Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update

As we know, inflammatory and oxidative stresses have a role in the pathogenesis of cardiovascular disease. This knowledge has triggered many investigations targeted to inflammatory markers. One such example, the neutrophil to lymphocyte ratio (NLR), is an inexpensive and easily accessible inflammatory marker whose role in cardiovascular disease has been studied extensively in the past few years. The neutrophil lymphocyte ratio has been shown to predict cardiac arrhythmias as well as short- and long-term mortality in patients with acute coronary syndromes (ACS). It has correlated well with ACS risk prediction models such as the GRACE and SYNTAX scores. A higher NLR has also been associated with frequent congestive heart failure decompensation and long-term mortality. The neutrophil to lymphocyte ratio also appears to have a prognostic role in patients undergoing transaortic valve replacement and the progression of valvular heart diseases. Despite the science of inflammatory biomarkers having been described decades ago, NLR appears to be enjoying a renaissance as a cost-effective biomarker with immediate clinical predictability and prognostication.     

神经胶质-免疫机制在疼痛中的作用

疼痛产生和维持的机制研究一直局限于神经元及由此形成的网络,对组成神经系统的另一类细胞——神经胶质细胞关注甚少。神经胶质细胞在疼痛机制中的作用,是今后疼痛研究的新方向。作者通过探讨神经胶质-免疫机制在神经病理痛发生和维持中的作用,希望为今后镇痛药物研究提供新的靶点。     

Molecular Cloning,Domain Analysis and Homology Modeling of Toll-Like Receptor 3 from Barilius bendelisis (Ham.)

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Toll-like receptors (TLRs) are the evolutionarily conserved pattern recognition receptors that form an...     

Identification of C-C Chemokine Receptor 1 (CCR1) as the Monocyte Hemofiltrate C-C Chemokine (HCC)-1 Receptor

Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1α. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1α activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1α for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC₅₀ = 93 nM versus 1.3 nM for MIP-1α). Similarly, HCC-1 was less potent than MIP-1α in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was ∼100-fold lower than that of MIP-1α (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.     

血清PCT和sTREM-1对急性胰腺炎患者病情的评估价值

[目的]探讨血清降钙素原(PCT)和可溶性髓样细胞触发受体-1(sTREM-1)对急性胰腺炎(AP)患者病情的评估价值.[方法]选取2009年10月至2013年12月本院收治的AP患者367例,按照病情危重程度分为重症急性胰腺炎组(SAP组,n=187)及轻症急性胰腺炎组(MAP组,n=180),并选择同期健康者180例作为对照(对照组).比较三组的血清PCT和sTREM-1水平,采用Spearman等级相关分析方法分别研究PCT、sTREM-1与急性生理性及慢性健康状况(APACHEⅡ)评分、CT严重程度指数(CTSI)评分、Ranson评分、床旁急性胰腺炎严重程度(BISAP)评分的相关关系,通过受试者工作特征曲线(ROC)评价各指标对SAP的诊断意义.[结果]AP患者在入院后d1、d3、d7的PCT及sTREM-1浓度明显高于对照组(P＜0.05).SAP组在入院后d1、d3、d7的PCT及sTREM-1浓度均明显高于MAP组(P＜0.05).PCT与APACHEⅡ评分、CTSI评分、Ranson评分和BISAP评分均呈正相关(P＜0.05).PCT与sTREM-1的ROC曲线下的面积分别为0.962及0.843(P＜0.05).[结论]AP患者的血清PCT和sTREM-1水平均显著升高,且AP的病情越重,PCT和sTREM-1水平越高,是两个理想的早期诊断SAP的炎症指标,值得临床推广.     

大鼠糖皮质激素受体结构域酵母双杂交系统的构建

目的构建大鼠糖皮质激素受体(GR)各个结构域的酵母双杂交系统,以研究不同结构域在糖皮质激素非基因组效应的作用。方法采用RT-PCR方法扩增GR各个结构域基因片段,酶切回收,将其连接至酵母双杂交系统诱饵蛋白质粒载体pGADT7,构建重组质粒pGADT7-GRAB,pGADT7-GRCD,pGADT7-GRC,pGADT7-GRD,pGADT7-GREF,并经鉴定,测序,体外转录,翻译等方法验证。结果RT-PCR扩增的各GR结构域基因片段电泳后,大小正确,酶切回收后,与质粒pGADT7过夜连接,转化大肠杆菌DH5α,挑选重组质粒,测序结果与Genebank中GR序列比对完全正确。重组质粒经体外转录、翻译试验方法证实重组质粒中的GR基因片段能够正确合成各个GR结构域蛋白。结论构建大鼠糖皮质激素受体结构域酵母双杂交系统重组质粒,为研究糖皮质激素受体在非基因组效应中的作用奠定了基础。     

