A complex Polycomb issue: the two faces of EZH2 in cancer

In the April 1, 2012, issue of Genes & Development, Simon and colleagues (pp. 651-656) demonstrated that the disruption of Ezh2 in mice is sufficient to cause T-acute lymphoblastic leukemia (T-ALL). Moreover, in concert with concurrent studies, the authors revealed that similar mechanisms are involved in human T-ALL. These data contrast with previous findings showing that increased EZH2 activity promotes cancer.     

The Retinohypothalamic tract: Comparison of axonal projection patterns from four major targets

The retinohypothalamic tract is one component of the optic nerve that transmits information about environmental luminance levels through medial and lateral branches to four major terminal fields in the hypothalamus. The spatial distribution and organization of axonal projections from each of these four terminal fields were analyzed and compared systematically with the anterograde pathway tracer PHAL in rats where the terminal fields had been labeled with intravitreal injections of a different anterograde pathway tracer, CTb. First, the well-known projections of two medial retinohypothalamic tract targets (the ventrolateral suprachiasmatic nucleus and perisuprachiasmatic region) were confirmed and extended. They share qualitatively similar projections to a well-known set of brain regions thought to control circadian rhythms. Second, the projections of a third medial tract target, the ventromedial part of the anterior hypothalamic nucleus, were analyzed for the first time and shown to resemble qualitatively those from the suprachiasmatic nucleus and perisuprachiasmatic region. And third, projections from the major lateral retinohypothalamic tract target were analyzed for the first time and shown to be quite different from those associated with medial tract targets. This target is a distinct core part of the ventral zone of the anterior group of the lateral hypothalamic area that lies just dorsal to the caudal two-thirds of the supraoptic nucleus. Its axonal projections are to neural networks that control a range of specific goal-oriented behaviors (especially drinking, reproductive, and defensive) along with adaptively appropriate and complementary visceral responses and adjustments to behavioral state.     

Behavioral despair is differentially affected by the length and timing of photic stimulation in the dark phase of an L/D cycle

The effect of varying the length and timing of photic stimulation in the dark phase of an L/D lighting cycle on behavioral despair was investigated in female Wistar rats. Animals were kept in a vivarium on an L/D 12 h:12 h light cycle (lights on at 0700 h) except for a single day of light exposure in an insulated chamber in the dark phase of the L/D schedule. Light pulses provided by an incandescent lamp (15- and 25-W, for Exps. 1 and 2, respectively) either 2-h (Exp. 1) or 30-min in length (Exp. 2) were administered to independent groups of rats (n=8 each) either in the early, middle or late hours of the dark phase of the L/D cycle in the insulated chamber. Light pulses were delivered beginning 2 1/2, 5 1/2 or 7 1/2 h (Exp. 1) or 3 1/4, 6 1/4 and 8 1/4 h (Exp. 2) after dark onset. Control animals were treated similarly except for photic stimulation. In each experiment, an additional group received a light pulse of the appropriate length both in the early and late portion of the dark phase (double double-pulse groups): beginning 2 1/2 and 7 1/2 h (Exp. 1) or 3 1/4 and 8 1/4 h (Exp. 2) after dark onset. All animals then underwent two forced swim tests separated by 24 h with the first test occurring in the light (starting at 1500 h) following the dark phase when photic stimulation was administered. Total duration of immobility in the second swim test was measured to gauge behavioral despair. In Exp. 1, the 2-h double double-pulse group showed significantly shorter immobility compared to controls (p<0.05). In Exp. 2, 30-min light pulse delivered late in the dark phase reduced immobility significantly compared to controls and all the other light-treated groups (p<0.01). Results indicate that photic stimulation may have antidepressant effect on behavioral despair depending on the timing and the duration of photic stimulation.     

大型综合性医院主诊医师负责制应用效果评价

目的：探讨大型综合性医院主诊医师负责制的应用效果。方法：通过医院HIS系统、人员管理系统抽取评价用数据,并通过满意度问卷调查,运用SAS统计软件对数据资料进行描述、分析,对实验组和对照组医疗数质量、经济效益、医疗服务质量以及人力资源管理等三个方面的指标进行了综合评价。结果：通过对实施主诊组前后病区医疗数质量指标综合分析、患者满意度调查、高中初级医师比例等指标的综合对比,实行主诊医师负责制能够明显提高医疗质量和效率,改善医疗服务和医患关系。结论：主诊组的实施有助于实现能级管理、精细化管理和激励管理,强化医务人员竞争意识．提升人力资源管理水平,促进医疗技术创新和医院信息化建设。     

