目的探究孕妇孕期血清样本中血清十八碳一不饱和脂肪酸硬脂酰鞘氨醇(serum stearoyl sphingosine,C18∶1-Cer)和1-硬脂酰基-sn-甘油-3-磷酸胆碱(lysophosphatidyl choline,LPC18∶0)水平在预测孕妇患妊娠期糖尿病(gestational diabetes ...目的探究孕妇孕期血清样本中血清十八碳一不饱和脂肪酸硬脂酰鞘氨醇(serum stearoyl sphingosine,C18∶1-Cer)和1-硬脂酰基-sn-甘油-3-磷酸胆碱(lysophosphatidyl choline,LPC18∶0)水平在预测孕妇患妊娠期糖尿病(gestational diabetes mellitus,GDM)方面的价值。方法回顾性分析126例孕妇的临床资料和实验室指标,根据GDM诊断结果,将研究对象分为GDM组(n=66)和对照组(n=60)。采用质谱法检测研究对象孕早期和孕中期血清C18∶1-Cer和LPC18∶0水平,通过Logistic回归分析筛选出GDM的危险因素,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估C18∶1-Cer,LPC188∶0和两者联合对GDM的预测价值。结果与对照组相比,GDM组血清C18∶1-Cer和LPC18∶0水平在孕早期(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)和孕中期(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml)均显著升高,差异具有统计学意义(t=7.127,15.637;-5.984,2.174,均P<0.05)。C18∶1-Cer与空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素(fasting plasma insulin,FPI)、胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)、糖化血红蛋白(glycated hemoglobin,HbA1c)和三酰甘油(triglyceride,TG)呈正相关(r=0.458,0.209,0.317,0.223,0.219,均P<0.05)。LPC18∶0与FPG,FPI,HOMA-IR,HbA1c,总胆固醇(total cholesterol,TC)和TG呈正相关(r=0.715,0.426,0.580,0.465,0.232,0.372,均P<0.05)。Logistic回归分析结果显示,C18∶1-Cer[OR(95%CI):1.522(1.136~.039),P<0.05]和LPC18∶0[OR(95%CI):1.198(1.102~1.302),P<0.001]是GDM的独立危险因素。ROC曲线分析结果显示,血清C18∶1-Cer,LPC18∶0和两指标联合的曲线下面积(area under the curve,AUC)分别为0.819,0.971和0.986,两者联合检测的预测效能优于单独检测。结论妊娠早期血清中的C18∶1-Cer和LPC18∶0与GDM的发生密切相关,C18∶1-Cer联合LPC18∶0对GDM早期诊断有一定的预测价值。展开更多
The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Ce...The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Cell Lung Carcinoma (NSCLC), colorectal cancer, adenocarcinomas, ovarian carcinoma, and endometrial tumors. KRAS activates 80 different signaling pathways, including Mitogen-activated protein kinases (MAPK) and Phosphoinositide 3-kinase (PI3K), and up-regulates transcription factors such as ETS like Protein (ELK), Jun Proto-Oncogene (JUN), and Myelocytomatosis (MYC), which are involved in cell differentiation, proliferation, transformation, and survival. KRAS mutations are also known to cause autocrine function, which further exacerbates the situation. In NSCLC, KRAS mutations have a strong positive correlation with the disease, particularly in patients with a smoking history. In pancreatic cancer, KRAS mutations are a dominant pathological basis, with most mutations being G12D, G12V, G13D, G13C, G13S, and G13R. These mutations serve as initial markers in tumorigenesis and are associated with poor prognosis and high mortality rates. In colorectal cancer, KRAS mutations contribute to 4/5 of cases, with cellular mechanisms involving the MAPK pathway, which resists anti-epidermal growth factor antibodies. In Low-grade Serous Ovarian Cancer (LGSOC), KRAS mutations are associated with altered signaling in the MAPK pathway and drug resistance. However, treatments such as Selumetinib, a down regulator of RAS/Rapidly Accelerated Fibrosarcoma (RAF)/Mitogen-activated protein kinase (MEK) pathways, and a combination of trametinib and buparlisib have shown promise in managing LGSOC when diagnosed early through KRAS mutation markers. Although KRAS mutations are commonly associated with many types of cancer, their use in clinical practice is limited due to the lack of accurate methods to identify them. It is needed to further isolate the KRAS mutation products and correlate the cancer-causing genes to make it a promising approach for cancer chemotherapy.展开更多
