Diet does not ensure normal development in galactosemia.

This review deals with the treatment of inherited classical galactosemia by a lactose-free diet. Although, with dietary treatment, there is a remarkable improvement in the acute phase of the disease, the long-term outcome has been disappointing for most patients, especially regarding the central nervous system and ovarian dysfunction in females. There is a need for new approaches to treatment, in combination with diet therapy, that could improve the outcome of patients with galactosemia.     

VIDEO GAMES AND A CULTURE OF CONFLICT

This paper is an examination of phonograph records marketed to children in the first decades of the phonograph industry and the cultural discourses that surrounded them. I focus on the first book and record hybrid marketed to children: a pioneering instance of cross-media synergy between the book publishing and record industries. The first edition of the “Bubble Books” was released in 1917, and indicates the design of home media texts that were considered to be “good for children,” as well as some of the anxieties that surrounded the arrival of such products into the home. The marketing of “the books that sing” provides a rich case study in the early implementation of techniques for marketing children's media that would become widespread later in the twentieth century. Advertising materials for Bubble Books reveal a lost phase in the development of the marketing of children's media products to parents and children. Ultimately, this essay is concerned not only with adding the phonograph industry to historical accounts of children's media, and with documenting early strategies for marketing children's media products, but also with identifying aspects of that marketing that allowed these pioneering instances of home media products for children to be woven into the fabric of everyday American family life.     

Does comorbidity interact with colorectal cancer to increase mortality? A nationwide population-based cohort study

Background:

It is unknown whether comorbidity interacts with colorectal cancer (CRC) to increase the rate of mortality beyond that explained by the independent effects of CRC and comorbid conditions.

Methods:

We conducted a cohort study (1995–2010) of all Danish CRC patients (n=56 963), and five times as many persons from the general population (n=271 670) matched by age, gender, and specific comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index (CCI) scores. We estimated standardised mortality rates per 1000 person-years, and calculated interaction contrasts as a measure of the excess mortality rate not explained by the independent effects of CRC or comorbidities.

Results:

Among CRC patients with a CCI score=1, the 0–1 year mortality rate was 415 out of 1000 person-years (95% confidence interval (CI): 401, 430) and the interaction accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person-years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the interaction accounted for 34% of the mortality (interaction contrast=262 out of 1000 person-years, 95% CI: 215, 310). The interaction between CRC and comorbidities had limited influence on mortality beyond 1 year after diagnosis.

Conclusion:

Successful treatment of the comorbidity is pivotal and may reduce the mortality attributable to comorbidity itself, and also the mortality attributable to the interaction.     

The mechanism of treatment of multiple myeloma with metformin by way of metabolism

IntroductionMultiple myeloma (MM) is a malignant hematologic tumor. Although many new drugs are currently found to significantly improve the median survival, MM is still not curable due partly to drug resistance recurrence. Epidemiological studies have shown that patients with type 2 diabetes have a high risk of malignancy, and patients’ treatment with metformin could reduce the risk of cancer as well as associated mortality.Material and methodsWe used chemotherapeutics – melphalan combined with metformin or the single drug – to treat RPMI8226 cells and used a series of tests to detect the drug sensitivity, apoptotic rate, DNA damage and the concentration of ATP. SPSS 17.0 was used to analyze the data.ResultsThe inhibitory effect of melphalan on RPMI8226 cells was significantly increased after metformin was added (p < 0.05), and the inhibitory effect was enhanced with the increasing concentration of melphalan. The comet assay showed that metformin increased melphalan-induced DNA damage and increased the apoptotic rate from 12.7 ±2.8% to 18.8 ±1.5% (p < 0.05). In the ATP concentration test, the concentration of ATP in the tumor cells was significantly decreased from 0.42 ±0.01 μmol/l to 0.08 ±0.02 μmol/l (p < 0.05).ConclusionsMetformin can promote DNA damage induced by melphalan and decrease the concentration of ATP in the process of repairing DNA damage to hinder the anti-apoptotic process of tumor cells, which showed the pesticide effect of the enhanced sensitivity of multiple myeloma cells to melphalan.     

Synthetic lipopeptides: a novel class of anti-infectives

Lipopeptide daptomycin is one of the few recently approved antibiotics based on the novel mechanism of action. Recent advances in synthetic lipopeptides, driven by the biochemical and biophysical research, expanded their spectrum of antimicrobial activity and reduced their size to achieve economically viable production. Lipopeptides, consisting of a short peptide chain conjugated with an acyl chain, form a structurally defined conformation, which inserts into the bacterial membrane and dissipates its transmembrane potential. In addition to antimicrobial activity, synthetic lipopeptides also suppress inflammation through the neutralization of bacterial agonists of the innate immune response, synergize with conventional antibiotics and have improved proteolytic stability. Activities in animal models indicate that synthetic lipopeptides may surpass the natural lipopeptides as the perspective class of anti-infective agents.     

我国适宜卫生技术推广模式研究

目的:总结适宜卫生技术的推广模式,分析存在的问题并提出解决措施。方法:采用归纳演绎的方法对我国适宜卫生技术的推广模式进行分析总结。结果:我国目前适宜卫生技术的推广主要依靠政府财政支持。单纯依靠政府通过政府财政进行推广见效快,但不能持久;单纯依靠市场机制进行推广,一些疗效好但没有经济优势的项目就可能无法得到推广。结论:发挥政府调控导向和市场竞争机制的协同作用,对不同的技术采取不同的推广模式是解决我国适宜卫生技术推广过程中存在问题的主要措施。     

Axial synergies during human upper trunk bending

Upper trunk bending movements were accompanied by opposite movements of the lower body segments. These axial kinematic synergies maintained equilibrium during the movement performance by stabilizing the center of gravity (CG), which shifted on average across all the subjects by 1±4 cm in the anteroposterior direction and thus always remained within the support area. The aim of the present investigation was to provide an insight into the central control responsible for the performance of these synergies. The kinematic analysis was performed by the method of principal components (PC) analysis applied to the covariation between ankle, knee and hip joint angles and compared with CG shifts during upper trunk bending. Subjects were asked to perform backward or forward upper trunk bending in response to a tone. They were instructed to move as fast as possible or slowly (2 s), with high or low movement amplitudes. PC analysis showed a strong correlation between hip, knee and ankle joint changes. The first principal component (PC1) representing a multijoint movement with fixed ratios between joint angular changes, accounted, on average, for 99.7%±0.2% of the total angular variance in the forward trunk movements and for 98.4%±1.4% in the backward movements. The instructed voluntary regulation of the amplitude and velocity of the movement was achieved by adapting the bell-shaped profile of the velocity time course without changes in interjoint angular relations. Fixed ratios between changes in joint angles, represented by PC1, ensured localization of the CG within the support area during trunk bending. The ratios given by PC1 showed highly significant dependence on subjects, suggesting the adaptability of the central control to each subject’s biomechanical peculiarities. Subject’s intertrial variability of PC1 ratios was small, suggesting a stereotyped automatic interjoint coordination. When changing velocity and amplitude of the movement, the ratios remained the same in about half the subjects while in others slight variations were observed. A weak second principal component (PC2) was shown only for fast movements. In forward movements PC2 reflected the early knee flexion that seems related to the disturbances caused by the passive interaction between body segments, rather than to the effect of a central command. In fast backward movements, PC2 reflected the delay in hip extension relative to the movement onset in the ankle and knee that mirrors intersubject differences in the initiation process of the axial synergy. The results suggest that PC1 reflects the centrally controlled multijoint movement, defining the time course and amplitude of the movement and fixing the ratios between changes in joint angles. They support the hypothesis that the axial kinematic synergies result from a central automatic control that stabilizes the CG shift in the anteroposterior direction while performing the upper trunk bending. Received: 8 August 1996 / Accepted: 7 July 1997     

拟康氏木霉胞外多糖联合奥沙利铂可体外协同抑制结直肠癌细胞的增殖

目的 探讨拟康氏木霉胞外多糖（EPS）联合奥沙利铂（Oxa）用药对结肠癌细胞HCT116的协同抑制作用。方法 实验分为Control组（0 μg/mL）、Oxa组（8 μg/mL Oxa）、EPS组（100 μg/mL EPS）、EPS+Oxa组（8 μg/mL Oxa+100 μg/mL EPS）。CCK-8检测细胞活力,CompuSyn软件拟合Fa-CI曲线评价联用效果。流式检测凋亡和周期、划痕实验和transwell实验检测细胞迁移能力,Oxa和EPS相关基因与结直肠癌相关基因取交集进行PPI分析以及GO和KEGG富集分析。结果 Oxa单用或与EPS联用处理HCT116细胞,均可使HCT116细胞活力受到抑制,并呈现剂量与时间依耐性,两者联用有明显的协同作用（CI<1）。两药联用组的细胞总凋亡率与Oxa组以及对照组比较均显著升高（P<0.05）;联合用药组处于S期的比例高于其他各组。EPS和Oxa均具有抑制HCT116细胞迁移的作用,两者联用后抑制作用更为明显。KEGG分析显示主要涉及耐药、凋亡、血管新生等通路。结论 EPS联合奥沙利铂可协同抑制HCT116细胞增殖,促进该细胞凋亡和细胞S周期阻滞、抑制细胞迁移,铂耐药、PI3K-Akt、MAPK等信号通路发挥了关键作用。     

肿瘤联合免疫治疗研究进展

免疫检查点是免疫系统中抑制性的信号通路,通过与共刺激分子保持平衡,维持对自身组织的耐受,避免自身免疫反应。肿瘤的发生伴随着共抑制分子与相关配体的上调,引起T细胞功能衰退或耗竭,从而发生肿瘤细胞的免疫逃逸。针对抑制性受体与配体开发单抗药物,调节T细胞活性提高抗肿瘤免疫反应,已经取得较好的临床效果。对免疫调节信号通路采取联合治疗也体现出一定的协同作用。本文对肿瘤联合免疫治疗方案与协同作用评价进行综述,并对联合免疫治疗的可行性及免疫方案的选择进行展望。