ObjectiveTo evaluate the one-year follow-up of the therapeutic efficacy of human umbilical cord derived-mesenchymal stem cell (UC-MSC) transplantations in decompensated liver cirrhosis patients with ascites.MethodsFifty-four liver cirrhosis patients with ascites in Research Center for Biological Therapy in 302 Military Hospital were divided into treatment group (n=38) and control group (n=16) in a prospective controlled single-blinded trial.UC-MSC (0.5-1.0) × 106/kg and saline were intravenously transplanted into patients monthly for 3 times in treatment group and control group,respectively.The liver function,hepatitis B virus (HBV) DNA level,ascites and the model for end-stage liver disease(MELD)scores at different time points were compared between two groups.The comparison between groups was done by Mann-Whitney U test,and the data before and after transplantations were compared by Wilcoxon signed rank sum test.ResultsThere were no significant differences of alanine transaminase (ALT),total bilirubin (TBil),cholinesterase (CHE),HBV DNA positive rate and MELD scores at different time points between two groups (P＞0.05).However, the albumin ( A1b)level was significantly increased after 36 weeks of UC-MSC transplantation in treatment group, which were (28.47±4.45)g/L at week 0 and ( 34.82±4.50)g/L at week 48 (P=0.046). Meanwhile, the ascites reduced markedly in treatment group with (46.6 ±30.6) mm at week 0 and (6.6±13.6) mm at week 48,which were significantly different from control group at the end of follow-up (P =0.037). Conclusion UC-MSC transplantations may help to increase A1b level and reduce ascites in patients with decompensated liver cirrhosis.

OBJECTIVETo study the role of tumor necrosis factor-alpha (TNFalpha) on enterocyte apoptosis in the experimental model of fulminant hepatic failure (FHF).

METHODSLiver damage was induced by lipopolysaccharide (LPS)/TNFalpha in D-galactosamine (GalN) sensitized BALB/c mice. Serum TNFalpha levels were determined by enzyme-linked immunosorbent assays (ELISA). The intestinal tissues were studied micro- and ultra-microscopically at 2 h, 6 h, 9 h, 12 h and 24 h time points in mice with fulminant hepatic failure. Enterocyte apoptosis was determined by TUNEL method. The TNFR I expression in the intestinal tissue was tested by immunohistochemistry.

RESULTS(1) Gut mucosa was morphologically normal at every time point in all groups, but typical apoptotic cells could be seen in the experimental groups under the electron microscope. Apoptosis rate of gut mucosal epithelial cells was significantly increased at 6 h (large intestine: 6.47e(-3)+/-2.91e(-4); small intestine: 6.64e(-3)+/-3.78e(-4)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 h (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)), and peaked at 12 h in mice with FHF. (2) TNFalpha induced apoptosis of enterocytes in mice with FHF. Anti-TNFalpha inhibited this effect. (3) The integrated OD (IOD) levels of TNFalpha receptor I protein expressed differently in the intestine of mice with GalN/LPS and GalN/ TNFalpha-induced FHF at 9 h after GalN/LPS and GalN/ TNFalpha administration, in comparison with those of the control groups. IOD level of TNFRI changed significantly at 6 h (large intestine: 2.82e(+4)+/-4.60e(+3); small intestine: 1.14e(+4)+/-2.13e(+3)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)) hours after GalN/LPS and GalN/ TNFa administration. The expression of TNFR1 protein was significantly higher at 9 and 12 h after GalN/LPS and GalN/TNFa administration than other time points. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis.

CONCLUSIONTNFa can induce enterocyte apoptosis in mice with FHF. Anti- TNFalpha IgG can inhibit this role. Excessive TNFRI expression of enterocyte in fulminant hepatic failure can be induced by TNFa, which suggests that TNFalpha can induce apoptosis of enterocyte by up-regulation of TNFRI protein expression.

Animals ; Apoptosis ; physiology ; Enterocytes ; pathology ; Galactosamine ; Lipopolysaccharides ; Liver Failure, Acute ; chemically induced ; pathology ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

Animals ; Blood-Brain Barrier ; drug effects ; Liver ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Necrosis ; physiopathology ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo explore the mechanism of fulminate hepatic failure (FHF) complicated with spontaneous peritonitis (SBP) through the research of bacteria invading the intestinal mucosa barrier.

METHODS240 BalB/c male mice were divided into four groups as isotonic NS group (n = 40), lipopolysaccharide (LPS) group (n = 40), galactosamine (GalN) group (n = 40) and FHF model group (n = 120). Each mouse received same volume of NS, LPS (10 ug/kg), GalN (800 mg/kg) or LPS (10 ug/kg)/GalN (800 mg/kg) intraperitoneal injection according to its group. 8 mice were executed at 2, 6, 9, 12 and 24 hours after injection, respectively, and the liver and intestinal tissue samples were taken at the same time. ALT was measured by automatic biochemical analyzer and was compared between groups using Mann-Whitney U test. Liver and intestinal tissue received HE staining. The ultrastructure of intestinal mucosa and the method by which bacteria invaded the intestinal mucosa were observed by transmission electron microscopy. All data were analyzed by SPSS13.0 statistic software.

RESULTSALT level, results of hepatic pathology, mortality and clinical manifestations of mice in the FHF model group met the diagnostic criteria of FHF. Intestinal tissue was found with slight edema and little inflammatory cells infiltration through HE staining in all the 4 groups of mice 9 hours after injection. Microvilli were found broken, shed and shorten in the intestinal epithelial cells with incomplete tight junction (TJs) and obviously changed organelles in the FHF model group of mice observed by transmission electron microscope. Mass hemorrhagic necrosis of liver cells with remnant liver cells swelling and many inflammatory cells infiltration by HE staining in the FHF model group. But the changes in hepatic pathology and intestinal mucosa ultrastructure were not so obvious in the mice of NS, LPS and GalN groups. Bacteria penetrated the intestinal wall by pinocytosis 6 to 9 hours after injection in the FHF model group, the microvilli were broken off and TJs turned rupture in the areas that the bacteria penetrated. The bacteria were found in the form of cyst 12 hours after injection.

CONCLUSIONLPS (10 mg/kg)/GalN (800 mg/kg) combined injection was successful in establishing the FHF mice model. The rupture of TJs may provide conditions for intestinal bacteria to penetrate the intestinal mucosa in FHF. Rupture of TJs may be one of the reasons why FHF was complicated with SBP.

Animals ; Disease Models, Animal ; Intestinal Mucosa ; microbiology ; pathology ; Liver ; pathology ; Liver Failure, Acute ; microbiology ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Tight Junctions ; microbiology ; pathology

OBJECTIVETo compare the diagnostic value between digital photography (DR) and multi-slice spiral CT (MSCT) in fracture and dislocation of foot and ankle.

METHODSFrom August 2010 to August 2012, the DR and MSCT data of 52 patients with fracture and dislocation of foot and ankle were compared according to results of surgery or discharge diagnosis. There were 37 males and 15 females, aged from 15 to 49 years old. Wilcoxon signed rank test was used for statistical analysis.

RESULTSThe results of 52 cases of MSCT were matched with the postoperative or discharge diagnosis. A total of 172 fractures were found on MSCT and 98 fractures were found on DR, the results had significant difference in detecting fracture (V=1 081, P<0.05); A total of 24 dislocations were found on MSCT and 16 dislocations were found on DR,the results also had significant difference in detecting dislocation (V=21, P<0.05). Fractures of 6 cases with DR diagnosis were corrected and located by MSCT.

CONCLUSIONMSCT is significantly better than DR in diagnosis of fracture and dislocation of foot and ankle. The examination of two parts should be performed in DR. MSCT and multi-planar reconstruction (MPR) examination should be further performed if DR results are unclear or do not match with clinical symptoms, missed diagnosis and misdiagnosis can be avoided.

Adolescent ; Adult ; Ankle Injuries ; diagnostic imaging ; Female ; Foot Injuries ; diagnostic imaging ; Fractures, Bone ; diagnostic imaging ; Humans ; Image Processing, Computer-Assisted ; methods ; Joint Dislocations ; diagnostic imaging ; Male ; Middle Aged ; Multidetector Computed Tomography ; methods ; Photography