肠外营养导致大鼠肝细胞周期基因的变化及临床意义

目的 本研究利用实时定量PCR芯片技术,检测TPN后肝脏细胞周期基因表达的变化,探讨哪些基因在肝脏损害中发挥作用,为临床预防和治疗PNALD提供资料.方法 选择12只雄性SD大鼠,随机分为TPN组(6只)和生理盐水对照组(6只),7d后应用实时定量PCR芯片检测方法 ,比较两组大鼠间肝脏细胞周期基因的表达.结果 TPN组大鼠肝脏病理表现为肝细胞弥漫的脂肪空泡变性,小叶中央区较周边区更为明显;TPN组大鼠肝脏细胞周期表达上调基因有Atm、Brea1、CAkn1b、Dnajc2、G2a、Nfatc1、Notch2、Pkd1、Ppp2r3a等,表达下调基因有CAc25b、Ccnd1、E2f1、Mcm3、Nek2、Wee1等.结论 TPN组与生理盐水对照组大鼠比较,肝脏细胞周期基因表达存在差异,肝细胞周期基因ATM、BRCA1、Cdkn1b 等表达的改变,提示肝细胞增生减少和凋亡的增加,从而阻止肝细胞的修复,可能TPN与肝脏损伤的发生和发展相关.     

坐骨棘筋膜固定术的临床解剖学研究

Objective The study was to explore the safety, firmness and convenience of the fascia around the ischial spine as a new fixation site for the vaginal fornix. Methods Between June 2007 and January 2008, detailed dissections and related measurements of the regions around the ischial spine were performed on 10 Chinese female cadavers (3 unembalmed and 7 embalmed cadavers). At the same time, the sacrospinous ligament,the fascia on the ischial spine, the iliococcygeus fascia as well as the vaginal fornix were exposed and the pull-out strength sequentially tested using a digital push-pull force gauge. Results The fascia on the ischial spine was firm and strong, with a thickness of 3 about mm. No major vessels or nerves were observed on the ischial spine. The greatest pullout strengths of the sacrospinous ligament,the fascia on the ischial spine, the iliococcygeus fascia as well as the vaginal fornix were (102±26),(64±15),(33±8)and(32±6)N, respectively. Conclusion The fascia at 1 cm from anterior lateral ischial spine, free of major vessels and nerves, is safe and strong and could be used as a new site for suspension in vaginal prolapse.     

不同高浓度CO_2对2-细胞小鼠胚胎体外发育的影响

目的 :观察不同高浓度二氧化碳 ( CO2 )对 2 -细胞小鼠胚胎体外发育的影响。方法 :获取小鼠 2 -细胞胚胎 ,置于 CZB培养液微滴 ,覆盖经三蒸水处理的石蜡油 ,分别在 5 % CO2 (对照组 )、5 .7%CO2 、6.0 % CO2 和 1 5 % CO2 浓度下体外培养 ;在 1 5 % CO2 时 ,另设覆盖经磷酸盐缓冲液 ( PBS)处理的石蜡油或不覆盖石蜡油的实验组 ,观察胚胎发育情况。结果 :5个实验组的囊胚率均显著低于对照组 ( P<0 .0 1 ) ,5 .7% CO2 时仅为 4.3% ,其余 4组的均为 0。 CO2 浓度 5 .7%和 6.0 %时 ,胚胎大部分停滞在 2 -细胞和 4-细胞期 ,两者间无统计学差异 ( P>0 .0 5 )。CO2 浓度 1 5 %时 ,覆盖经三蒸水处理的石蜡油组 ,有 1 5 %的胚胎发育到 4-细胞阶段 ,但 4-细胞胚胎的卵裂球不规则 ,很快退化 ;覆盖经 PBS处理过的石蜡油组 ,有 2 .2 %的胚胎发育到 4-细胞 ,其余出现严重的退化。结论 :高浓度 CO2 对小鼠胚胎发育有强毒性效应 ,引致胚胎发育停滞和严重降解 ;高浓度 CO2 时 ,胚胎覆盖三蒸水处理石蜡油的效果优于经 PBS处理的石蜡油 ;严密监控 CO2 浓度对胚胎体外发育是重要的     

宫颈癌患者HPV感染与血清STNFR水平的研究

目的 :探讨可溶性肿瘤坏死因子受体 (STNFR)以及人乳头瘤病毒 (HPV)感染与宫颈癌的关系。方法 :采用PCR法检测 6 2例宫颈癌患者癌组织中的HPV ,用双抗体夹心ELISA法检测患者血清中STNFRⅠ、STNFRⅡ ,并与正常 35例对照。结果 :宫颈癌患者癌组织中HPV感染率明显高于正常对照组 (P <0 0 0 1) ;宫颈癌患者血清STNFRⅠ、STNFRⅡ水平较正常对照组明显增高 (P <0 0 0 1) ;在宫颈癌患者中HPV感染阳性组STNFRⅠ、STNFRⅡ水平均高于阴性组 (P <0 0 1) ;宫颈癌患者术后 3月血清中STNFRⅠ和STNFRⅡ明显低于术前 (P <0 0 0 1)。结论 :STNFR与宫颈癌的发生发展有关 ,术后明显降低 ,STNFR水平的增高可能与宫颈癌HPV感染有关 ,其发生原理有待进一步研究。     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.     

