Prognostic value of complete metabolic response on 18F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer

ObjectiveWe investigated the prognostic value of complete metabolic response (CMR) on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC).MethodsPET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis.ResultsBetween 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552–0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542–0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490–0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27–0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05–0.99; p=0.048).ConclusionCMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.     

Study of a Modified Time Hardening Model for the Creep Consolidation Effect of Asphalt Mixtures

In the past, most researchers have explained the three-stage creep behavior of asphalt mixture in detail. Still, there is no reasonable model to describe the creep of the consolidation effect. To accurately describe the consolidation effect of an asphalt mixture during the viscoelastic deformation process, a modified time hardening model was established by using the Malthus model and the Logistic function to change its creep strain and creep compliance. According to the characteristics of asphalt mixture creep, a single penetration creep test was conducted for high-elasticity modified asphalt mixtures at different temperatures (20 °C, 40 °C, 60 °C) and various loading levels (0.55 MPa, 0.70 MPa, 0.85 MPa, 1.00 MPa). The test results showed that the effect of stress on deformation within the normal range of variation was more significant than that of temperature. In addition, the test results were simulated by the modified time hardening model using surface fitting and compared with a time hardening model and a modified Burgers model. A fitting analysis showed that the modified time hardening model more accurately represents the asphalt mixture’s consolidation effect and creep behavior. Therefore, the modified time hardening model can better show the consolidation effect in the creep process.     

蛛网膜对儿童缺血型烟雾病间接颅内外血管重建术疗效的影响

目的探讨儿童缺血型烟雾病行间接颅内外血管重建术时打开蛛网膜对术后血管重建疗效的影响。方法回顾性分析2010年8月至2015年11月21例(28侧)行间接颅内外血管重建术的儿童缺血型烟雾病患者临床资料,术中打开蛛网膜组12例(18侧),术中未打开蛛网膜组9例(10侧);术后12个月时复查MRI和DSA以及结合临床症状来评价打开蛛网膜与未打开蛛网膜组颅内外血管重建术后疗效。结果两组术后均有不同程度侧支循环形成及PWI改善,术中打开组术后12月时DSA侧支循环的良好及一般率达94.44%明显优于未打开组的60%,且构成的差异有统计学意义(P0.05);两组术后临床症状改善差异无统计学意义,而术中打开蛛网膜组的优秀及良好率达88.89%,高于未打开组的60%;两组并发症差异无统计学意义。结论术中打开蛛网膜较未打开者可能更有利于改善儿童缺血型烟雾病间接颅内外血管重建术的疗效。     

Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8

Erythropoietin (EPO) modulates primarily the proliferation of immature erythroid precursors, but little is known of the potential protective mechanisms of EPO in the central nervous system. We therefore examined the ability of EPO to modulate a series of death-related cellular pathways during anoxia and free radical induced neuronal degeneration. Neuronal injury was evaluated by trypan blue, DNA fragmentation, membrane phosphatidylserine exposure, protein kinase B phosphorylation, cysteine protease activity, mitochondrial membrane potential, and mitogen-activated protein (MAP) kinase phosphorylation. We demonstrate that constitutive neuronal EPO is insufficient to prevent cellular injury, but that signaling through the EPO receptor remains biologically responsive to exogenous EPO administration. Exogenous EPO is both necessary and sufficient to prevent acute genomic DNA destruction and subsequent phagocytosis through membrane PS exposure, because neuronal protection by EPO is completely abolished by co-treatment with an anti-EPO neutralizing antibody. Through pathways that involve the initial activation of protein kinase B, EPO maintains mitochondrial membrane potential. Subsequently, EPO inhibits caspase 8-, caspase 1-, and caspase 3-like activities linked to cytochrome c release through mechanisms that are independent from the MAP kinase systems of p38 and JNK. Elucidating some of the novel neuroprotective pathways employed by EPO may further the development of new therapeutic strategies for neurodegenerative disorders.     

