男性海洛因依赖者性机能研究

目的 研究海洛因对男性性机能的影响。方法 对91例男性海洛因依赖者进行了性机能调查研究，并做性激素测定和分析。结果 男性海洛因依赖者性机能明显障碍，表现为性幻想减少，性欲减退，性高潮减退，性交频率降低。男性睾酮（T）及催乳素（PRL）均低于正常对照组（Z=8．118，P〈0．01；Z=4．444，P〈0．01），促黄体生成素（LH）及促卵泡刺激素（FSH）均高于正常对照组（Z=2．094，P〈0．05；Z=2．086，P〈0．05），雌二醇（E2）与正常对照组无统计学意义。结论 海洛因可致机体下丘脑-垂体-性腺轴功能紊乱，影响性机能，并且性问题在海洛因依赖性形成机制和戒断上的意义值得进一步探讨。     

多发性骨髓瘤预后相关性研究

多发性骨髓瘤(MM)是一种好发于中老年的,以浆细胞恶性增生,分泌单克隆免疫球蛋白并伴有正常免疫球蛋白减少以及广泛溶骨病变和(或)骨质疏松为特征的肿瘤.当前治疗该病仍然十分困难,因此,随着我国人口的老龄化进程,MM对人们的生命和生存质量已构成越来越严重的威胁.近年来,众多国内外专家学者不断把细胞遗传学、分子遗传学以及分子免疫学的许多新方法引入MM的研究,使得MM的预后判断以及骨髓瘤细胞潜在的生存及生长机制取得了很大的进展.     

对发展中国家改善用药的10点建议

WHO建议改善药品管理的工作要在国家药物政策保障之下.在许多国家,执行国家药物政策的机制是实施国家基本药物计划,其要点是强调公共领域的药品选择、采购、流通与使用的合理性.不适当的处方使医疗质量降低并导致资源浪费.本文以探讨在国家药物政策范畴内鼓励更合理地使用药品的问题为重点,在已有证据的基础上,详细阐明基本药物计划内容中的合理用药问题.本文评述了在发展中国家改善用药状况的有效策略及最新知识,并为决策者与管理者提出达到改善用药目标的建议.     

Jararhagin and its multiple effects on hemostasis

Jararhagin is a 52 kDa hemorrhagic P-III metalloproteinase isolated from the venom of the medically important Brazilian pit-viper Bothrops jararaca. It is a member of the reprolysin family of zinc metalloproteinases containing a catalytic metalloproteinase domain followed by a disintegrin-like and a cysteine-rich domain. The impact of jararhagin on hemostasis has been extensively studied using in vitro and in vivo model systems as well as in clinical studies. Jararhagin-induced hemorrhage is the result of the degradation of sub-endothelial matrix proteins leading to the disruption of the blood vessel endothelium, with accompanying disturbances in platelet function. The versatility of jararhagin is further demonstrated by its direct action on von Willebrand factor, the degradation of fibrinogen, by its inhibition of platelet adhesion to collagen and by its inability to be affected by the plasma inhibitor ₂-macroglobulin. Collagen-induced platelet aggregation is inhibited by jararhagin though the binding of the molecule to the ₂ subunit I domain of the platelet surface ₂β₁ integrin (collagen receptor). Jararhagin also cleaves the β₁ subunit of the same integrin, inhibiting platelet interaction and ultimately causing impairment of signal transduction. The effect of jararhagin on cell systems other than platelets is evaluated; in fibroblasts, jararhagin functions as a collagen-mimetic substrate and, in endothelial cells, it causes apoptosis and indirectly inhibits cell proliferation by release of angiostatin-like compounds. Jararhagin induces a strong pro-inflammatory response characterized by intense leukocyte accumulation at the site of the injection. Although hemorrhage and edema are a response to the direct effect of jararhagin, jararhagin-induced inflammation and necrosis are dependent on macrophages and key pro-inflammatory cytokines or their receptors. Some data also indicate that the toxin possesses anti-tumorgenic properties. Methods for inhibiting jararhagin are reviewed; this encompasses the use of synthetic peptides to the isolation of naturally occurring mammalian peptides and the development of toxin-specific antibodies through DNA immunisation and monoclonal antibody technologies. The availability of jararhagin makes it an important tool for research into the mechanisms of action of similar toxins, for insights into cellular interactions and for clinical investigations into the treatment of envenomings from B. jararaca.     

