Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and investigate factors influencing prognosis.METHODS: One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study. They were divided into four groups and underwent different treatments: conservative treatment group (n = 18),chemotherapy group (n = 53), surgical resection group (n = 24) and surgical resection with postoperative chemotherapy group (n = 84). Survival rates of the patients were analyzed by the Kaplan-Meier method. A log-rank analysis was performed to identify group differences. Cox's proportional hazards model was used to analyze variables associated with survival.RESULTS: The mean survival periods of the patients in four groups were 3.6, 7.3, 10.1, and 15.1 mo respectively.There were significant differences in the survival rates among the groups. The survival rates at 0.5-, 1-, 2-, and 3-year in surgical resection with postoperative chemotherapy group were 55.8%, 39.3%, 30.4%, and 15.6% respectively, which were significantly higher than those of other groups (P＜0.001). Multivariate analysis revealed that the strategy of treatment (P＜0.001) and the number of chemotherapy cycles (P = 0.012) were independent survival predictors for patients with HCC and PVTT.CONCLUSION: Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation.Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve.

Blockage of transforming growth factor β receptors prevents progression of pig serum-induced rat liver fibrosis

AIM: To test the hypothesis that introduction of antisense TβR Ⅰ and TβR Ⅱ eukaryotic expressing plasmids into a rat model of immunologically induced liver fibrosis might block the action of TGF-β1 and halt the progression of liver fibrosis. METHODS: RT-Nest-PCR and gene recombination techniques were used to construct rat antisense TβR Ⅰ and TβR Ⅱ recombinant plasmids which could be expressed in eukaryotic cells. The recombinant plasmids and empty vector (pcDNA3) were encapsulated by glycosyl-poly-L-lysine and then transducted into rats of pig serum-induced liver fibrosis model. Expression of exogenously transfected gene was assessed by Northern blot, and hepatic expressions of TβR Ⅰ and TβR Ⅱ were evaluated by RT-PCR and Western blot.We also performed ELISA for serum TGF-β1, hydroxyproline of hepatic tissues, immunohistochemistry for collagen types Ⅰ and Ⅲ, and VG staining for pathological study of the liver tissues. RESULTS: The exogenous antisense TβR Ⅰ and TβR Ⅱ plasmids could be well expressed in vivo, and block mRNA and protein expression of TβR Ⅰ and TβR Ⅱ in the fibrotic liver at the level of mRNA respectively. These exogenous plasmid expressions reduced the level of TGF-β1 (antisense TβR Ⅰ group 23.998+3.045 ng/mL, antisense TβR Ⅱ group 23.156+3.131 ng/mL, disease control group 32.960+3.789 ng/mL; F-=-38.19, 36.73, P<0.01). Compared with disease control group, the contents of hepatic hydroxyproline (antisense TβR Ⅰ group 0.169+0.015 mg/g liver, antisense TβR Ⅱ group 0.167+0.009 mg/g liver, disease control group 0.296+0.026 mg/g liver; F=14.39, 15.48, P<0.01) and the deposition of collagen types Ⅰ and Ⅲ decreased in the two antisense treatment groups(antisense TβR Ⅰ group, collagen type Ⅰ 669.90+50.67, collagen type Ⅲ 657.29+49.48; antisense TβR Ⅱ group, collagen type Ⅰ 650.26+51.51, collagen type Ⅲ 661.58+55.28; disease control group, collagen type I 1209.44+116.60, collagen type Ⅲ 1175.14+121.44; F=15.48 to 74.89, P<0.01). Their expression also improved the pathologic classification of liver fibrosis models (compared with disease control group, X^2=17.14, 17.24, P<0.01). No difference was found in the level of TGF-β1, the contents of hepatic hydroxyproline and collagen types Ⅰ and Ⅲ and pathologic grade between pcDNA3 control group and disease control group or between the two antisense treatment groups (F=0.11 to1.06, X^2=0.13 to 0.16, P>0.05). CONCLUSION: Antisense TβR Ⅰ and TβR Ⅱ recombinant plasmids have certain reverse effects on liver fibrosis and can be used as possible candidates for gene therapy.

