BACKGROUND & AIMS: BACKGROUND:It was recently reported that genetic polymorphisms of UDP glucuronyltransferase-1 polypeptide A1 (UGT1A1), a glucuronidation enzyme, were associated with irinotecan (CPT-11) metabolism. The active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38) was glucuronidated (SN-38G) by UGT1A1. Genetic polymorphisms of UGT1A1 were associated with potentially serious adverse events, including neutropenia. Several studies have suggested that the dose of CPT-11 should be decreased in patients homozygous for UGT1A1*6 or UGT1A1*28, or double heterozygotes (*6/*28). However, the reference dose for patients with these genetic polymorphisms is unclear. METHODS:We investigated the relationship between the SN-38G/SN-38 concentration ratio and the dose of CPT-11 in 70 patients with colorectal cancer who received FOLFIRI-based regimens, by measuring the plasma concentrations of CPT-11, SN-38, and SN-38G. RESULTS:The SN-38G/SN-38 concentration ratio was lower in patients who were homozygous for UGT1A1*6, heterozygous for UGT1A1*6 or UGT1A1*28, or were double heterozygotes compared with patients with wild-type genes. The relative decreases in the SN-38G/SN-38 concentration ratio in patients homozygous for UGT1A1*6 and in double heterozygotes were greater than in patients heterozygous for UGT1A1*6 or UGT1A1*28. Interestingly, decreases in the SN-38G/SN-38 concentration ratio were associated with decreases in the neutrophil count and the final infusion dose of CPT-11. CONCLUSION:Our results suggest that the SN-38G/SN-38 concentration ratio is an important factor for guiding dose adjustments, even in patients with wild-type genes. Therefore, the SN-38G/SN-38 concentration ratio, as an index of the patient's metabolic capacity, is useful for assessing dose adjustments of CPT-11.

背景与目标：

BACKGROUND & AIMS: :One of the most intriguing features of biological systems is their ability to regulate the steady-state fluxes of the underlying biochemical reactions; however, the regulatory mechanisms and their physicochemical properties are not fully understood. Fundamentally, flux regulation can be explained with a chemical kinetic formalism describing the transitions between discrete states, with the reaction rates defined by an underlying free energy landscape. Which features of the energy landscape affect the flux distribution? Here we prove that the ratios of the steady-state fluxes of quasi-first-order biochemical processes are invariant to energy perturbations of the discrete states and are only affected by the energy barriers. In other words, the nonequilibrium flux distribution is under kinetic and not thermodynamic control. We illustrate the generality of this result for three biological processes. For the network describing protein folding along competing pathways, the probabilities of proceeding via these pathways are shown to be invariant to the stability of the intermediates or to the presence of additional misfolded states. For the network describing protein synthesis, the error rate and the energy expenditure per peptide bond is proven to be independent of the stability of the intermediate states. For molecular motors such as myosin-V, the ratio of forward to backward steps and the number of adenosine 5'-triphosphate (ATP) molecules hydrolyzed per step is demonstrated to be invariant to energy perturbations of the intermediate states. These findings place important constraints on the ability of mutations and drug perturbations to affect the steady-state flux distribution for a wide class of biological processes.

背景与目标： : 生物系统最有趣的特征之一是它们调节潜在生化反应的稳态通量的能力; 但是，其调节机制及其理化性质尚未完全了解。从根本上讲，通量调节可以用描述离散状态之间过渡的化学动力学形式主义来解释，反应速率由潜在的自由能景观定义。能源格局的哪些特征会影响通量分布？在这里，我们证明了准一阶生化过程的稳态通量之比与离散状态的能量扰动是不变的，并且仅受能量壁垒的影响。换句话说，非平衡通量分布是在动力学而不是热力学控制下的。我们说明了这一结果对三个生物学过程的一般性。对于描述蛋白质沿竞争途径折叠的网络，通过这些途径进行的概率显示出对中间体的稳定性或其他错误折叠状态的存在不变。对于描述蛋白质合成的网络，误差率和每个肽键的能量消耗被证明与中间状态的稳定性无关。对于诸如肌球蛋白V之类的分子马达，向前步与向后步的比率以及每步水解的5 '-三磷酸腺苷 (ATP) 分子的数量被证明对中间状态的能量扰动是不变的。这些发现对突变和药物扰动影响各种生物过程的稳态通量分布的能力构成了重要限制。