文摘目的探究孕妇孕期血清样本中血清十八碳一不饱和脂肪酸硬脂酰鞘氨醇(serum stearoyl sphingosine,C18∶1-Cer)和1-硬脂酰基-sn-甘油-3-磷酸胆碱(lysophosphatidyl choline,LPC18∶0)水平在预测孕妇患妊娠期糖尿病(gestational diabetes mellitus,GDM)方面的价值。方法回顾性分析126例孕妇的临床资料和实验室指标,根据GDM诊断结果,将研究对象分为GDM组(n=66)和对照组(n=60)。采用质谱法检测研究对象孕早期和孕中期血清C18∶1-Cer和LPC18∶0水平,通过Logistic回归分析筛选出GDM的危险因素,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估C18∶1-Cer,LPC188∶0和两者联合对GDM的预测价值。结果与对照组相比,GDM组血清C18∶1-Cer和LPC18∶0水平在孕早期(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)和孕中期(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml)均显著升高,差异具有统计学意义(t=7.127,15.637;-5.984,2.174,均P<0.05)。C18∶1-Cer与空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素(fasting plasma insulin,FPI)、胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)、糖化血红蛋白(glycated hemoglobin,HbA1c)和三酰甘油(triglyceride,TG)呈正相关(r=0.458,0.209,0.317,0.223,0.219,均P<0.05)。LPC18∶0与FPG,FPI,HOMA-IR,HbA1c,总胆固醇(total cholesterol,TC)和TG呈正相关(r=0.715,0.426,0.580,0.465,0.232,0.372,均P<0.05)。Logistic回归分析结果显示,C18∶1-Cer[OR(95%CI):1.522(1.136~.039),P<0.05]和LPC18∶0[OR(95%CI):1.198(1.102~1.302),P<0.001]是GDM的独立危险因素。ROC曲线分析结果显示,血清C18∶1-Cer,LPC18∶0和两指标联合的曲线下面积(area under the curve,AUC)分别为0.819,0.971和0.986,两者联合检测的预测效能优于单独检测。结论妊娠早期血清中的C18∶1-Cer和LPC18∶0与GDM的发生密切相关,C18∶1-Cer联合LPC18∶0对GDM早期诊断有一定的预测价值。
文摘The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Cell Lung Carcinoma (NSCLC), colorectal cancer, adenocarcinomas, ovarian carcinoma, and endometrial tumors. KRAS activates 80 different signaling pathways, including Mitogen-activated protein kinases (MAPK) and Phosphoinositide 3-kinase (PI3K), and up-regulates transcription factors such as ETS like Protein (ELK), Jun Proto-Oncogene (JUN), and Myelocytomatosis (MYC), which are involved in cell differentiation, proliferation, transformation, and survival. KRAS mutations are also known to cause autocrine function, which further exacerbates the situation. In NSCLC, KRAS mutations have a strong positive correlation with the disease, particularly in patients with a smoking history. In pancreatic cancer, KRAS mutations are a dominant pathological basis, with most mutations being G12D, G12V, G13D, G13C, G13S, and G13R. These mutations serve as initial markers in tumorigenesis and are associated with poor prognosis and high mortality rates. In colorectal cancer, KRAS mutations contribute to 4/5 of cases, with cellular mechanisms involving the MAPK pathway, which resists anti-epidermal growth factor antibodies. In Low-grade Serous Ovarian Cancer (LGSOC), KRAS mutations are associated with altered signaling in the MAPK pathway and drug resistance. However, treatments such as Selumetinib, a down regulator of RAS/Rapidly Accelerated Fibrosarcoma (RAF)/Mitogen-activated protein kinase (MEK) pathways, and a combination of trametinib and buparlisib have shown promise in managing LGSOC when diagnosed early through KRAS mutation markers. Although KRAS mutations are commonly associated with many types of cancer, their use in clinical practice is limited due to the lack of accurate methods to identify them. It is needed to further isolate the KRAS mutation products and correlate the cancer-causing genes to make it a promising approach for cancer chemotherapy.
基金Supported by the National Natural Science Foundation of China (No. 81603342)the Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization (No. 2021B1212040007)+5 种基金the Guangdong Basic and Applied Basic Re-search Foundation (No. 2022A1515012641No. 2024A1515012948)the Guangdong Provincial Bureau of Traditional Chinese Medi-cine Research Project (No. 20221107)the Guangzhou Science and Technology Projects (No. 2024A03J0154No. 2023B01J1004)the Foshan “Summit Plan” of Building High-Level Hospitals。