Glutamine supplemented parenteral nutrition prevents intestinal ischemia-reperfusion injury in rats

AIM: To examine whether glutamine prevents the injury to the intestinal mucosa after intestinal ischemia-reperfusion (I/R) in rats.METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups: a standard parenteral nutrition (PN) group (n = 10); an I/R-PN group (n = 10); an I/R-glutamine enriched PN (I/R-Gln) group (n = 10). The superior rnesenteric artery (SMA) was clamped. After 60 min of ischemia,reperfusion was initiated and infusion was started. All rats received isocaloric and isonitrogenous nutritional support for 48 h. Spleen, liver, mesenteric lymph nodes (MLN), and intestinal segments were removed for morphological and biochemical analyses, and blood samples were collected for bacterial culture and measurement of endotoxin levels.The permeability of intestinnal mucosa was assayed by measurement of D-(-)-Iactate levels in plasma.RESULTS: In I/R-PN group, extensive epithelial atrophy was observed, mucosal thickness, villous height, crypt depth and villous surface area were decreased significantly compared with PN group, whereas these findings did not occur in the I/R-GIn group. The incidence of intestinal bacterial translocation to spleen, liver, MLN, and blood was significantly higher in I/R-PN group than that in other groups.Plasma endotoxin levels significantly increased in the I/R-PN group compared with the I/R-GIn group. Remarkably higher values of D-(-)-Iactate were also detected in PN group compared with that in I/R-GIn group.CONCLUSION: Glutamine protects the morphology and function of intestinal mucosa from injury after I/R in rats.

Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai:an epidemiological survey

AIM: To determine the prevalence of nonalcoholic fatty liver in a specific population in Shanghai by an epidemiological survey, and to analyze risk factors of fatty liver.METHODS: Total 4009 administrative officers who denied regular alcohol drinking participated in the survey, and underwent physical examination and laboratory tests. The important parameters were body mass index (BMI), waist hip circumferences ratio (WHR) and levels of serum lipids.Diagnosis of fatty liver was based on established real-time ultrasonographic criteria, the presence of an ultrasonographic pattern consistent with 'bright liver', with evident ultrasonographic contrast between hepatic and renal parenchyma, vessel blurring, and narrowing of the lumen of the hepatic veins. Analysis of data was performed through SPSS for Windows statistical package.RESULTS: The overall prevalence of fatty liver was 12.9 %,15.8 % in males and 7.5 % in females, and the prevalence of fatty liver in males younger than 50 years old, was significantly higher (13.3 %) than that of in females (2.7 %).But the difference between the sexes became less significant in people older than 50 years (19.1% vs 18.1%). The prevalence of fatty liver was increased with age; this was markedly presented in females younger than 50 years.Multiple variant regression analysis demonstrated that the prevalence of fatty liver was positively correlated to several risk factors, including male, aging (＞50yr), hyperlipidemia,impaired glucose tolerance/diabetes mellitus, hypertension and overweight/obesity.CONCLUSION: There is a high prevalence of nonalcoholic fatty liver among certain population in Shanghai, to which overweight and hyperlipidemia are closely relevant.

Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis

AIM: To establish the methylation profile of the promoter CpG islands of 31 genes that might play etiological roles in colon carcinogenesis.METHODS: The methylation specific PCR in conjunction of sequendng verification was used to establish the methylationprofile of the promoter CpG islands of 31 genes in colorectal cancer (n = 65), the neighboring non-cancerous tissues (n = 5), colorectal adenoma (n = 8), and normal mucosa (n = 1). Immunohistochemically, expression of 10 genes was assessed on the home-made tissue microarrays of tissues from 58 patients. The correlation of tumor specific changes with each of clinical-pathologic features was scrutinized with relevant statistic tools.RESULTS: In comparison with the normal mucosa of the non-cancer patients, the following 14 genes displayed no tumor associated changes: breast cancer 1, early onset (BRCA1), cadherin 1, type 1, E-cadherin (epithelial) (CDH1),death-associated protein kinase 1 (DAPK1), DNA (cytosine-5-)-methyltransferase 1 (DNMT1), melanoma antigen, family A, 1 (directs expression of antigen MZ2-E) (MAGEA1), tumor suppressor candidate 3 (N33), cyclin-dependent kinase inhibitor 1A (p21, Cipl) (p21^WAF1), cyclin-dependent kinase inhibitor 1B (p27, 10pl) (p27^WAF1), phosphatase and tensin hornolog (mutated in multiple advanced cancers 1) (PTEN), retinoic acid receptor, beta (RAR-, Ras association (RaIGDS/AF-6) domain family 1 C (RASSFIC), secreted frizzled-related protein 1 (SFRP1), tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinfiammatory) (TIMP3),and von HippeI-Lindau syndrome (VHL). The rest 17 targets exhibited to various extents the tumor associated changes.As changes in methylation of the following genes occurred marginally, their impact on the formation of colorectal cancer were trivial: adenomatous polyposis coli (APC) (8%, 5165),Ras association (RaIGDS/AF-6) domain family 1A (RASSFIA) (3%, 2/65) and cyclin-dependent kinase inhibitor 2A,alternated reading frame Co14~) (6%, 4/65). The following genes exhibited moderate changes in rnethylation: O-6rnethylguanine-DNA rnethyltransferase (MGMT) (20%, 13/65),rnutL hornolog 1, colon cancer, nonpolyposis type 2 (E. coli) (hMLH1) (18%, 12/65), cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) P16^NK4a) (10%, 10/65),rnethylated in tumor 1 (MINT1) (15%, 10/65), methylated in tumor 31 (MINT31) (11%, 7/65). The rest changed greatly in the rnethylation pattern in colorectal cancer (CRC): cyclin A1 (cyclin al) (100%, 65/65), caudal type homeobox transcriptdon factor 1 (CDX1) (100%, 65/65), RAR(85%, 55/65), myogenic factor 3 (MYOD1) (69%, 45/65),cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)(p15^INK4b) (68%, 44/65), prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (COX2) (72%, 47/65), cadherin 13, H-cadherin (heart) (CDH13) (65%, 42/65), CAAX box 1 (OO~/) (58%, 38/65),tumor protein p73 (p73) (63%, 41/65) and Wilrns tumor 1 (WT/) (58%, 38/65). However, no significant correlation of changes in rnethylation with any given clinical-pathological features was detected. Furthermore, the frequent changes in rnethylation appeared to be an early phase event of colon carcinogenesis. The in situ expression of 10 genes was assessed by the irnrnunohistochernical approach at the protein level: CDH1, CDH13, COX2, cyclin A1, hMLH1,MGMT, p14^ARF, p73, RAR-, and TIMP3 genes in the context of the rnethylation status in colorectal cancer. No clear correlation between the hyperrnethylation of the promoter CpG islands and the negative expression of the genes was established.CONCLUSION: The methylation profile of 31 genes was established in patients with colon cancer and colorectal adenornas, which provides new insights into the DNA rnethylation mediated mechanisms underlying the carcinogenesis of colorectal cancer and may be of prognostic values for colorectal cancer.

CT perfusion at early stage of hepatic diffuse disease

AIM: To determine the validity of the non-invasive method of CT perfusion (CTP) in rat model of hepatic diffuse disease. METHODS: Twenty-eight Wistar rats were divided into two groups. Liver diffuse lesions were induced by diethyln-itrosamine in 14 rats of test group. Rats in control group were bred with pure water. From the 1st to 12th wk after the test group was intervened, both groups were studied every week with CTP. CTP parameters of liver parenchyma in different periods and pathologic changes in two groups were compared and analyzed. RESULTS: The process of hepatic diffuse lesions in test groups was classified into three stages or periods according to the pathologic alterations, namely hepatitis, hepatic fibrosis, and cirrhosis. During this period, hepatic artery flow (HAF) of control group declined slightly, mean transit time (MTT), blood flow (BF) and volume (BV) increased, but there were no significant differences between different periods. In test group, HAF tended to increase gradually, MTT prolonged obviously, BV and BF decreased at the same time. The results of statistical analysis revealed that the difference in the HAF ratio of test group to control group was significant. The ratio of BV and BF in test group to control group in stage of hepatitis and hepatic cirrhosis, hepatic fibrosis and early stage of hepatic cirrhosis was significantly different, but there was no significant difference between hepatitis and hepatic fibrosis. The main pathological changes in stage of hepatitis were swelling of hepatic cells, while sinusoid capillarization and deposition of collagen aggravated gradually in the extravascular Disse's spaces in stage of fibrosis and early stage of cirrhosis. CONCLUSION: The technique could reflect some early changes of hepatic blood perfusion in rat with liver diffuse disease and is valuable for their early diagnosis.

