Blindness, Cortical ; etiology ; Chemical and Drug Induced Liver Injury ; complications ; Humans ; Liver Diseases ; complications

Objective To investigate the effects of tripterygium glycosides combined with methotrexate in treatment of rheumatoid arthritis (RA) curative effect and peripheral blood of patients with IL-6, effects of IL-10 and TNF- alpha. Methods 80 patients with RA from February 2014 to August 2016 in our hospital were retrospectively analyzed. According to the different treatment methods by for the observation group, the control group (40 cases). To compare and analyze the curative effect before and after short-term treatment and treatment of patients in the 2 groups were the main clinical symptoms and signs of change and ESR, RF, CRP, IL-6, TNF- alpha, IL-10 index. Results The total effective rate of observation group (92.50％) was significantly higher than the control group (77.50％), the difference was statistically significant (P<0.05), 2 groups of patients before treatment of main clinical symptoms and signs, there was no significant difference, after treatment, clinical symptoms and signs of 2 groups of patients were compared with those before treatment was statistically significant to alleviate the differences (P<0.05), and the observation group of main clinical symptoms and signs were lower than the control group and the remission (down), the difference was statistically significant (P<0.05).Before ESR, the treatment of 2 patients with RF, CRP, TNF- IL-6, alpha, IL-10 index level, no statistical significance, the 2 groups after treatment in patients with ESR, RF, CRP, IL-6, TNF- alpha, IL-10 index level than before treatment with significant difference (P<0.05), and the observation group ESR, RF, CRP, TNF- alpha, IL-6 average index of water compared with the control group decreased significantly, IL-10 index increased significantly than the control group. The difference was statistically significant (P<0.05). Conclusion Tripterygium glycosides combined with methotrexate in treatment of rheumatoid arthritis And it can effectively inhibit the expression of peripheral serum L-6 and TNF- alpha, promote the expression of IL-10 and alleviate the inflammatory reaction

Objective To determine the effect of hypoxia conditions on the expression of autophagyrelated genes including P62,LC3 and Beclin-1 in the gastrocnemius muscles of rats with alimentary obesity and the possible mechanism of cellular autophagy induced by hypoxia exercises.Methods The model of rats with alimentary obesity was induced in Sprague-Dawley rats using high-fat diet.Then the obese rats were randomly divided into a control(C) group,a hypoxia-exercises-for-1-week(E1) group,a hypoxia-exercises-for-2-weeks (E2) group,a hypoxia-exercises-for-3-weeks (E3) group and a hypoxia-exercises-for-4-weeks(E4) group,each of 10.The rats were exposed to the environment where the simulated hypoxia was of about 13.6％ oxygen concentration(about the oxygen concentration at an actual altitude of 3,500 m),and underwent treadmill running with the speed at 20 m/min on a slope of 0 gradient every day,five days a week.After the last training,the rats were killed and sampled.The RT-PCR was used to detect the level of P62,LC3 and Beclin-1 mRNA and Western Blotting was conducted to examine the changes of protein P62 and LC3 before and after the intervention.Results Compared with group C,the expression of Beclin-1 mRNA in group E1,E2 and E3 increased significantly(P＜0.05),while the expression of protein Beclin-1 decreased significantly in group E2.The expression of protein Beclin-1 of group E2 and E3 was significantly lower than that of group E4,but there were no significant differences between group E2 and E3.Compared with group C,the relative expression of P62 mRNA in group E1 and E2 increased significantly(P＜0.05,P＜0.01),with that of group E2 significantly higher than group E1 (P＜0.05).Moreover,the relative expression of P62 mRNA in group E3 was significantly lower than that of E2(P＜0.01),and that of group E4 was significantly higher than group C,E1 and E3(P＜0.01).The relative expression of protein P62 in the obese rats in group E3 was significantly higher than that of group E2(P＜0.05).The relative expression of LC3 mRNA in group E2,E3 and E4 was significantly higher than that of group C(P＜0.01).Moreover,there were no significant differences in LC3-Ⅱ/LC3-Ⅰ protein among the five groups.Conclusion Hypoxia exercise can significantly enhance the relative expression of autophagy genes,and promote,to some extent,the autophagy.However,the transcription of autophagy genes does not happen synchronically with the synthesis of autophagy proteins.Moreover,an increase in autophagy in the skeletal muscle can be seen in the first two weeks of hypoxia exercises,followed by a gradual decrease with time prolonged,which may be the result of the gradual adaptation to hypoxia stimulation of the body.

