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Objective To establish a method of a new type of liver fibrosis model in rats induced by repeated injection of rabbits' liver homogenate. Methods Female Wistar rats were randomly divided into a normal control group (8 rats), a human albumin induced liver fibrosis model group (15 rats) and a rabbits'liver homogenate induced liver fibrosis group (15 rats). The induction of liver fibrosis began with an immune sensitizing period (4 weeks) and was followed by an immune attacking period (8 weeks). After 8 weeks'attacking, all rats were sacrificed under anesthesia. Liver enzymes in serum and hydroxyproline in liver tissue were measured by standard methods and pathological scores were assessed by pathologists. Results The rats' liver weight, ratio of liver weight to body weight in the model group of liver homogenate were significantly increased compared with the normal control group. Serum globulin, tissue hydroxyproline were significantly increased, whereas serum albumin was significantly decreased in the homogenate group. There was only 20.0 percent of liver fibrosis score (2/10) exceeding a degree of 3 in the albumin group whereas 73.3 percent of that (11/15) were exceeding a degree of 3 in the homogenate group and the difference was significant (x2 = 4. 87,P = 0. 027). Conclusion In the study, we established a method of a new type of experimental liver fibrosis model in rats. The method has a significantly high success rate and this model can be used to study the mechanism of liver fibrosis and the efficacy of antifibrotic medicine.
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Objective To study the present situation of misdiagnosed acute pancreatitis(AP)in China and to im prove the identification of AP.Methods One hundred and forty.four documents of Chinese-language cases studies involving the misdiagnosis of AP published from 1988 to 2007 were identified by searching in the China National Knowledge Infrastructure(CNKI).Retrospective study of misdiagnosed diseases,clinical manifestations,risk fac tors and accessory examinations etc,Was made in 1098 patients with AP.Results(1)The patients related to the departments of internal medicine,surgery,obstetrics and gynecology,and pediatrics and so on.The misdiagnosed diseases were over 63 kinds.The first five places successively were:cholelithiasis combined with biliary infection (182 times),acute gastroenteritis(158 times),coronary heart disease(108 times),acute appendicitis(102 times),and intestinal obstruction(90 times).(2)Abdominal pain(878 cases)is the main manifestation in AP, and the first five regions of abdominal pain successively were:upper-middle abdomen(434 cases),whole abdomen (220 cases),right lower quadrant(79 cases),right upper quadrant(74 cases),left upper quadrant(71 cases). (3)Cholecystolithiasis(145 cases)was the first risk factor,and followed the order of fat meal(106 cases)>chronic cholecystitis(72 eases)>alcohol(67 times).(4)The number of cases diagnosed by operation was the most,up to 378;others successively were serum and urine amylase examinations(35 1 CtLSe8)and abdominal CT scan(135 cases),and abdominal ultrasound imaging(59 cases).Conclusions(1)The main causes of misdiag nasis were superficial understanding of predisposing condition,lack of correct analysis on clinical manifestations, and mistakes in the analysis Oil the accessory examinations.(2)Although amylase in serum or urine has limitation in diagnosis,it still Was the main method of diagnosis;and it Was necessary to be examined by abdominal CT or sur gical exploration for patients who were highly suspected as having AP but could not be diagnosed.
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Objective To investigate the incidence, consequence and short-term prognosis of noninflammatory ascitic bacterial translocation (BT) in cirrhotic patients. Methods A set of universal primers was designed based on the conservative regions in bacterial 16S ribosomal RNA (16S rRNA) genes. Eighty-seven ascitie and/or serum samples from cirrhotic patients were amplified using PCR, and bacterial DNA was detected as molecular marker of BT. The corresponding bacteria were identified by nucleotide sequencing of purified PCR products. All patients were followed up of six months. The outcome of the patients were observed and bacterial DNA in ascites were detected again in some patients. Results Among 87 cirrhotic patients, bacterial DNA was positive in 33 aseites and 12 serum samples with E. coli in predominant. The bacterial DNA identification indicated that similarity of 99% between the sequence was found in both ascites and blood from one patients. Six months later, the bacterial DNA in ascites was dynamically changed. The variables correlatied with prognosis of the patients were liver function and BT. Conclusions Non-inflammatory BT is a dynamic process in cirrhotic patients, which may either lead to infection or be eliminated by the host. Liver function and the incidence of BT can influence the short-time prognosis of cirrhotic patients.
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Objective: To observe the clinical effect of Tongfu granules(通腑颗粒) on the gastro- intestinal dysfunction in patients with multiple organ dysfunction syndrome(MODS).Methods: The trial was prospective,multi-centric and clinically controlled.One hundred and forty patients with MODS who had been selected were randomly divided into two groups: mosapride citrate group and Tongfu granules group.Respectively at 0 hour,the 48 th hour,the 7 th day or before death, the following scoring systems were calculated: the intestinal dysfunction score,acute physiology and chronic health evaluationⅡ((APACHEⅡ)) score and Marshall score.The duration of mechanical ventilation,hospitalization in intensive care unit(ICU) and the prognosis within 28 days were recorded.Results: After treatments,the intestinal dysfunction score,(APACHEⅡ) score and Marshall score of all patients decreased,at the same time,the therapeutic effects of Tongfu granules group were more significant than those in mosapride citrate group(P20 scores.The mortality was elevated with the increased number of dysfunction organs.Conclusion: Tongfu granules can ameliorate the severity of the disease situation andimprove the prognosis of patients with MODS.
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60 years old)was significantly higher (41)than that in patients
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OBJECTIVE To study the characteristic change of the expression of caspase 3 of spleen in different sepsis rats.METHODS We designed sepsis model by cecal ligation puncture,divided into five groups,sampled tissue in 3,24 and 72 h after model built,and compared the change between groups.We employed the immuno-histochemistry to examine the positive expression of caspase 3 in spleen,and examined the index of apoptosis in different groups.RESULTS The result showed that three traditional Chinese medicine compounds could significantly cut down the expression of caspase 3 in spleen lymphocyte.CONCLUSIONS The three traditional Chinese medicine compounds could decrease the apoptosis of lymphocyte,and adjust the immunity.
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OBJECTIVE To establish a simple and stable animal model with abdominal infection due to drug-resistant bacteria.METHODS Forty healthy rabbit were infected by Klebsiella pneumoniae ATCC700603,and divided into three test groups:A1(bacterial dose 8?109CFU/kg),A2(bacterial dose 16?109 CFU/kg) and A3(bacterial dose 24?109 CFU/kg).Normal control group B was established at the same time.Vital signs,white blood cell count(WBC),blood and abdominal irrigating solution cultures and strain identification were observed at 12,24,48,72 and 96h after infection.Patho-samples were obtained after being executed.RESULTS The body temperature,WBC,heart rate(HR) and respiratory rate(R) in group A3 were significantly higher than groups A1 and B,after rabbits having being infected 12-24 hours.And it continued for 96 hours(P
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<p><b>OBJECTIVE</b>To investigate the effects of herbal compound 861 (Cpd861) on hepatocarcinogenesis induced by diethylntrosamine and 2-acetylaminofluorene (DEN-AAF) in female Sprague Dawley rats.</p><p><b>METHODS</b>Liver preneoplastic foci were induced using the DEN-AAF method in female Sprague Dawley rats, which were then treated with Cpd861. For quantitative assessment of liver preneoplastic foci, the placental form of glutathione-S-transferase (GST-P) positive foci were measured using immunohistochemical staining and image analysis. GST-P protein expression was measured by Western blotting, mRNA expression was assessed by Northern blotting.</p><p><b>RESULTS</b>Treatment using DEN-AAF caused a significant decrease in body weight and increase in liver weight compared to the control group. Oral Cpd861 administration essentially prevented DEN-AAF-induced body weight loss and liver weight increase. When 2-AAF was followed by treatment with Cpd861, there was a decrease in the number of large foci as compared to 2-AAF alone. However, there were still considerable numbers of small mixed clear/vacuolated cell foci, some of which were positive for GST-P. Significant increase in GST-P protein and mRNA expression were observed in the DEN-AAF group, while treatment with Cpd861 inhibited the increase. The effect of Cpd861 on hepatocarcinogenesis occurred in a concentration-dependent manner.</p><p><b>CONCLUSION</b>Chinese herbal compound Cpd861 prevents hepatocarcinogenesis in DEN-AAF-induced liver preneoplastic lesions in rats.</p>
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Animals , Female , Rats , 2-Acetylaminofluorene , Blotting, Northern , Blotting, Western , Body Weight , Diethylnitrosamine , Drugs, Chinese Herbal , Therapeutic Uses , Glutathione Transferase , Genetics , Liver , Pathology , Liver Neoplasms, Experimental , Drug Therapy , Pathology , Organ Size , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of herbal compound 861 (Cpd 861) on MMP-2 expression and its enzymatic activities, and the antifibrotic mechanism of this herbal compound.</p><p><b>METHODS</b>Forty five female rats were randomly divided into normal control (sham operation) group, common bile duct ligation (BDL) group and Cpd 861 therapeutic group. In the last group, daily gastric feeding of Cpd 861 (9 g/kg.bw) started on day 7 after BDL operation. At 49 days, all animals were sacrificed and mRNA expression of MMP-2 in liver tissue was evaluated by semi-quantitive RT-PCR. In addition, enzymatic activities of MMP-2 were analyzed by zymography.</p><p><b>RESULTS</b>In comparison with model group, MMP-2 mRNA levels in Cpd 861 therapeutic group were significantly decreased. MMP-2 enzymatic activities were not detectable in normal group, slightly elevated in model group, higher in Cpd 861 therapeutic group.</p><p><b>CONCLUSIONS</b>Cpd 861 decreases the mRNA level of MMP-2, but transiently increases the enzymatic activities of MMP-2. The latter effect of Cpd 861 may be mediated by decreasing TIMPs, the inhibitors of MMPs, during resolution stage of fibrosis. This is probably one of the mechanisms whereby herbal Cpd 861 exerted its antifibrotic action in this kind of experimental liver fibrosis.</p>
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Animals , Female , Rats , Drugs, Chinese Herbal , Therapeutic Uses , Liver Cirrhosis, Experimental , Drug Therapy , Matrix Metalloproteinase 2 , Genetics , Metabolism , Phytotherapy , RNA, Messenger , Random Allocation , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To observe the in vitro effect of compound 861 (Cpd 861) on tissue inhibitor of metalloprotenase 1 (TIMP1) mRNA levels of HSC-T6 cell.</p><p><b>METHODS</b>HSC-T6 cells were exposed in different concentrations of Cpd 861 (0.25~1.0 mg/ml) for 48 hours. The TIMP1 level was measured by the quantitative reverse-transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The TIMP1 mRNA levels of HSC-T6 cells at different concentrations of Cpd 861 were lower (2.50 0.71, 0.50 0.01, 0.11 0.03) than those of the normal control (3.78 0.67, P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>The antifibrotic mechanism of Cpd 861 is partly due to its downregulation on TIMP1 mRNA levels of HSC-T6 cells.</p>
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Animals , Rats , Down-Regulation , Drugs, Chinese Herbal , Pharmacology , Gene Expression , RNA, Messenger , Rats, Sprague-Dawley , Tissue Inhibitor of Metalloproteinase-1 , GeneticsABSTRACT
<p><b>OBJECTIVE</b>Protein induced by vitamin K absence or antagonist II (PIVKA II), also called des-gamma carboxy prothrombin (DCP), is a sensitive marker for the diagnosis of hepatocellular carcinoma (HCC), in Japan and the United States since the sensitive kits were available (1998). PIVKA II is not used in clinical diagnosis in China so far. The aim of this study was to assess the diagnostic value of PIVKA II in Chinese patients with HCC.</p><p><b>METHODS</b>Serum PIVKA II and alpha-fetoprotein (AFP) levels were determined in 60 patients with HCC and 30 patients with cirrhosis not carrying HCC.