胆石症患者血清微小RNA-122、高迁移率族蛋白1和角蛋白-18水平及其临床意义
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摘要
目的探讨胆石症患者血清微小RNA-122(miR-122)、高迁移率族蛋白1(HMGB 1)和半胱氨酸天冬氨酸蛋白酶裂解角蛋白-18(CCK-18)水平变化及其临床意义。方法 2015年1月～2018年2月我院收治的201例胆石症患者和健康体检者103例,比较两组人群血清miR-122、HMGB 1和CCK-18水平差异。采用Logistic回归分析影响单纯性胆石症进展为复杂性胆石症的相关因素。采用受试者工作特征曲线(ROC)下面积(AUC)分析血清指标诊断复杂性胆石症的效能。结果胆石症患者血清miR-122、HMGB 1和CCK-18水平分别为4.7(0.9,14.3)、(2.5±0.7) ng/mL和(126.8±20.5)U/L,显著高于健康人【0.9(0.4,3.1)、(2.1±0.4) ng/mL和(101.4±18.7) U/L,均P<0.05】;97例单纯性胆石症组血清miR-122、HMGB 1和CCK-18分别为3.5(0.7,8.5)、(2.2±0.5)ng/m L和(112.4±19.4)U/L,显著低于104例复杂性胆石症组【分别为5.8(0.9,16.2)、(2.8±0.8) ng/m L和(140.2±23.5) U/L,均P<0.05】;单因素和多因素Logistic回归分析显示,肝硬化、腹腔积液、血清miR-122、HMGB 1和CCK-18为单纯性胆石症进展为复杂性胆石症的危险因素;血清miR-122、HMGB 1和CCK-18水平三者联合检测诊断复杂性胆石症的AUC为0.819(0.758～0.962),显著高于miR-122【0.724(0.657～0.815)】、HMGB 1【0.701(0.633～0.804)或CCK-18【0.767(0.702～0.873)】单指标检测。结论对血清miR-122、HMGB 1和CCK-18水平升高的胆石症患者,应想到复杂性胆石症的可能,而给予更仔细的检查和特别处理。
Objects To investigate serum microRNA-122(miR-122),high mobility group protein 1(HMGB1)and caspase-aspartate proteolytic keratin-18(CCK-18) level changes in patients with cholelithiasis and their clinical significance. Methods 201 patients with cholelithiasis and 103 healthy persons admitted to our hospital between January 2015 and February 2018 were enrolled,and serum miR-122,HMGB1 and CCK-18 levels were compared between the two groups. Logistic regression analysis was applied to analyze the risk factors affecting the progression of simple cholelithiasis into complex cholelithiasis. The efficacy of serum markers in the diagnosis of complex cholelithiasis was analyzed by area under the receiver operating characteristic curve(AUC). Results Serum levels of miR-122,HMGB1 and CCK-18 in patients with cholelithiasis were 4.7(0.9,14.3),(2.5±0.7) ng/mL and(126.8±20.5) U/L,respectively,significantly higher than[0.9(0.4,3.1),(2.1±0.4) ng/mL and(101.4±18.7)U/L,all P<0.05] in control;serum miR-122,HMGB1 and CCK-18 in 97 patients with simple cholelithiasis were 3.5(0.7,8.5),(2.2±0.5) ng/mL and(112.4±19.4) U/L,respectively,significantly lower than in 104 patients with complex cholelithiasis [5.8(0.9,16.2),(2.8±0.8) ng/mL and(140.2±23.5) U/L,respectively,P<0.05];univariate and multivariate Logistic regression analysis showed that liver cirrhosis,peritoneal effusion,serum miR-122,HMGB1 and CCK-18 were the risk factors related to simple cholelithiasis turned to complex one;our findings also showed that the combination of the three serum parameters increased the diagnostic efficacy of complex cholelithiasis[AUC 0.819(0.758～0.962) vs. AUC miR-122 0.724(0.657～0.815),AUC HMGB 1 0.701(0.633～0.804) or AUC CCK-18 0.767(0.702～0.873)]. Conclusion The patients with cholelithiasis and high serum mir-122,HMGB1 and CCK-18 levels might be sophisticated in disease severity,and should be taken into consideration and carefully managed.
