Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incomplet...Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated.In addition to genetic predisposition and hepatic hypersecretion,the pathogenesis of cholelithiasis might involve the gastrointestinal(GI)microbiome,consisting of microorganisms and their metabolites.High-throughput sequencing studies have elucidated the role of bile,gallstones,and the fecal microbiome in cholelithiasis,associating microbiota dysbiosis with gallstone formation.The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways.This review examines the literature implicating the GI microbiome in cholelithiasis,specifically gallbladder stones,choledocholithiasis,and asymptomatic gallstones.We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.展开更多
Colitis-associated colorectal cancer(CAC)is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease(IBD).Patients with IBD,includin...Colitis-associated colorectal cancer(CAC)is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease(IBD).Patients with IBD,including ulcerative colitis and Crohn’s disease,are known to have an increased risk of developing CAC.Although the incidence of CAC has significantly decreased over the past few decades,individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer,and the incidence of CAC increases with duration.Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC.CAC has been shown to progress from colitis to dysplasia and finally to carcinoma.Accumulating evidence suggests that multiple immune-mediated pathways,DNA damage pathways,and pathogens are involved in the pathogenesis of CAC.Over the past decade,there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients.Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers.It is generally recommended that CAC patients undergo endoscopic removal or colectomy.This review summarizes the current understanding of CAC,particularly its epidemiology,mechanisms,and management.It focuses on the mechanisms that contribute to the development of CAC,covering advances in genomics,immunology,and the microbiome;presents evidence for management strategies,including endoscopy and colectomy;and discusses new strategies to interfere with the process and development of CAC.These scientific findings will pave the way for the management of CAC in the near future.展开更多
目的:从人胶质瘤U251细胞系分离培养胶质瘤干细胞样细胞,鉴定其放射敏感性,并考察信号转导与转录活化因子3(signal transducer and activator of transcription 3,STAT3)基因与胶质瘤干细胞放射敏感性的关系。方法:采用磁珠分选法分离CD...目的:从人胶质瘤U251细胞系分离培养胶质瘤干细胞样细胞,鉴定其放射敏感性,并考察信号转导与转录活化因子3(signal transducer and activator of transcription 3,STAT3)基因与胶质瘤干细胞放射敏感性的关系。方法:采用磁珠分选法分离CD133;胶质瘤U251细胞,并对CD133;U251细胞进行成球能力及放射敏感性检测。分别构建STAT3基因的shRNA沉默表达质粒和慢病毒过表达质粒并鉴定,再转染CD133;U251细胞,通过流式细胞术、Western blot考察STAT3表达与胶质瘤细胞放射敏感性的关系。结果:经磁珠分选的CD133;U251细胞有较强成球生长能力。经2、4、6、8和10 Gy剂量射线照射后,CD133;组细胞抑制率明显低于CD133-组和正常细胞组(P=0.000),且细胞凋亡比例更低。转染STAT3基因shRNA沉默表达质粒和慢病毒过表达质粒的CD133;U251细胞通过Western blot检测发现沉默组中STAT3蛋白表达降低。经2、4、6、8和10 Gy剂量射线照射后,STAT3沉默组相较于STAT3过表达组有更高的细胞抑制率(P=0.000),且细胞周期抑制及凋亡增加。结论:磁珠分选的CD133;胶质瘤细胞有放射性抵抗的干性特征,下调STAT3表达可提高胶质瘤细胞的放射敏感性。展开更多
文摘Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated.In addition to genetic predisposition and hepatic hypersecretion,the pathogenesis of cholelithiasis might involve the gastrointestinal(GI)microbiome,consisting of microorganisms and their metabolites.High-throughput sequencing studies have elucidated the role of bile,gallstones,and the fecal microbiome in cholelithiasis,associating microbiota dysbiosis with gallstone formation.The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways.This review examines the literature implicating the GI microbiome in cholelithiasis,specifically gallbladder stones,choledocholithiasis,and asymptomatic gallstones.We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.
基金Supported by the National Key Research and Development Program,No.2022YFC2504003Young Scholar Independent Innovation Science Fund of Chinese PLA General Hospital,No.22QNCZ020Medical Science and Technology Young Scholar Fostering Fund,No.21QNPY109.
文摘Colitis-associated colorectal cancer(CAC)is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease(IBD).Patients with IBD,including ulcerative colitis and Crohn’s disease,are known to have an increased risk of developing CAC.Although the incidence of CAC has significantly decreased over the past few decades,individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer,and the incidence of CAC increases with duration.Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC.CAC has been shown to progress from colitis to dysplasia and finally to carcinoma.Accumulating evidence suggests that multiple immune-mediated pathways,DNA damage pathways,and pathogens are involved in the pathogenesis of CAC.Over the past decade,there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients.Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers.It is generally recommended that CAC patients undergo endoscopic removal or colectomy.This review summarizes the current understanding of CAC,particularly its epidemiology,mechanisms,and management.It focuses on the mechanisms that contribute to the development of CAC,covering advances in genomics,immunology,and the microbiome;presents evidence for management strategies,including endoscopy and colectomy;and discusses new strategies to interfere with the process and development of CAC.These scientific findings will pave the way for the management of CAC in the near future.
