Data-independent acquisition-based quantitative proteomic analysis of m.3243A>G MELAS reveals novel potential pathogenesis and therapeutic targets

The pathogenesis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS) syndrome has not been fully elucidated. The m.3243A > G mutation which is responsible for 80% MELAS patients affects proteins with undetermined functions. Therefore, we performed quantitative proteomic analysis on skeletal muscle specimens from MELAS patients. We recruited 10 patients with definitive MELAS and 10 age- and gender- matched controls. Proteomic analysis based on nanospray liquid chromatography-mass spectrometry (LC-MS) was performed using data-independent acquisition (DIA) method and differentially expressed proteins were revealed by bioinformatics analysis. We identified 128 differential proteins between MELAS and controls, including 68 down-regulated proteins and 60 up-regulated proteins. The differential proteins involved in oxidative stress were identified, including heat shock protein beta-1 (HSPB1), alpha-crystallin B chain (CRYAB), heme oxygenase 1 (HMOX1), glucose-6-phosphate dehydrogenase (G6PD) and selenoprotein P. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis showed significant enrichment in phagosome, ribosome and peroxisome proliferator-activated receptors (PPAR) signaling pathway. The imbalance between oxidative stress and antioxidant defense, the activation of autophagosomes, and the abnormal metabolism of mitochondrial ribosome proteins (MRPs) might play an important role in m.3243A > G MELAS. The combination of proteomic and bioinformatics analysis could contribute potential molecular networks to the pathogenesis of MELAS in a comprehensive manner.     

口腔健康素养测量工具的构建及验证

目的:构建口腔健康素养(Oral Health Literacy,OHL)测量工具,并对其进行信度和结构效度检验,为我国居民口腔健康素养评估提供科学工具.方法:采用方便抽样方法,于2020年3月-4月选择山西省太原市小店区某社区的常住人口为调查对象,通过文献查阅、专家咨询和认知访谈,形成口腔健康素养测量工具.采用SPS...     

衰老相关分泌表型的作用机制及相关药物研究进展

衰老相关分泌表型(senescence-associated secretory phenotype, SASP)是促炎因子、趋化因子和蛋白酶等一系列细胞因子的总称,是衰老细胞的关键特征。SASP是一柄双刃剑,在正常细胞中能抵御外界有害环境,但随着身体机能下降, SASP大量分泌,在诱发机体炎症的同时,加速机体衰老,导致多种衰老相关疾病的产生。本文概述了SASP的组成及其生理功能、SASP在衰老过程中的变化、调节途径以及调节SASP的抗衰老药物,旨在对SASP有一个更加全面深刻的认识,为基于SASP的抗衰老机制研究及相关药物新靶点的发现奠定基础。     

Surface state modulation of blue-emitting carbon dots with high quantum yield and high product yield

In order to explore the surface state modulation mechanism of carbon dots (CDs) with high quantum yield (QY) and high product yield (PY), CDs were synthesized from different carbon sources with different contents of oxygen-containing functional groups and different silane coupling agents with nitrogen-containing functional groups. The highest QY of as-prepared CDs can reach 97.32% and the PY values of CDs are all high ranging from 46.33–58.76%. It is found that the high content of C O and pyrrolic N on the surface of CDs can endow CDs with high QY. Moreover, the PY of CDs not only depends on whether CDs have the crosslinked structure, but also is closely and positively correlated with pyridinic N. Consequently, our findings suggest that raw materials rich in carboxyl groups and amino groups are beneficial to the synthesis of CDs with high QY, and whether CDs with crosslinked structure and high content of pyridinic N decide the high PY of CDs. This work provides a theoretical guidance for large-scale synthesis of CDs with high QY and high PY.

Carbon dots (CDs) with high quantum yield (QY) and product yield (PY) were achieved benefited from higher content of C O bond, pyrrolic N, and pyridinic N, as well as lower content of amino N and crosslinking structure of CDs.     

