Determination of an Optimal Standardized Uptake Value of Fluorodeoxyglucose for Positron Emission Tomography Imaging to Assess Pathological Volumes of Cervical Cancer: A Prospective Study

Purpose

To determine the optimal standardized uptake value (SUV) of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) for positron emission tomography (PET) imaging, at which the PET-defined gross tumor volume (GTV_PET) best matches with the pathological volume (GTV_PATH) in the cervical cancer.

Materials and Methods

Ten patients with the cervical cancer who underwent surgery were enrolled in this study. The excised specimens were processed for whole-mount serial sections and H-E staining. The tumor borders were outlined in sections under a microscope, histopathological images were scanned and the GTV_PATH calculated. The GTV_PET was delineated automatically by using various percentages relative to the maximal SUV and absolute SUV. The optimal threshold SUV was further obtained as the value at which the GTV_PET best matched with the GTV_PATH.

Results

An average of 85±10% shrinkage of tissue was observed after the formalin fixation. The GTV_PATH was 13.38±2.80 cm³ on average. The optimal threshold on percentile SUV and absolute SUV were 40.50%±3.16% and 7.45±1.10, respectively. The correlation analysis showed that the optimal percentile SUV threshold was inversely correlated with GTV_PATH (p<0.05) and tumor diameter (p<0.05). The absolute SUV was also positively correlated with SUV_max (p<0.05).

Conclusion

The pathological volume could provide the more accurate tumor volume. The optimal SUV of FDG for PET imaging by use of GTV_PATH as standard for cervical cancer target volume delineation was thus determined in this study, and more cases are being evaluated to substantiate this conclusion.     

Pro-inflammatory cytokines modulate iron regulatory protein 1 expression and iron transportation through reactive oxygen/nitrogen species production in ventral mesencephalic neurons

Both inflammatory processes associated with microglia activation and abnormal iron deposit in dopaminergic neurons are involved in the pathogenesis of Parkinson's disease (PD). However, the relationship between neuroinflammation and iron accumulation was not fully elucidated. In the present study, we aimed to investigate whether the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) released by microglia, could affect cellular iron transportation in primary cultured ventral mesencephalic (VM) neurons. The results showed that IL-1β or TNF-α treatment led to increased ferrous iron influx and decreased iron efflux in these cells, due to the upregulation of divalent metal transporter 1 with the iron response element (DMT1 + IRE) and downregulation of ferroportin1 (FPN1). Increased levels of iron regulatory protein 1 (IRP1), transferrin receptor 1 (TfR1) and hepcidin were also observed in IL-1β or TNF-α treated VM neurons. IRP1 upregulation could be fully abolished by co-administration of radical scavenger N-acetyl-l-cysteine and inducible NO synthetase inhibitor N_ω-nitro-l-arginine methyl ester hydrochloride. Further experiments demonstrated that IL-1β and TNF-α release was remarkably enhanced by iron load in activated microglia triggered by lipopolysaccharide or 1-methyl-4-phenylpyridinium (MPP⁺). In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice, salicylate application could not block DMT1 + IRE upregulation in dopaminergic neurons of substantia nigra. These results suggested that IL-1β and TNF-α released by microglia, especially under the condition of iron load, might contribute to iron accumulation in VM neurons by upregulating IRP1 and hepcidin levels through reactive oxygen/nitrogen species production. This might provide a new insight into unraveling that microglia might aggravate this iron mediated neuropathologies in PD.     

Chemoirradiation for Glioblastoma Multiforme: The National Cancer Institute Experience

Purpose

Standard treatment for glioblastoma (GBM) is surgery followed by radiation (RT) and temozolomide (TMZ). While there is variability in survival based on several established prognostic factors, the prognostic utility of other factors such as tumor size and location are not well established.

Experimental Design

The charts of ninety two patients with GBM treated with RT at the National Cancer Institute (NCI) between 1998 and 2012 were retrospectively reviewed. Most patients received RT with concurrent and adjuvant TMZ. Topographic locations were classified using preoperative imaging. Gross tumor volumes were contoured using treatment planning systems utilizing both pre-operative and post-operative MR imaging.

