Identification of candidate alkylator-induced cancer susceptibility genes by whole genome scanning in mice

Secondary malignancies are a serious adverse consequence of alkylator chemotherapy. The risk of developing an alkylator-associated malignancy is influenced by genetic background, although the relevant genetic factors are poorly understood. To screen for novel susceptibility factors, we established a mouse model of alkylator-induced malignancy. We exposed mice from 20 inbred strains to the prototypical alkylating agent, N-nitroso-N-ethylurea (ENU). ENU was a potent carcinogen in many of the strains tested, inducing 140 tumors in 240 ENU-treated mice (66% incidence of at least one tumor in evaluable mice), compared with a background incidence of 8% spontaneous tumors in 240 strain-, age-, and sex-matched control mice (relative risk, 8.4; P < 0.0001). A wide variety of tumor histologies were noted, including epithelial carcinomas, soft tissue sarcomas, and hematopoietic tumors. Cancer susceptibility was a heritable trait for the most common tumor types, lung adenocarcinoma (H(2) = 0.25), T cell lymphoma (H(2) = 0.19), and myeloid malignancies (H(2) = 0.10). Quantitative trait locus mapping identified regions on chromosomes 3, 6, 9, and 15 containing candidate genes associated with lung adenoma, lung carcinoma, and lymphoma susceptibility. This novel mouse model recapitulates many features of human alkylator-associated cancer and supports the hypothesis that susceptibility to this syndrome is influenced by inherited polymorphisms that could be used to make informed clinical treatment decisions.     

The diagnosis of ectopic focal hyperinsulinism of infancy with [18F]-dopa positron emission tomography

BACKGROUND: Congenital hyperinsulinism (CHI) is a cause of severe hypoglycemia in the neonatal and infancy period. Histologically, there are two subtypes with diffuse and focal disease. The preoperative differentiation of these two forms is very important because the surgical management is radically different. The focal form of the disease can be cured if the focal lesion can be localized accurately and completely resected with surgery. AIM: We report the case of a child who underwent three pancreatectomies with a choledochoduodenostomy and a cholecystectomy but continued to have severe hyperinsulinemic hypoglycemia. METHODS/RESULTS: Radiological investigations including imaging with (18)fluoro-L-Dopa positron emission tomography scan showed a clear focus of increased (18)F-fluoro-L-Dopa uptake in the vicinity of the former head of the pancreas. On the magnetic resonance imaging scan, this focal uptake appeared to localize adjacent or next to duodenum (in the wall or cavity of the duodenum). CONCLUSIONS: This unique case highlights the importance of correctly localizing and completely resecting the focal lesion in patients with CHI. (18)Fluoro-L-Dopa positron emission tomography scan can identify ectopic focal lesions in patients with CHI.     

Reproducibility of common semi-quantitative parameters for evaluating lung cancer glucose metabolism with positron emission tomography using 2-deoxy-2-[18F]fluoro-D-glucose.

PURPOSE: Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been used for various cancers, but reproducibility of common utilized semi-quantitative parameters, such as the maximal single pixel standardized uptake value (SUV) and effective glycolytic volume (EGV), remains unknown. Knowledge of precision is essential for applying these parameters to treatment monitoring. The purpose of this investigation was to assess the precision of PET results obtained by repeated examinations of patients with untreated lung cancer. PATIENTS AND METHODS: Ten patients with lung cancer underwent two PET examinations within a week with no intervening treatment. The reproducibility of three parameters:((1) maximal SUV of 1 x 1 pixel anywhere in the tumor, calculated on the basis of predicted lean body mass [SULmax]; (2) highest average SUV at 4 x 4 pixels in the tumor adjusted by predicted lean body mass [SULmean]; and (3) EGV calculated by multiplying SUL by tumor volume), using PET images obtained at 50-60 min post-injection, were examined. Plasma glucose, insulin and free fatty acid levels were also monitored. RESULTS: The SULmax, SULmean, and EGV were measured with a mean +/- S.D. difference of 11.3% +/- 8.0, 10.1% +/- 8.2, and 10.1% +/- 8.0%, respectively. By multiplying SUL by plasma glucose concentration, the mean differences were slightly reduced to 7.2% +/- 5.8, 6.7% +/- 6.2, and 9.5% +/- 8.2, respectively. CONCLUSION: These data indicate that commonly used semi-quantitative indices of glucose metabolism on PET show high reproducibly. This supports their use in sequential quantitative analysis in PET, such as in treatment response monitoring.     

