Serum metabolic profiling of targeted bile acids reveals potentially novel biomarkers for primary biliary cholangitis and autoimmune hepatitis

BACKGROUND Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are two unexplained immune diseases.The golden standard for diagnosis of these diseases requires a liver biopsy.Liver biopsy is not widely accepted by patients because of its invasive nature,and atypical liver histology can confuse diagnosis.In view of the lack of effective diagnostic markers for PBC and AIH,combined with the increasingly mature metabolomics technologies,including full-contour metabolomics and target.AIM To determine non-invasive,reliable,and sensitive biochemical markers for the differential diagnosis of PBC and AIH.METHODS Serum samples from 54 patients with PBC,26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatographytandem mass spectrometry serum metabolomics.The metabolites and metabolic pathways were identified,and the metabolic changes,metabolic pathways and inter-group differences between PBC and AIH were analyzed.Fifteen kinds of target metabolites of bile acids(BAs)were quantitatively analyzed by SRM,and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.RESULTS We found the changes in the levels of amino acids,BAs,organic acids,phospholipids,choline,sugar,and sugar alcohols in patients with PBC and AIH.Furthermore,the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid,lithocholic acid(LCA),taurolithocholic acid(TLCA),and LCA+TLCA in the PBC group compared with those in the AIH group.The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases.The levels of glycochenodeoxycholic acid,glycochenodeoxycholic sulfate,and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class,which was correlated with the severity of disease.CONCLUSION The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.

Association of Serum Dkk-1 Levels with β-catenin in Patients with Postmenopausal Osteoporosis

Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25（OH）D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25（OH）D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group（P〈0.001）. Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin（r=–0.161, P=0.003） and OPG（r=–0.106, P=0.047）, while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin（β=–0.165, P=0.009） and BMD（β=–0.139, P=0.027）, and a positive correlation between serum Dkk-1 levels and CTX（β=0.122, P=0.040） in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.

Effect of Trimetazidine on Diabetic Patients with Coronary Heart Diseases: A Meta-Analysis of Randomized, Controlled Trials

Objective To explore the therapeutic effects of trimetazidine(TMZ)on diabetic patients with coronary heart diseases.Methods We conducted a comprehensive electronic search of PubMed,EMBASE,and Cochrane databases between the inception dates of databases and May 2019(last search conducted on 30 May 2019)to identify randomized controlled trials.The evaluation method recommended by Cochrane Collaboration for bias risk assessment was employed for quality assessment.Random or fixed models were used to investigate pooled mean differences in left ventricular function,serum glucose metabolism,serum lipid profile,myocardial ischemia episodes and exercise tolerance with effect size indicated by the 95%confidence interval(CI).Results Additional TMZ treatment contributed to considerable improvement of left ventricular ejection fraction(WMD=4.39,95%CI:3.83,4.95,P<0.00001),left ventricular end diastolic diameter(WMD=-3.17,95%CI:-4.90,-1.44,P=0.0003)and left ventricular end systolic diameter(WMD=-4.69,95%CI:-8.66,-0.72,P=0.02).TMZ administration also significantly decreased fasting blood glucose(SMD=-0.43,95%CI:-0.70,-0.17,P=0.001),glycosylated hemoglobin level(WMD=-0.59,95%CI:-0.95,-0.24,P=0.001),serum level of total cholesterol(WMD=-20.36,95%CI:-39.80,-0.92,P=0.04),low-density lipoprotein cholesterol(WMD=-20.12,95%CI:-32.95,-7.30,P=0.002)and incidence of myocardial ischemia episodes(SMD=-0.84,95%CI:-1.50,-0.18,P=0.01).However,there were no significant differences in serum triglyceride level,high-density lipoprotein cholesterol,exercise tolerance between the TMZ group and the control group.Conclusion TMZ treatment in diabetic patients with coronary heart disease is effective to improve cardiac function,serum glucose and lipid metabolism and clinical symptoms.

Relationship between serum osteocalcin levels and glucolipid metabolism in elderly type 2 diabetic patients with non-alcoholic fatty liver disease

Objective To explore the relationship between serum osteocalcin levels and glucolipid metabolism in elderly type 2 diabetic patients with non-alcoholic fatty liver disease(NAFLD).Methods Data collected from 97 pa-tients with type 2 diabetes mellitus(T2DM)admitted to the Department of Geriatric Endocrinology of the First Affiliated hospital of Zhengzhou University from June