多发性骨髓瘤中表观遗传学修饰的研究进展北大核心

多发性骨髓瘤(multiple myeloma,MM)是一种病因不明,目前仍无法治愈的恶性血液系统性疾病。研究显示MM是一种复杂的表观遗传学修饰所驱动的恶性肿瘤,表观遗传学修饰是改变MM发病进展的重要机制,并影响治疗及预后。本文将对表观遗传学异常调控在MM的发生发展过程中的作用及相关耐药机制和治疗的现状进行综述。     

New era for myelofibrosis treatment with novel agents beyond Janus kinase-inhibitor monotherapy: Focus on clinical development of BCL-XL/BCL-2 inhibition with navitoclax

Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g., ruxolitinib) provide significant spleen and symptom relief but demonstrate limited ability to lead to a durable disease modification. There is an urgent unmet medical need for treatments with a novel mechanism of action that can modify the underlying pathophysiology and affect the disease course of myelofibrosis. This review highlights the role of B-cell lymphoma (BCL) protein BCL-extra large (BCL-X_L) in disease pathogenesis and the potential role that navitoclax, a BCL-extra large/BCL-2 inhibitor, may have in myelofibrosis treatment.     

兰州百合多糖BHP-1的化学结构与形貌分析

目的:以兰州百合鳞茎中分离和纯化得到的多糖BHP-1为主要研究对象,综合运用仪器分析和化学反应等手段研究其初步的形貌特征和化学结构。方法:采用热重分析(TG)及扫描电镜(SEC)技术分别分析多糖BHP-1的热稳定性和形貌结构特征;通过气相色谱-质谱联用(GC-MS)技术,结合部分酸水解、高碘酸钠氧化-Smith降解以及核磁共振波谱(NMR)分析等方法对多糖BHP-1的化学结构进一步的进行解析。结果:BHP-1是以1,4连接的α-D-吡喃葡萄糖和1,4连接的β-D-吡喃甘露糖为基本骨架的甘露葡聚糖,在葡萄糖和甘露糖的2位和/或3位形成主要的分支,主链或支链的末端残基主要为T-α-D-吡喃葡萄糖,同时在其结构片段中含有少量的O-乙酰基。热重分析显示BHP-1在220℃开始发生降解,520℃基本结束,说明BHP-1热稳定性良好。形貌分析显示BHP-1表面光滑有大量凹陷,凹陷处多为片层结构错落紧密堆积而成,并交织下陷呈不规则的孔洞。结论:多糖BHP-1是一种热稳定性良好,表面光滑有大量的凹陷和孔洞,并含少量O-乙酰基的甘露葡聚糖,其化学结构为首次报道。     

Systemic disruption of the homeostasis of transfer RNA isopentenyltransferase causes growth and development abnormalities in Bombyx mori

Isopentenylation at A37 (i⁶A37) of some transfer RNAs (tRNAs) plays a vital role in regulating the efficiency and fidelity of protein synthesis. However, whether insects, which are well known for their highly efficient protein synthesis machinery, employ this regulatory mechanism remains uninvestigated. In the current study, a candidate tRNA isopentenyltransferase (IPT) gene with three alternative splicing isoforms (BmIPT1–BmIPT3) was identified in Bombyx mori (silkworm). Only BmIPT1 could complement a yeast mutant lacking tRNA IPT. Phylogenetic analysis showed that silkworm tRNA IPT is conserved in the Lepidoptera. BmIPT was expressed in all B. mori tissues and organs that were investigated, but was expressed at a significantly higher level in silk glands of the fourth instar compared to the first day of the fifth instar. Interestingly, BmIPT was expressed at a significantly higher level in the domesticated silkworm, B. mori, than in wild Bombyx mandarina in multiple tissues and organs. Knock‐down of BmIPT by RNA interference caused severe abnormalities in silk spinning and metamorphosis. Constitutive overexpression of BmIPT1 using a cytoplasmic actin 4 promoter in B. mori raised its messenger RNA level more than sixfold compared with nontransgenic insects and led to significant decreases in the body weight and cocoon shell ratio. Together, these results confirm the first functional tRNA IPT in insects and show that a suitable expression level of tRNA IPT is vital for silk spinning, normal growth, and metamorphosis. Thus, i⁶A modification at position A37 in tRNA probably plays an important role in B. mori protein synthesis.     

Neuroimaging the pain network – Implications for treatment

In this chapter, we provide an overview of neuroimaging studies in chronic pain. We start with an introduction about the phenomenology of pain. In the following section, the application of functional and structural imaging techniques is shown in selected chronic pain syndromes (chronic back pain, fibromyalgia syndrome (FMS), phantom limb pain, and complex regional pain syndrome (CRPS)), and commonalities and peculiarities of imaging correlates across different types of chronic pain are discussed. We conclude this chapter with implications for treatments, with focus on behavioral interventions, sensory and motor trainings, and mirror and motor imagery trainings.     

基于结构方程模型构建护理本科生人文关怀对职业精神态度的影响模式

目的 应用结构方程模型构建人文关怀对职业精神态度的影响模式,了解人文关怀、社会支持及职业精神态度之间的关系。方法 采用分层随机整群抽样法从南京和南通两所高等护理院校抽取全日制在校护理本科一年级至三年级在校学生450名进行问卷调查,应用AMOS 21.0构建人文关怀对职业精神态度的影响模式。 结果 人文关怀对职业精神态度影响模式的结构方程模型最终模型适配度指标分别为RMSEA = 0. 066、GFI = 0. 951、AGFI = 0. 918、NFI = 0. 901、ＲFI = 0. 860、IFI = 0. 932、TLI = 0. 903、CFI = 0. 931、PGFI = 0. 573、PNFI = 0.641、PCFI = 0. 663、χ_²/DF=2.965,说明模型拟合效果较好；人文关怀对社会支持的直接效应为0.571,社会支持对职业精神态度的直接效应为0.778,人文关怀对职业精神态度的总效应为0.554。结论 此模型可用于护生职业精神态度评价与干预工作,进一步提高护生人文关怀能力、社会支持水平及职业精神态度水平。