冷冻干燥法制备阿糖胞苷冻干脂质体粉针研究

本文采用冷冻干燥法制备阿糖胞苷冻干脂质体粉针，并建立了质量控制标准。在扫描电镜和透射电镜观察下，将此脂质体冻干品加注射用水溶解后，能很快重新形成脂质体。算术平均粒径为０．４７５６±０．０８３３μｍ，包封率约３０％。     

Responses of periodontal nerve terminals to experimentally induced occlusal trauma in rat molars: an immunohistochenmical study using PGP 9.5 antibody

The response of periodontal nerves to experimentally induced occlusal trauma in rat molars was assessed by immunohistochemistry for protein gene product 9.5 (PGP 9.5) at light and electron microscopic levels, and by computerized image analysis. The occlusal surface on the left upper first molar of 8-wk-old male Wistar rats was raised approximately 1 min under ether anaesthesia. The rats were perfusion-fixed on d 1, 2, 3, 4, and 7 after bite-raising and then decalcified for 2–3 wk. Frozen sagittal cryostat sections were stained by the avidin-biotin complex method. By the second day after bite-raising many Ruffini endings were swollen and their outline unclear at the light microscopic level. Transmission electron microscopy disclosed PGP 9.5 reaction products within Ruffini endings that had unusually long cytoplasmic projections extending through enlarged slits of the Schwann sheaths and also diffuse extracellular PGP 9.5-immunoreactivity near the Ruffini endings. From d 2 to 4, thin nerve fibres on the pressure side of the periodontal ligament were orientated irregularly and had a prominent beaded appearance. An increase in beaded nerve terminals occurred at d 2–4 post elevation, and decreased later. These results suggest that occlusal trauma induces specific changes in the distribution and shape of nerve terminals in the periodontal ligament.     

苯妥英钠血清浓度监测（31例报告）

报告31例口服DPH治疗的门诊癫痫病人RIA法血清DPH浓度监测结果。在随访中记录的临床治疗反应。病人平均药物剂量为4．39±1．19mg/kg／d，不同病人服用同一剂量DPH，其血清药物旅度可相差9倍。22例获良好(较好)的治疗反应，其平均有效血清药物浓度为24．1±10．1μg／ml。9例出现中毒反应；血清药物浓度在25μg／ml以上时可出现眼球震颤、视物模糊，共济失调。DPH血清浓度监测有功于实现个体化给药方案，提高疗效并避免中毒。     

Biochemical analysis of plasma-soluble invariant chains and their complex formation with soluble HLA-DR

The invariant chain (CD74) is preferentially localized in the cytoplasm and regulates the loading of exogenous derived peptides into HLA class II heterodimers. In addition, a small proportion of CD74:class II complexes is also expressed on the cell surface. We identified and quantified soluble CD74 (sCD74) molecules in the plasma and sCD74:sHLA-DR complexes by ELISA. EDTA plasma samples from 86 healthy probands were analyzed. sCD74 could be detected in all samples with a mean concentration of 1.14 relative units±1.04 SD (range 0.17-4.31). Approximately 10% of the samples had increased amounts of sCD74 (3.0 relative units). Complexes of sCD74 and sHLA-DR were detected in all samples and their quantities were positively correlated (r=0.83, p0.001) with the sCD74 concentrations. SDS-PAGE analysis of plasma samples with high sCD74 concentrations (3.0 relative units) revealed four isoforms of sCD74 with molecular weights of 45, 43, 35, 31 kDa corresponding to known sizes of intracellular CD74. However, only molecular weights of the 45 and 43 kDa isoforms of sCD74 are found complexed with sHLA-DR. Our data demonstrate, that CD74 molecules are present in their soluble form in the plasma of healthy probands and form complexes with soluble HLA-DR molecules.     

Estimates of global research productivity in virology

The quantity and quality of published research in the field of Virology by different world regions was estimated in this study. Using the PubMed database, articles from journals included in the "Virology" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995-2003 were retrieved. The world was divided into nine regions based on geographic, economic, and scientific criteria. Data on the country of origin of the research was available for 33,425 out of 33,712 articles (99.2% of all articles from the included journals). USA exceeds all other world regions in research production for the period studied (42% of total articles), with Western Europe ranking second (35.7%). The mean impact factor in articles published in Virology journals was highest for the USA (4.60), while it was 3.90 for Western Europe and 3.22 for the rest of the world (seven regions combined). USA and Canada ranked first in research productivity when both gross national income per capita (GNIPC) and population were taken into account. The results of this analysis show a distressing fact; the absolute and relative production of research in the field of Virology by the developing regions is very low, although viral diseases cause considerable morbidity and mortality in these areas. It is evident from this study that developing regions need more help from the developed regions to enhance research infrastructure.     

Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibodies to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human pro-bombesin

Several recent studies have confirmed the endocrine nature of small cell carcinoma of the lung. In extra-pulmonary sites, small cell 'undifferentiated' carcinomas have classical morphological features similar to their pulmonary counterpart. We therefore investigated, using immunocytochemistry, the possibility that the non-pulmonary neoplasms may also be endocrine in nature. Sections of 29 small cell carcinomas from oesophagus, stomach, larynx, colon and urinary bladder were immunostained using antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), cytokeratin, leucocyte common antigen and peptides including bombesin, the C-flanking peptide of human probombesin, adrenocorticotrophic hormone, neurotensin, calcitonin and pancreatic polypeptide. All the tumours showed immunoreactivity for at least one of the two general endocrine markers PGP 9.5 and NSE. Twenty-three of the 29 cases were immunoreactive for PGP 9.5, 27 for NSE. All were positive for cytokeratin and negative for leucocyte common antigen. Of the regulatory peptides, immunoreactivity was obtained with antisera to bombesin (one case), the C-flanking peptide of human pro-bombesin (14 cases), adrenocorticotrophic hormone (one case) and calcitonin (three cases). No PGP 9.5-, NSE- or peptide-like immunoreactivity was detected in 25 control tumours from similar sites, including lymphomas and poorly differentiated tumours. These results suggest that non-pulmonary small cell carcinoma has an endocrine character.     

Kinetics of methotrexate binding to dihydrofolate reductase from Neisseria gonorrhoeae

The kinetics of methotrexate inhibition of dihydrofolate reductase from Neisseria gonorrhoeae have been investigated. Methotrexate was shown to be a tight-binding inhibitor (Kt = 13 pM) competitive with dihydrofolate. However, "stoichiometric" or "pseudoirreversible" inhibition could not be demonstrated. Progress curves of inhibited assays quickly attained steady state regardless of the order of substrate addition, indicating that methotrexate association and dissociation processes were rapid. Kinetic techniques were used to measure the rate of methotrexate dissociation from the enzyme-NADPH-methotrexate ternary complex. At 30 degrees, the first-order off-rate constant (koff) was calculated to be 0.56 min-1. This value is approximately 40-fold greater than the dissociation rate constant of methotrexate for Escherichia coli dihydrofolate reductase. At lower temperatures, progress curves of methotrexate-inhibited gonococcal enzyme assays displayed marked increases in both curvature and the time to reach steady state. At 9 degrees, the methotrexate dissociation rate was slow enough (koff = 0.04 min-1) so that initial velocities of the reaction could be measured, and under these conditions methotrexate inhibition was shown to be "stoichiometric".     

人体测量指标预测肥胖儿童非酒精性脂肪肝的研究

目的 研究人体测量指标对儿童肥胖伴非酒精性脂肪肝的预测作用,探讨不同指标筛查非酒精性脂肪肝的切点值。方法 选取自2018年6月—2019年12月在西安交通大学第二附属医院小儿内分泌门诊就诊的94例肥胖儿童为研究对象,进一步分为肥胖伴非酒精性脂肪肝组与肥胖不伴非酒精性脂肪肝组,52例正常儿童为对照组。测量身高(H)、体重(W)、腰围(WC)、臀围(HC)和血甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C);行肝脏B超的检查。计算体质指数(BMI)、腰臀比(WHR)、腰高比(WHtR)、腹部体积指数(AVI)、脂质蓄积指数(LAP)和内脏脂肪指数(VAI)等指标。通过绘制人体测量指标的受试者工作特征曲线(ROC曲线)评估人体测量指标与肥胖儿童非酒精性脂肪肝的相关性,并比较各项人体测量指标的曲线下面积(AUC)确定切点值。结果 肥胖组BMI、WC、WHR、WHtR、AVI、LAP、VAI及TG均高于对照组(t=23.090、21.068、12.547、22.855、17.578、8.159、5.394、6.183,P＜0.001)。肥胖伴非酒精性脂肪肝组BMI、WC、AVI、LAP、VAI均高于肥胖不伴非酒精性脂肪肝组(t=2.180、2.389、2.362、3.643、2.839,P＜0.05)。人体测量指标的ROC曲线下面积按从大到小的顺序依次为 LAP、VAI、 WC、 AVI、 BMI。对肥胖伴非酒精性脂肪肝的联合诊断指标进行筛查效能分析结果显示,LAP+AVI 曲线下面积为0.706(95%CI:0.595~0.817,P＜0.001);AVI+VAI 曲线下面积为0.685(95%CI:0.570~0.800,P＜0.01);BMI+WC 曲线下面积为0.652(95%CI:0.537~0.768,P＜0.05)。联合指标的ROC曲线下面积从大到小为LAP+AVI、AVI+VAI、BMI+WC。结论 LAP联合AVI对儿童肥胖伴非酒精性脂肪肝具有较好的筛查作用。     