抗NMDA受体脑炎30例误诊分析

目的探讨抗N-甲基-D-天冬氨酸(N-methyl-D-asparate,NMDA)受体脑炎患者发病及临床特点。方法收集北京协和医院2011年3月—2014年7月诊治的30例抗NMDA受体脑炎患者的临床资料,包括首诊临床表现、是否合并畸胎瘤、脑脊液病毒学检测及免疫学特殊抗体检测结果等,对其进行回顾性分析。结果 30例早期表现无特异性,依出现频率表现为精神行为异常、癫痫发作或肢体不自主运动、发热、头痛、意识障碍,除1例首诊我院确诊外,29例曾于当地医院误诊为病毒性脑炎、精神疾病及癫痫予抗病毒治疗或联合控制癫痫治疗效果欠佳。本组均经抗NMDA受体抗体检测阳性明确诊断,初诊误诊率达100%,确诊时间(270.15±114.97)d。确诊后予糖皮质激素、丙种球蛋白及免疫抑制剂等治疗,合并畸胎瘤者予手术切除。预后与病程有一定相关性。结论临床医生应熟悉抗NMDA受体脑炎的早期常见临床表现,建议将早期抗NMDA受体抗体筛查作为高危人群鉴别诊断的常规检测项目,以提高早期诊断率,为患者赢得早期治疗时间,改善预后。     

RDW、NLR、hs-CRP检测对急性胰腺炎严重程度的评估价值

目的 探讨检测红细胞分布宽度（RDW）、中性粒细胞与淋巴细胞比值(NLR)、超敏C反应蛋白（hs CRP）水平对急性胰腺炎（AP）严重程度的评估价值。方法 根据中国急性胰腺炎诊治指南(2019年,沈阳)将175例AP患者分为轻症组和重症组。比较两组一般资料及相关指标水平。比较RDW、NLR、hs CRP及联合检测对AP严重程度的评估价值。结果 重症组RDW、NLR、hs CRP水平均高于轻症组(P<0.05)。RDW、NLR、hs CRP均可评估AP的严重程度,联合检测对AP严重程度的评估具有更高的诊断效能,其灵敏度、特异度分别为90.9%、90.8%,其曲线下面积明显高于RDW、NLR、hs CRP。结论 RDW、NLR、hs CRP 均可不同程度的评估AP的严重程度,联合检测可提高对AP严重程度的诊断效能。     

N-甲基-D-天门冬氨酸受体、脑缺血性损伤和运动训练

N-甲基-D-天门冬氨酸(NMDA)受体是一种离子型谷氨酸受体,与突触可塑性、皮质和海马神经元长时程增强和抑制效应等中枢神经系统的生理、病理过程相关。本文就近年来NMDA受体在脑缺血中所起作用的研究进展进行综述。     

Pharmacokinetic Evaluation of the Interactions of Amenamevir (ASP2151) with Ketoconazole,Rifampicin, Midazolam,and Warfarin in Healthy Adults

Introduction

Amenamevir is a nonnucleoside antiherpes virus compound available for treating herpes zoster infections. Four studies aimed to determine any potential interactions between amenamevir and ketoconazole, rifampicin, midazolam, or warfarin in healthy male participants.

Methods

Two studies were open-label studies that evaluated the effects of multiple doses of ketoconazole (400 mg) and rifampicin (600 mg) on the pharmacokinetics of a single oral dose of amenamevir. The other two studies were randomized, double-blind, parallel-group studies that evaluated the effects of multiple doses of amenamevir on the pharmacokinetics of a single dose of midazolam (7.5 mg) and warfarin (25 mg). A drug interaction was considered to occur if the 90% confidence interval (CI) of the least squares geometric mean ratio (GMR) of amenamevir to the comparator was outside the prespecified interval of 0.80–1.25.

Results

Interactions were observed between amenamevir and ketoconazole, rifampicin, and midazolam, but not between amenamevir and warfarin. After a single 400-mg dose of amenamevir, the GMRs of amenamevir plus ketoconazole or rifampicin versus amenamevir alone for C _max and the area under the plasma concentration–time curve from time zero to infinity (AUC_inf) were 1.30 (90% CI 1.17–1.45) and 2.58 (90% CI 2.32–2.87), respectively, for ketoconazole and 0.42 (90% CI 0.37–0.49) and 0.17 (90% CI 0.15–0.19), respectively, for rifampicin. Following multiple doses of amenamevir (400 mg), the GMRs of midazolam plus amenamevir versus midazolam alone for AUC_inf and C _max were 0.53 (90% CI 0.47–0.61) and 0.63 (90% CI 0.50–0.80), respectively. After a single dose of warfarin, the (S)-warfarin and (R)-warfarin mean C _max increased and mean AUC_inf decreased in the presence of amenamevir; however, the 90% CIs of the GMRs for these parameters remained within the predefined limits.

Conclusion

These findings confirm that amenamevir (as a cytochrome P450 3A4 substrate) can interact with ketoconazole or rifampicin, and (as a cytochrome P450 3A4 inducer) can interact with midazolam; however, no interaction between amenamevir and (S)-warfarin was observed, indicating that amenamevir is not an inducer of cytochrome P450 2C9.

