肿瘤坏死因子α对人肝癌多药耐药逆转作用的实验研究

目的研究肿瘤坏死因子α（TNF-α）对体外培养的人肝癌耐阿霉素细胞系（HepG2／ADM）多药耐药现象的逆转作用。方法不同浓度（100、500及2500U／ml）TNF-α作用于HepG2／ADM细胞72h后进行以下试验：用实时荧光定量聚合酶链反应技术检测各组多药耐药相关基因（MDR1）及脂质过氧化物酶体增殖物激活受体α（PPAR-α）基因的mRNA表达情况;用罗丹明外排法检测各组P-糖蛋白活性;用Annexin V检测0．5mg／L阿霉素诱导的各组细胞凋亡情况;利用MTF法检测各组耐药性的改变。结果TNF-α能诱导HepG2／ADM细胞的MDR1基因表达下调,PPAR-α基因表达上调,且能增加阿霉素诱导的凋亡细胞的比例及细胞毒作用。结论TNF-α可能分别通过抑制MDR1表达及促进PPAR-α表达而逆转HepG2／ADM细胞的耐药性。     

ERK/MAPK通路参与肝癌产生多药耐药的胞内信号传导

目的探讨微环境诱导肝癌产生多药耐药的胞内信号传导途径。方法分别使HepG2细胞在缺氧、低糖环境下生长或稳定整合HBX基因,运用Western蛋白印迹法检测这些细胞内ERK／MAPK的活性。用ERK／MAPK特异性阻断剂U0126处理这些细胞后,用Western蛋白印迹法检测缺氧诱导因子-1α（HIF—1α）和多药耐药相关蛋白的表达变化,逆转录聚合酶链反应和免疫细胞化学技术分别检测HIF-1α在mRNA水平表达量和部位的改变。结果不同环境下生长的HepG2细胞中,磷酸肜非磷酸化ERK／MAPK比例均有不同程度的增高。用U0126处理12h后,这些细胞中HIF-1α和多药耐药相关蛋白的表达下降,且HIF-1α表达由胞核向胞质转位,其mRNA水平无显著变化。结论ERK／MAPK信号通路是微环境诱导肝癌产生多药耐药的重要胞内信号传导途径。     

经尿道双极等离子体电切术治疗膀胱肿瘤的疗效观察

目的:探讨经尿道双极等离子体电切术治疗膀胱肿瘤的安全性与有效性。方法:采用英国Gyrus公司的经尿道双极等离子体电切系统行经尿道膀胱肿瘤电切术(TURBt)治疗膀胱肿瘤271例,患者年龄18～90岁,平均63.6岁。其中单发肿瘤160例,多发肿瘤111例,膀胱侧壁有肿瘤分布者96例。结果:首次诊断为膀胱肿瘤行经尿道双极电切术的时间为46±21(15～75)min,膀胱穿孔21例;96例侧壁肿瘤切除时出现明显的闭孔神经反射56例。随访6～72个月,复发149例,其中再次行电切术102例,行部分膀胱切除加输尿管移植术24例,行全膀胱切除术20例。结论:用双极等离子体电切术治疗膀胱肿瘤是一种安全、有效的手术方式,但不能防止闭孔神经反射的发生。     

Comparison of parent and teacher reports of attention-deficit/hyperactivity disorder symptoms from two placebo-controlled studies of atomoxetine in children.

BACKGROUND: The validity of parent reports regarding children's attention-deficit/hyperactivity disorder (ADHD) symptoms has been questioned. This study assessed whether parent reports were as sensitive as teacher reports to document change in ADHD symptoms during clinical trials with atomoxetine. METHODS: Data were compared from two randomized, double-blind, placebo-controlled clinical trials of atomoxetine using different versions (parent or teacher) of the same rating scale (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV [parent or teacher] Version: Investigator Administered and Scored - ADHD RS). Exclusion criteria included history of bipolar disorder, psychosis, seizures, alcohol abuse, or positive drug screen. Patients (6-16 years old) were treated with atomoxetine (titrated to a maximum dose of 1.8 mg/kg/day) administered once daily for up to 7 weeks. Parent and teacher ratings were compared using an analysis of covariance (ANCOVA) model. RESULTS: The analysis (n = 318) showed that treatment effects (mean change, baseline to endpoint) were similar between parent and teacher ratings (total, p = .762; inattention, p = .519; hyperactive/impulsive, p = .955). Effect sizes also were similar based on total scores (parent ratings = .69; teacher ratings = .63). CONCLUSIONS: Parent reports are as sensitive as teacher reports in assessing the efficacy of long-acting pharmacologic treatment for ADHD in children during clinical trials using the nonstimulant atomoxetine.     

Repair of rat cranial bone defects with nHAC/PLLA and BMP‐2‐related peptide or rhBMP‐2

An ideal artificial substitute has good biocompatibility properties and is able to provide for rapid bone formation. Bone morphogenetic protein‐2 (BMP‐2) is considered as one of the most important growth factors for bone regeneration. In this study, a synthetic BMP‐2‐related peptide (designated P24) corresponding to residues of the knuckle epitope of BMP‐2 was introduced into a bioactive scaffold based on nano‐hydroxyapatite/collagen/poly(L ‐lactic acid) (nHAC/PLLA); its in vitro release kinetics was then measured. A 5 mm diameter cranial bone defect was created in the calvariae of 30 rats and randomly implanted with three groups of biomaterials: Group A (nHAC/PLLA alone); Group B (P24/nHAC/PLLA composite); and Group C (recombinant human BMP‐2 (rhBMP‐2)/nHAC/PLLA composite). The P24/nHAC/PLLA implants significantly stimulated bone growth similarly to the rhBMP‐2/nHAC/PLLA implants based on the radiographic and three‐dimensional CT evaluation and histological examination, thereby confirming the enhanced bone healing rate of these compounds compared with the stand‐alone nHAC/PLLA scaffold material. The osteoinductive ability of 3 mg P24 was similar to that of 1 µg rhBMP‐2. P24/nHAC/PLLA is a promising scaffold biomaterial for bone tissue regeneration. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1745–1752, 2011     

