Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

教师心理健康素质问卷编制

目的：在理论分析和借鉴前人研究的基础上,对教师心理健康素质进行了理论维度探索。方法：通过访谈调查、探索性因素分析、验证性因素分析,编制了适合中小学教师的心理健康素质问卷（ TMHDQ）。结果：教师心理健康素质问卷由一般心理健康素质问卷的8个维度和职业心理健康素质问卷的5个维度构成,各维度的内部一致性系数为0．708～0．879,0．702～0．838,因子的累积贡献率分别为70．38％、60．849％。结论：经验证,本研究编制的教师心理健康素质问卷具有良好的信度和效度,符合心理测量学的要求,可以在今后相关研究中作为了解中小学教师心理健康素质状况的测量工具使用。     

大鼠膝关节周围微小动脉网分布及计数法的评价

背景：随着骨组织工程研究的不断深入和对骨代谢过程的不断认识,分析组织工程骨的血液供应和营养状况已成为目前的研究重点。目的：比较和评价常用的微小血管检测方法,明确各种方法的利弊,为研究组织工程骨内微血管的分布和计数提供借鉴意义。方法：分别用3种常用的血管评价法对SD大鼠膝关节周围微小动脉网进行分析对比,18只SD大鼠均分为免疫组化组、血管造影组、CT扫描重建组。结果与结论：免疫组化技术能观察到血管的分布范围,但是无法评价血管空间分布的整体情况。血管造影技术和CT检查则可以提供形象的血管空间分布图,但是CT检测时部分微小血管显示不清。免疫组化检出（26．50±3．02）条血管数明显多于血管造影（14．12±1．47）条和CT检测（9．00±1．79）条,其中CT检测组可检出的血管数最少。说明免疫组化和血管造影可以为微小血管提供微观和宏观的评价方法,从两个层面一起观察,更好的分析血管的情况,对微血管的评价有很好的借鉴意义。     

Comparison of glomerular filtration rate measurements with the two plasma sample and single plasma sample, gamma camera Gates, creatinine clearance, and prediction equation methods in potential kidney donors with normal renal function

OBJECTIVE: To compare measured glomerular filtration rate (GFR) by single plasma sample methods (SPSMs), gamma camera Gates, 24-h endogenous creatinine clearance, and prediction equations (Cockcroft-Gault and modification of renal disease (MDRD)) with the two plasma sample method (TPSM) considered as the reference in potential kidney donors with normal renal function. METHODS: One hundred and fifteen subjects (50 male, 65 female; mean age 41.9+/-12.2 years) with normal renal function were prospectively included in this study. GFR was calculated by TPSM (120-min and 240-min samples) and SPSM (180-min sample). RESULTS: While there was strong statistically significant correlation between the TPSM and all SPSMs, low correlation was found in Gates, creatinine clearance, Cockcroft-Gault and MDRD. In all SPSMs, 95% limits of agreements were consistent with each other and within clinically acceptable limits. The lowest bias, median absolute difference, mean percentage error, and the best precision were found for Christensen and Groth's method as modified by Watson (CGmW). CONCLUSIONS: Among the SPSMs, CGmW can reflect GFR more accurately than the other methods. Neither the gamma camera Gates method nor the creatinine clearance method nor the prediction equations (Cockcroft-Gault and MDRD) could calculate GFR accurately. All these techniques could result in mistakes in the management of potential kidney donors.     

全国社区卫生服务现状调查--研究背景与设计

为了保证2003年全国社区卫生服务现状抽样调查的真实性、可靠性，本课题组在文献复习的基础上，组织专家反复讨论，设计出一套研究方案，对具体实施情况提出了严格的质量控制措施，并对调查员培训等情况进行了详细的规定。     

超声与CT检查对小儿颅内出血诊断价值的比较

①目的 比较超声与CT检查对小儿颅内出血的诊断价值。②方法 应用超声和CT对41例颅内出血病儿和50例正常儿童进行检查，对超声检查与CT检查的结果进行比较。③结果 超声诊断为脑实质出血10例、硬脑膜下隙出血5例与CT相符；超声诊断蛛网膜下隙出血7例，漏诊2例，误诊1例；超声诊断脑室出血2例，漏诊1例，误诊1例；混合型出血12例，超声与CT检查诊断结果相符。PW显示血流频谱异常者39例，占95％。④结论 超声与CT检查诊断脑实质及硬脑膜下隙出血无明显差别。CT诊断蛛网膜下隙、脑室出血优于超声。CT确定出血部位优于超声。     

子宫内膜癌组织中p16 mRNA及P16蛋白的表达

①目的　探讨抑癌基因 p16与子宫内膜癌发生、发展的关系。 ②方法　应用逆转录聚合酶链反应(RT PCR)和免疫组织化学技术 ,对 4 2例子宫内膜癌及 15例正常子宫内膜组织中 p16mRNA及P16蛋白进行检测 ,并结合临床病理特征进行分析。③结果　子宫内膜癌组织中p16mRNA及P16蛋白的阳性表达率分别为6 9.0 5 %和 5 9.5 2 % ,显著低于正常组织 (χ2 =6 .0 15、8.6 2 5 ,P <0 .0 5 )。p16mRNA及P16蛋白的表达缺失与肿瘤的组织学类型无关 (χ2 =0 .10 0、0 .2 94 ,P >0 .0 5 ) ,而与组织学分级和临床分期有关 (χ2 =3.95 4、6 .873,P <0 .0 5 )。④结论　p16mRNA和P16蛋白的表达缺失在子宫内膜癌的发生和发展中可能起重要作用     

Pilon骨折的手术治疗

目的评价Pilon骨折的手术疗效。方法对1997年5月～2001年5月我科收治的25例Pilon骨折患者进行外固定和内固定治疗。结果术后所有患者的平均随防时间为10个月，根据Baird等评分标准，优17例，良4例，总体优良率为84％。结论Pilon骨折内固定治疗效果较佳，尽可能采用内固定治疗，尽量避免一期关节融合术。     

Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.

BACKGROUND: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. PATIENTS AND METHODS: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. RESULTS: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. CONCLUSION: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors.