γ-干扰素对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的影响

为了研究γ-干扰素(IFNγ)对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的作用,采用免疫组织化学方法对胆碱能神经元的特异性标记酶-胆碱乙酰基转移酶(ChAT)进行染色,ChAT阳性细胞的数量反映了胆碱能神经元的数量,并用14C-乙酰CoA作底物来检测ChAT活性。结果显示,IFNγ处理过的实验组,ChAT阳性细胞数量显著增加,ChAT活性也增加,这种增加被大鼠抗小鼠IFNγ单克隆抗体(Ab-IFNγ)完全拮抗。采用流式细胞术对细胞周期进行分析,细胞周期及细胞百分率无明显改变。用MAP2标记神经细胞,神经细胞数基本未增加。以上结果提示:IFNγ不能促进基底前脑和隔区神经元增殖,胆碱能神经元表达增加不是因为神经元数目增加而是分化的结果。     

丙泊酚麻醉对老龄大鼠认知功能和海马神经元γ-氨基丁酸A受体表达的影响

目的 观察丙泊酚麻醉对老龄大鼠认知功能及海马神经元γ-氨基丁酸A(GABA)受体表达的影响.方法 50只SD老年大鼠随机分为丙泊酚组和对照组,每组25只.丙泊酚组大鼠腹腔注射1％丙泊酚中/长链脂肪乳注射液6 mL/kg,对照组腹腔注射等体积的生理盐水.麻醉后1d进行Morris水迷宫实验,分别采用HE染色和尼氏体染色观...     

Pharmacological approaches to mitigate neuroinflammation in Alzheimer’s disease

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases characterized by the formation of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Growing evidence suggested that there is an association between neuronal dysfunction and neuroinflammation (NI) in AD, coordinated by the chronic activation of astrocytes and microglial cells along with the subsequent excessive generation of the proinflammatory molecule. Therefore, a better understanding of the relationship between the nervous and immune systems is important in order to delay or avert the neurodegenerative events of AD. The inflammatory/immune pathways and the mechanisms to control these pathways may provide a novel arena to develop new drugs in order to target NI in AD. In this review, we represent the influence of cellular mediators which are involved in the NI process, with regards to the progression of AD. We also discuss the processes and the current status of multiple anti-inflammatory agents which are used in AD and have gone through or going through clinical trials. Moreover, new prospects for targeting NI in the development of AD drugs have also been highlighted.     

A novel likely pathogenic PLCG2 variant in a patient with a recurrent skin blistering disease and B-cell lymphopenia

Pathogenic variants of PLCG2 encoding phospholipase C gamma 2 (PLCγ2) were first reported in 2012 and their clinical manifestations vary widely. PLCG2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation (APLAID) are representative examples of PLCG2 pathogenic variants. In this report, we describe a 17-year-old male with recurrent blistering skin lesions, B-cell lymphopenia, and asthma. Distinct from the patients in previous reports, this patient had the heterozygous de novo c.2119T > C missense variant (NM_002661.4) resulting in a serine to proline amino acid substitution (p.Ser707Pro). The variant located to the PLCγ2 C-terminal Src homology 2 (cSH2) domain, which is a critical site for the restriction of intrinsic enzyme activity. This variant could be classified as “likely pathogenic” according to American College of Medical Genetics and Genomics guidelines. Laboratory results showed a reduction in circulating B cells without a decrease of serum IgG and IgA. Our findings expand the variety of clinical phenotypes for PLCG2 missense variants.     

炎症相关细胞因子在弥漫大B细胞淋巴瘤中作用的研究进展

IL-6由肿瘤细胞自分泌，与肿瘤侵袭性密切相关；TNF-α在机体肿瘤免疫应答中起到了重要作用，可引起肿瘤细胞坏死，且可诱导IL-6的表达；IFN-γ具有抗病毒，抗肿瘤和免疫调控的作用；IL-10 具有双向免疫调节作用，在肿瘤环境中对免疫应答具有负向调节作用，同时也能发挥刺激作用。上述细胞因子在弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）的发生发展中或起到协同作用，并可能作为DLBCL诊断及预后的指标。     

Interleukin-22 ameliorates acute-on-chronic liver failure by reprogramming impaired regeneration pathways in mice

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γ-谷氨酰转移酶和尿酸水平与PICU患儿预后的相关性

目的探讨γ-谷氨酰转移酶(GGT)和尿酸水平与儿科重症监护病房(PICU)患儿预后的相关性。方法回顾性分析2016年7月至2018年12月新疆维吾尔自治区人民医院PICU收治的247例患儿,根据患儿在PICU期间的临床结局将其分为存活组和死亡组。比较2组患儿临床资料、儿童死亡风险(PRISM)评分、GGT及尿酸水平。采用多因素Logistic回归方程分析影响患儿PICU期间死亡的危险因素,绘制受试者工作特征曲线(ROC曲线)分析不同指标预测患儿PICU期间预后的诊断效能。结果247例患儿在PICU住院期间共出现31例死亡,死亡率为12.55%。死亡组的GGT、尿酸水平、PRISM评分及菌血症发生率均高于存活组,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,GGT、尿酸水平及PRISM评分是患儿PICU期间死亡的独立危险因素(P<0.05)。ROC曲线显示,GGT、尿酸与PRISM评分联合预测的曲线下面积(AUC=0.967,95%CI 0.920~1.000)显著高于三项指标单独预测,联合预测在评估PICU患儿死亡的灵敏度和特异度分别为93.55%和94.91%。结论GGT、尿酸水平在评估患儿PICU住院期间死亡风险方面具有良好的预测价值,两者与PRISM评分联合预测患儿PICU死亡风险的效能更好。