Objects To investigate serum microRNA-122(miR-122),high mobility group protein 1(HMGB1)and caspase-aspartate proteolytic keratin-18(CCK-18) level changes in patients with cholelithiasis and their clinical significance. Methods 201 patients with cholelithiasis and 103 healthy persons admitted to our hospital between January 2015 and February 2018 were enrolled,and serum miR-122,HMGB1 and CCK-18 levels were compared between the two groups. Logistic regression analysis was applied to analyze the risk factors affecting the progression of simple cholelithiasis into complex cholelithiasis. The efficacy of serum markers in the diagnosis of complex cholelithiasis was analyzed by area under the receiver operating characteristic curve(AUC). Results Serum levels of miR-122,HMGB1 and CCK-18 in patients with cholelithiasis were 4.7(0.9,14.3),(2.5±0.7) ng/mL and(126.8±20.5) U/L,respectively,significantly higher than[0.9(0.4,3.1),(2.1±0.4) ng/mL and(101.4±18.7)U/L,all P<0.05] in control;serum miR-122,HMGB1 and CCK-18 in 97 patients with simple cholelithiasis were 3.5(0.7,8.5),(2.2±0.5) ng/mL and(112.4±19.4) U/L,respectively,significantly lower than in 104 patients with complex cholelithiasis [5.8(0.9,16.2),(2.8±0.8) ng/mL and(140.2±23.5) U/L,respectively,P<0.05];univariate and multivariate Logistic regression analysis showed that liver cirrhosis,peritoneal effusion,serum miR-122,HMGB1 and CCK-18 were the risk factors related to simple cholelithiasis turned to complex one;our findings also showed that the combination of the three serum parameters increased the diagnostic efficacy of complex cholelithiasis[AUC 0.819(0.758～0.962) vs. AUC miR-122 0.724(0.657～0.815),AUC HMGB 1 0.701(0.633～0.804) or AUC CCK-18 0.767(0.702～0.873)]. Conclusion The patients with cholelithiasis and high serum mir-122,HMGB1 and CCK-18 levels might be sophisticated in disease severity,and should be taken into consideration and carefully managed.
引文
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[11]Abdallah A,Hewson J,Francoz D,et al.Systematic review of the diagnostic accuracy of hap toglobin,serum amyloid a,and fibrinogen versus clinical reference standards for the diagnosis of bovine respiratory disea se.J Vet Intern Med,2016,30(4):1356-1368.
[12]Valdmanis PN,Gu S,Chu K,et al.RNA interference-induced hepatotoxicity results from loss of the first synthesized isoform of microRNA-122 in mice.Nat Med,2016,22(5):557-562.
[13]Lorente L,Martín MM,Agustín F,et al.Serum levels of caspase-cleaved cytokeratin-18 and mortality are associated in severe septic patients:pilot study.Plos One,2014,9(10):e109618.
[14]Sakoda M,Ueno S,Iino S,et al.Survival benefits of small anatomical resection of the liver for patients with hepatocellular carcinoma and impaired liver function,based on new-era imaging studies.J Cancer,2016,7(9):1029-1036.
[15]Bajaj J S,Kakiyama G,Zhao D,et al.Continued alcohol misuse in human cirrhosis is associated with an impaired gut-liver axis.Alcohol Clin Exp Res,2017,16(1):673-679.
[16]Toouli J,Kow L,Saccone GT,et al.Changes in gallbladder motility and gallstone,formation following laparoscopic gastric banding for morbid obesity.Can J Gastroenterol,2016,17(3):169-174.
[17]Galve J,Martín Santiago A,Clavero C,et al.Spontaneous repigmentation of silvery hair in an infant with congenital hydrops fetalis and hypoproteinemia.Cutis,2016,97(6):1-5.
[18]Moschetta AL,Stolk MF,Rehfeld JF,et al.Severe impairment of postprandial cholecystokinin release and gall-bladder emptying and high risk of gallstone formation in acromegalic patients during sandostatin LAR.Aliment Pharmacol Ther,2001,15(2):181-185.
[19]Toouli J,Kow L,Saccone GT,et al.Changes in gallbladder motility and gallstone,formation following laparoscopic gastric banding for morbid obesity.Can J Gastroenterol,2016,17(3):169-174.
[20]Wu W,Ouyang B,Lu Z,et al.CCK1 receptor is involved in the regulation of protein lysine acetylation in GBC-SD cells and gallbladder carcinoma.Ir J Med Sci,2017,186(4):883-888.