Funding

Astellas Pharma.

Trial registration

EudraCT2007-002227-33 (study 15L-CL-008), EudraCT2007-002228-14 (study 15L-CL-009), EudraCT2007-002761-13 (study 15L-CL-010), and EudraCT2007-002779-14 (study 15L-CL-018).

     

Nogo的作用机制和受体干预

Nogo是一个与中枢髓磷脂结合的特异性的抑制因子。脊髓损伤后,少突胶质细胞和髓磷脂释放出Nogo-A到细胞外基质,抑制轴突再生。通过分析Nogo受体的细胞外分子干预、细胞内信息干预和基因干预,了解对Nogo受体介导的髓磷脂相关抑制因子的抑制,为脊髓损伤后轴突的再生提供了新的思路和方法。     

血清 sPDL1水平和外周血 NLR在判断晚期胆管癌患者生存预后中的意义

目的　探究血清可溶性细胞程序性死亡配体1（soluble programmed death-ligand 1,sPDL1）水平和中性粒 与淋巴细胞比值（neutrophil-to-lymphocyte ratio,NLR）在晚期胆管癌（biliary tract cancer,BTC）患者中生存预后 的意义。方法　2017 年2 月~2019 年3 月收集西安市第三医院144 例晚期BTC 且进行姑息化疗的患者临床资料,包 括sPDL1 水平,NLR,血小板与淋巴细胞比值（platelet-tolymphocyte ratio,PLR）以及全身免疫炎症指数（systemic immune-inflammation index, SII）。采用单纯随机抽样方法验证每项标志物的分界值,将患者分为发展组与稳定组。比 较不同组患者的sPDL1 水平及总生存时间（overall survival,OS）,分析影响患者生存预后的因素。结果　所有患者 OS 为9.12 个月（95% CI 8.24~11.41）,sPDL1 中值为1.19（0.04~7.31）ng/ml,平均为1.45±1.18 ng/ml。NLR,PLR 及SII 的中位值分别为2.58,141.78 和583.95。高水平sPDL1（≥ 0.96 ng/ml）患者的OS 少于低水平sPDL1 患者, 差异具有统计学意义（P ＜ 0.001）。高水平sPDL1（HR=2.048,95%CI=1.26~3.34,P =0.004）及NLR（HR=1.565, 95%CI=1.07~2.30,P =0.023）是患者预后较差的独立风险因素。结论　血清sPDL1 水平可以测定,且sPDL1 及NLR 在 晚期BTC 患者生存预后判断中具有重要临床意义。     

Evaluation of acute confusion (delirium)

Acute confusion in the elderly is a problem that has high prevalence with significant morbidity and mortality, and that may lead to institutional placement. It is imperative that delirium be recognized promptly and its underlying cause(s) identified and treated. Management requires a multifaceted approach that addresses the precipitating cause(s), maintenance and support of vital functions, management of behaviors with use of nursing staff and family, attention to the environment, and sometimes the use of appropriate psychotropic medication. Prompt treatment is likely to result in a return to normalcy.     

Increased age,neutrophil-to-lymphocyte ratio (NLR) and white blood cells count are associated with higher COVID-19 mortality

ObjectiveCoronavirus disease 19 (COVID-19) caused by the highly pathogenic SARS-CoV-2, was first reported from Wuhan, China, in December 2019. The present study assessed possible associations between one-month mortality and demographic data, SpO₂, underlying diseases and laboratory findings, in COVID-19 patients. Also, since recent studies on COVID-19, have focused on Neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor of the in-hospital death and a significant prognostic biomarker of outcomes in critically ill patients, in this study, we assessed predictive potential of this factor in terms of one-month mortality.MethodsPatients admitted to Imam Reza hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran, from March to June 2020, with positive RT-PCR results for SARS-CoV-2, were included in this study. Kaplan-Meier survival analysis and Cox proportional hazard model were used to respectively estimate one-month mortality since admission and determine factors associated with one-month mortality.ResultsIn this retrospective cohort study, 219 patients were included (137 men and 82 women (mean age 58.2 ± 16 and 57 ± 17.3 years old, respectively)). Hypertension, ischemic heart disease and diabetes were respectively the most common comorbidities. Among these patients, 63 patients were admitted to the ICU and 31 deaths occurred during one-month follow-up. With respect to mean peripheral capillary oxygen saturation (SpO₂), 142 patients had SpO₂ ≤ 90%. Based on our analysis, older age and increased Neutrophil-to-lymphocyte ratio (NLR), and White blood cells (WBC) count were associated with increased risk of one-month mortality. Patients with SpO₂ ≤ 90% had a 3.8-fold increase in risk of one-month death compared to those with SpO₂ > 90%, although the difference did not reach a significant level.ConclusionMultivariate analysis introduced age, WBC count, and NLR as predictors of one-month mortality in COVID-19 patients.