小鼠海马结构与脊髓损伤后抑郁症高发病率的关系研究

目的:探究脊髓损伤引发的抑郁高风险率是否与海马生理结构的改变有关。方法:制作小鼠脊髓损伤模型,分别在损伤后不同时期采用Basso Mouse Scale(BMS)评分对小鼠术后运动功能进行评估;并通过糖水偏好实验和悬尾实验评估小鼠的抑郁情况;HE染色观察海马组织内部细胞的变化;电镜观察海马亚细胞结构突触的结构变化;RT-qPCR检测突触蛋白标志物突触小泡蛋白(SYP)和突触后致密蛋白95(PSD-95)在mRNA水平上的变化。结果:行为学实验显示模型组小鼠有显著的抑郁行为,且在第7天抑郁程度最显著(P<0.01);HE染色显示,与对照组相比,模型组海马细胞排列紊乱,数量减少,形态欠规则;电镜结果显示,与对照组相比,模型组海马超微结构突触数量减少,突触活动区长度变短,突触后致密物厚度变薄,突触间隙宽度增加,突触界面曲率减小(P<0.05);RT-qPCR结果显示模型组SYP和PSD-95 mRNA表达水平较对照组降低(P<0.05)。结论:海马生理结构的改变是脊髓损伤后抑郁症高风险的原因之一。     

A carboxylesterase-activatable near-infrared phototheranostic probe for tumor fluorescence imaging and photodynamic therapy

Phototheranostic probes have been proven to be a promising option for cancer diagnosis and treatment. However, near-infrared phototheranostic probes with specific tumor microenvironment responsiveness are still in demand. In this paper, a carboxylesterase (CES)-responsive near-infrared phototheranostic probe was developed by incorporating 6-acetamidohexanoic acid into a hemicyanine dye through an ester bond. The probe exhibits highly sensitive and selective fluorescence enhancement towards CES because CES-catalyzed cleavage of the ester bond leads to the release of the fluorophore. By virtue of its near-infrared analytical wavelengths and high sensitivity, the probe has been employed for endogenous CES activatable fluorescence imaging of tumor cells. Moreover, under 660 nm laser irradiation, the probe can generate toxic reactive oxygen species and efficiently kill tumor cells, with low cytotoxicity in dark. As far as we know, the probe was the first CES-responsive phototheranostic probe with both near-infrared analytical wavelengths and photosensitive capacity, which may be useful in the real-time and in situ imaging of CES as well as imaging-guided photodynamic therapy of tumors. Therefore, the proposed probe may have wide application prospect in cancer theranostics.

A carboxylesterase-responsive near-infrared phototheranostic probe is developed, which has been employed for activatable fluorescence imaging of tumor cells. The probe triggers significant cell death upon 660 nm laser, with low cytotoxicity in dark.     

基于社交网络服务的医学图书馆健康信息服务模式构建

介绍医学图书馆健康信息服务现有模式,分析医学图书馆基于社交网络服务提供健康信息服务的必要性和可行性,构建包含服务主体、对象、内容、渠道4个关键要素的基于社交网络服务的医学图书馆健康信息服务模式,以期为医学图书馆健康信息服务提供理论创新和实践指导.     

心脑血管疾病用药不良反应与药品品种关系的聚类分析

目的寻找心脑血管疾病用药的不良反应与药品品种间聚类关系,促进临床安全合理用药。方法运用数据挖掘技术中的两阶段聚类算法对药品的严重不良反应与药品品种间的关系进行聚类分析。结果由聚类结果可知,在使用心脑血管疾病用药时,出现的严重和新的严重不良反应为肝功能异常、肾功能异常、呼吸困难、横纹肌溶解,导致这些严重不良反应的药物有受体类药物、钙离子拮抗剂、降低胆固醇类药物。结论在选择心脑血管疾病用药时,受体类药物、钙离子拮抗剂、降低胆固醇类药物应慎用、少用,尽量避免严重的不良反应发生。     

反相高效液相色谱法同时检测肉汤培养基（CM129）中左氧氟沙星和阿奇霉素的药物浓度

目的：建立使用HPLC同时测定CM129培养基中左氧氟沙星和阿奇霉素的药物浓度的方法,为检测阿奇霉素促进左氧氟沙星透过生物膜实验提供检测方法。方法：色谱柱为Waters反相C18柱,流动相为甲醇-磷酸二氢钾缓冲液（29∶71,pH 2.53）,流速1.0 ml/min,检测波长210 nm,内标为西司他丁钠。结果：本法在10～160μg/ml范围内左氧氟沙星及阿奇霉素呈线性,相关系数r分别为0.999 9和0.999 9,平均回收率分别为99.83%和100.34%,RSD分别为1.08%和0.47%,在此范围内检测结果重复性良好。结论：该方法适合同时检测肉汤培养基中左氧氟沙星和阿奇霉素的药物浓度。