Docetaxel inhibits SMMC-7721 human hepatocellular carcinoma cells growth and induces apoptosis

AIM: To investigate the in vitro anti-hepatocellular carcinoma (HCC) activity of docetaxel against SMMC-7721 HCC cells and its possible mechanism.METHODS: The HCC cells were given different concentrations of docetaxel and their growth was measured by colony forming assay. Cell cycle and apoptosis were analyzed by flow cytometry and fluorescence microscopy (acridine orange/ethidium bromide double staining, AO/EB), as well as electronic microscopy. The SMMC-7721 HCC cell reactive oxygen species (ROS) and glutathione (GSH) were measured after given docetaxel.RESULTS: Docetaxel inhibited the hepatocellular carcinoma cells growth in a concentration dependent manner with IC505×10-10 M. Marked cell apoptosis and G2/M phase arrest were observed after treatment with docetaxel ≥10-8M.Docetaxel promoted SMMC-7721 HCC cells ROS generation and GSH deletion.CONCLUSION: Docetaxel suppressed the growth of SMMC7721 HCC cells in vitro by causing apoptosis and G2/M phase arrest of the human hepatoma cells, and ROS and GSH may play a key role in the inhibition of growth and induction of apoptosis.

The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications

It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.

Role of endoscopic miniprobe ultrasonography in diagnosis of submucosal tumor of large intestine

AIM: To evaluate the role of miniprobe ultrasonography under colonoscope in the diagnosis of submucosal tumor of the large intestine, and to determine its imaging characteristics.METHODS: Thirty-five patients with submucosal tumors of the large intestine underwent miniprobe ultrasonography under colonoscope. The diagnostic results of miniprobe ultrasonography were compared with pathological findings of specimens by biopsy and surgical resection.RESULTS: Lipomas were visualized as hyperechoic homogeneous masses located in the submucosa with adistinct border. Leiomyomas were visualized as hypoechoic homogeneous mass originated from the muscularis propria.Leiomyosarcomas were shown with inhomogeneous echo and irregular border. Carcinoids were presented as submucosal hypoechoic masses with homogenous echo and distinct border. Lymphangiomas were shown as submocosal hypoechoic masses with cystic septal structures.Malignant lymphomas displayed as hypoechoic masses from mucosa to muscularis propria, while pneumatosis cystoids intestinalis originated from submucosa with aspecial sonic shadow. One large leiomyoma was misdiagnosed as leiomyosarcoma.CONCLUSION: Endoscopic miniprobe ultrasonography can provide precise information about the size, layer of origin,border of submucosal tumor of the large intestine and has a high accuracy in the diagnosis of submucosal tumor of the large intestine, Pre-operative rniniprobe ultrasonography under colonoscope may play an important role in the choice of therapy for submucosal tumor of the large intestine,

Role of hepatitis B virus infection in pathogenesis of IgA nephropathy

AIM: To investigate the role of hepatitis B virus (HBV) in the pathogenesis of IgA nephropathy (IgAN).METHODS: HBV antigens (HBAg, or HBsAg, HBcAg, and HBeAg) in renal tissues with IgAN were detected by immunohistochemical technique. The distribution and localization of HBV DNA were observed by using in situ hybridization. Southern blot analysis was performed to reveal the state of renal HBV DNA.RESULTS: Among 100 patients with IgAN, HBs antigenemia was detected in 18 patients (18.00 %). HBAg in renal tissues was detected in 31 patients (31.00 %), the positive rate of HBAg, HBsAg and HBcAg was 64.52 % (20/31), 32.26 %(10/31), 32.26 % (10/31), respectively in glomeruli. HBcAg was also found in tubular epithelia and interstitia, which was 45.16 % (14/31) and 6.45 % (2/31), respectively. Five out of six cases with positive HBV DNA by in situ hybridization were proved to be HBV DNA positive by Southern blot analysis, and all were of the integrated form. Eight specimens were demonstrated to be HBV DNA positive by in situ hybridization, which was localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as in infiltrated interstitial lymphocytes.CONCLUSION: There is a relationship between HBV infection and IgAN. In addition to the humoral immune damage mediated by HBAg-HBAb immune complex, the cellular mechanism mediated by HBV originating from renal cells in situ may be also involved in the pathogenesis of IgAN.

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

Objective To assess the efficacy and safety of lornoxicam, one non-steroidal anti-inflammatory drug (NSAID) in patient-controlled analgesia (PCA) in patients undergoing abdominal surgeries. Methods Thirty-nine patients scheduled for abdominal surgeries were randomly assigned to different PCA treatment groups using either lornoxicam or fentanyl postoperatively. Pain intensity difference (PID) and sum of pain intensity difference (SPID) were used to assess the analgesic efficacy of both drugs during a 24-hour period. Results The analgesic efficacy of lornoxicam is 1/66 of fentanyl, which was shown by SPID value of 3.250 and 3.058, respectively (P > 0.05). Lornoxicam caused fewer adverse events than fentanyl (33% vs. 68%, P < 0.05). Conclusion In clinic, we can use lornoxicam to treat postoperative pain effectively and with less adverse reactions com-pared with fentanyl.

Hepatitis B virus infection and coronary atherosclerosis: Results from a population with relatively high prevalence of hepatitis B virus

AIM: To investigate the possible association between hepatitis B virus (HBV) infection and angiographically proven coronary artery disease (CAD) in a population with relatively high prevalence of HBV.METHODS: Sera from 434 patients who underwent coronary angiography were tested for HBV antigens (HBsAg, HBeAg) and antibodies (Anti-HBs, Anti-HBc and Anti-HBe) by ELISA.RESULTS: Seventy-seven percent (224/291) of the patients with CAD and 73.4% (105/143) of the patients without angiographic evidence of atherosclerosis were seropositive for HBV (P＞0.05). However, C-reactive protein (CRP) levels were significantly higher in patients with CAD (P = 0.008), while lower in HBV seropositive population (P= 0.043 and P = 0.021 after adjustment for conventional risk factors).CONCLUSION: Our results suggested HBV infection negatively correlates with CRP levels, but seems not to be associated with coronary atherosclerosis.

Effect of cisapride on intestinal bacterial and endotoxin translocation in cirrhosis

AIM: To investigate the effects of cisapride on intestinal bacterial overgrowth (IBO), bacterial and endotoxin translocation, intestinal transit and permeability in cirrhotic rats.METHODS: All animals were assessed with variables including bacterial and endotoxin translocation, intestinal bacterial overgrowth, intestinal transit and permeability.Bacterial translocation (BT) was assessed by bacterial culture of MLN, liver and spleen, IBO by a jejunal bacterial count of the specific organism, intestinal permeability by determination of the 24-hour urinary 99mTc-DTPA excretion and intestinal transit by measurement of the distribution of 51Cr in the intestine.RESULTS: Bacterial translocation (BT) and IBO was found in 48 % and 80 % cirrhotic rats respectively and none in control rats. Urinary excretion of 99mTc-DTPA in cirrhotic rats with BT (22.2±7.8) was greater than these without BT (10.5±2.9). Intestinal transit (geometric center ratio) was significantly delayed in cirrhotic rats (0.31±0.06) and further more delayed in cirrhotic rats with BT (0.24±0.06) than these without BT (0.38±0.11). Cirrhotic rats with IBO had significantly higher rates of intestinal bacterial and endotoxin translocation, slower intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT was closely associated with IBO and the injury of intestinal barrier. Compared with the placebo group,cisapride-treated rats had lower rates of bacterial/endotoxin translocation and IBO, which was closely associated with increased intestinal transit and improved intestinal permeability by cisapride.CONCLUSION: These results indicate that endotoxin and bacterial translocation in cirrhotic rats may be attributed to IBO and increased intestinal permeability. Cisapride that accelerates intestinal transit and improve intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

Preparation of magnetic polybutylcyanoacrylate nanospheres encapsulated with aclacinomycin A and its effect on gastric tumor