BACKGROUND & AIMS: BACKGROUND:Persons with mental health disorders (MHD) have higher rates of smoking and poorer cessation of smoking outcomes than those without MHD. A decreased level of motivation may partially explain lower cessation rates, but there is little information on motivation among inpatients with MHD. OBJECTIVES:Primary aims were to compare (1) motivation to cease smoking among those hospitalised with MHD or non-MHD, (2) the proportion that attempted smoking cessation, and (3) use of aids to cessation. A secondary aim was to assess cessation up to six months post-discharge. METHODS:Smokers were recruited at a tertiary hospital in Perth, Western Australia. Surveys were administered upon admission and at 5 and 14 days and 6 months post-discharge. RESULTS:We recruited 64 MHD inpatients and 43 non-MHD inpatients. At baseline there were no significant differences between the groups on any measures of the five measures of motivation. Significantly more of the MHD sample attempted smoking cessation than those in the non-MHD sample (34 versus 13: chi(2)(1)=5.472, P=0.028). Nicotine replacement therapy (NRT) alone was used by 70% of those attempting to quit but was only provided as part of discharge medication to two people and few persons (<21%) in either group used NRT post-discharge. By 14 days, three (4.7%) of the MHD group and none (0%) of the non-MHD group reported abstinence, at 6-months one from each group reported continuous abstinence since discharge from hospital. CONCLUSIONS:Motivation to cease smoking among inpatients with MHD was similar to those without MHD, as was use of NRT while hospitalised. The low provision of post-discharge NRT may contribute to the poor cessation of smoking outcomes and does not fulfil evidence based guidelines.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:We use a simulation-based model to study the impact of female philopatry and heterogeneity of habitat quality on the evolution of primary sex ratio. RESULTS:We show that these conditions may lead to strongly biased ESS habitat-dependent sex ratios, under two kinds of density-dependent population regulation. ESS sex ratios are always biased towards females in good habitats, towards males in poor habitats, and are generally equilibrated considering the whole population. Noticeably, the predicted bias of sex ratio usually increases with decreasing female philopatry. CONCLUSION:The selection forces responsible for these results are fully described. This study provides a new perspective on the evolutionary significance of temperature sex determination. We discuss the case of turtles by comparing our theoretical results with field observations.

背景与目标：

BACKGROUND & AIMS: Purpose:To investigate monocyte to high-density lipoprotein (HDL) ratio (MHR) and neutrophil-to-lymphocyte ratio (NLR) as indicators of systemic inflammation in acute central serous chorioretinopathy (CSC). Methods:The HDL levels, hematological profiles, erythrocyte sedimentation rates (ESR), and C-reactive protein (CRP) levels of 38 patients with acute CSC (Group I) and 38 controls without CSC (Group II) were measured. Results:MHRs were significantly higher in Group I (13.30 ± 2.95) than in Group II (11.52 ± 2.42, P = 0.005), whereas NLRs, CRP values, and ESR values did not significantly differ between the groups (P = 0.726, P = 0.219, and P = 0.441, respectively). Multivariate analysis revealed that the MHR was an independent predictor of acute CSC (OR = 1.266, 95% CI = 1.054-1.521, P = 0.012). Conclusion:Indicating an association between increased MHRs and acute CSC, the MHR might represent simple, inexpensive, reliable biomarkers of inflammation in acute CSC.