Antibodies to the neuronal cytoskeleton are elicited by Alzheimer paired helical filament fractions

Antibodies were raised to paired helical filament (PHF) enriched fractions obtained from brains of individuals with Alzheimer disease by extraction with ionic detergent followed by sucrose gradient centrifugation. Electron microscopic examination showed that the fractions were enriched in Alzheimer PHF but contained also lipofuscin, amyloid, granular material and membranous elements. Analysis of these fractions with SDS-PAGE stained with Coomassie blue showed only a faint band at approximately 60 kDa while most of the material was excluded from the stacking gel. BALB/c mice were injected weekly with 100 or 200 μg of these fractions or corresponding fractions from age-matched control brains. The 3 mice injected with Alzheimer brain, but not the 5 mice injected with control brain fractions, produced antibodies that reacted with central and peripheral nervous system axons, Alzheimer neurofibrillary tangles in intact tissue as well as with isolated, SDS-treated paired helical filaments. In gel strips antibodies from all 3 mice injected with Alzheimer brain fractions reacted with the 200-kDa and 168-kDa but not the 68-kDa neurofilament subunits. The 3 antisera reacted also with some forms of the microtubule-associated protein τ. Adsorptions with the insoluble fraction from Alzheimer but not from control brains blocked staining of axons and NFT by all 3 antisera. Adsorption with highly purified neurofilament proteins or with a preparation containing the 200-kDa 168-kDa neurofilament subunits blocked axon and NFT immunostaining only in one antiserum. Adsorptions with microtubule protein, heat-stable microtubule-associated protein, or a preparation of τ did not completely block immunostaining by any of the 3 antisera. These results demonstrate that fractions enriched with Alzheimer paired helical filaments contain insoluble neurofilament, τ and other yet unidentified antigens.     

Thiazolidinedione derivatives as novel GPR120 agonists for the treatment of type 2 diabetes

GPR120, also called FFAR4, is preferentially expressed in the intestines, and can be stimulated by long-chain free fatty acids to increase the secretion of glucagon-like peptide-1 (GLP-1) from intestinal endocrine cells. It is known that GLP-1, as an incretin, can promote the insulin secretion from pancreatic cells in a glucose-dependent manner. Therefore, GPR120 is a potential drug target to treat type 2 diabetes. In this study, thiazolidinedione derivatives were found to be novel potent GPR120 agonists. Compound 5g, with excellent agonistic activity, selectivity, and metabolic stability, improved oral glucose tolerance in normal C57BL/6 mice in a dose-dependent manner. Moreover, compound 5g exhibited anti-diabetic activity by promoting insulin secretion in diet-induced obese mice. In summary, compound 5g might be a promising drug candidate for the treatment of type 2 diabetes.

GPR120 has emerged as an attractive target for the treatment of type 2 diabetes and obesity. Thiazolidinedione derivatives were found to be novel potent GPR120 agonists.     

家庭监测系统在双腔起搏器植入患者中的多中心注册研究

目的:评价家庭监测系统(HM)在植入双腔起搏器患者中的临床应用。方法:连续入选2009-03至2010-12在全国97家医院植入德国Biotronic公司具有家庭监测功能的起搏器患者,共628例。应用远程无线家庭监测系统每日自动传输起搏器信息,特殊报警事件随时传送。所有信息进行分析,将异常报警事件分为两类:疾病相关事件和系统相关事件;前者主要包括房性和室性心律失常,植入后3个月、6个月对所有入选患者进行常规诊室随访。结果:628例患者中,13例患者一直没有信息传输(2.1%),其余615例患者有137例患者没有异常事件的报警(22.3%),其余478例(77.7%)均可见异常报警事件;HM发现异常事件的时间均早于3个月和6个月门诊随访时发现相应事件的时间。房颤事件中共141例记录到至少一次房颤发作,且6个月随访期间,房颤平均负荷逐渐而显著性降低(P<0.05)。结论:对于植入双腔起搏器的患者,HM是一项安全可靠的远程监测方法,可以早期发现疾病相关事件及起搏系统相关异常,特别是对房颤进行早期诊断与及时治疗,并可能给病人带来临床长远益处。