NLR对卒中预警综合征患者预后的预测价值

目的 研究中性粒细胞与淋巴细胞比值( neutrophil–lymphocyte ratio, NLR) 对卒中预警综合征(stroke warning syndrome, SWS)患者预后的预测价值。方法 回顾性连续纳入2013年7月至2020年1月于我院住院治疗的SWS患者83例,根据改良Rankin 量表(modified Rankin Scale, mRS)评分,分为预后良好组(mRS≤2分)71例和预后不良组( mRS＞2分)11例。记录患者基本临床特点、实验室及影像学等资料,根据急诊血常规计算NLR值。采用Logistics 回归分析SWS预后不良的影响因素,受试者工作特征(receiver operating characteristic, ROC)曲线评价NLR值对SWS患者预后的预测作用。结果 SWS患者平均年龄59.1±13.11岁,65例患者明确新发脑梗死。预后不良组患者入院NIHSS评分、NLR值均高于预后良好组,但血红蛋白水平较预后良好组低,差异有统计学意义(均P＜0.05)。两组间ABCD2评分、是否溶栓及有无新发梗死的比例没有统计学差异(均P＞0.05)。多因素Logistics 回归分析显示入院NIHSS评分(OR 1.463, 95%CI 1.154-1.856, P=0.002)和NLR值(OR 2.045, 95%CI 1.068-3.916, P=0.031)是SWS患者预后不良的独立危险因素。ROC分析显示当诊断界值为2.82时,曲线下面积为0.753,NLR值对SWS患者预后不良诊断的敏感度为72.7%,特异度为81.9%。结论 较高的入院NIHSS评分和NLR值与SWS患者预后不良独立相关,且NLR值对SWS患者预后不良具有中度诊断价值。     

The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

Transient receptor potential (TRP) channels are one primary type of calcium (Ca²⁺) permeable channels, and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems. Nowadays, however, accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression, inducing tumor invasion and metastasis. However, the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive. Therefore, in this review, we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance (MDR), metastasis, apoptosis, proliferation, immune surveillance evasion, and the alterations of relevant tumor micro-environment. Moreover, we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’ efficacy. The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented. Furthermore, it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.     

Effects of neutrophil-to-lymphocyte ratio,serum calcium,and serum albumin on prognosis in patients with diabetic foot

The purpose of this study is to investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR), serum calcium, and serum albumin on the prognosis of patients with diabetic foot. A total of 156 patients who were treated in the Department of Burn and Plastic Surgery of Qilu Hospital of Shandong University from 1 January 2014 to 1 August 2020 were selected. All the patients were randomly divided into a healing group, minor amputation group, major amputation group, and death group according to their treatment outcomes. The levels of NLR, serum calcium and serum albumin in each group were examined and compared. The correlations between NLR, serum calcium, and serum albumin with the prognosis of diabetic foot were analysed to investigate their predictive effects on the prognosis of diabetic foot. The results of one-way ANOVA showed that among the 4 groups of patients, the difference in NLR values between the healing group and the minor amputation group was slightly smaller, but they were significantly different from the major amputation group and the death group, respectively. There was no significant difference in serum calcium levels between the healing group and the minor amputation group, but the serum calcium levels of the major amputation group and the death group gradually decreased. The levels of NLR in the 4 groups gradually increased, while the albumin levels gradually decreased. Spearman's rank correlation test indicated that NLR was significantly related to the prognosis of patients with diabetic foot. The group with higher NLR had a worse prognosis in diabetic foot patients. Serum calcium and serum albumin were strongly correlated with the prognosis of patients with diabetic foot. The group with lower serum calcium and serum albumin values had a worse prognosis in diabetic foot patients. The areas under the receiver operator characteristic curve of NLR, serum calcium and serum albumin were 0.901, 0.803, and 0.816, respectively. NLR, serum calcium and serum albumin can be used as reliable indicators to predict the prognosis of diabetic foot. Preoperative diabetic foot patients with higher NLR values or lower serum calcium and serum albumin have a poorer prognosis.     

Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.     

