Objective:To explore the value of magnetic resonance diffusion kurtosis imaging (DKI) in the assessment of the condition and prognosis of neonatal acute bilirubin encephalopathy (ABE).Methods:A retrospective selection was made of 196 neonates with acute hyperbilirubinemia who were hospitalized in the Second Affiliated Hospital of Shantou University Medical College from June 2021 to September 2023 as the research subjects. According to the presence or absence of brain injury, they were divided into the ABE group ( n=112) and the non-ABE group ( n=84). Based on the neonatal Bilirubine-induced Neurological Dysfunction (BIND) scoring system, children in the ABE group were divided into the mild group ( n=50, score 1-3 points), the moderate group ( n=33, score 4-6 points), and the severe group ( n=29, score 7-9 points). The clinical data and DKI parameters among each group were analyzed. Univariate and multivariate analyses were used to evaluate the influencing factors of prognosis in children with ABE. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of DKI parameters for the prognosis of children with ABE. Results:The birth weight and gestational age in the ABE group were significantly lower than those in the non-ABE group, and the peak value of total bilirubin (TBIL) was significantly higher than that in the non-ABE group (all P<0.05). There was no statistically significant difference in fractional anisotropy (FA) values and mean diffusivity (MD) values among each group of children (all P>0.05). The mean kurtosis (MK) values, axial kurtosis (KA) values, and radial kurtosis (KR) values of children with ABE in the severe group were significantly higher than those in the other groups (all P<0.05). After Spearman correlation analysis, the FA value and MD value of children with ABE were not correlated with the severity of the disease (all P>0.05), while the MK value, KA value and KR value were positively correlated with the severity of the disease (all P<0.05). The patients were followed up for 12 months. Among them, 87 cases had a normal prognosis and 25 cases had a poor prognosis, including 2 cases of cerebral palsy, 5 cases of hearing loss, 4 cases of movement disorders, 12 cases of cerebral palsy combined with hearing loss, and 2 cases of movement disorders combined with hearing loss. The results of univariate analysis showed that there were statistically significant differences in birth weight, peak TBIL, BIND score, MK value, KA value, and KR value between the two groups of children with different prognoses (all P<0.05). The results of Cox multivariate regression analysis showed that birth weight, peak TBIL, BIND score, MK value, KA value, and KR value were independent influencing factors for poor prognosis in children with ABE (all P<0.05). The results of the ROC curve showed that the area under the curve and specificity of the MK value in predicting the poor prognosis of children with ABE were significantly higher than those of the KA and KR values (all P<0.05). Conclusions:The DKI parameters MK value, KA value, and KR value are sensitive indicators reflecting the severity of brain injury and predicting prognosis in children with ABE, among which the MK value has the highest predictive value.

Objective:To explore the value of magnetic resonance diffusion kurtosis imaging (DKI) in the assessment of the condition and prognosis of neonatal acute bilirubin encephalopathy (ABE).Methods:A retrospective selection was made of 196 neonates with acute hyperbilirubinemia who were hospitalized in the Second Affiliated Hospital of Shantou University Medical College from June 2021 to September 2023 as the research subjects. According to the presence or absence of brain injury, they were divided into the ABE group ( n=112) and the non-ABE group ( n=84). Based on the neonatal Bilirubine-induced Neurological Dysfunction (BIND) scoring system, children in the ABE group were divided into the mild group ( n=50, score 1-3 points), the moderate group ( n=33, score 4-6 points), and the severe group ( n=29, score 7-9 points). The clinical data and DKI parameters among each group were analyzed. Univariate and multivariate analyses were used to evaluate the influencing factors of prognosis in children with ABE. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of DKI parameters for the prognosis of children with ABE. Results:The birth weight and gestational age in the ABE group were significantly lower than those in the non-ABE group, and the peak value of total bilirubin (TBIL) was significantly higher than that in the non-ABE group (all P<0.05). There was no statistically significant difference in fractional anisotropy (FA) values and mean diffusivity (MD) values among each group of children (all P>0.05). The mean kurtosis (MK) values, axial kurtosis (KA) values, and radial kurtosis (KR) values of children with ABE in the severe group were significantly higher than those in the other groups (all P<0.05). After Spearman correlation analysis, the FA value and MD value of children with ABE were not correlated with the severity of the disease (all P>0.05), while the MK value, KA value and KR value were positively correlated with the severity of the disease (all P<0.05). The patients were followed up for 12 months. Among them, 87 cases had a normal prognosis and 25 cases had a poor prognosis, including 2 cases of cerebral palsy, 5 cases of hearing loss, 4 cases of movement disorders, 12 cases of cerebral palsy combined with hearing loss, and 2 cases of movement disorders combined with hearing loss. The results of univariate analysis showed that there were statistically significant differences in birth weight, peak TBIL, BIND score, MK value, KA value, and KR value between the two groups of children with different prognoses (all P<0.05). The results of Cox multivariate regression analysis showed that birth weight, peak TBIL, BIND score, MK value, KA value, and KR value were independent influencing factors for poor prognosis in children with ABE (all P<0.05). The results of the ROC curve showed that the area under the curve and specificity of the MK value in predicting the poor prognosis of children with ABE were significantly higher than those of the KA and KR values (all P<0.05). Conclusions:The DKI parameters MK value, KA value, and KR value are sensitive indicators reflecting the severity of brain injury and predicting prognosis in children with ABE, among which the MK value has the highest predictive value.