二甲双胍治疗抗精神病药物引起的血脂异常:两项随机、安慰剂的对照研究

目的：验证二甲双胍治疗抗精神病药引起的血脂异常的疗效和安全性。方法：将两项随机、安慰剂的 对照研究纳入分析。共有201例服用抗精神病药物后出现血脂异常的首发精神分裂症患者,并将其分为1 000 mg/d 二甲双胍组(以下简称为二甲双胍组,n=103)和安慰剂组(n=98),观察24周。在基线、治疗后第12周和第24周进行 临床症状及体重、血糖、血脂等代谢指标的评估。结果：二甲双胍治疗后,二甲双胍组和安慰剂组之间低密度脂 蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)的平均差异从基线时的0.16 mmol/L,降低到第24周结束时的 –0.86 mmol/L,降低了1.02 mmol/L,差异有统计学意义(P<0.01)。而24周结束时,二甲双胍组LDL-C≥3.37 mmol/L的 患者有25.3%,显著低于安慰剂组24周结束时的64.8%(P<0.01)。与安慰剂组相比,二甲双胍组的体重、体重指数、 胰岛素、胰岛素抵抗指数、总胆固醇、三酰甘油和高密度脂蛋白胆固醇也有显著变化,差异均有统计学意义(均 P<0.05)。治疗对体重和胰岛素抵抗的影响出现在第12周,并且在第24周进一步改善,但对改善血脂异常的作用在第 24周结束时才出现。结论：二甲双胍治疗对于改善抗精神病药物引起的血脂异常和胰岛素抵抗是有效的,并且改善 抗精神病药物诱导的胰岛素抵抗出现的时间早于降低血脂异常的时间。     

Lymphocytopenia in high cancer risk population: Evidence in automobile pattern makers

A total of 1454 automobile pattern makers were studied to determine the degree of lymphocyte reduction. These occupational workers have been known to be at high risk for colorectal cancer. As a group, pattern makers had significantly lower lymphocyte counts than the comparison group. The proportion of lymphocytopenia (less than 1500/mm³) in pattern makers was 26.2% as compared with 5.6% in the comparison group. Continuous monitoring of lymphocyte reduction in pattern makers may be worthwhile to evaluate whether these workers face a high risk for deficiency in lymphocytes in association with their risk for high rates of colorectal cancer.     

硼替佐米作用不同时间对K562耐药细胞株核因子-κB途径的影响

 目的　观察硼替佐米（商品名：万珂,PS-341）对柔红霉素（DNR）诱导的K562耐药细胞株（K562／DNR）核因子-κB（NF-κB）、抑制蛋白κB（IκB）及P-糖蛋白（P-gp）表达的影响,探讨PS-341逆转耐药的分子机制。方法　以100 μg／ml DNR单用或联合应用4 μg／L PS-341分别作用于K562／DNR 12、24及36 h,检测不同时间点各组NF-κB、IκB及P-gp表达情况,同时测定NF-κB p65活性,检测各组细胞凋亡率。结果　Western blot结果显示：与阴性对照组相比,DNR可诱导NF-κB表达上调及活性增强、IκB表达下调、P-gp表达上调;加用PS-341可显著抑制 DNR诱导的NF-κB及P-gp表达,使IκB表达增加。加用PS-341后,NF-κB活性12 h为（15.3±1.87）%[DNR组为（23.8±2.27）%],24 h为（10.2±1.69）%[DNR组为（25.4±1.98）%],36 h为（6.08±2.53）%[DNR组为（26.9±2.58）%],与相应单用DNR组相比均有明显下降,差异有统计学意义（P值均＜0.05）。DNR与PS-341联用后,细胞凋亡率12 h为（35.23±5.15）%[DNR组为（15.56±4.12）%],24 h为（40.26±6.89）%[DNR组为（17.25±2.89）%],36 h为（43.58±7.69）%[DNR组为（22.47±4.58）%],与DNR组相比,细胞凋亡率均明显增加,差异具有统计学意义（P值均＜0.05）。上述作用呈时间依赖性。结论　PS-341可减少K562／DNR细胞NF-κB的活化,降低P-gp表达,逆转细胞耐药,促进细胞凋亡。     

