TomoDirect技术在全脑全脊髓放疗中的应用

目的 为全脑全脊髓放疗建立新的TomoDirect技术(TD)布野方案,并评价剂量学参数。方法 对本院收治的7例全脑全脊髓放疗患者进行回顾性研究,在Tomo计划系统分别设计5野TD、3野TD和螺旋断层治疗(helical tomotherapy, HT)计划,比较3种计划的靶区适形指数(CI)、均匀性指数(HI)、危及器官受量、治疗时间和机器跳数(MU)。结果 除3野TD计划外其余两者均能获得较好的靶区适形度和均匀性。其中5野TD计划靶区受量明显优于3野TD计划,但略逊于HT计划;危及器官受量则各有优势。5野TD、3野TD和HT计划的靶区平均CI分别为0.79、0.57和0.88;靶区HI分别为1.06、1.16和1.05;双肺V₂₀分别为1.99%、3.30%和2.16%;心脏平均剂量分别为6.17、12.38和10.72 Gy;肝脏平均剂量分别为5.21、5.14和4.62 Gy;左侧肾脏平均剂量分别为4.30、1.99和5.03 Gy;右侧肾脏平均剂量分别为4.42、2.09和4.91 Gy。靶区以外的正常组织V₅分别为46.80%、28.06%和55.54%。5野TD计划的治疗时间最短,5野TD、3野TD及HT计划的平均治疗时间分别为677、721和907 s,MU数分别是8 773、9 657和12 581。结论 5野的TD技术应用于全脑全脊髓放疗具有一定优势,适用于难以坚持长时间治疗,且希望减少低剂量范围的患者。     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays

Tumoral cells in Hodgkin lymphoma (HL) display an increased growth fraction and diminished apoptosis, implying a profound disturbance of the cell cycle and apoptosis regulation. However, limitations of molecular techniques have prevented the analysis of the tumor suppressor pathways and cell-cycle checkpoints. Tissue microarray (TMA) is a powerful tool for analyzing a large number of molecular variables in a large series of tumors, although the feasibility of this technique has not yet been demonstrated in heterogeneous tumors. The expression of 29 genes regulating the cell cycle and apoptosis were analyzed by immunohistochemistry and in situ hybridization in 288 HL biopsies using TMA. The sensitivity of the technique was validated by comparing the results with those obtained in standard tissue sections. The results revealed multiple alterations in different pathways and checkpoints, including G1/S and G2/M transition and apoptosis. Striking findings were the overexpression of cyclin E, CDK2, CDK6, STAT3, Hdm2, Bcl2, Bcl-X(L), survivin, and NF-kappaB proteins. A multiparametric analysis identified proteins associated with increased growth fraction (Hdm2, p53, p21, Rb, cyclins A, B1, D3, and E, CDK2, CDK6, SKP2, Bcl-X(L), survivin, STAT1, and STAT3), and proteins associated with apoptosis (NF-kappaB, STAT1, and RB). The analysis also demonstrated that Epstein-Barr virus (EBV)-positive cases displayed a characteristic profile, confirming the pathogenic role of EBV in HL. Survival probability depends on multiple biologic factors, including overexpression of Bcl2, p53, Bax, Bcl-X(L), MIB1, and apoptotic index. In conclusion, Hodgkin and Reed-Sternberg cells harbor concurrent and overlapping alterations in the major tumor suppressor pathways and cell-cycle checkpoints. This appears to determine the viability of the tumoral cells and the clinical outcome.     

Vitamin D Receptor Genetic Polymorphism Is Significantly Associated With Decreased Risk of Hypertension in a Chinese Han Population

The aim of this study was to investigate the association of vitamin D receptor (VDR) gene polymorphism and hypertension in a Chinese Han population. The authors genotyped 3 tagSNPs (rs11574129, rs2228570, and rs739837) of the VDR gene using TaqMan assays in a case‐control study including 2409 patients with hypertension and 3063 controls. The results showed that rs2228570 presented statistical correlations with decreased risk of male hypertension after adjustment for confounding factors, odds ratios (ORs) and 95% confidence intervals (CIs) of additive, dominant, and recessive models were 0.828 (0.74–0.927), 0.75 (0.631–0.89), and 0.816 (0.67–0.995), and P values were .001, .001, and .044, respectively. Significant associations were found in the smoking population and ORs (95% CIs) of additive and dominant models were 0.81 (0.69–0.952) and 0.71 (0.552–0.913) (P values .011 and .008), respectively, after adjustment for covariates. Quantitative trait analysis indicated that the untreated cases with TT genotype of rs2228570 showed higher systolic blood pressure compared with the TC/CC genotype (P=.015). Our findings suggest that VDR genetic polymorphism rs2228570 is significantly associated with the decreased risk of hypertension in Chinese men and smokers.     

