2型糖尿病患者不同脂质参数与糖尿病肾病的关系

目的:探讨2型糖尿病(T2DM)患者不同脂质参数与糖尿病肾病(DKD)发生的相关性。方法:检测226例T2DM患者血清TC、TG、LDL-C、HDL-C水平及相关生化指标,计算血浆致动脉硬化指数(AIP)以及脂质三角相关指标(TC/HDL-C、TG/HDL-C、LDL-C/HDL-C)。根据DKD临床诊断标准和Mogensen分期标准分为:Ⅰ~Ⅱ期组136例,Ⅲ期组55例,Ⅳ~Ⅴ期组35例。应用多因素logistic回归分析不同脂质参数与DKD发生的关系。结果:与Ⅰ~Ⅱ期组相比,随着DKD分期加重,TC、TG、LDL-C、LDL-C/HDL-C、AIP水平明显增高(P<0.01)。LDL-C/HDL-C和AIP与24 h尿蛋白水平呈正相关(r=0.724;r=0.769,均P<0.05)。LDL-C/HDL-C和AIP是T2DM合并DKD患者的独立预测因子(P=0.002;P=0.004)。结论:LDL-C/HDL-C和AIP对T2DM合并DKD病情进展有较高的预测价值,可为临床诊治提供参考。     

2009-2018年资阳市手足口病流行病学及病原学特征分析

目的 研究2009-2018年资阳市手足口病的流行病学及病原学特征，为有效防控手足口病提供理论依据。方法 从中国疾病控制中心监测信息报告管理系统获取以乡镇为单位的手足口病数据，进行三间分布描述，利用ArcGIS 10.1软件制作专题地图。结果 资阳市2009-2018年累计报告病例19195例，年平均发病率为61.72/10万，虽总体上呈升高的趋势；各乡镇均有手足口病报告；每年有两个发病高峰，分别是5-7月和9-11月，其中5-7月为主高峰，9-11月为次高峰；男女性别比为1.44[DK]∶1，5岁以下儿童共发病18209例，占比为94.9%。2015年之前优势毒株为EV71和CoxA16，2015年之后优势毒株为其他肠道病毒。结论 资阳市手足口病发病呈持续升高态势。手足口病的优势毒株近年来在改变，应增加人肠道病毒的监测种类，落实综合性防控措施，预防和控制手足口病的流行。     

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

HER2-positive advanced breast cancer treatment in 2020

HER2-positive breast cancer is an aggressive subtype identified in the 1980s. The development of therapies targeting the HER2 has improved outcomes. The current standard of care, established in 2012 is dual blockade with trastuzumab + pertuzumab as first-line followed by TDM-1 as second-line. Several suboptimal choices are available in third-line or more. In 2019 the presentation of several trials evaluating new drugs and regimens in third-line has re-opened questions about sequencing, treatment of triple positive disease and treatment choice after exposure to TDM-1. These include tucatinib, neratinib and trastuzumab-deruxtecan. Other agents – including other antibody drug conjugates and bispecific antibodies as well as combinations - will lead to further changes in coming years. Additionally, should the numerous putative biomarkers thus identified ever come into use at the clinic, choice of treatment and response evaluation may be substantially changed.     

美托洛尔用于老年COPD合并冠心病史治疗的临床疗效观察

目的:探讨美托洛尔(β1受体阻滞剂)用于老年COPD合并冠心病史治疗的临床疗效。方法:选取2018年6月—2019年6月在我院接受治疗的60岁以上(包括60岁)COPD合并冠心病史老年患者,分为对照组与观察组。对照组给予接受布地奈德福莫特罗粉吸入剂治疗,观察组在使用布地奈德福莫特罗粉吸入剂治疗的基础上口服琥珀酸美托洛尔缓释片治疗,观察对比两组治疗效果。结果:观察组临床治疗效果优于对照组,观察组住院时长以及并发症的发生率低于对照组(P<0.05),差异具有统计学意义。结论:老年COPD合并冠心病史接受美托洛尔治疗,可有效缩短住院时长、用药效果明显、有效提升用药安全性,值得临床推广。     

Association of four CpG-SNPs in the vascular-related genes with coronary heart disease

Vascular-related gene polymorphism can affect the susceptibility of coronary heart disease. In current study, we aimed to evaluate the contribution of four vascular-related gene CpG-SNPs to coronary heart disease (CHD). A total of 784 angiography-proven CHD patients and 746 non-CHD controls were included in the current association study. The four CpG-SNPs (including VEGFA rs1005230, ACE rs4316, CST3 rs3827143 and AGTR1 rs275653) were genotyped using the Sequenom MassARRAY platform. All genotype distribution of four SNPs met HWE. Among the four CpG-SNPs, none was found to be associated with CHD on both genotype and allele levels. Further subgroup tests by age or gender were unable to observe any significant associations of them with CHD. Our case-control study showed that none of four CpG-SNPs in the vascular-related genes was associated with the risk of CHD in Han Chinese, although we could not exclude other genetic variants of these vascular-related genes with contribution to CHD.     

The association between the decreased expression levels of FOXJ1 and the activation of NF-κB pathway in interstitial lung disease of MRL/Lpr mice

Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between decreased expression levels of Forkhead Box J1 (FOXJ1) and the activation of the NF-κB pathway in autoimmune pulmonary inflammation of MRL/Lpr mice. Methods: The female BALB/c mice (n=6) and MRL/Lpr mice (n=30) were divided into 5 groups including a control group (BALB/c), and five MRL/Lpr mice groups (8W, 12W, 16W, 24W, and 32W). The infiltration of the inflammatory cells was determined in lung tissue by performing the histological analysis. The western blotting was used to examine the expression levels of the age-related FOXJ1, and p50 and p65 proteins in the lungs of MRL/Lpr mice. The expression levels of MMP2 and MMP9 were determined via immunohistochemistry and immunofluorescence. Results: There were severe infiltrates of lung cells with high levels of tracheal damage, perivascular injury and interstitial inflammatory cell infiltration when the MRL/Lpr mice from 16w to 32w comparing to the 8w old healthy MRL/Lpr mice in the control group (p <0.05). Moreover, the reduced expression levels of FOXJ1 were associated with the activation of the NF-κB pathway in interstitial lung disease of MRL/Lpr mice via the modulation of p50 and p65. In addition, the expression levels of MMP2 and MMP9 pro-inflammation factors increased in the lungs of the MRL/Lpr mice from 16w to 32w. Conclusions: The expression level of FOXJ1 might be an indicator of the degree of lung disease in lupus-prone mice.