目的分析亚甲基四氢叶酸还原酶(MTHFR)基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化(HT)的影响。方法回顾性分析2020年7月—2023年7月在安徽医科大学附属阜阳人民医院接受治疗的120例脑梗死患者的临床资料。依据治疗后24~72 h H...目的分析亚甲基四氢叶酸还原酶(MTHFR)基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化(HT)的影响。方法回顾性分析2020年7月—2023年7月在安徽医科大学附属阜阳人民医院接受治疗的120例脑梗死患者的临床资料。依据治疗后24~72 h HT发生情况分为HT组(15例)、无HT组(105例)。比较两组基线资料、MTHFR基因多态性、纤维蛋白原(Fib)、同型半胱氨酸(Hcy)。采用多因素一般Logistic回归模型分析脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素。绘制受试者工作特征(ROC)曲线,分析入院时美国国立卫生院卒中量表(NIHSS)评分、Hcy预测脑梗死患者阿替普酶静脉溶栓后HT发生的价值。结果HT组心房颤动发生率、MTHFR基因型677CT占比、入院时NIHSS评分、Hcy水平均高于无HT组(P<0.05)。多因素一般Logistic回归分析结果显示:心房颤动史[OR=1.478(95%CI:1.126,1.940)]、入院时NIHSS评分升高[OR=1.656(95%CI:1.125,2.438)]、MTHFR基因型为677CT[OR=1.871/2.362(95%CI:1.052,3.328/1.081,4.652)]、Hcy水平升高[OR=2.149(95%CI:1.108,4.168)]均为脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素(P<0.05)。ROC曲线分析结果显示,入院时NIHSS评分、Hcy均可预测脑梗死患者阿替普酶静脉溶栓后HT发生,其敏感性分别为80.0%(95%CI:0.765,0.883)、73.3%(95%CI:0.717,0.834),特异性分别为74.3%(95%CI:0.659,0.817)、74.3%(95%CI:0.824,0.931)。677CT型患者Hcy水平高于677CC、677TT型患者(P<0.05)。结论心房颤动、MTHFR基因型、入院时NIHSS评分、Hcy均为影响脑梗死患者阿替普酶静脉溶栓后HT发生的重要因素,临床应结合以上指标对高危患者进行重点筛查,尽早采取干预措施。展开更多
Background: Homocysteine (tHcy) has emerged as a new risk factor for cardiovascular diseases (CVD) The Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are seen to give rise to high levels of tHcy which can b...Background: Homocysteine (tHcy) has emerged as a new risk factor for cardiovascular diseases (CVD) The Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are seen to give rise to high levels of tHcy which can be a causative factor in the progression of CVD due to its thrombogenic effect. Serum cardiac biomarkers help in the diagnosis, prognosis, or surveillance of CVD. The present study evaluated the association of the two MTHFR mutations, rs1801133 and rs1801131 with 16 well-established serum cardiac markers. Additionally, the influence of age and gender on the association of the two MTHFR polymorphisms with serum cardiac marker levels was also investigated. Methods: The study was carried out on 1295 individuals who visited Vibrant America Clinical Lab for regular or suspected CVD check-ups. The serological markers and genomic variant analysis were carried out as per the standard laboratory protocol under CLIA. The association between serological markers and the rs1801133 and rs1801131 genetic variants with respect to age and gender was evaluated using a one-way ANNOVA test. Results: No significant association was observed in tHcy levels with respect to gender, however, plasma total tHcy levels were higher in males than females. tHcy levels increased with increasing age in the wild and heterozygous genotypes for the mutations, rs1801133 and rs1801131. Additionally, the serum cardiac markers, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Cholesterol (CHOL), Apolipoprotein A (APOA), Apolipoprotein B (APOB), N-terminal (NT)-pro hormone BNP (BNPNT), LDL calculated (LDLCAL), Small Density Low Density Lipoprotein (SDLDL), APOBAR, Oxidised Low Density Lipoprotein (OXLDL), Lipoprotein (A) (LPA), Triglycerides (TRIG), and Lipoprotein-Associated Phospholipase (Lp-PLA2) Test (PLAC) showed significant associations with respect to gender and age for rs1801133 and rs1801131 (P Conclusions: The present study reports the association of tHcy, HDL, LDL, CHOL, APOA, APOB, BNPNT, LDLCAL, SDLDL, APOBAR, OXLDL, LPA, TRIG, and PLAC with respect to age and gender for the mutations, rs1801133 and rs1801131. We observed that tHcy levels were high in males and the levels increased with increasing age in males for both polymorphisms. rs1801131 mutant males have high levels of triglyceride whereas rs1801133 mutant postmenopausal females showed high levels of cholesterol. Further analysis will be required to understand the pattern of association of the rest of the serum cardiac markers with age and gender for rs1801133 and rs1801131 mutations.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
文摘目的分析亚甲基四氢叶酸还原酶(MTHFR)基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化(HT)的影响。方法回顾性分析2020年7月—2023年7月在安徽医科大学附属阜阳人民医院接受治疗的120例脑梗死患者的临床资料。依据治疗后24~72 h HT发生情况分为HT组(15例)、无HT组(105例)。比较两组基线资料、MTHFR基因多态性、纤维蛋白原(Fib)、同型半胱氨酸(Hcy)。采用多因素一般Logistic回归模型分析脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素。绘制受试者工作特征(ROC)曲线,分析入院时美国国立卫生院卒中量表(NIHSS)评分、Hcy预测脑梗死患者阿替普酶静脉溶栓后HT发生的价值。结果HT组心房颤动发生率、MTHFR基因型677CT占比、入院时NIHSS评分、Hcy水平均高于无HT组(P<0.05)。多因素一般Logistic回归分析结果显示:心房颤动史[OR=1.478(95%CI:1.126,1.940)]、入院时NIHSS评分升高[OR=1.656(95%CI:1.125,2.438)]、MTHFR基因型为677CT[OR=1.871/2.362(95%CI:1.052,3.328/1.081,4.652)]、Hcy水平升高[OR=2.149(95%CI:1.108,4.168)]均为脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素(P<0.05)。ROC曲线分析结果显示,入院时NIHSS评分、Hcy均可预测脑梗死患者阿替普酶静脉溶栓后HT发生,其敏感性分别为80.0%(95%CI:0.765,0.883)、73.3%(95%CI:0.717,0.834),特异性分别为74.3%(95%CI:0.659,0.817)、74.3%(95%CI:0.824,0.931)。677CT型患者Hcy水平高于677CC、677TT型患者(P<0.05)。结论心房颤动、MTHFR基因型、入院时NIHSS评分、Hcy均为影响脑梗死患者阿替普酶静脉溶栓后HT发生的重要因素,临床应结合以上指标对高危患者进行重点筛查,尽早采取干预措施。
文摘Background: Homocysteine (tHcy) has emerged as a new risk factor for cardiovascular diseases (CVD) The Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are seen to give rise to high levels of tHcy which can be a causative factor in the progression of CVD due to its thrombogenic effect. Serum cardiac biomarkers help in the diagnosis, prognosis, or surveillance of CVD. The present study evaluated the association of the two MTHFR mutations, rs1801133 and rs1801131 with 16 well-established serum cardiac markers. Additionally, the influence of age and gender on the association of the two MTHFR polymorphisms with serum cardiac marker levels was also investigated. Methods: The study was carried out on 1295 individuals who visited Vibrant America Clinical Lab for regular or suspected CVD check-ups. The serological markers and genomic variant analysis were carried out as per the standard laboratory protocol under CLIA. The association between serological markers and the rs1801133 and rs1801131 genetic variants with respect to age and gender was evaluated using a one-way ANNOVA test. Results: No significant association was observed in tHcy levels with respect to gender, however, plasma total tHcy levels were higher in males than females. tHcy levels increased with increasing age in the wild and heterozygous genotypes for the mutations, rs1801133 and rs1801131. Additionally, the serum cardiac markers, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Cholesterol (CHOL), Apolipoprotein A (APOA), Apolipoprotein B (APOB), N-terminal (NT)-pro hormone BNP (BNPNT), LDL calculated (LDLCAL), Small Density Low Density Lipoprotein (SDLDL), APOBAR, Oxidised Low Density Lipoprotein (OXLDL), Lipoprotein (A) (LPA), Triglycerides (TRIG), and Lipoprotein-Associated Phospholipase (Lp-PLA2) Test (PLAC) showed significant associations with respect to gender and age for rs1801133 and rs1801131 (P Conclusions: The present study reports the association of tHcy, HDL, LDL, CHOL, APOA, APOB, BNPNT, LDLCAL, SDLDL, APOBAR, OXLDL, LPA, TRIG, and PLAC with respect to age and gender for the mutations, rs1801133 and rs1801131. We observed that tHcy levels were high in males and the levels increased with increasing age in males for both polymorphisms. rs1801131 mutant males have high levels of triglyceride whereas rs1801133 mutant postmenopausal females showed high levels of cholesterol. Further analysis will be required to understand the pattern of association of the rest of the serum cardiac markers with age and gender for rs1801133 and rs1801131 mutations.
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
