Clinical features and autoantibody characteristics of patients with drug-induced liver injury: An analysis of 419 cases / 临床肝胆病杂志

Objective To investigate the clinical features and autoantibody characteristics of patients with drug-induced liver injury (DILI). Methods A retrospective analysis was performed for the patients with abnormal liver function who were admitted to Beijing Ditan Hospital, Capital Medical University, from September 2014 to September 2018 and were diagnosed with DILI based on RUCAM score, and related data on admission were collected, including baseline liver function, renal function, routine blood test results, five immune indices, autoantibody, and liver biopsy results. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used to compare the detection rate of autoantibody between the patients with different sexes or types of liver injury. A logistic regression analysis was used to investigate whether autoantibody had a regression relationship with sex, age, and type of injury, and an ordinal logistic regression analysis was performed with baseline laboratory results as independent variables and anti-nuclear antibody (ANA) titer as the dependent variable. Results A total of 419 patients with DILI were enrolled in the study, with a median age of 47 (35-55) years, among whom male patients accounted for 32.5% (136/419) and female patients accounted for 67.5% (283/419). Among these 419 patients, 88 (21.5%) had hepatocellular-type liver injury, 87 (21.2%) had mixed-type liver injury, and 235 (57.3%) had cholestasis-type liver injury. The detection rate of autoantibodies was 50.6% (212/419), and the detection rate of ANA was 42.9% (180/419), with a titer of mainly 1∶ 100 (104/180). There was no significant difference in the detection rate of autoantibodies between the patients with different sexes ( χ 2 =2.658, P =0.103) or different types of injury ( χ 2 =0.859, P =0.651). The binary logistic regression analysis showed that autoantibody did not have a regression relationship with sex, age, and type of injury (all P > 0.05) There were significant differences in prothrombin time activity (PTA) and international normalized ratio (INR) between the positive autoantibody group and the negative autoantibody group ( t =2.161, P =0.031; Z =-3.010, P =0.003). The ordinal logistic regression analysis showed that INR (odds ratio [ OR ]=3.101, P =0.040) and IgG ( OR =1.043, P =0.014) were associated with ANA grade. Conclusion There is a relatively high detection rate of autoantibodies in patients with DILI, and the detection rate of autoantibodies is not associated with sex, age, or type of injury. There are differences in PTA and INR between autoantibody-positive patients and autoantibody-negative patients, and the levels of INR and IgG are correlated with antibody titer.

Cytokine Profiles and Virological Marker Monitoring during 48 Weeks Peginterferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B / 生物医学与环境科学（英文）

Objective@#This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB).@*Methods@#HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks.@*Results@#A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log 10 IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05).@*Conclusion@#There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.

Value of HBsAg level in predicting liver inflammation in patients with HBeAg-positive chronic hepatitis B virus infection and normal alanine aminotransferase / 临床肝胆病杂志

Objective To investigate the onset of liver inflammation and related predictive factors in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection who have normal alanine aminotransferase (ALT) and a high viral load. Methods A retrospective analysis was performed for the clinical data of 183 patients with HBeAg-positive chronic HBV infection who had normal ALT and a high viral load and were treated from October 2008 to May 2015, and according to the results of liver biopsy, they were divided into hepatitis group and non- hepatitis group. The t -test or Mann-Whitney U testwas used for comparison of normally distributed continuous data between groups, the chi-square test was used for comparison of categorical data. The predictive factors were analyzed by univariate binary logistic regression, the multivariate binary logistic regression was carried out by stepback method, and the cut-off values were analyzed by receiver operating characteristic curve (ROC) and Jordan index. Results There were 37 patients (20.2%) in the hepatitis group and 146 patients (79.8%) in the non-hepatitis group. Compared with the non-hepatitis group, the hepatitis group had a significantly lower proportion of male patients (45.9% vs 68.5%, χ 2 =6.508, P =0.011), a significantly higher level of aspartate aminotransferase [24 (21.25~35.55) U/L vs 21.2 (18.08~ 24.65) U/L, Z =-3.344, P =0.001], and a significantly lower log(HBsAg) value [4.4(4.28~4.49) vs 4.46(4.4~4.74), Z =-2.184, P =0.029]. Log(HBsAg) value was a predictive factor for hepatitis (odds ratio=0.077, P =0.017), and the cutoff value of HBsAg was 33884.4I U/mL. Conclusion Among the patients with HBeAg-positive chronic HBV infection who have normal ALT and a high viral load, 20.2% have liver inflammation, and HBsAg may be a predictive factor for liver inflammation.

Changes in the Cytokine Profiles of Patients with Chronic Hepatitis B during Antiviral Therapy / 生物医学与环境科学（英文）

Objective@#To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months.@*Results@#In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) ( @*Conclusion@#During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.

Advances in research of the strategies for promoting angiogenesis in tissue engineering / 中华烧伤杂志

Rapid angiogenesis is one of the major issues in the field of tissue engineering, and it is an urgent problem to be solved. The process and related mechanism of angiogenesis have been deeply researched. Meanwhile, various methods or strategies for promoting angiogenesis, involving the application of stem cells and growth factors, and construction and modification of biomaterial scaffolds, have also been reported. On one hand, many remarkable advances in the field of promoting angiogenesis have been achieved; on the other hand, the complexity of mechanism and regulation of angiogenesis have gradually been recognized and emphasized. This paper presents a comprehensive overview of advances in research of the strategies for promoting angiogenesis in the field of tissue engineering.

Effect of Tianhuang Granule on intracranial pressure and serum matrix metalloproteinase-9 in patients with acute cerebral hemorrhage / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect and mechanism of Tianhuang Granule (, THG) on: hydrocephalus in the patients with acute cerebral hemorrhage (ACH) through intracranial pressure (ICP) monitoring, serum matrix metalloproteinase-9 (MMP-9) level observation, and National Institutes of Health Stroke Scale (NIHSS) scoring (for nerve function de ficit).</p><p><b>METHODS</b>Sixty patients with ACH were equally randomized: into two groups by lottery, the control group and the THG group; all were treated with conventional therapy, but to the patients in the THG group, THG was given orally in addition for 28 days. Changes of ICP, MMP-9 expression, and NIHSS scores, as well as the degree of cerebral hematoma and hydrocephalus (by cranial CT scanning) in the patients, were estimated and compared.</p><p><b>RESULTS</b>(1) ICP was lowered more significantly in the: THG group, showing a significant difference between groups on day 7 (P<0.05). (2) MMP-9 expression was down-regulated in the THG group more significantly and earlier than that in the control group. (3) The degrees of cerebral hematoma and hydrocephalus in the THG group on day 7 were reduced significantly as compared with those on day 3 (P<0.05), but in the control group, the day of significant reduction was delayed to day 14, and the degrees on day 7 and day 14 in the two groups were significantly different (P<0.05 and P<0.01). (4) NIHSS score was significantly lower in the THG group than that in the control group on day 14 and day 28 (P<0.05 and P<0.01).</p><p><b>CONCLUSION</b>THG can effectively lower ICP, down-regulate MMP-9 expression, promote the absorption: of cerebral hematoma and hydrocephalus, and improve the nerve function, showing a clinical effectiveness than conventional therapy.</p>