Increased soluble TNF receptor 2 in antidepressant-free patients with late-life depression

Increased pro-inflammatory state has been implicated in the pathophysiology of major depressive disorder. The aim of this study was to determine serum levels of TNF-α and soluble TNF-α receptors 1 and 2 (sTNFR1 and sTNFR2) in anti-depressant free depressed elderly patients as compared to healthy controls. Sixty-seven older adults (28 with major depression and 39 controls) were enrolled to this study. Participants were assessed by the SCID and diagnosis of major depressive episode was made according to the DSM-IV criteria. Serum TNF-α, sTNFR1 and sTNFR2 were determined by ELISA. Anti-depressant free patients with late-life depression showed an increased level of the sTNFR2 as compared to controls (p = 0.03). No significant differences were found in serum TNF-α and sTNFR1 levels (p = 0.1 and p = 0.4, respectively). There was no correlation between serum levels of these inflammatory markers and the severity of depression. Our findings provide additional evidence of the involvement of abnormal pro-inflammatory state in late-life depression.     

AD患者外周血单核细胞中TLR-4表达 水平变化的临床意义

目的 探讨外周血单核细胞Toll样受体-4(Toll-like receptor 4,TLR-4)的表达水平变化与AD发病及进展的关系。方法 检测阿尔茨海默病(Alzheimer's disease,AD)及轻度认知功能障碍(Mild cognitive impairment,MCI)患者及同年龄正常对照者(Healthy Controls,HC)外周血单核细胞Toll样受体-4(Toll-like receptor 4,TLR-4)的表达水平; 采集并分离AD(n=28)、MCI(n=26)及NC组(n=20)外周血单核细胞; 用实时荧光定量PCR(Quantitative Real-Time,Q-PCR)、流式细胞术(Flow Cytometry)检测TLR-4的表达水平; 双抗体夹心法(Double antibody sandwich method,ELISA)检测各组血清中肿瘤坏死因子(Tumor necrosis factor-α(TNF-α)、白介素6(Interleukin 6,IL-6)的水平。结果 与HC组比较,AD患者外周血单核细胞TLR-4表达水平均明显上调(P均<0.05)。MCI组略有上升,但无统计学意义; AD患者外周血单核细胞TLR-4表达水平与血清TNF-a、IL-6水平呈正相关(r=0.3885和0.3270,P均<0.05)。结论 外周血单个核细胞TLR-4表达水平上调提示炎性机制在AD的发病中发挥了作用,TLR4可作为评估疾病进展的潜在生物学标志物。     

NGAL and other markers of inflammation as competitive or complementary markers for depressive symptom dimensions in heart failure

Objectives. Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory marker associated with the pathophysiology of heart failure (HF), the psychopathology of depression and the co-existing symptoms of depression in HF patients. The aim of this study is to determine whether the association of serum NGAL levels with depressive symptoms dimensions in HF is independent of well-known inflammatory markers. Methods. Serum NGAL, high sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α), its two soluble receptors; sTNFR1, sTNFR2, Interleukin-6 (IL-6) and leukocytes were measured in 104 patients with HF at baseline and 12 months. Depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at both timepoints. Correlations between NGAL and inflammatory markers and depressive symptoms dimensions were determined. The effect of hsCRP, IL-6, TNF-α, sTNFR1, sTNFR2 and leukocytes on the association of NGAL with depressive symptoms was determined and adjusted for time, demographics, cardiac disease severity, and kidney function. Results. NGAL levels were significantly correlated with hsCRP, TNF-α, sTNFR1, sTNFR2 and leukocytes. NGAL was significantly associated with somatic depressive symptoms, independent of abovementioned markers. Conclusions. Serum NGAL is an independent inflammatory marker for somatic depressive symptoms in HF and may function as an immunopathogen linking somatic symptoms of depression to HF.     

Macrophage migration inhibitory factor in mild cognitive impairment and Alzheimer’s disease

Inflammatory processes may substantially contribute to the cerebral pathology in Alzheimer’s disease (AD) and accelerate the disease progression. The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine which promotes the production of several inflammatory mediators such as TNF-α, IL-6 and IFN-γ, and plays a central regulatory role in the pathogenesis of several inflammatory and autoimmune diseases. There is now first evidence that MIF may be involved in the neuroinflammation in AD. To determine whether MIF production is up-regulated early in the course of AD, we compared the levels of MIF assessed by ELISA in the cerebrospinal fluid (CSF) of 31 patients with AD, 28 patients with amnestic mild cognitive impairment (MCI), and 19 subjects without cognitive deficits. Additionally, we measured the CSF concentrations of the inflammatory mediators TNF-α, IL-6 and IFN-γ, which are thought to be both up-regulated by MIF and involved in the pathophysiology of AD. CSF MIF concentrations were significantly increased in AD (p = 0.003) and MCI patients (p < 0.001) compared to controls. The levels of TNF-α, IL-6 and IFN-γ did not differ significantly between the groups. There was a correlation only between the concentrations of MIF and of TNF-α in the AD group (r = 0.407; p = 0.023). These results demonstrate increased MIF production in AD and MCI suggesting that MIF may be involved in the occurring neuroinflammatory process at a clinical pre-dementia disease stage.     

Increased levels of adipokines in bipolar disorder

Bipolar disorder (BD) is associated with considerable higher chronic medical comorbidities, overweight and obesity. Adipokines are adipocyte-derived secretory factors which have functions in immune response and seem to be associated with both BD and overweight. The aim of this study was to evaluate the plasma levels of adipokines (adiponectin, resistin and leptin) and TNF-α and its receptors (sTNFR1 and sTNFR2) in BD overweight patients in comparison with overweight controls. Thirty euthymic BD type-I patients and thirty controls matched by age, gender and body-mass index (BMI) were assessed by Mini-International Neuropsychiatric Interview, Young Mania and Hamilton Depression rating scales (YMRS and HDRS, respectively). Plasma levels of adiponectin, resistin, leptin, TNF-α and its soluble receptors were measured by ELISA. BD patients presented increased plasma levels of adiponectin (p < 0.001), leptin (p < 0.001) and sTNFR1 (p = 0.01). Plasma levels of adipokines were not correlated neither with clinical parameters nor TNF-α, sTNFR1 and sTNFR2 plasma levels. This study provides further support to the hypothesis of the immune/inflammatory imbalance in BD.     

Increased plasma levels of BDNF and inflammatory markers in Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Neurotrophic factors and inflammatory markers may play considerable roles in AD. In this study we measured, through Enzyme-Linked Immunosorbent Assay, the plasma levels of brain derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and neuronal growth factor (NGF), as well as tumor necrosis factor-alpha soluble receptors, sTNFR1 and sTNFR2, and soluble intercellular adhesion molecule 1 (sICAM-1), in 50 AD patients, 37 patients with mild cognitive impairment (MCI) and 56 healthy elderly controls. BDNF levels, expressed as median and interquartile range, were higher for AD patients (2545.3, 1497.4–4153.4 pg/ml) compared to controls (1503.8, 802.3–2378.4 pg/ml), P < 0.001. sICAM-1 was also higher in AD patients. sTNFR1 levels were increased in AD when compared to controls and also to MCI. GDNF, NGF and sTNFR2 levels showed no significant differences among the studied groups. The increase in BDNF might reflect a compensatory mechanism against early neurodegeneration and seems to be related to inflammation. sTNFR1 appears to mark not only the inflammatory state but also differentiates between MCI and AD, which may be an additional tool for differentiating degrees of cognitive impairment.     

Expression of 8-oxoguanine DNA glycosylase 1 (OGG1) and the level of p53 and TNF-αlpha proteins in peripheral lymphocytes of patients with Alzheimer's disease

The aim of the study was to determine the extent of oxidative DNA damage (levels of 8-oxo2dG) and expression of OGG1 and p53 and TNF-α proteins in lymphocytes of Alzheimer's disease (AD) patients and a control group. The studies were conducted on 41 patients with AD, including 25 women and 16 men aged 34-84 years. The control group included 51 individuals, 20 women and 31 men aged 22-83 years. The level of 8-oxo2dG was determined using HPLC/EC/UV, and the level of OGG1 and p53 and TNF-α proteins was determined with the Western blot method. The results showed that both proteins participating in DNA repair (OGG1, p53) and the inflammatory protein TNF-α are involved in pathogenesis of neurodegenerative diseases. It also seems that a specific system for DNA repair (OGG1) may contribute to downregulation of the inflammatory factor (TNF-α) level, especially in the early stages of dementia. Moreover, the results showed that p53 protein can fulfil its function in DNA damage repair only in early stages of dementia. It is possible that OGG1 and p53 and TNF-α proteins together or separately may be involved in pathogenesis of AD by repair of oxidative DNA damage and/or apoptosis.     

脑梗死患者血清TNF-α、IL-1β含量的变化及其临床意义的研究

目的　了解脑梗死患者血清TNF-α、IL-1β含量在恢复期和急性期的变化及意义。方法　运用双抗夹心酶联免疫吸附法（ELISA）测定血清中TNF-α、IL-1β的含量。结果　急性期、恢复期脑梗死患者血清TNF-α、IL-1β水平较对照组显著增高（P＜0.01）,急性期又较恢复期高（P＜0.05,P＜0.01）;增高程度与神经功能缺损程度及梗死体积大小密切相关。结论　TNF-α、IL-1β可能参与脑梗死早期的炎症反应及再灌注损伤,并在其中起重要作用。     

Blood levels of histamine,IL-1β, and TNF-α in patients with mild to moderate alzheimer disease

In this study, we have evaluated the levels of blood histamine, serum interleukin-1 beta (IL-1β), and plasma tumor necrosis factor-alpha (TNF-α) in 20 patients with mild to moderate Alzheimer disease (AD; 13 early onset and 7 late-onset AD subjects) and in 20 agematched control subjects (C). AD patients showed higher concentrations of histamine (AD=452.9±237.9 pmol/mL; C=275.3±151.5 pmol/mL;p<0.05) and IL-1β (AD=211.2±31.1 pg/mL; C=183.4±24.4 pg/mL;p<0.01), and lower values of TNF-α (AD=3.59±2.02 pg/mL; C=9.47±2.64 pg/mL;p<0.001) than elderly controls. Increased levels of histamine and decreased levels of TNF-α were observed in both early onset AD (EOAD) and late-onset AD (LOAD) patients, but only EOAD subjects had elevated serum IL-1β values compared with age-matched controls. Age negatively correlated with histamine (r=?0.57;p<0.05) and positively with IL-1β levels (r=0.48;p<0.05) in healthy subjects, but not in AD, whereas a positive correlation between TNF-α scores and age was only found in AD patients (r=0.46;p<0.05). Furthermore, histamine and TNF-α values correlated negatively in AD (r=?0.50,p<0.05). In addition, cognitive impairment increased in patients with lower TNF-α and higher histamine and IL-1β levels, as indicated by the correlations between mental performance scores and histamine (r=?0.37, ns), IL-1β (r=?0.33, ns) and TNF-α levels (r=0.42,p<0.05). Finally, histamine concentrations decreased as depression scores increased in AD (r=?0.63,p<0.01). These data suggest a dysfunction in cytokine and histamine regulation in AD, probably indicating changes associated with inflammatory processes.     

Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer’s Disease

Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) as compared to cognitively healthy elders and to correlate these levels with clinical and cognitive parameters. We further evaluated whether circulating adiponectin levels could predict progression from MCI to Alzheimer’s disease upon follow-up. We recruited 157 subjects (41 with AD, 65 with MCI and 51 elderly controls) in the baseline assessment. Follow-up data were available for 54 subjects with MCI and 43 controls in whom we ascertained the conversion to AD and the progression of cognitive impairment. Adiponectin was assayed by sandwich ELISA. Serum levels of adiponectin were significantly lower in MCI and AD as compared to controls (p < 0.001). After controlling for age, educational level and APOE genotype, adiponectin levels remained significantly reduced in these groups (p < 0.001). Circulating adiponectin levels did not predict cognitive decline in the elderly controls (i.e., progression from normal cognition to MCI) or progression to Alzheimer’s disease in subjects with MCI. We conclude that lower levels of adiponectin were associated with cognitive dysfunction, though it did not predict additional cognitive decline and conversion to dementia in this cohort of elderly subjects. Decreased adiponectin may be a surrogate marker of the pathological process in AD, linking clinical comorbidities, inflammation and cognitive dysfunction.     

脑小血管病患者病程进展与血管内皮功能障碍因子表达水平的相关性研究

目的 探讨脑小血管病（CSVD）患者病程进展与血管内皮功能障碍（ED）因子[同型半胱氨酸（Hcy）、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和C反应蛋白（CRP）]表达水平的相关性。方法 选取2016年6月至2017年9月在我科诊断为CSVD的患者60例作为研究对象,所有患者均进行了头颅MRI检查。采集外周血,利用ELISA检测与血管内皮功能障碍相关因子Hcy、TNF-α、IL-6和CRP的表达水平。对所纳入患者进行1年时间的随访,随访期内均进行头颅MRI检查。根据随访观察结果,将所纳入患者分为进展组和无进展组,比较两组患者血清Hcy、TNF-α、IL-6和CRP表达水平的差异,并分析它们与CSVD进展的相关性。结果 在60例患者中,病程进展的有38例,病程无进展的有22例。与病程无进展组相比,病程进展组患者血清Hcy（17.62±7.23 VS 11.35±5.41,P=0.007）和IL-6（17.46±6.97 VS 8.48±4.67,P=0.001）的表达水平高;TNF-α和CRP的表达水平在两组间无差异。经Spearman等级相关分析发现,CSVD患者的病程进展与血清Hcy（r=0.587,P=0.015）和IL-6（r=0.644,P=0.009）的表达水平存在相关性;而与TNF-α和CRP的表达水平不存在相关性。结论 CSVD患者血清中血管内皮功能障碍因子Hcy、IL-6的表达水平与病程进展存在相关性,检测这些因子的表达对于判断病情预后具有一定参考意义。     

阿尔茨海默病患者外周血IL-6、IL-8、TNF-α水平与认知功能的相关性

目的 探讨阿尔茨海默病(AD)患者外周血白细胞介素-6(IL-6)、IL-8及肿瘤坏死因子α(TNF-α)水平与认知功能的相关性.方法 选择2015年1月~2016年1月在济宁医学院附属医院兖州院区治疗的AD患者90例作为研究组,并选择同期在我院体检的90名健康人作为对照组,采用酶联免疫吸附法(ELISA)检测两组研究对象的外周血IL-6、IL-8及TNF-α水平,并采用简易精神状态量表(MMSE)和临床痴呆评定量表(CDR)对其认知功能和日常行为能力进行评估.比较各组间炎性因子水平的差异,分析炎性因子表达水平与认知功能的相关性.结果 研究组AD患者外周血的IL-6、IL-8及TNF-α水平均明显高于对照组[(128.64±10.28)pg/ml比(103.59±8.72)pg/ml,(134.32±9.67)pg/ml比(101.45±7.32)pg/ml,(221.39±23.54)pg/ml比(109.68±18.76)pg/ml],差异均有统计学意义(P<0.05).受教育年限为AD患者认知功能的保护因素,IL-6、IL-8及TNF-α水平为危险因素(P<0.05).整体人群中IL-6、TNF-α水平与MMSE得分呈负相关(r=-0.314,-0.079;P<0.05),IL-8与MMSE无相关性.结论 外周血IL-6及TNF-α水平与轻度AD患者的认知功能相关.     

Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease

BACKGROUND: Immunoreactivity for several chemokines and for their related receptors has been demonstrated in resident cells of the central nervous system, and the up-regulation of some of them is associated with pathological changes found in Alzheimer disease (AD). OBJECTIVE: To determine interferon-gamma-inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and interleukin 8 (IL-8) levels in cerebrospinal fluid (CSF) from subjects with amnestic mild cognitive impairment (MCI) and patients with AD as compared with age-matched controls. PATIENTS: Thirty-eight subjects with amnestic MCI, 36 patients with AD, and 41 age-matched subjects with noninflammatory affections of the nervous system. DESIGN: Evaluation of CSF chemokine production at time of diagnosis of MCI and AD; correlation with clinical and personal data. Longitudinal evaluation of subjects with MCI until conversion to AD. RESULTS: Cerebrospinal fluid IP-10 concentration was significantly increased in patients with MCI and mild AD but not in patients with severe AD (Mini-Mental State Examination score <15), whereas MCP-1 and IL-8 levels were increased in patients with MCI and all patients with AD. A significant positive correlation between Mini-Mental State Examination score and CSF IP-10 or MCP-1 concentration was observed in patients with AD. No correlation between IP-10 levels and age was found, whereas MCP-1 and IL-8 levels correlated positively with age. Out of 38 subjects with MCI, 19 developed AD within a 1- to 3-year follow-up. CONCLUSIONS: The presence of inflammatory molecules is likely to be a very early event in AD pathogenesis, even preceding the clinical onset of the disease, as demonstrated by subjects with MCI who developed AD over time. Interferon-gamma-inducible protein 10 is specifically increased in MCI and seems to decrease with the progression of AD, whereas MCP-1 and IL-8 are up-regulated also in late stages of the disease, suggesting a role in phases in which neurodegeneration is prevalent.     

不同严重程度阿尔茨海默病患者血清miR-128,miR-223表达水平变化与炎症反应及认知功能的相关性分析

目的 探讨不同严重程度阿尔茨海默病(Alzheimer’s disease,AD)患者血清微小RNA(MicroRNA,miR)-128,miR-223表达水平变化与炎症反应及认知功能的相关性。方法 选择2018年6月-2020年1月本院收治的200例AD患者(AD组),根据临床痴呆评定量表(Clinical dementia rating scale,CDR)评分将AD患者分为轻度组(CDR评分1分,66例)、中度组(CDR评分2分,83例)、重度组(CDR评分3,51例)3个亚组,另选择207例体检健康志愿者为对照组; 采用简易智能精神状态检查量表(Mini-mental state examination,MMSE)评估AD患者认知功能; 检测所有受试者血清miR-128,miR-223表达水平; 检测AD患者血清白介素-6(Interleukin-6,IL-6)、白介素-1β(Interleukin-1,IL-1β)、肿瘤坏死因子-α(Tumor necrosis factor-,TNF-α)、C反应蛋白(C-reactive protein,CRP)水平; 分析血清miR-128,miR-223表达水平与TNF-α,IL-1β,IL-6,CRP水平、MMSE总分的相关性。结果 AD组血清miR-128表达水平高于对照组(P<0.05),miR-223表达水平低于对照组(P<0.05)。重度组血清miR-128表达水平、TNF-α,IL-1β,IL-6,CRP水平高于中度和轻度组(P<0.05),且中度组高于轻度组(P<0.05); 重度组血清miR-223表达水平、MMSE总分低于中度和轻度组(P<0.05),且中度组低于轻度组(P<0.05)。miR-128表达水平与TNF-α,IL-1β,IL-6,CRP呈正相关(r≥0.496,P<0.05),与MMSE总分呈负相关(r =-0.571,P<0.05); miR-223表达水平与TNF-α,IL-1β,IL-6,CRP呈负相关(r ≤-0.572,P<0.05),与MMSE总分呈正相关(r=0.531,P<0.05)。结论 AD患者血清miR-128表达水平上调,miR-223表达水平下调,两者异常变化可能诱导炎症反应,进而参与AD患者认知功能损伤过程。     

高血压脑出血患者血清和颅内血肿液中IL-1β、IL-6、TNF—α的含量研究

目的通过测定高血压脑出血患者静脉血清及颅内血肿液中白细胞介素-1β（IL-1β）、白细胞介素．6（IL-6）、肿瘤坏死因子-α（TNF—α）水平,探讨这些炎症因子与脑出血病灶及外周血之间的关系。方法在高血压脑出血后24h,72h,7d和14d取80例高血压脑出血患者静脉血清及血肿液检测IL-1β、IL-6、TNF-α的含量（实验组）,并与30例正常体检的患者（对照组）对比。结果高血压脑出血患者血肿液IL-1β、IL-6、TNF-α含量显著高于对照组人群静脉血,并且显著高于实验组患者自身静脉血。实验组患者静脉血清中IL-1β、IL-6、TNF-α含量显著高于对照组人群静脉血清,且病情越重几种炎症因子水平越高。脑出血不同时期静脉血清IL-1β、IL-6、TNF—α．含量比较,在72h最高,此后呈下降趋势。结论高血压脑出血患者IL-1β、IL-6、TNF-α参与了脑出血的炎症反应,是脑出血后脑组织损伤的重要机制之一。     

Interaction of BDNF with cytokines in chronic schizophrenia

Brain-derived neurotrophic factor (BDNF) interacts with cytokines. Although both BDNF and cytokines occur at abnormal levels in schizophrenia patients, their interactions have not yet been examined. We therefore compared serum BDNF, TNF-α, interleukin (IL)-2, IL-6, and IL-8 levels in 92 chronically medicated schizophrenia patients and 60 healthy controls. We correlated these serum levels within these subject groups with each other and with clinical symptoms assessed according to the Positive and Negative Syndrome Scale (PANSS). Compared to the control group, the schizophrenia patients had significantly lower BDNF and TNF-α levels, and higher IL-2, IL-6, and IL-8 levels. The patients also showed a significant positive correlation between BDNF and both IL-2 and IL-8 levels, and low BDNF and TNF-α levels together were associated with poor performance on the PANSS cognitive factor. Thus, an interaction between cytokines and neurotrophic factors may be implicated in the pathophysiology of chronic schizophrenia. In particular, the cytokine TNF-α may interact with BNDF causing cognitive impairment.     

Potential utility of soluble p3-alcadeinα plasma levels as a biomarker for sporadic Alzheimer's disease

Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins (α, β, γ) that share identical localization and function to the amyloid-β protein precursor (AβPP) in the brain. Alcs are proteolyzed in neurons through successive cleavages via secretases, resulting in non-aggregative p3-Alc, where p3 corresponds to the AβPP-fragment. We found p3-Alcα detected in human plasma reflected the pathological process of amyloid-β accumulation in Alzheimer's disease (AD) patients and therefore investigated the utility of p3-Alcα as a plasma biomarker in AD. We measured p3-Alcα plasma levels in 83 sporadic-AD, 18 mild cognitive impaired (MCI), and 24 control subjects using the sandwich-ELISA system. Pooled samples with previously published data (171 AD and 45 controls) were also analyzed. The plasma p3-Alcα concentrations in patients with AD and MCI were significantly higher compared with control subjects (224.7 ± 40.4, 223.3 ± 53.9, and 189.1 ± 32.9 pg/ml, respectively; p = 0.0012). In AD patients, the plasma p3-Alcα concentration significantly correlated with age (r = 0.23, p = 0.037) and serum creatinine levels (r = 0.23, p = 0.0012). Even after adjusting for confounding factors of age, gender, renal function, and ApoE-ε4, high plasma p3-Alcα levels were correlated with significant AD risk, with an odds ratio 1.47 (95% confidence interval: 1.18-1.93, p = 0.0019) for every 10 pg/ml increase. Pooled analysis further confirmed these findings. Increased plasma p3-Alcα, evident in the early stages of cognitive impairment, suggests that Alc metabolites are useful plasma biomarkers of AD.     

