ABSTRACT
Objective:To reevaluate the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) by retrospectively analyzing the ALT levels in healthy people in Ningbo area.Methods:A total of 56 140 people who underwent health examination and detection of liver biochemical indexes in the Affiliated Hospital of Medical School of Ningbo University and Yinzhou Huamao Hospital of Ningbo from 2018 to 2020 were enrolled. After excluding relevant factors that may lead to liver injury, 11 411 people were included to compare the difference of serum ALT levels among different genders and age groups (20 to 29 years, 30 to 39 years, 40 to 49 years and 50 to 59 years) to determine the ALT ULN in different gender groups. Statistical methods were performed using two independent samples t test and analysis of variance. Results:The serum ALT of males was (19.20±7.90) U/L, which was higher than that of females ((13.75±6.17) U/L), with statistical significance ( t=41.16, P<0.001). The serum ALT ULN in males and in females were 35 U/L and 26 U/L, respectively. The serum ALT levels of 20 to 29, 30 to 39, 40 to 49 and 50 to 59 years old groups were (15.48±7.61) U/L, (16.21±7.40) U/L, (17.36±7.52) U/L and (18.77±7.57) U/L, respectively.The difference was statistically significant ( F=71.51, P<0.001). Serum ALT level in 50 to 59 years old group was higher than that in 20 to 29 years old group, and the difference was statistically significant ( t=13.11, P<0.01). In males, the ALT ULN of 20 to 29 years old was the lowest of 34.43 U/L, and highest of 35.29 U/L in 40 to 49 years old. In females, the ALT ULN in the 20 to 29 years old group was the lowest of 23.01 U/L, and the ALT ULN in the 50 to 59 years old group was the highest of 30.79 U/L. ALT ULN increased with age in females. The serum ALT of males was higher than that of females in all age groups ( t=29.55, 26.91, 13.43 and 4.62, respectively, all P<0.05). Conclusions:The serum ALT level is significantly correlated to gender and age. The serum ALT ULNs of healthy adult are 35 U/L in males and 26 U/L in females in Ningbo area.
ABSTRACT
Objective:To investigate the changes of liver pathology and its influencing factors in patients with chronic hepatitis B viral (HBV) infection and low level of serum alanine aminotransferase (ALT).Methods:The clinical data of 135 with chronic HBV infection patients, in whom the serum ALT levels were less than two times of the upper limit of normal (ULN), were collected from the Affiliated Hospital of Medical School of Ningbo University and the First Affiliated Hospital, Zhejiang University School of Medicine during July 2017 and July 2019. The result of hepatic histological examination was reviewed, and the risk factors of obvious liver inflammation (G≥2) or fibrosis (S≥2) in patients were analyzed with Logistic regression analysis.Results:The pathological examination of liver tissue revealed G≥2 or S≥2 in 52 cases (38.5%). The univariate analysis showed that age, family history of HBV infection, ALT 1-<2×ULN, aspartate aminotransferase(AST)≥1×ULN, low platelet count(PLT)and prolongation of prothrombin time(PT)were associated with G≥2 or S≥2 in chronic HBV infection patients with low level ALT ( P<0.05 or <0.01). Multivariate Logistic regression analysis showed that age( OR=1.052, 95% CI 1.007-1.100), family history of HBV infection( OR=5.448, 95% CI 2.191-13.548)and AST( OR=1.042, 95% CI 1.005-1.081)were independent risk factors of G≥2 or S≥2 in chronic HBV infection patients with low level ALT ( P<0.05 or <0.01). Conclusion:Age, family history of HBV infection and AST level can be used to judge the severity of liver pathological changes and necessity of antiviral treatment for patients with chronic HBV infection having ALT<2×ULN.
ABSTRACT
Objective To investigate the effect of caveolin-1 scaffolding domain (CSD) peptides on heme oxygenase-1 (HO-1) activity increasing and M1/M2 phenotype polarization in rat alveolar macrophages (AMs) induced by lipopolysaccharide (LPS).Methods Bioinformatics was used to analyze the binding of full-length wild-type CSD polypeptide and 101 amino acid deleted truncated mutant CSD polypeptide (Δ101CSD) to HO-1. Primary AMs were isolated from rats, when cell fusion reached 80％, they were synchronized with serum-free medium and divided into five groups: no treatment was given to the blank control group; LPS group was treated with 100μg/L LPS for 16 hours;LPS+ hemin group was treated with 100μg/L LPS and 20μmol/L hemin for 16 hours; wild-type CSD polypeptide+ LPS+hemin group was pretreated with 10μmol/L wild-type CSD polypeptide 6 hours before LPS treatment; Δ101CSD+ LPS+hemin group was pretreated with 10μmol/L Δ101CSD polypeptide 6 hours before LPS treatment. After treatment for 16 hours, the co-localization between caveolin-1 (Cav-1) and HO-1 was displayed by confocal microscope; the mRNA expressions of inflammatory cytokines interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) and M1/M2 polarization cytokines tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), leukocyte differentiation antigen 206 (CD206) and IL-10 were determined by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-qPCR); the HO-1 activity and nitric oxide (NO) production were determined by spectrophotometry.Results Bioinformatics analysis showed: both wild-type CSD and Δ101CSD peptides could bind to HO-1, and there was no significant difference in the binding ability between the two peptides, but the deletion of 101 Arg resulted in the disappearance of part of the binding region between Δ101CSD and HO-1. The results of laser confocal microscopy showed: the expressions of Cav-1 and HO-1 were lowed in the blank control group, and Cav-1 was bound to HO-1 in LPS group and LPS+ hemin group. Both wild-type CSD and Δ101CSD peptides pretreatment could significantly reduce the binding of HO-1 to Cav-1 induced by LPS. HO-1 activity analysis showed: after LPS stimulation, the activity of HO-1 was significantly higher than that of the blank control group; the activity of HO-1 induced by LPS was increased by hemin; after pretreatment with two kinds of CSD peptides, the activity of HO-1 was further increased, and the effect of wild-type CSD peptide was more significant, which showed a statistically significant difference as compared with that of LPS+ hemin group (pmol·mg-1·h-1: 3683±266 vs. 2408±132,P < 0.05). RT-qPCR results showed: LPS could induce elevation of cytokines and M1 markers and decrease of M2 markers, while hemin could inhibit LPS-induced inflammatory response and M1/M2 phenotypic polarization. Compared with LPS+ hemin group, after pretreatment with wild-type CSD peptide, the levels of inflammatory factors in AMs were decreased, and the mRNA expression levels of TNF-α and iNOS, M1 markers, were decreased [TNF-α mRNA (2-??Ct): 6.82±0.05 vs. 8.70±0.24, iNOS mRNA (2-??Ct): 331.50±32.05 vs. 506.70±0.10, bothP < 0.05], and IL-10 mRNA expression level was increased (2-??Ct: 269.09±6.54 vs. 119.05±3.30,P < 0.05). The deletion of 101 site partially weakened the inhibitory effect of CSD peptides on inflammatory factors and only reduced the expression of iNOS mRNA (2-??Ct: 429.11±8.92 vs. 506.70±0.10,P < 0.05), indicating that its ability to transform AMs from M1 phenotype to M2 phenotype was poor. The two peptides had no effect on the expression of CD206.Conclusion Wild-type CSD had beneficial effects of anti-inflammation by reducing Cav-1 binding to HO-1 induced by LPS, restoring the HO-1 activity and driving M2 phenotype in alveolar macrophages.