Peroxisome proliferator-activated receptor-α is renoprotective in doxorubicin-induced glomerular injury

Doxorubicin (DOX) is an anthracycline antibiotic utilized in antitumor therapy; however, its clinical use is frequently impeded by renal toxic effects. As peroxisome proliferator-activated receptor-α (PPAR-α) has renoprotective effects in drug-related kidney injuries, we tested its ability to inhibit DOX-induced renal injury. Although both male PPAR-α knockout mice and their wild-type littermates (pure 129/SvJ background) had significant proteinuria 4 weeks after DOX treatment, those with deletion of PPAR-α had more severe proteinuria. This was associated with more serious podocyte foot process effacement compared with wild-type mice. In contrast, the PPAR-α agonist fenofibrate effectively reduced proteinuria and attenuated DOX-induced podocyte foot process effacement. Consistently, glomerular nephrin expression was significantly lower in the knockout compared with wild-type mice following DOX treatment. Fenofibrate therapy significantly blunted the reduction in glomerular nephrin levels in DOX-treated wild-type mice. In cultured podocytes, DOX induced apoptosis, increased cleaved caspase-3 levels, and decreased Bcl-2 expression, all attenuated by pretreatment with fenofibrate. Thus, PPAR-α deficiency exacerbates DOX-related renal injury, in part, due to increased podocyte apoptosis.     

经鼻内镜切除良性鼻-颅底肿瘤（附11例报告）

目的探讨鼻内镜下切除良性鼻-颅底肿瘤的疗效。方法 2004年3月～2009年11月对11例良性鼻-颅底肿瘤,鼻内镜下先切除鼻腔鼻窦肿瘤,逐渐接近颅底,仔细辨认颈内动脉等重要解剖结构,然后分块切除肿瘤,最后修复颅底缺损。结果 11例鼻-颅底肿瘤鼻内镜下全部切除,术中出血量100～450 ml,平均175 ml;手术时间105～210 min,平均146 min。术后未出现脑脊液鼻漏、细菌性脑膜炎等并发症。病理类型：巨大筛额窦囊肿2例,鼻咽纤维血管瘤3例,上颌窦内翻性乳头状瘤3例,蝶窦骨化纤维瘤1例,翼腭窝神经鞘瘤1例,侧颅底炎性肌母细胞瘤1例。11例随访6～58个月,平均41个月,鼻窦CT扫描和鼻内镜复查无肿瘤局部复发。结论鼻内镜手术利于辨别颅底重要的解剖结构和肿瘤的彻底切除,是治疗鼻-颅底良性肿瘤的理想方法。     

社会影响量表中文版应用于尿失禁患者羞耻感的信效度测量

目的 考查社会影响量表中文版在国内女性尿失禁患者中应用的信度和效度.方法 采用便利抽样法选取社区女性尿失禁患者246例,进行信度分析和探索性因素分析,评定量表的信度和结构效度.结果 探索性因素分析最终保留20个条目共3个因子,累积贡献率为54.418%,3个因子是社会隔离、社会排斥、内在羞耻感.经过调整后量表的内部一致...     

低温等离子射频消融治疗腰椎间盘突出症初步探讨

目的评价低温等离子刀射频消融术治疗腰椎间盘突出症的临床疗效。方法 2006年1月～2009年12月应用低温等离子射频消融治疗腰椎间盘突出症共44例,男20例,女24例;年龄30～52岁,平均40岁。局部麻醉,在C型臂引导下操作。共46个椎间隙：单间隙42例,双间隙2例。术后随访近期效果。结果全部病例均获得随访,随访时间6～48个月,平均24个月。VAS评分术前（8.40±0.50）分,术后1周（2.60±0.53）分,末次随访（2.80±0.34）分。Oswestry评分术前（59.00±1.90）分,术后1周（30.00±1.80）分,末次随访（34.00±1.50）分。各指标术后及末次随访时与术前比较有显著性差异（P〈0.05或P〈0.01）,而术后两次随访差异无统计学意义（P〉0.05）。患者满意度80%,无任何并发症。结论经皮低温等离子刀髓核消融术是治疗腰椎间盘突出症行之有效的方法,这种技术简单、微创、安全、疗效肯定。关键是选择合适的适应证。     

恒河猴中TTV感染的回顾性实验研究

目的：了解接种患者血清的恒河猴能否复制ＴＴ病毒（ＴＴ ｖｉｒｕｓ,ＴＴＶ）,正常恒河猴中是否有ＴＴＶ感染,分析猴中ＴＴＶ基因结构特点。方法：用ＰＣＲ方法检测血清标本中ＴＴＶ ＤＮＡ,对ＴＴＶ ＤＮＡ阳性的标本进行序列测定。结果：健康猴中无ＴＴＶ感染;１０只接种患者血清的恒河猴中,经验检测有４只为ＴＴＶ阳性,将其中一株ＴＴＶ进行序列测定,该序列与日本ＴＴＶ部分基因相对应位置的核苷酸同源性为９６％,将