[Research of the relationship of ubiquinone and beclin-1 and liver mitochondria].

OBJECTIVE: To study whether CO-Q10 can protect liver injury caused by acute on chronic liver failure (ACLF) by autophagy. METHODS: Rats were separated into three groups: control group, acute on chronic liver failure (ACLF) and intervenient group, liver tissues were observed by optical microscopy and electron microscopy. The levels of Beclin-1 expression were determined by real-time PCR. And Western Blot. RESULTS: Areas of necrosis detected in intervenient group were alleviated than in ACLF significantly. Most mitochondrias had been degradated in ACLF group while alive in intervenient group. Real-time PCR and Western Blot revealed level of beclin-1 in ACLF was lower than control and intervenient group. CONCLUSION: Intervenient group may ameliorate rat liver injury by promoting autophagy.

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy.

Acute-on-chronic liver failure (ACLF) is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells (mDCs) and the efficacy of methylprednisolone (MP) treatment for hepatitis B virus (HBV)-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at 10-day intervals; 26 patients received conservative medical (CM) management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.

[The analysis of clinical character in different age patients suffered from A-H1N1].

OBJECTIVE: To describe the feature of different age patients with A-H1N1. METHODS: Cross-sectional study was performed in 95 patients who were confirmed to be infected with A-H1N1 from May, 2009 to July, 2009, in according to their age. RESULTS: The average age of patients with A-H1N1 infection was 23.44 +/- 14.73. Accumulative prevalence in children and young adult reached 74.7% of total patients. There was a trend that the subclinical infection rate raised gradually from 0-15 years group to over 45 years group. The percent of lymphocyte in 0-15 years group was significantly higher than other age groups, P = 0.039. The average time of virus shedding were 6.5 +/- 2.10 days (from 2 days to 12 days) , and there were no significant difference in diverse age groups, P = 0.272. 13 out of 95 (13.7%) patients presented complications related with A-H1N1 infection, and 4 of 6 patients complicated with pneumonia were in the 0-15 years group. CONCLUSION: The distribution of age in A-H1N1 infection is markedly different from seasonal influenza, with more cases in school children and young adults and fewer cases in older adults. Flu-like symptoms in children were apparent and pneumonia was the major complication in children.

[Experimental study of Qishen Yiqi Dropping Pills on liver fibrosis in rats].

OBJECTIVE: To investigate the anti-fibrotic effects of Qishen Yiqi Dropping Pills (QYDP) in rats with liver fibrosis (LF). METHODS: The LF model was induced by intraperitoneal injection with dimethylnitrosamine (DMN). Sixty Wistar rats were randomly divided into the normal group, the model group A, the QYDP intervened group , the model group B , and the QYDP treated group B. The degree of LF was evaluated according to 6-phase grading method. The expressions of collagen type I and III and tissue inhibitor of metalloproteinase-1 (TIMP-1) in liver tissues were determined by immunohistochemistry and the levels of collagen type I and III and TIMP-1 mRNA determined by semi-quantitive RT-PCR. RESULTS: Compared with the model group A and B, the degree of LF, the positive expressions of TIMP-1 mRNA and the content of collagen type I and III in liver tissue in the QYDP intervened and treated groups were significantly lower. CONCLUSION: QYDP could reduce the pathological changes and degree of LF in rats, which may be partially through inhibiting the expressions of collagen type I and III and TIMP-1.

[Dynamic evolution of MMP-2 gene expression and its enzymatic activities in experimental liver fibrosis].