Results

At a median follow-up of 18.7 months, the median overall survival (OS) and progression-free survival (PFS) for all patients was 17.9 and 7.6 months. Patients with the smallest tumors had a median OS of 52.3 months compared to 16.3 months among patients with the largest tumors, P = 0.006. The patients who received bevacizumab after recurrence had a median OS of 23.3 months, compared to 16.3 months in patients who did not receive it, P = 0.0284. The median PFS and OS in patients with periventricular tumors was 5.7 and 17.5 months, versus 8.9 and 23.3 months in patients with non-periventricular tumors, P = 0.005.

Conclusions

Survival in our cohort was comparable to the outcome of the defining EORTC-NCIC trial establishing the use of RT+TMZ. This study also identifies several potential prognostic factors that may be useful in stratifying patients.     

三种绿叶挥发性物质对云南切梢小蠹寄主定位行为的干扰作用

为了研究环境中非寄主阔叶植物释放出的绿叶挥发性物质（GLVs）对针叶树蛀干害虫云南切梢小蠹Tomicus yunnanesis的影响, 选取了(E)-2-己烯醛、 (E)-2-己烯醇和(Z)-3-己烯醇3种释放量较大的绿叶挥发性物质, 通过室内松梢取食试验测试了单组分及两两混合后对云南切梢小蠹寄主定位行为的干扰作用。结果表明： 源于阔叶植物的3种绿叶挥发性物质及其混合物能够不同程度干扰云南切梢小蠹的寄主定位行为。当虫放入广口瓶12 h后, 3个单组分绿叶挥发性物质处理组［A： (E)-2-己烯醛, P＜0.01; B： (E)-2-己烯醇, P＜0.01; C： (Z)-3-己烯醇, P＜0.01］及2个混合组分［D： (E)-2-己烯醛+(E)-2-己烯醇, P＜0.01）; E： (E)-2-己烯醛+(Z)-3-己烯醇, P＜0.01］中滞留在松梢外部的虫数与对照组相比都有显著性差异, 绿叶挥发性物质的存在显著降低了云南切梢小蠹侵害云南松松梢的概率。但是, 24 h后只有D组（P＜0.01）和E组（P＜0.01）滞留在松梢外部的虫数与对照组相比具有显著性差异, 在48 h后只有D组（P＜0.01）与对照相比仍具有显著性差异。本研究为利用非寄主植物的次生代谢产物防治云南切梢小蠹进行了有益的探索。     

琥珀酸脱氢酶或琥珀酰辅酶A合成酶缺失促进大肠杆菌积累5-氨基乙酰丙酸

5-氨基乙酰丙酸 (ALA) 是生物体内四吡咯类化合物的合成前体,在农业及医药领域应用广泛,是极具开发价值的高附加值生物基化学品。目前利用外源C4途径的重组大肠杆菌发酵生产ALA的研究主要利用LB培养基并添加葡萄糖和琥珀酸、甘氨酸等合成前体,成本较高。琥珀酸在C4途径中以琥珀酰辅酶A的形式直接参与ALA的合成。文中在以葡萄糖为主要碳源的无机盐培养基中研究了琥珀酰辅酶A下游代谢途径琥珀酸脱氢酶编码基因sdhAB和琥珀酰辅酶A合成酶编码基因sucCD缺失对ALA积累的影响。与仅表达异源ALA合成酶的对照菌株相比,sdhAB和sucCD缺失菌株ALA的产量分别提高了25.59%和12.40%,且ALA的积累不依赖于琥珀酸的添加和LB培养基的使用,从而大幅降低了生产成本,显示出良好的工业应用前景。     

糖尿病肾病与非糖尿病肾病维持性血液透析患者血钙、血磷及甲状旁腺激素水平的分析

目的：探讨糖尿病肾病（diabtic nephropgthy,DN）与非糖尿病肾病（non-DN）维持性血液透析患者（maintenance hemodialysis,MHD）血钙、血磷、甲状旁腺激素（intact parathyroid hormone,iPTH）水平的差异;分析其血钙、血磷、iPTH和糖化血红蛋白（glycosylated hemoglobin,HbA1c）水平的相关性。方法：选择沈阳军区总医院血液透析中心收治的148例MHD患者,分为糖尿病组（58例）和非糖尿病组（90例）,比较两组间血钙、血磷、甲状旁腺激素水平的差异,并分析其血钙、血磷、iPTH、HbA1c水平的相关性。结果：糖尿病组iPTH、血磷水平均明显低于非糖尿病组（P〈0.05）,两组血钙水平比较无明显差异。在非DN组中,iPTH与血钙水平呈显著负相关（r=-0.320,P=0.036）,iPTH与血磷水平呈明显正相关（r=0.426,P=0.005）。在DN组中,iPTH与血钙、血磷无显著相关性,而iPTH与HbA1C水平呈显著负相关（r=-0.732,P=0.007）。结论：糖尿病肾病血液透析患者的iPTH水平和血磷水平明显低于非糖尿病肾病血液透析患者,HbA1c可能抑制iPTH的分泌。     