Comparison of Carbon Supports in Anion Exchange Membrane Fuel Cells

Anion exchange membrane fuel cells (AEMFCs) are attractive alternatives to proton exchange membrane fuel cells due to their ability to employ nonprecious metals as catalysts, reducing the cost of AEMFC devices. This paper presents an experimental exploration of the carbon support material effects on AEMFC performance. The silver (Ag) nanoparticles supported on three types of carbon materials including acetylene carbon (AC), carbon black (CB), and multiwalled carbon nanotube (MWCNT)—Ag/AC, Ag/CB, and Ag/MWCNT, respectively—were prepared using the wet impregnation method. The silver loading in the catalysts was designed as 60 wt.% during the synthesizing process, which was examined using thermogravimetric analysis. The elemental composition of the prepared Ag/AC, Ag/CB, and Ag/MWCNT catalysts was confirmed using X-ray diffraction analysis. The nanoparticle size of Ag attached on carbon particles or carbon nanotubes, as observed by scanning electron microscopy (SEM), was around 50 nm. For the performance tests of a single AEMFC, the obtained results indicate that the maximum power density using Ag/MWCNT as the cathode catalyst (356.5 mW·cm⁻²) was higher than that using Ag/AC (329.3 mW·cm⁻²) and Ag/CB (256.6 mW·cm⁻²). The better cell performance obtained using a MWCNT support can be ascribed to the higher electrical conductivity and the larger electrochemical active surface area calculated from cyclic voltammetry measurements.     

Synthesis and biological evaluation of quinoxaline derivatives as tubulin polymerization inhibitors that elevate intracellular ROS and triggers apoptosis via mitochondrial pathway

A series of novel quinoxaline derivatives were synthesized and evaluated for their antiproliferative activity in three human cancer cell lines. Compound 12 exhibited the most potent antiproliferative activity with IC₅₀ in the range of 0.19–0.51 μM. The compound inhibited tubulin polymerization and disrupted the microtubule network, leading to G2/M phase arrest. Furthermore, compound 12 induced ROS production and malfunction of mitochondrial membrane potential. Compound 12 led to cancer cells apoptosis in a dose‐dependent manner. Western blot analysis showed that compound 12 induced up‐regulation of p21 and affected the expression of cell cycle‐related proteins. The binding mode was also probed by molecular docking.     

Gestational exposure to low‐dose zearalenone disrupting offspring spermatogenesis might be through epigenetic modifications

Zearalenone (ZEA), a F‐2 mycotoxin produced by Fusarium, has been found to be an endocrine disruptor through oestrogen receptor signalling pathway to impair spermatogenesis. The disruption on reproductive systems by ZEA exposure might be transgenerational. In our previous report, we have found that low dose (lower than no‐observed effect level, NOEL) of ZEA impaired mouse spermatogenesis and decreased mouse semen quality. The purpose of the current investigation was to explore the impacts of low‐dose ZEA on spermatogenesis in the offspring after prenatal exposure and the underlying mechanisms. And it demonstrated that prenatal low‐dose ZEA exposure disrupted the meiosis process to inhibit the spermatogenesis in offspring and even to diminish the semen quality by the decrease in spermatozoa motility and concentration. The DNA methylation marker 5hmC was decreased, the histone methylation markers H3K9 and H3K27 were elevated, and oestrogen receptor alpha was reduced in the offspring testis after prenatal low‐dose ZEA exposure. The data suggest that the disruption in spermatogenesis by prenatal low‐dose ZEA exposure may be through the modifications on epigenetic pathways (DNA methylation and histone methylation) and the interactions with oestrogen receptor signalling pathway. Moreover, in the current study, the male offspring were indirectly exposed to low‐dose ZEA through placenta and the spermatogenesis in offspring was disrupted which suggested that the toxicity of ZEA on reproductive systems was very severe. Therefore, we strongly recommend that greater attention should be paid to this mycotoxin to minimize its adverse impact on human spermatogenesis.