某宝石加工厂矽肺的调查分析

目的　调查某宝石加工厂工人矽肺的发病特征。方法　对某宝石加工厂接尘工人进行矽肺横断面流行病学调查。结果　该厂作业场所矽尘浓度平均为 3 3mg/m3 ,游离SiO2 含量平均为 93 1%。该厂矽肺发病率为 3 94%( 10 /2 5 4) ,发病年龄 ( 2 3 8± 3 0 2 )岁 ,接尘工龄为 ( 3 3 3± 1 47)年。患者X线胸片表现以q影为主。矽肺肺结核并发率为2 0 % ;矽肺患者肺活量 (VC)、用力肺活量 (FVC)、1秒钟用力呼气量 (FEV1) ,最大通气量 (MVV)值明显低于接尘工人 (P <0 0 5或P <0 0 1) ;完全丧失劳动能力者占 70 %。结论　宝石加工工人矽肺符合急进型矽肺的诊断 ,其特点为发病年龄小 ,接尘工龄短 ,肺通气功能明显损伤 ,致病残程度较重 ,预后较差。     

吉西他滨单药或与顺铂联合治疗胰腺癌的临床疗效评价

目的 评价吉西他滨单药以及与顺铂联合治疗局部晚期或转移性胰腺炎的疗效。临床受益反应,生存时间和毒性反应。方法 42例患者随机分为吉西他滨单药组（A组20例）和吉西他滨 顺铂联合组（B组22例）,A组;吉西他滨1000mg/m^2,每周1次,连用7周,休息1周;随后相同剂量每周1次,连用3周,休息1周,B组;吉西他滨1000mg/m^2,每周1次,连用3周,顺铂60mg/m^2,第15天给药,休息1周,每4周重复,边境用药3个周期。结果 42例患者中,可评价客观疗效者34例（A组16例,B组18例,可评价临床受益反应（CBR）者36例（A组16例,B组20例）,可进行毒性反应评估者40例（A组19例,B组21例）,A组：PR1例（6.3%)。MR4例（25.0%),SD7例（43.8%)。PD4例（25.0%)。B组;PR2例（11.0%)。MR3例（16.7%),SD8例（44.4%),PD5例（27.8%)。PR MR SD率A组为75.0%。B组为72.2%。CBR有效率A组为87.5%(14/16),B组为70.0%(14/20)。两组3个月生存率均为100%,6个月生存率分别为81.3%和61.6%。12个月生存率分别为31.3%和11.1%。B组Ⅲ、Ⅳ度血液学毒性反应发生率略高于A组,两组相比,差异无显著性。结论 吉西他滨单药以及与顺铂联合一线治疗局部晚期或转移性胰腺癌有一定的客观疗效。可明显改善患者的生活质量。延长了生存时间,患者耐受良好。     

An increase of cytochrome C oxidase mediated disruption of gemcitabine incorporation into DNA in a resistant KB clone

Mechanistic aberrations leading to Gemcitabine (2',2'-dFdCyd,2,2-difluorodeoxycytidine, Gem) resistance may include alteration in its transport, metabolism and incorporation into DNA. To explore the mechanism of Gem resistance, the restriction fragment differential display PCR (RFDD-PCR) was employed to compare the mRNA expression patterns of KBGem (Gem resistant), KBHURs (hydroxyurea resistant) and KBwt (parental KB cell). Nine gene fragments were overexpressed specifically in the KBGem clone. Sequencing and BLAST results showed that three fragments represent cytochrome C oxidase (CCOX, respiration complex IV) subunit III (CCOX3). The cDNA microarray confirmed that the mRNAs of CCOX and ATP synthase subunits were upregulated in KBGem as compared to KBwt and KBHURs. The increase in CCOX1 protein and activity led to the increase of free ATP concentration, which is consistent with the gene expression profile of KBGem. Furthermore, the sensitivity to Gem could be reversed by sodium azide, a CCOX inhibitor. Following the treatment of sodium azide, the cellular accumulation of [3H]-Gem increased in a dose (of azide)-dependent manner, which is associated with increase of [3H]-Gem incorporation into DNA in KBGem. In summary, an increase of CCOX activity and free ATP level may reduce the transport, metabolism and DNA incorporation of Gem, resulting in Gem resistance.     

Leukotrienes: clinical significance

The leukotrienes, so named because of their initial identification in leukocyte preparations and the presence of three conjugated double bonds (a conjugated triene), are metabolites of the same polyunsaturated fatty acids (e.g., arachidonic acid) that give rise to the prostaglandins, thromboxanes, and several other families of biologically active lipids. Their potential clinical importance derives from their effects on vascular and other smooth muscle reactivity and on leukocyte function. Several leukotrienes may markedly influence the cellular and vascular responses that constitute an integral part of hypersensitivity and inflammatory reactions of the skin. Preliminary data from several laboratories have been presented that implicate a specific leukotriene in the evolution of the lesions of psoriasis.     

改良八珍糕治疗小儿厌食症43例

目的:观察改良八珍糕治疗小儿厌食症的临床疗效。方法:将86例小儿厌食症患儿随机分为观察组和对照组,每组各43例。观察组患儿给予改良八珍糕,对照组患儿给予现有八珍糕。比较两组患儿的临床疗效及便秘改善情况。结果:观察组有效率为95.3%,对照组有效率为86.0%,两组患儿临床疗效比较,差异具有统计学意义(P0.05)。观察组开始出现便秘时间为4.6 d,对照组为9.1 d;观察组便秘率为18.6%,对照组为51.2%,两组患儿便秘情况比较,差异均有统计意义(P0.01)。结论:改良八珍糕治疗小儿厌食症疗效明显,且可显著减少便秘的不良反应。     

UBE2M-mediated p27 degradation in gemcitabine cytotoxicity

Gemcitabine (2′-deoxy-2′, 2′-difluorocytidine; Gem) is a nucleoside anti-metabolite and is commonly used for treating various human cancers including human bladder carcinoma. Gemcitabine not only functions as a suicide nucleoside analog but also inhibits DNA polymerase activity and results in the termination of chain elongation. Using 2-dimensional gel electrophoresis analysis, a Gem-induced protein was identified as UBE2M (a.k.a. UBC12), a NEDD8 conjugation E2 enzyme which contributes to protein degradation. Gem induced UBE2M expression at both RNA and protein levels in several human cancer cell lines. The induction of UBE2M by Gem was accompanied by a reduction in p27^Kip1 protein levels, which could be restored by silencing UBE2M expression with siRNA or by treating cells with the proteasome inhibitor MG132, indicating that UBE2M mediates Gem-induced p27^Kip1 protein degradation. The induction of UBE2M and reduction of p27^Kip1 by Gem were prevented by the PI3K inhibitor LY294002. These results indicate that PI3K activity is necessary for Gem-induced UBE2M expression and that UBE2M facilitates degradation of p27^Kip1. Notably, silencing of UBE2M expression reduced Gem sensitivity in NTUB1 cells, suggesting that UBE2M mediates in part cell sensitivity to Gem, possibly by degradation of p27^Kip1. Analysis of Gem-resistant sub lines also showed that loss of UBE2M and increased p27^Kip1 expression were associated with the acquisition of drug resistance. In conclusion, our results demonstrate a role for UBE2M in mediating cytotoxicity of gemcitabine in human urothelial carcinoma cells while also suggesting a potential function of p27^Kip1 in drug resistance.     

角质细胞生长因子受体转基因对急性肺损伤时肺泡上皮细胞钠离子通道的影响

目的 观察角质细胞生长因子受体(KGFR)腺病毒表达载体在大鼠急性肺损伤前后对肺泡Ⅱ型上皮细胞钠离子通道表达的促进作用,从而验证基因治疗急性肺损伤的效果.方法 将雄性SD大鼠40只分成4组:正常对照组(n=8),致伤对照组(n=10),正常转基因组(n=10),致伤转基因组(n=12).用脂多糖(LPS)造成急性肺损伤模型,以肺组织明显肿大病变为制模成功标准.正常转基因组和致伤转基因组均通过大鼠尾静脉注射KGFR基因的腺病毒表达载体应用液1 mL,72 h后致伤转基因组和致伤对照组分别通过大鼠尾静脉以5 mg/kg注射LPS,正常转基因组和正常对照组则注射等量的生理盐水.过48 h后,断头处死所有实验组大鼠,取肺组织进行实验.通过免疫组化和免疫电镜检测各组大鼠肺泡Ⅱ型上皮细胞钠离子通道的表达情况.数据采用完全随机区组设计的方差分析,行LSD-t检验,以P<0.05为差异具有统计学意义.结果 肺泡Ⅱ型上皮细胞钠离子通道表达水平(免疫组化)由高到低依次为:正常对照组(PU值=47.7±3.33),正常转基因组(PU值=46.9±5.21),致伤转基因组(PU值=29.19±4.11)和致伤对照组(PU值=5.1±2.3);致伤转基因组的钠离子通道表达水平低于正常转基因组(t=9.134,P<0.001)和正常对照组(t=10.601,P<0.001),但明显高于致伤对照组(t=16.466,P<0.001).结论 KGFR腺病毒表达载体转基因效果明显,能够在LPS致伤情况下有效促进钠离子通道的表达,缓解肺泡腔内钠水潴留,达到转基因治疗肺损伤的效果.     

健择、顺铂支气管动脉导管介入灌注治疗肺非小细胞癌疗效评价

[目的]观察支气管动脉灌注顺铂(DDP 80mg／m^2)、健择(1．2g)治疗中、晚肺癌的疗效。[方法]80例中晚期肺癌病人随机分为支气管动脉灌注治疗组(A组)40例，静脉注射治疗组(V组)40例。[结果]A组缓解率65％，中位生存期10个月，生存1年以上患占52．5％；V组缓解率30％，中位生存期6个月，生存1年以上患占30％。[结论]支气管动脉灌注治疗肺癌的临床疗效优于静脉滴注。     

mTOR信号通路介导产生XCL1可促进乳腺癌耐药细胞株的增殖

背景与目的：统计表明90%以上肿瘤患者的死亡与肿瘤耐药相关,而在乳腺癌中常见PI3K/Akt/mTOR信号通路的异常激活,以此通路为靶点的药物已成为乳腺癌治疗的研究热点。本研究主要分析C族趋化因子配基1(C chemokine ligand 1,XCL1)对乳腺癌耐药细胞增殖的影响及其产生机制。方法：建立吉西他滨耐药性人乳腺癌细胞系MDA-MB-231/Gem。采用CCK8检测MDA-MB-231和MDA-MB-231/Gem的增殖能力,RT-PCR、ELISA检测2株细胞株XCL1表达差异,Western blot检测mTOR的表达。结果：与MDA-MB-231相比,MDA-MB-231/Gem的增殖能力增强,XCL1在耐药细胞株表达增强。mTOR在耐药细胞株表达水平及磷酸化水平增强。在MDAMB-231中加入外源性XCL1 24 h后,细胞增殖能力增强。而在MDA-MB-231/Gem中加入抗XCL1抗体后,细胞增殖能力降低。mTOR抑制剂处理MDA-MB-231/Gem后,细胞增殖能力降低,XCL1产生减少。结论：趋化因子XCL1的分泌可促进乳腺癌耐药细胞的增殖并由mTOR信号通路介导产生。