Nucleosome-binding activities within JARID2 and EZH1 regulate the function of PRC2 on chromatin

Polycomb-repressive complex 2 (PRC2) comprises specific members of the Polycomb group of epigenetic modulators. PRC2 catalyzes methylation of histone H3 at Lys 27 (H3K27me3) through its Enhancer of zeste (Ezh) constituent, of which there are two mammalian homologs: Ezh1 and Ezh2. Several ancillary factors, including Jarid2, modulate PRC2 function, with Jarid2 facilitating its recruitment to target genes. Jarid2, like Ezh2, is present in poorly differentiated and actively dividing cells, while Ezh1 associates with PRC2 in all cells, including resting cells. We found that Jarid2 exhibits nucleosome-binding activity that contributes to PRC2 stimulation. Moreover, such nucleosome-binding activity is exhibited by PRC2 comprising Ezh1 (PRC2–Ezh1), in contrast to PRC2–Ezh2. The presence of Ezh1 helps to maintain PRC2 occupancy on its target genes in myoblasts where Jarid2 is not expressed. Our findings allow us to propose a model in which PRC2–Ezh2 is important for the de novo establishment of H3K27me3 in dividing cells, whereas PRC2–Ezh1 is required for its maintenance in resting cells.     

High haematocrit in cyanotic congenital heart disease affects how fibrinogen activity is determined by rotational thromboelastometry

Introduction

Viscoelastometry enables rapid evaluation of coagulopathy in settings such as cardiac surgery but may be influenced by red cell concentration.

Methods

In order to study the effects of supra-physiological red cell concentrations on viscoelastometry, we compared ROTEM® viscoelastometry and plasma coagulation assay results in high haematocrit (HCT; 0.55-0.76 L/L) blood from patients with cyanotic congenital heart disease (CCHD), and in model high HCT blood (HCT 0.45-0.70 L/L).

Results

High HCT blood from CCHD patients (median HCT 0.66 L/L) displayed prolonged clot initiation in the EXTEM® test compared to controls and reduced maximum clot firmness (MCF) in the EXTEM (median 51 mm vs 64 mm in controls) and FIBTEM® (7 mm vs 14 mm) tests. The plasma fibrinogen (Clauss; CF) was similar in CCHD blood to controls (median 2.94 g/L vs 2.49) but the whole blood fibrinogen concentration (WBFC) was reduced (1.27 g/L vs 1.58). The FIBTEM MCF correlated linearly with the CF (r² = 0.68; p < 0.0001) and WBFC (r² = 0.65; p < 0.0001) in control blood but this relationship was maintained only with WBFC in CCHD blood. Model high HCT blood showed abnormal ROTEM test results that were similar to CCHD blood, including reduced FIBTEM MCF (14 mm with HCT 0.32-0.44 vs 6 mm with HCT 0.63-0.70). The ROTEM results were HCT dependent but independent of plasma clotting times and fibrinogen concentration.

Conclusion

Supra-physiologic HCT causes abnormal ROTEM test results consistent with increased dilution of fibrinogen and coagulation factors in whole blood by red cells. High HCT should be considered during interpretation of ROTEM test results in clinical settings.     

Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses

Immunotherapy strategies targeting the programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer. However, owing to the heterogeneity of tumors and individual immune systems, PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients. Accumulating evidence has shown that an effective response to anti-PD-L1/anti-PD-1 therapy requires establishing an integrated immune cycle. Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure. Impairments in the immune cycle can be restored by epigenetic modification, including reprogramming the environment of tumor-associated immunity, eliciting an immune response by increasing the presentation of tumor antigens, and by regulating T cell trafficking and reactivation. Thus, a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.     

耳鼻喉科门诊病人保健需求调查与保健指导

采用问卷法调查了632名耳鼻喉科门诊病人,获得了有关初级保健、次级保健和高级保健需求资料。统计分析表明,病人对心理保健、医疗保健和预防保健为内涵的次级保健需求量最大,其中又以医疗保健所占比重最高(75％)。分别对次级保健的3种需求进行了较详细的分析,得出了病人对疾病预防、治疗与护理知识的需求大,渴望得到心理支持和疾病防治的措施。在调查的基础上,根据耳鼻喉科门诊病人的需求特点开展了门诊保健指导工作。从常见病的预防保健知识宣传入手,加强了医疗护理保健技术的指导;同时改善医患关系,开展心理疏导,创造良好的心理气氛。