[Clinical analysis of 2 820 cases of drug-induced liver injury].

Objective: To investigate the clinical characteristics, incidence trend, underlying diseases, causative drug and prognosis of drug-induced liver injury (DILI), so as to provide basis for its prevention and treatment. Methods: A retrospective study was conducted on 2 820 DILI cases who were admitted to our hospital from January 2002 to December 2015, and their clinical characteristics, incidence trends, underlying related diseases, causative drug, treatment and outcome were analyzed. Results: Among 2 820 DILI cases, the ratio of male to female was 1:1.44, and the age was (44.00±16.32) years old. According to the clinical classification of DILI, there were 2 353 cases (83.43%) of hepatocyte injury, 353 cases (12.51%) of cholestatic type and 114 cases (4.04%) of mixed type. In the three clinical classification of DILI, there was no statistically significant difference in the ratio of male to female (χ(2) = 3.032, P > 0.05). However, the difference in the ratio of male to female between different age groups was statistically significant (χ(2) = 48.367, P < 0.001). Among the patients with liver disease and acute liver disease admitted to our hospital from January 2002 to December 2015, the proportion of DILI and acute DILI showed an overall upward trend. The main underlying related diseases of 2 820 DILI cases were fever (15.14%), skin diseases (11.84%), cardiovascular and cerebrovascular diseases (11.17%). Chinese herbal patent medicines (37.49%), antibiotics (15.85%), antipyretic-analgesics (14.37%), and so on were the main causative drugs involved, and the prognostic differences among the three clinical classifications of DILI in terms of cure, improvement, ineffectiveness, and death were statistically significant (H = 61.300, P < 0.001). Conclusion: In recent years, among the patients with liver disease in our hospital, the proportion of DILI has shown an obvious upward trend, involving a variety of underlying diseases and causative drugs, and thus it needs clinical attention.

miR-132 weakens proliferation and invasion of glioma cells via the inhibition of Gli1.

OBJECTIVE: Transcriptional factor Gli1 in Hedgehog signal pathway facilitates epithelial mesenchymal transition (EMT) and is associated with invasion or proliferation of multiple tumor cells. The previous study showed the correlation between miR-132 down-regulation and glioma pathogenesis. We investigated the role of miR-132 in mediating Gli1 expression and in affecting proliferation or invasion of glioma cells. PATIENTS AND METHODS: Dual luciferase reporter gene assay was used to confirm the targeted regulation between miR-132 and Gli1. Tumor tissues at different pathological grades (grade II, III and IV) were collected from glioma patients, in parallel with brain tissues from contusion surgery. The expression of miR-132 and Gli1 was measured by RT-PCR. Glioma cell line U251 was treated with miR-132 or si-Gli1 followed by measuring the expression of Gli1, E-cadherin, Vimentin and Cyclin D1. In addition, flow cytometry and transwell assay were performed to evaluate cell invasion potency. RESULTS: Bioinformatics analysis showed the complementary binding sites between miR-132 and 3'-UTR of Gli1 mRNA. Transfection of miR-132 mimic significantly reduced luciferase activity, indicating the targeted regulatory relationship between miR-132 and Gli1 mRNA. Compared with control group, miR-132 expression was decreased and Gli1 level was elevated in glioma tissues, both of which were correlated with the pathological grade. Transfection of miR-132 mimic or si-Gli1 remarkably suppressed the expression of Gli1, Vimentin or Cyclin D1 in U251 cells, up-regulated E-cadherin expression, suppressed cell proliferation and invasion. CONCLUSIONS: Our data indicated that over-expression of miR-132 could inhibit proliferation or invasion of glioma cells via targeted inhibition of Gli1 expression.

Insulin in combination with selenium inhibits HG/Pal-induced cardiomyocyte apoptosis by Cbl-b regulating p38MAPK/CBP/Ku70 pathway.

OBJECTIVE: In this study, we investigated whether insulin and selenium in combination (In/Se) suppresses cardiomyocyte apoptosis and whether this protection is mediated by Cbl-b regulating p38MAPK/CBP/Ku70 pathway. MATERIALS AND METHODS: Firstly, H9c2 cardiomyocytes were treatment with high glucose (25 mmol/L) and palmitate (600 µmol/L) (HG/Pal). Next, H9c2 cardiomyocytes were treatment with HG/Pal+In/Se (10 nmol/L Insulin in combination with 10 nmol/L selenium). Finally, cells were treated with siRNA against Cbl-b, followed by HG/Pal and HG/Pal+In/Se treatment. Then, Cell apoptosis was observed by flow cytometry (FCM). The levels of Cbl-b, p-p38MAPK, CBP and Bax were examined by Western blotting. The acetylated Ku70 was detected by immunoprecipitation. RESULTS: Insulin and selenium in combination reduced cell apoptosis, up-regulated Cbl-b expression, down-regulated p38MAPK, CBP and acetylated Ku70 expressions and prevented Bax translocation, whereas Cbl-b knockdown strongly suppressed In/Se-induced these effects in HG/Pal-treated cardiomyocytes. CONCLUSIONS: Insulin and selenium synergistically suppressed cardiomyocyte apoptosis by Cbl-b regulating p38MAPK/CBP/Ku70 pathway.