复方酪萨维口腔速崩片中冰片β-环糊精包合物制备工艺

目的:研究复方酪萨维口腔速崩片中冰片β-环糊精包合物的最佳工艺。方法:采用正交试验设计,以龙脑的包合率和包合物收率为评价指标,优选最佳工艺条件。结果:最佳包合工艺为:冰片与β-环糊精质量比1:6,β-环糊精与加水量比1:10,包合温度40℃,包合时间1 h。结论:该制备工艺简便、合理、可行。     

Comparability of different methods for estimating influenza infection rates over a single epidemic wave

Estimation of influenza infection rates is important for determination of the extent of epidemic spread and for calculation of severity indicators. The authors compared estimated infection rates from paired and cross-sectional serologic surveys, rates of influenza like illness (ILI) obtained from sentinel general practitioners (GPs), and ILI samples that tested positive for influenza using data from similar periods collected during the 2009 H1N1 epidemic in Singapore. The authors performed sensitivity analyses to assess the robustness of estimates to input parameter uncertainties, and they determined sample sizes required for differing levels of precision. Estimates from paired seroconversion were 17% (95% Bayesian credible interval (BCI): 14, 20), higher than those from cross-sectional serology (12%, 95% BCI: 9, 17). Adjusted ILI estimates were 15% (95% BCI: 10, 25), and estimates computed from ILI and laboratory data were 12% (95% BCI: 8, 18). Serologic estimates were least sensitive to the risk of input parameter misspecification. ILI-based estimates were more sensitive to parameter misspecification, though this was lessened by incorporation of laboratory data. Obtaining a 5-percentage-point spread for the 95% confidence interval in infection rates would require more than 1,000 participants per serologic study, a sentinel network of 90 GPs, or 50 GPs when combined with laboratory samples. The various types of estimates will provide comparable findings if accurate input parameters can be obtained.     

上海市中老年人群睡眠质量和睡眠时间与2型糖尿病患病关系研究

目的 分析睡眠质量和睡眠时间与上海市中老年人群2型糖尿病患病之间的关系。方法 利用2017年上海市社区≥35岁居民2型糖尿病流行病学调查数据,采用限制性立方样条曲线绘制PSQI得分和睡眠时间与2型糖尿病关系的剂量-反应曲线,采用logistic回归模型分析睡眠质量、睡眠时间对2型糖尿病患病的影响,并对睡眠质量和睡眠时间与2型糖尿病患病风险的交互作用进行分析。结果 上海市中老年人PSQI分数为（4.09±0.10）分,睡眠质量差的比例为12.55%（95% CI：10.77～14.58）,睡眠时间为（7.19±0.03）h。PSQI得分与糖尿病患病呈线性关系,睡眠时间与糖尿病患病呈近似“U”形关系。多因素调整后,睡眠质量差（PSQI得分>7分）和睡眠时间过短（睡眠时间<6 h）能显著增加2型糖尿病的患病风险,OR值分别为1.17（95% CI：1.06～1.30）和1.20（95% CI：1.01～1.41）。进一步分层分析结果显示,仅睡眠时间<6 h且睡眠质量差和睡眠时间≥8 h且睡眠质量差者糖尿病患病风险增加,OR值分别为1.30（95% CI：1.12～1.52）和1.79（95% CI：1.04～3.07）。结论 睡眠质量差和睡眠时间过短与糖尿病患病风险密切相关,而睡眠过长只有在伴随睡眠质量差的情况下与糖尿病患病风险相关。     

Correlation of the frequency of petite formation by isolates of Saccharomyces cerevisiae with virulence.