</p><p><b>RESULTS</b>The mean serum concentration of PIVKA II in HCC patients (784.3 +/- 1364.1 mean +/- s) was higher than that in cirrhosis patients (16.1 +/- 31.7); this difference was highly significant (P < 0.0001). When the cutoff level of 40 mAU/ml was used as the level of discriminating HCC from cirrhosis, 51.7% of patients (31/60) with HCC had PIVKA II values above this level (sensitivity). Only 4 patients with cirrhosis had such high PIVKA II levels. Thus, the specificity of this test was 86.7% (26/30). Total accuracy was 62.2% [(31 + 26)/(60 + 30)]. Seven of 19 small HCCs (36.84%) had PIVKA II values above the cutoff level. Concentrations of AFP above 20 ng/ml were observed in 34 of 60 patients with HCC (56.7%) and in 11 patients with cirrhosis (36.7%). Eleven of 26 patients with HCC (46.2%) without increased AFP had concentrations of PIVKA II greater than 40 mAU/ml. No significant correlation was found between serum levels of AFP and PIVKA II that were measured in 60 HCC patients (rs = 0.101, P = 0.247). Combining the information from PIVKA II and AFP showed an increase of approximately 21.6% over AFP and 26.7% over PIVKA II alone. For small HCC patients, combining the information from PIVKA II and AFP showed an increase of approximately 15.8% over AFP alone and 21.1% over PIVKA II alone.</p><p><b>CONCLUSION</b>PIVKA II is a useful early diagnostic marker for HCC and may be more sensitive when combined with AFP in Chinese patients.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Biomarkers , Biomarkers, Tumor , Blood , Carcinoma, Hepatocellular , Blood , Diagnosis , Pathology , Liver Cirrhosis , Blood , Liver Neoplasms , Blood , Diagnosis , Pathology , Protein Precursors , Blood , Prothrombin , alpha-FetoproteinsABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical and histopathological features of primary biliary cirrhosis (PBC).</p><p><b>METHODS</b>The clinical, laboratory, as well as histological features of 27 cases of PBC were retrospectively analyzed.</p><p><b>RESULTS</b>The male to female ratio was 1:8 (3:24), aged from 22 to 69 years. The main clinical manifestations included: fatigue (62.9%, 17/27), jaundice (59.2%, 16/27) and pruritus (29.6%, 8/27), with all of patients having markedly elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase and 95.8% (23/27) of the patients being positive for anti-mitochondrial antibody (AMA). The main histopathological changes were: necroinflammation of interlobular bile ducts (100%, 27/27), lymphocyte aggregation or lymphocyte follicles (15%, 4/27), granuloma (26%, 7/27), decreased number of interlobular bile ducts and smaller bile duct proliferation (55%, 15/27), feathery degeneration of hepatocytes (59%, 16/27); bilirubinostasis in hepatocytes and/or canaliculi (52%, 14/27); fibrosis and distortion of lobules (26%, 7/27), pseudolobular formation (11%, 3/27).</p><p><b>CONCLUSIONS</b>The main clinical features of PBS are fatigue and pruritus, markedly elevated phosphatase and gamma-glutamyl transpeptidase, and positive AMA with or without jaundice. Its histopathological hallmarks are (1)necroinflammmation and ductopenia involved mainly in interlobular bile ducts; (2)lymphocyte aggregation, granuloma formation and bile ductular proliferation in the portal area; and (3)feathery degeneration of hepatocytes.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Bile Ducts, Intrahepatic , Fatigue , Hepatocytes , Liver Cirrhosis, Biliary , Mitochondria , Pruritus , gamma-GlutamyltransferaseABSTRACT
<p><b>OBJECTIVE</b>To evaluate the long-term efficacy and safety of lamivudine therapy for the treatment of chronic hepatitis B and the clinical influence of emergence of tyrosine methionine aspartic acid (YMDD) motif mutation of hepatitis B virus (HBV).</p><p><b>METHODS</b>This multicenter, double-blind, randomized, placebo controlled trial began in 1996. A total of 429 patients with HBsAg, HBeAg and HBV CNA positives were enrolled. They were randomized to receive either lamivudine 100 mg daily (n = 322) or placebo (n = 107) on 3 : 1 ratio for the first 12 weeks. Thereafter all patients were offered open label lamivudine treatment and assessed every 4 weeks for a total of 104 weeks.</p><p><b>RESULTS</b>After 1 year treatment 72.7% patients (285/392) had a sustained serum HBV DNA response. HBV DNA continued to be substantially suppressed at the second year, except in patients with the emergence of YMDD mutation whose mean HBV DNA levels increased to 86 Meq/ml (bDNA assay) but were much more lower than that of pre-treatment baseline level. lamivudine therapy resulted in increased HBeAg loss and HBeAg/anti-HBe seroconversion, which were correlated with both baseline alanine transaminase (ALT) levels and also with duration of lamivudine treatment. HBeAg loss was achieved in 26.8% of patients with ALT > 1-fold upper limit of normal at 2 yeas and in 35.6% and 55.6% of patients with ALT > 2-fold upper limit of normal and ALT > 5-fold upper limit of normal, respectively. For HBeAg seroconversion, these figures were 17.4%, 22.2%, and 33.3% respectively. By the end of 2 years, ALT levels were remained in normal ranges in 50.3% whose ALT were abnormal before treatment, and in 83% whose ALT were mormal before treatment. YMDD mutation were developed in 49.7% of the patients. Their serum HBV DNA levels were slightly increased to bDNA median level 86 Meq/ml and 15% of the patients they were ALT exceeded baseline levels. Four patients clinically flared-up and recovered after stop treatment. The adverse drug reactions (ADRs) of lamivudine were mild to moderate, only two patients were reported as drug related severe ADR.</p><p><b>CONCLUSION</b>Sustained HBV replication and clinical improvement could be obtained by the long-term lamivudine therapy with good tolerance and safety.</p>
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Adolescent , Adult , Aged , Humans , Middle Aged , Alanine Transaminase , Blood , Antiviral Agents , Therapeutic Uses , DNA, Viral , Blood , DNA-Directed DNA Polymerase , Genetics , Double-Blind Method , Hepatitis B e Antigens , Blood , Hepatitis B virus , Genetics , Hepatitis B, Chronic , Drug Therapy , Virology , Lamivudine , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To study the clinical features of patients with primary biliary cirrhosis (PBC) in order to improve the doctors' awareness of the disease.</p><p><b>METHODS</b>General status, clinical manifestations and laboratory findings of 40 patients with PBC were reviewed.Thirty-seven patients were females (37/40), and the mean age at diagnosis was 50.5 +/- 7.8 years. The time interval from initial symptoms or preliminary diagnosis to final diagnosis was 24.0 +/- 23.6 months.</p><p><b>RESULTS</b>The most frequently reported symptoms were fatigue (67.5%, 27/40), jaundice (60%, 24/40) and pruritus (32.5%, 17/40). Eight patients (20%) had associated auto-immune diseases (Sjogren's syndrome and/or rheumatoid a(c)arthritis). Serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (gamma-GT) levels were markedly elevated (520.3 +/- 382.3 IU/L and 648.6 +/- 529.1 IU/L, respectively) in all patients, while alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were mildly elevated (82.6 +/- 54.5 IU/L and 100.7 +/- 47.2 IU/L, respectively). Twenty-four patients (60%) had a total bilirubin level >/= 34.2 micromol/L. Thirty-five patients (87.5%) had elevated serum immunoglobin M,and 97.5% of patients (39/40 ) were anti-mitochondrial antibody (AMA)/AMA-M2 positive.</p><p><b>CONCLUSION</b>Elevated serum ALP and gamma-GT levels, together with a positive AMA/AMA-M2, can help the diagnosis of PBC. Liver biopsy is useful to confirm the diagnosis and to differentiate histopathological stages.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Biopsy, Needle , Hepatitis B, Chronic , Liver , Pathology , Liver Cirrhosis, Biliary , PathologyABSTRACT
Objective To evaluate clinical features and mortality of primary biliary cirrhosis (PBC) in the aged patients. Methods Clinical data of 108 patients diagnosed with PBC was reviewed. The diagnosis of PBC was made according to the 2000 practice guidelines of American Association for the study of liver Diseases (AASLD). Elderly patients (≥60 years) were compared in terms of clinical, biochemical, immunological features and mortality with younger patients (0.05). After a median follow-up of 36 months, the mortality ratio for liver diseases was higher in the elderly than in younger group (21.4% vs 2.5%, ~P
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AIM: To investigate the effect of endotoxin on rat hepatic mitochondria. METHODS: Rats were randomly divided into two groups:endotoxin group and the control. 8 cases of animals were included in each group. The effect of electron leak on the production of endogenous oxygen free radicals and the changes of mitochondria function were studied.RESULTS: Treated with endotoxin, a significant increase in O 2 and the rate of state 3,4 were observed in liver mitochondria; The rate of electron transfer to proton pump of mitochondria respiratory chain complex Ⅱ+Ⅲ( H +/2e -), respiratory control rate and ADP/O decreased significantly. CONCLUSION: A increase in production of endogenous oxygen free radicals induced by endotoxin plays an important role in the injury of rat liver mitochondria.