Neutrophil-to-lymphocyte and hypopharyngeal cancer prognosis: System review and meta-analysis

Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also been published. We aimed to clarify the effect of NLR on the prognosis of hypopharyngeal cancer through meta-analysis. Systematic search of PubMed and other database with study selection and data extraction. The combined hazard ratio (HR) and 95% confidence intervals (CI) were calculated using STATA, applying either a fixed-effects or random-effects model. Meta-regression, subgroup analysis, and sensitivity analysis were used to analyze sources of heterogeneity. Publication bias were also assessed. This meta-analysis included 2232 patients with hypopharyngeal cancer from seven studies. The combined HR (OS, HR = 1.80, 95CI%, 1.14–2.82; PFS, HR = 1.88, 95CI%, 1.26–2.79) suggested that high NLR was associated with poor overall survival (OS) and progression-free survival (PFS). Pretreatment NLR can be used as an effective serological indicator to assess the prognosis of patients with hypopharyngeal cancer.     

NLR、PLR及LDL-C/HDL-C与急性冠脉综合症在院主要不良心脏事件的关联

【摘要】 目的 研究中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）及低密度脂蛋白与高密度脂蛋白比值（LDL-C/HDL-C）与急性冠脉综合症（ACS）在院主要不良心脏事件的关系，探讨NLR、PLR、LDL-C/HDL-C对ACS患者在院主要不良心脏事件发生的预测作用。方法 将340例患者依据临床症状、辅助检查及冠脉造影分为正常对照组及ACS组，ACS组以临床诊断及预后分为UA组、NSTEMI组、STEMI组、MACEs组；ACS组又以NLR=5.44分为高NLR组、低NLR组，以PLR=129.70分为高PLR组、低PLR组，以LDL-C/HDL-C=2.75分为高LDL-CL/HDL-C组、低LDL-C/HDL-C组。检测外周血白细胞分类计数、血生化并计算NLR、PLR和LDL-C/HDL-C，应用SPSS 22.0软件进行统计分析。结果 （1）NLR在正常对照组、UA组、NSTEMI组、STEMI组、MACEs组中依次升高，且两组指标比较差异有统计学意义（P<0.05）；PLR值在正常对照组、UA组、NSTEMI组、STEMI组、MACEs组依次升高，且MACEs组、STEMI组与正常对照组及UA组差异具有统计学意义（P<0.05）；ACS患者LDL-C/HDL-C值高于正常对照组LDL-C/HDL-C值，且两组之间差异有统计学意义(P<0.05)。（2）高NLR组患者在院主要不良心脏事件发生率明显高于低NLR组，两组间差异有统计学意义（P<0.05）；高PLR组患者在院主要不良心脏事件发生率高于低PLR组，两组间差异有统计学意义（P<0.05）。（3）多因素Logistic回归分析显示年龄、高血压、NLR、LDL-C/HDL-C均是ACS的独立危险因素。结论 NLR、LDL-C/HDL-C是ACS的独立危险因素，NLR、PLR对ACS患者在院发生主要不良心脏事件有预测作用。     

Similarities and differences in autoinflammatory diseases with urticarial rash,cryopyrin-associated periodic syndrome and Schnitzler syndrome

Cryopyrin-associated periodic syndromes (CAPS) and Schnitzler syndrome (SchS) are autoinflammatory diseases that present with urticaria-like rashes. CAPS is characterized by periodic or persistent systemic inflammation caused by the dysfunction of the NLRP3 gene. With the advent of IL-1-targeted therapies, the prognosis of CAPS has improved remarkably. SchS is considered an acquired form of autoinflammatory syndrome. Patients with SchS are adults of relatively older age. The pathogenesis of SchS remains unknown and is not associated with the NLRP3 gene. Previously, the p.L265P mutation in the MYD88 gene, which is frequently detected in Waldenström macroglobulinemia (WM) with IgM gammopathy, was identified in several cases of SchS. However, because persistent fever and fatigue are symptoms of WM that require therapeutic intervention, it is a challenge to determine whether these patients truly had SchS or whether advanced WM was misidentified as SchS. There are no established treatments for SchS. The treatment algorithm proposed with the diagnostic criteria is to use colchicine as first-line treatment, and systemic administration of steroids is not recommended due to concerns about side effects. In difficult-to-treat cases, treatment targeting IL-1 is recommended. If targeted IL-1 treatment does not improve symptoms, the diagnosis should be reconsidered. We hope that the efficacy of IL-1 therapy in clinical practice will serve as a stepping stone to elucidate the pathogenesis of SchS, focusing on its similarities and differences from CAPS.