The synthetic antimicrobial peptide LTX21 induces inflammatory responses in a human whole blood model and a murine peritoneum model

The global spread of antimicrobial resistance and the increasing number of immune‐compromised patients are major challenges in modern medicine. Targeting bacterial virulence or the human host immune system to increase host defence are important strategies in the search for novel antimicrobial drugs. We investigated the inflammatory response of the synthetic short antimicrobial peptide LTX21 in two model systems: a human whole blood ex vivo model and a murine in vivo peritoneum model – both reflecting early innate immune response. In the whole blood model, LTX21 increased the secretion of a range of different cytokines, decreased the level of tumour necrosis factor (TNF) and activated the complement system. In a haemolysis assay, we found 2.5% haemolysis at a LTX21 concentration of 500 mg/L. In the murine model, increased influx of white blood cells (WBCs) and polymorphonuclear neutrophils (PMNs) in the murine peritoneal cavity was observed after treatment with LTX21. In addition, LTX21 increased monocyte chemoattractant protein‐1 (MCP‐1). In conclusion, LTX21 affected the inflammatory response; the increase in cytokine secretion, complement activation and WBC influx indicates an activated inflammatory response. The present results indicate the impact of LTX21 on the host–pathogen interplay. Whether this will also affect the course of infection has to be investigated.     

From micro‐ to macro‐structures in multiple sclerosis: what is the added value of diffusion imaging

Diffusion imaging has been instrumental in understanding damage to the central nervous system as a result of its sensitivity to microstructural changes. Clinical applications of diffusion imaging have grown exponentially over the past couple of decades in many neurological and neurodegenerative diseases, such as multiple sclerosis (MS). For several reasons, MS has been extensively researched using advanced neuroimaging techniques, which makes it an ‘example disease’ to illustrate the potential of diffusion imaging for clinical applications. In addition, MS pathology is characterized by several key processes competing with each other, such as inflammation, demyelination, remyelination, gliosis and axonal loss, enabling the specificity of diffusion to be challenged. In this review, we describe how diffusion imaging can be exploited to investigate micro‐, meso‐ and macro‐scale properties of the brain structure and discuss how they are affected by different pathological substrates. Conclusions from the literature are that larger studies are needed to confirm the exciting results from initial investigations before current trends in diffusion imaging can be translated to the neurology clinic. Also, for a comprehensive understanding of pathological processes, it is essential to take a multiple‐level approach, in which information at the micro‐, meso‐ and macroscopic scales is fully integrated.     

Real‐time multi‐directional flow MRI using model‐based reconstructions of undersampled radial FLASH – A feasibility study

The purpose of this work was to develop an acquisition and reconstruction technique for two‐ and three‐directional (2d and 3d) phase‐contrast flow MRI in real time. A previous real‐time MRI technique for one‐directional (1d) through‐plane flow was extended to 2d and 3d flow MRI by introducing in‐plane flow sensitivity. The method employs highly undersampled radial FLASH sequences with sequential acquisitions of two or three flow‐encoding datasets and one flow‐compensated dataset. Echo times are minimized by merging the waveforms of flow‐encoding and radial imaging gradients. For each velocity direction individually, model‐based reconstructions by regularized nonlinear inversion jointly estimate an anatomical image, a set of coil sensitivities and a phase‐contrast velocity map directly. The reconstructions take advantage of a dynamic phase reference obtained by interpolating consecutive flow‐compensated acquisitions. Validations include pulsatile flow phantoms as well as in vivo studies of the human aorta at 3 T. The proposed method offers cross‐sectional 2d and 3d flow MRI of the human aortic arch at 53 and 67 ms resolution, respectively, without ECG synchronization and during free breathing. The in‐plane resolution was 1.5 × 1.5 mm² and the slice thickness 6 mm. In conclusion, real‐time multi‐directional flow MRI offers new opportunities to study complex human blood flow without the risk of combining differential phase (i.e., velocity) information from multiple heartbeats as for ECG‐gated data. The method would benefit from a further reduction of acquisition time and accelerated computing to allow for extended clinical trials.     

Effectiveness of a health belief model intervention using a lay health advisor strategy on mouth self-examination and cancer screening in remote aboriginal communities: A randomized controlled trial

ObjectiveOral cancers caused by chewing betel nuts have a poor prognosis. Using a lay health advisor (LHA) can increase access to health care among underprivileged populations. This study evaluated a health belief model (HBM) intervention using LHAs for oral cancer screening (OCS) and mouth self-examination (MSE) in remote aboriginal communities.MethodsThe participants were randomly assigned to intervention (IG; n = 171) and control groups (CG; n = 176). In the IG, participants received a three-chapter one-on-one teaching course from LHAs, whereas those in the CG received only a leaflet.ResultsThe IG participants were 2.04 times more likely to conduct a monthly MSE than those in the CG (95% confidence interval: 1.31–3.17) and showed significantly higher self-efficacy levels toward OSC and MSE (β = 0.53 and 0.44, effect size = 0.33 and 0.25, respectively) and a lower barrier level for OSC (β = −1.81, effect size = −0.24).ConclusionThe LHA intervention had a significantly positive effect on MSE, strengthening self-efficacy and reducing barriers to OCS among aboriginal populations.Practice ImplicationsThe effectiveness of the clinical treatment of underprivileged group can be improved through early diagnosis, which can be achieved using LHAs to reduce barriers to OSC.     