胃癌患者血清肝细胞生长因子的检测及意义

Objective To explore the clinical significance of serum HGF level changes in gastric cancer pa-tients. Methods 60 cases of patients who operatied and clinicopathological confirmed gastric cancer, were detected serum HGF level by enzyme linked immunosorbent assay(ELISA) .40 cases were administered radical gastrectomy,20 cases of patients who had distant metastasis and loss operative chance were detected 7 days and 3 months preopera-tive,postoperative serum HGF level respectively. At the same time 40 cases of chronic gastritis patients and 40 cases of healthy examination people were selected as control group. Results Serum HGF level in patients with gastric canc-er was significantly higher than that of chronic gastritis and normal controls(P <0. 01). The serum HGF level of pa-tients with tumor vascular invasion significantly increased(P <0. 05). The patients with lymph node metastasis,serum HGF level was significantly higher than that patients with no lymph node metastasis(P <0. 05). The serum HGF level of patients with liver metastasis was significantly higher than that patients with no liver metastasis(P <0. 05). The se-rum HGF level of gastric cancer patients whose maximum diameter of the tumor ≥3cm were significantly higher than that maximum diameter of the tumor <3cm(P<0. 05). According to TNM staging of gastric cancer,the serum HGF level of Ⅰ phase and Ⅱ phase patients were significantly lower than that Ⅲ phase and Ⅳ phase patients(P <0.05).The serum HGF level of gastric cancer patients had no significant correlation with sex ,age and histological type(P <0.05). The serum HGF level of 40 cases of patients who were 1 week after surgery were significantly decreased,the patients who were 3 months after surgery were more obvious(P <0. 05 and P <0. 001). Conclusion HGF may play an important role in gastric cancer occurrence and development. The detection of serum HGF level can become an im-portant index for monitoring the degree of gastric cancer and prognosis of patients.     

"乳癌术后方"对乳腺癌患者生活质量影响的临床研究

为评价“乳癌术后方”对 35 8例乳腺癌患者生活质量的影响。采用欧洲癌症治疗研究组织生活质量核心量表E ORTCQLQ -C30 ,对 35 8例乳腺癌患者运用“乳癌术后方”治疗前后分别进行问卷调查 ,并设对照组 96例。结果“乳癌术后方”治疗 6个月 ,临床症状明显改善 ,与对照组比较 ,P <0 0 5 ;患者生理功能、情感功能、认识功能等都有不同程度的提高 ;生活质量总评价各项治疗前后有明显改变 ,与对照组比较 ,P <0 0 5。提示该方能明显提高乳腺癌患者的生活质量 ,有很好的临床应用价值。     

末治脾肾,能起沉疴--单纯中药治疗乙肝相关性肝癌1例

探讨中药审因论治对乙肝相关性肝癌的治疗作用。应用调补脾肾、搜邪泄浊法 ,对一例乙肝相关性肝癌患者进行单纯中药治疗。结果 :经过 12个月治疗 ,AFP由最高 10 0 0 0 μg/L降至正常 (<2 0 μg/L) ,AFP异质体同步转阴 ,B超、MRI显示肝部实质性肿块消散 ,肝功能好转。提示本治法对肝癌具有较好的治疗作用。     

恶性肿瘤中TGF-β1信号传递分子DPC4/Smad4的研究进展

DPC4/Smad4基因是新近被鉴定的一个肿瘤抑制基因 ,其编码的DPC4/Smad4蛋白是TGF β信号传导通路中的重要传导蛋白 ,是TGF β配体、受体结合后后续信号传导的胞质递质 ,参与TGF β受体激活后的信号传导。DPC4/Smad4调控的下游目的基因有p2 1WAF1、uPA、PAI 1、VEGF、TSP 1。转化生长因子 -β(transforminggrowthfactorbeta ,TGF β)信号传导通路的配体、受体、胞内信号传导分子Smad蛋白及其调控的下游目的基因等组成一个肿瘤生长的负性调节 ,通路中任何一个元件的异常都可引起信号传导紊乱 ,导致肿瘤发生     

鼻咽癌放射治疗后颅神经损伤的临床分析

目的　探讨鼻咽癌放射治疗后颅神经损伤的临床特点、诊断、治疗及预后因素。方法　对 1990年 4月至 2 0 0 3年 2月收治的 86例鼻咽癌放射治疗后颅神经损伤患者的临床资料进行回顾性分析。结果　首程放疗患者颅神经损伤的潜伏期为 0 .5～2 1.0年 ,中位潜伏期为 4.5年。以舌下神经损伤最为多见 ( 68.6% )。 63例早期使用激素、抗生素、大量维生素等药物治疗的患者中 ,18例症状轻微改善 ,3 3例无明显变化 ,12例病情进展。随访 77例 ,死亡 2 8例 ,49例生存 ,出现神经症状者生存期 0 .6～ 13 .0年 ,3 2例生活不便 ,17例生活困难。结论　放射性颅神经损伤缺乏有效的治疗手段 ,它的发生与照射剂量、照射技术及分次剂量等因素有关 ,放射性颅神经损伤严重影响患者生存质量 ,应尽量减少其发生