Objective:To explore the early predictors for clinical cure by sequential combined interferon therapy in nucleos(t)ide analogues (NAs) experienced patients with chronic hepatitis B(CHB).Methods:CHB patients received NAs treatment≥one year with hepatitis B surface antigen (HBsAg) ≤1 500 IU/mL, hepatitis B e antigen (HBeAg) negative and hepatitis B virus (HBV) DNA <100 IU/mL in the Third Affiliated Hospital of Sun Yat-sen University from June 2016 to September 2019 were included. According to the different treatment regimens, the patients were divided into interferon alone for 48 weeks group (group A), interferon combined with NAs for 12 weeks and continued NAs treatment for 48 weeks group (group B), interferon combined with NAs for 48 weeks group (group C). Basic data such as age and gender of patients were collected. HBsAg, hepatitis B surface antibody (anti-HBs) and alanine aminotransferase (ALT) were monitored at week 4, 8, 12, 24, 36 and 48. The decline of HBsAg from baseline, and the rates of clinical cure at 48 weeks were analyzed. The independent sample t test, chi-square test and rank sum test were used for statistical analysis. Logistic regression analysis was used to achieve the early prediction index of clinical cure at week 48. Results:A total of 1 020 CHB patients were followed up regularly for at least five time points. The rates of clinical cure at week 48 in group A, B and C were 34.6%(157/454), 32.7%(69/211) and 33.5%(119/355), respectively, with no statistical significance ( χ2=0.25, P=0.883). Patients were divided into the cured group (345 cases) and the uncured group (675 cases) according to the clinical outcomes at week 48. The age ((38±13) years old vs (43±12) years old), baseline HBsAg (131.00(359.80) IU/mL vs 437.60(531.50) IU/mL) and the proportion of male patients (81.7%(282/345) vs 89.5%(604/675)) of patients in the cured group were all lower than those of patients in the uncured group. The differences were all statistically significant ( t=6.32, Z=12.67, χ2=11.99, respectively, all P<0.050). There were 212 patients in the cured group who achieved clinical cure within 24 weeks of treatment. The rate of clinical cure at 48 weeks in patients whose HBsAg at week 4 decreased from baseline was higher than that in patients with increased HBsAg (41.6%(149/358) vs 28.2%(108/383)). The difference was statistically significant ( χ2=14.13, P<0.001). The rate of clinical cure at week 48 in patients with HBsAg at week 12 decreased ≤34.03% of baseline was only 6.9%(13/188). Multivariate logistic regression analysis showed that age (odds ratio ( OR)=0.962, 95% confidence interval ( CI) 0.936 to 0.989, P=0.006), HBsAg level at week 24 ( OR=0.950, 95% CI 0.934 to 0.966, P<0.001) and anti-HBs level at week 24 ( OR=1.012, 95% CI 1.005 to 1.019, P=0.001) were early predictors for clinical cure at week 48 of treatment in NAs experienced CHB patients. Conclusions:Clinical cure of NAs experienced CHB patients received sequential combined interferon therapy mostly occurs in the early stage (within 24 weeks). Age, HBsAg level at week 24, and anti-HBs level at week 24 are early predictors for clinical cure of 48-week sequential combined interferon treatment.

