磷酸镁骨水泥粘接固定犬胫骨平台骨折的实验研究

目的:应用磷酸镁骨水泥(MPC)粘接固定犬胫骨平台骨折,探讨MPC治疗骨折的效果、粘接和降解机理及在犬体内MPC粘接强度的变化情况等.方法:38只犬随机分为A与B两组,其中A组8只,B组30只.通过开放截骨法建立犬胫骨平台骨折模型,复位后用MPC粘接固定骨折断端,术中、术后不再使用其它内、外固定.术后不同时期对A组犬胫骨进行大体和显微镜下观察,对B组犬分别进行影像学检查、大体检查以及生物力学分析等.结果:MPC在犬体内的吸收速度和骨折的愈合速度一致,不影响骨折的愈合.通过对犬胫骨标本的组织学检查发现,其粘接机理可能为机械镶嵌固定,并通过溶解而逐步吸收.MPC在犬体内具有一定的骨粘接强度,但其抗拉强度小于体外.结论:MPC具有一定的粘接强度,在动物体内的吸收速度和骨折的愈合速度一致,可用于非负重部位骨折的粘接固定,但其抗水性能和粘接强度尚需进一步提高.     

Role of eIF3 p170 in controlling synthesis of ribonucleotide reductase M2 and cell growth

Translation initiation in eukaryotes is a rate-limiting step in protein synthesis. It is a complicated process that involves many eukaryotic initiation factors (eIFs). Altering the expression level or the function of eIFs may influence the synthesis of some proteins and consequently cause abnormal cell growth and malignant transformation. P170, the largest putative subunit of eIF3, has been found elevated in human breast, cervical, esophageal, and lung cancers, suggesting that p170 may have a potential role in malignant transformation and/or cell growth control. Our recent studies suggested that p170 is likely a translational regulator and it may mediate the effect of mimosine on the translation of a subset mRNAs. Mimosine, a plant nonprotein amino acid, inhibits mammalian DNA synthesis, an essential event of cell growth. The rate-limiting step in DNA synthesis is the conversion of the ribonucleotides to their corresponding deoxyribonucleotides catalysed by ribonucleotide reductase of which the activity is regulated by the level of its M2 subunit. It has been reported that inhibiting the activity of M2 also inhibits cell growth. To understand the relationship between protein and DNA synthesis and between p170 and cell growth control, we investigated in this study whether p170 regulates the synthesis of M2 and, thus, cell growth. We found that altering the expression level of p170 changes the synthesis rate of both M2 and DNA. Decreasing p170 expression in human lung cancer cell line H1299 and breast cancer cell line MCF7 significantly reversed their malignant growth phenotype. However, the overall [35S]methionine incorporation following dramatic decrease in p170 expression was only approximately 25% less than the control cells. These observations, together with our previous findings, suggest that p170 may regulate the translation of a subset mRNAs and its elevated expression level may be important for cancer cell growth and for maintaining their malignant phenotype.     

水飞蓟宾丹酚酸衍生物的制备及成药性研究

[目的] 使水飞蓟宾（SLB）通过酯化缩合反应对其进行分子结构改造,生成丹酚酸酯衍生物,并对其成药性进行初步研究。[方法] 将水飞蓟宾分别与丹参活性成分迷迭香酸（RA）和丹参素（DSS）,采用酯化缩合反应依次得到水飞蓟宾迷迭香酸酯（RA-SLB）和水飞蓟宾丹参素酯（DSS-SLB）,通过氢谱、碳谱和质谱确证了丹酚酸酯衍生物的结构,比较了丹酚酸酯衍生物与水飞蓟宾溶解度差异,并对其进行抗肝损伤作用研究、脂肪肝的保护作用等的成药性评价。[结果] 与水飞蓟宾相比,丹酚酸酯衍生物溶解度显著提高,并且在水中的稳定性良好。与刀兰球蛋白引起急性免疫性肝损伤模型组相比,RA-SLB的低剂量组对血清丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）和乳酸脱氢酶（LDH）含量升高均有显著降低作用,差异具有统计学意义（P<0.05）,DSS-SLB组对刀兰球蛋白引起的肝损伤在实验中有改善肝功能的趋势,但与模型组比较无统计学差异（P>0.05）。与DL-乙硫氨酸诱导脂肪肝模型组相比,RA-SLB组能显著降低肝组织中的三酰甘油（TG）含量（P<0.05）,其他各给药组对TG含量的升高无显著影响,差异无统计学意义（P>0.05）。[结论] RA-SLB具有显著的保护肝损伤及改善脂肪肝活性作用,具有很好的成药前景。     

