膝症状性骨关节炎335例临床分析

对335例膝骨关节炎(OA)临床分析结果显示:膝OA患病率随着增龄而增加,且病情也随之加重,部分可合并骨质疏松,并以女性多见。本组体块指数(BMI)平均值为26.1,有12％为肥胖,61％为超重。提示BMI过高是引起膝OA原因之一。以往临床不太重视的体征如骨摩擦音、骨关节肿胀等体征十分常见。因此,作好细致的体检,对提高本病的临床诊断有着重要意义。无论X线或MRI均可见病膝胫股关节的内侧部OA发生率较外侧部严重,可能与胫骨上端内翻、致承重线内移有关。MRI在显示关节结构以及早期诊断方面均优于X线。根据MRI特点可将膝OA分为三种类型,即①单纯型,②软组织型,③骨型。这将有利于提高对膝OA异质性的认识,达到治疗个体化的目的。     

原发性肝癌介入治疗中化疗栓塞模式的探索

为探讨空气作为栓塞剂在原发性肝癌介入中的应用并作出评价，选择１３例不能切除的原发性肝癌经肝动脉静灌注化疗后用空气２０～３０ｍｌ栓塞，２～３周一次，反复治疗２～４次，疗程末用碘油阿霉素乳剂作最后栓塞，治疗中观察血象，肝功能，ＡＦＰ和肿瘤大小的变化，并作长期随访。结果：治疗后肿瘤缩小５０％以上者３例，不足５０％者９例，变化不明显１例，随访结果６例生存不足６月，３例生存１０月，２例１２月，另２例生存超过     

用荧光探剂DPH研究家蝇线粒体膜脂流动性

本文探讨了用ＤＰＨ作为荧光探剂，研究家蝇飞翔肌线粒体膜脂流动性的方法。实验表明：ＤＰＨ确是用来研究家蝇生物膜流动性的有效探剂。同时，初步观察了不同杀虫剂对ＤＰＨ与线粒体膜结合后荧光强度的影响。其中氯菊酯和倍硫磷、马拉硫磷、敌百虫、氧化乐果，可使ＤＰＨ探剂与线粒体膜结合后的荧光相对强度增加；而氰戊菊酯、氯氰菊酯，溴氰菊酯及辛硫磷、乙酰甲胺磷，则可使荧光强度减弱。     

危险管理法在农村儿童保健中应用效果评价

在儿保领域应用危险管理法目的是充分利用有限的卫生资源,减轻基层儿保人员负担,提高儿保服务效果和儿童健康水平。通县农村于1990年以来婴幼儿保健中应用危险管理法的研究显示,高危儿健康状况在加强管理后与非高危儿的相近;实验组与对照组儿童在婴幼儿期的死亡及婴幼儿后期生长发育方面差别无统计学意义;儿童满5岁时,两组生长发育水平无显著性差别。提示在我国有限卫生资源基础上,应用危险管理法于儿保领域有重要现实意义。     

二氧化硅活化巨噬细胞中早期生长反应因子-1及其信号转导通路的研究

目的 探讨早期生长反应因子(Egr-1)及其信号转导在矽肺发生发展中的作用。方法用细胞免疫荧光、原位杂交方法检测二氧化硅(SiO2)刺激后Egr-1的表达定位,用报道质粒及EMSA检测其活性改变;用激酶活性分析法检测si0：刺激巨噬细胞后ERK1／2活性改变,进一步用激酶抑制剂初步探讨SiO2活化Egr-1的信号转导通路。结果SiO2刺激RAW264．7细胞短时间Egr-1核蛋白表达及转录因子明显增加;且在处理后30～60min,Egr-1核蛋白结合活性明显升高(为未处理组的20倍);在刺激后15min ERK1／2活性开始升高,30min达高峰(活性为对照组的29倍)而后渐降至基础水平;进一步用激酶阻断发现,Egr-1 mRNA及蛋白表达均减少。结论SiO2能激活巨噬细胞中Egr-1,且此过程可能由ERK1／2、p38介导,提示SiO2-ERK1／2、p38-Egr-1通路可能在矽肺发生发展过程中起重要作用。     

Concomitant translocation of Puralpha with its binding proteins (PurBPs) from nuclei to cytoplasm during neuronal development

Two Puralpha-binding proteins (PurBPs) were found in nuclear extract from mouse brain during P4-P10 by the overlay assay. At P14, they were decreased significantly in nuclear extract and increased in the S3 fraction, indicating their dynamic translocation during development. Western blot analysis also demonstrated concomitant translocation of Puralpha with the PurBPs during P7-P14, when neuronal circuit proceeds. Immunocytochemical study with cultured hippocampal neurons from rat E18 confirmed that nuclear Puralpha was translocated to cytoplasm after plating for 7-14 days. These results suggest that spatiotemporal translocation of Puralpha with the PurBPs from nuclei to cytoplasm has a crucial role in neuronal development.     

