Network Structure and Properties of Lithium Aluminosilicate Glass

Based on lithium aluminosilicate glass, the composition of glass was optimized by replacing SiO₂ with B₂O₃, and the influence of glass composition on structure and performance was studied. With the increase in B₂O₃ concentrations from 0 to 6.5 mol%, Al₂O₃ always existed in the form of four-coordinated [AlO₄] in the network structure, and B₂O₃ mainly entered the network in the form of four-coordinated [BO₄]. The content of Si-O-Si linkages (Q₄^(0Al)) was always dominant. The incorporation of boron oxide improved the overall degree of polymerization and connectivity of the lithium aluminosilicate glass network structure. An increase in the degree of network polymerization led to a decrease in the thermal expansion coefficient of the glass and an increase in Vickers hardness and density. The durability of the glass in hydrofluoric acid and NaOH and KOH solutions was enhanced overall.     

Impact of Freeze–Thaw Cycles on the Long-Term Performance of Concrete Pavement and Related Improvement Measures: A Review

Freeze–thaw damage is one of the most severe threats to the long-term performance of concrete pavement in cold regions. Currently, the freeze–thaw deterioration mechanism of concrete pavement has not been fully understood. This study summarizes the significant findings of concrete pavement freeze–thaw durability performance, identifies existing knowledge gaps, and proposes future research needs. The concrete material deterioration mechanism under freeze–thaw cycles is first critically reviewed. Current deterioration theories mainly include the hydrostatic pressure hypothesis, osmolarity, and salt crystallization pressure hypothesis. The critical saturation degree has been proposed to depict the influence of internal saturation on freeze–thaw damage development. Meanwhile, the influence of pore solution salinity on freeze–thaw damage level has not been widely investigated. Additionally, the deterioration mechanism of the typical D-cracking that occurs in concrete pavement has not been fully understood. Following this, we investigate the coupling effect between freeze–thaw and other loading or environmental factors. It is found that external loading can accelerate the development of freeze–thaw damage, and the acceleration becomes more evident under higher stress levels. Further, deicing salts can interact with concrete during freeze–thaw cycles, generating internal pores or leading to crystalline expansion pressure. Specifically, freeze–thaw development can be mitigated under relatively low ion concentration due to increased frozen points. The interactive mechanism between external loading, environmental ions, and freeze–thaw cycles has not been fully understood. Finally, the mitigation protocols to enhance frost resistance of concrete pavement are reviewed. Besides the widely used air-entraining process, the freeze–thaw durability of concrete can also be enhanced by using fiber reinforcement, pozzolanic materials, surface strengthening, Super Absorbent Polymers (SAPs), and Phase Change Materials. This study serves as a solid base of information to understand how to enhance the freeze–thaw durability of concrete pavement.     

MR灌注影像指导下大脑中动脉供血区急性脑梗死的r-tPA静脉溶栓治疗研究

目的 观察在MR灌注影像指导下,重组组织型纤溶酶原激活剂(r-tPA)静脉内溶栓治疗大脑中动脉供血区急性脑梗死的时效及并发症.方法 分别对15 例发病后3 h和12例3～6 h内头颅MR PWI/DWI不匹配≥20%的急性缺血性脑梗死患者行静脉内r-tPA(0.9 mg/kg)溶栓治疗,治疗前后NIHSS评定神经功能恢复状况,治疗后和随访期用Barthel指数(BI)评价临床疗效.结果 不同时间窗内的t-rPA溶栓静脉治疗后NIHSS的评分均有明显改善,临床疗效明显,分别有1例出现皮下淤斑和梗死区渗血.结论 在MR的PWI/DWI不匹配≥20%的情况下,急性大脑中动脉脑梗死3 h内和3～6 h内两个时间窗,用r-tPA静脉溶栓均安全有效.     

警惕“高功能陷阱”——双相抑郁患者的过度状态期望

维持病情长期稳定是双相障碍治疗的关键,而准确判断患者的疾病状态是维持治疗的重点和难点。过度状态期望常见于双相抑郁患者,通过影响患者对自身疾病状态的判断,最终干扰临床决策,此现象应当引起高度关注。本文就双相障碍患者过度状态期望的现象和可能的机制进行探讨,为有关诊疗和研究提供思路。     

抑郁障碍患者主观与客观认知功能的差异性研究

背景 抑郁障碍患者的主观认知功能与客观认知功能存在差异。目前,关于主客观认知功能差异影响因素的研究有限。目的 探索抑郁障碍患者主观和客观认知功能的差异及其影响因素,为进一步理解抑郁障碍患者认知功能受损情况提供参考。方法 纳入2022年1月13日—2023年12月11日在成都市第四人民医院门诊就诊或住院治疗的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）抑郁障碍诊断标准的77例患者为研究对象。采用蒙哥马利-艾森贝格抑郁量表（MADRS）评定患者抑郁症状严重程度,采用抑郁感知缺陷问卷（PDQ-D）和中国简版神经认知成套测验（C-BCT）分别评定患者的主观认知功能和客观认知功能,采用席汉残疾量表（SDS）评定患者的社会功能,以临床总体印象量表-疾病严重程度量表（CGI-SI）评定患者病情严重程度。采用Pearson相关分析考查年龄、受教育年限、MADRS总评分、SDS总评分、CGI-SI评分与主客观认知功能及其差异的相关性。采用多元线性回归探索主客观认知功能差异的影响因素。结果 是否用药的抑郁障碍患者PDQ-D总评分和主客观认知功能差异（D值）比较差异均有统计学意义（t=-4.2...     

Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis

AimsThe potential signaling pathways and core genes in ulcerative colitis (UC) were investigated in this study. Furthermore, potential mechanisms of BBR in treating UC were also explored.MethodsExpression profiling by array of UC patients were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were determined with the differential analysis. The biological functions of DEGs were analyzed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Gene Set Enrichment Analysis (GSEA) was applied to analyze the expression differences between two different phenotype sample sets. Dextran sulfate sodium (DSS) was applied to establish UC model of mice and lipopolysaccharide (LPS) was utilized to induce inflammatory damage of NCM460 cells. Therapeutic effects of berberine (BBR) on disease performance, pathologic changes and serum supernatant indices were analyzed in vivo. To further investigate the potential mechanisms of BBR in treating UC, the expression of genes and proteins in vivo and in vitro were examined by RT-qPCR, immunohistochemical staining and western blotting.ResultsImmune-inflammatory genes were identified and up-regulated significantly in UC patients. In addition, IFN-γ signaling pathway and its core genes were significantly up-regulated in the phenotype of UC. All disease performance and the pathologic changes of UC in mice were evidently ameliorated by BBR treatment. The pro-inflammatory cytokines of serum, including CXCL9, CXCL1, IL-17 and TNF-α, in UC mice were significantly reduced by treatment of BBR. In terms of mechanisms of BBR in treating UC, the pro-inflammatory and immune-related genes, encoding IFN-γ, IRF8, NF-κB and TNF-α decreased significantly in UC mice followed by BBR treatment. Meanwhile, the expression of IFN-γ and its initiated targets, including IRF8, Ifit1, Ifit3, IRF1, were suppressed significantly by BBR treatment in vivo. The blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Furthermore, the blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR.ConclusionBBR holds anti-inflammatory activity and can treat UC effectively. The anti-inflammatory property of BBR is tightly related to the suppression of IFN-γ signaling pathway, which is crucial in immune-inflammatory responses of the colon mucosa.     

系统生物学在中药ADME性质研究中的应用

本文从中医的研究角度综述了系统生物学的定义、研究框架、范围和方法论特点, 并以PBPK和PBPD 研究为实例, 详述了系统生物学方法论在药学研究中的最新应用和进展, 阐明了系统生物学是还原论基础上的整体论。中医药是中医整体辩证理论指导下的复杂体系, 拟乘系统生物学之势将面对诸多基础问题的挑战, 然而中药ADME 性质的阐明将成为中医药系统生物学研究的基石, 从而将分子水平和整体水平有力地衔接起来。本文中同时简略地综述了作者研究组在该领域的有益尝试, 结果表明中药的早期ADME性质研究方法将是揭开中药之谜并过渡到系统生物学水平的有力手段。     

Clinical course and outcomes of COVID-19 patients with chronic obstructive pulmonary disease: A retrospective observational study in Wuhan,China

Information about coronavirus disease 2019 (COVID-19) patients with pre-existing chronic obstructive pulmonary disease (COPD) is still lacking. The aim of this study is to describe the clinical course and the outcome of COVID-19 patients with comorbid COPD.This retrospective study was performed at Wuhan Huoshenshan Hospital in China. Patients with a clear diagnosis of COVID-19 who had comorbid COPD (N = 78) were identified. COVID-19 patients without COPD were randomly selected and matched by age and sex to those with COPD. Clinical data were analyzed and compared between the two groups. The composite outcome was the onset of intensive care unit admission, use of mechanical ventilation, or death during hospitalization. Multivariable Cox regression analyses controlling for comorbidities were performed to explore the relationship between comorbid COPD and clinical outcome of COVID-19.Compared to age- and sex-matched COVID-19 patients without pre-existing COPD, patients with pre-existing COPD were more likely to present with dyspnea, necessitate expectorants, sedatives, and mechanical ventilation, suggesting the existence of acute exacerbations of COPD (AECOPD). Greater proportions of patients with COPD developed respiratory failure and yielded poor clinical outcomes. However, laboratory tests did not show severer infection, over-activated inflammatory responses, and multi-organ injury in patients with COPD. Kaplan–Meier analyses showed patients with COPD exhibited longer viral clearance time in the respiratory tract. Multifactor regression analysis showed COPD was independently correlated with poor clinical outcomes.COVID-19 patients with pre-existing COPD are more vulnerable to AECOPD and subsequent respiratory failure, which is the main culprit for unfavorable clinical outcomes. However, COPD pathophysiology itself is not associated with over-activated inflammation status seen in severe COVID-19.     

IL‐27 improves adoptive CD8+ T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation

IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8⁺ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8⁺ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8⁺ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8⁺ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8⁺ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8⁺ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.