Objective To investigate the level of serum macrophage migration inhibitory factor (MIF) and its correlation with serum precollagen Ⅲ peptide (PⅢP) and tissue inhibitor of metalloproteinase (TIMP)-1 in patients with chronic hepatitis B (CHB) and hepatitis B virus (HBV)-related cirrhosis. Methods Forty-four CHB patients (hepatitis B group), 44 patients with HBV-related cirrhosis (cirrhosis group) and 30 healthy controls (control group) were enrolled in this study. The venous blood was collected and MIF level was detected by enzyme-linked immunosorbent assay (ELISA). Correlations between MIF and PⅢP, TIMP-1 were analyzed in observed groups. Comparison between groups was done using t test. The correlations between MIF level and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), plasma thromboplastin antecedent (PTA), PⅢP and TIMP-1 were analyzed by rectilinear correlation. Results The levels of serum MIF, PⅢP and TIMP-1 in CHB group and cirrhosis group were all significantly higher than those in control group (t=12.87,5.28, 10.98,t=11.22,14.84,11.17;all P<0.05), while there were no significant differences between CHB group and cirrhosis group (t= -1.05,1.52,--2.07;all P>0.05). There was no correlation between MIF level and ALT, AST, TBil and PTA. MIF level in CHB patients with hepatitis B e antigen (HBeAg) positive and high viral load were both higher than that in patients with HBeAg negative and low viral load. MIF level was both positively correlated with PⅢP level in CHB group and cirrhosis group (r=0. 603, P<0.05 and r=0. 415, P<0. 05, respectively). MIF level was also positively correlated with TIMP-1 level in CHB group (r=0. 458, P<0.05), while not correlated in cirrhosis group (r=0. 210, P>0.05). Levels of PⅢP and T1MP-1 were both correlated in CHB group and cirrhosis group (r=0. 849, P< 0.05 and r=0. 424, P<0.05, respectively). Conclusions The levels of serum MIF are significantly increased both in patients with CHB and cirrhosis. The early production of MIF might be related with viral replication, but not with liver function. MIF participates in formations of hepatitis, liver fibrosis and cirrhosis, which could reflect the degree of liver cirrhosis.

Objective To investigate the therapeutic effects of recombinant yeast hepatitis B virus(HBV)vaccine combined with interferon(IFN)α-1b and determine the rational dosage of HBV vaccine for the further clinical study with larger sample.Methods Two hundreds and sixteen patients with chronic hepatitis B(CHB)were enrolled in this randomized,multi-center,double-blinded and placebo-controlled clinical trial.All the subjects were not treated with antiviral drugs within 6 months and randomly divided into 90μg,60μg and placebo groups with a ratio of 1:1:1.All the patients were intramuscularly administrated with 90μg or 60μg recombinant HBV vaccine or placebo at week 0,2,6,10,14,18,22,respectively.Meanwhile,they were also treated with IFNα-1b 50μg,3 times a wcek for 24 weeks.All patients were followed up for 24 weeks after withdrawal of anti-HBV therapy.Serum HBV DNA level,HBeAg titer and liver function were monitored frequently.Interferon-γ secreting lymphoeytes were detected by Enzyme-linked immunospot(ELISPOT)in part of the patients.Results The serum HBV DNA levels were(6.03±1.79),(5.52±1.82)and(6.29±1.70)log10 copy/mL at week 24 of treatment in high dose,low dose and placebo groups,respectively (P=0.458).And the serum HBV DNA levels were(5.92±1.98),(5.49±1.99)and(6.16±1.76)log10 copy/mL at weck 24 after withdrawal of treatment,respectively(P=0.720).The rates of patients whose HBV DNA＜1×105 copy/mL in these three groups were 30.4%,39.4% and 20.8% at week 24 of treatment,respectively and there was significant difference between high dose group and low dose group(P=0.015).The rate of patients whose HBV DNA＜1×105 copy/mL at week 24 after withdrawal was highest in low dose group,but no significant differences before and after treatment in these three groups(P=0.257).The HBV DNA negative rates were 17.4%,25.4% and 6.9% in these three groups,respectively,which were significantly different(P=0.012).At week 24 of treatment and week 24 after withdrawal of treatment,the alanine aminotransferase normalization rate,HBeAg seroconversion rate were highest in low dose group,but no significant differences in these three groups.ELISPOT positive rates at week 24 of treatment and week 24 after withdrawal of treatment in high close and low dose groups were higher than that in placebo group(P＜0.05).The incidence of adverse events was similar and there was no drug related severe adverse events in each group.Conclusion Recombinant HBV vaccine maybe contribute to anti-HBV therapy and 60μg of dosage seems to be rational.