／28）;Ann—Arbor分期Ⅰ-Ⅱ期占37％（1l／30）,Ⅲ-Ⅳ期占63％（19／30）;IPI评分2分以下10例,3分4例,4—5分16例,3—5分的患者占67％（20／30）;初诊时有43％（13／30）患者的LDH高于正常。全组病例均采用改良R—CHOP为基础的个体化方案化疗,4个疗程后CR14例,PR13例,PD2例,SDl例,治疗总反应率为90％;全组病例1年、2年总生存率分别为73．3％、43．3％;半年、1年无进展生存率分别为62．2％、54．9％;COX回归多变量分析显示,B组症状和Ann—Arbor分期是影响老年NHL生存的独立预后因素（P=0．014、0．039;RR=6．678、4．939）结论：老年NHL患者症状不典型,初诊时分期较晚,合并基础疾病多,由于个体差异大,应根据不同预后采取个体化治疗;以脂质体阿霉素为基础的CHOP方案对心脏的毒性低,对老年NHL可能是一种安全有效的方案;老年NHL患者无B组症状和Ann—Arbor分期≤Ⅱ期是老年NHL患者预后良好的指标。     

抗童虫表膜单克隆抗体与吡喹酮协同杀血吸虫作用

目的为观察抗血吸虫童虫表膜单克隆抗体与吡喹酮协同杀灭血吸虫的作用。方法用药物加单克隆抗体被动转移小鼠试验，计算小鼠抗攻击感染的减虫率和减卵率。结果在单抗被动转移小鼠感染3d后加吡喹酮组，其减虫率减卵率分别为91.9％和90.3％，均明显高于单用药物组17.2％、26.9％的减虫率和减卵率;在单抗被动转移小鼠感染38d后加吡喹酮组，其减虫率、减卵率分别为96.9％和83.4％，亦明显高于单用药物组84.9％、31.9％的减虫率和减卵率。结论被动转移的单抗与吡喹酮表现为一种明显的协同杀虫减卵作用。宿主免疫水平的高低明显影响吡喹酮的杀虫作用，提高宿主体内特异性抗体水平，可显著加强吡喹酮预防血吸虫感染和杀灭血吸虫的作用。     

Effects of chlorpyrifos and chlorpyrifos-oxon on the dynamics and movement of mitochondria in rat cortical neurons

Organophosphate (OP)-based pesticides have been used extensively for decades, and as a result, they have become almost ubiquitous in our environment. There is clinical and animal evidence to suggest that chronic exposures to OPs can lead to cognitive dysfunction and other neurological abnormalities, although the mechanism for these effects is unknown. We previously reported that repeated, subthreshold exposures (defined as doses not associated with signs of acute toxicity) to the commonly used OP chlorpyrifos (CPF) resulted in protracted impairments in the performance of attention and memory-related tasks in rodents as well as deficits in axonal transport ex vivo (in the sciatic nerve). Here, we investigated the effects of CPF and its active metabolite CPF oxon (CPO) on the dynamics and movement of mitochondria in rat primary cortical neurons using time-lapse imaging techniques. Exposure to CPF (1.0-20.0 μM) or CPO (5.0 nM-20.0 μM) for 1 or 24 h resulted in a concentration-dependent increase in mitochondrial length, a decrease in mitochondrial number (indicative of increased fusion events), and a decrease in their movement in axons. The changes occurred at concentrations of CPF and CPO that did not inhibit acetylcholinesterase activity (the commonly cited mechanism of acute OP toxicity), and they were not blocked by cholinergic receptor antagonists. Furthermore, the changes did not seem to be associated with direct (OP-related) effects on mitochondrial viability or function (i.e., mitochondrial membrane potential or ATP production). The results suggest that an underlying mechanism of organophosphate-based deficits in cognitive function might involve alterations in mitochondrial dynamics and/or their transport in axons.     

原发性闭角型青光眼持续高眼压状态下的手术时机探讨

目的探讨持续高眼压状态下原发性闭角型青光眼小梁切除术的最佳手术时机。方法选取持续高眼压状态下原发性闭角型青光眼患者130例168眼,随机分为两组,试验组65例(84眼)患者行前房穿刺后3～7d行小梁切除术,对照组65例(84眼)患者行前房穿刺后即时行小梁切除术。术后眼压在8～21mmHg(1kPa=7.5mmHg)为手术成功的标准,所有患者术后随访6个月～1a,对比观察2组患者术后眼压、视力及并发症。结果试验组59例(77眼)患者手术成功,手术成功率为91.67%;对照组51例(68眼)患者手术成功,手术成功率为80.95%,2组手术成功率比较,差异有统计学意义(χ2=4.08,P<0.05)。术后早期的并发症:试验组角膜水肿5例(5眼),虹膜炎症反应13例(19眼);对照组角膜水肿32例(41眼),虹膜炎症反应60例(79眼),瞳孔大18例(18眼),前房出血4例(4眼),脉络膜脱离3例(3眼)。试验组并发症发生率明显低于对照组。结论高眼压持续状态下的小梁切除手术宜在前房穿刺术后3～7d进行,手术成功率更高,并发症更少。     

中国山西人群中叶酸代谢基因MTRR 和MTHFR 与复杂先天畸形关联研究

目的 探讨叶酸代谢基因蛋氨酸合成酶还原酶（MTRR）和5,10 甲基四氢叶酸还原酶（MTHFR）基因多态性是否与复杂先天畸形相关,进一步研究其是否与三胚层发育来源的复杂先天畸形相关。方法 选取中国山西省250 例出生缺陷病例（包括先心病、神经管畸形和颅面畸形等复杂先天畸形）为研究对象,选择MTRR 单核苷酸多态性位点 rs1801394 和MTHFR 单核苷酸多态性位点rs1801133,利用SNaPshot 方法进行基因分型,并与420 例正常对照人群进行比较。结果 rs1801394 和 rs1801133 分别与多个先天出生缺陷有关。在隐性模型下,rs1801394 GG 基因型和rs1801133 CC 基因型的个体发生先天缺陷的概率低, 为出生缺陷的保护性因素。rs1801133 隐性纯合作为保护性因素与外胚层和内胚层器官来源复杂先天畸形相关,rs1801394 隐性纯合作为保护性因素与外胚层、中胚层和内胚层器官来源的复杂先天畸形相关。结论 中国山西人群中叶酸代谢基因MTRR 和MTHFR 与复杂先天畸形相关,并与胚层发育相关。     

光学相干断层成像术测量视网膜神经纤维层厚度在青光眼早期诊断中的意义

目的:探讨光学相干断层成像术(optical coherence tomography,OCT)测量视网膜神经纤维层厚度(retinal nerve fiber layer,RNFL)在青光眼早期诊断中的意义.方法:应用OCT测量正常人62例101眼和青光眼患者41例64眼的RNFL厚度,将正常人和青光眼患者的各象限和平均RNFL厚度进行比较;并比较各期青光眼的RNFL厚度;计算平均RNFL厚度和视野平均缺损的相关性,计算OCT测量平均RNFL厚度的敏感性和特异性.结果:青光眼患者和早期青光眼患者的各象限和平均RNFL厚度均比正常人减少,差异有统计学意义(P＜0.05).随着青光眼病程的发展,RNFL厚度逐渐下降.平均RNFL厚度和视野平均缺损呈高度正相关(r=0.722,P=0.000),OCT测量平均RNFL厚度的敏感性为85.9%,特异性为97.0%.结论:OCT测量RNFL厚度为青光眼早期诊断提供了一种新的手段.