背景与目标：

BACKGROUND & AIMS: :Determining the mechanisms governing sex-ratio variation in dioecious organisms represents a central problem in evolutionary biology. It has been proposed that in plants with sex chromosomes competition between pollen tubes of female- versus male-determining microgametophytes (certation) causes female-biased primary sex ratios. Experimental support for this hypothesis is limited and recent workers have cast doubt on whether pollen-tube competition can modify sex ratios in dioecious plants. Here we investigate the influence of variation in pollination intensity on sex ratios in Rumex nivalis, a wind-pollinated alpine herb with strongly female-biased sex ratios. In a garden experiment, we experimentally manipulated pollination intensity using three concentric rings of female recipient plants at different distances from a central group of male pollen donors. This design enabled us to test the hypothesis that increasing pollen load size, by intensifying gametophyte competition, promotes female-biased sex ratios in R. nivalis. We detected a significant decline in pollen load at successive distance classes with concomitant reductions in seed set. Sex ratios of progeny were always female biased, but plants at the closest distance to male donors exhibited significantly greater female bias than more distant plants. The amount of female bias was positively correlated with the seed set of inflorescences. Hand pollination of stigmas resulted in approximately 100-fold higher stigmatic pollen loads than wind-pollinated stigmas and produced exceptionally female-biased progenies (female frequency = 0.96). Our results are the first to demonstrate a functional relation between stigmatic pollen capture, seed set, and sex ratio and suggest that certation can contribute towards female-biased sex ratios in dioecious plants.

背景与目标： : 确定控制雌雄异株生物性别比例变化的机制是进化生物学的核心问题。有人提出，在具有性染色体的植物中，决定雌性与雄性的微配子体 (certation) 的花粉管之间的竞争会导致女性偏向的主要性别比。对该假设的实验支持有限，最近的工人对花粉管竞争是否可以改变雌雄异株植物的性别比例表示怀疑。在这里，我们研究了授粉强度的变化对Rumex nivalis性别比例的影响，Rumex nivalis是一种风授粉的高山草本植物，具有强烈的女性偏向性别比。在花园实验中，我们使用距雄性花粉供体中心组不同距离的三个雌性受体植物同心环，通过实验控制授粉强度。此设计使我们能够检验以下假设: 通过加剧配子体竞争来增加花粉负荷大小，从而促进了R. nivalis的女性偏向性别比。我们检测到连续距离等级的花粉负荷显着下降，同时种子结实减少。后代的性别比总是有女性偏见，但是与男性供体距离最近的植物比较远的植物表现出更大的女性偏见。雌性偏倚的数量与花序的种子组呈正相关。柱头的手工授粉导致柱头花粉负荷比风授粉的柱头高约100倍，并产生异常偏向雌性的后代 (雌性频率 = 0.96)。我们的结果首次证明了柱头花粉捕获，种子结实和性别比之间的功能关系，并表明certation可以促进雌雄异株植物中女性偏向的性别比。

BACKGROUND & AIMS: :Large-scale and rapid improvement in wastewater treatment is common practice in developing countries, yet this influence on nutrient regimes in receiving waterbodies is rarely examined at broad spatial and temporal scales. Here, we present a study linking decadal nutrient monitoring data in lakes with the corresponding estimates of five major anthropogenic nutrient discharges in their surrounding watersheds over time. Within a continuous monitoring dataset covering the period 2008 to 2017, we find that due to different rates of change in TN and TP concentrations, 24 of 46 lakes, mostly located in China's populated regions, showed increasing TN/TP mass ratios; only 3 lakes showed a decrease. Quantitative relationships between in-lake nutrient concentrations (and their ratios) and anthropogenic nutrient discharges in the surrounding watersheds indicate that increase of lake TN/TP ratios is associated with the rapid improvement in municipal wastewater treatment. Due to the higher removal efficiency of TP compared with TN, TN/TP mass ratios in total municipal wastewater discharge have continued to increase from a median of 10.7 (95% confidence interval, 7.6 to 15.1) in 2008 to 17.7 (95% confidence interval, 13.2 to 27.2) in 2017. Improving municipal wastewater collection and treatment worldwide is an important target within the 17 sustainable development goals set by the United Nations. Given potential ecological impacts on biodiversity and ecosystem function of altered nutrient ratios in wastewater discharge, our results suggest that long-term strategies for domestic wastewater management should not merely focus on total reductions of nutrient discharges but also consider their stoichiometric balance.