AIM: To evaluate the effect of aclacinomycin A-loaded magnetic polybutylcyanoacrylate nanoparticles on gastric tumor growth in vivo and in vitro.METHODS: Magnetic polybutylcyanoacrylate (PBCA)nanospheres encapsulated with aclacinomycin A (MPNS-ACM) were prepared by interracial polymerization. Particle size, shape and drug content were examined. Female BABL/c nude mice were implanted with MKN-45 gastric carcinoma tissues subcutaneously to establish human gastric carcinoma model. The mice were randomly divided into 5 groups of 6 each: ACM group (8 mg/kg bin); group of high dosage of MPNS-ACM (8 mg/kg bin); group of low dosage of MPNS-ACM (1.6 mg/kg bin); group of magnetic PBCA nanosphere (MPNS) and control group(normal saline). Magnets (2.5 T) were implanted into the tumor masses in all of the mice one day before the therapy.Above-mentioned drugs were administered intravenously to the mice of every group on the first day and sixth day.When the mice were sacrificed, tumor weight was measured, and the assay of granulocyte- macrophage colony forming-unit (CFU-GM) was performed on semi-solid culture. White blood cell, alanine aminotransferase and creatine were examined. 3-[4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was used to examine the viability of MKN-45 cells afger incubation with different concentrations of ACM, MPNS and MPNS-ACM suspension respectively for 48 h.RESULTS: Content of ACM in MPNS-ACM was 12.0% and the average diameter of the particles was 210 nm. The inhibitory rates of ACM (8 mg/kg bin), high dosage of MPNS-ACM (8 mg/kg bin), low dosage of MPNS-ACM (1.6 mg/kg bin)and MPNS on human gastric carcinoma in nude mice were 22.63%, 52.55%, 30.66% and 10.22%, respectively. There was a significant decrease in the number of CFU-GM of bone marrow in ACM group compared with control group,whereas no obvious change was observed in that of the nanosphere groups. The values of 50% inhibition concentration (IC50) of ACM, MPNS and MPNS-ACM were 0.09, 97.78 and 1.07 μg/mL, respectively.CONCLUSION: The tumor inhibitory rate of MPNS-ACM was much higher than that of ACM under magnetic field and the inhibition on bone marrow was alleviated significantly compared with ACM group.

Oxymatrine therapy for chronic hepatitis B:A randomized doubleblind and placebo-controlled multi-center trial

AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B.METHODS: A randomised double-blind and placebocontrolled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo.After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed.RESULTS: Among the 216 patients, six were dropped off,and 11 inconsistent with the standard were excluded.Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47 % became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33 % became normal in ALT level,43.33 % and 39.29 % became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00 % became normal in ALT level, 7.46 % and 6.45 % became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84 % in the capsule treated patients, and 33.33 % and 50.00 % in the injection treated patients, and 2.99 % and 41.79 % in the placebo treated patients, respectively.There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule,injection and placebo were 7.77 %, 6.67 % and 8.82 %,respectively. There was no statistically significant difference among them.CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

Total vascular exclusion technique for resection of hepatocellular carcinoma

AIM: To improve the low resection rate, poor prognosis and to control the massive hemorrhage during operation,total vascular exclusion (TVE) technique was used in hepatectomies of advanced and complicated hepatocellular carcinomas (HCCs).METHODS: Five hundred and thirty patients with HCCs were admitted in our hospital. They were divided into TVE technique group (group A:n＝78), Pringle maneuver method group (group B:n=176) and unresectable group (group C:n=276). The clinical, operative, pathological parameters and outcome of the patients were statistically evaluated.RESULTS: Group A had a significantly higher resection rate than group B (accounting for 47.92% and 33.21%respectively). There was no significant difference in blood loss, blood transfusion and perioperative mortality betweengroups A and B. Both groups had the similar median disease free survival time (14.6 VS 16.3 months) and 1 year survival rate (92.9% VS95.5%). The TVE group had a medial survival time of 40.5 months and its 5-year survival rate was 34.6%.CONCLUSION: As compared with Pringle maneuver method, the total vascular exclusion is a safe and effective technique to increase the total resection rate of advanced and complicated HCCs.

Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis:A randomized,double blind,placebo-controlled,multicenter clinical study

AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebocontrolled, multicenter clinical study. One hundred and fortyfour patients were divided into oxymatrine capsule group (group A) and placebo group (group B). The course was 52wk. Patients were visited once every 12wk and the last visit was at 12wk after cessation of the treatment. All patients had liver biopsy before treatment, part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol, 49 patients had liver biopsy twice (25 patients in group A and 24 in group 13). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P<0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type Ⅲ procollagenic peptide (PⅢ P) in group A was seen (P<0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P<0.05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P<0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.