多肿瘤标志物蛋白芯片与化学发光检测临床应用的对比分析

目的:探讨多肿瘤标志物蛋白芯片与化学发光检测对肿瘤诊断的临床应用价值.方法:应用多肿瘤标志物蛋白芯片与化学发光技术,对180名健康体检者和已患肿瘤的210例病人进行12种肿瘤标志物联合检测,并对检测结果进行对比分析.结果:多肿瘤标志物蛋白芯片与化学发光检测两种方法在对健康体检组阳性率和特异性经统计学分析没有显著性差异(P＞0.05);对已患肿瘤的210例12种肿瘤标志物检测两种方法的检测结果为AFP 、 PSA、f-PSA、CA199、CA153、NSE有显著性差异(P＜0.05),CA242、β-HCG 、HGH、CA125、Fer、CEA没有显著性差异(P＞0.05).结论:多肿瘤标志物蛋白芯片与化学发光检测在对提高肿瘤诊断的阳性率和特异性方面具有一定的相关性,但多肿瘤标志物蛋白芯片在健康体检中的应用价值优于化学发光检测,而对确诊的肿瘤患者,化学发光检测优于多肿瘤标志物蛋白芯片检测.     

^68Ga—DOTA—cNGR的制备及对荷肺腺癌裸鼠的显像研究

目的制备^68Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-环状NGR（DOTA-cNGR）,并评价其在正常小鼠体内的生物分布及对荷肺腺癌裸鼠的靶向显像能力。方法以羟乙基哌嗪乙硫磺酸（HEPES）为缓冲体系（pH值5．0）,水浴合成^68Ga—DOTA—cNGR,HPLC测定标记率及放化纯,观察其在人血清中的稳定性。进行^68Ga—DOTA—cNGR的正常小鼠体内生物分布和荷肺腺癌裸鼠活体microPET显像,对荷肺腺癌裸鼠的瘤组织进行病理及氨肽酶N（APN）的免疫组织化学分析。采用两样本t检验分析数据。结果^68Ga—DOTA—cNGR标记率为（99．8±0．1）％,性状稳定,在人血清中37℃保温2h后放化纯仍〉95％。正常小鼠体内生物分布结果表明,^68Ga—DOTA-cNGR主要经肾排泄,血液清除迅速,肝、胃肠道摄取较少;1h肾、血液、肝、胃、肠的放射性摄取分别为（1．61±0．22）、（0．19±0．07）、（0．25±0．24）、（0．16±0．04）、（0．12±0．05）％ID／g。荷肺腺癌裸鼠microPET显像可见肿瘤部位有放射性浓聚影,1h肿瘤与对侧正常肌肉T／NT高达7．61±0．47,经DOTA—cNGR特异性阻断后降至1．83±0．25,阻断前后差异有统计学意义（t=18．80,P〈0．05）。免疫组织化学检查证实APN特异性聚集于肿瘤新生血管表面。结论^68Ga-DOTA—cNGR易于制备,标记率和放化纯高,在人血清中的稳定性好,具有良好的代谢及肺腺瘤靶向特性,有望用于肺癌显像。     

Role of 99mTc-octreotide acetate scintigraphy in suspected lung cancer compared with 18F-FDG dual-head coincidence imaging.

The aim of this study was to evaluate the clinical value of tomographic (99m)Tc-octreotide acetate (hereafter, (99m)Tc-octreotide) scintigraphy in the detection of patients with suspected lung cancer in comparison with that of (18)F-FDG dual-head coincidence imaging (DHC). METHODS: Forty-four consecutive patients with suspected pulmonary neoplasms underwent tomographic (99m)Tc-octreotide scintigraphy and (18)F-FDG coincidence imaging using the same gantry. The region of interest was drawn on the entire primary lesion. The tumor-to-normal tissue tracer values for both (99m)Tc-octreotide and (18)F-FDG were determined using region of interests and expressed as T/N(r) and T/N(m), respectively. Final diagnosis was confirmed by histopathologic analysis or clinical follow-up. RESULTS: Thirty-one of the 44 patients had lung cancer-6 with small cell lung cancer (SCLC) and 25 with non-small cell lung cancer (NSCLC). Thirteen of the 44 patients had benign lung lesions. The sensitivity, specificity, positive predictive value, and negative predictive value of (99m)Tc-octreotide were 100%, 75.7%, 90.1%, and 100%, respectively, and of (18)F-FDG DHC were 100%, 46.1%, 83.8%, and 100%, respectively. In the 31 patients with malignant tumors, all 38 abnormal lymph nodes in 20 patients showed abnormal high focal uptake of (18)F-FDG; only 7 patients with 10 regional lymph adenopathies showed moderate uptake of (99m)Tc-octreotide. Thirteen patients with 39 distant sites of abnormal uptake visualized (imaging stage IV) with (99m)Tc-octreotide included 2 patients with brain metastases, 6 patients with pleural invasion and multiple bone metastasis, 2 patients with contralateral internal lung metastasis and pleural invasion, and 3 patients with only multiple bone metastasis. The final diagnosis was confirmed by histopathology or clinical follow-up. CONCLUSION: The sensitivity of (99m)Tc-octreotide for the detection of lung cancer at the primary lesion was comparable with that of (18)F-FDG coincidence imaging. Tomographic (99m)Tc-octreotide scintigraphy had lower sensitivity for the detection of hilar and mediastinal lymph node metastasis compared with that of (18)F-FDG coincidence PET, but it had high sensitivity for the detection of remote metastatic lesions. However, because of the small population, further investigation is necessary.     

