A human cancer-associated truncation of MBD4 causes dominant negative impairment of DNA repair in colon cancer cells

MBD4 binds to methylated DNA and acts as a thymine DNA glycosylase in base excision repair. Deficiency of MBD4 in mice enhances mutation at CpG sites and alters apoptosis in response to DNA damage, but does not increase tumorigenesis in mismatch repair-deficient mice. However, in humans, frameshift mutation of MBD4, rather than deletion, is what occurs in up to 43% of microsatellite unstable colon cancers. There is no murine equivalent of this mutation. We now show that recombinant truncated MBD4 (MBD4(tru)) inhibits glycosylase activities of normal MBD4 or Uracil DNA glycosylase in cell-free assays as a dominant negative effect. Furthermore, overexpression of MBD4(tru) in Big Blue (lacI)-transfected, MSI human colorectal carcinoma cells doubled mutation frequency, indicating that the modest dominant negative effect on DNA repair can occur in living cells in short-term experiments. Intriguingly, the whole mutation spectrum was increased, not only at CpG sites, suggesting that truncated MBD4 has a more widespread effect on genomic stability. This demonstration of a dominant negative effect may be of significance in tumour progression and acquisition of drug resistance.     

XH-超高频皮肤整形手术仪的临床应用

目的：寻找一种治疗各种良性皮肤赘生物及色素性病变安全简单有效的方法。方法：用ＸＨ－超高频皮肤整形手术仪，可使皮肤病变组织产生完全气化及精细分层之特点治疗各种良性皮肤赘生物及色素性病变。结果：所有病例均获成功、效果良好。结论：ＸＨ－超高频皮肤整形手术仪可治疗各种良性皮肤赘生物及色素性病变。     

城市居民膳食行为干预效果探讨

目的 为增强城市居民预防心血管疾病的意识，以减盐，控油为重点，探讨膳食干预措施的效果和可行性，方法 在安贞，新街口社区将合理膳食的相关知识以板报，宣传册及现场膳食烹饪表演的形式进行，结果 在主区前后分别随机抽样的300人群中膳食频率及相关知识的调查应答率分别是：98．6％，99．3％，结论干扰后提高了居民中烹饪者的合理膳食的知识水平，尤其是在减盐和控油的认识上都有了明显的提高（P＜0．05），在摄取植物油，油炸食品，粗杂,粮,水果，豆制品等的膳食频率都显示出较为合理的改变P＜0．05，体现了干预的效果。     

Estimation of gene–environment interaction by pooling biospecimens

Case‐control studies are prone to low power for testing gene–environment interactions (GXE) given the need for a sufficient number of individuals on each strata of disease, gene, and environment. We propose a new study design to increase power by strategically pooling biospecimens. Pooling biospecimens allows us to increase the number of subjects significantly, thereby providing substantial increase in power. We focus on a special, although realistic case, where disease and environmental statuses are binary, and gene status is ordinal with each individual having 0, 1, or 2 minor alleles. Through pooling, we obtain an allele frequency for each level of disease and environmental status. Using the allele frequencies, we develop a new methodology for estimating and testing GXE that is comparable to the situation when we have complete data on gene status for each individual. We also explore the measurement process and its effect on the GXE estimator. Using an illustration, we show the effectiveness of pooling with an epidemiologic study, which tests an interaction for fiber and paraoxonase on anovulation. Through simulation, we show that taking 12 pooled measurements from 1000 individuals achieves more power than individually genotyping 500 individuals. Our findings suggest that strategic pooling should be considered when an investigator designs a pilot study to test for a GXE. Published 2012. This article is a US Government work and is in the public domain in the USA.     

肺结核合并肺癌15例临床分析

近年来由于肺结核病死率的降低，肺结核患者的年龄分布逐渐向高龄推进，同时肺癌患者剧增，肺结核与肺癌并存的机率逐渐增加，临床重视不够易于漏诊。1994年7月至2006年6月本院胸外科经病理确诊肺结核合并肺癌15例，现结合文献对15例患者的临床资料进行回顾性分析。     

射频消融术损伤心肌的检测方法

射频消融术（FRCA）必然造成心肌细胞不同程度的损伤。作者综述了心肌酶学标志物（CK和CK-MB）、心肌肌钙蛋白（cTnT和cTnI）和高频心电图（HFECG）等三种方法，在监测RFCA引起的心肌损伤方面的应用，认为cTnT和cTnI是目前监测RFCA对心肌损伤最可靠的方法。     

False alarm rates of statistical methods used in determining increased frequency of reports on adverse drug reaction

Several statistical methods have been proposed or used in the determination of an increase in frequency of reports of adverse drug reactions. Some of the methods are based on large sample approximation or equal sample sizes assumption. The actual type I error may differ significantly from the predetermined nominal level of 5% when the methods are applied to rare adverse events. Simulated false alarm rates of the methods were compared under the assumption of 10 or less expected reports in the reference period.     

J6-Ⅲ模拟座舱屋角主动消声系统的研制

目的研制对低频噪声有较好消声作用的J6-Ⅲ模拟座舱屋角主动消声系统。方法通过将简正振动模式分析理论应用于驾驶舱内声场分析研究中,确定消声系统的传输曲线,利用声电反馈控制系统来实现,并在歼6-Ⅲ歼击机模拟座舱进行实际测量。结果系统对歼6-Ⅲ飞机模拟座舱内500 Hz窄带噪声主动消声效果超过8 dB;作用范围65 Hz～1000 Hz。结论主动消声对低频噪声作用明显,本系统推广范围大,但是实际应用尚有差距。     

Tolerance of low‐frequency ultrasound sonophoresis: a double‐blind randomized study on humans

Background: Sonophoresis [low‐frequency ultrasound (US)] has been used in animals and in vitro to investigate enhanced percutaneous absorption of drugs. No study focused on its clinical human tolerance has been published as yet. Methods: We aimed to assess the bioeffects of low‐frequency US in vivo on human skin in a double‐blind randomized‐controlled study. We applied pulse‐mode US at 36 kHz for 5 min in a step procedure of increasing dosage, from 1.57 to 3.50 W/cm², and placebo. The primary outcome was toxic effects of the procedure, defined as a pain score >40 on a 0–100 mm visual analogue scale or necrosis. Erythema (scored from 0 to 3 in severity) was also evaluated. The secondary outcomes were measurements of skin thickness by high‐resolution skin imaging, of skin capacitance and temperature. Results: We included 34 healthy volunteers. We found no pain score >38 and no skin necrosis with either US or placebo. Erythema was systematically observed immediately after US application, but after 1 day, we observed three cases in the knee group. The most frequent adverse effect was tinnitus. We observed no marked increase in temperature or cutaneous thickness after US or placebo. Cutaneous capacitance increased immediately after both applications. Conclusion: Such data demonstrating good tolerance of sonophoresis can be useful before the initiation of a clinical trial of the therapeutic use of low‐frequency sonophoresis in humans.