Existence and significance of hepatitis B virus DNA in kidneys of IgA nephropathy

AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy(IgAN).METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg, or HBsAg, HBcAg)detected by immunohistochemistry in renal tissues were enrolled in our study. The distribution and localization of HBV DNA were observed using in situ hybridization.Southern blot analysis was performed to reveal the state of renal HBV DNA.RESULTS: Among the 50 patients with IgAN, HBs antigenemia was detected in 17 patients (34%). HBAg in renal tissues was detected in 48 patients (96%), the positive rate of HBAg, HBsAg, and HBcAg was 82% (41/50), 58% (29/50),and 42% (21/50) in glomeruli, respectively; and was 94%(47/50), 56% (28/50) and 78% (39/50) in tubular epithelia,respectively. Positive HBV DNA was detected in 72% (36/50)and 82% (41/50) cases in tubular epithelia and glomeruli respectively by in Situ hybridization, and the positive signals were localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as infiltrated interstitial lymphocytes. Moreover, 68% (34/50) cases were proved to be HBV DNA positive by Southern blot analysis, and all were the integrated form.CONCLUSION: HBV infection might play an important role in occurrence and progress of IgAN. In addition to humoral immune damages mediated by HBAg-HBAb immune complex,renal tissues of some IgAN are directly infected with HBV and express HBAg in situ, and the cellular mechanism mediated by HBV originating from renal cells in situ may also be involved in the pathogenesis of IgAN.

Relationship between trefoil factor 1 expression and gastric mucosa injuries and gastric cancer

AIM:To determine whether trefoil factor 1 (TFF1) is associated with mucosa healing and carcinoma suppression, we assess the expression of trefoil factor 1 in normal and pathologic gastric mucosa. METHODS: TFF1 in normal and pathologic gastric mucosa was assessed by immunohistochemical method, and the average positive A was estimated by Motic Images Advanced 3.0 software. RESULTS: Increased TFF1 was detected in gastritis, gastric ulcer and duodenal ulcer compared with normal mucosa. The same result could be seen in multiple and compound ulcer compared with simple ulcer. There was no significant difference between gastric ulcer and duodenal ulcer, gastritis and simple ulcer respectively. Increased TFF1 was detected in the peripheral mucosa of the gastric adenocarcinoma compared with normal mucosa. The expression of TFF1 in gastric adenocarcinoma was related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma, the weaker the expression of TFF1. There was no TFF1 expressed in low-differentiated adenocarcinoma. The expression of TFF1 in middle and highly differentiated adenocarcinoma was a little lower than that in normal mucosa. But there was no significant difference. No TFF1 was assessed in esophageal squamous carcinoma and peripheral tissue. There was no significant difference between male and female. CONCLUSION: The expression of TFF1 was higher in gastritis and peptic ulcer than that in normal mucosa, and was also higher in multiple and compound ulcer than in simple ulcer. It seems that TFF1 plays a role in gastric mucosa protection and epithelial restitution. Increased expression of TFF1 in peripheral tissue suggests that TFF1 is associated with mechanism of carcinoma suppression and differentiation. Decreased expression of TFF1 in carcinoma and its relativity to the differentiation suggests that TFF1 is related to gland and cell destruction of carcinoma.

Relationship between clinical and pathologic findings in patients with chronic liver diseases

AIM: To explore the relationship between clinical findings of patients with chronic liver diseases and the pathologic grading and staging of liver tissues.METHODS: The inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients were determined according to the diagnosis criteria of chronic hepatitis in China established in 1995. A comparative analysis was carried out for 200 patients with chronic liver diseases by comparing their clinical manifestations, serum biochemical markers with the grading and staging of liver tissues.RESULTS: It was revealed that age, index of clinical symptoms and physical signs were obviously relevant to the pathologic grading and staging of liver tissues (P＜0.05). Blood platelet, red blood cells, aspartate aminotransferase (AST),N-terminal procollagen Ⅲ (PⅢ NP) were apparently correlated with the degree of inflammation. PGA (prothrombin time,GGT, apoprotein A1) index, PGAA (PGA+△2-macroglobublin)index, albumin and albumin/globulin were relevant to both inflammation and fibrosis. Hyaluronic acid (HA) was an accurate variable for the severity of hepatic inflammation and fibrosis. The combination of serum markers for fibrosis could increase the diagnostic accuracy. It was notable that viral replication markers were not relevant to the degree of inflammation and fibrosis.CONCLUSION: There is a good correlation between clinical findings and the pathologic grading and staging of liver tissues, which may give aid to the noninvasive diagnosis of liver fibrosis.