The roles of RACK1 in the pathogenesis of Alzheimer's disease

The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.

Predictive values of multidetector-row computed tomography combined with serum tumor biomarkers in preoperative lymph node metastasis of gastric cancer

Objective: Multidetector-row computed tomography(MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer(GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC.Methods: The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery.Results: With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen(CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis(up to 89.3%) before surgery.Conclusions: MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.

Prognostic impact of D2-plus lymphadenectomy and optimal extent of lymphadenectomy in advanced gastric antral carcinoma: Propensity score matching analysis

Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior(No. 8 p,No. 12 b/p, No. 13, and No. 14 v), and para-aortic(No. 16 a2, and No. 16 b1) lymph nodes(LNs) in subtotal gastrectomy for advanced gastric antral carcinoma.Methods: A total of 203 patients with advanced gastric cancer(GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled.Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses. The therapeutic value index(TVI) was calculate to evaluate the survival benefit of dissecting each LN station.Results: Of 102 patients with D2-plus lymphadenectomy, 21(20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy. After matching, the overall survival(OS) was significantly better in the D2-plus than the D2 group(P=0.030). In the multivariate survival analysis, D2-plus lymphadenectomy(hazard ratio, 0.516;P=0.006) was confirmed to significantly improve the survival rate. In the logistic regression analysis, p N stage [odds ratio(OR), 2.533;95% confidence interval(95% CI), 1.368-4.691;P=0.003] and extent of LNs metastasis(OR, 5.965;95% CI, 1.335-26.650;P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy. The TVI of patient with metastasis to LNs station was 7.1(No. 8p), 5.7(No. 12p), 5.1(No. 13), and 7.1(both No. 16a2 and No. 16b1), respectively.Conclusions: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16.

727例胃癌根治术标本淋巴结精细分拣的临床价值探讨

目的:探讨胃癌根治术标本中淋巴结精细分拣的临床应用价值。方法:回顾性分析2016年1月至2017年12月就诊于天津医科大学肿瘤医院实施胃癌根治术的727例胃癌患者临床病理资料,按照手术切除标本中淋巴结分拣方式分为精细淋巴结分拣组和区域淋巴结分拣组,分析两组患者送检淋巴结数目、转移淋巴结数目的差异并进行相关性分析比较。结果:两组患者的性别、年龄、肿瘤大小等因素间差异均无统计学意义(P>0.05),两组之间具有可比性。精细淋巴结分拣组患者淋巴结送检数目明显多于区域淋巴结分拣组(P<0.001)。在T分期、N分期以及TNM分期相同的情况下,精细淋巴结分拣组送检淋巴结数目显著多于区域淋巴结分拣组(P<0.001);精细淋巴结分拣组淋巴结转移数目也显著多于区域淋巴结分拣组(P<0.001)。此外,两组患者送检淋巴结数目与转移淋巴结数目均呈正相关,差异具有统计学意义(精细淋巴结分拣组r=0.181,P=0.023;区域淋巴结分拣组r=0.227,P<0.001),且精细淋巴结分拣组患者的送检淋巴结数目与转移淋巴结数目之间相关性弱于区域淋巴结分拣组患者。结论:胃癌根治术后精细淋巴结分拣可以提高送检淋巴结数目,提供精确的术后淋巴结分期,减少分期迁移,可以在临床上规范性推广。