Biotherapy for xenografted human central nervous system leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19)- pokeweed antiviral protein immunotoxin

The study of central nervous system (CNS) leukemia has been hampered by the lack of a suitable animal model. We report that severe combined immunodeficiency (SCID) mice invariably develop rapidly progressive fatal CNS leukemia within 3 weeks after intravenous injection of NALM-6 pre-B acute lymphoblastic leukemia (ALL) cells. Colonization of the dura mater and subarachnoid space, usually of the distal spinal cord with occasional extension into the Virchow-Robin spaces of blood vessels subjacent to the meninges, followed involvement of bone marrow in the skull, vertebrae, and, occasionally, the appendicular skeleton. Occult CNS leukemia was detectable by polymerase chain reaction amplification of human DNA as early as 8 days postinoculation of leukemia cells. We used this in vivo model of human CNS leukemia to examine the therapeutic efficacy and toxicity of intrathecally administered B43 (anti-CD19)-pokeweed antiviral protein (PAP), an anti- B-lineage ALL immunotoxin directed against the pan-B-cell antigen CD19/Bp95. Intrathecal therapy with B43 (anti-CD19)-PAP immunotoxin at nontoxic dose levels significantly improved survival of SCID mice and was superior to intrathecal methotrexate therapy.     

Synthesis and Stability of Hydrogen Storage Material Aluminum Hydride

Aluminum hydride (AlH₃) is a binary metal hydride with a mass hydrogen density of more than 10% and bulk hydrogen density of 148 kgH2/m3. Pure aluminum hydride can easily release hydrogen when heated. Due to the high hydrogen density and low decomposition temperature, aluminum hydride has become one of the most promising hydrogen storage media for wide applications, including fuel cell, reducing agents, and rocket fuel additive. Compared with aluminum powder, AlH₃ has a higher energy density, which can significantly reduce the ignition temperature and produce H₂ fuel in the combustion process, thus reducing the relative mass of combustion products. In this paper, the research progress about the structure, synthesis, and stability of aluminum hydride in recent decades is reviewed. We also put forward the challenges for application of AlH₃ and outlook the possible opportunity for AlH₃ in the future.     

Insulin-like growth factor-I regulates proliferation and osteoblastic differentiation of calcifying vascular cells via extracellular signal-regulated protein kinase and phosphatidylinositol 3-kinase pathways

Vascular calcification develops within atherosclerotic lesions and results from a process similar to osteogenesis. One of the paracrine regulators of bone-derived osteoblasts, insulin-like growth factor-I (IGF-I), is also present in atherosclerotic lesions. To evaluate its possible role in vascular calcification, we assessed its in vitro effects on proliferation and differentiation in calcifying vascular cells (CVCs), a subpopulation of bovine aortic medial cells. Results showed that IGF-I inhibited spontaneous CVC differentiation and mineralization as evidenced by decreased alkaline phosphatase (AP) activity and decreased matrix calcium incorporation, respectively. Furthermore, IGF-I inhibited the AP activity induced by bacterial lipopolysaccharide, TNF-alpha, or H2O2. It also induced CVC proliferation based on 3H-thymidine incorporation. Results from Northern analysis and tests using IGF-I analogs suggest that IGF-I effects are mediated through the IGF-I receptor. IGF-I also activated both the extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) pathways. Inhibition of either the ERK or PI3K pathway reversed IGF-I effects on CVC proliferation and AP activity, suggesting a common downstream target. Overexpression of ERK activator also mimicked IGF-I inhibition of lipopolysaccharide-induced AP activity. These results suggest that IGF-I promotes proliferation and inhibits osteoblastic differentiation and mineralization of vascular cells via both ERK and PI3K pathways.     