Serum TNF-α and neurodegeneration in isolated REM sleep behavior disorder

ObjectiveTo investigate serum inflammatory cytokine profiles in patients with isolated REM sleep behavior disorder (iRBD) and to explore whether these markers are associated with phenoconversion risk to α-synucleinopathies.MethodsIn this prospective cohort study, we analyzed serum samples from patients with polysomnography-confirmed iRBD (n = 30) and healthy controls (n = 12). We measured the following cytokines: interleukin (IL)-1β, IL-2, IL-6, IL-10, and tumor necrosis factor-α (TNF-α). All patients underwent motor and non-motor evaluations and dopamine transporter imaging at baseline for predicting the phenoconversion risk. We followed the patients quarterly over up to 6 years to identify disease conversion. We also assessed longitudinal changes in cytokine levels from baseline at the 2- and 4-year follow-up visits.ResultsThe baseline cytokine levels did not differ between the patients and controls. However, the TNF-α levels were significantly increased in a subgroup of the patients with multiple markers (≥3) for phenoconversion risk compared to those without (p = 0.008) and controls (p = 0.003). At longitudinal analyses, patients with TNF-α levels above the median showed a higher incidence of phenoconversion than those with lower TNF-α levels (47% vs. 7%; p = 0.008), and this significant association persisted after adjusting for covariates (p = 0.026). The cytokine levels over 4 years of follow-up period did not change significantly.ConclusionsOur data suggest a possible link between serum TNF-α and phenoconversion risk in iRBD. Further studies are warranted to confirm the role of peripheral TNF-α in the pathogenesis of neurodegeneration in this disorder.     

Prolactin serum levels correlate with inflammatory status in drug-naïve first-episode schizophrenia

Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. Methods. Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Results. Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1β, IL-6 and TNF-α compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1β, IL-6 and TNF-α within the schizophrenia group. Within the schizophrenia group, TNF-α was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Conclusions. Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.     

脑梗死患者血清miR-497,TNF-α表达水平变化及其临床意义

目的 探讨急性脑梗死(Acute cerebral infarction,ACI)患者血清微小RNA-497(MicroRNA-497,miR-497)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)的表达水平变化及其临床意义。方法 选取2016年1月-2019年11月本院收治的96例ACI患者,称ACI组,并选取本院同期98例体检健康者,称对照组; 采用实时荧光定量PCR(Real-time fluorescent quantitative PCR,qRT-PCR)法检测所有研究对象血清miR-497表达水平; 采用酶联免疫吸附法(Enzyme-linked immunosorbent assay,ELISA)检测所有研究对象血清肿瘤坏死因子-α水平; 评估ACI患者神经功能缺损程度、计算脑梗死体积,比较不同神经功能缺损程度/脑梗死体积的ACI患者血清miR-497、TNF-α水平; Pearson法分析ACI患者血清miR-497、TNF-α水平与神经功能缺损程度评分(National institutes of health stroke scale,NIHSS)、脑梗死体积的关系; 采用受试者工作特征曲线(Receiver operating characteristic curve,ROC)评价血清miR-497、TNF-α对ACI的诊断价值。结果 ACI组血清miR-497、TNF-α水平均明显高于对照组(P<0.05); ACI患者血清miR-497、TNF-α水平随神经功能缺损程度加重、脑梗死体积增加均呈递增趋势(P均<0.05); ACI患者血清miR-497、TNF-α水平与脑梗死体积、NIHSS评分均呈正相关(r=0.423,0.514,0.542,0.399,P均<0.05); 血清miR-497、TNF-α对ACI诊断的曲线下面积(Area under curve,AUC)为0.848、0.806,截断值分别为1.29、1.27,相应灵敏度分别为82.3%、81.3%,特异度分别为76.5%、77.6%; 两者联合诊断ACI的AUC为0.907,其灵敏度、特异度分别为81.3%、90.8%。结论 miR-497、TNF-α在ACI患者血清中表达均上调,且与神经功能缺损程度、脑梗死体积有关,均可能在ACI进展中起一定作用,两者联合可有效提高ACI的诊断效能,有助于诊断、评估ACI患者的病情。