针灸对MNNG诱导大鼠癌前病变胃黏膜病理及血清CEA影响观察

目的：研究针灸预处理对Wistar大鼠癌前病变胃黏膜干预作用和对血清CEA的影响。方法：将50只Wistar雄性大鼠随机分为4组,其中空白对照组10只;其余40只大鼠自由饮用100gg／mL的N-甲基-N’-硝基-N-亚硝基胍（MNNG）6个月诱发大鼠胃癌模型,模型组20只;艾灸组和针刺组均10只,在造模3个月以后对足三里和梁门穴进行相应的治疗干预。处死大鼠后取胃黏膜进行HE染色,光镜下观察各组大鼠胃黏膜形态,并采用IPP6．0图像分析软件比较各组胃黏膜细胞核质比。股动脉留取大鼠血液,ELlSA法检测血清CEA。结果：光镜结果显示,艾灸和针刺预处理组大鼠胃黏膜相对于模型组大鼠炎症和异型性等变化较轻;模型组核质（面积）比为1．51±0．69,明显高于空白对照组0．85±0．33,P〈0．001;艾灸组为0．70±0．29,小于模型组,P-0．0064;针刺组为0．99±0．43,亦小于模型组,P=0．0400。酶联免疫吸附实验（enzyme—linked immuno sorbent assay,ELISA）结果显示,模型组血清CEA为（372．42±137．61）og／mL,较空白组（243．13±59．07）iog／mL升高,P-0．0072;艾灸组为（285．63±122．14）pg／mL,较模型组降低,P=0．0445;针刺组为（302．89±ll0．02）pg／mL,较模型组降低,但差异无统计学意义,P=0．4020。结论：针灸预处理能够改善MNNG导致的大鼠胃黏膜癌前病变的组织学表现和降低血清CEA浓度。     

Genomic Analysis of Shiga Toxin-Producing E. coli O157 Cattle and Clinical Isolates from Alberta,Canada

Shiga toxin (stx) is the principal virulence factor of the foodborne pathogen, Shiga toxin-producing Escherichia coli (STEC) O157:H7 and is associated with various lambdoid bacterio (phages). A comparative genomic analysis was performed on STEC O157 isolates from cattle (n = 125) and clinical (n = 127) samples to characterize virulence genes, stx-phage insertion sites and antimicrobial resistance genes that may segregate strains circulating in the same geographic region. In silico analyses revealed that O157 isolates harboured the toxin subtypes stx1a and stx2a. Most cattle (76.0%) and clinical (76.4%) isolates carried the virulence gene combination of stx1, stx2, eae and hlyA. Characterization of stx1 and stx2-carrying phages in assembled contigs revealed that they were associated with mlrA and wrbA insertion sites, respectively. In cattle isolates, mlrA and wrbA insertion sites were occupied more often (77% and 79% isolates respectively) than in clinical isolates (38% and 1.6% isolates, respectively). Profiling of antimicrobial resistance genes (ARGs) in the assembled contigs revealed that 8.8% of cattle (11/125) and 8.7% of clinical (11/127) isolates harboured ARGs. Eight antimicrobial resistance genes cassettes (ARCs) were identified in 14 isolates (cattle, n = 8 and clinical, n = 6) with streptomycin (aadA1, aadA2, ant(3’’)-Ia and aph(3’’)-Ib) being the most prevalent gene in ARCs. The profound disparity between the cattle and clinical strains in occupancy of the wrbA locus suggests that this trait may serve to differentiate cattle from human clinical STEC O157:H7. These findings are important for stx screening and stx-phage insertion site genotyping as well as monitoring ARGs in isolates from cattle and clinical samples.