遗传算法在256阵元相控阵高强度聚焦超声治疗系统多焦点控制中的应用

阐述了遗传算法优化多点超声聚焦的方法以及球面相控阵声场计算方法。对实验室研发的256阵元相控阵聚焦超声治疗系统作了简介。利用此遗传算法和声场计算方法，对轴上和离轴单焦点以及轴对称六焦点和非轴对称四焦点进行了256阵元相控阵的声场仿真，并观察了实验室研发的256阵元相控阵聚焦超声治疗系统作用于有机玻璃和透明仿体的实验结果。用遗传算法和声场计算方法的仿真和系统实验结果表明，此方法可在实际聚焦手术中准确地控制3维单焦点和3维多焦点。     

Gemins modulate the expression and activity of the SMN complex

Reduction in the expression of the survival of motor neurons (SMN) protein results in spinal muscular atrophy (SMA), a common motor neuron degenerative disease. SMN is part of a large macromolecular complex (the SMN complex) that includes at least six additional proteins called Gemins (Gemin2-7). The SMN complex is expressed in all cells and is present throughout the cytoplasm and in the nucleus where it is concentrated in Gems. The SMN complex plays an essential role in the production of spliceosomal small nuclear ribonucleoproteins (snRNPs) and likely other RNPs. To study the roles of the individual proteins, we systematically reduced the expression of SMN and each of the Gemins (2-6) by RNA interference. We show that the reduction of SMN leads to a decrease in snRNP assembly, the disappearance of Gems, and to a drastic reduction in the amounts of several Gemins. Moreover, reduction of Gemin2 or Gemin6 strongly decreases the activity of the SMN complex. These findings demonstrate that other components of the SMN complex, in addition to SMN, are critical for the activity of the complex and suggest that Gemin2 and Gemin6 are potentially important modifiers of SMA as well as potential disease genes for non-SMN motor neuron diseases.     

SARS病毒S1蛋白重组C端片段免疫效果的实验研究

为获得纯化的重组SARS病毒S1蛋白C端 ,研究其刺激机体产生针对SARS病毒免疫应答的规律和机制 ,将编码SARS病毒S1蛋白C端 311个氨基酸残基的基因克隆 ,并在原核表达系统中表达 ,纯化获得了的重组蛋白。利用SARS患者恢复期的血清 ,对纯化的重组S1蛋白进行血清学分析。结果表明 ,本研究中克隆表达的重组蛋白序列与公布的SARS病毒S1蛋白C端的序列相同 ,其编码的重组蛋白相对分子质量约为 5 90 0 0Mr。SARS患者恢复期的血清均与重组蛋白反应 ,在5 9 0 0 0Mr处形成特异性的反应条带 ,而来自SARS流行前的正常人对照血清则不能与重组蛋白反应。在本研究中获得的重组蛋白可以为研究SARS病毒识别宿主细胞受体的过程及其机制提供条件。     

Ⅱ期高血压病高胰岛素血症对血液粘度及血脂的影响

以２１例Ⅱ期高血压患者、２１例Ⅱ期高血压病高胰岛素血症患者及２０例正常人为研究对象，以全血比粘度、全血还原比粘度、血浆比粘度、红细胞压积及血浆甘油三酯、总胆固醇、高密度脂蛋白为指标；结果表明Ⅱ期高血压病患者全血比粘度、全血还原比粘度较正常人高，Ⅱ期高血压病高胰岛素血症患者亦较单纯高血压病患者进一步增高，同时其血浆甘油三酯较单纯高血压病患者增高，高密度脂蛋白降低．而血浆比粘度、红细胞压积、总胆固醇三组间无显著性差异。单纯高血压病患者与正常人组比较血脂无差异。因而认为高血压病患者的高胰岛素血症可使高血压病患者增高的血粘度进一步增高，且血粘度的增高主要是红细胞机能、代谢的改变所致。单纯高血压病患者血脂改变不明显，高血压病患者血脂的改变主要是由高胰岛素血症所致。     