背景与目标： : 在发展中国家，大规模，快速地改善废水处理是普遍的做法，但是很少在广泛的时空尺度上研究这种对接收水体养分状况的影响。在这里，我们提出了一项研究，将湖泊的年代际养分监测数据与周围流域中五个主要人为养分排放的相应估计值联系起来。在覆盖2008 2017年时期的连续监测数据集中，我们发现，由于TN和TP浓度的变化率不同，46个湖泊中有24个 (主要位于中国人口稠密地区) 显示TN/TP质量比增加; 只有3个湖泊显示下降。湖泊中养分浓度 (及其比率) 与周围流域人为养分排放之间的定量关系表明，湖泊TN/TP比率的增加与城市废水处理的快速改善有关。由于TP的去除效率比TN更高，城市总废水排放中的TN/TP质量比从中位数10.7 (95% 置信区间，7.6至15.1) 2008年17.7 (95% 置信区间，13.2至27.2) 2017年持续增加。在联合国设定的17个可持续发展目标中，改善全球城市废水的收集和处理是一个重要目标。考虑到废水排放中养分比率改变对生物多样性和生态系统功能的潜在生态影响，我们的结果表明，家庭废水管理的长期策略不仅应关注养分排放的总减少，还应考虑其化学计量平衡。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :To achieve maximal force output, clinicians and coaches have been experimenting with upper extremity plyometric exercises for years, without sufficient scientific validation of this training method. The goal of this study was to examine the effects of an 8-week course of high volume upper extremity plyometric training on the isokinetic strength and throwing velocity of a group of intercollegiate baseball players. Twenty-four Division I collegiate baseball players (age: 19.7 +/- 1.3 years; height: 183.9 +/- 5.9 cm; mass: 90.7 +/- 10.5 kg) were recruited to participate in this study. Throwing velocity, isokinetic peak torque, isokinetic functional strength ratios, and time to peak torque were measured pre- and posttraining. Subjects were rank-ordered according to concentric internal rotation (IR) strength and were assigned randomly to either the plyometric training group (PLY) or the control group (CON). Training consisted of 6 upper extremity plyometric exercises ("Ballistic Six") performed twice per week for 8 weeks. Subjects assigned to CON performed regular off-season strength and conditioning activities, but did not perform plyometric activities. PLY demonstrated significant increases (p < 0.05) in throwing velocity following 8 weeks of training when compared with CON (83.15 mph [pre] vs. 85.15 mph [post]). There were no statistically significant differences in any of the isokinetic strength measurements between PLY and CON groups pre- to posttraining. Statistically significant differences were seen within PLY for concentric IR and eccentric external rotation (ER) isokinetic strength at 180 degrees x s(-1) and 300 degrees x s(-1); and within CON for eccentric ER isokinetic strength at 300 degrees x s(-1) and concentric IR isokinetic strength at 180 degrees x s(-1). The Ballistic Six training protocol can be a beneficial supplement to a baseball athlete's off-season conditioning by improving functional performance and strengthening the rotator cuff musculature.

背景与目标： : 为了实现最大的力量输出，临床医生和教练多年来一直在尝试上肢测力练习，而这种训练方法没有得到足够的科学验证。这项研究的目的是研究为期8周的大批量上肢测距训练对一组大学间棒球运动员的等速力量和投掷速度的影响。招募了24名I级大学棒球运动员 (年龄: 19.7/- 1.3岁; 身高: 183.9/-5.9厘米; 质量: 90.7/-10.5千克) 参加这项研究。训练前和训练后测量了投掷速度，等速峰值扭矩，等速功能强度比以及达到峰值扭矩的时间。根据同心内旋 (IR) 强度对受试者进行排序，并将其随机分配到plymetric训练组 (PLY) 或对照组 (CON)。训练包括每周两次进行8周的6次上肢测距练习 (“弹道六号”)。分配给CON的受试者定期进行淡季力量和调节活动，但未进行综合测量活动。与CON相比，PLY在训练8周后的投掷速度显着增加 (p < 0.05) (83.15 mph [pre] vs. 85.15 mph [post])。训练前后，PLY组和CON组之间的任何等速强度测量值均无统计学上的显着差异。在180度x s(-1) 和300度x s(-1) 下，同心IR和偏心外旋 (ER) 等速强度在层内有统计学差异; 在CON内，偏心ER等速强度为300度x s(-1)，同心IR等速强度为180度x s(-1)。弹道六号训练方案可以通过改善功能表现和增强肩袖肌肉组织来补充棒球运动员的淡季条件。

