目的探讨弥漫大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)中髓样分化因子88(Myeloid differentiation factor 88,MYD88)、腺苷三磷酸-柠檬酸裂解酶(ATP-citrate lyase,ACLY)和磷酸化ACLY(pACLY)蛋白的表达情况,并分析与患者预...目的探讨弥漫大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)中髓样分化因子88(Myeloid differentiation factor 88,MYD88)、腺苷三磷酸-柠檬酸裂解酶(ATP-citrate lyase,ACLY)和磷酸化ACLY(pACLY)蛋白的表达情况,并分析与患者预后及临床病理特征的关系。方法收集新疆医科大学第一附属医院2012年1月1日至2017年12月31日126例DLBCL患者的肿瘤组织石蜡标本,用免疫组化方法检测MYD88、ACLY、pACLY的表达水平,通过Spearman检测变量间的相关性,单因素及多因素Cox分析预后的影响因素。结果在DLBCL肿瘤细胞中,MYD88阳性表达率为84.13%(106/126),ACLY阳性表达率为71.43%(90/126),pACLY阳性表达率为72.22%(91/126)。MYD88高表达与肿瘤发生部位相关(P=0.037),ACLY高表达与肿瘤发生部位和分期相关(P分别为0.002和0.048),pACLY高表达与肿瘤分型和血清LDH水平相关(P分别为0.048和0.044)。MYD88与ACLY、pACLY蛋白表达呈正相关。Kaplan-Meier单因素生存分析显示,MYD88表达(P=0.005)、ACLY表达(P=0.001)、肿瘤Hanns分型(P=0.017)、年龄(P=0.010)、IPI评分(P=0.014)、PS评分(P=0.018)、B症状(P=0.026)及骨髓累及(P=0.005)均与患者的OS相关。多因素分析显示,MYD88高表达和肿瘤分型为OS的独立影响因素,ACLY高表达和骨髓累及为PFS的独立影响因素。结论MYD88、ACLY和pACLY在DLBCL肿瘤细胞中阳性表达率较高,MYD88和ACLY是DLBCL的独立预后影响因素,可作为预测DLBCL患者预后的潜在标志物。展开更多
Background:Modified Qiangli Dingxuan Tablets(ZYSJ)is an optimized formulation derived from the classic Chinese patent medicine Qiangli Dingxuan Tablet.It targets the pathological features associated with metabolic hyp...Background:Modified Qiangli Dingxuan Tablets(ZYSJ)is an optimized formulation derived from the classic Chinese patent medicine Qiangli Dingxuan Tablet.It targets the pathological features associated with metabolic hypertension(MH)and metabolic disorders,although its antihypertensive mechanism remains unclear.Methods:A rat model of metabolic hypertension was established using a high-sugar,high-fat diet combined with progressively increasing concentrations of ethanol.Blood pressure,serum lipids,inflammatory cytokines,and endothelial function markers were assessed.Serum pharmacochemistry combined with network pharmacology was employed to predict key targets and pathways,followed by in vivo validation using qRT-PCR,Western blotting,immunofluorescence,and immunohistochemistry.Results:ZYSJ significantly reduced blood pressure and serum lipid levels in model rats.Thirty absorbed bioactive components were identified.Mechanistic studies revealed that ZYSJ downregulated the TLR4/MyD88/NF-κB signaling pathway at both the mRNA and protein levels,upregulated endothelial nitric oxide synthase(eNOS)expression,and decreased the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6),thereby improving vascular endothelial function.Conclusion:ZYSJ effectively lowers blood pressure and serum lipids in rats with metabolic hypertension.Its mechanism of action is closely associated with regulation of the TLR4/MyD88/NF-κB signaling pathway,improvement of vascular endothelial function,and alleviation of inflammation.展开更多
文摘目的探讨弥漫大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)中髓样分化因子88(Myeloid differentiation factor 88,MYD88)、腺苷三磷酸-柠檬酸裂解酶(ATP-citrate lyase,ACLY)和磷酸化ACLY(pACLY)蛋白的表达情况,并分析与患者预后及临床病理特征的关系。方法收集新疆医科大学第一附属医院2012年1月1日至2017年12月31日126例DLBCL患者的肿瘤组织石蜡标本,用免疫组化方法检测MYD88、ACLY、pACLY的表达水平,通过Spearman检测变量间的相关性,单因素及多因素Cox分析预后的影响因素。结果在DLBCL肿瘤细胞中,MYD88阳性表达率为84.13%(106/126),ACLY阳性表达率为71.43%(90/126),pACLY阳性表达率为72.22%(91/126)。MYD88高表达与肿瘤发生部位相关(P=0.037),ACLY高表达与肿瘤发生部位和分期相关(P分别为0.002和0.048),pACLY高表达与肿瘤分型和血清LDH水平相关(P分别为0.048和0.044)。MYD88与ACLY、pACLY蛋白表达呈正相关。Kaplan-Meier单因素生存分析显示,MYD88表达(P=0.005)、ACLY表达(P=0.001)、肿瘤Hanns分型(P=0.017)、年龄(P=0.010)、IPI评分(P=0.014)、PS评分(P=0.018)、B症状(P=0.026)及骨髓累及(P=0.005)均与患者的OS相关。多因素分析显示,MYD88高表达和肿瘤分型为OS的独立影响因素,ACLY高表达和骨髓累及为PFS的独立影响因素。结论MYD88、ACLY和pACLY在DLBCL肿瘤细胞中阳性表达率较高,MYD88和ACLY是DLBCL的独立预后影响因素,可作为预测DLBCL患者预后的潜在标志物。
基金supported by Natural science foundation of Zhejiang province(No.ZCLMS25H2801 to Ying-Jie Dong)Zhejiang Provincial"Vanguard"and"Leading Goose"R&D Tackling Program(No.2025C02183 to Su-Hong Chen)+1 种基金National Natural Science Foundation of China(No.82274134 to Su-Hong Chen and No.82404900 to Ying-Jie Dong)the Key Laboratory of Zhejiang Province(No.2012E10002 to Gui-Yuan Lv).
文摘Background:Modified Qiangli Dingxuan Tablets(ZYSJ)is an optimized formulation derived from the classic Chinese patent medicine Qiangli Dingxuan Tablet.It targets the pathological features associated with metabolic hypertension(MH)and metabolic disorders,although its antihypertensive mechanism remains unclear.Methods:A rat model of metabolic hypertension was established using a high-sugar,high-fat diet combined with progressively increasing concentrations of ethanol.Blood pressure,serum lipids,inflammatory cytokines,and endothelial function markers were assessed.Serum pharmacochemistry combined with network pharmacology was employed to predict key targets and pathways,followed by in vivo validation using qRT-PCR,Western blotting,immunofluorescence,and immunohistochemistry.Results:ZYSJ significantly reduced blood pressure and serum lipid levels in model rats.Thirty absorbed bioactive components were identified.Mechanistic studies revealed that ZYSJ downregulated the TLR4/MyD88/NF-κB signaling pathway at both the mRNA and protein levels,upregulated endothelial nitric oxide synthase(eNOS)expression,and decreased the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6),thereby improving vascular endothelial function.Conclusion:ZYSJ effectively lowers blood pressure and serum lipids in rats with metabolic hypertension.Its mechanism of action is closely associated with regulation of the TLR4/MyD88/NF-κB signaling pathway,improvement of vascular endothelial function,and alleviation of inflammation.