Pentasomy 8q in therapy-related myelodysplastic syndrome due to cyclophosphamide therapy for fibrosing alveolitis

Trisomy 8/8q is a common cytogenetic event in myelocytic malignancies, ranging from myelodysplastic syndrome (MDS) to acute myelocytic leukemia (AML) to blastic transformation of chronic myelocytic leukemia. Isochromosome 8q results in the same gene dosage effect. Duplication of i(8q), resulting in pentasomy 8q, has been reported only in two cases of AML. A patient with fibrosing alveolitis on prolonged cyclophosphamide treatment developed therapy-related MDS. Karyotyping, FISH, and CGH analysis showed a duplicated i(8q) among other complex abnormalities. The clinical features of 11 cases of myelocytic leukemia with pentasomy and hexasomy 8/8q were summarized. Compared with trisomy and tetrasomy 8, significant features included reduced median survival (90 days), treatment refractoriness (even with transplantation), monocytic differentiation, trilineage dysplasia, and radiation or toxin exposure. Increasing copy numbers of chromosome 8/8q may therefore be a marker of advanced leukemic evolution, exposure to toxins, underlying myelodysplasia, and an overall poor prognosis.     

Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects

Background  

Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties.     

The role of mPer1 in morphine dependence in mice

Investigations using Drosophila melanogaster have shown that the circadian clock gene period can influence behavioral responses to cocaine, and the mouse homologues, mPer1 and mPer2, modulate cocaine sensitization and reward. In the present study, we applied DNAzyme targeting mPer1 to interfere the expression of mPer1 in CNS in mice and studied the role of mPer1 on morphine dependence. We found that the DNAzyme could attenuate the expression of mPer1 in CNS in mice. Mice treated with DNAzyme and morphine synchronously did not show preference to the morphine-trained side, whereas the control group did. In contrast, mice treated with DNAzyme after morphine showed preference to the morphine-trained side as well as the control group did. These results indicate that drug dependence seems to be influenced at least partially by mPer1, but mPer1 cannot affect morphine dependence that has been formed.     

A Multidisciplinary,Community-Based Program to Reduce Unplanned Hospital Admissions

ObjectivesTo evaluate the effect of Hospital Admission Risk Program (HARP) on unplanned hospitalization, bed days, and mortality of enrolled individuals and to evaluate the cost-effectiveness of HARP.DesignA retrospective longitudinal analysis of hospital administrative data.InterventionIndividuals at risk of hospitalization were provided with multidisciplinary, community-based care support managed by care coordinators including integrated care planning, education, monitoring, service linkages, and general practitioner liaison over 6-9 months.Setting and ParticipantsIndividuals who were enrolled into 1 of 8 HARP chronic disease management programs between July 1, 2017, and June 30, 2018, at the Royal Melbourne Hospital, Australia.MethodsHospital admissions between 18 months before and 18 months after HARP enrollment were analyzed. Total hospital costs were compared between 18 months before and 12 months after HARP enrollment.ResultsA total of 1553 individuals with a median age of 71 years (interquartile range 60-81), 63.4% males, were admitted to HARP. Both unplanned hospitalizations and bed days were reduced during the HARP intervention compared to within 3 months before enrollment in each of the HARP management programs. After the HARP intervention, cardiac coach, cardiac heart failure, chronic respiratory, diabetes comanagement, and medication management programs had higher hospitalizations and bed days than individuals’ baseline of at least 3 months before HARP enrollment. Individuals in cardiac heart failure and chronic respiratory management programs had a higher mortality rate than other HARP chronic disease management programs. Individuals in cardiac coach, diabetes comanagement, and medication management programs had lower hospital costs during the HARP intervention compared to within 3 months before HARP enrollment.Conclusions and ImplicationsHARP reduced unplanned hospitalization and bed days but did not return individuals’ hospital use to baseline before the intervention. The variations in mortality between HARP chronic disease management programs implies that condition-specific goals between programs is preferable.