BACKGROUND & AIMS: :Standardized mortality ratios and standardized incidence ratios are widely used in cohort studies to compare mortality or incidence in a study population to that in the general population on a age-time-specific basis, but their computation is not included in standard statistical software packages. Here we present a user-friendly Microsoft Windows program for computing standardized mortality ratios and standardized incidence ratios based on calculation of exact person-years at risk stratified by sex, age and calendar time. The program offers flexible import of different file formats for input data and easy handling of general population reference rate tables, such as mortality or incidence tables exported from cancer registry databases. The application of the program is illustrated with two examples using empirical data from the Bavarian Cancer Registry.

背景与目标： : 标准化死亡率和标准化发病率在队列研究中广泛使用，以根据特定年龄的时间将研究人群的死亡率或发病率与普通人群的死亡率或发病率进行比较，但标准统计软件包中未包含它们的计算。在这里，我们提出了一个用户友好的Microsoft Windows程序，用于根据按性别，年龄和日历时间分层的确切风险人年计算标准化死亡率和标准化发病率。该计划为输入数据提供了不同文件格式的灵活导入，并轻松处理一般人群参考汇率表，例如从癌症注册数据库导出的死亡率或发病率表。使用来自巴伐利亚癌症登记处的经验数据，通过两个示例说明了该程序的应用。

BACKGROUND & AIMS: :A method of calculating dose for a 6 MV X-ray beam using tissue standard ratios (TSR) is described. TSRs may be divided into a primary component and a scatter component, and the latter can then be further divided into contributions from elemental scattering volumes of 1 cm x 1 cm cross-sectional area at 1 m from the source. The magnitude of the various components have been determined by analysing measurements of square and rectangular fields, involving the fitting of the scatter data to an exponential function of radial distance from the scatter element. The coefficient and exponent of this function were found to be functions of depth, and this variation is described. A method of utilizing reconstructed scatter data that is compatible with the motion of a multileaf collimator system is presented. Results obtained by re-combining the data for various non-standard geometries are compared with further experimental work.

背景与目标： : 描述了一种使用组织标准比 (TSR) 计算6 MV x射线束剂量的方法。TSRs可以分为主要成分和散射成分，然后后者可以进一步分为来自源1 m处的1厘米 × 1厘米横截面积的元素散射体积的贡献。通过分析正方形和矩形场的测量值来确定各种分量的大小，包括将散射数据拟合到距散射元件的径向距离的指数函数。发现该函数的系数和指数是深度的函数，并描述了这种变化。提出了一种利用与多叶准直器系统运动兼容的重建散射数据的方法。通过重新组合各种非标准几何形状的数据获得的结果与进一步的实验工作进行了比较。

