Myelin ultrastructure of sciatic nerve in rat experimental autoimmune neuritis model and its correlation with associated protein expression

Objective:To explore the relationship of peripheral nerve ultrastructure and its associated protein expression in experimental autoimmune neuritis(EAN).Methods:EAN was established in Lewis rats using an emulsified mixture of P0 peptide 180-199,Mycobacterium tuberculosis,and incomplete Freund's adjuvant.Rats given saline solution were used as a control group.Sciatic nerve ultrastructure and immunofluorescence histopathology were measured at the neuromuscular severity peak on day 18 post-induction.Cell-specific protein markers were used for immunofluorescence histopathology staining to characterize sciatic nerve cells:CD3(T cell),Iba-1(microglia),S100(myelin),and neurofilament 200(axon).Results:The results showed that swelling of the myelin lamellae,vesicular disorganization,separation of the myelin lamellae,and an attenuation or disappearance ofthe axon were observed by transmission electron microscopy in the EAN group.CD3 and Iba-1 increased significantly in the structures characterized by separation or swelling of the myelin lamellae,and increased slightly in the structures characterized by vesicular of the myelin lamellae,S100 decreased in the structures characterized by vesicular disorganization or separation of the myelin lamellae.And neurofilament 200 decreased in the structures characterized by separation of the myelin lamellae.Moreover,we found that Iba1 were positive in the myelin sheath,and overlapped with S100,which significantly indicated that Schwann cells may play as macrophage-like cells during the disease progression of ENA.Our findings may be a significant supplement for the knowledge of EAN model,and may offer a novel sight on the treatment of GBS.     

N-Butylphthalide (NBP) ameliorated cerebral ischemia reperfusion-induced brain injury via HGF-regulated TLR4/NF-κB signaling pathway

N-Butylphthalide (NBP) has been known to have potential neuroprotective effects in Alzheimer’s disease and stroke animal models. Hepatocyte-growth factor (HGF), with strong angiogenic properties, exerted protective role in brain injury. The present study was aimed to investigate the possible anti-inflammatory effects of NBP on the brain injury of rats with cerebral ischemia reperfusion (IR) and astrocytes activation induced by lipopolysaccharide (LPS) treatment. Our results showed that cerebral IR induced brain damage with down-regulation of HGF and astrocytes activation. NBP treatment significantly increased HGF expression and activated cMet/PI3K/AKT signaling pathway, stimulating mTOR activity and suppressing apoptosis in brain tissues. Also NBP inhibited pro-inflammatory cytokines expression, including IL-6, IL-1β, and TNFα, via TLR4/NF-κB suppression. Anti-HGF treatment enhanced TLR4 expression while HGF could suppress TLR4 activation and its down-streaming signals, attenuating inflammation finally. Notably, NBP up-regulated HGF and down-regulated TLR4 expression significantly in the astrocytes combined with the treatment of TLR4 inhibitor than the cells only treated with TLR4 inhibitor, suggesting that NBP could further suppress TLR4 activation, suggesting that NBP might impede TLR4 through up-regulating HGF expression. These results suggested that NBP treatment significantly ameliorated cerebral IR-induced brain injury by inhibiting TLR4/NF-κB-associated inflammation regulated by HGF.     

体外培养-力学刺激模型与周期性张应力的影响

背景：内质网应激参与多种疾病的发生发展过程,如动脉粥样硬化、糖尿病、阿尔茨海默病,GRP78是内质网应激的标志蛋白,GRP78的表达水平反映内质网应激的程度。目的：研究周期性张应力对 L6大鼠成肌细胞 GRP78表达的影响,以明确周期性张应力与内质网应激的关系。方法：在成功构建L6大鼠成肌细胞体外培养力学刺激模型的基础上,采用RT-PCR和Western blot法分析周期性张应力对GRP78 mRNA和蛋白表达的影响。加力组分别给予1,6,12,24 h的力学刺激,加载频率为10 cycles/min,拉伸变形幅度为15%。对照组与实验组在同时种板,不给予力刺激。结果与结论：GRP78 mRNA随着加力时间的延长呈一致上升趋势,与对照组相比,差异均有显著性意义（P＜0.05）;GRP78蛋白在加力1 h后,蛋白表达量开始升高,加力6 h后蛋白表达量显著升高,到24 h达到峰值,与对照组相比,差异均有显著性意义（P＜0.05）。由以上结果得出,在一定时间范围内,周期性张应力可引起内质网应激,并且随着时间的延长逐渐增强;持续的应力刺激,可引起严重的内质网应激导致成肌细胞凋亡。     

Cryptococcosis in patients with liver cirrhosis: Death risk factors and predictive value of prognostic models

BackgroundLiver cirrhosis is associated with immune deficiency, which causes these patients to be susceptible to various infections, including cryptococcus infection. Mortality in cirrhotic patients with cryptococcosis has increased. The present study was to explore the risk factors of mortality and the predictive ability of different prognostic models.MethodsForty-seven cirrhotic patients with cryptococcosis at a tertiary care hospital were included in this retrospective study. Data on demographics, clinical parameters, laboratory exams, diagnostic methods, medication during hospitalization, severity scores and prognosis were collected and analyzed. Student's t test and Mann-Whitney test were used to compare characteristics of survivors and non-survivors at a 90-day follow-up and cerebrospinal fluid (CSF) manifestations of cryptococcal meningitis. Multivariate Cox regression analysis was used to identify the independent risk factors for mortality. Kaplan-Meier curves were used to analyze patient survival. Receiver operating characteristic (ROC) curves were used to evaluate the different prognostic factors.ResultsThe 30- and 90-day survival rates were 93.6% and 80.9%, respectively, in cirrhotic patients with cryptococcosis. Cryptogenic liver diseases [hazard ratio (HR) = 7.567, 95% confidence interval (CI): 1.616-35.428, P = 0.010], activated partial thromboplastin time (APTT) (HR = 1.117, 95% CI: 1.016-1.229, P = 0.022) and Child-Pugh score (HR = 2.146, 95% CI: 1.314-3.504, P = 0.002) were risk factors for 90-day mortality in cirrhotic patients with cryptococcosis. Platelet count (HR = 0.965, 95% CI: 0.940-0.991, P = 0.008) was a protective factor. APTT (HR = 1.120, 95% CI: 1.044-1.202, P = 0.002) and Child-Pugh score (HR = 1.637, 95% CI: 1.086-2.469, P = 0.019) were risk factors for 90-day mortality in cirrhotic patients with cryptococcal meningitis. There was significant difference in the percentage of lymphocytes in CSF between survivors and non-survivors [60.0 (35.0-75.0) vs. 95.0 (83.8-97.2), P < 0.001]. The model of end-stage liver disease-sodium (MELD-Na) score was more accurate for predicting 30-day mortality both in patients with cryptococcosis [area under curve (AUC): 0.826, 95% CI: 0.618-1.000] and those with cryptococcal meningitis (AUC: 0.742, 95% CI: 0.560-0.924); Child-Pugh score was more useful for predicting 90-day mortality in patients with cryptococcosis (AUC: 0.823, 95% CI: 0.646-1.000) and those with cryptococcal meningitis (AUC: 0.815, 95% CI: 0.670-0.960).ConclusionsThese results showed that cryptogenic liver diseases, APTT and Child-Pugh score were associated with mortality in cirrhotic patients with cryptococcosis and cryptococcal meningitis. MELD-Na score was important for predicting 30-day mortality, and Child-Pugh score was critical for predicting 90-day mortality.     

Plasma-based proteomics reveals lipid metabolic and immunoregulatory dysregulation in post-stroke depression

BackgroundPost-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.MethodsHere, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.ResultsThe significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.ConclusionsEarly perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.     

男女教师高血压的患病特点

目的分析比较高校男女教师高血压患病特点。方法对2009年山东部分地区高校教师健康体检资料完整的1034人进行高血压患病情况统计分析。结果 1）高校教师高血压男、女患病率分别是22.9%和6.1%。2）随年龄增长男女患病率均逐渐增高,经统计学分析差异有统计学意义（P〈0.001）;3）各年龄组男性患病率明显高于女性,经统计学分析除60~69岁组可能因样本小以外,其余各年龄组差异有统计学意义（P〈0.05）;4）伴发血脂异常、尿酸高、超重等心血管危险因素男性明显高于女性,经统计学分析差异有统计学意义（P〈0.05）。结论高校教师男性高血压患病率与其他心血管危险因素的并存率均明显高于女性,因而男性有更高的发生心脑血管事件的危险,应加强对高校男性教师高血压的健康管理,包括一级和二级预防。     

黄连、吴茱萸及其药对对大鼠结肠异变腺窝的影响

目的:研究黄连、吴茱萸及其药对对大鼠结肠癌前病变(异常腺窝病灶,aberrant crypt foci,ACF)的影响。方法:皮下注射二甲肼(1,2-di m-ethylhydrazine,DMH)诱发大鼠结肠ACF形成,根据形态法观察亚甲蓝染色后ACF在结肠上皮的数量和分布变化。同时通过测定肝重指标评估药物对肝的损伤情况。结果:与模型组相比,黄连、吴茱萸及其药对在大剂量和中剂量时,都能明显抑制ACF形成(P<0.01);在小剂量时,黄连组亦能抑制ACF形成(P<0.05);黄连大、中剂量组和吴茱萸大剂量组的肝重指数有所增加(P<0.01),而药对组的肝重指数小于黄连组及吴茱萸组,且3给药组间有统计学差异(P<0.01)。结论:黄连、吴茱萸及其药对在一定程度上能抑制ACF形成,且配伍后能减轻对肝的损伤。     

导乐分娩的临床研究

目的探讨导乐分娩的效果。方法本研究包括在我院定期做产前检查并且入院后经全身检查没有剖宫产指征拟阴道分娩者500例,随机抽取250例作为导乐分娩组,余下250例作为传统模式分娩组。观察两组产妇的产程、产后出血量及新生儿窒息率。结果导乐分娩组产妇第一产程(8.78±1.03)h,第二产程(0.80±0.19)h;对照组第一产程(11.83±1.24)h,第二产程(1.13±0.43)h。导乐分娩组第一产程、第二产程时间短于对照组(P<0.05)。产后出血量导乐分娩组(110.67±10.83)ml,对照组(130.24±10.46)ml,导乐分娩组产后出血量低于对照组(P<0.05)。导乐分娩组新生儿窒息率为1.6%,对照组为6.4%,导乐分娩组新生儿窒息率低于对照组(P<0.05)。结论导乐分娩大大缩短了产程,减少了产后出血情况,降低了新生儿窒息率,有利于母婴健康,是一种值得提倡的新的分娩方式。