非杓型高血压对左心室肥厚的影响及其临床意义

目的：以杓型高血压患者为对照，探讨非杓型高血压在左心室肥厚发生和发展中的作用。方法：应用２４小时动态血压和超声心动图检测２３０例高血压患者，选择年龄、病程、昼间血压基本相同的杓型、非杓型高血压患者１５０例，其中男性各４５例，女性各３０例。结果：非杓型高血压患者舒张末期左心房内径显著大于杓型高血压患者，男性分别为３５．８±２．９ｍｍ与３１．２±２．７ｍｍ（Ｐ＜０．０１）；女性分别为３２．４±２．５ｍｍ与２９．４±１．８ｍｍ（Ｐ＜０．０５）。女性杓型、非杓型高血压患者间舒张末期左心室内径的差异（４９．５±３．２ｍｍ与５４．８±３．７ｍｍ，Ｐ＜０．０１）比男性（５３．８±４．６ｍｍ与５７．４±４．５ｍｍ，Ｐ＜０．０５）更为显著。非杓型高血压患者左心室重量指数显著大于杓型高血压患者，男性分别为１５８．０±７．９ｇ／ｍ２与１３０．０±６．７ｇ／ｍ２（Ｐ＜０．０１）；女性分别为１３８．０±５．６ｇ／ｍ２与１１５．０±４．７ｇ／ｍ２（Ｐ＜０．０１）。结论：非杓型高血压患者左心室肥厚的检出率比杓型高血压患者为高。     

Localization of denaturation bubbles in random DNA sequences

We study the thermodynamic and dynamic behaviors of twist-induced denaturation bubbles in a long, stretched random sequence of DNA. The small bubbles associated with weak twist are delocalized. Above a threshold torque, the bubbles of several tens of bases or larger become preferentially localized to AT-rich segments. In the localized regime, the bubbles exhibit "aging" and move around subdiffusively with continuously varying dynamic exponents. These properties are derived by using results of large-deviation theory together with scaling arguments and are verified by Monte Carlo simulations.     

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T])

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.     

Relationship between Fas/FasL expression and apoptosis of colon adenocarcinoma cell lines

INTRODUCTIONFas/ FasL system has been identified as a keymediator of apoptosis in tumor cells[1-4]. Theoccurrence and development of neoplasm are closelyrelated to apoptosis[5-7] Most chemotherapeuticdrugs kill cancer cells mainly by inducingapoptosis[8-14].'     

TSC1-mTOR-PLK轴以阶段特异性方式调节从施旺细胞增殖到髓鞘形成的内稳态开关

恰如其分的外周髓鞘形成取决于雪旺细胞增殖与分化进程间的平衡。丝氨酸/苏氨酸激酶(mTOR)整合多种环境因素,是细胞生长、代谢、发挥作用的中枢调节者。本文报道了一种mTOR的负性调节剂——结节性硬化复合体(TSC1),通过控制细胞增殖和髓鞘稳态,建立了雪旺细胞谱系进展和髓鞘形成的阶段依赖性程序。小鼠雪旺细胞祖细胞中TSC1的解离导致mTOR信号通路激活,继而导致雪旺细胞过量增殖,分化受阻,髓鞘形成减少。转录组分析显示,TSC1突变体中的mTOR活化使得polo样激酶(PLK)依赖性通路和细胞周期调节剂上调。弱化mTOR或者对PLK进行药理抑制部分挽救了因TSC1缺失导致的外周神经发育过程中的髓鞘形成减少。相较之下,成年小鼠成熟雪旺细胞中TSC1缺失可导致髓鞘的过度增殖和过度生长。本文的发现提示了TSC1-mTOR-PLK信号轴在控制雪旺细胞的发育过程中,从增殖到分化和髓鞘内稳态中起到的阶段特异性功能。     

中西医结合治疗骨折后膝关节粘连性僵硬的临床疗效

目的：探讨中西医结合治疗骨折后膝关节粘连性僵硬患者的临床效果。方法：运用随机抽样的方法选取我院2013年1月～2014年9月收治的140例骨折后膝关节粘连性僵硬患者,依据随机数字表法将这些患者分为研究组和对照组两组,各70例。给予对照组患者单纯西医治疗,给予研究组患者中西医结合治疗,然后对两组患者的临床疗效进行统计分析。结果：研究组患者中显效46例,有效22例,治疗的总有效率为97.1%（68/70）;对照组患者中显效36例,有效18例,治疗的总有效率为77.1%（54/70）。研究组患者治疗的总有效率显著高于对照组。结论：中西医结合治疗骨折后膝关节粘连性僵硬患者的临床效果显著。