[2]Lin X,Cai J,Wang J,et al.Minimally invasive cholecystolithotomy to treat cholecystolithiasis in children:a single-center experience with 23 cases.Surg Laparosc Endosc Percutan Tech,2017,27(5):108-110.
[3]Cen L,Pan J,Zhou B,et al.Helicobacter pylori infection of the gallbladder and the risk of chronic cholecystitis and cholelithiasis:a systematic review and Meta-analysis.Helicobacter,2018,23(1):e12457.
[4]Liu P,Wu M,Hsieh M,et al.Hepatobiliary and pancreatic:development from gallbladder stone to gallstone ileus.J Gastroenterol Hepatol,2017,32(9):1539-1539.
[5]Horiuchi T,Sakata N,Narumi Y,et al.Metformin directly binds the alarmin HMGB 1 and inhibits its proinflammatory activity.J Biol Chem,2017,292(20):8436-8446.
[6]Woolbright BL1,Antoine DJ,Jenkins RE,et al.Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice.Toxicol Appl Pharmacol,2013,273(3):524-531.
[7]Berhane T,Vetrhus M,Hausken T,et al.Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients:the results of a prospective study.Scand J Gastroenterol,2006,41(1):93-101.
[8]Joly P,Céline R,Lacan P,et al.UGT1A1(TA)n,genotype is not the major risk factor of cholelithiasis in sickle cell disease children.Eur J Haematol,2017,98(3):296-301.
[9]Jabbari NA,Hassanpour M,Jangjoo A.Conse quences of lost gallstones during laparoscopic cholecystectomy:a review article.Surg Laparosc Endosc Percutan Tech,2016,26(3):183-192.
[10]Wang L,Dong P,Zhang Y,et al.Gallstone ileus displaying the typical rigler triad and an occult second ectopic stone:a case report.Medicine,2017,96(45):e8541.
[11]Abdallah A,Hewson J,Francoz D,et al.Systematic review of the diagnostic accuracy of hap toglobin,serum amyloid a,and fibrinogen versus clinical reference standards for the diagnosis of bovine respiratory disea se.J Vet Intern Med,2016,30(4):1356-1368.
[12]Valdmanis PN,Gu S,Chu K,et al.RNA interference-induced hepatotoxicity results from loss of the first synthesized isoform of microRNA-122 in mice.Nat Med,2016,22(5):557-562.
[13]Lorente L,Martín MM,Agustín F,et al.Serum levels of caspase-cleaved cytokeratin-18 and mortality are associated in severe septic patients:pilot study.Plos One,2014,9(10):e109618.
[14]Sakoda M,Ueno S,Iino S,et al.Survival benefits of small anatomical resection of the liver for patients with hepatocellular carcinoma and impaired liver function,based on new-era imaging studies.J Cancer,2016,7(9):1029-1036.
[15]Bajaj J S,Kakiyama G,Zhao D,et al.Continued alcohol misuse in human cirrhosis is associated with an impaired gut-liver axis.Alcohol Clin Exp Res,2017,16(1):673-679.
[16]Toouli J,Kow L,Saccone GT,et al.Changes in gallbladder motility and gallstone,formation following laparoscopic gastric banding for morbid obesity.Can J Gastroenterol,2016,17(3):169-174.
[17]Galve J,Martín Santiago A,Clavero C,et al.Spontaneous repigmentation of silvery hair in an infant with congenital hydrops fetalis and hypoproteinemia.Cutis,2016,97(6):1-5.
[18]Moschetta AL,Stolk MF,Rehfeld JF,et al.Severe impairment of postprandial cholecystokinin release and gall-bladder emptying and high risk of gallstone formation in acromegalic patients during sandostatin LAR.Aliment Pharmacol Ther,2001,15(2):181-185.
[19]Toouli J,Kow L,Saccone GT,et al.Changes in gallbladder motility and gallstone,formation following laparoscopic gastric banding for morbid obesity.Can J Gastroenterol,2016,17(3):169-174.
[20]Wu W,Ouyang B,Lu Z,et al.CCK1 receptor is involved in the regulation of protein lysine acetylation in GBC-SD cells and gallbladder carcinoma.Ir J Med Sci,2017,186(4):883-888.
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