A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion

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麻黄细辛附子汤对肾阳虚外感小鼠及正常小鼠的效-毒作用研究

目的研究麻黄细辛附子汤(MXF)干预肾阳虚外感小鼠的药效作用及其对正常小鼠的毒性作用差异,并考察其效-毒作用机制。方法BABL/C雄性小鼠随机分为正常组、正常毒性低、中、高剂量组;肾阳虚外感模型组;肾阳虚外感低、中、高剂量组,连续灌胃给药6 d,记录体重、肛温等药理指标并观察小鼠的一般体征,检测生化指标、炎症因子。结果药效实验中,与正常组小鼠相比,肾阳虚外感模型组小鼠生化指标肌酸激酶(CK)、肌酸激酶-同工酶(CK-MB)、羟丁酸脱氢酶(α-HBDH)、乳酸盐脱氢酶(LDH)、丙氨酸氨基转移酶(ALT)、天冬氨酸转移酶(AST)、碱性磷酸酶(ALP)、尿素(urea)含量明显升高(P<0.05),炎症因子白介素-6(IL-6)、单核细胞去化蛋白(MCP-1)、肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10)、干扰素-γ(INF-γ)以及白介素12(IL-12p70)含量升高明显(P<0.05)。经给药治疗后,各给药组CK、ALT、urea等生化指标含量较模型组有所回调,各给药组IL-6、IL-10、IFN-γ等炎症因子含量较模型组有不同程度的回调;毒性研究中,各给药组生化指标CK、urea、半胱氨酸(CYS-C)的含量较正常组显著升高(P<0.05),炎症因子白介素-10(IL-10)含量明显上升、白介素-12(IL-12p70)含量明显下降(P<0.05)。结论经MXF给药治疗后,肾阳虚外感给药组小鼠的一些生化指标均有不同程度的回调,MXF可通过调节IL-6、IL-10、IFN-γ、MCP-1、肿瘤坏死因子-α(TNF-α)等炎症因子改善机体的炎症反应;而正常小鼠给予不同剂量的MXF后心脏、肝脏和肾脏功能出现失调,机体通过细胞转移、打破免疫应答的平衡,从而使正常小鼠出现炎症反应。     

针刺手法效应规律及神经电信息机制研究

针刺手法是影响针刺疗效的关键,然而其作用规律、机制尚不完全清楚。天津中医药大学实验针灸学研究中心郭义教授团队与天津大学电气自动化与信息工程学院王江教授团队,长期以来围绕针刺手法作用规律及神经电信息机制开展合作研究,构建了常见针刺手法的数学模型,用数学语言解析了针刺手法操作过程,实现了针刺手法的科学表征;揭示了基于神经电信息的针刺手法部分作用规律;刻画了针刺手法电信号的非线性动力学特征,明确不同针刺手法诱发神经电信息编码存在差异,是针刺手法效应差异的机制之一。研究成果为针刺手法的科学性奠定了提供了实验依据,对针刺手法的传承、应用和发展具有促进作用。     

医教协同模式对强化本科生临床实践作用的探索

“医教协同”模式强调医学基础与临床课程整合，以提升医学生临床思维和临床实践能力。5年制本科医学教育作为“5+3”医学教育连续体的第一阶段，在临床课程教学过程中存在理论与实践分离、教学保障体系不完善和学生自主学习能力不强等现实问题。通过围绕如何提高5年制临床医学本科生培养质量，从统一思想认识、注重顶层设计、夯实师资队伍、优化教学条件、加强督导考评等方面，持续强化以培养岗位胜任力为目标的教学改革，可为培养全面发展的应用型临床医学人才打下坚实基础。     

2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione,isolated from the root of Averrhoa carambola L., protects against diabetic kidney disease by inhibiting TLR4/TGFβ signaling pathway

ObjectiveDiabetic kidney disease (DKD) is the leading cause of death and disability of diabetes mellitus. However, there is still a lack of specific drugs for the treatment of DKD. The chief aim of this research is to investigate the role and mechanism of 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) for DKD.MethodsWild type and TLR4 knockout mice were induced to diabetes. After 4-week treatment with DMDD, blood sugar, renal function, blood lipid and pathological changes were assessed. Real-time PCR, western blotting, and immunohistochemistry were employed to detect the expressions of TLR4, TGFβ1 and Smad2/3 in the renal tissue.ResultsDMDD improved the serum lipid and decreased fasting blood glucose levels in diabetic mice. CysC and urinary albumin levels increased markedly in the diabetic group, and they were obviously decreased after 4 weeks of DMDD treatment. Compared with the WT diabetic mice, the urinary albumin and CysC in the TLR4^-/- mice were expressed at lower levels. HE and Masson’s staining revealed that DMDD clearly ameliorated pathological changes and renal fibrosis. When TLR4 gene was knock out, the pathological was improved. Mechanistically, TLR4, TGF-β1 and Smad2/3 were obvious up-regulation in the renal tissues of diabetic mice. The expressions of these proteins were significantly down-regulated after DMDD treatment (p < 0.05). In the TLR4^-/- mice, mRNA and protein levels of TGF-β1 and Smad2/3 were obviously lower than those in the WT mice. In addition, IHC revealed that a strong in situ expressions of TLR4, TGF-β1 and Smad2/3 were seen in the kidney tissues of diabetic mice, which were distinctly weakened in the DMDD-treated mice. In the TLR4^-/- mice, however, expressions of TGF-β1 and Smad2/3 were not remarkable increase in the diabetic mice compared with normal mice.ConclusionsThese results strongly indicate that TLR4 is essential for DMDD protection against renal dysfunction in diabetic mice. Its hypoglycemic and anti-fibrosis effects were likely mediated by the TLR4/TGFβ signaling pathway.