Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HB...Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin BI) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency. Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved. The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed. Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecu展开更多
目的系统评价前蛋白转化酶枯草杆菌蛋白酶9(PCSK9)抑制剂用于动脉粥样硬化性心血管病(ASCVD)的一级预防及二级预防时,对脑卒中的预防作用及安全性。方法应用计算机检索PubMed、Embase、Web of Science、Cochrane图书馆、中国知网、万方...目的系统评价前蛋白转化酶枯草杆菌蛋白酶9(PCSK9)抑制剂用于动脉粥样硬化性心血管病(ASCVD)的一级预防及二级预防时,对脑卒中的预防作用及安全性。方法应用计算机检索PubMed、Embase、Web of Science、Cochrane图书馆、中国知网、万方数据库中自建库起至2024年3月收录的关于依洛尤单抗、阿利西尤单抗、托莱西单抗或英克司兰(试验组)治疗高脂血症和ASCVD的随机对照试验研究(对照组使用安慰剂或采用常规治疗)。筛选及应用Cochrane文献质量评估工具评估文献质量后提取有效数据,有效性指标包括脑卒中发生率、缺血性脑卒中发生率,安全性指标包括心血管死亡、转氨酶升高3倍以上、肌酸激酶升高3倍以上、过敏反应、出血性脑卒中发生率。使用Stata软件对提取数据进行Meta分析,统计风险差异(RD)。结果共纳入20篇文献(21项随机对照试验研究),包含62799例患者。Meta分析显示:一级预防时试验组与对照组患者脑卒中发生率(RD=0.000,95%CI:-0.002~0.003,P=0.905)、缺血性脑卒中发生率(RD=0.001,95%CI:-0.005~0.006,P=0.824)的差异无统计学意义;试验组患者肌酸激酶升高3倍以上发生率低于对照组,差异有统计学意义(RD=-0.005,95%CI:-0.010~0.000,P=0.039)。二级预防时试验组患者脑卒中发生率(RD=-0.004,95%CI:-0.006~-0.002,P<0.001)、缺血性脑卒中发生率(RD=-0.003,95%CI:-0.005~-0.002,P<0.001)低于对照组,差异均有统计学意义;试验组和对照组患者心血管死亡、转氨酶升高3倍以上、肌酸激酶升高3倍以上、过敏反应及出血性脑卒中发生率的差异均无统计学意义(P>0.05)。结论PCSK9抑制剂用于ASCVD的一级预防时,对脑卒中及缺血性脑卒中发生率无显著影响,但能降低肌酸激酶升高3倍以上发生率;用于ASCVD的二级预防时,能有效降低脑卒中和缺血性卒中的发生风险,且不增加并发症的发生率,临床应用具有一定的安全性。展开更多
文摘Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin BI) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency. Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved. The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed. Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecu
文摘目的系统评价前蛋白转化酶枯草杆菌蛋白酶9(PCSK9)抑制剂用于动脉粥样硬化性心血管病(ASCVD)的一级预防及二级预防时,对脑卒中的预防作用及安全性。方法应用计算机检索PubMed、Embase、Web of Science、Cochrane图书馆、中国知网、万方数据库中自建库起至2024年3月收录的关于依洛尤单抗、阿利西尤单抗、托莱西单抗或英克司兰(试验组)治疗高脂血症和ASCVD的随机对照试验研究(对照组使用安慰剂或采用常规治疗)。筛选及应用Cochrane文献质量评估工具评估文献质量后提取有效数据,有效性指标包括脑卒中发生率、缺血性脑卒中发生率,安全性指标包括心血管死亡、转氨酶升高3倍以上、肌酸激酶升高3倍以上、过敏反应、出血性脑卒中发生率。使用Stata软件对提取数据进行Meta分析,统计风险差异(RD)。结果共纳入20篇文献(21项随机对照试验研究),包含62799例患者。Meta分析显示:一级预防时试验组与对照组患者脑卒中发生率(RD=0.000,95%CI:-0.002~0.003,P=0.905)、缺血性脑卒中发生率(RD=0.001,95%CI:-0.005~0.006,P=0.824)的差异无统计学意义;试验组患者肌酸激酶升高3倍以上发生率低于对照组,差异有统计学意义(RD=-0.005,95%CI:-0.010~0.000,P=0.039)。二级预防时试验组患者脑卒中发生率(RD=-0.004,95%CI:-0.006~-0.002,P<0.001)、缺血性脑卒中发生率(RD=-0.003,95%CI:-0.005~-0.002,P<0.001)低于对照组,差异均有统计学意义;试验组和对照组患者心血管死亡、转氨酶升高3倍以上、肌酸激酶升高3倍以上、过敏反应及出血性脑卒中发生率的差异均无统计学意义(P>0.05)。结论PCSK9抑制剂用于ASCVD的一级预防时,对脑卒中及缺血性脑卒中发生率无显著影响,但能降低肌酸激酶升高3倍以上发生率;用于ASCVD的二级预防时,能有效降低脑卒中和缺血性卒中的发生风险,且不增加并发症的发生率,临床应用具有一定的安全性。
