Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Glycine‐modified growth hormone secretagogues identified in seized doping material

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography–high resolution mass spectrometry (LC–HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP‐2 (Pralmorelin), GHRP‐6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1–29), which can be used as performance‐enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N‐terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.     

《黄帝内经》影响下的《金匮要略》“气化观”探析

探究《黄帝内经》影响下的《金匮要略》"气化观"。运用历史考察、文本分析等文献研究方法，对先秦两汉文化背景下，《黄帝内经》等著作中"气化"这一概念所体现的哲学、医学内涵进行分析，从道、法、术3个层面揭示在其影响下的《金匮要略》"气化观"的形成原因。秦汉哲学认为"气化"是宇宙万物生成的原因和运动的法则，古代医学认为人体气化遵循天地四时阴阳、五行的运行方式，这些都影响了《金匮要略》健康观、诊疗观及其遣方用药原则的形成。《黄帝内经》对《金匮要略》气化理论的构建产生重要影响。     

基于“气道神经源性炎症-TRP通路”探讨慢性咳嗽发病机制及中医治疗

咳嗽临床常见，尤其是胸部影像学无明显异常的慢性咳嗽，病因复杂、易误诊误治，逐渐受到重视，国内外相继颁发相关指南，目前认为咳嗽高敏感性是其重要的病理生理机制。中医将慢性咳嗽归于"久咳""久嗽"范畴，在病因病机、治法方药上积累了丰富的临床经验，史利卿教授团队针对该病开展了专项临床及基础研究15年，根据传统中医理论及其突出临床症状提出"风邪伏肺"病机，应用祛风宣肺法治疗效果显著。文章结合西医学相关咳嗽机制研究进展及既往研究结果，初步探讨祛风宣肺法治疗该病的疗效机制，丰富慢性咳嗽风邪伏肺致咳相关学术理论的科学内涵，有利于提高中医药防治慢性咳嗽学术水平。     

Chronic inflammation and risk of lung cancer in older adults in the health,aging and body composition cohort study

Objectives

We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.     

Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C‐terminal domain

Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT₁ and MT₂, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT₁ and MT₂. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT₁ and MT₂ by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT₁ or MT₂. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT₂ expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies.