Physiology of cold-stored platelets

Platelet transfusions are a life-saving medical intervention used for the treatment of thrombocytopenia or hemorrhage. Extensive research has gone into trying to understand how to store platelets prior to the transfusion event. Much has been learned about storage bag materials, synthetic solutions, and how temperature impacts platelet viability and function. While room temperature storage of platelets preserves 24-hour in vivo platelet recovery and survival there is a greater risk for bacterial growth. Therefore, cold storage of platelets has become attractive due to the reduction in potential bacterial proliferation and the maintenance of platelet function beyond 5 days of storage. Cold stored platelets, however, have their own set of challenges. Cold stored platelets become activated through several mechanisms. The morphological and molecular changes that occur due to cold exposure enhance their ability to participate in the hemostatic process at the cost of rapid clearance from circulation. This review focuses on the underlying mechanisms leading to cold platelet activation and the receptor modifications involved in platelet clearance.     

A randomized study on the effect of modified behavioral activation treatment for depressive symptoms in rural left-behind elderly

Objective: To evaluate the effectiveness of a modified behavioral activation treatment (MBAT) intervention on reducing depressive symptoms in rural left-behind elderly.

Method: This is a randomized study registered in Chinese Clinical Trial Registry (ChiCTR-IOR-17011289). Eighty rural left-behind elderly people who had a Geriatric Depression Scale (GDS) score between 11 and 25 were randomly assigned to the intervention (n?=?40) and control group (n?=?40). The intervention group received both MBAT and regular treatment for 8 weeks while the control group received regular treatment. Both groups were assessed with the GDS, Beck Anxiety Inventory (BAI), and Oxford Happiness Questionnaire (OHQ) at baseline, immediately post-intervention, and at 3 months post-intervention.

Results: There were a total of 73 participants that completed the intervention. The scores of GDS and BAI decreased significantly, but the scores of OHQ increased significantly in the intervention group after 8 sessions of MBAT (P?<?.01). The reduction in depression symptoms after the intervention was maintained at the 3-month follow-up. Significant differences in GDS, BAI, and OHQ scores were observed between the intervention group and the control group (P?<?.01).

Conclusion: MBAT produced a significantly greater reduction in depressive symptoms than regular care in rural left-behind elderly.

Clinical or methodological significance of this article: A modified behavioral activation (BA) psychotherapy can significantly reduce the recurrence and seriousness of depression symptoms in the left-behind elderly with mild to moderate depression. This study also suggests that further study of the MBAT as an intervention will provide a direction for the management of mental health in rural left-behind elders.     

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

How does measurement of platelet P-selectin compare with other methods of measuring platelet function as a means of determining the effectiveness of antiplatelet therapy?

Measurement of P-selectin on activated platelets as a means of measuring platelet function utilizing the technology described here has the advantage of not requiring immediate access to specialist equipment and expertise. Blood samples are activated, fixed, stored, and transported to a central laboratory for flow cytometric analysis. Here we have compared P-selectin with other more traditional approaches to measuring platelet function in blood and/or platelet-rich plasma (PRP) from patients with acute coronary syndromes on treatment for at least 1 month with either aspirin and clopidogrel or aspirin with prasugrel. The comparators were light transmission aggregometry (LTA), VerifyNow and Multiplate aggregometry (for determining the effects of aspirin) and LTA, VerifyNow and Multiplate together with the BioCytex VASP phosphorylation assay (for the P2Y₁₂ antagonists). The P-selectin Aspirin Test revealed substantial inhibition of platelet function in all but three of 96 patients receiving aspirin with clopidogrel and in none of 51 patients receiving aspirin and prasugrel. The results were very similar to those obtained using LTA. There was only one patient with high residual platelet aggregation and low P-selectin expression. The same patients identified as “non-responders” to aspirin also presented with the highest residual platelet activity as measured using the VerifyNow system, although not quite as well separated from the other values. With the Multiplate test only one of these patients clearly stood out from the others. The results obtained using the P-selectin P2Y₁₂ Test in 102 patients taking aspirin and clopidogrel were similar to the more traditional approaches in that a wide scatter of results was obtained. Generally, high values seen with the P-selectin P2Y₁₂ Test were also high with the LTA, VerifyNow, Multiplate, and BioCytex VASP P2Y₁₂ Tests. Similarly, low residual platelet function using the P2Y₁₂ test was seen irrespective of the testing procedure used. However, there were differences in some patients. Prasugrel was always more effective than clopidogrel in inhibiting platelet function with none of 56 patients (P-selectin and VerifyNow), only 2 of 56 patients (Multiplate) and only 3 of 56 patients (Biocytex VASP) demonstrating high on-treatment residual platelet reactivity (HRPR) defined using previously published cut-off values. The exception was LTA where there were 11 of 56 patients with HRPR. It remains to be seen which experimental approach provides the most useful information regarding outcomes after adjusting therapies in treated patients.     

A Multi-Scale DNN Algorithm for Nonlinear Elliptic Equations with Multiple Scales

Algorithms based on deep neural networks (DNNs) have attracted increasing attention from the scientific computing community. DNN based algorithms are easy to implement, natural for nonlinear problems, and have shown great potential to overcome the curse of dimensionality. In this work, we utilize the multi-scale DNN-based algorithm (MscaleDNN) proposed by Liu, Cai and Xu (2020) to solve multi-scale elliptic problems with possible nonlinearity, for example, the p-Laplacian problem. We improve the MscaleDNN algorithm by a smooth and localized activation function. Several numerical examples of multi-scale elliptic problems with separable or non-separable scales in low-dimensional and high-dimensional Euclidean spaces are used to demonstrate the effectiveness and accuracy of the MscaleDNN numerical scheme.     

骨外固定器行胫骨迁移治疗血栓闭塞性脉管炎的护理

目的总结利用骨外固定器行胫骨迁移治疗血栓闭塞性脉管炎的护理经验.方法对35例血栓闭塞性脉管炎37条患肢应用骨外固定器迁移胫骨治疗.术前积极处理患肢、有效的心理护理,术后严密观察,做好骨外固定器迁移胫骨的护理.结果 32例间歇性跛行距离增加;27例夜间静息痛均得到缓解;7例足趾缺血坏死中除3例术后患肢缺血加重截肢外,余4例患肢供血改善,坏死区域结痂愈合;总有效率91.9%.结论全面、准确地评估患者,完善术前准备及术后正确迁移指导可提高骨外固定器行胫骨迁移治疗血栓闭塞性脉管炎的有效性.     

有关医院空调水系统若干问题的探讨

主要阐述空调水系统利用平衡阀调节系统阻力,保持系统水力稳定;利用软启动器实施水泵的平滑软启动;压差旁通阀的作用及选型安装;系统管道热膨胀等问题。     

老年脑梗死患者急性期血小板活化功能定量检测

目的 :探讨老年脑梗死患者外周血中血小板膜糖蛋白变化的临床意义。　方法 :应用流式细胞术检测了 6 8例急性期老年脑梗死患者外周血血小板活化分子标记物CD4 1、CD6 2p和CD6 3的含量水平 ,与 4 2例正常老年人对照 ;并对脑梗死组病灶大小、梗死部位、病情分级等与血小板活化分子表达的变化进行分析 ,应用统计学进行处理。　结果 :急性期脑梗死患者血小板粘附分子CD4 1、CD6 2 p和CD6 3的表达水平显著高于正常对照组 (P <0 .0 1) ,且与梗死灶大小及病情分级密切相关 ,与梗死部位无关。　结论 :老年脑梗死患者急性期外周血血小板活化功能明显增强 ,为早期应用抗血小板聚集药物的治疗提供了实验依据