In previous studies on the colony phenotype switching of Saccharomyces cerevisiae, we observed that the least virulent isolates formed greater numbers of petite colonies when grown at body temperature, 37 degrees C. To determine if there is a link between virulence and petite formation, we examined the frequency of spontaneous petite formation for virulent clinical isolates (YJM128, YJM309), an intermediate virulent segregant of YJM128 (YJM145) and avirulent clinical (YJM308) and nonclinical S. cerevisiae (Y55, YJM237) after growth at 37 degrees C. The rank order of increasing frequency of petite formation was YJM128 = YJM145 < YJM309 < Y 55 < YJM308 = YJM237, which is similar to the rank-order of virulence in CD-1 mice. To assess the virulence of petites in vivo, two mouse models, CD-1 and DBA/ 2N, were infected i.v. with 10(7) cfu of either the parental grand or a spontaneously derived petite from one of four isolates previously classified with differing degrees of virulence: YJM128, YJM309, YJM145 and Y55. In both CD-1 and DBA/2N, the mean log10 cfu of grands recovered from the brain was significantly higher than that of the petites (P<0001). Overall, petites were significantly less virulent than the parental strains. However, death of some DBA/2N mice caused by YJM128 petite 1 showed that petites are not totally avirulent. To see if S. cerevisiae isolates form petite colonies in vivo, both mouse models were infected with parental grands of YJM128 and Y55. Recovered colonies were counted and confirmed as grand or petite, and the frequency of petite colonies in the brain, the target organ, correlated with the in vitro results. Overall, these studies show an inverse correlation between the frequency of petite-colony formation and the previously determined virulence of S. cerevisiae in CD-1 mice. Furthermore, petites were significantly less virulent than the parental grands, in most cases, and petites are spontaneously formed in vivo at a frequency inversely correlated to the virulence of the strain.     

自制软体冰袋联合芙蓉膏外敷在脂肪乳输液外渗患者中的应用

目的 探讨自制软体冰袋联合芙蓉膏外敷治疗脂肪乳外渗效果.方法 将40例脂肪乳输液外渗患者通过抽签法简单随机分组,其中对照组(20例)按常规方法外渗处湿敷50％硫酸镁,观察组(20例)用自制软体冰袋联合芙蓉膏外敷.运用视觉模拟评分法(VAS)分别在外渗发生(T0)、外渗4 h(T1)、外渗12 h(T2)、外渗24 h(T3)对患者进行疼痛评估,并观察两组局部肿胀,皮肤颜色的变化.结果 观察组T1、T2、T3疼痛程度显著轻于对照组(均P＜0.05).观察组的治愈率和有效率分别为60.00％和100.00％,对照组分别为25.00％和65.00％,观察组在临床疗效方面明显优于对照组(P＜0.05).结论 对于脂肪乳输液外渗患者,自制软体冰袋联合芙蓉膏外敷可有效缓解疼痛,且对外渗后处理效果佳,使用简便,值得临床推广.     

Imaging of tumor hypoxia to predict treatment sensitivity

Non-invasive detection of tumor hypoxia using radiolabeled 2-nitroimidazoles has been a major effort during the last two decades. Recent years have witnessed the introduction of several new compounds which are chemically related to [(18)F]fluoromisonidazole (FMISO) but show slight but distinct differences in biodistribution and metabolic clearance. Although [(18)F]FMISO has shown clinical potential it suffers from suboptimal oxygen dependent tissue contrast and newer agents seek to improve this essential feature. The limited data on other interesting tracers keeps the investigators busy at demonstrating the potential advantages over [(18)F]FMISO while efforts should start to concentrate on proving the clinical significance of such techniques in the form of outcome data from image-guided therapy modification. We review here our experiences with two hypoxia-avid agents [(18)F]fluoroerythronitromidazole (FETNIM) and [(18)F] 2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) and focus on the similarities and differences of these two tracers in comparison to other radiolabeled 2-nitroimidazoles. It is recognized that only [(18)F]FMISO has thus far shown clinical utility and newer tracers need to be tested against this circumstance.