脑血流断层显像Bullseye显示

为了探讨用Bullseye显示脑血流灌注显像数据的可能性,对8例典型脑梗塞病例及15例脑血流断层显像常规分析可疑病例的脑血流断层显像的横断面数据进行Bullscye显示,结果8例典型病人病灶用普通Bullseye即显示良好;常规分析可疑病例病变用普通Bullseye 8例显示良好,变黑Bullseye 13例显示出病灶;结果提示利用Bullseye显示脑血流灌注显像数据的可能。     

Apoptosis incidence and protein expression of p53, TGF-beta receptor II, p27Kip1, and Smad4 in benign, premalignant, and malignant human prostate

Deregulation of apoptosis is involved in prostate cancer development and progression. This study involved an immunohistochemical "profiling" of prostate tissue specimens from patients who underwent prostatectomy for localized prostate cancer, to identify apoptosis-specific alterations associated with premalignant precursor lesions. Prostate tissue was pathologically evaluated, and areas of benign acini, high-grade prostate intraepithelial neoplasia (HGPIN), and prostate cancer were identified. Immunohistochemical analysis was performed to determine the expression of p27Kip1, a key cell cycle regulator, transforming growth factor (TGF)-beta receptor II (TbetaRII), a critical signaling effector of TGF-beta; Smad4, a downstream intracellular effector of TGF-beta signaling; p53, a key apoptosis regulator; and prostate-specific antigen (PSA), a clinical marker of prostate cancer. The apoptotic index of the same cell populations was determined using the transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end labeling assay. Our findings indicate a significant reduction in p27Kip1 immunoreactivity in HGPIN (P<0.0001) and prostate cancer (P<0.0001) compared with the benign tissue. A significant down-regulation was detected in TbetaRII expression in HGPIN and prostate cancer compared with benign prostatic hyperplasia (BPH)(P<0.001). A significant decrease was also observed in Smad4 levels in HGPIN and prostate cancer compared with BPH (P<0.001). Evaluation of the incidence of apoptosis revealed a significant decrease in the apoptotic index among the epithelial cell populations in HGPIN and a further decrease in prostate carcinoma (P<0.01). This reduced apoptotic index correlated with a significant increase in p53 immunoreactivity in the prostatic carcinoma foci. Prostate cancer cells exhibited strong nuclear staining for p53 compared with adjacent HGPIN (P<0.05) and the benign lesions of the same prostate specimens (P<0.05). A significant reduction in PSA immunostaining was detected in HGPIN and prostate carcinoma foci compared with the benign glandular epithelia (P<0.001). These results further define deregulation of TGF-beta signaling effectors as a molecular basis for loss of apoptotic control contributing to the development of prostate tumors. Identification of apoptotic regulators in precursor premalignant lesions may have prognostic significance in disease progression as well as therapeutic value for targeting prostate cancer.     

Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model

Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer, and its absolute incidence is increasing dramatically. Compared to human lung AC, the A/J mouse-urethane model exhibits similar histological appearance and molecular changes. We examined the gene expression profiles of human and murine lung tissues (normal or AC) and compared the two species' datasets after aligning approximately 7500 orthologous genes. A list of 409 gene classifiers (P value <0.0001), common to both species (joint classifiers), showed significant, positive correlation in expression levels between the two species. A number of previously reported expression changes were recapitulated in both species, such as changes in glycolytic enzymes and cell-cycle proteins. Unexpectedly, joint classifiers in angiogenesis were uniformly down-regulated in tumor tissues. The eicosanoid pathway enzymes prostacyclin synthase (PGIS) and inducible prostaglandin E(2) synthase (PGES) were joint classifiers that showed opposite effects in lung AC (PGIS down-regulated; PGES up-regulated). Finally, tissue microarrays identified the same protein expression pattern for PGIS and PGES in 108 different non-small cell lung cancer biopsies, and the detection of PGIS had statistically significant prognostic value in patient survival. Thus, the A/J mouse-urethane model reflects significant molecular details of human lung AC, and comparison of changes in orthologous gene expression may provide novel insights into lung carcinogenesis.     

Construction of a risk model of steroid-induced necrosis of the femoral head and prediction of potential Chinese medicine treatments北大核心

背景:随着疾病治疗模式的改变,人们已经意识到中医药在激素性股骨头坏死治疗过程中的重要性,因此利用生物信息学从分子水平分析激素性股骨头坏死的发病机制,构建疾病风险模型,并预测具有潜在治疗作用的中药,为后期中医药治疗激素性股骨头坏死提供一定的理论依据。目的:基于生物信息学挖掘激素性股骨头坏死的竞争性内源RNA(ceRNA)调控网络,分析其在激素性股骨头坏死中的分子调控机制,预测相关疾病靶点并构建疾病风险模型,同时预测具有潜在治疗作用的中药。方法:检索GEO数据库,下载激素性股骨头坏死的矩阵文件GSE123568和基因注释文件GPL15207。借助R语言等软件分析得到差异表达的长链非编码RNA与mRNA,并通过公共数据库预测与差异表达长链非编码RNA关联的miRNA-mRNA,再将预测到的mRNA与差异表达mRNA取交集,整合得到ceRNA网络。随后采用STRING数据库和Cytoscape软件筛选关键基因,利用R语言分析关键基因的功能与相关通路,并挖掘关键ceRNA网络。最后根据关键基因构建激素性股骨头坏死的风险模型,并进行中药预测。结果与结论:(1)与健康对照相比,激素性股骨头坏死患者共有7个长链非编码RNA和1763个mRNAs存在差异表达;(2)筛选出STAT3、KAT2B、AGO4、JAK2、JAK1、PTGS2共6个关键基因;(3)关键基因所富集的功能包括对肽激素的反应、白细胞介素6介导的信号通路、细胞对白细胞介素6的反应等生物学过程,涉及JAK-STAT、脂肪细胞因子、催乳素等信号通路;(4)4种mi RNAs(mi R-135a-5p、mi R-137、mi R-17-5p、miR-20b-5p)和2种长链非编码RNA(SNHG11、C20orf197)可能在导致激素性股骨头坏死发生发展过程中发挥关键作用;(5)KAT2B最有可能是激素性股骨头坏死发生发展的风险因子;(6)郁金、淫羊藿、黄芪具备治疗激素性股骨头坏死疾病靶点的可能。通过对激素性股骨头坏死相关长链非编码RNA介导的ceRNA网络进行分析,识别出潜在的疾病靶点、信号通路及潜在治疗中药,为进一步阐明其发病机制,并为后续的实验研究提供参考依据。