Acacetin antagonized lipotoxicity in pancreatic β-cells via ameliorating oxidative stress and endoplasmic reticulum stress

Molecular Biology Reports - During the pathogenesis and progression of diabetes, lipotoxicity is a major threat to the function and survival of pancreatic β-cells. To battle against the...     

餐厨垃圾高温好氧生物减量菌种的筛选及特性

【背景】随着餐厨垃圾产生量的逐步提高,如何实现其快速降解,成为餐厨垃圾处理亟待解决的问题。餐厨垃圾的高温好氧生物减量技术是一种可以快速降解餐厨垃圾的有效方法。【目的】筛选能够适应餐厨垃圾环境且具有高效降解餐厨垃圾中有机物能力的菌株,以提高餐厨垃圾的降解效率和减量效果。【方法】采用温度梯度耐受性实验和餐厨垃圾浸出液高油高盐耐受性实验进行菌种初筛,并利用产酶培养基复筛及餐厨垃圾生物减量实验验证。【结果】通过初筛、复筛和功能验证,最终获得4株生物减量效果优良的菌株N3-1、C7、N3-3和G6-1,其对餐厨垃圾挥发性固体(volatile solid,VS)的降解率分别为36.95%、33.23%、32.83%和31.91%,是对照组的3.02、2.71、2.68和2.61倍。经鉴定,这4株菌分别属于热嗜油地芽孢杆菌(Geobacillus thermoleovorans)、史氏芽孢杆菌(Bacillus smithii)、热解木糖地芽孢杆菌(Geobacillus caldoxylosilyticus)和立陶宛地芽孢杆菌(Geobacillus lituanicus)。【结论】筛选出的4株菌均具有较强的餐厨垃圾原料适应性和高效的生物降解能力,为开发餐厨垃圾高温好氧复合菌剂奠定了基础,并为实现餐厨垃圾减量化、无害化处理和资源化利用提供了技术支持。     

GST pull-down筛选冠突曲霉MAT的互作蛋白*

目的: 冠突曲霉(Aspergillus cristatus)是一种同宗结合菌,它的产孢受渗透压调控,与构巢曲霉的光调控产孢机制存在较大差异。冠突曲霉的有性生殖主要受MAT1-1-1和MAT1-2-1调控,但MAT基因对该菌有性生殖的调控机制仍不清楚。期望筛选得到冠突曲霉MAT的互作蛋白,为深入研究冠突曲霉有性产孢机制奠定基础。方法: 利用GST pull-down联合液相色谱-串联质谱(LC-MS/MS)技术筛选可能与冠突曲霉MAT1-1-1和MAT1-2-1互作的蛋白,结合ProteinPilot和冠突曲霉基因组注释结果进行互作蛋白的注释及GO分析,其中互作蛋白SI65_00917和SI65_03348利用RT-qPCR探索它们与有性发育的联系,并利用酵母双杂交技术初步验证它们与MAT蛋白的互作关系。结果: 成功构建了GST-MAT1-1-1、GST-MAT1-2-1表达载体,诱导表达纯化出目的诱饵蛋白,分别利用诱饵蛋白捕获冠突曲霉总蛋白中的互作蛋白,经分析、筛选共鉴定出与MAT1-1-1互作的蛋白56个,与MAT1-2-1互作的蛋白413个。GO分析表明,这些蛋白参与翻译调控、代谢过程、蛋白质转运及蛋白结合等生物学过程,具有核苷酸结合活性、催化活性、蛋白结合活性;RT-qPCR结果表明互作蛋白SI65_00917可能与有性发育相关。酵母双杂交结果表明,SI65_00917蛋白具有自激活作用,可能是转录因子;SI65_03348蛋白与MAT1-1-1、MAT1-2-1在酵母中均有互作。结论: MAT通过与其他蛋白直接或间接的相互作用调控其有性发育过程。