喉癌及癌旁不同距离组织中ras、c-myc、p53蛋白的复合表达

目的 :研究癌基因 (ras,c myc)及抗癌基因 (p5 3)蛋白在喉癌及癌旁不同距离处的复合表达及意义。方法 :应用LSAB微波免疫组织化学法 ,检测了ras、c myc及p5 3在 30例喉癌组织、边缘区、癌旁 0 .5cm ,1.0cm ,1.5cm ,2 .0cm处粘膜组织和 4例正常喉粘膜组织中的复合表达情况。结果 :① 2种以上基因蛋白产物同时表达阳性者在喉癌组织中为 2 8例 (93.3 % ) ,其中ras +c myc +p5 3为 17例 (5 6 .7% ) ,癌旁组织中也存在着不同程度的复合表达 ,而正常喉粘膜组织中无一例复合表达 ;②复合表达阳性率依正常粘膜组织→癌旁 2 .0cm→ 1.5cm→ 1.0cm→0 .5cm→边缘区→癌组织递增 ,且癌旁 1.0cm处与 0 .5cm范围内的表达存在显著差异 (P <0 .0 5 ) ;③ 3种癌基因产物的复合表达与喉癌的部位 ,分化程度 ,临床分期无关 (P >0 .0 5 )。结论 :喉癌及癌旁组织中存在着 3种癌基因的复合表达 ,其在喉癌的发生中有协同作用 ;距癌 0 .5cm以内的癌旁组织应视为危险性病变。     

海绵共附生链霉菌Streptomyces parvulus 162432次级代谢产物研究

目的 研究海绵共附生链霉菌Streptomyces parvulus 162432的化学成分。方法 采用十八烷基硅烷键合硅胶填料（ODS）中压柱色谱和半制备高效液相色谱等技术进行分离纯化,得到的单体化合物采用HR-ESI-MS、NMR以及文献比对等方法进行鉴定,新化合物的绝对构型通过计算NMR和圆二色谱（ECD）确定。结果 从菌株Streptomyces parvulus 162432中分离纯化了9个环二肽类化合物,包括1个新化合物链霉菌二肽A（1）和8个已知化合物：环-(D-顺式-羟脯氨酸-L-苯丙氨酸)（2）、环-(D-脯氨酸-D-苯丙氨酸)（3）、环-(L-羟脯氨酸-L-亮氨酸)（4）、环-(L-羟脯氨酸-D-亮氨酸)（5）、环-(D-脯氨酸- L-亮氨酸)（6）、环-(L-脯氨酸-D-亮氨酸)（7）、环-(D-脯氨酸-L-异亮氨酸)（8）、环-(L-亮氨酸-D-缬氨酸)（9）。对分离得到的化合物1～9进行肿瘤细胞增殖细胞毒和抗菌活性评价,活性结果显示,化合物1～9在10 μg/mL下对肿瘤细胞增殖均未显示出明显的细胞毒活性;化合物9对苏云金芽孢杆菌显示抑菌活性,最小抑菌浓度（minimum inhibitory concentration,MIC）为25 μg/mL。结论 化合物1为新化合物,化合物2和4～9为首次从链霉菌Streptomyces parvulus中分离得到,化合物9具有一定的抗菌活性。