Objective To investigate the correlation between interferon γ-inducible protein-10 and expression of peroxisome proliferator-activated receptor (PPAR) and fatty acid-binding protein-4 (FABP-4) in pregnant women with preeclampsia. Methods 62 PE pregnant women who were treated in our hospital from January 2016 to January 2017 were enrolled in this study. They were divided into mild PE group (34 cases) and severe PE group (28 cases) according to their severity of disease. In addition, 30 healthy pregnant women in our hospital were selected as the control group. The levels of IP-10 in the three groups were measured by enzyme-linked immunosorbent assay (ELISA), and the levels of PPAR and FABP-4 and the correlation between them were analyzed using western blot assay. Results The levels of IP-10 in mild and severe PE pregnant women were significantly higher than those in the control group, and the mild group was lower than the severe group(P＜0. 05). Compared with the control group, the level of PPAR in mild and severe PE pregnant women decreased significantly, and the severe group was lower than the mild group (P＜0. 05). Compared with the control group, FABP-4 levels in mild and severe PE groups were significantly elevated, and the mild groups was lower than the severe group(P＜0. 05). There was a negative correlation between the level of PPAR and IP-10 (r=-0. 529, P＜0. 05), and a positive correlation between FABP-4 and IP-10(r=0. 692, P＜0. 05). Conclusion There is a certain correlation between PPAR and FABP-4 and the level of IP-10 in pre-PE pregnant women. lt can be used to determine the condition of pre-PE in pregnant women.

Objective To investigate the clinical features of drug-induced autoimmune hepatitis (DIAIH) and its therapeutic strategies,and to provide a reference for early diagnosis and treatment of this disease and prevention of chronicity.Methods The clinical data of 116 patients with drug-induced liver injury (DILI) or DIAIH confirmed by medical history,liver biochemistry,and liver biopsy were analyzed retrospectively.Among these patients,13 had DIAIH and 103 had simple DILI (30 patients in the hepatocytetype group and 73 in the cholestasis/mixed-type group).The population characteristics,major drugs inducing the diseases,clinical manifestations,liver biochemical parameters,liver pathological features,and clinical outcome were compared between groups.The Kruskal-wallis H test was used for comparison and the Mann-Whitney U test was used for comparison between any two groups.The chi-square test was used for comparison of categorical data,and the R×C chi-square test was used for comparison of rates between the three groups;in the case of significant differences,the R×C contingency table was used for comparison between any two groups.Results The patients with DIAIH had a mean age of 53.54±8.28 years,and the mean age was 35.13±13.46 and 46.99±14.82 years for the hepatocyte-type group and cholestasis/mixedtype group,respectively.The disease was mainly induced by a combination of various drugs.The patients with DIAIH had significantly higher serum levels of alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,and alkaline phosphatase and a significantly higher positive rate of anti-nuclear antibody than those with DILI (all P ＜ 0.05).In patients with DIAIH,the liver pathological features and the features of response to treatment were as follows:obvious interface hepatitis,proliferation of small bile ducts,and mixed inflammatory cell infiltration in the portal area,including eosinophils and plasma cells,and the short-term corticosteroid therapy had a good therapeutic effect.Conclusion DIAIH has a low incidence and is more common in the female population,with the features of tissue injury in both DILI and autoimmune hepatitis.The short-term corticosteroid therapy can prevent disease progression and reduce chronicity.

Objective: To investigate the role and mechanism of action of Yiqi Huoxue Recipe (YQHXR) in regulating autophagy and reversing liver fibrosis in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Healthy male Wistar rats were intraperitoneally injected with a mixture of CCl4 (30%) and olive oil (70%) twice a week for 8 weeks to establish a rat model of liver fibrosis. The rats administered normal diet were used as control group. Furthermore, YQHXR or Fuzheng Huayu Recipe (FZHYR) was intragastrically administered to the rats. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic biochemical analyzer. Hematoxylin-eosin (HE) staining and Masson staining were performed to observe the degree of fibrosis in rat liver. The protein expression of α-smooth muscle actin (α-SMA) and type I collagen α1 chain (Col1A1) in liver tissue was measured by immunohistochemistry. Furthermore, the mRNA and protein expression of α-SMA, Col1A1, autophagy-related protein 7 (Atg7), microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (SQSTM1/p62) were determined using qRT-PCR and Western blotting, respectively. Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups was made using the LSD test. P < 0.05 was considered as statistically significant. Results: The YQHXR group and FZHYR group had significantly lower serum levels of ALT and AST than the model group (ALT: 66.8±10.42 U/L and 73.2±10.33 U/L vs 106.80±18.24 U/L, F = 31.672, P < 0.001; AST: 122.6±16.65 U/L and 125.4±16.92 U/L vs 278.4±66.14 U/L, F = 25.539, P < 0.001). The pathological grades of hepatic fibrosis were S5.64±0.22, S3.70±0.35, and S3.90±0.34 in the model group, YQHXR group, and FZHYR group, respectively (F = 362.188, P < 0.001). Compared with the control group, the YQHXR group and FZHYR group had significantly reduced mRNA and protein expression of α-SMA, Col1A1, Atg7, and LC3B and significantly increased expression of p62 (all P < 0.05), and the differences were greatest in the YQHXR group. Conclusion YQHXR and FZHYR can prevent or reverse liver fibrosis by regulating hepatocyte autophagy and inhibiting hepatic stellate cell activation and collagen deposition.

Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) can negatively regulate innate immunity and adaptive immunity and participate in the development and progression of various liver diseases, such as hepatitis, liver cirrhosis, and hepatocellular carcinoma, by affecting a variety of signaling pathways. This article summarizes the current research on the involvement of TIPE2 in the pathogenesis of different liver diseases and points out that TIPE2 may become a new target for the treatment of liver diseases.

Objective:To analyze the clinical and pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and not receiving antiviral therapy.Methods:This study retrospectively included CHB patients diagnosed by liver biopsy at the Third Hospital of Hebei Medical University from January 2008 to December 2022. According to the HBV DNA and HBeAg status of "immune tolerance period and immune control period", these patients were divided into three groups: chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group including the patients that did not meet the inclusion criteria of the above two groups. Kruskal-Wallis H test was used for comparison of continuous data between multiple groups. Mann-Whitney U test was used for comparison of continuous data and ordered categorical data between two groups. Chi-square test or Fisher′s exact test was used for comparison of categorical data between two groups. Results:A total of 284 CHB patients with normal ALT were enrolled. There were 64, 88 and 132 cases in the chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group, respectively. Histopathological analysis revealed that there were 182 (64.08%) cases with pathological inflammation grade (G) and/or fibrosis stage (S)≥2, 155 (54.58%) with S≥2 and 120 (42.25%) with G≥2. The proportion of patients with G and/or S≥2 in the indeterminate group [70.45% (93/132)] was higher than that in the chronic HBV carrier group [48.44% (31/64)] and inactive HBsAg carrier group [65.91% (58/88)] (both P<0.05). Patient′s age and the ratio of patients with S≥2 in the chronic HBV carrier group [33 years old, 39.06% (25/64)] were smaller than those in the inactive HBsAg carrier group [39 years old, 56.82% (50/88)] and the indeterminate group [39 years old, 60.61% (80/132)] (all P<0.05). Patients in the inactive HBsAg carrier group (19 U/L) had lower ALT levels than those in the chronic HBV carrier group (26 U/L) and the indeterminate group (23 U/L) (both P<0.05). The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 [73.08% (57/78) vs 32.08% (17/53), P<0.05], and the proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg increased gradually with age. The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 in the chronic HBV carrier status and indeterminate groups [93.33% (28/30) vs 43.33%(13/30), P<0.05; 59.46% (22/37) vs 12.50% (2/16); both P<0.05]. There was a statistically significant difference in the incidence of significant liver injury between patients≤ 30 years old and >30 years old [52.7% (39/74) vs 68.1% (143/210), P<0.05]. Conclusions:Significant liver injury occurred in 64.08% (182/284) of CHB patients with normal ALT not receiving antiviral therapy, which required the attention of clinicians. Among CHB patients with normal ALT, the expression site of HBcAg in hepatocytes was related to the occurrence of significant liver injury and could be expected to serve as an important indicator for predicting the patient′s status and the necessity of antiviral treatment. CHB patients with positive HBV DNA who were older than 30 years required antiviral treatment, and CHB patients≤30 years with normal ALT and significant hepatic tissue damage also required antiviral treatment.

Liver fibrosis occurs due to damages caused by liver diseases of various etiologies and activation of hepatic stellate cells, leading to the repairing and damaging cycle by secreting a large amount of extracellular matrix and formation of fibrosis tissues in the liver. Early reversal of this process could prevent further development and progression of the disease, which may reduce incidence of the end-stage liver disease and even liver cancer. This review summarized and discussed recent advancements and mechanisms of liver sinusoidal endothelial cells, Notch signaling pathway, YAP/TAZ signaling pathway, and autophagy in regulation of liver fibrosis and then enumerated the Traditional Chinese Medicine in reversal of liver fibrosis process and the underlying molecular mechanisms. It expects to provide novel approaches and research ideas for future control of liver fibrosis using Traditional Chinese Medicine.