BACKGROUND & AIMS: AIM:Using nicotine gum can reduce the amount of weight gained when quitting. Here we examine the relationship between weight gain and use of adequate amounts of gum. To mitigate the confounders associated with correlational analyses, we contrast the effects of active gum and placebo, and analyze outcomes prospectively. DESIGN AND SETTING:Randomized double-blind placebo-controlled trial of nicotine gum. Participants were instructed to use nine to 15 pieces of gum/day for the first 2 months of treatment. PARTICIPANTS:Participants (n = 103) were randomized to either active (2 mg or 4 mg) or placebo gum. MEASUREMENTS:We examined the effect on weight gain of the interaction between treatment (active versus placebo) and daily gum use [≥9 pieces/day (compliant use) versus < 9 pieces/day]. FINDINGS:After 30 days of abstinence, smokers treated with active gum had not gained significantly less weight than those on placebo (1.1 kg versus 1.6 kg, P = 0.175). However, a significant compliance-treatment interaction was observed (P = 0.005): active gum users who used ≥9 pieces/day during the first 14 days of treatment had gained less weight at follow-up (0.6 kg versus 1.6 kg for those who used <9 pieces/day, P = 0.017), but participants randomized to the placebo group saw no such benefit from compliant use. A similar compliance-treatment interaction (P = 0.046) was also observed when the effect of compliance was examined within active treatment (2 mg versus 4 mg). CONCLUSIONS:When smokers are quitting, those who use more pieces of nicotine gum experience less weight gain in the first 30 days. This relationship is not seen for smokers on placebo gum.

背景与目标：

BACKGROUND & AIMS: :In euthyroidism, as thyroid Stimulating hormone (TSH) levels increase, the free triiodothyronine (FT3) to free thyroxine (FT4) ratio increases. The aim of this study was to assess if beyond the euthyroid range of TSH levels FT3/FT4 ratio continues to increase and if levothyroxine treatment reduces this ratio, possibly through TSH suppression. This cross sectional retrospective study included a total of 77 832 patients [age 22.76±15.17 years (4 days to 112 years)] evaluated and treated in community clinics between January 2009 and September 2013. Blood samples drawn in community clinics for which TSH, FT4, FT3, age, and gender were available were included. Tests with TSH below 0.5 IU/l were excluded as were samples taken during pregnancy. The FT3/FT4 ratio continued to increase significantly even with TSH above 50 mIU/l (p for trend<0.001) with an increase of more than 50% over the entire TSH range. With increasing age and female gender, the phenomenon was less prominent (p<0.001). Levothyroxine treated patients had significantly lower FT3/FT4 ratios in comparison to untreated patients up to TSH levels of 5.0 mIU/l. In conclusion, increasing TSH increases FT3/FT4 ratio even with severe hypothyroidism, less so with aging. With levothyroxine therapy, a ratio similar to untreated patients is achieved at TSH of above 5.0 mIU/l. Since T3 suppresses TSH better than T4, administration of T3 would likely normalize the FT3/FT4 ratio at a lower, ostensibly more physiological, TSH level. This could be seen as a rationale for add-on T3 therapy.

背景与目标： : 在甲状腺功能正常时，随着促甲状腺激素 (TSH) 水平的增加，游离三碘甲状腺原氨酸 (FT3) 与游离甲状腺素 (FT4) 的比例增加。这项研究的目的是评估TSH水平FT3/FT4的正常甲状腺范围是否继续增加，以及左旋甲状腺素治疗是否降低了该比率，可能是通过抑制TSH。这项横断面回顾性研究包括总共77名832患者 [年龄22.76 ± 15.17岁 (4天至112岁)] 在2009年1月至2013年9月之间的社区诊所进行评估和治疗。包括在社区诊所抽取的血液样本，其中有TSH，FT4，FT3，年龄和性别。排除了TSH低于0.5  IU/l的测试，以及在怀孕期间采集的样本。即使TSH高于50  mIU/l (趋势p <0.001)，FT3/FT4比率仍继续显着增加，在整个TSH范围内增加超过50%。随着年龄和女性性别的增加，这一现象不太突出 (p<0.001)。与未治疗的患者相比，接受左甲状腺素治疗的患者的FT3/FT4比率显着降低，高达5.0  mIU/l的TSH水平。总之，即使在严重的甲状腺功能减退症中，TSH的增加也会增加FT3/FT4的比率，而随着年龄的增长，TSH的增加会增加FT3/FT4的比率。使用左甲状腺素治疗，在5.0  mIU/l以上的TSH达到与未治疗患者相似的比率。由于T3比T4更好地抑制TSH，因此给予T3可能会使FT3/FT4比率在较低的，表面上更生理的TSH水平下正常化。这可以被视为附加T3治疗的基本原理。

