治伤巴布剂对大鼠创伤性软组织肿胀模型骨骼肌中AQP-1表达的影响

目的:观察治伤巴布剂对大鼠急性软组织损伤模型骨骼肌中AQP-1表达的影响.方法:SD大鼠54只,随机分成3组,分别为正常对照组、模型组和药物处理组.造模后1h、6h、1d、3d、5d、7d6个时相点处死动物,每组每个时相点3只,在标记的区域内肌肉组织取材,采用干湿比重法测定骨骼肌组织的含水量,应用Western Blot、qPCR法检测AQP-1蛋白及基因的表达水平,并进行相关分析.结果:检测的6个时相点中,模型组和药物处理组的肌肉组织含水量均高于正常对照组,在3d、5d、7d3个时相点,药物处理组的含水量低于模型组,药物处理组、模型组的AQP-1蛋白及基因表达水平均高于正常对照组,而药物处理组与模型组相比,差异具有统计学意义.结论:治伤巴布剂具有减轻急性软组织肿胀的作用,从而加速急性软组织损伤后修复的进程.     

可逆性后部白质脑病综合征患者临床表现与磁共振影像学特点分析

目的分析可逆性后部白质脑病综合征(RPLS)患者的临床表现及磁共振(MRI)影像学特点。方法回顾性分析115例RPLS患者的临床及影像学资料。结果 115例RPLS患者表现为血压升高(89.56%)、痫性发作(74.78%)、头痛(59.13%)、视觉障碍(32.17%)、神经系统体征(20.00%)和意识改变(15.65%),其中101例(87.83%)患者头颅MRI异常,累及枕叶(71.29%)、顶叶(59.40%)、额叶(49.50%)、颞叶(38.26%)、侧室脑旁(1.98%)、脑干(3.96%)、小脑(3.96%)、皮质(3.96%)、丘脑(0.99%)、基底节区(0.99%),病灶为等或低T1WI信号,高T2WI信号,等或低DWI信号,高ADC及FLAIR信号。治疗后随访3～60月,81例预后良好,21例预后不良,5例死亡。预后不良组头痛发生率、住院期间m RS评分≥3分及并发症比例高于预后良好组(P<0.05)。结论 RPLS的MRI表现具有特征性,结合临床表现可作出正确判断,及时治疗,改善预后。     

Anti-tumor pharmacology of natural products targeting mitosis

Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer’s main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.     

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8⁺ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.     

An integrated strategy for the comprehensive profiling of the chemical constituents of Aspongopus chinensis using UPLC-QTOF-MS combined with molecular networking

ContextThe extracts of Aspongopus chinensis Dallas (Pentatomidae), an insect used in traditional Chinese medicine, have a complex chemical composition and possess multiple pharmacological activities.ObjectiveThis study comprehensively characterizes the chemical constituents of A. chinensis by an integrated targeted and untargeted strategy using UPLC-QTOF-MS combined with molecular networking.Materials and methodsThe ultra-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with molecular networking-based dereplication was proposed to facilitate the identification of the chemical constituents of aqueous and ethanol extracts of A. chinensis. The overall strategy was designed to avoid the inefficiency and costliness of traditional techniques. The targeted compounds discovered in the A. chinensis extracts were identified by searching a self-built database, including fragment ions, precursor ion mass, and other structural information. The untargeted compounds were identified by analyzing the relationship between different categories, fragmentation pathways, mass spectrometry data, and the structure of the same cluster of nodes within the molecular network. The untargeted strategy was verified using commercial standard samples under the same mass spectrometry conditions.ResultsThe proposed integrated targeted and untargeted strategy was successfully applied to the comprehensive profiling of the chemical constituents of aqueous and ethanol extracts of A. chinensis. A total of 124 compounds such as fatty acids, nucleosides, amino acids, and peptides, including 74 compounds that were reported for the first time, were identified in this study.ConclusionsThe integrated strategy using LC tandem HRMS combined with molecular networking could be popularised for the comprehensive profiling of chemical constituents of other traditional insect medicines.     

The effect of apolipoprotein E gene polymorphism and Lp(a) levels on coronary artery disease with atrial fibrillation

ObjectiveTo explore the influence of apolipoprotein E (APOE) genotypes and blood lipid metabolism on coronary artery disease (CAD) with atrial fibrillation (AF).MethodsPatients with suspected CAD were consecutively enrolled and divided into groups with or without CAD and/or AF. Blood lipid levels and APOE genotypes were determined and analysed for associations with CAD and AF.ResultsA total of 2048 patients were included (400 patients without CAD or AF [controls], 126 patients without CAD but with AF, 1294 patients with CAD without AF, and 228 patients with CAD and AF). Age and lipoprotein (a) (Lp[a]) levels were significantly higher in patients with CAD and AF versus those with CAD without AF. Among patients with CAD, the E3/E3 genotype and ε3 allele frequencies were significantly lower in patients with AF than in those without AF, and the E4/E4 genotype and ε4 allele frequencies were significantly increased. Multivariate logistic regression revealed that increased Lp(a) levels and age were independent risk factors for AF in patients with CAD.ConclusionAmong patients with CAD, those with AF had increased age, ε4 frequencies and Lp(a) levels. Age and Lp(a) levels may be independent risk factors for AF in patients with CAD.     

简易小鼠镇咳实验法

本文报告了一项简易的小鼠镇咳实验方法,系利用恒压条件下喷氢氧化铵气雾,引起小鼠咳嗽反应,并以引起半数小鼠咳嗽的喷雾时间(EDT₅₀)为指标。本法能比较稳定地反映出已知止咳药的作用和作用强度。曾用本法筛选出杜鹃酮、止咳酮,金丝桃甙等得到临床证实的新止咳药。本法简便、快速、耗药量少,节省动物,适用于作大量筛选试验。     

骨髓干细胞移植治疗缺血性心脏病的研究进展

干细胞具有自我更新，多向分化能力，在适宜的体外培养中干细胞能够稳定生存增殖并保持多向分化潜能，是便于体外操作的理想的靶细胞。本综合近几年国内外献，阐述了骨髓干细胞通过移植技术移植至试验动物的病损心脏，可以分化增殖为心肌细胞和血管结构，从而改善缺血的心脏功能。因此具有广阔的临床应用前景，值得进一步研究。     

Feasibility of sentinel lymph node biopsy omission after integration of 18F-FDG dedicated lymph node PET in early breast cancer:a prospective phase Ⅱ trial

Objective:Sentinel lymph node biopsy(SLNB) is currently the standard of care in clinically node negative(cN0) breast cancer.The present study aimed to evaluate the negative predictive value(NPV) of ¹⁸F-FDG dedicated lymph node positron emission tomography(LymphPET) in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients ...