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The transcription factor nuclear factor kappa B (NF-B) is activated in hepatocytes in the pathogenesis of hepatic steatosis. However, the action mechanism of NF-B remains to be established in the hepatic steatosis. In this study, the subunit of NF-B was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes. The activity was supported by the phenotypes of knockout (-KO) mice and knockout (-KO) mice. Hepatic steatosis was reduced in the -KO mice, but not in the -KO mice. The reduction was a result of inhibition of HDAC1 activity in the -KO cells. Knockdown of gene led to suppression of hepatocyte steatosis in HepG2 cells. A decrease in sterol-regulatory element binding protein 1c (SREBP1c) protein was observed in the liver of -KO mice and in cell with knockdown. The decrease was associated with an increase in succinylation of SREBP1c protein. The study suggests that stabilizes HDAC1 to support the SREBP1c activity in hepatic steatosis in the pathophysiological condition. Interruption of this novel pathway in the -KO, but not the -KO mice, may account for the difference in hepatic phenotypes in the two lines of transgenic mice.
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Objective To explore the preventive effect of percutaneous endoscopic gastrostomy (PEG) on aspiration pneumonia in patients with dysphagia.Methods The clinical data of 43 patients undertaking PEG was retrospectively collected and the incidence of aspiration pneumonia,microbiological examination of sputum and antibiotics use before and after PEG in all the patients were compared.Results After PEG,the incidence of aspiration pneumonia decreased significantly from 90.7％ to 53.5％ according to clinical diagnosis,from 70.4％ to 18.5％ according to the chest imaging.The use of β-lactamase inhibitor compound decreased significantly,but the detection rate of pseudomonas aeruginosa increased significantly compared with that before PEG.Conclusion PEG can decrease the incidence of aspiration and antibiotics use,and may increase the chances of pseudomonas aeruginosa colonization in the lower respiratory tract.
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ObjectiveTo prospectively study the safety and feasibility of sedation with propofol plus fentanyl for cirrhotic patients undergoing upper gastrointestinal endoscopy (UGIE).MethodsA total of 50cirrhotic patients and 50 control subjects without liver diseases referred to UGIE were assigned to the cirrhotic sedation group and the non-cirrhotic sedation group,respectively.Patients of both groups received sedation with propofol plus fentanyl.Meanwhile,30 cirrhotic patients underwent conventional UGIE.Vital signs of all subjects were recorded before sedation and procedure,five minutes,ten minutes and one hour after the procedure.Number connection test A (NCT-A) and line tracing test (LTT) were completed for all patients before sedation or procedures and 4 hours after endoscopy procedures.Occurrence of sedation-related complications was measured.ResultsIn the cirrhotic sedation group and the non-cirrhotic sedation group,blood pressure,heart rate,respiratory rate and saturation of pulse oximetry decreased of different degrees after secation (P ＞ 0.05 or P＜ 0.05),but returned to normal one hour after endoscopy procedures ( P ＞ 0.05).The total complication rates differed significantly between the cirrhotic sedation group and the non-cirrhotic sedation group [ 36％ (18/50) v.s.14％ (7/50),P ＜0.05 ].However,the rate of such complications as hypotension,bradycardia and hypoxemia in both groups was of no statistical difference (P ＞0.05 ).No cirrhotic patient developed overt hepatic encephalopathy after procedures.In addition,the NCT-A and LTT times before and after sedation in the cirrhotic sedation group and the cirrhotic non-sedation group were longer than those before and after procedure in the non-cirrhotic sedation group ( before sedation or procedure:(55.1 ±22.1)s,(58.6±23.1)s v.s.(36.9±7.0)s,(98.6±33.1)s,(89.5±15.6)s v.s.(81.4±13.6)s,P＜0.05; four hours after procedure:(54.4 ±21.6)s,(58.3 ±22.4)s v.s.(36.3 ±6.3)s,(88.4 ±30.6)s,(80.2 ±15.9)s v.s.(71.8 ± 12.0)s,P＜0.05,while there was no difference between cirrhotic sedation group and cirrhotic non-sedation group ( P ＞ 0.05 ).Within-group comparison showed NCT-A did not change ( P ＞ 0.05 ),whereas,LTT was obviously shorter than pre-sedation or pre-procedure ( P ＜ 0.05) due to learning effect.The differences in the NCT-A and LTT times before and after sedation or procedure were not significant among the three groups (P ＞ 0.05 ).ConclusionSedation with propofol plus fentanyl is relatively safe in cirrhotic patients during UGIE,which will not precipitate hepatic encephalopathy or cause irreversible complications.
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Objective To compare the double-guide wire technique (DGT) with the standard cannulation technique (SCT) in patients with difficult access due to biliary complications after liver transplantation.Methods Difficult CBD cannulation is characterized by unsuccessful cannulation in 10 minutes.A total of 91 patients with biliary complications after liver transplantation were assigned to the DGT group (44patients,including 6 difficult cannulation,41 males and 3 females,30 to 61 years) and the SCT group (47patients,41 males and 6 females,33 to 56 years).An extra 20-minute cannulation was performed on the two groups.Success rate,procedure time and complications were compared.Results CBD cannulation was successful in 36 (81.8％) patients of DGT group and 33 (70.2％ ) patients of SCT group,which was not different ( P ＞ 0.05 ).The time of successful CBD cannulation in the DGT group ( 11.7 ± 3.2 minutes) was shorter than that in the SGT group ( 16.8 ±2.8 minutes,P ＜0.05).The incidence of post-ERCP hyperamylnsemia had no difference in the two groups ( P ＞ 0.05 ).There were no serious complications like infection,hemorrhage or perforation in either group.Mild pancreatitis occurred in 2 cases in the SCT group,but none in DGT.Conclusion DGT is an effective and safe technique in patients with biliary complications after liver transplantation,with no more complications than the SCT group.It is recommended in difficult cannulation of common bile duct (CBD).
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Objective To observe the expression of TLR4 in hepatocellular carcinoma cell line HepG2 after transient and stable HBV genome transfection. Methods Immunofluorescence flow cytometry was used to detect mean fluorescence intensity (MFI) of TLR4 and TLR4 positive cell percentage in hepetocellular carcinoma cell lines HepG2 and HepG2. 2.15. Various doses of HBV DNA plasmid were transfected into HepG2 cells with lipefectamine 2000. Immunofluoroscenee flow cytometry was used to detect MFI of TLR4 and TLR4 positive ceil rate of infected HepG2 ceils. Trypan blue staining was used to examine the sum of living cells. Results MFI of TLR4 and TLR4 positive cell rate of HepG2.2.15 cells were significantly higher than those in HepG2 cells (both P' <0. Ol). MFI of TLR4 and TLR4 positive cell rate of HepG2 cells transfected by various doses of HBV DNA were significantly higher than those in control group (all P' < 0. 01). MFI of TLR4 and TLR4 positive cell rate of infected HepG2 cells were positively correlated with the doses of HBV DNA (both P' <0. 01) and negatively correlated with the sum of living cells (both P' <0. 01). Conclusions Enhanced expression of TLR4 appeared in HepG2 cells with both transient and stable HBV infection, along with reduction of living cells.
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Objective To study the change of TLR4 on peripheral blood monoeytes (PBMCs) and its role in the pathogenesis of chronic severe hepatitis B. Methods The expression of TLR4 on 10000 CDI4 + PBMCs was determined by flow eytometer in 30 healthy control,31 patients with chronic hepatitis B and 30 patients with chronic severe hepatitis B. The level of serum tumor necrosis factor α(TNF- α) was determined by ELISA. Results The values of TLR4 on PBMCs and serum TNF-αof the groups of healthy control, patients with chronic hepatitis B and patients with chronic severe hepatitis B were 2.3±1.1,3.7±2.3, (6.9±4.1 ) mean fluorescence intensity (MFI) and (53.8±38.1 ), ( 164.3±89.9) and (359.8±140.0) ng/L. The TLR4 value in patients with chronic severe hepatitis B was signifi- cant higher than those in healthy control and the patients with chronic hepatitis B ( P <0.05). However, there was no significant difference between the patients with chronic hepatitis B and healthy control ( P > O. 05 ). TNF-α increased gradually and significantly from the healthy control to the patients with chronic hepatitis B and patients with chronic severe hepatitis B. There was a significant positive correlation be- tween the value of TLR4 and the value of serum TNF-αin the patients with chronic severe hepatitis B( r=0.666, P <0.01). Conclusion There may be a role of TLR4 in the pathogenesis of chronic severe hepatitis B.
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Objective To observe the effects of 5-fluorouraeil(5-FU)and eisplatin(DDP)on the expression of Toll-like receptor 2 (TLR2)and Toll-like receptor4(TLR4)in hepatocellular carcinoma cell lines HepG2 and HepG2.2.15.Methods Direct immanotlaorescenee flow cytometry was used to detect mean flubrescence intensity(MFI)of TLR2 and TLR4,and TLR2 and TLR4 positive cell percentage in HepG2 and HepG2.2.15 cells before and after treated with 5-FU.and DDP at various concentrations for 24h,48h and 72h.Results MFI of TLR2 and TLR4.and TLR2 and 11LR4 positive cell percentage in HepG2.2.15 cells were significantly higher than those in HepG2(P＜0.01).After HepG2 and HepG2.2.15 cells were treated with different concentration of 5-FU and DDP,MFI of TLR2 and TLR4,TLR2 and TLR4 positive cell percentage in HepG2 and HepG2.2.15 cells almost had no change.only MFI of TLR2 in HepG2.2.15 cells decreased after cells were treated with 5-FU at the concentrations of 100,200μg/ml and DDP at the concentrations of 20μg/ml for 72h(P＜0.05 for all).Conclusions 5-FU and DDP can not activate TLR2 and TLR4 signal pathway in hepatocellular carcinoma cell lines HepG2 and HepG2.2.15.To find the activated pathway in TLR2 and TLR4 signal pathway,some other methods should be used,and this will be helpful in antieancer therapy.
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Objective To investigate the role of TLR4 in the pathogenesis of chronic hepatitis B(CHB) by study the expression of TLR4 in liver tissues in patients with CHB, and the relationship among TLR4 and serum HBV DNA level, clinical severity degrees and histo-logical grades and stages. Methods Expression of TLR4 in liver tissues was semi-quantitatively determined by immunohistochemistry and e-valuated by a scoring system in 75 patients with CHB and 10 health controls. Results The positive staining of TLR4 mainly located in the cytoplasm and some on cell membrane of bepatocytes. Expression of TLR4 in the liver tissues of patients with CHB was stronger than that of health controls. The scores of TLR4 expression in patients with mild, moderate and severe CHB were 1.0±0.5,2.3±0.5 and 2.9±0.4. The scores increased gradually and significantly along with the increase of clinical severity degrees( F = 104.8, P<0.01). The scores of TLR4 expression in the liver tissues of patients with CHB were positively correlated with the clinical severity degrees (r=0.838, P<0.01) and histological grades (r=0.579, P<0.05), but not correlated with Lg (serum HBV DNA) or histological stages. Conclusion TLR4 was up-regulated in the hepatocytes of patients with CHB. There may be a role of TLR4 in the pathogenesis of CHB.
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Objective To study the effect of matrine on the expression of a proliferation-inducing ligand (APRIL) in colorectal cancer cell line (SW480 cell). Methods MTT assay was used to evaluate the inhibitory effect of matrine on SW480 cells. The protein and mRNA levels of APRIL in SW480 cells were determined by immunohistochemistry and real-time fluorescence quantitative PCR (RFQ-PCR). SW480 cells were treated with 0.5,1.0,2.0 mg/ml of matrine for 24 h, 48 h and 72 h. FU and blank were served as drug control and blank control groups, respectively. Results Matrine had obviously inhibitory effect on proliferation of SW480 cells in a time- and dose-dependant manner. The expression of APRIL was strong in SW480 cells. When treated with 50,100,200 ug/ml of FU, the APRIL mRNA levels in SW480 cells raised gradually and reached the highest levels at 72 h after treatment, which were significantly higher than those in blank control group (all P value<0.001). When treated with 0. 5,1.0, 2.0 mg/ml of matrine, the APRIL mRNA levels in SW480 cells increased at 24 h after treatment, which were significantly higher than those in blank control group (all P value<0. 001), and then decreased gradually and almost equal to level of blank control group at 72 h. Conclusion In treatment with FU, the survival cells.may have stronger ability of proliferation due to higher expression of APRIL in SW480 cells. Anti-APRIL therapy might be an important assistant treatment to counter the impact of APRIL. Matrine will not cause persistent increase of APRIL mRNA levels in SW480 cells, so it might be a helpful drug in anti-tumor theraphy.
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Objective To investigate the effect of glycyrrhizin(GL) on the expression of hepatitis B virus e antigen(HBeAg),hepatitis B virus surface antigen(HBsAg),HBV DNA levels and cell proliferation in HepG2.2.15 cell line.Methods HBV DNA level was examined by Real-time PCR.HBsAg and HBeAg levels were examined by ELASA,and cell proliferation was examined by MTT before and after stimulated with GL.The GL groups were compared with the blank control group.Results HBsAg levels in the GL groups were inhibited in dose-dependent manner compared with the blank control group(P
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In order to study the clinical features and therapeutic status of ulcerative colitis(UC) in south China.Method A retrospective analysis was performed in 141 patients with UC diagnosed in past 12 years.Results The most frequent age at onset of disease was 20～45 years and the second was 57～67.Diarrhea and bloody stools were the most common symptoms which were present in 87.2% and 87.9% of cases.Severe complications and colon carcinoma were few in the cases.There was significant correlation in the extent of colonic involvement,the severity of illness and extracolonic manifestations.Severe complication and total colitis were more frequently seen in the patients with extracolonic manifestations than that in the patients without extracolonic manifestations(P
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AIM:To investigate the expression of TLR2 and TLR4 in hepatocellular carcinoma(HCC),and to analyze their correlations to clinicopathologic features of HCC.METHODS:The protein and mRNA levels of TLR2 and TLR4 in HCC and para-tumor tissue were determined by immunohistochemistry and real-time fluorescence quantitative PCR(RFQ-PCR).RESULTS:The protein and mRNA levels of TLR2 and TLR4 in HCC were lower than those in para-tumor tissue(P