BACKGROUND & AIMS: BACKGROUND:Glioblastoma (GBM), a malignant grade IV tumor, is the most malignant brain tumor due to its hyper-proliferative and apoptosis-evading characteristics. The signal transducer and activators of transcription (STAT) family genes, including STAT3 and STAT5A, have been indicated to play important roles in GBM progression. Increasing number of reports suggest that garcinol, a polyisoprenylated benzophenone and major bioactive component of Garcinia indica contains potent anti-cancer activities. MATERIAL AND METHODS:The present study investigated the anti-GBM effects of garcinol, focusing on the STAT3/STAT5A activation, using a combination of bioinformatics, in vitro, and ex vivo assays. RESULTS:Our bioinformatics analysis of The Cancer Genome Atlas (TCGA)-GBM cohort (n = 173) showed that STAT3 and STAT5A are preferentially elevated in primary and recurrent GBM, compared to non-tumor brain tissues, and is significantly correlated with reduced overall survival. In support, our immunohistochemical staining of a GBM cohort (n = 45) showed an estimated 5.3-fold (p < 0.001) elevation in STAT3 and STAT5A protein expression in primary and recurrent GBM versus the non-tumor group. In vitro, garcinol treatment significantly suppressed the proliferative, invasive, and migratory potential of U87MG or GBM8401 cells, dose-dependently. In addition, garcinol anticancer effect significantly attenuated the GBM stem cell-like phenotypes, as reflected by diminished ability of U87MG or GBM8401 to form colonies and tumorspheres and suppressed expression of OCT4 and SOX2. Furthermore, analysis on GBM transcriptome revealed an inverse correlation between the level of STAT3/5A and hsa-miR-181d. Garcinol-mediated anti-GBM effects were associated with an increased hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratio. The results were further verified in vivo using U87MG mouse xenograft model where administration of garcinol significantly inhibited tumor growth. CONCLUSIONS:We present evidence of anti-GBM efficacy of garcinol mediated by enhancing the hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratios in GBM cells. Our findings suggest a potential new therapeutic agent for combating aggressive GBM.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Grave disparities in smoking prevalence exist between indigenous Māori, Pacific Island peoples, and other New Zealanders. Primary care nurses routinely provide brief stop smoking interventions to achieve national targets but they are constrained by time. Innovations using new technologies offer opportunities to enhance brief interventions and improve uptake and outcomes. Objectives/Aims/Hypotheses: This study explored the feasibility of adding a novel scratch card and internet-based, quit and win contest with mobile phone support messages, to practice nurses' brief smoking cessation interventions. DESIGN:Pragmatic exploratory mixed methods pilot study comprising a quantitative two-group comparison and qualitative interviews. METHODS:In two intervention clinics, practice nurses added supportive mobile phone messages, novelty scratch cards to win online prizes and $1000 prize draw entry following 1 month smokefree, to routine brief stop smoking interventions. In three control clinics, patients who smoked received brief stop smoking interventions only. Practice nurses collected baseline and 1-month data describing patients' smoking status, quit attempts, and cessation support. Researchers conducted qualitative interviews with two nurses and ten patients and collected 3-month data. RESULTS:Five primary care clinics recruited 67 smokers (37 intervention; 30 control). The contest was readily incorporated into nurses' practice. It appealed to nurses and Māori and Pacific Island patients, increased time to first cigarette, and attracted first time quitters. However, it had no extra effect on smoking cessation compared with usual care. Pacific Island patients' participation in the online elements was limited by low access to the internet. CONCLUSIONS:While the exploratory study did not indicate the potential for triggering mass quitting, reduced dependency was suggested. The intervention attracted Māori and Pacific Island smokers and engaged first time quitters. Low cost, novelty activities could be used to refresh routine brief stop smoking interventions, and to motivate practice nurses to engage more smokers in quitting.

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