幽门螺杆菌感染与口腔扁平苔藓和鳞状细胞癌相关性的初步探讨

目的研究正常口腔黏膜、口腔扁平苔藓（OLP）和口腔鳞状细胞癌（OSCC）中幽门螺杆菌（Hmylori）感染情况及其与p53蛋白和p16蛋白表达的关系．探讨H．pylori感染与OLP和OSCC的相关性。方法OLP标本23例、OSCC标本50例和正常口腔黏膜标本10例,采用免疫组化sP法检测其H．pylori的感染、p53蛋白、p16蛋白的表达．应用SPSS13．0软件包对结果进行卡方分析检验．单因素方差分析和线性回归检验分析。结果正常口腔黏膜组织组、0LP组及0SCC组中H．pylori阳性率分别为0、47．8％和48．0％,正常口腔黏膜组与OLP组和OSCC组间差异有统计学意义（X2=7．17．P=0.013;X^2=8．00,P=0．004）;OLP标本中H．pylor／阳性组和阴性组p53蛋白表达率分别为45．5％和16．7％,p16蛋白表达率为分别36．4％和66．7％,组间差异有统计学意义（X^2=3．86,P=0．043：X^2=3．89,P=0．048）;OSCC标本中H.pylori阳性组和阴性组p53蛋白表达率分别为91．7％和84．6％,p16蛋白表达率为分别20．8％和30．8％,组间差异无统计学意义（X^2=0．58,P=0．669;x2=0．65,P=0．526）。结论H．pylori感染与OLP和OSCC存在一定的相关性。H．pytori感染在OLP和OSCC发生、发展中的作用有待于进一步研究。     

99Tcm-3P4-RGD2显像探测肺癌骨骼转移的临床价值研究

目的:探讨99Tcm-HYNIC-PEG4-E[PEG4-c(RGDfk)]2(99Tcm-3P4-RGD2)显像探测肺癌骨骼转移灶的临床应用价值?方法:回顾性分析2012年7月—2013年9月45例经病理证实的肺癌患者,所有患者均接受99Tcm-3P4-RGD2显像(RGD显像,包括平面和断层显像)?99Tcm-MDP显像(MDP显像,包括平面和断层显像),同时行SPECT-CT融合显像?所有病灶均以病史?病理检查或6个月以上的影像学随访为最终诊断结果?探讨RGD显像对肺癌骨骼转移病变的诊断效能?结果:45例肺癌并发骨骼病灶122处,成骨性转移病灶102处,溶骨性病灶20处 (其中5处尚未出现明显骨质密度改变),良性骨病变51处?溶骨性转移灶对99Tcm-3P4-RGD2摄取(T/NT:6.90 ± 2.31)显著高于99Tcm-MDP(1.18 ± 1.24,P=0.010),RGD显像对溶骨性?成骨性转移灶的探测灵敏度(84.8%和55.9%)分别与MDP显像(25.0%和91.2%)差异显著(P均<0.05),融合CT显像后,两种显像方法对骨转移的诊断特异性无统计学差异,但MDP融合显像对骨转移灶的探测灵敏度(92.6%)和准确性(93.4%)均高于RGD融合显像(78.7%,P=0.008;80.3%,P=0.010)?另外,RGD融合显像可对骨骼病变原发肺癌灶和其他转移灶进行有效探测?结论:99Tcm-3P4-RGD2靶向结合肿瘤细胞?破骨细胞的整合素αvβ3受体,在肺癌溶骨性骨转移的早期发现中具有一定优势,是常规骨显像的有效补充?