OBJECTIVES: To explore the dynamic changes and interactions between MMP-2 and TIMP-2 during experimental liver fibrosis. METHODS: Wistar rats were randomly allocated into a normal group and a model group. To induce liver fibrosis, rats were injected intraperitoneally with dimethylnitrosamine (DMN) three consecutive times in the first week, then two consecutive times per week, totally for 6 weeks. In the normal control group, rats were injected with saline by the same method as the model group. Animals were sacrificed 1, 4, 10, 17, 28, 42, 56 days after starting DMN injections. Conventional histological examinations of the livers were performed with hematoxylin and eosin and Masson staining. The fibrosis was classified into 0 to 4 stages. Hydroxyproline content was determined after liver tissues were hydrolyzed in HCl at 160 degree C for 2 hrs and then measured with spectrometry at 560 nm wavelength. mRNA levels of MMP-2 and TIMP-2 were determined by semi-quantitive RT-PCR. Gelatinase activity of MMP-2 was examined by zymography using gelatin substrate. RESULTS: In the model group the hepatic MMP-2 mRNA expression started to increase 10 days after DMN administration and remained at a much higher level than in the normal group throughout the study period, while TIMP-2 mRNA expression started to be lower than in the normal group 17 days after DMN administration and reached the lowest level on the 28th day. Then it rapidly rebounded and remained higher than that in the normal group from the 42nd day to the end of the study period. TIMP-2/MMP-2 began to be lower by several days than that of the normal group after DMN administration through the remaining study period. Zymography showed that the enzymatic activities of both latent MMP-2 and active MMP-2 were increased during the process of liver fibrosis. CONCLUSION: In liver fibrosis, MMP-2 expression increases, while TIMP-2 expression relatively decreases. The enzymatic activities of MMP-2 increase as the liver fibrosis develops.

[The effect of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats].

OBJECTIVE: To observe the effects of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats. METHODS: Except rats in the control group, all were given intraperitoneal injections of 1% dimethylnitrosamine (DMN 1 ml/kg, two or three consecutive days/a week for 6 weeks). From the first day of the intraperitoneal injection, rats in treatment groups were given valsartan for 8 weeks by gastric gavage. Liver tissue and blood samples of all rats were examined at 56 days (8 weeks). AngII levels were determined by radioimmunoassay. Hepatic mRNA levels of Collagen type I (Col I) and tissue inhibitor of metalloproteinase1 (TIMP1) were evaluated by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Valsartan significantly attenuated the degree of liver fibrosis and decreased the hepatic AngII content compared with DMN treated rats (P<0.01). mRNA levels of Col I and TIMP1 were upregulated in DMN treated rats compared with normal rats. Valsartan downregulated the elevation of Col I and TIMP1 mRNA levels (P<0.01). CONCLUSION: Hepatic AngII content of the model group was increased, the local tissue RAS was activated in DMN induced liver fibrosis. Valsartan can retard the progression of hepatic fibrosis and may provide an effective new strategy for anti-liver fibrosis therapy.

[Dynamic evolution of MMP-13, TIMP-1, type I and III collagen and their interaction in experimental liver fibrosis].

OBJECTIVE: To obtain a detailed pattern of the dynamic evolution and interactions among MMP-13, TIMP-1, type I and III collagen during experimental liver fibrosis. METHODS: Wistar rats were randomly allocated into a normal group, and a model group. To induce liver fibrosis, rats were intraperitoneally injected with dimethylnitrosamine (DMN) three consecutive times in the first week, then two consecutive times per week, totally for 6 weeks. In the normal control group, rats were treated with saline by the same means. Animals were sacrificed 1, 4, 10, 17, 28, 42, 56 days after starting DMN injections. Conventional histological examinations were performed after hematoxylin and eosin, and Masson stain. Fibrosis stages were classified into 0 to 4. Hydroxyproline contents were determined after liver tissues were hydrolyzed in HCl at 160 degrees C for 2 h and then measured with spectrometry at 560 nm wavelength. mRNA levels of MMP-13, TIMP-1, type I and III collagen were determined by semi-quantitive RT-PCR. RESULTS: In the model group, hepatic type I pro-collagen mRNA expression started to increase on the 10th day after DMN administration (t = 2.85, P < 0.05), type III started to increase on the 28th day (t = 4.16, P< 0.01), and TIMP-1 mRNA expression started to increase on the 4th day (t = 2.60, P < 0.05). They all remained much higher than in the normal group throughout the remaining study period. Hepatic MMP-13 mRNA expression started to increase on the 17th day after DMN administration and remained at a higher level than in the normal group until he 28th day (t = 4.08, P < 0.01), then gradually returned to normal level at the end of the study period. CONCLUSION: Although hepatic MMP-13 expression transiently increased during liver fibrosis, enhanced expression of TIMP-1 from the early periods of liver fibrosis inhibited the collagen degrading ability of MMP-13, therefore, over-expressed collagen accumulated in the liver. Thus, it is hypothesized that TIMPs play a pivotal role in liver fibrosis.