Serum chitinase-3-like protein 1 is a biomarker of liver fibrosis in patients with chronic hepatitis B in China

Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Methods:Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B(CHB)patients.Significant fibrosis was defined as a liver stiffness>9.7 kPa.The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic(ROC)analysis.Results:Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis(≥F2)than in those without significant hepatic fibrosis(<F2)(56.5 ng/mL vs.81.9 ng/mL,P<0.001).In CHB patients,the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6%and 59.1%,respectively,with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728(95%CI:0.637–0.820).Conclusions:Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver fibrosis.Moreover,CHI3L1 is feasible in monitoring disease progression.

Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

Background:Visinin-like protein-1(VILIP-1)and chitinase-3-like protein 1(CHI3L1 or YKL-40)in cerebrospinal fluid(CSF)are newly discovered markers indicating neuronal damage and microglial activation,respectively.Phosphorylated tau(p-tau)reflects the neuropathology of Alzheimer’s disease(AD)and is useful as diagnostic markers for AD.However,it is unknown whether these biomarkers have similar or complementary information in AD.Methods:We stratified 121 participants from the Alzheimer’s Disease Neuroimaging Initiative(ADNI)database into cognitively normal(CN),stable mild cognitive impairment(sMCI),progressive MCI(pMCI),and dementia due to AD.Analysis of covariance(ANOVA)and chi-square analyses,Spearman correlation,and logistic regression models were performed to test the demographic,associations between biomarkers,and diagnostic accuracies,respectively.Linear mixed-effects models were used to evaluate the effects of CSF amyloid-β(Aβ)on above biomarkers within diagnostic groups,the combination of diagnostic group and Aβstatus as predictor,and CSF biomarkers as predictors of AD features,including cognition measured by Mini–Mental State Examination(MMSE)and brain structure and white matter hyperintensity(WMH)measured by magnetic resonance imaging(MRI).Results:P-tau,VILIP-1,and YKL-40 were all predictors of AD diagnosis,but combinations of biomarkers did not improve the diagnostic accuracy(AUC 0.924 for p-tau,VILIP-1,and YKL-40)compared to p-tau(AUC 0.922).P-tau and VILIP-1 were highly correlated(r=0.639,p<0.001)and strongly associated with Aβpathology across clinical stages of AD,while YKL-40 was correlated with Aβpathology in CN and AD groups.VILIP-1 was associated with acceleration of cognitive decline,hippocampal atrophy,and expansion of ventricles in longitudinal analyses.YKL-40 was associated with hippocampal atrophy at baseline and follow-up,while p-tau was only associated with worsening WMH at baseline.Conclusions:CSF levels of p-tau,VILIP-1,and YKL-40 may have utility for discriminating between cognitively normal subjects and patients with AD.Increased levels of both VILIP-1 and YKL-40 may be associated with disease degeneration.These CSF biomarkers should be considered for future assessment in the characterization of the natural history of AD.

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome

Background： Acute coronary syndrome （ACS） is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1（ICAM-1 ）, chitinase-3-like protein I （YKL-40）, and lipoprotein-associated phospholipase A2 （Lp-PLA2） in patients with ACS and its clinical significance. Methods： A total of 120 patients with coronary heart disease （CHD） were categorized into 2 groups： 69 with ACS and 51 with stable angina pectoris （SAP）： 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score 〈26 （n = 36）, moderate CHD group with its Gensini score being 26-54 （n = 48） and severe CHD group with its Gensini score 〉54 （n = 36）. Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. Results： The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group （all P 〈 0.05）： and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group （P 〉 0.05）.The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group （all P 〉 0.05）. The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group （Gensini score 〈26）, moderate CHD group （Gensini score 26-54）, and severe CHD group （Gensini score 〉54） （all P 〉 0.05）. Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients （r=0.093, r=-0.149, and r= -0.085, all P 〉 0.05; respectively）. Conclusions： The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 rnight be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

Relationship between Two Blood Stasis Syndromes and Inflammatory Factors in Patients with Acute Coronary Syndrome

Objective： To investigate the relationship between inflammatory factors and two Chinese medicine（CM） syndrome types of qi stagnation and blood stasis（QSBS） and qi deficiency and blood stasis（QDBS） in patients with acute coronary syndrome（ACS）. Methods： Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups： 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1（ICAM-1）, chitinase-3-like protein 1（YKL-40） and lipoprotein-associated phospholipase A2（Lp-PLA2）. Results： Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference（P〉0.05）; ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS（P〈0.05）. Conclusion： Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.