Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

骨碎补化学成分和生物活性研究进展＊

骨碎补是历代临床常用中药，具有疗伤止痛、补肾强骨、消风祛斑等功效。其主要含黄酮、苯丙素、三萜、酚酸及其苷等类化学成分，现代研究表明骨碎补具有抗骨质疏松、促进骨折愈合、促软骨再生、护牙健齿、保护肾功能、抗炎、防治中毒性耳聋、降血脂等多种生物活性，开发前景广阔。本文对近年来骨碎补的化学成分、药理作用及临床应用研究进行综述，以期为骨碎补的进一步深入系统的研究和开发利用提供依据。     

富亮氨酸胶质瘤失活1蛋白抗体阳性边缘性脑炎 临床分析及文献复习

目的：总结富亮氨酸胶质瘤失活1蛋白（LGI1）抗体阳性边缘性脑炎的临床和影像特点及诊疗预后。 方法：报道我院1例LGI1抗体阳性相关边缘性脑炎并文献复习。结果：患者女性，60岁，表现为渐进性加重 的记忆力减退、癫痫发作（全身强直阵挛发作，面-臂肌张力障碍发作）、低钠血症和轻度精神行为异常。颅 脑MRI-T2/Flair序列提示双侧颞叶（左侧为甚）内侧、海马异常高信号。脑脊液抗LGI1抗体阳性（++）。经激 素治疗症状有所改善。检索既往报道LGI1抗体阳性边缘性脑炎患者237例，多数呈急性、亚急性起病，最 常见是记忆障碍、癫痫（含面-臂肌张力障碍发作）和低钠血症，头颅MRI（特别是MRI-T2/Flair序列）显示单 侧或者双侧海马区、颞叶异常多见，早期免疫治疗预后良好。结论：LGI1抗体阳性相关边缘性脑炎有其特 有的临床特点，免疫治疗可明显改善患者预后。     

基于UPLC-LTQ-Orbitrap-MS分析刺果番荔枝叶的化学成分

目的利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶的化学成分进行定性分析。方法采用Waters Acquity UPLC HSS T 3色谱柱(2.1 mm×100 mm,1.8μm),流动相为0.1%甲酸水(A)和乙腈(B)梯度洗脱,流速为0.3 mL/min,进样量2μL,在电喷雾正负离子模式下采集数据。经Reaxys数据库检索番荔枝属类化合物信息,通过质谱信息比对各化合物的m/z值、保留时间、质谱特征碎片等,并结合文献数据对鉴定的化合物进行验证。结果根据各化合物的特征裂解规律,从刺果番荔枝叶中共鉴定出45个化合物,包括16个生物碱类,14个番荔枝内酯类,7个黄酮类和8个其他类化合物,其中以番荔枝内酯类和生物碱类成分居多,与文献报道番荔枝内酯与生物碱类化合物是发挥抗癌的主要活性成分一致。结论利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶中的化学成分进行了快速、准确的定性分析,为刺果番荔枝叶的提取分离与药效物质基础的研究提供依据。     

实验家兔莱姆病血液学研究

本实验复制了莱姆病实验家兔模型，对血液生化23项进行了动态观察。结果表明，血液中谷丙转氨酶、γ-谷氨酰转肽酶、乳酸脱氢酶、谷草转氨酶、β-羟丁酸脱氢酶、磷酸肌酸激酶、胆固醇、尿素氮随病情加重而升高。葡萄糖、尿酸、磷随病情加重而减低。     

对我国目前麻风防治策略的思考

1949-2008年我国累计登记麻风患者48万余例,主要分布在北纬38°以南的东南沿海和长江流域省份.新中国成立后,经过积极防治,至20世纪80年代初,以氨苯砜单疗治愈的患者达31万余例;1986年在全国普遍推广WHO联合化疗方案,至2008年底全国累计接受联合化疗的麻风患者近8万例.     

Chemical composition and cytotoxic activity of the leaf essential oil of <Emphasis Type="Italic">Eugenia zuchowskiae</Emphasis> from Monteverde,Costa Rica

The leaf essential oil of Eugenia zuchowskiae from Monteverde, Costa Rica, has been obtained by hydrodistillation and analyzed by GC–MS. The principal constituents of E. zuchowskiae leaf oil were α-pinene (28.3%), β-caryophyllene (13.2%), α-humulene (13.1%), and α-copaene (8.1%). The leaf essential oil of E. zuchowskiae showed pronounced in-vitro cytotoxic activity against MCF-7, MDA-MB-468, and UACC-257 human tumor cell lines. The major components showed cytotoxic activities comparable to doxorubicin (LC₅₀ 14–70 μg/ml).     

Chemical traumatization of adult mouse olfactory epithelium in situ stimulates growth and differentiation of olfactory neurons in vitro

This study demonstrates that ZnSO₄ induced chemical trauma results in an in situ regeneration of the olfactory epithelium which, when maintained in vitro, provides an enriched population of olfactory neurons. Therefore, the ability of the olfactory epithelium to respond to chemical trauma with increased mitotic activity can be used to increase growth of neurons in culture. Tissue obtained from normal or vehicle-treated adult mice produced few olfactory neurons, when maintained in culture, compared to cultures established from tissue following an in situ ZnSO₄ trauma. Maximal neuronal yields were obtained in cultures established from tissue that was removed 4–6 days following chemical trauma. The morphological appearance and the presence of cell specific intermediate filament proteins were used to classify the cell types in these olfactory epithelial cultures. Single cells and aggregates of cells which were immunopositive for keratin, but immunonegative for neurofilament protein and GFAP, were identified as epithelioid. Flattened polygonal cells immunopositive for GFAP were identified as glia. A small population of flattened cells was immunonegative for all of the antibodies used in this study. Cells that had processes were immunonegative for GFAP and keratin. Some were immunopositive for 200 kDa and 160 kDa neurofilament proteins but immunonegative for the 68 kDa neurofilament protein. A few of these cells showed positive immunoreactivity with the olfactory marker protein (OMP) antibody and most likely represented the most mature olfactory neurons in the cultures. This trauma-induced culture model using olfactory tissue from adult mice can serve as a source of CNS neurons for comparison with cultured embryonic neurons.     

化工行业职业性机械伤害危险因素的病例-交叉方法研究

目的 研究化工行业机械伤害的有关诱发因素，估计其作用强度。方法 采用病例-交叉设计的方法。以操作和检修时受伤的化工工人为研究对象，每个对象在受伤后2d内完成调查，收集他们受伤前10min、上一工作日同一段时间和受伤前1周内有关诱发因素暴露的信息，用配对时间段方法和一般频数法进行分析，评估各种诱发因素的危险度。结果 一般频数法分析的结构表明，操作方法异常、设备工具缺陷、工作紧迫、注意力不集中、不使用防护用品、精神状况较差、与同事配合不协调、工作环境发生变化等瞬时危害因素的RR值及95%可信限的下限均大于1。配对时间段方法分析的结果与其相拟，但95%可信限较宽。结论 化工行业职业性机械伤害的发生存在着诸多诱发因素。病例-交叉研究中的一般频数法与配对时间段方法相比，前者所得结果较为可靠，研究的相对效率较高。建议进一步使用多个时间段方法进行研究，以减小混杂因素的影响。